HETEROCYCLE-SUBSTITUTED BICYCLIC AZOLE PESTICIDES
20220135562 · 2022-05-05
Inventors
Cpc classification
A01N43/82
HUMAN NECESSITIES
C07D403/04
CHEMISTRY; METALLURGY
C07D401/04
CHEMISTRY; METALLURGY
A01N43/72
HUMAN NECESSITIES
International classification
A01N43/72
HUMAN NECESSITIES
A01N43/82
HUMAN NECESSITIES
A01N43/90
HUMAN NECESSITIES
C07D401/04
CHEMISTRY; METALLURGY
C07D403/04
CHEMISTRY; METALLURGY
Abstract
Disclosed are compounds of Formula 1, including all geometric and stereoisomers, N oxides, and salts thereof, wherein A, X.sup.1, X.sup.2, X.sup.3 and R.sup.2 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.
##STR00001##
Claims
1. A compound selected from Formula 1, an N-oxide or salt thereof, ##STR00034## wherein A is CH; X.sup.1 is CH and X.sup.2 is CR.sup.1; X.sup.3 is CH or CF; R.sup.1 is phenyl, pyridinyl, thiazolyl, oxazolyl, thiadiazolyl or oxadiazolyl, each being substituted with one R.sup.3, and optionally further substituted with 1 to 3 R.sup.x. R.sup.2 is H, halogen, cyano, nitro, C.sub.1-C.sub.4 alkyl, C.sub.1-C.sub.4 haloalkyl, C.sub.1-C.sub.4 alkoxy or C.sub.1-C.sub.4 haloalkoxy; R.sup.3 is selected from the group consisting of ##STR00035## each R.sup.4 is independently H or C.sub.1-C.sub.4 alkyl; each R.sup.5 is independently H or C.sub.1-C.sub.4 alkyl; or R.sup.4 and R.sup.5 are taken together with the carbon atom to which they are attached to form a 3- to 6-membered ring containing ring members selected from carbon atoms and up to 2 heteroatoms independently selected from one oxygen atom, one sulfur atom, and up to 2 nitrogen atoms, wherein up to 2 carbon atom ring members are independently selected from C(═O) and C(═S) and the sulfur atom ring member is selected from S, S(O) or S(O).sub.2, said ring being unsubstituted or substituted with up to 4 R.sup.x; provided that R.sup.4 and R.sup.5 are attached to the same carbon atom; p is 1, 2, 3 or 4; R.sup.6 is NR.sup.13R.sup.14, OR.sup.15 or C(═NR.sup.8)R.sup.9; or C.sub.1-C.sub.6 alkyl substituted with at least one R.sup.y; or C.sub.3-C.sub.6 cycloalkyl, C.sub.2-C.sub.6 alkenyl or C.sub.2-C.sub.6 alkynyl, each unsubstituted or substituted with at least one R.sup.x; R.sup.7 is H; each R.sup.x is independently halogen, cyano, nitro, hydroxy, C.sub.1-C.sub.6 alkyl, C.sub.1-C.sub.6 haloalkyl, C.sub.3-C.sub.6 cycloalkyl, C.sub.1-C.sub.6 alkoxy, C.sub.1-C.sub.6 haloalkoxy, C.sub.3-C.sub.6 cycloalkoxy, C(═NR.sup.8)R.sup.9, C(O)OR.sup.16, C(O)NR.sup.13R.sup.14, OC(O)R.sup.17, NR.sup.20R.sup.21, NR.sup.19C(O)R.sup.17, C(O)R.sup.17, S(O).sub.nR.sup.18, Si(R.sup.23).sub.3, OSi(R.sup.23).sub.3 or Q; each R.sup.y is independently cyano, nitro, hydroxy, C.sub.3-C.sub.6 cycloalkyl, C.sub.1-C.sub.6 alkoxy, C.sub.1-C.sub.6 haloalkoxy, C.sub.3-C.sub.6 cycloalkoxy, C(═NR.sup.8)R.sup.9, C(O)OR.sup.16, C(O)NR.sup.13R.sup.14, OC(O)R.sup.17, NR.sup.20R.sup.21, NR.sup.19C(O)R.sup.17, C(O)R.sup.17, S(O).sub.nR.sup.18, Si(R.sup.23).sub.3, OSi(R.sup.23).sub.3 or Q; each R.sup.8 is independently OR.sup.10, S(O).sub.nR.sup.11 or NHR.sup.12; each R.sup.9 is independently H; or C.sub.1-C.sub.6 alkyl, C.sub.3-C.sub.6 cycloalkyl, C.sub.2-C.sub.6 alkenyl or C.sub.2-C.sub.6 alkynyl, each unsubstituted or substituted with at least one R.sup.x; or C.sub.1-C.sub.6 alkoxy, C.sub.1-C.sub.6 haloalkoxy, C.sub.3-C.sub.6 cycloalkoxy, C(O)OR.sup.16, C(O)NR.sup.13R.sup.14, NR.sup.20R.sup.21, NR.sup.19C(O)R.sup.17, C(O)R.sup.17 or Q; each R.sup.10 is independently C.sub.1-C.sub.4 alkyl, C.sub.3-C.sub.6 cycloalkyl, C.sub.1-C.sub.4 haloalkyl, C(O)R.sup.17, S(O).sub.nR.sup.11 or Q; each R.sup.11 is independently C.sub.1-C.sub.4 alkyl or C.sub.1-C.sub.4 haloalkyl; R.sup.12 is C.sub.1-C.sub.4 alkyl, C.sub.3-C.sub.6 cycloalkyl, C.sub.1-C.sub.4 haloalkyl, C(O)R.sup.17 or C(O)OR.sup.16; or phenyl, unsubstituted or substituted with at least one substituent independently selected from the group consisting of halogen, cyano, nitro, C.sub.1-C.sub.4 alkyl, C.sub.3-C.sub.6 cycloalkyl, C.sub.1-C.sub.4 haloalkyl, C.sub.1-C.sub.4 alkoxy and C.sub.1-C.sub.4 haloalkoxy; each R.sup.13 is independently H, C.sub.1-C.sub.6 alkyl, C.sub.1-C.sub.4 haloalkyl, C.sub.1-C.sub.4 hydroxyalkyl, C(O)R.sup.22 or S(O).sub.2R.sup.22; or phenyl or a 5- or 6-membered heterocyclic aromatic ring, each unsubstituted or substituted with at least one substituent independently selected from the group consisting of halogen, cyano, nitro, C.sub.1-C.sub.4 alkyl, C.sub.3-C.sub.6 cycloalkyl, C.sub.1-C.sub.4 haloalkyl, C.sub.1-C.sub.4 alkoxy and C.sub.1-C.sub.4 haloalkoxy; each R.sup.14 is independently H, C.sub.1-C.sub.6 alkyl or C.sub.1-C.sub.4 haloalkyl; or R.sup.13 and R.sup.14 are taken together with the nitrogen atom to which they are attached to form a 3- to 7-membered ring containing ring members selected from carbon atoms and up to 2 heteroatoms independently selected from one oxygen atom, one sulfur atom, and up to 2 nitrogen atoms, wherein up to 2 carbon atom ring members are independently selected from C(═O) and C(═S) and the sulfur atom ring member is selected from S, S(O) or S(O).sub.2, said ring being unsubstituted or substituted with at least one substituent independently selected from the group consisting of halogen, cyano, nitro, C.sub.1-C.sub.4 alkyl, C.sub.3-C.sub.6 cycloalkyl, C.sub.1-C.sub.4 haloalkyl, C.sub.1-C.sub.4 alkoxy and C.sub.1-C.sub.4 haloalkoxy; R.sup.15 is C.sub.1-C.sub.4 alkyl, C.sub.3-C.sub.6 cycloalkyl, C.sub.3-C.sub.6 cycloalkoxy or C.sub.1-C.sub.4 haloalkyl; or phenyl, unsubstituted or substituted with at least one substituent independently selected from the group consisting of halogen, cyano, nitro, C.sub.1-C.sub.4 alkyl, C.sub.3-C.sub.6 cycloalkyl, C.sub.1-C.sub.4 haloalkyl, C.sub.1-C.sub.4 alkoxy and C.sub.1-C.sub.4 haloalkoxy; each R.sup.16 is independently H, C.sub.1-C.sub.4 alkyl, C.sub.1-C.sub.4 haloalkyl, C.sub.3-C.sub.6 cycloalkyl or C.sub.3-C.sub.6 halocycloalkyl; or phenyl, unsubstituted or substituted with at least one substituent independently selected from the group consisting of halogen, cyano, nitro, C.sub.1-C.sub.4 alkyl, C.sub.3-C.sub.6 cycloalkyl, C.sub.1-C.sub.4 haloalkyl, C.sub.1-C.sub.4 alkoxy and C.sub.1-C.sub.4 haloalkoxy; each R.sup.17 is independently C.sub.1-C.sub.4 alkyl, C.sub.1-C.sub.4 haloalkyl, C.sub.3-C.sub.6 cycloalkyl or C.sub.3-C.sub.6 halocycloalkyl; or phenyl, unsubstituted or substituted with at least one substituent independently selected from the group consisting of halogen, cyano, nitro, C.sub.1-C.sub.4 alkyl, C.sub.3-C.sub.6 cycloalkyl, C.sub.1-C.sub.4 haloalkyl, C.sub.1-C.sub.4 alkoxy and C.sub.1-C.sub.4 haloalkoxy; each R.sup.18 is independently C.sub.1-C.sub.4 alkyl, C.sub.1-C.sub.4 haloalkyl, C.sub.3-C.sub.6 cycloalkyl, C.sub.3-C.sub.6 halocycloalkyl, C.sub.3-C.sub.6 cycloalkylalkyl or C.sub.3-C.sub.6 halocycloalkylalkyl; or phenyl, unsubstituted or substituted with at least one substituent independently selected from the group consisting of halogen, cyano, nitro, C.sub.1-C.sub.4 alkyl, C.sub.3-C.sub.6 cycloalkyl, C.sub.1-C.sub.4 haloalkyl, C.sub.1-C.sub.4 alkoxy and C.sub.1-C.sub.4 haloalkoxy; each R.sup.19 is independently H or C.sub.1-C.sub.4 alkyl; each R.sup.20 is independently H, C.sub.1-C.sub.4 alkyl or C.sub.1-C.sub.4 haloalkyl; or phenyl, unsubstituted or substituted with at least one substituent independently selected from the group consisting of halogen, cyano, nitro, C.sub.1-C.sub.4 alkyl, C.sub.3-C.sub.6 cycloalkyl, C.sub.1-C.sub.4 haloalkyl, C.sub.1-C.sub.4 alkoxy and C.sub.1-C.sub.4 haloalkoxy; each R.sup.21 is independently H, C.sub.1-C.sub.4 alkyl or C.sub.1-C.sub.4 haloalkyl; or phenyl, unsubstituted or substituted with at least one substituent independently selected from the group consisting of halogen, cyano, nitro, C.sub.1-C.sub.4 alkyl, C.sub.3-C.sub.6 cycloalkyl, C.sub.1-C.sub.4 haloalkyl, C.sub.1-C.sub.4 alkoxy and C.sub.1-C.sub.4 haloalkoxy; or R.sup.20 and R.sup.21 are independently taken together with the nitrogen atom to which they are attached to form a 3- to 7-membered ring containing ring members selected from carbon atoms and up to 2 heteroatoms independently selected from one oxygen atom, one sulfur atom, and up to 2 nitrogen atoms, wherein up to 2 carbon atom ring members are independently selected from C(═O) and C(═S) and the sulfur atom ring member is selected from S, S(O) or S(O).sub.2, said ring being unsubstituted or substituted with at least one substituent independently selected from the group consisting of halogen, cyano, nitro, C.sub.1-C.sub.4 alkyl, C.sub.3-C.sub.6 cycloalkyl, C.sub.1-C.sub.4 haloalkyl, C.sub.1-C.sub.4 alkoxy and C.sub.1-C.sub.4 haloalkoxy; each R.sup.22 is independently C.sub.1-C.sub.6 alkyl, C.sub.1-C.sub.6 haloalkyl, C.sub.1-C.sub.6 alkoxy, C.sub.1-C.sub.6 haloalkoxy or NR.sup.24R.sup.25; or phenyl or a 5- or 6-membered heterocyclic aromatic ring, each unsubstituted or substituted with at least one substituent independently selected from the group consisting of halogen, cyano, nitro, C.sub.1-C.sub.4 alkyl, C.sub.3-C.sub.6 cycloalkyl, C.sub.1-C.sub.4 haloalkyl, C.sub.1-C.sub.4 alkoxy and C.sub.1-C.sub.4 haloalkoxy; each R.sup.23 is independently C.sub.1-C.sub.6 alkyl, C.sub.3-C.sub.6 cycloalkyl or phenyl; each R.sup.24 is independently H or Q; or C.sub.1-C.sub.6 alkyl, C.sub.3-C.sub.6 cycloalkyl, C.sub.2-C.sub.6 alkenyl or C.sub.2-C.sub.6 alkynyl, each unsubstituted or substituted with at least one substituent