TITLE ARTHROPODICIDAL SEMICARBAZONES This invention pertains to substituted semicarbazones useful as broad spectrum arthropodicides, particularly for control of pests of the Orders Lepidoptera and Coleoptera. WO 90/07495 generically discloses the compounds of the present invention.

SUMMARY OF THE INVENTION The present invention comprises compounds:

Compound I Compound π

including enantiomers, agriculturally suitable salts thereof, agricultural compositions containing them and their use to control arthropods in both agronomic and nonagronomic environments. The compounds can exist as enantiomers. One skilled in the art will appreciate that one enantiomer may be more active and how to separate said enantiomers. Accordingly, the present invention comprises the racemic mixture, individual enantiomers and optically active mixtures of the enantiomers of the compounds as well as their agriculturally suitable salts. DETAILS OF THE INVENTION

Compound I and Compound π can be synthesized by the procedures taught in WO 90/07495 and, in particular, as illustrated in Schemes 1 and 2 and detailed in Examples 1 and 2.

Scheme 1

Scheme 2

1) LDA

VI

EXAMPLE 1 Preparation of 2-(2-ethyl-4-fluoro-2.3-dihvdro-lH-inden-l-ylidene.-N-r(4- Irifluoromethoxylphenyl .hydrazinecarboxamide (Compound I) To a suspension of sodium hydride (13.8 g, 50% suspension in mineral oil, 0.34 mol) in tetrahydrofuran (400 mL) was added diethyl ethylmalonate

(III, 59.7 g, 0.32 mol). The resulting exothermic reaction was stirred until the solution became clear. A solution of 2-fluorobenzylbromide (50.0 g, 0.265 mol) in tetrahydrofuran (50 mL) was added slowly. After complete addition, the mixture was heated to reflux for five hours, cooled to room temperature and poured into 5% aqueous hydrochloric acid (300 mL). The aqueous phase was washed with ether (3 x 300 mL) and the combined organic phases were washed with saturated sodium chloride solution, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure to give 78 g of a yellow oil. This oil (78 g) was dissolved in methanol (200 mL) and treated with a 35% solution of sodium hydroxide in water (200 mL) and the resulting suspension heated to reflux for 4 h. The mixture was poured into water (200 mL) and washed once with ether (200 rnL). The aqueous phase was acidified to a pH of 2 with concentrated hydrochloric acid and then extracted with ether (3 x 200 mL). The combined organic phases were dried over magnesium sulfate, filtered and concentrated under reduced pressure. The resulting oil was dissolved in xylenes (300 mL) and heated to reflux for 18 h. After cooling to room temperature, the mixture was concentrated under reduced pressure to give 55.3 g of an oil. This oil 55.3 g was added in three portions over 30 min to 610 g of mechanically stirred polyphosphoric acid (PPA) heated to 60°C. The mixture was then heated to 100°C for 1.5 h. After cooling to 60°C, ice was added and the mixture washed with toluene (2 x 300 mL). The combined organic phases were washed with saturated aqueous sodium bicarbonate solution (100 mL) and saturated aqueous sodium chloride solution (100 mL), dried over magnesium sulfate, filtered and concentrated under reduced pressure. The resulting dark oil was chromatographed on silica gel using a 5:95 ethyl acetate:hexanes eluent to provide 31.4 g of 2-ethyl-4-fluoro-2,3-dihydro-l H-inden- 1 -one (IV). -1H ΝMR (200 Mz, CDC1 ₃ ) δ 7.6 (d,lH), 7.4 (m,lH), 7.3 (t,lH), 3.1 (AB of ABX,2H), 2.65 (m,lH), 2.0 (m,lH), 1.6 (m,lH), 1.0 (t,3H).

Compound IV (30.9 g) was dissolved in anhydrous ethanol (75 mL) and treated with hydrazine monohydrate (10.5 g, 0.21 mol) and the resulting mixture

was heated to reflux for 48 h. After cooling to room temperature, ethanol was removed under reduced pressure. The resulting oil was diluted with ether and washed once with 5.0% sodium bicarbonate solution. The organic layer was washed with brine, dried over magnesium sulfate and filtered. The filtrate was treated with p rα-(trifluoromethoxy)phenyl isocyanate (34.5 g, 0.17 mol) causing a white precipitate to form. After 10 min, the precipitate was collected and dried under vacuum to provide 44.0 g of the title compound. After 24 h, the mother liquor was reflltered to provide an additional 1.5 g of the title compound that was identical to the first precipitate by 1H NMR. The two precipitates were combined, mp 177-179°C. *H NMR (400 Mz, Me ₂ SO-d ₆ ) δ 10.2 (s,lH), 9.15 (s,lH), 7.8 (m,3H), 7.3 (m,3H), 7.2 (t,lH), 3.5 (m,lH), 3.2 (dd,lH), 2.8 (d, 1H), 1.8 (m,lH), 1.3 (m,3H), 0.9 (t,3H).

