Classifications

• • A—HUMAN NECESSITIES
  • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
  • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
  • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
  • A01N43/90—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having two or more relevant hetero rings, condensed among themselves or with a common carbocyclic ring system
• • A—HUMAN NECESSITIES
  • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
  • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
  • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
  • A01N43/34—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one nitrogen atom as the only ring hetero atom
  • A01N43/40—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one nitrogen atom as the only ring hetero atom six-membered rings
• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07D—HETEROCYCLIC COMPOUNDS
  • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
  • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
  • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
  • C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
  • C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
  • C07D213/81—Amides; Imides
• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07D—HETEROCYCLIC COMPOUNDS
  • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
  • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
  • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
  • C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
  • C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
  • C07D213/83—Thioacids; Thioesters; Thioamides; Thioimides
• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07D—HETEROCYCLIC COMPOUNDS
  • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
  • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
  • C07D213/89—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members with hetero atoms directly attached to the ring nitrogen atom
• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07D—HETEROCYCLIC COMPOUNDS
  • C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
  • C07D498/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
  • C07D498/04—Ortho-condensed systems

Definitions

• Fungicides are compounds, of natural or synthetic origin, which act to protect and/or cure plants against damage caused by agriculturally relevant fungi. Generally, no single fungicide is useful in all situations. Consequently, research is ongoing to produce fungicides that may have better performance, are easier to use, and cost less.
• the present disclosure relates to picolinamides and their use as fungicides.
• the compounds of the present disclosure may offer protection against ascomycetes, basidiomycetes, deuteromycetes and oomycetes.
• One embodiment of the present disclosure may include compounds of Formula I: [0004] wherein
• X is hydrogen or C(O)R5;
• Y is hydrogen, C(O)R 5 , or Q;
• R1 and R11 are independently hydrogen or alkyl, optionally substituted with 0, 1 or multiple R 8 , alternatively, R 1 and R 11 may be taken together to form a 3– 6 membered saturated or partially saturated carbocycle or heterocycle, optionally substituted with 0, 1 or multiple R 8 ;
• R2 and R12 are hydrogen or methyl
• R 3 is aryl or heteroaryl, each optionally substituted with 0, 1 or multiple R 8 ;
• R 4 is alkyl, aryl, heteroaryl, or acyl, each optionally substituted with 0, 1 or multiple R8;
• R5 is alkoxy or benzyloxy, each optionally substituted with 0, 1, or multiple R8;
• R 6 is hydrogen, alkoxy, or halo, each optionally substituted with 0,1, or multiple R 8 ;
• R7 is hydrogen,–C(O)R9, or–CH2OC(O)R9;
• R8 is hydrogen, alkyl, aryl, acyl, halo, alkenyl, alkoxy, or heterocyclyl, each optionally substituted with0, 1, or multiple R 10;
• R 9 is alkyl, alkoxy, or aryl, each optionally substituted with 0, 1, or multiple R 8 ;
• R10 is hydrogen, alkyl, aryl, acyl, halo, alkenyl, alkoxy, or heterocyclyl.
• Another embodiment of the present disclosure may include a fungicidal composition for the control or prevention of fungal attack comprising the compounds described above and a phytologically acceptable carrier material.
• Yet another embodiment of the present disclosure may include a method for the control or prevention of fungal attack on a plant, the method including the steps of applying a fungicidally effective amount of one or more of the compounds described above to at least one of the fungus, the plant, and an area adjacent to the plant.
• alkyl refers to a branched, unbranched, or saturated cyclic carbon chain, including, but not limited to, methyl, ethyl, propyl, butyl, isopropyl, isobutyl, tertiary butyl, pentyl, hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, and the like.
• alkenyl refers to a branched, unbranched or cyclic carbon chain containing one or more double bonds including, but not limited to, ethenyl, propenyl, butenyl, isopropenyl, isobutenyl, cyclobutenyl, cyclopentenyl, cyclohexenyl, and the like.
• aryl and“Ar” refer to any aromatic ring, mono- or bi-cyclic, containing 0 heteroatoms.
• heterocyclyl refers to any aromatic or non-aromatic ring, mono- or bi- cyclic, containing one or more heteroatoms
• alkoxy refers to an–OR substituent.
• hydroxyl refers to a–OH substituent.
• amino refers to an–N(R) 2 substituent.
• halogen refers to one or more halogen atoms, defined as F, Cl, Br, and I.
• nitro refers to a–NO 2 substituent.
• thioalkyl refers to a–SR substituent.
• Formula (I) is read as also including salts or hydrates thereof.
• Exemplary salts include, but are not limited to: hydrochloride, hydrobromide, hydroiodide, trifluoroacetate, and trifluoromethane sulfonate.