independently selected from the group consisting of halogen, cyano, nitro, C.sub.1-C.sub.4 alkyl, C.sub.3-C.sub.6 cycloalkyl, C.sub.1-C.sub.4 haloalkyl, C.sub.1-C.sub.4 alkoxy and C.sub.1-C.sub.4 haloalkoxy; each R.sup.25 is independently H or Q; or C.sub.1-C.sub.6 alkyl, C.sub.3-C.sub.6 cycloalkyl, C.sub.2-C.sub.6 alkenyl or C.sub.2-C.sub.6 alkynyl, each unsubstituted or substituted with at least one substituent independently selected from the group consisting of halogen, cyano, nitro, C.sub.1-C.sub.4 alkyl, C.sub.3-C.sub.6 cycloalkyl, C.sub.1-C.sub.4 haloalkyl, C.sub.1-C.sub.4 alkoxy and C.sub.1-C.sub.4 haloalkoxy; or R.sup.24 and R.sup.25 are taken together with the nitrogen atom to which they are attached to form a 3- to 10-membered ring containing ring members selected from carbon atoms and up to 2 heteroatoms independently selected from one oxygen atom, one sulfur atom, and up to 2 nitrogen atoms, wherein up to 2 carbon atom ring members are independently selected from C(═O) and C(═S) and the sulfur atom ring member is selected from S, S(O) or S(O).sub.2, said ring being unsubstituted or substituted with up to 4 substituents independently selected from the group consisting of halogen, cyano, nitro, C.sub.1-C.sub.4 alkyl, C.sub.3-C.sub.6 cycloalkyl, C.sub.1-C.sub.4 haloalkyl, C.sub.1-C.sub.4 alkoxy and C.sub.1-C.sub.4 haloalkoxy; each Q is independently phenyl, a 5- or 6-membered heterocyclic aromatic ring or a 3- to 6-membered heterocyclic non-aromatic ring, each ring containing ring members selected from carbon atoms and up to 2 heteroatoms independently selected from one oxygen atom, one sulfur atom, and up to 2 nitrogen atoms, wherein up to 2 carbon atom ring members are independently selected from C(═O) and C(═S) and the sulfur atom ring member is selected from S, S(O) or S(O).sub.2, each ring unsubstituted or substituted with at least one substituent independently selected from the group consisting of halogen, cyano, nitro, C.sub.1-C.sub.4 alkyl, C.sub.3-C.sub.6 cycloalkyl, C.sub.1-C.sub.4 haloalkyl, C.sub.1-C.sub.4 alkoxy and C.sub.1-C.sub.4 haloalkoxy; and each n is independently 0, 1 or 2; provided that when X.sup.3 is CH; R.sup.2 is H; R.sup.3 is R.sup.3b; R.sup.6 is a cyclopropyl substituted at the 1 position with R.sup.x; R.sup.x is C(O)NR.sup.13R.sup.14; R.sup.13 is CH.sub.3 and R.sup.14 is H, then R.sup.1 is other than pyridine-4-yl substituted with one R.sup.3 at the 2 position.
2. (canceled)
3. (canceled)
4. (canceled)
5. The compound of claim 4 wherein R.sup.1 is phenyl, pyridinyl, thiazolyl, oxazolyl or oxadiazolyl, each being substituted with one R.sup.3, and optionally further substituted with 1 to 3 R.sup.x.
6. (canceled)
7. 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, said composition optionally further comprising at least one additional biologically active compound or agent.
8. The composition of claim 7 wherein the at least one additional biologically active compound or agent is selected from the group consisting of abamectin, acephate, acequinocyl, acetamiprid, acrinathrin, afidopyropen, amidoflumet, amitraz, avermectin, azadirachtin, azinphos-methyl, benfuracarb, bensultap, bifenthrin, bifenazate, bistrifluron, borate, buprofezin, carbaryl, carbofuran, cartap, carzol, chlorantraniliprole, chlorfenapyr, chlorfluazuron, chlorpyrifos, chlorpyrifos-methyl, chromafenozide, clofentezin, clothianidin, cyantraniliprole, cyclaniliprole, cycloprothrin, cycloxaprid, 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, fenitrothion, fenothiocarb, fenoxycarb, fenpropathrin, fenvalerate, fipronil, flometoquin, flonicamid, flubendiamide, flucythrinate, flufenerim, flufenoxuron, flufenoxystrobin, flufensulfone, fluorpyram, flupiprole, flupyradifurone, fluvalinate, tau-fluvalinate, fonophos, formetanate, fosthiazate, halofenozide, heptafluthrin, hexaflumuron, hexythiazox, hydramethylnon, imidacloprid, indoxacarb, insecticidal soaps, isofenphos, lufenuron, malathion, meperfluthrin, metaflumizone, metaldehyde, methamidophos, methidathion, methiodicarb, methomyl, methoprene, methoxychlor, metofluthrin, monocrotophos, monofluthrin, methoxyfenozide, nitenpyram, nithiazine, novaluron, noviflumuron, oxamyl, parathion, parathion-methyl, permethrin, phorate, phosalone, phosmet, phosphamidon, pirimicarb, profenofos, profluthrin, propargite, protrifenbute, pyflubumide, pymetrozine, pyrafluprole, pyrethrin, pyridaben, pyridalyl, pyrifluquinazon, pyriminostrobin, pyriprole, pyriproxyfen, rotenone, ryanodine, silafluofen, 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, all strains of Bacillus thuringiensis, entomopathogenic bacteria, all strains of Nucleo polyhedrosis viruses, entomopathogenic viruses and entomopathogenic fungi.
9. The composition of claim 8 wherein the at least one additional biologically active compound or agent is selected from the group consisting of abamectin, acetamiprid, acrinathrin, afidopyropen, amitraz, avermectin, azadirachtin, benfuracarb, bensultap, bifenthrin, 3-bromo-1-(3-chloro-2-pyridinyl)-N-[4-cyano-2-methyl-6-[(methylamino)carbonyl]phenyl]-1H-pyrazole-5-carboxamide, buprofezin, carbaryl, cartap, chlorantraniliprole, chlorfenapyr, chlorpyrifos, clothianidin, cyantraniliprole, cyclaniliprole, cycloprothrin, cyfluthrin, beta-cyfluthrin, cyhalothrin, lambda-cyhalothrin, gamma-cyhalothrin, cypermethrin, alpha-cypermethrin, zeta-cypermethrin, cyromazine, deltamethrin, dieldrin, dinotefuran, diofenolan, emamectin, endosulfan, esfenvalerate, ethiprole, etofenprox, etoxazole, fenitrothion, fenothiocarb, fenoxycarb, fenvalerate, fipronil, flometoquin, flonicamid, flubendiamide, flufenoxuron, flufenoxystrobin, flufensulfone, flupiprole, flupyradifurone, fluvalinate, formetanate, fosthiazate, heptafluthrin, hexaflumuron, hydramethylnon, imidacloprid, indoxacarb, lufenuron, meperfluthirn, metaflumizone, methiodicarb, methomyl, methoprene, methoxyfenozide, metofluthrin, monofluthrin, nitenpyram, nithiazine, novaluron, oxamyl, pyflubumide, pymetrozine, pyrethrin, pyridaben, pyridalyl, pyriminostrobin, pyriproxyfen, ryanodine, spinetoram, spinosad, spirodiclofen, spiromesifen, spirotetramat, sulfoxaflor, tebufenozide, tetramethrin, thiacloprid, thiamethoxam, thiodicarb, thiosultap-sodium, tralomethrin, tetramethylfluthrin, triazamate, triflumuron, all strains of Bacillus thuringiensis and all strains of Nucleo polyhedrosis viruses.
10. 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.
11. 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.
Description
SYNTHESIS EXAMPLE 1
Preparation of 5-[2-(3-pyridinyl)-2H-indazol-5-yl]-N-(2-pyrimidinylmethyl)-4-thiazolecarboxamide (Compound 78)
Step A: Preparation of 5-bromo-N-(2-pyrimidinylmethyl)-4-thiazolecarboxamide
[0212] A mixture of 5-bromothiazole-4-carbonyl chloride (0.30 g, 1.3 mmol), pyrimidin-2-ylmethanamine (0.21 g, 1.94 mmol), and trimethylamine (0.52 g, 5.1 mmol) in dichloromethane was stirred at room temperature for 18 hours. The reaction mixture was then quenched with saturated aqueous sodium bicarbonate solution (20 mL) and dichloromethane (20 mL). The phases were separated, and the aqueous phase was extracted with dichloromethane (3×20 mL). The combined organic phases were dried with sodium sulfate, concentrated, and purified by column chromatography (silica gel eluted with a gradient of 20% ethyl acetate/hexanes to 100% ethyl acetate) to give the title compound.
Step B: Preparation of 2-(3-pyridinyl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2H-indazole
[0213] 5-Bromo-2-(3-pyridinyl)-2H-indazole was prepared according to the method described in WO 2015/038503. A mixture of this bromide (1.0 g, 3.6 mmol), bis(pinacolato)diboron (1.65 g, 6.5 mmol), Pd(dppf)Cl.sub.2 (0.090 g, 0.11 mmol), and potassium acetate (1.1 g, 10 mmol) in 1,4-dioxane was stirred at room temperature for 1.5 hours. The reaction mixture was then filtered through a pad of Celite®, and concentrated under reduced pressure to remove 1,4-dioxane. The residue was purified by MPLC column chromatography (silica gel eluted with a gradient of 0 to 50% ethyl acetate in hexanes) to obtain the title compound, which was used directly for the next step.
Step C: Preparation of 5-[2-(3-pyridinyl)-2H-indazol-5-yl]-N-(2-pyrimidinylmethyl)-4-thiazolecarboxamide
[0214] A mixture of the bromide prepared in Step A (0.13 g, 0.43 mmol), the borate prepared in Step B (0.14 g, 0.44 mmol), Pd(dppf)Cl.sub.2 (0.010 g, 0.012 mmol), and potassium carbonate (0.18 g, 1.3 mmol) in dioxane-water (4:1) was purged with nitrogen gas. The mixture was then heated to 100° C. under nitrogen for 18 hours. The reaction mixture was then concentrated, and the residue was purified by MPLC column chromatography (silica gel eluted with a mixture of 40% acetone in dichloromethane) to give the desired product. This product was titrated with diethyl ether and stored in a freezer to give the title compound (52 mg), a compound of this invention, as a crystalline solid.
SYNTHESIS EXAMPLE 2
Preparation of 2-methyl-N-[[5-[2-(3-pyridinyl)-2H-indazol-5-yl]-1,3,4-oxadiazol-2-yl]carbonyl]alanine methyl ester (Compound 105)
Step A: Preparation of 2-(3-pyridinyl)-2H-indazole-5-carboxylic acid 2-[(1,1-dimethylethoxy)carbonyl]hydrazide
[0215] This compound was prepared by the method disclosed in WO 2015/038503 for the synthesis of methyl 2-[[2-(3-pyridinyl)-2H-indazol-5-yl]carbonyl]hydrazinecarboxylate (Compound 42 in WO 2015/038503).