EXAMPLE 2 Preparation of 2-(5-chloro-2.3-dihydro-2-propyl- 1 H-inden- 1 -ylidene .- N-r(4-trifluoromethoxy .phenyllhvdrazinecarboxamide (Compound ID

Lithium diisopropylamide (LDA) was prepared by combining 7.0 mL (50 mmol) of diisopropyl amine and 100 mL of tetrahydrofuran. To this mixture cooled to approximately -78°C was added via a syringe 20.0 mL of n-BuLi (2.5 M in hexane). The reaction mixture was stirred for approximately 3 min and 6.5 g of ethyl valerate (7.4 mL, 50 mmol) was added dropwise. The reaction mixture was stirred for an additonal 3 min and then 8.0 g of 3-chlorobenzylchloride (V, 50 mmol) was added dropwise. The reaction mixture was allowed to warm to -10°C over 30 min, quenched by adding 100 mL of 0.2 Ν HC1 and then partitioned between water and diethyl ether. The ether layer was washed twice with water, dried over magnesium sulfate, filtered and concentrated under reduced pressure to yield 14.2 g of a yellow oil. The oil was purified by chromatography on silica gel eluting with 2.5% ethyl acetate in hexane to yield a mixture of products by thin layer chromatography (silica gel, 5:95 ethyl acetate:hexane). The product was then chromatographed on silica gel and eluted using hexane to obtain 2.07 g of a clear oil. ^H ΝMR was consistent with ethyl 3-propyl-α-propylbenzenepropanoate.

To hydrolyze to the acid, the oil (2.07 g) was combined with 40 mL of methanol, 10 mL of water and 3.0 mL of 50% aqueous sodium hydroxide. This mixture was heated to reflux and allowed to reflux overnight. The methanol was removed under reduced pressure, and the residue partitioned in diethyl ether and

water. The ether layer was washed with water and the combined water layers were acidified, extracted 3 times with diethyl ether. The ether layers were combined, dried over magnesium sulfate, filtered and concentrated under reduced pressure. The resulting oil was dissolved in carbon tetrachloride and reconcentrated under reduced pressure to yield 1.58 g of a yellow oil. H NMR was consistent with the acid.

This oil (1.58 g) dissolved in a small amount of toluene was added with stirring to 30 g of polyphosphoric acid (PPA) heated to 60°C. The mixture was then heated to 115°C for 1.5 h. After cooling, the reaction was quenched with 60 mL of water and partitioned between water and toluene. The organic layer was washed with 5.0% sodium bicarbonate, dried over magnesium sulfate, filtered and concentrated under reduced pressure to yield 1.35 g of a yellow oil. This oil was chromatographed on silica gel and eluted with 7.0% ethyl acetate in hexane to yield 0.73 g of 5-chloro-2,3-dihydro-2-propyl-lH-inden-l-one (VI) as a yellow oil. The H NMR was consistent with the assigned structure (VI).

Compound VI (0.73 g) was dissolved in anhydrous ethanol (10 mL) and treated with hydrazine monohydrate (0.5 mL) and the resulting mixture was heated and allowed to reflux overnight. After cooling to room temperature, ethanol was removed under reduced pressure. The resulting oil was partitioned between ether and 5.0% aqueous sodium bicarbonate solution. The aqueous layer was washed twice with ether, the ether layers combined, washed with water, dried over magnesium sulfate and filtered. The ether was removed under reduced pressure to yield 0.67 g of a yellow oil. To 0.34 g of this oil in 5 mL of tetrahydrofuran was added /?αrα-(trifluoromethoxy)phenyl isocyanate (0.31 g, 1.51 mmol). The reaction mixture was allowed to stir overnight and concentrated under reduced pressure. The resulting residue was triturated with diethyl ether, filtered and dried to yield 0.26 g of the title compound, mp 174-176°C: *H NMR (200 Mz, CDC1 ₃ ) δ 8.28 (s,lH), 7.95 (s,lH), 7.6 (m,3H), 7.3-7.1 (m,4H), 3.3-3.1 (m,2H), 2.82 (d,lH), 1.7 (m,lH), 1.4 (m,3H), 0.94 (t,3H).