• Another embodiment of the present disclosure is a use of a compound of Formula I, for protection of a plant against attack by a phytopathogenic organism or the treatment of a plant infested by a phytopathogenic organism, comprising the application of a compound of Formula I, or a composition comprising the compound to soil, a plant, a part of a plant, foliage, and/or roots.
• composition useful for protecting a plant against attack by a phytopathogenic organism and/or treatment of a plant infested by a phytopathogenic organism comprising a compound of Formula I and a phytologically acceptable carrier material.
• the compounds of the present disclosure may be applied by any of a variety of known techniques, either as the compounds or as formulations comprising the compounds.
• the compounds may be applied to the roots or foliage of plants for the control of various fungi, without damaging the commercial value of the plants.
• the materials may be applied in the form of any of the generally used formulation types, for example, as solutions, dusts, wettable powders, flowable concentrate, or emulsifiable concentrates.
• the compounds of the present disclosure are applied in the form of a formulation, comprising one or more of the compounds of Formula I with a phytologically acceptable carrier.
• Concentrated formulations may be dispersed in water, or other liquids, for application, or formulations may be dust-like or granular, which may then be applied without further treatment.
• the formulations can be prepared according to procedures that are conventional in the agricultural chemical art.
• the present disclosure contemplates all vehicles by which one or more of the compounds may be formulated for delivery and used as a fungicide.
• formulations are applied as aqueous suspensions or emulsions.
• Such suspensions or emulsions may be produced from water-soluble, water-suspendible, or emulsifiable formulations which are solids, usually known as wettable powders; or liquids, usually known as emulsifiable concentrates, aqueous suspensions, or suspension concentrates.
• any material to which these compounds may be added may be used, provided it yields the desired utility without significant interference with the activity of these compounds as antifungal agents.
• Wettable powders which may be compacted to form water-dispersible granules, comprise an intimate mixture of one or more of the compounds of Formula I, an inert carrier and surfactants.
• concentration of the compound in the wettable powder may be from about 10 percent to about 90 percent by weight based on the total weight of the wettable powder, more preferably about 25 weight percent to about 75 weight percent.
• the compounds may be compounded with any finely divided solid, such as prophyllite, talc, chalk, gypsum, Fuller's earth, bentonite, attapulgite, starch, casein, gluten, montmorillonite clays, diatomaceous earths, purified silicates or the like.
• the finely divided carrier and surfactants are typically blended with the compound(s) and milled.
• Emulsifiable concentrates of the compounds of Formula I may comprise a convenient concentration, such as from about 1 weight percent to about 50 weight percent of the compound, in a suitable liquid, based on the total weight of the concentrate.
• the compounds may be dissolved in an inert carrier, which is either a water-miscible solvent or a mixture of water-immiscible organic solvents, and emulsifiers.
• the concentrates may be diluted with water and oil to form spray mixtures in the form of oil-in-water emulsions.
• Useful organic solvents include aromatics, especially the high-boiling naphthalenic and olefinic portions of petroleum such as heavy aromatic naphtha. Other organic solvents may also be used, for example, terpenic solvents, including rosin derivatives, aliphatic ketones, such as cyclohexanone, and complex alcohols, such as 2- ethoxyethanol.
• Emulsifiers which may be advantageously employed herein may be readily determined by those skilled in the art and include various nonionic, anionic, cationic and amphoteric emulsifiers, or a blend of two or more emulsifiers.
• nonionic emulsifiers useful in preparing the emulsifiable concentrates include the polyalkylene glycol ethers and condensation products of alkyl and aryl phenols, aliphatic alcohols, aliphatic amines or fatty acids with ethylene oxide, propylene oxides such as the ethoxylated alkyl phenols and carboxylic esters solubilized with the polyol or polyoxyalkylene.
• Cationic emulsifiers include quaternary ammonium compounds and fatty amine salts.
• Anionic emulsifiers include the oil-soluble salts (e.g., calcium) of alkylaryl sulphonic acids, oil-soluble salts or sulfated polyglycol ethers and appropriate salts of phosphated polyglycol ether.
• Representative organic liquids which may be employed in preparing the emulsifiable concentrates of the compounds of the present disclosure are the aromatic liquids such as xylene, propyl benzene fractions; or mixed naphthalene fractions, mineral oils, substituted aromatic organic liquids such as dioctyl phthalate; kerosene; dialkyl amides of various fatty acids, particularly the dimethyl amides of fatty glycols and glycol derivatives such as the n-butyl ether, ethyl ether or methyl ether of diethylene glycol, the methyl ether of triethylene glycol, petroleum fractions or hydrocarbons such as mineral oil, aromatic solvents, paraffinic oils, and the like; vegetable oils such as soy bean oil, rape seed oil, olive oil, castor oil, sunflower seed oil, coconut oil, corn oil, cotton seed oil, linseed oil, palm oil, peanut oil, safflower oil, sesame oil, tung oil and the like; vegetable oils
• Organic liquids include xylene, and propyl benzene fractions, with xylene being most preferred in some cases.