Step B: Preparation of ethanedioic acid 1-ethyl ester 2-[2-[[2-(3-pyridinyl)-2H-indazol-5-yl]carbonyl]hydrazide]
[0216] 2-(3-pyridinyl)-2H-indazole-5-carboxylic acid 2-[(1,1-dimethylethoxy)carbonyl]-hydrazide prepared in Step A (90 g, 255 mmol) was mixed with 1,4-dioxane-hydrogen chloride (4 N, 100 mL) at 0° C. The resulting mixture was stirred and warmed up to room temperature for 30 minutes, and maintained at room temperature for an additional 2 hours. The reaction mixture was then concentrated under reduced pressure to dryness to yield 62 g of the crude hydrazide-hydrogen chloride salt. A portion of this material (13 g, 44.9 mmol) was mixed with ethyl 2-chloro-2-oxo-acetate (8.3 g, 67.7 mmol) and triethylamine (18.1 g, 179.6 mmol) in dichloromethane (120 mL) and DMF (60 mL). The resulting mixture was stirred and warmed up to room temperature for 30 minutes, and maintained at room temperature for an additional 16 hours. The reaction mixture was then concentrated under reduced pressure to dryness to yield the title compound (11.2 g, 31.7 mmol, 70.6%).
Step C: Preparation of ethyl 5-[2-(3-pyridinyl)-2H-indazol-5-yl]-1,3,4-oxadiazole-2-carboxylate
[0217] Ethanedioic acid 1-ethyl ester 2-[2-[[2-(3-pyridinyl)-2H-indazol-5-yl]carbonyl]hydrazide]oxo-acetate prepared in Step B (11.0 g, 31.15 mmol) was mixed with 4-toluenesulfonyl chloride (5.94 g, 31.15 mmol) and triethylamine (6.29 g, 62.3 mmol) in dichloromethane (100 mL) and DMF (100 mL) at 0° C. The resulting mixture was stirred and warmed up to room temperature for 1 hour, and maintained for at room temperature for an additional 15 hours. The reaction mixture was then concentrated under reduced pressure to provide a solid. The crude solid was purified by silica gel chromatography (0-100% ethyl acetate/hexanes) to yield the title compound (8.5 g, 25.3 mmol, 81.4%).
Step D: Preparation of 2-methyl-N-[[5-[2-(3-pyridinyl)-2H-indazol-5-yl]-1,3,4-oxadiazol-2-yl]carbonyl]alanine methyl ester
[0218] Ethyl 5-[2-(3-pyridinyl)-2H-indazol-5-yl]-1,3,4-oxadiazole-2-carboxylate prepared in Step C (3.0 g, 8.95 mmol) was mixed with lithium hydroxide (0.32 g, 13.4 mmol) in THE (10 mL) and water (5 mL) at 0° C. The resulting mixture was stirred and warmed up to room temperature for 1 hour, and maintained at room temperature for an additional 3 hours. The reaction mixture was then concentrated under reduced pressure to provide the crude acid. A mixture of this crude acid, methyl 2-amino-2-methyl-propanoate (1.26 g, 10.74 mmol), HATU (5.1 g, 13.43 mmol) and DIPEA (2.9 g, 22.4 mmol) in DMF (10 mL) was stirred at room temperature for 16 hours. A precipitate formed which was collected via suction filtration. The collected solid was washed with EtOAc, then with water, and finally dried in a vacuum oven to yield the title compound, a compound of this invention as a white solid (1.5 g, 3.69 mmol, 41.2%).
SYNTHESIS EXAMPLE 3
Preparation of 2-methyl-N-[[5-[2-(3-pyridinyl)-2H-indazol-5-yl]-1,3,4-thiadiazol-2-yl]carbonyl]alanine methyl ester (Compound 128)
Step A: Preparation of ethyl 5-[2-(3-pyridinyl)-2H-indazol-5-yl]-1,3,4-thiadiazole-2-carboxylate
[0219] Ethanedioic acid 1-ethyl ester 2-[2-[[2-(3-pyridinyl)-2H-indazol-5-yl]carbonyl]hydrazide]oxo-acetate prepared in Synthesis Example 2 Step B (5.0 g, 14.16 mmol) was mixed with Lawesson's Reagent (5.73 g, 14.16 mmol) in toluene (30 mL) at room temperature The resulting mixture was stirred and heated to 111° C., and maintained at this temperature for 2 hours. The suspension was then cooled, passed through a short pad of silica gel, and washed with 100 mL of ethyl acetate to provide the title compound as pale yellow solid (3.0 g, 8.54 mmol, 60.3%).
Step B: Preparation of 2-methyl-N-[[5-[2-(3-pyridinyl)-2H-indazol-5-yl]-1,3,4-thiadiazol-2-yl]carbonyl]alanine methyl ester
[0220] The title compound was prepared by the same method as described for Synthesis Example 2 Step D.
SYNTHESIS EXAMPLE 4
Preparation of N-(2,2-dimethoxyethyl)-3-[2-(3-pyridinyl)-2H-indazol-5-yl]benzamide (Compound 25)
Step A: Preparation of methyl 3-[2-(3-pyridinyl)-2H-indazol-5-yl]benzoate
[0221] A mixture of 5-bromo-2-(3-pyridinyl)-2H-indazole (3.4 g, 11.64 mmol), (3-methoxycarbonylphenyl)boronic acid (2.55 g, 14.2 mmol) and potassium phosphate (3.0 g, 14.2 mmol) in DMF (60 mL) was degassed using nitrogen for 15 minutes. Pd(PPh.sub.3).sub.4 was then added, and the reaction mixture was stirred at 100° C. overnight. Water was then added, and the reaction mixture was extracted three times with EtOAc. The combined organic extracts were washed with saturated aqueous NaCl and dried over anhydrous Na.sub.2SO.sub.4. After evaporation of the solvent under reduced pressure, the residue was purified by MPLC (40 g silica, 15-60% EtOAc in hexanes) to yield the title compound (3.0 g) as a white solid. .sup.1H NMR (500 MHz, DMSO-d.sub.6): δ ppm 9.35 (br s, 1H), 9.25 (s, 1H), 8.66 (d, J=3.91 Hz, 1H), 8.45-8.57 (m, 1H), 8.21-8.29 (m, 1H), 8.09 (s, 1H), 8.01 (d, J=7.83 Hz, 1H), 7.94 (d, J=7.83 Hz, 1H), 7.85 (d, J=8.80 Hz, 3H), 7.57-7.72 (m, 3H), 3.89 (s, 3H).
Step B: Preparation of 3-[2-(3-pyridinyl)-2H-indazol-5-yl]benzoic acid
[0222] To a stirred suspension of methyl 3-[2-(3-pyridyl)-2H-indazol-5-yl]benzoate (2.9 g, 8.35 mmol) in MeOH/THF (30 mL/30 mL) was added 2 M sodium hydroxide (10 mL), and the suspension was heated at 70° C. for 2 hours. The reaction mixture was then cooled to room temperature and concentrated under reduced pressure. The resulting residue was diluted with water and acidified with 2 M hydrochloric acid to pH ˜4. This mixture was then heated to reflux for 30 minutes, and then cooled. The precipitated solid was collected by filtration and dried to yield the title compound as white solid (2.5 g). .sup.1H NMR (500 MHz, DMSO-d.sub.6): δ ppm 9.34 (d, J=2.45 Hz, 1H), 9.24 (s, 1H), 8.65 (dd, J=4.65, 1.22 Hz, 1H), 8.44-8.54 (m, 1H), 8.24 (t, J=1.71 Hz, 1H), 8.08 (s, 1H), 7.89-8.01 (m, 1H), 7.85 (d, J=9.29 Hz, 2H), 7.55-7.74 (m, 3H).
Step C: Preparation of N-(2,2-dimethoxyethyl)-3-[2-(3-pyridinyl)-2H-indazol-5-yl]benzamide
[0223] T.sub.3P (280 VL, 0.47 mmol, 50 wt % in EtOAc) was added to a stirred suspension of 3-[2-(3-pyridyl)-2H-indazol-5-yl]benzoic acid (100 mg, 0.31 mmol), 2,2-dimethoxyethanamine (50 μL, 0.47 mmol) and triethyl amine (90 μL, 0.62 mmol) in dry dichloromethane (5 mL) under a nitrogen atmosphere. After stirring the reaction mixture at room temperature overnight, dichloromethane (20 mL) was added, the resulting solution was washed with water, and the organic phase was dried over Na.sub.2SO.sub.4. The dried solution was concentrated under reduced pressure to provide a solid which was triturated with 1:1 ether/hexane, and further washed with 1:1 ether/hexane to yield the title compound, a compound of this invention, as a white solid (100 mg). .sup.1H NMR (500 MHz, DMSO-d.sub.6): δ ppm 9.19-9.29 (m, 1H), 8.64-8.74 (m, 1H), 8.53 (s, 1H), 8.31-8.40 (m, 1H), 8.09 (s, 1H), 7.93 (s, 1H), 7.87 (d, J=8.80 Hz, 1H), 7.70-7.82 (m, 2H), 7.65 (d, J=1.47 Hz, 1H), 7.54 (d, J=7.34 Hz, 2H), 6.36-6.48 (m, 1H), 4.53 (m, 1H), 3.66 (t, J=5.62 Hz, 2H), 3.46 (m, 6H).
SYNTHESIS EXAMPLE 5
Preparation of N-(2-hydroxyethyl)-3-[2-(3-pyridinyl)-2H-indazol-5-yl]benzamide (Compound 31)
Step A: Preparation of N-(2-hydroxyethyl)-3-[2-(3-pyridinyl)-2H-indazol-5-yl]benzamide
[0224] DIPEA (880 μL, 5.07 mmol) was added to a stirred suspension of 3-[2-(3-pyridyl)-2H-indazol-5-yl]benzoic acid (200 mg, 0.63 mmol) and HATU (290 mg, 0.76 mmol) in DMF (3 mL). The mixture was stirred at room temperature for 1 hour, 2-aminoethanol (200 μL, 3.17 mmol) was added, and the reaction mixture was stirred overnight. The reaction mixture was concentrated under reduced pressure, and the resulting residue was redissolved in methanol (˜2 mL) and diluted with water. The precipitated product was collected by filtration and dried under reduced pressure to yield the title compound, a compound of this invention, as white solid (170 mg). .sup.1H NMR (500 MHz, DMSO-d.sub.6): δ ppm 9.36 (d, J=2.45 Hz, 1H), 9.26 (s, 1H), 8.66 (dd, J=4.65, 1.22 Hz, 1H), 8.57-8.64 (s, 2H), 8.20 (s, 1H), 8.11 (s, 1H), 7.80-7.93 (m, 3H), 7.75 (dd, J=9.05, 1.71 Hz, 1H), 7.65 (dd, J=8.31, 4.89 Hz, 1H), 7.51-7.59 (m, 1H), 4.71 (m, 1H), 3.54 (d, J=5.87 Hz, 2H) 3.36-3.38 (m, 2H).
SYNTHESIS EXAMPLE 6
Preparation of N-[1-[(methylamino)carbonyl]cyclopropyl]-4-[2-(3-pyridinyl)-2H-indazol-5-yl]-2-pyridinecarboxamide (Compound 85)
Step A: Preparation of 2-(3-pyridinyl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2H-indazole
[0225] A mixture of 5-bromo-2-(3-pyridyl)-2H-indazole (3 g, 10.9 mmol), 4,4,5,5-tetramethyl-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,3,2-dioxaborolane (5.5 g, 21.8 mmol) and potassium acetate (3.6 g, 33.0 mmol) in dioxane (35 mL) was degassed using nitrogen for 15 minutes. Pd(dppf)Cl.sub.2 was then added, and the reaction mixture was stirred and heated to reflux overnight. The reaction mixture was then allowed to cool to room temperature and was filtered through a Celite® plug. The filtrate was concentrated under reduced pressure, and the resulting residue was purified by MPLC (40 g silica, 25-60% EtOAc in hexanes) to yield the title compound (2.1 g) as a light brown solid. .sup.1H NMR (500 MHz, CDCl.sub.3): δ ppm 9.21 (br s, 1H), 8.58-8.81 (m, 1H), 8.48 (s, 1H), 8.30-8.25 (m, 2H), 7.73 (d, J=9.29 Hz, 2H), 7.30-7.55 (m, 1H), 1.38 (s, 12H).