Formulation Utility

Compounds of this invention will generally be used in formulation with an agriculturally suitable carrier comprising a liquid or solid diluent. Useful formulations include dusts, granules, baits, pellets, solutions, suspensions, emulsions, wettable powders, emulsifiable concentrates, dry flowables and the

like, consistent with the physical properties of the active ingredient, mode of application and environmental factors such as soil type, moisture and temperature. Sprayable formulations can be extended in suitable media and used at spray volumes from about one to several hundred liters per hectare. High strength compositions are primarily used as intermediates for further formulation. The formulations will typically contain effective amounts of active ingredient, diluent and surfactant within the following approximate ranges which add up 100 weight percent.

Weight Percent

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

Typical solid diluents are described in Watkins, et al., Handbook of

Insecticide Dust Diluents and Carriers, 2nd Ed., Dorland Books, Caldwell, New Jersey. Typical liquid diluents and solvents are described in Marsden, Solvents Guide, 2nd Ed., Interscience, New York, 1950. McCutcheon's Detergents and Emulsifiers Annual, Allured Publ. Corp., Ridgewood, New Jersey, as well as Sisely and Wood, Encyclopedia of Surface Active Agents, Chemical Publ. Co., Inc., New York, 1964, list surfactants and recommended uses. All formulations can contain minor amounts of additives to reduce foam, caking, corrosion, microbiological growth, and the like.

Solutions are prepared by simply mixing the ingredients. Fine solid compositions are made by blending and, usually, grinding as in a hammer mill or fluid energy mill. Water-dispersible granules can be produced by agglomerating a fine powder composition; see for example, Cross et al., Pesticide Formulations, Washington, D.C., 1988, pp 251-259. Suspensions are prepared by wet-milling; see, for example, U.S. 3,060,084. Granules and pellets can be made by spraying the active material upon preformed granular carriers or by agglomeration

techniques. See Browning, "Agglomeration", Chemical Engineering, December 4, 1967, pp 147-148, Perry's Chemical Engineer's Handbook, 4th Ed., McGraw-Hill, New York, 1963, pages 8-57 and following, and WO 91/13546. For further information regarding the art of formulation, see U.S. 3,235,361, Col. 6, line 16 through Col. 7, line 19 and Examples 10-41 ; U.S. 3,309,192, Col. 5, line 43 through Col. 7, line 62 and Examples 8, 12, 15, 39, 41, 52, 53, 58, 132, 138 -140, 162-164, 166, 167 and 169-182; U.S.2,891,855, Col. 3, line 66 through Col. 5, line 17 and Examples 1-4; Klingman, Weed Control as a Science, John Wiley and Sons, Inc., New York, 1961, pp 81-96; and Hance et al., Weed Control Handbook, 8th Ed., Blackwell Scientific Publications, Oxford, 1989.

In the following Examples, all percentages are by weight and all formulations are prepared in conventional ways.

Example A Wettable Powder

Compound I 65.0% dodecylphenol polyethylene glycol ether 2.0% sodium ligninsulfonate 4.0% sodium silicoaluminate 6.0% montmorillonite (calcined) 23.0%.

Example B Granule

Compound I 10.0% attapulgite granules (low volatile matter, 0.71/0.30 mm; U.S.S. No.

25-50 sieves) 90.0%.

Example C Extruded Pellet

Compound II 25.0% anhydrous sodium sulfate 10.0% crude calcium ligninsulfonate 5.0% sodium alkylnaphthalenesulfonate 1.0% calcium/magnesium bentonite 59.0%.

Example D Emulsifiable Concentrate

Compound II 20.0% blend of oil soluble sulfonates and polyoxyethylene ethers 10.0% isophorone 70.0%.