• Surface-active dispersing agents are typically employed in liquid formulations and in an amount of from 0.1 to 20 percent by weight based on the combined weight of the dispersing agent with one or more of the compounds.
• the formulations can also contain other compatible additives, for example, plant growth regulators and other biologically active compounds used in agriculture.
• Aqueous suspensions comprise suspensions of one or more water-insoluble compounds of Formula I, dispersed in an aqueous vehicle at a concentration in the range from about 1 to about 50 weight percent, based on the total weight of the aqueous suspension.
• Suspensions are prepared by finely grinding one or more of the compounds, and vigorously mixing the ground material into a vehicle comprised of water and surfactants chosen from the same types discussed above.
• Other components such as inorganic salts and synthetic or natural gums, may also be added to increase the density and viscosity of the aqueous vehicle.
• the compounds of Formula I can also be applied as granular formulations, which are particularly useful for applications to the soil.
• Granular formulations generally contain from about 0.5 to about 10 weight percent, based on the total weight of the granular formulation of the compound(s), dispersed in an inert carrier which consists entirely or in large part of coarsely divided inert material such as attapulgite, bentonite, diatomite, clay or a similar inexpensive substance.
• Such formulations are usually prepared by dissolving the compounds in a suitable solvent and applying it to a granular carrier which has been preformed to the appropriate particle size, in the range of from about 0.5 to about 3 mm.
• a suitable solvent is a solvent in which the compound is substantially or completely soluble.
• Such formulations may also be prepared by making a dough or paste of the carrier and the compound and solvent, and crushing and drying to obtain the desired granular particle.
• Dusts containing the compounds of Formula I may be prepared by intimately mixing one or more of the compounds in powdered form with a suitable dusty agricultural carrier, such as, for example, kaolin clay, ground volcanic rock, and the like. Dusts can suitably contain from about 1 to about 10 weight percent of the compounds, based on the total weight of the dust.
• a suitable dusty agricultural carrier such as, for example, kaolin clay, ground volcanic rock, and the like. Dusts can suitably contain from about 1 to about 10 weight percent of the compounds, based on the total weight of the dust.
• the formulations may additionally contain adjuvant surfactants to enhance deposition, wetting, and penetration of the compounds onto the target crop and organism.
• adjuvant surfactants may optionally be employed as a component of the formulation or as a tank mix.
• the amount of adjuvant surfactant will typically vary from 0.01 to 1.0 percent by volume, based on a spray-volume of water, preferably 0.05 to 0.5 volume percent.
• Suitable adjuvant surfactants include, but are not limited to ethoxylated nonyl phenols, ethoxylated synthetic or natural alcohols, salts of the esters or sulphosuccinic acids, ethoxylated organosilicones, ethoxylated fatty amines, blends of surfactants with mineral or vegetable oils, crop oil concentrate (mineral oil (85%) + emulsifiers (15%)); nonylphenol ethoxylate; benzylcocoalkyldimethyl quaternary ammonium salt; blend of petroleum hydrocarbon, alkyl esters, organic acid, and anionic surfactant; C9– C11
• alkylpolyglycoside phosphated alcohol ethoxylate; natural primary alcohol (C 12 – C 16 ) ethoxylate; di-sec-butylphenol EO-PO block copolymer; polysiloxane-methyl cap; nonylphenol ethoxylate + urea ammonium nitrrate; emulsified methylated seed oil; tridecyl alcohol (synthetic) ethoxylate (8EO); tallow amine ethoxylate (15 EO); PEG(400) dioleate-99.
• the formulations may also include oil-in-water emulsions such as those disclosed in U.S. Patent Application Serial No.11/495,228, the disclosure of which is expressly incorporated by reference herein.
• the formulations may optionally include combinations that contain other pesticidal compounds.
• additional pesticidal compounds may be fungicides, insecticides, herbicides, nematocides, miticides, arthropodicides, bactericides or combinations thereof that are compatible with the compounds of the present disclosure in the medium selected for application, and not antagonistic to the activity of the present compounds.
• the other pesticidal compound is employed as a supplemental toxicant for the same or for a different pesticidal use.
• the compounds of Formula I and the pesticidal compound in the combination can generally be present in a weight ratio of from 1:100 to100:1.
• the compounds of the present disclosure may also be combined with other fungicides to form fungicidal mixtures and synergistic mixtures thereof.
• the fungicidal compounds of the present disclosure are often applied in conjunction with one or more other fungicides to control a wider variety of undesirable diseases.