Step B: Preparation of 4-[2-(3-pyridinyl)-2H-indazol-5-yl]-2-pyridinecarboxylic acid
[0226] A mixture of 2-(3-pyridinyl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2H-indazole (400 mg, 1.2 mmol), methyl 4-bromopyridine-2-carboxylate (300 mg, 1.36 mmol) and potassium carbonate (2M aqueous solution; 1.2 mL, 2.4 mmol) in DMF (6 mL) was degassed using nitrogen for 10 minutes. Pd(PPh.sub.3).sub.4 was then added, and the reaction mixture was stirred and heated to 100° C. for 15 hours. The reaction mixture was then cooled to room temperature and diluted with acetone (˜10 mL). Upon addition of acetone, a solid was formed which was then collected by filtration. This solid was redissolved in water and acidified with 1 M hydrochloric acid to pH ˜4. The precipitated product was collected by filtration and dried under reduced pressure to yield the title compound (350 mg) as tan white solid. LC-MS (ES+) [M+H].sup.+=317.3.
Step C: Preparation of methyl 1-[[[4-[2-(3-pyridinyl)-2H-indazol-5-yl]-2-pyridinyl]carbonyl]amino]cyclopropanecarboxylate
[0227] Methyl 1-aminocyclopropanecarboxylate hydrochloride (40 mg, 0.27 mmol) was added to a stirred suspension of 4-[2-(3-pyridinyl)-2H-indazol-5-yl]-2-pyridinecarboxylic acid (70 mg, 0.22 mmol) and HATU (100 mg, 0.26 mmol) in DMF (4 mL). The reaction mixture was stirred at room temperature for 1 hour, DIPEA (115 μL, 0.66 mmol) was added, and stirring was continued overnight. The reaction mixture was then concentrated under reduced pressure, and the residue was purified by MPLC (12 g silica, 0-10% MeOH in dichloromethane) to obtain the title compound (80 mg) as white solid. .sup.1H NMR (500 MHz, DMSO-d.sub.6): δ ppm 9.29-9.45 (m, 2H), 8.64-8.77 (m, 2H), 8.49-8.59 (m, 1H), 8.31-8.40 (m, 1H), 8.09-8.22 (m, 11H), 7.98-8.07 (m, 1H), 7.88-7.96 (m, 1H), 7.79-7.87 (m, 1H), 7.62-0.72 (m, 11H), 3.66 (s, 3H), 1.42-1.54 (m, 2H), 1.23-1.28 (m, 2H).
Step D: Preparation of 1-[[[4-[2-(3-pyridinyl)-2H-indazol-5-yl]-2-pyridinyl]carbonyl]amino]cyclopropanecarboxylic acid
[0228] To a stirred suspension of methyl 1-[[[4-[2-(3-pyridinyl)-2H-indazol-5-yl]-2-pyridinyl]carbonyl]amino]cyclopropanecarboxylate (260 mg, 0.63 mmol) in MeOH/THF (5 mL/5 mL) was added 2 M sodium hydroxide (5 mL), and the reaction mixture was heated to 65° C. for 2 hours. The reaction mixture was then cooled to room temperature and concentrated under reduced pressure. The residue was diluted with water, acidified with 2 M hydrochloric acid to pH ˜4, and then heated to reflux for 30 minutes. After cooling, the precipitated product was collected by filtration and dried under reduced pressure to yield the title compound (240 mg) as white solid. LC-MS (ES−) [M−H].sup.−=398.2.
Step E: Preparation of N-[1-[(methylamino)carbonyl]cyclopropyl]-4-[2-(3-pyridinyl)-2H-indazol-5-yl]-2-pyridinecarboxamide
[0229] Triethylamine (140 μL, 1.0 mmol) was added to a stirred suspension of 1-[[[4-[2-(3-pyridinyl)-2H-indazol-5-yl]-2-pyridinyl]carbonyl]amino]cyclopropanecarboxylic acid (80 mg, 0.2 mmol), methylamine hydrochloride (54 mg, 0.8 mmol) and HATU (90 mg, 0.24 mmol) in DMF (3 mL). The reaction mixture was then stirred at room temperature overnight. The reaction mixture was then cooled and concentrated under reduced pressure. The resulting residue was redissolved in methanol (˜2 mL) and diluted with water. The precipitated solid was collected by filtration and dried under reduced pressure to yield the title compound, a compound of this invention, as white solid (78 mg). .sup.1H NMR (500 MHz, DMSO-d.sub.6): δ ppm 9.31-9.41 (m, 2H), 9.17-9.24 (m, 111), 8.67-8.75 (m, 2H), 8.49-8.58 (m, 1H), 8.31-8.41 (m, 2H), 7.99-8.07 (m, 1H), 7.88-7.96 (m, 1H), 7.80-7.88 (m, 1H), 7.73-7.80 (m, 1H), 7.63-7.71 (m, 1H), 2.54-2.63 (m, 3H), 1.32-1.41 (m, 2H), 1.01-1.10 (m, 2H).
SYNTHESIS EXAMPLE 7
Preparation of N-[1-(aminocarbonyl)cyclopropyl]-4-[2-(3-pyridinyl)-2H-indazol-5-yl]-2-pynridinecarboxamide (Compound 86)
Step A: Preparation of N-[1-(aminocarbonyl)cyclopropyl]-4-[2-(3-pyridinyl)-2H-indazol-5-yl]-2-pyridinecarboxamide
[0230] Triethylamine (140 μL, 1.0 mmol) was added to a stirred suspension of 1-[[[4-[2-(3-pyridinyl)-2H-indazol-5-yl]-2-pyridinyl]carbonyl]amino]cyclopropanecarboxylic acid (80 mg, 0.2 mmol), ammonium chloride (53 mg, 1.0 mmol) and HATU (90 mg, 0.24 mmol) in DMF (3 mL). The reaction mixture was then stirred at room temperature overnight. The reaction mixture was then cooled and concentrated under reduced pressure. The resulting residue was redissolved in methanol (˜2 mL) and diluted with water. The precipitated solid was collected by filtration and dried under reduced pressure to yield the title compound, a compound of this invention, as a white solid (70 mg). .sup.1H NMR (500 MHz, DMSO-d.sub.6): δ ppm 9.29-9.42 (m, 2H), 9.2 (s, 1H), 8.64-8.74 (m, 2H), 8.49-8.60 (m, 1H), 8.29-8.38 (m, 2H), 7.97-8.04 (m, 1H), 7.89-7.96 (m, 1H), 7.78-7.86 (m, 1H), 7.63-7.73 (m, 1H), 7.24 (br s, 1H), 7.01 (br s, 1H), 1.30-1.41 (m, 2H), 1.01-1.12 (m, 2H).
SYNTHESIS EXAMPLE 8
Preparation of N-[1-[(dimethylamino)carbonyl]cyclopropyl]-4-[2-(3-pyridinyl)-2H-indazol-5-yl]-2-pyridinecarboxamide (Compound 87)
Step A: Preparation of N-[1-[(dimethylamino)carbonyl]cyclopropyl]-4-[2-(3-pyridinyl)-2H-indazol-5-yl]-2-pyridinecarboxamide
[0231] Dimethylamine (0.5 mL, 1.0 mmol; 2M in THF) was added to a stirred suspension of 1-[[4-[2-(3-pyridyl)-2H-indazol-5-yl]pyridine-2-carbonyl]amino]cyclopropanecarboxylic acid (80 mg, 0.2 mmol) and HATU (90 mg, 0.24 mmol) in DMF (3 mL). The reaction mixture was then stirred at room temperature overnight. The reaction mixture was then concentrated under reduced pressure, and the residue was purified by MPLC (24 g silica, 0-10% MeOH in dichloromethane) to yield the title compound, a compound of this invention, as white solid (78 mg). .sup.1H NMR (500 MHz, DMSO-d.sub.6): δ ppm 9.46 (s, 1H), 9.30-9.40 (m, 2H), 8.65-8.75 (m, 2H), 8.47-8.58 (m, 1H), 8.28-8.39 (m, 2H), 7.98-8.07 (m, 1H), 7.88-7.95 (m, 1H), 7.77-7.86 (m, 1H), 7.61-7.74 (m, 1H), 2.90 (br s, 6H), 1.22-1.32 (m, 211), 1.06-1.17 (m, 2H).
SYNTHESIS EXAMPLE 9
Preparation of 2-[2-(3-pyridinyl)-2H-indazol-5-yl]-N-(tetrahydro-2H-pyran-4-yl)-4-thiazolecarboxamide (Compound 64)
Step A: Preparation of 2-[2-(3-pyridinyl)-2H-indazol-5-yl]-4-thiazolecarboxylate
[0232] 2-(3-Pyridinyl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2H-indazole (563 mg, 1.75 mmol, prepared by the method of Synthesis Example 6 Step A) was added to a solution of 2-bromothiazole-4-carboxylic acid methyl ester (300 mg, 1.35 mmol) in toluene:methanol (8:2 ratio, 10 mL), followed by the addition of potassium acetate (399 mg, 4.05 mmol). The reaction mixture was purged with nitrogen gas for 5 minutes. Pd(dba).sub.3 (62 mg, 0.067 mmol) and Pd(PPh.sub.3)Cl.sub.2 (47 mg, 0.067 mmol) were added, and the reaction mixture was purged again with nitrogen gas. The reaction mixture was then heated to reflux, and kept at reflux overnight. The reaction mixture was then cooled and concentrated under reduced pressure. The residue was extracted with ethyl acetate, and the organic extracts were concentrated under reduced pressure. This residue was purified by column chromatography (30% EtOAc in petroleum ether) to obtain the title compound (260 mg) as a solid. .sup.1H NMR (500 MHz, chloroform-d): 6 ppm 4.00 (s, 2H), 7.31-7.64 (m, 1H), 7.77-7.93 (m, 1H), 7.95-8.06 (m, 1H), 8.25-8.35 (m, 1H), 8.40-8.48 (m, 1H), 8.56 (s, 1H), 8.63-8.77 (m, 1H), 8.98-9.33 (m, 1H).
Step B: Preparation of 2-[2-(3-pyridinyl)-2H-indazol-5-yl]-4-thiazolecarboxylic acid
[0233] LiOH—H.sub.2O (250 mg, 5.95 mmol) was added to a solution of 2-[2-(3-pyridinyl)-2H-indazol-5-yl]-4-thiazolecarboxylate (250 mg, 0.74 mmol) in THF:water (1:1 ratio, 10 mL), and the reaction mixture was stirred for 8 hours at room temperature. The reaction mixture was then acidified with 1N HCl to pH 2. After stirring, the precipitated solid was isolated by filtration and dried under reduced pressure to yield 200 mg of the title compound as a solid. 1H NMR (500 MHz, DMSO-d.sub.6): δ ppm 7.53-7.73 (m, 1H), 7.78-7.92 (m, 1H), 7.90-7.99 (m, 1H), 8.36-8.55 (m, 1H), 8.60-8.76 (m, 1H), 9.34 (s, 1H).
Step C: Preparation of 2-[2-(3-pyridinyl)-2H-indazol-5-yl]-N-(tetrahydro-2H-pyran-4-yl)-4-thiazolecarboxamide
[0234] Oxalyl chloride (0.05 mL, 0.646 mmol) was added at 0° C. to a solution of 2-[2-(3-pyridinyl)-2H-indazol-5-yl]-4-thiazolecarboxylic acid (145 mg, 0.432 mmol) in dichloromethane (5 mL), followed by the addition of few drops of dry DMF. The reaction mixture was stirred for 2 h at room temperature, and then concentrated under reduced pressure. The resulting residue was dissolved in dichloromethane, and tetrahydropyran-4-ylamine (0.09 mL, 0.863 mmol) and triethylamine (0.12 mL, 0.863 mmol) were added; the reaction mixture was then stirred at room temperature for 12 hours. After completion of the reaction, water was added, and the reaction mixture was extracted with dichloromethane. The organic extracts were dried over sodium sulfate and concentrated under reduced pressure. The resulting solid was purified by column chromatography (30% EtOAc in petroleum ether) to yield the title compound, a compound of this invention, as a solid (29 mg). .sup.1H NMR (500 MHz, chloroform-d): δ ppm 2.00-2.14 (m, 2H), 2.88 (s, 2H), 3.39 (br s, 3H), 3.52-3.65 (m, 1H), 3.96 (br s, 4H), 4.14-4.32 (m, 1H), 7.32-7.42 (m, 1H), 7.48-7.56 (m, 1H), 7.79-7.91 (m, 1H), 7.94-8.05 (m, 1H), 8.07-8.17 (m, 1H), 8.26-8.41 (m, 1H), 8.58 (s, 1H), 8.65-8.76 (m, 1H), 9.06-9.29 (m, 1H).