The compounds of this invention exhibit activity against a wide spectrum of foliar-feeding, fruit-feeding, stem or root feeding, seed-feeding, aquatic and soil-inhabiting arthropods (term "arthropods" includes insects, mites and nematodes) which are pests of growing and stored agronomic crops, forestry, greenhouse crops, ornamentals, nursery crops, stored food and fiber products, livestock, household, and public and animal health. Those skilled in the art will appreciate that not all compounds are equally effective against all growth stages of all pests. Nevertheless, all of the compounds of this invention display activity against pests that include: eggs, larvae and adults of the Order Lepidoptera; eggs, foliar-feeding, fruit-feeding, root-feeding, seed-feeding larvae and adults of the Order Coleoptera; eggs, immatures and adults of the Orders Hemiptera and Homoptera; eggs, larvae, nymphs and adults of the Order Acari; eggs, immatures and adults of the Orders Thysanoptera, Orthoptera and Dermaptera; eggs, immatures and adults of the Order Diptera; and eggs, junveniles and adults of the Phylum Nematoda. The compounds of this invention are also active against pests of the Orders Hymenoptera, Isoptera, Siphonaptera, Blattaria, Thysanura and Psocoptera; pests belonging to the Class Arachnida and Phylum Platyhelminthes. Specifically, the compounds are active against southern corn rootworm (Diabrotica undecimpunctata howardi), aster leafhopper (Mascrosteles fascifrons), boll weevil (Anthonomus grandis), two-spotted spider mite (Tetranychus urticae), fall armyworm (Spodopterafrugiperda), black bean aphid (Aphis fabae), tobacco budworm (Heliothis virescens), rice water weevil (Lissorhoptrus oryzophilus), rice leaf beetle (Oulema oryzae), whitebacked planthopper (Sogatellafurcifera), green leafhopper (Nephotettix cincticeps), brown planthopper (Nilaparvata lugens), small brown planthopper (Laodelphax striatellus), rice stem borer (Chilo suppressalis), rice leafroller (Cnaphalocrocis medinalis), black rice stink bug (Scotinophara lurida), rice stink bug (Oebalus pugnax), rice bug (Leptocorisa chinensis), slender rice bug (Cletus puntiger), and southern green stink bug (Nezara viridula). The compounds are active on mites,

demonstrating ovicidal, larvicidal and chemosterilant activity against such families as Tetranychidae including Tetranychus urticae, Tetranychus cinnabarinus, Tetranychus mcdanieli, Tetranychus pacificus, Tetranychus turkestani, Byrobia rubrioculus, Panonychus ulmi, Panonychus citri, Eotetranychus carpini borealis, Eotetranychus, hicoriae, Eotetranychus sexmaculatus, Eotetranychus yumensis, Eotetranychus banksi and Oligonychus pratensis; Tenuipalpidae including Brevipalpus lewisi, Brevipalpus phoenicis, Brevipalpus calif ornicus and Brevipalpus obovatus; Eriophyidae including Phyllocoptruta oleivora, Eriophyes sheldoni, Aculus cornutus, Epitrimerus pyri and Eriophyes mangiferae. See WO 90/10623 and WO 92/00673 for more detailed pest descriptions.

Compounds of this invention can also be mixed with one or more other insecticides, fungicides, nematocides, bactericides, acaricides, growth regulators, chemosterilants, semiochemicals, repellants, attractants, pheromones, feeding stimulants or other biologically active compounds to form a multi-component pesticide giving an even broader spectrum of agricultural protection. Examples of other agricultural protectants with which compounds of this invention can be formulated are: insecticides such as avermectin B, monocrotophos, carbofuran, tetrachlorvinphos, malathion, parathion-methyl, methomyl, chlordimeform, diazinon, deltamethrin, oxamyl, fenvalerate, esfenvalerate, permethrin, profenofos, sulprofos, triflumuron, diflubenzuron, methoprene, buprofezin, thiodicarb, acephate, azinphosmethyl, chlorpyrifos, dimethoate, fipronil, flufenprox, fonophos, isofenphos, methidathion, metha-midophos, phosmet, phosphamidon, phosalone, pirimicarb, phorate, terbufos, trichlorfon, methoxychlor, bifenthrin, biphenate, cyfluthrin, tefluthrin, fenpropathrin, fluvalinate, flucythrinate, tralomethrin, imidacloprid, metaldehyde and rotenone; fungicides such as carbendazim, thiuram, dodine, maneb, chloroneb, benomyl, cymoxanil, fenpropidine, fenpropimorph, triadimefon, captan, thiophanate- methyl, thiabendazole, phosethyl-Al, chlorothalonil, dichloran, metalaxyl, captafol, iprodione, oxadixyl, vinclozoliK. kasugamycin, myclobutanil, tebuconazole, difenoconazole, diniconazole, fluquinconazole, ipconazole, metconazole, penconazole, propiconazole, uniconzole, flutriafol, prochloraz, pyrifenox, fenarimol, triadimenol, diclobutrazol, copper oxychloride, furalaxyl, folpet, flusilazol, blasticidin S, diclomezine, edifenphos, isoprothiolane, iprobenfos, mepronil, neo-asozin, pencycuron, probenazole, pyroquilon,

tricyclazole, validamycin, and flutolanil; nematocides such as aldoxycarb, fenamiphos and fosthietan; bactericides such as oxytetracyline, streptomycin and tribasic copper sulfate; acaricides such as binapacryl, oxythioquinox, chlorobenzilate, dicofol, dienochlor, cyhexatin, hexythiazox, amitraz, propargite, tebufenpyrad and fenbutatin oxide; and biological agents such as entomopathogenic bacteria, virus and fungi.