SYNTHESIS EXAMPLE 10
Preparation of N-(1-cyano-1-methylethyl)-2-[2-(3-pyridinyl)-2H-indazol-5-yl]-4-oxazolecarboxamide (Compound 155)
Step A: Preparation of N-(1-cyano-1-methylethyl)-2-[2-(3-pyridinyl)-2H-indazol-5-yl]-4-oxazolecarboxamide
[0235] The title compound was prepared by a method analogous to the one described in Synthesis Example 9 Steps A-C. .sup.1H NMR (500 MHz, DMSO-d.sub.6): δ ppm 1.72 (s, 6H), 7.66 (dd, J=8.31, 4.89 Hz, 1H), 7.85-7.94 (m, 1H), 8.00 (dd, J=9.29, 1.47 Hz, 1H), 8.54 (br d, J=16.14 Hz, 3H), 8.68 (dd, J=4.65, 1.22 Hz, 1H), 8.80 (s, 1H), 9.27-9.43 (m, 2H).
SYNTHESIS EXAMPLE 11
Preparation of N-methyl-2-[3-[2-(3-pyridinyl)-2H-indazol-5-yl]phenoxy]acetamide (Compound 102)
Step A: Preparation of 3-[2-(3-pyridinyl)-2H-indazol-5-yl]phenol
[0236] (3-Hydroxyphenyl)boronic acid (1.2 g, 0.008 mol) was added to 5-bromo-2-(3-pyridyl)-2H-indazole (2 g, 0.007 mol) in toluene:ethanol (10 mL:10 mL). Sodium carbonate solution (2.3 g, 2M, 0.021 mol) was added, and the reaction mixture was purged with nitrogen gas for 5 minutes. Pd(PPh.sub.3).sub.4 (421 mg, 0.0003 mol) was then added, and the reaction mixture was purged again with nitrogen for 5 minutes. The reaction mixture was then heated to reflux and stirred at reflux for 2 hours. The reaction mixture was then cooled and concentrated under reduced pressure. The resulting solid was stirred with ethyl acetate, and then the solid was isolated by filtration (1.3 g). This solid was dried under reduced pressure and used directly in the next step. .sup.1H NMR (500 MHz, DMSO-d.sub.6): δ ppm 6.53-6.83 (m, 1H), 6.99-7.16 (m, 2H), 7.20-7.33 (m, 1H), 7.54-7.67 (m, 3H), 7.75-7.87 (m, 1H), 7.89-8.07 (m, 1H), 8.39-8.54 (m, 1H), 8.60-8.71 (m, 1H), 9.11-9.25 (m, 1H), 9.29-9.41 (m, 1H), 9.44-9.54 (m, 1H).
Step B: Preparation of methyl 2-[3-[2-(3-pyridinyl)-2H-indazol-5-yl]phenoxy]acetate
[0237] Sodium hydride (167 mg, 0.006 mol) was added at 0° C. to a solution of 3-[2-(3-pyridinyl)-2H-indazol-5-yl]phenol (1 g, 0.003 mol) in DMF (2 mL). Methyl 2-bromoacetate (639 mg, 0.004 mol) was then slowly added, and the reaction mixture was stirred for 5 hours at room temperature. Water was added, and the reaction mixture was extracted with ethyl acetate; the organic phase was separated, dried over sodium sulfate, and concentrated under reduced pressure. The residue was purified by MPLC (20% EtOAc in petroleum ether) to yield the title compound as a pale yellow solid (1 g). .sup.1H NMR (500 MHz, chloroform-d): 6 ppm 3.83 (s, 3H), 4.72 (s, 2H), 6.82-6.96 (m, 1H), 7.22 (s, 1H), 7.27-7.32 (m, 1H), 7.39 (s, 11H), 7.44-7.49 (m, 1H), 7.51-7.56 (m, 1H), 7.59-7.64 (m, 1H), 7.65-7.71 (m, 11H), 7.87 (s, 2H), 8.01 (s, 1H), 8.31-8.41 (m, 1H), 8.51 (s, 1H), 8.62-8.72 (m, 1H), 9.15-9.27 (m, 1H).
Step C: Preparation of 2-[3-[2-(3-pyridinyl)-2H-indazol-5-yl]phenoxy]acetic acid
[0238] Methyl 2-[3-[2-(3-pyridinyl)-2H-indazol-5-yl]phenoxy]acetate (1 g, 0.002 mol) was dissolved in a solution of methanol (10 mL) and 1N NaOH solution (10 mL). The reaction mixture was heated to reflux for 2 hours, cooled, and concentrated under reduced pressure. The pH of the resulting residue was adjusted to pH 4-5 by the addition of 1N HCl, and this reaction mixture was heated to reflux and stirred at reflux for 1 hour. The reaction mixture was then cooled, and the precipitated solid was isolated by filtration (850 mg) and dried under reduced pressure. .sup.1H NMR (500 MHz, DMSO-d.sub.6): δ ppm 4.78 (s, 2H), 6.77-6.94 (m, 1H), 7.18-7.27 (m, 1H), 7.29-7.34 (m, 1H), 7.34-7.43 (m, 1H), 7.57-7.71 (m, 3H), 7.73-7.90 (m, 1H), 7.94-8.08 (m, 1H), 8.42-8.57 (m, 1H), 8.59-8.73 (m, 1H), 9.19-9.29 (m, 1H), 9.30-9.39 (m, 1H).
Step D: Preparation of N-methyl-2-[3-[2-(3-pyridinyl)-2H-indazol-5-yl]phenoxy]acetamide
[0239] HATU (131 mg, 0.34 mmol) was added to a solution of 2-[3-[2-(3-pyridinyl)-2H-indazol-5-yl]phenoxy]acetic acid (100 mg, 0.289 mmol) in dry DMF (10 mL), and the reaction mixture was stirred for 20 minutes; methylamine hydrochloride (97 mg, 1.44 mmol) was then added and the reaction mixture stirred for 1 hour. DIPEA (0.35 mL, 2.02 mmol) was added, and the reaction mixture was stirred at room temperature for 16 hours. Water was added, and the reaction mixture was extracted with ethyl acetate. The organic phase was separated, dried over sodium sulfate, and concentrated under reduced pressure. The resulting residue was purified by column chromatography (5% MeOH in dichloromethane) to obtain the title compound, a compound of this invention, as an off white solid (70 mg). .sup.1H NMR (500 MHz, DMSO-d.sub.6): δ ppm 2.66 (d, J=4.89 Hz, 3H), 4.56 (s, 2H), 6.87-7.01 (m, 1H), 7.32 (br d, J=16.14 Hz, 2H), 7.40 (s, 1H), 7.61-7.70 (m, 2H), 7.82 (d, J=9.29 Hz, 1H), 8.03 (s, 2H), 8.45-8.53 (m, 1H), 8.65 (d, J=4.40 Hz, 1H), 9.25 (s, 1H), 9.35 (d, J=1.96 Hz, 1H).
[0240] Specific compounds of Formula 1, prepared by the methods and variations as described in preceding Schemes 1-9 and Synthesis Examples 1-11, are shown in the Index Tables below. The following abbreviations may be used: Cmpd means Compound, t is tertiary, c is cyclo, Me is methyl, Et is ethyl and Ph is phenyl. A wavy line or “—” in a structure fragment denotes the attachment point of the fragment to the remainder of the molecule. The representation “—C(-ring members-)” is used to denote a ring in which the first and last ring members are bonded to a single carbon atom; for example, “—C(—CH.sub.2CH.sub.2—)CO.sub.2Me” denotes the following structure:
##STR00020##
[0241] The abbreviation “Ex.” stands for “Example” and is followed by a number indicating in which Synthesis Example the compound is prepared.
TABLE-US-00001 INDEX TABLE A-1
TABLE-US-00002 INDEX TABLE A-2
TABLE-US-00003 INDEX TABLE B-1
TABLE-US-00004 INDEX TABLE B-2
TABLE-US-00005 INDEX TABLE B-3
TABLE-US-00006 INDEX TABLE C-1
TABLE-US-00007 INDEX TABLE C-2
TABLE-US-00008 INDEX TABLE D
TABLE-US-00009 INDEX TABLE E-1
TABLE-US-00010 INDEX TABLE E-2
TABLE-US-00011 INDEX TABLE E-3
TABLE-US-00012 INDEX TABLE F
TABLE-US-00013 INDEX TABLE G
[0242] 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.
[0243] Useful formulations include both liquid and solid compositions. Liquid compositions include solutions (including emulsifiable concentrates), suspensions, emulsions (including microemulsions, oil in water emulsions, flowable concentrates 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, oil in water emulsion, flowable concentrate and suspoemulsion. The general types of nonaqueous liquid compositions are emulsifiable concentrate, microemulsifiable concentrate, dispersible concentrate and oil dispersion.
[0244] 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.
[0245] 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, but occasionally another suitable medium like an aromatic or paraffinic hydrocarbon or vegetable oil. 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.
[0246] 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.
TABLE-US-00014 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 0.001-99 5-99.999 0-15 High Strength Compositions 90-99 0-10 0-2
[0247] 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, N.J.
[0248] Liquid diluents include, for example, water, N,N-dimethylalkanamides (e.g., N,N-dimethylformamide), limonene, dimethyl sulfoxide, N-alkylpyrrolidones (e.g., N-methylpyrrolidinone), alkyl phosphates (e.g., triethylphosphate), 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, 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 alkyl and aryl benzoates, 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, cresol and benzyl alcohol. Liquid diluents also include glycerol esters of saturated and unsaturated fatty acids (typically C.sub.6-C.sub.22), 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 may 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.
[0249] 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.
[0250] 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 may be 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.
[0251] 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.
[0252] 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.
[0253] 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.
[0254] Compositions of this invention may also contain formulation auxiliaries and additives, known to those skilled in the art as formulation aids (some of which may be considered to also function as solid diluents, liquid diluents or surfactants). Such formulation auxiliaries and additives may 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.
[0255] 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 μm can be wet milled using media mills to obtain particles with average diameters below 3 μm. Aqueous slurries can be made into finished suspension concentrates (see, for example, U.S. Pat. No. 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 m 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, Dec. 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. Pat. No. 4,172,714. Water-dispersible and water-soluble granules can be prepared as taught in U.S. Pat. Nos. 4,144,050, 3,920,442 and DE 3,246,493. Tablets can be prepared as taught in U.S. Pat. Nos. 5,180,587, 5,232,701 and 5,208,030. Films can be prepared as taught in GB 2,095,558 and U.S. Pat. No. 3,299,566.
[0256] 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. Pat. No. 3,235,361, Col. 6, line 16 through Col. 7, line 19 and Examples 10-41; U.S. Pat. No. 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. Pat. No. 2,891,855, Col. 3, line 66 through Col. 5, line 17 and Examples 1-4; Klingman, 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, U K, 2000.
[0257] In the following Examples, all formulations are prepared in conventional ways. Compound numbers refer to compounds in Index Tables A-G. 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
[0258]
TABLE-US-00015 High Strength Concentrate Compound 11 98.5% silica aerogel 0.5% synthetic amorphous fine silica 1.0%
EXAMPLE B
[0259]
TABLE-US-00016 Wettable Powder Compound 12 65.0% dodecylphenol polyethylene glycol ether 2.0% sodium ligninsulfonate 4.0% sodium silicoaluminate 6.0% montmorillonite (calcined) 23.0%
EXAMPLE C
[0260]
TABLE-US-00017 Granule Compound 20 10.0% attapulgite granules 90.0% (low volatile matter, 0.71/ 0.30 mm; U.S.S. No. 25-50 sieves)
EXAMPLE D
[0261]
TABLE-US-00018 Extruded Pellet Compound 24 25.0% anhydrous sodium sulfate 10.0% crude calcium ligninsulfonate 5.0% sodium alkylnaphthalenesulfonate 1.0% calcium/magnesium bentonite 59.0%
EXAMPLE E
[0262]
TABLE-US-00019 Emulsifiable Concentrate Compound 25 10.0% polyoxyethylene sorbitol hexoleate 20.0% C.sub.6—C.sub.10 fatty acid methyl ester 70.0%
EXAMPLE F
[0263]
TABLE-US-00020 Microemulsion Compound 26 5.0% polyvinylpyrrolidone-vinyl acetate copolymer 30.0% alkylpolyglycoside 30.0% glyceryl monooleate 15.0% water 20.0%
EXAMPLE G
[0264]
TABLE-US-00021 Seed Treatment Compound 30 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
[0265]
TABLE-US-00022 Fertilizer Stick Compound 31 2.5% pyrrolidone-styrene copolymer 4.8% tristyrylphenyl 16-ethoxylate 2.3% talc 0.8% corn starch 5.0% slow-release fertilizer 36.0% kaolin 38.0% water 10.6%
EXAMPLE I
[0266]
TABLE-US-00023 Suspension Concentrate compound 47 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% 1,2-benzisothiazolin-3-one 0.1% water 53.7%
EXAMPLE J
[0267]
TABLE-US-00024 Emulsion in Water compound 56 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% 1,2-benzisothiazolin-3-one 0.1% aromatic petroleum based hydrocarbon 20.0 water 58.7%
EXAMPLE K
[0268]
TABLE-US-00025 Oil Dispersion compound 59 25% polyoxyethylene sorbitol hexaoleate 15% organically modified bentonite clay 2.5% fatty acid methyl ester 57.5%.sup.
EXAMPLE L
[0269]
TABLE-US-00026 Suspoemulsion compound 62 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% 1,2-benzisothiazolin-3-one 0.1% aromatic petroleum based hydrocarbon 20.0% water 53.7%
[0270] 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.
[0271] 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®, INVICTA RR2 PRO™, and herbicide-tolerant varieties of corn, cotton, soybean and rapeseed such as ROUNDUP READY®, LIBERTY LINK®, IMI®, 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.
[0272] 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.
[0273] 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.
[0274] 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 suitable for systemic and/or non-systemic control of infestation or infection by parasites on animals. 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 combating parasites that infest agricultural working animals, such as cattle, sheep, goats, horses, pigs, donkeys, camels, buffalos, rabbits, hens, turkeys, ducks, geese and bees; pet animals and domestic animals such as dogs, cats, pet birds and aquarium fish; as well as so-called experimental animals, such as hamsters, guinea pigs, rats and mice. By combating these 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.
[0275] 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 (Spodoplera eridania Cramer), fall armyworm (Spodoptera frugiperda J. E. Smith), beet armyworm (Spodoptera exigua Hubner), cotton leafworm (Spodoptera littoralis Boisduval), yellowstriped armyworm (Spodoptera ornithogalli Guenée), black cutworm (Agrotis ipsilon Hufnagel), velvetbean caterpillar (Anticarsia gemmatalis Hubner), green fruitworm (Lithophane antennata Walker), cabbage armyworm (Barathra brassicae Linnaeus), soybean looper (Pseudoplusia includens Walker), cabbage looper (Trichoplusia ni Hubner), tobacco budworm (Heliothis virescens Fabricius)); borers, casebearers, webworms, coneworms, cabbageworms and skeletonizers from the family Pyralidae (e.g., European corn borer (Ostrinia nubilalis Hubner), 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 Guenée), green leafroller (Cnaphalocrocis medinalis), grape leaffolder (Desmia funeralis Hubner), melon worm (Diaphania nitidalis Stoll), cabbage center grub (Helluala hydralis Guenée), 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), striped riceborer (Chilo suppressalis Walker), 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 Hubner), apple bud moth (Pandemis pyrusana Kearfott), omnivorous leafroller (Platynota stultana Walsingham), barred fruit-tree tortrix (Pandemis cerasana Hubner), 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 (Lithocollelis 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 (Alaenius sprelulus 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.
[0276] 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.
[0277] 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. differentialis 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., Simuliun 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 pennslyvanicus 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 formosanis 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 (Goniocoles 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).
[0278] 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 caslaneum), granary weevil (Stiophilus granarius), Indian meal moth (Plodia interpunctella), Mediterranean flour beetle (Ephestia kuhniella) and flat or rusty grain beetle (Cryptolestis ferrugineus).
[0279] Compounds of the present invention may 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 Pralylenchus, 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.).
[0280] Compounds of the invention may have activity against pests in the order Lepidoptera (e.g., Alabama argillacea Hubner (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 Guenée (rice leaf roller), Crambus caliginosellus Clemens (corn root webworm), Crambus teterrellus Zincken (bluegrass webworm), Cydiapomonella Linnaeus (codling moth), Earias insulana Boisduval (spiny bollworm), Earias vittella Fabricius (spotted bollworm), Helicoverpa armigera Hubner (American bollworm), Helicoverpa zea Boddie (corn earworm), Heliothis virescens Fabricius (tobacco budworm), Herpetogramma licarsisalis Walker (sod webworm), Lobesia botrana Denis & Schiffermiller (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 Hubner (beet armyworm), Spodoptera litura Fabricius (tobacco cutworm, cluster caterpillar), Spodoptera frugiperda J. E. Smith (fall armyworm), Trichoplusia ni Hubner (cabbage looper) and Tuta absoluta Meyrick (tomato leafminer)).
[0281] Compounds of the invention 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 whitefly, 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 Stål (rice leafhopper), Nilaparvata lugens Stål (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).
[0282] Compounds of this invention 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), Halymorpha halys Stål (brown marmorated stink bug), 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 fleahopper). 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).
[0283] Note that some contemporary classification systems place Homoptera as a suborder within the order Hemiptera.
[0284] Of note is use of compounds of this invention for controlling western flower thrips (Frankliniella occidentalis). 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 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 sweetpotato whitefly (Bemisia tabaci).
[0285] Compounds of the present invention may also be useful for increasing vigor of a crop plant. This method comprises contacting the crop plant (e.g., foliage, flowers, fruit or roots) or the seed from which the crop plant is grown with a compound of Formula 1 in amount sufficient to achieve the desired plant vigor effect (i.e. biologically effective amount). Typically the compound of Formula 1 is applied in a formulated composition. Although the compound of Formula 1 is often applied directly to the crop plant or its seed, it can also be applied to the locus of the crop plant, i.e. the environment of the crop plant, particularly the portion of the environment in close enough proximity to allow the compound of Formula 1 to migrate to the crop plant. The locus relevant to this method most commonly comprises the growth medium (i.e. medium providing nutrients to the plant), typically soil in which the plant is grown. Treatment of a crop plant to increase vigor of the crop plant thus comprises contacting the crop plant, the seed from which the crop plant is grown or the locus of the crop plant with a biologically effective amount of a compound of Formula 1.
[0286] Increased crop vigor can result in one or more of the following observed effects: (a) optimal crop establishment as demonstrated by excellent seed germination, crop emergence and crop stand; (b) enhanced crop growth as demonstrated by rapid and robust leaf growth (e.g., measured by leaf area index), plant height, number of tillers (e.g., for rice), root mass and overall dry weight of vegetative mass of the crop; (c) improved crop yields, as demonstrated by time to flowering, duration of flowering, number of flowers, total biomass accumulation (i.e. yield quantity) and/or fruit or grain grade marketability of produce (i.e. yield quality); (d) enhanced ability of the crop to withstand or prevent plant disease infections and arthropod, nematode or mollusk pest infestations; and (e) increased ability of the crop to withstand environmental stresses such as exposure to thermal extremes, suboptimal moisture or phytotoxic chemicals.
[0287] The compounds of the present invention may increase the vigor of treated plants compared to untreated plants by killing or otherwise preventing feeding of phytophagous invertebrate pests in the environment of the plants. In the absence of such control of phytophagous invertebrate pests, the pests reduce plant vigor by consuming plant tissues or sap, or transmitting plant pathogens such as viruses. Even in the absence of phytophagous invertebrate pests, the compounds of the invention may increase plant vigor by modifying metabolism of plants. Generally, the vigor of a crop plant will be most significantly increased by treating the plant with a compound of the invention if the plant is grown in a nonideal environment, i.e. an environment comprising one or more aspects adverse to the plant achieving the full genetic potential it would exhibit in an ideal environment.
[0288] Of note is a method for increasing vigor of a crop plant wherein the crop plant is grown in an environment comprising phytophagous invertebrate pests. Also of note is a method for increasing vigor of a crop plant wherein the crop plant is grown in an environment not comprising phytophagous invertebrate pests. Also of note is a method for increasing vigor of a crop plant wherein the crop plant is grown in an environment comprising an amount of moisture less than ideal for supporting growth of the crop plant. Of note is a method for increasing vigor of a crop plant wherein the crop is rice. Also of note is a method for increasing vigor of a crop plant wherein the crop is maize (corn). Also of note is a method for increasing vigor of a crop plant wherein the crop is soybean.
[0289] 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, 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.
[0290] 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, afidopyropen ([(3S,4R,4aR,6S,6aS,12R,12aS,12bS)-3-[(cyclopropylcarbonyl)oxy]-1,3,4,4a,5,6,6a,12,12a,12b-decahydro-6,12-dihydroxy-4,6a,12b-trimethyl-11-oxo-9-(3-pyridinyl)-2H,11H-naphtho[2,1-b]pyrano[3,4-e]pyran-4-yl]methyl cyclopropanecarboxylate), amidoflumet, amitraz, avermectin, azadirachtin, azinphos-methyl, benfuracarb, bensultap, bifenthrin, bifenazate, bistrifluron, borate, buprofezin, cadusafos, carbaryl, carbofuran, cartap, carzol, chlorantraniliprole, chlorfenapyr, chlorfluazuron, chlorpyrifos, chlorpyrifos-methyl, chromafenozide, clofentezin, clothianidin, cyantraniliprole (3-bromo-1-(3-chloro-2-pyridinyl)-N-[4-cyano-2-methyl-6-[(methylamino)carbonyl]phenyl]-1H-pyrazole-5-carboxamide), cyclaniliprole (3-bromo-N-[2-bromo-4-chloro-6-[[(1-cyclopropylethyl)amino]carbonyl]phenyl]-1-(3-chloro-2-pyridinyl)-1H-pyrazole-5-carboxamide), cycloprothrin, cycloxaprid ((5S,8R)-1-[(6-chloro-3-pyridinyl)methyl]-2,3,5,6,7,8-hexahydro-9-nitro-5,8-Epoxy-1H-imidazo[1,2-a]azepine) 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, fenitrothion, fenothiocarb, fenoxycarb, fenpropathrin, fenvalerate, fipronil, flometoquin (2-ethyl-3,7-dimethyl-6-[4-(trifluoromethoxy)phenoxy]-4-quinolinyl methyl carbonate), flonicamid, flubendiamide, flucythrinate, flufenerim, flufenoxuron, flufenoxystrobin (methyl (αE)-2-[[2-chloro-4-(trifluoromethyl)phenoxy]methyl]-α-(methoxymethylene)benzeneacetate), flufensulfone (5-chloro-2-[(3,4,4-trifluoro-3-buten-1-yl)sulfonyl]thiazole), fluhexafon, fluopyram, flupiprole (1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-5-[(2-methyl-2-propen-1-yl)amino]-4-[(trifluoromethyl)sulfinyl]-1H-pyrazole-3-carbonitrile), flupyradifurone (4-[[(6-chloro-3-pyridinyl)methyl](2,2-difluoroethyl)amino]-2(5H)-furanone), fluvalinate, tau-fluvalinate, fonophos, formetanate, fosthiazate, halofenozide, heptafluthrin ([2,3,5,6-tetrafluoro-4-(methoxymethyl)phenyl]methyl 2,2-dimethyl-3-[(1Z)-3,3,3-trifluoro-1-propen-1-yl]cyclopropanecarboxylate), hexaflumuron, hexythiazox, hydramethylnon, imidacloprid, indoxacarb, insecticidal soaps, isofenphos, lufenuron, malathion, meperfluthrin ([2,3,5,6-tetrafluoro-4-(methoxymethyl)phenyl]methyl (1R,3S)-3-(2,2-dichloroethenyl)-2,2-dimethylcyclopropanecarboxylate), metaflumizone, metaldehyde, methamidophos, methidathion, methiodicarb, methomyl, methoprene, methoxychlor, metofluthrin, methoxyfenozide, metofluthrin, monocrotophos, monofluorothrin ([2,3,5,6-tetrafluoro-4-(methoxymethyl)phenyl]methyl 3-(2-cyano-1-propen-1-yl)-2,2-dimethylcyclopropanecarboxylate), nicotine, nitenpyram, nithiazine, novaluron, noviflumuron, oxamyl, parathion, parathion-methyl, permethrin, phorate, phosalone, phosmet, phosphamidon, pirimicarb, profenofos, profluthrin, propargite, protrifenbute, pyflubumide (1,3,5-trimethyl-N-(2-methyl-1-oxopropyl)-N-[3-(2-methylpropyl)-4-[2,2,2-trifluoro-1-methoxy-1-(trifluoromethyl)ethyl]phenyl]-1H-pyrazole-4-carboxamide), pymetrozine, pyrafluprole, pyrethrin, pyridaben, pyridalyl, pyrifluquinazon, pyriminostrobin (methyl (αE)-2-[[[2-[(2,4-dichlorophenyl)amino]-6-(trifluoromethyl)-4-pyrimidinyl]oxy]methyl]-α-(methoxymethylene)benzeneacetate), pyriprole, pyriproxyfen, rotenone, ryanodine, silafluofen, spinetoram, spinosad, spirodiclofen, spiromesifen, spirotetramat, sulprofos, sulfoxaflor (N-[methyloxido[1-[6-(trifluoromethyl)-3-pyridinyl]ethyl]-λ.sup.4-sulfanylidene]cyanamide), tebufenozide, tebufenpyrad, teflubenzuron, tefluthrin, terbufos, tetrachlorvinphos, tetramethrin, tetramethylfluthrin ([2,3,5,6-tetrafluoro-4-(methoxymethyl)phenyl]methyl 2,2,3,3-tetramethylcyclopropanecarboxylate), tetraniliprole, thiacloprid, thiamethoxam, thiodicarb, thiosultap-sodium, tioxazafen (3-phenyl-5-(2-thienyl)-1,2,4-oxadiazole), tolfenpyrad, tralomethrin, triazamate, trichlorfon, triflumezopyrim (2,4-dioxo-1-(5-pyrimidinylmethyl)-3-[3-(trifluoromethyl)phenyl]-2H-pyrido[1,2-a]pyrimidinium inner salt), triflumuron, Bacillus thuringiensis delta-endotoxins, entomopathogenic bacteria, entomopathogenic viruses and entomopathogenic fungi.