In certain instances, combinations with other arthropodicides having a similiar spectrum of control but a different mode of action will be particularly advantageous for resistance management. Arthropod pests are controlled and protection of agronomic, horticultural and specialty crops, animal and human health is achieved by applying one or both of the compounds of this invention, in an effective amount, to the environment of the pests including the agronomic and/or nonagronomic locus of infestation, to the area to be protected, or directly on the pests to be controlled. Thus, the present invention further comprises a method for the control of foliar and soil inhabiting arthropods and nematode pests and protection of agronomic and/or nonagronomic crops, comprising applying one or both of the compounds of Formula I and π, or compositions containing at least one such compound, in an 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. A preferred method of application is by spraying. Alternatively, granular formulations of these compounds can be applied to the plant foliage or the soil. Other methods of application include direct and residual sprays, aerial sprays, seed coats, microencapsulations, systemic uptake, baits, eartags, boluses, foggers, fumigants, aerosols, dusts and many others. The compounds can be incorporated into baits that are consumed by the arthropods or in devices such as traps and the like.

The compounds of this invention can be applied in their pure state, but most often application will be of a formulation comprising one or more compounds with suitable carriers, diluents, and surfactants and possibly in combination with a food depending on the contemplated end use. A preferred method of application involves spraying a water dispersion or refined oil solution of the compounds. Combinations with spray oils, spray oil concentrations, spreader stickers, adjuvants, and synergists and other solvents such as piperonyl butoxide often enhance compound efficacy.

The rate of application required for effective control will depend on such factors as the species of arthropod to be controlled, the pest's life cycle, life stage, its size, location, time of year, host crop or animal, feeding behavior, mating behavior, ambient moisture, temperature, and the like. Under normal circumstances, application rates of about 0.01 to 2 kg of active ingredient per hectare are sufficient to control pests in agronomic ecosystems, but as little as 0.001 kg/hectare may be sufficient or as much as 8 kg hectare may be required. For nonagronomic applications, effective use rates will range from about 1.0 to 50 mg/square meter but as little as 0.1 mg/ square meter may be sufficient or as much as 150 mg/square meter may be required.

The following TESTS demonstrate the control efficacy of Compounds I and II on specific pests. Compounds I and π have also been found to be active on Colorado Potato Beetle. The pest control protection afforded by Compounds I and II are not limited, however, to these species. TEST A

Fall Army worm

Test units, each consisting of an 8-ounce (230 mL) plastic cup containing a layer of wheat germ diet, approximately 0.5 cm thick, were prepared. Ten third- instar larvae of fall armyworm (Spodopterafrugiperda) were placed into a cup. A solution of the test compound (acetone/distilled water 75/25 solvent) was sprayed into the cups, a single solution per set of three cups. Spraying was accomplished by passing the cups, on a conveyer belt, directly beneath a flat fan hydraulic nozzle which discharged the spray at a rate of 0.5 pounds of active ingredient per acre (about 0.55 kg/ha) at 30 p.s.i. (207 kPa). The cups were then covered and held at 27°C and 50% relative humidity for 72 h, after which time both Compounds I and π gave 100% mortality.

TEST B Tobacco Budworm

The test procedure of Test A was repeated for efficacy against third-instar larvae of the tobacco budworm (Heliothis virescens) except that mortality was assessed at 48 h after which time both Compounds I and II gave 100% mortality.

TEST C Southern Corn Rootworm

Test units, each consisting of an 8-ounce (230 mL) plastic cup containing 1 sprouted corn seed, were prepared. A set of three test units was sprayed as

described in Test A with a solution of Compound I. After the spray on the cups had dried, five third-instar larvae of the southern corn rootworm (Diabrotica undecimpunctata howardi) were placed into each cup. A moistened dental wick was inserted into each cup to prevent drying and the cups were then covered. The cups were then held at 27°C and 50% relative humidity for 48 h, after which time both Compounds I and II gave 100% mortality.

TEST D Boll Weevil

Five adult boll weevils (Anthonomus grandis) were placed into each of a series of 9 ounce (260 mL) cups. The test procedure employed was then otherwise the same as in Test A using three cups. Mortality readings were taken 48 h after treatment after which time both Compounds I and II gave 100% mortality.