[0291] Of note are insecticides such as abamectin, acetamiprid, acrinathrin, afidopyropen, amitraz, avermectin, azadirachtin, benfuracarb, bensultap, bifenthrin, buprofezin, cadusafos, carbaryl, cartap, chlorantraniliprole, chlorfenapyr, chlorpyrifos, clothianidin, cyantraniliprole, cyclaniliprole, cycloprothrin, cyfluthrin, beta-cyfluthrin, cyhalothrin, gamma-cyhalothrin, lambda-cyhalothrin, cypermethrin, alpha-cypermethrin, zeta-cypermethrin, cyromazine, deltamethrin, dieldrin, dinotefuran, diofenolan, emamectin, endosulfan, esfenvalerate, ethiprole, etofenprox, etoxazole, fenitrothion, fenothiocarb, fenoxycarb, fenvalerate, fipronil, flometoquin, flonicamid, flubendiamide, flufenoxuron, flufenoxystrobin, flufensulfone, flupiprole, flupyradifurone, fluvalinate, formetanate, fosthiazate, heptafluthrin, hexaflumuron, hydramethylnon, imidacloprid, indoxacarb, lufenuron, meperfluthrin, metaflumizone, methiodicarb, methomyl, methoprene, methoxyfenozide, metofluthrin, monofluorothrin, nitenpyram, nithiazine, novaluron, oxamyl, pyflubumide, pymetrozine, pyrethrin, pyridaben, pyridalyl, pyriminostrobin, pyriproxyfen, ryanodine, spinetoram, spinosad, spirodiclofen, spiromesifen, spirotetramat, sulfoxaflor, tebufenozide, tetramethrin, tetramethylfluthrin, thiacloprid, thiamethoxam, thiodicarb, thiosultap-sodium, tralomethrin, triazamate, triflumezopyrim, triflumuron, Bacillus thuringiensis delta-endotoxins, all strains of Bacillus thuringiensis and all strains of nucleo polyhedrosis viruses.
[0292] 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, Ind., 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).
[0293] 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, acetylcholinesterase (AChE) inhibitors such as the carbamates methomyl, oxamyl, thiodicarb, triazamate, and the organophosphates chlorpyrifos; GABA-gated chloride channel antagonists such as the cyclodienes dieldrin and endosulfan, and the phenylpyrazoles ethiprole and fipronil; sodium channel modulators such as the pyrethroids bifenthrin, cyfluthrin, beta-cyfluthrin, cyhalothrin, lambda-cyhalothrin, cypermethrin, deltamethrin, dimefluthrin, esfenvalerate, metofluthrin and profluthrin; nicotinic acetylcholinereceptor (nAChR) agonists such as the neonicotinoids acetamiprid, clothianidin, dinotefuran, imidacloprid, nitenpyram, nithiazine, thiacloprid, and thiamethoxam, and sulfoxaflor; nicotinic acetylcholine receptor (nAChR) allosteric activators such as the spinosyns spinetoram and spinosad; chloride channel activators such as the avermectins abamectin and emamectin; juvenile hormone mimics such as diofenolan, methoprene, fenoxycarb and pyriproxyfen; selective homopteran feeding blockers such as pymetrozine and flonicamid; mite growth inhibitors such as etoxazole; inhibitors of mitochondrial ATP synthase such as propargite; ucouplers of oxidative phosphorylation via disruption of the proton gradient such as chlorfenapyr; nicotinic acetylcholine receptor (nAChR) channel blockers such as the nereistoxin analogs cartap; inhibitors of chitin biosynthesis such as the benzoylureas flufenoxuron, hexaflumuron, lufenuron, novaluron, noviflumuron and triflumuron, and buprofezin; dipteran moulting disrupters such as cyromazine; ecdysone receptor agonists such as the diacylhydrazines methoxyfenozide and tebufenozide; octopamine receptor agonists such as amitraz; mitochondrial complex III electron transport inhibitors such as hydramethylnon; mitochondrial complex I electron transport inhibitors such as pyridaben; voltage-dependent sodium channel blockers such as indoxacarb; inhibitors of acetyl CoA carboxylase such as the tetronic and tetramic acids spirodiclofen, spiromesifen and spirotetramat; mitochondrial complex II electron transport inhibitors such as the β-ketonitriles cyenopyrafen and cyflumetofen; ryanidine receptor modulators such as the anthranilic diamides chlorantraniliprole, cyantraniliprole and cyantraniliprole, diamides such as flubendiamide, and ryanodine receptor ligands such as ryanodine; compounds wherein the target site responsible for biological activity is unknown or uncharacterized such as azadirachtin, bifenazate, pyridalyl, pyrifluquinazon and triflumezopyrim; microbial disrupters of insect midgut membranes such as Bacillus thuringensis and the delta-endotoxins they produce and Bacillus sphaericus; and biological agents including nucleo polyhedro viruses (NPV) and other naturally occurring or genetically modified insecticidal viruses.
[0294] Further examples of biologically active compounds or agents with which compounds of this invention can be formulated are: fungicides such as acibenzolar-S-methyl, aldimorph, ametoctradin, amisulbrom, anilazine, azaconazole, azoxystrobin, benalaxyl (including benalaxyl-M), benodanil, benomyl, benthiavalicarb (including benthiavalicarb-isopropyl), benzovindiflupyr, bethoxazin, binapacryl, biphenyl, bitertanol, bixafen, blasticidin-S, boscalid, bromuconazole, bupirimate, buthiobate, carboxin, carpropamid, captafol, captan, carbendazim, chloroneb, chlorothalonil, chlozolinate, copper hydroxide, copper oxychloride, copper sulfate, coumoxystrobin, cyazofamid, cyflufenamid, cymoxanil, cyproconazole, cyprodinil, dichlofluanid, diclocymet, diclomezine, dicloran, diethofencarb, difenoconazole, diflumetorim, dimethirimol, dimethomorph, dimoxystrobin, diniconazole (including diniconazole-M), dinocap, dithianon, dithiolanes, dodemorph, dodine, econazole, etaconazole, edifenphos, enoxastrobin (also known as enestroburin), epoxiconazole, ethaboxam, ethirimol, etridiazole, famoxadone, fenamidone, fenaminstrobin, fenarimol, fenbuconazole, fenfuram, fenhexamide, fenoxanil, fenpiclonil, fenpropidin, fenpropimorph, fenpyrazamine, fentin acetate, fentin hydroxide, ferbam, ferimzone, flometoquin, fluazinam, fludioxonil, flufenoxystrobin, flumorph, fluopicolide, fluopyram, fluoxastrobin, fluquinconazole, flusilazole, flusulfamide, flutianil, flutolanil, flutriafol, fluxapyroxad, folpet, fthalide (also known as phthalide), fuberidazole, furalaxyl, furametpyr, hexaconazole, hymexazole, guazatine, imazalil, imibenconazole, iminoctadine albesilate, iminoctadine triacetate, iodicarb, ipconazole, isofetamid, iprobenfos, iprodione, iprovalicarb, isoprothiolane, isopyrazam, isotianil, kasugamycin, kresoxim-methyl, mancozeb, mandipropamid, mandestrobin, maneb, mapanipyrin, mepronil, meptyldinocap, metalaxyl (including metalaxyl-M/mefenoxam), metconazole, methasulfocarb, metiram, metominostrobin, metrafenone, myclobutanil, naftitine, neo-asozin (ferric methanearsonate), nuarimol, octhilinone, ofurace, orysastrobin, oxadixyl, oxathiapiprolin, oxolinic acid, oxpoconazole, oxycarboxin, oxytetracycline, penconazole, pencycuron, penflufen, penthiopyrad, perfurazoate, phosphorous acid (including salts thereof, e.g., fosetyl-aluminm), picoxystrobin, piperalin, polyoxin, probenazole, prochloraz, procymidone, propamocarb, propiconazole, propineb, proquinazid, prothiocarb, prothioconazole, pyraclostrobin, pyrametostrobin, pyraoxystrobin, pyrazophos, pyribencarb, pyributacarb, pyrifenox, pyriofenone, perisoxazole, pyrimethanil, pyrifenox, pyrrolnitrin, pyroquilon, quinconazole, quinmethionate, quinoxyfen, quintozene, silthiofam, sedaxane, simeconazole, spiroxamine, streptomycin, sulfur, tebuconazole, tebufloquin, teclofthalam, tecloftalam, tecnazene, terbinafine, tetraconazole, thiabendazole, thifluzamide, thiophanate, thiophanate-methyl, thiram, tiadinil, tolclofos-methyl, tolprocarb, tolyfluanid, triadimefon, triadimenol, triarimol, triazoxide, tribasic copper sulfate, triclopyricarb, tridemorph, trifloxystrobin, triflumizole, trimoprhamide tricyclazole, trifloxystrobin, triforine, triticonazole, uniconazole, validamycin, valifenalate (also known as valifenal), vinclozolin, zineb, ziram, zoxamide and 1-[4-[4-[5-(2,6-difluorophenyl)-4,5-dihydro-3-isoxazolyl]-2-thiazolyl]-1-piperidinyl]-2-[5-methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl]ethanone; nematocides such as fluopyram, spirotetramat, thiodicarb, fosthiazate, abamectin, iprodione, fluensulfone, dimethyl disulfide, tioxazafen, 1,3-dichloropropene (1,3-D), metam (sodium and potassium), dazomet, chloropicrin, fenamiphos, ethoprophos, cadusaphos, terbufos, imicyafos, oxamyl, carbofuran, tioxazafen, Bacillus firmus and Pasieuria nishizawae; bactericides such as streptomycin; acaricides such as amitraz, chinomethionat, chlorobenzilate, cyhexatin, dicofol, dienochlor, etoxazole, fenazaquin, fenbutatin oxide, fenpropathrin, fenpyroximate, hexythiazox, propargite, pyridaben and tebufenpyrad.
[0295] 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.
[0296] 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.
[0297] 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, 2.sup.nd Edition, L. G. Copping, Ed., British Crop Protection Council, Farnham, Surrey, U. K., 2001.
[0298] 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.
[0299] 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.
[0300] 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.
[0301] 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).
[0302] Compounds of the invention are useful in treating all plants, plant parts and seeds. Plant and seed varieties and cultivars can be obtained by conventional propagation and breeding methods or by genetic engineering methods. Genetically modified plants or seeds (transgenic plants or seeds) are those in which a heterologous gene (transgene) has been stably integrated into the plant's or seed's genome. A transgene that is defined by its particular location in the plant genome is called a transformation or transgenic event.
[0303] Genetically modified plant and seed cultivars which can be treated according to the invention include those that are resistant against one or more biotic stresses (pests such as nematodes, insects, mites, fungi, etc.) or abiotic stresses (drought, cold temperature, soil salinity, etc.), or that contain other desirable characteristics. Plants and seeds can be genetically modified to exhibit traits of, for example, herbicide tolerance, insect-resistance, modified oil profiles or drought tolerance.
[0304] Treatment of genetically modified plants and seeds with compounds of the invention may result in super-additive or synergistic effects. For example, reduction in application rates, broadening of the activity spectrum, increased tolerance to biotic/abiotic stresses or enhanced storage stability may be greater than expected from just simple additive effects of the application of compounds of the invention on genetically modified plants and seeds.
[0305] 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. Seed treatments with compounds of this invention can also increase vigor of plants growing from the seed.
[0306] 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.
[0307] 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.
[0308] Other insecticides with which compounds of Formula 1 can be formulated to provide mixtures useful in seed treatment include abamectin, acetamiprid, acrinathrin, amitraz, avermectin, azadirachtin, bensultap, bifenthrin, buprofezin, cadusafos, carbaryl, carbofuran, 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, methiocarb, methomyl, methoprene, methoxyfenozide, nitenpyram, nithiazine, novaluron, oxamyl, pymetrozine, pyrethrin, pyridaben, pyridalyl, pyriproxyfen, ryanodine, spinetoram, spinosad, spirodiclofen, spiromesifen, spirotetramat, sulfoxaflor, tebufenozide, tetramethrin, thiacloprid, thiamethoxam, thiodicarb, thiosultap-sodium, tralomethrin, triazamate, triflumuron, Bacillus thuringiensis delta-endotoxins, all strains of Bacillus thuringiensis and all strains of nucleo polyhedrosis viruses.
[0309] Fungicides with which compounds of Formula 1 can be formulated to provide mixtures useful in seed treatment include 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.
[0310] 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 subtilis and Pasteuria penetrans. A suitable Bacillus firmus strain is strain CNCM I-1582 (GB-126) which is commercially available as BioNem™. A suitable Bacillus cereus strain is strain NCMM I-1592. Both Bacillus strains are disclosed in U.S. Pat. No. 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.
[0311] 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.
[0312] 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.
[0313] 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.
[0314] 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.
[0315] 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.
[0316] 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.
[0317] One embodiment of the present invention relates to a method for controlling invertebrate pests, comprising diluting the pesticidal composition of the present invention (a compound of Formula 1 formulated with surfactants, solid diluents and liquid diluents or a formulated mixture of a compound of Formula 1 and at least one other pesticide) with water, and optionally adding an adjuvant to form a diluted composition, and contacting the invertebrate pest or its environment with an effective amount of said diluted composition.
[0318] Although a spray composition formed by diluting with water a sufficient concentration of the present pesticidal composition can provide sufficient efficacy for controlling invertebrate pests, separately formulated adjuvant products can also be added to spray tank mixtures. These additional adjuvants are commonly known as “spray adjuvants” or “tank-mix adjuvants”, and include any substance mixed in a spray tank to improve the performance of a pesticide or alter the physical properties of the spray mixture. Adjuvants can be surfactants, emulsifying agents, petroleum-based crop oils, crop-derived seed oils, acidifiers, buffers, thickeners or defoaming agents. Adjuvants are used to enhancing efficacy (e.g., biological availability, adhesion, penetration, uniformity of coverage and durability of protection), or minimizing or eliminating spray application problems associated with incompatibility, foaming, drift, evaporation, volatilization and degradation. To obtain optimal performance, adjuvants are selected with regard to the properties of the active ingredient, formulation and target (e.g., crops, insect pests).
[0319] Among the spray adjuvants, oils including crop oils, crop oil concentrates, vegetable oil concentrates and methylated seed oil concentrates are most commonly used to improve the efficacy of pesticides, possibly by means of promoting more even and uniform spray deposits. In situations where phytotoxicity potentially caused by oils or other water-immiscible liquids are of concern, spray compositions prepared from the composition of the present invention will generally not contain oil-based spray adjuvants. However, in situations where phytotoxicity caused by oil-based spray adjuvants is commercially insignificant, spray compositions prepared from the composition of the present composition can also contain oil-based spray adjuvants, which can potentially further increase control of invertebrate pests, as well as rainfastness.
[0320] Products identified as “crop oil” typically contain 95 to 98% paraffin or naphtha-based petroleum oil and 1 to 2% of one or more surfactants functioning as emulsifiers. Products identified as “crop oil concentrates” typically consist of 80 to 85% of emulsifiable petroleum-based oil and 15 to 20% of nonionic surfactants. Products correctly identified as “vegetable oil concentrates” typically consist of 80 to 85% of vegetable oil (i.e. seed or fruit oil, most commonly from cotton, linseed, soybean or sunflower) and 15 to 20% of nonionic surfactants. Adjuvant performance can be improved by replacing the vegetable oil with methyl esters of fatty acids that are typically derived from vegetable oils. Examples of methylated seed oil concentrates include MSO® Concentrate (UAP-Loveland Products, Inc.) and Premium MSO Methylated Spray Oil (Helena Chemical Company).
[0321] The amount of adjuvants added to spray mixtures generally does not exceed about 2.5% by volume, and more typically the amount is from about 0.1 to about 1% by volume. The application rates of adjuvants added to spray mixtures are typically between about 1 to 5 L per hectare. Representative examples of spray adjuvants include: Adigor® (Syngenta) 47% methylated rapeseed oil in liquid hydrocarbons, Silwet® (Helena Chemical Company) polyalkyleneoxide modified heptamethyltrisiloxane and Assist® (BASF) 17% surfactant blend in 83% paraffin based mineral oil.
[0322] 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 the case may be. 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.
[0323] 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. See Index Tables A-G for compound descriptions.
BIOLOGICAL EXAMPLES OF THE INVENTION
Formulation and Spray Methodology for Tests A-F
[0324] 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, Colo., USA). The formulated compounds were applied in 1 mL of liquid through a SUJ2 atomizer nozzle with ⅛ JJ custom body (Spraying Systems Co. Wheaton, Ill., USA) positioned 1.27 cm (0.5 inches) above the top of each test unit. Test compounds were sprayed at the rates indicated, and each test was replicated three times.
Test A
[0325] For evaluating control of diamondback moth (Plutella xylostella (L.)) the test unit consisted of a small open container with a 12-14-day-old mustard plant inside. This was pre-infested with ˜50 neonate larvae that were dispensed into the test unit via corn cob grits using an inoculator. The larvae moved onto the test plant after being dispensed into the test unit.
[0326] Test compounds were formulated and sprayed at 250. After spraying of the formulated test compound, each test unit was allowed to dry for 1 hour 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, and larvae were assessed for mortality.
[0327] 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): 11 and 111.
Test B
[0328] For evaluating control of green peach aphid (Myzus persicae (Sulzer)) 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.
[0329] Test compounds were formulated and sprayed at 250 and/or 50 ppm. After spraying of the formulated test compound, each test unit was allowed to dry for 1 hour 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.
[0330] Of the compounds of Formula 1 tested at 250 ppm, the following resulted in at least 80% mortality: 10, 11, 12, 19, 20, 22, 24, 25, 26, 29, 31, 35, 36, 39, 43, 45, 46, 60, 61, 62, 64, 65, 66, 71, 72, 73, 74, 75, 78 and 79.
[0331] Of the compounds of Formula 1 tested at 50 ppm, the following resulted in at least 80% mortality: 10, 11, 12, 20, 24, 25, 26, 29, 30, 31, 35, 45, 46, 47, 56, 58, 59, 60, 61, 62, 64, 65, 66, 68, 69, 70, 71, 72, 73, 74, 75, 78, 79, 80, 84, 85, 86, 87, 96, 102, 103, 104, 106, 107, 122, 123, 125, 135, 137, 139, 145, 146, 151, 153, 154, 155, 156, 158, 160, 161, 162 and 163.
Test C
[0332] For evaluating control of cotton melon aphid (Aphis gossypii (Glover)) 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, and the soil of the test unit was covered with a layer of sand.
[0333] Test compounds were formulated and sprayed at 250 and/or 50 ppm. After spraying, the test units were maintained in a growth chamber for 6 days at 19° C. and 70% relative humidity. Each test unit was then visually assessed for insect mortality.
[0334] Of the compounds of Formula 1 tested at 250 ppm, the following resulted in at least 80% mortality: 10, 11, 12, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 29, 31, 33, 34, 35, 37, 38, 45, 46, 62, 64, 65, 66, 71, 72, 76 and 77.
[0335] Of the compounds of Formula 1 tested at 50 ppm, the following resulted in at least 80% mortality: 10, 11, 12, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 29, 30, 31, 33, 34, 35, 45, 46, 47, 52, 54, 56, 59, 62, 64, 65, 66, 67, 69, 70, 71, 72, 76, 77, 78, 80, 84, 85, 86, 87, 96, 101, 102, 103, 104, 105, 106, 107, 112, 114, 119, 122, 123, 125, 128, 129, 131, 135, 137, 139, 145, 146, 151, 154, 155, 156, 158, 160, 161, 162, 163, 164 and 169.
Test D
[0336] For evaluating control of potato leafhopper (Empoasca fabae (Harris)) 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 of the test compound.
[0337] Test compounds were formulated and sprayed at 250 and/or 50 ppm. After spraying of the formulated test compound, the test units were allowed to dry for 1 hour before they were post-infested with 5 potato leafhoppers (18-to-21-day-old adults). A black, screened cap was placed on the top of the test unit, and the test units were held for 6 days in a growth chamber at 20° C. and 70% relative humidity. Each test unit was then visually assessed for insect mortality.
[0338] Of the compounds of Formula 1 tested at 250 ppm, the following resulted in at least 80% mortality: 80, 81, 83 and 163.
Test E
[0339] For evaluating control of the sweetpotato whitefly (Bemisia tabaci (Gennadius)) through contact and/or systemic means, the test unit consisted of a small open container with a 12-14-day-old cotton plant inside. Prior to the spray application, both cotyledons were removed from the plant, leaving one true leaf for the assay. Adult whiteflies were allowed to lay eggs on the plant and then were removed from the test unit. Cotton plants infested with at least 15 eggs were submitted to the test for spraying.
[0340] Test compounds were formulated and sprayed at 250 and/or 50 ppm. After spraying, the test units were allowed to dry for 1 hour. The cylinders were then removed, and the units were taken to a growth chamber and held for 13 days at 28° C. and 50-70% relative humidity. Each test unit was then visually assessed for insect mortality.
[0341] Of the compounds of Formula 1 tested at 250 ppm, the following resulted in at least 50% mortality: 2, 12, 25, 29, 47, 48, 55, 56, 57, 58, 59, 62, 64, 84, 102, 104 and 106.
[0342] Of the compounds of Formula 1 tested at 50 ppm, the following resulted in at least 50% mortality: 24, 25, 47, 62, 65, 66, 102 and 104.
Test F
[0343] For evaluating control of the Western Flower Thrips (Frankliniellla occidentalis (Pergande)) 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.
[0344] Test compounds were formulated and sprayed at 250 and/or 50 ppm. After spraying, the test units were allowed to dry for 1 hour, and then 22-27 adult thrips were added to each unit. A black, screened cap was placed on top, and the test units were held for 6 days at 25° C. and 45-55% relative humidity.
[0345] Of the compounds of Formula 1 tested at 250 ppm, the following provided very good to excellent levels of control efficacy (30% or less plant damage and/or 100% mortality): 18, 29, 31, 79 and 90.
[0346] Of the compounds of Formula 1 tested at 50 ppm, the following provided very good to excellent levels of control efficacy (30% or less plant damage and/or 100% mortality): 18.