• the presently claimed compounds may be formulated with the other fungicide(s), tank-mixed with the other fungicide(s) or applied sequentially with the other fungicide(s).
• Such other fungicides may include 2-(thiocyanatomethylthio)-benzothiazole, 2-phenylphenol, 8-hydroxyquinoline sulfate, ametoctradin, amisulbrom, antimycin, Ampelomyces quisqualis, azaconazole, azoxystrobin, Bacillus subtilis, Bacillus subtilis strain QST713, benalaxyl, benomyl, benthiavalicarb-isopropyl, benzovindiflupyr benzylaminobenzene-sulfonate (BABS) salt, bicarbonates, biphenyl,
• BABS benzylaminobenzene-sulfonate
• pyrametostrobin pyraoxystrobin, pyrazophos, pyribencarb, pyributicarb, pyrifenox, pyrimethanil, pyriofenone, pyroquilon, quinoclamine, quinoxyfen, quintozene, Reynoutria sachalinensis extract, sedaxane, silthiofam, simeconazole, sodium 2-phenylphenoxide, sodium bicarbonate, sodium pentachlorophenoxide, spiroxamine, sulfur, SYP-Z048, tar oils, tebuconazole, tebufloquin, tecnazene, tetraconazole, thiabendazole, thifluzamide, thiophanate-methyl, thiram, tiadinil, tolclofos-methyl, tolylfluanid, triadimefon, triadimenol, triazoxid
• hydrochloride pyracarbolid, pyridinitril, pyroxychlor, pyroxyfur, quinacetol; quinacetol sulfate, quinazamid, quinconazole, rabenzazole, salicylanilide, SSF-109, sultropen, tecoram, thiadifluor, thicyofen, thiochlorfenphim, thiophanate, thioquinox, tioxymid, triamiphos, triarimol, triazbutil, trichlamide, urbacid, zarilamid, and any combinations thereof.
• the compounds described herein may be combined with other pesticides, including insecticides, nematocides, miticides, arthropodicides, bactericides or combinations thereof that are compatible with the compounds of the present disclosure in the medium selected for application, and not antagonistic to the activity of the present compounds to form pesticidal mixtures and synergistic mixtures thereof.
• the fungicidal compounds of the present disclosure may be applied in conjunction with one or more other pesticides to control a wider variety of undesirable pests.
• the presently claimed compounds may be formulated with the other pesticide(s), tank-mixed with the other pesticide(s) or applied sequentially with the other pesticide(s).
• Typical insecticides include, but are not limited to: 1,2-dichloropropane, abamectin, acephate, acetamiprid, acethion, acetoprole, acrinathrin, acrylonitrile, alanycarb, aldicarb, aldoxycarb, aldrin, allethrin, allosamidin, allyxycarb, alpha-cypermethrin, alpha-ecdysone, alpha-endosulfan, amidithion, aminocarb, amiton, amiton oxalate, amitraz, anabasine, athidathion, azadirachtin, azamethiphos, azinphos-ethyl, azinphos-methyl, azothoate, barium hexafluorosilicate, barthrin, bendiocarb, benfuracarb, bensultap, beta-cyfluthr
• chlorfenapyr chlorfenvinphos, chlorfluazuron, chlormephos, chloroform, chloropicrin,
• chlorphoxim chlorprazophos, chlorpyrifos, chlorpyrifos-methyl, chlorthiophos, chromafenozide, cinerin I, cinerin II, cinerins, cismethrin, cloethocarb, closantel, clothianidin, copper acetoarsenite, copper arsenate, copper naphthenate, copper oleate, coumaphos, coumithoate, crotamiton, crotoxyphos, crufomate, cryolite, cyanofenphos, cyanophos, cyanthoate, cyantraniliprole, cyclethrin, cycloprothrin, cyfluthrin, cyhalothrin, cypermethrin, cyphenothrin, cyromazine, cythioate, DDT, decarbofuran, deltamethrin, demephi
• ecdysterone emamectin, emamectin benzoate, EMPC, empenthrin, endosulfan, endothion, endrin, EPN, epofenonane, eprinomectin, esdepalléthrine, esfenvalerate, etaphos, ethiofencarb, ethion, ethiprole, ethoate-methyl, ethoprophos, ethyl formate, ethyl-DDD, ethylene dibromide, ethylene dichloride, ethylene oxide, etofenprox, etrimfos, EXD, famphur, fenamiphos, fenazaflor, fenchlorphos, fenethacarb, fenfluthrin, fenitrothion, fenobucarb, fenoxacrim, fen
• methamidophos methidathion, methiocarb, methocrotophos, methomyl, methoprene,
• methoxychlor methoxyfenozide, methyl bromide, methyl isothiocyanate, methylchloroform, methylene chloride, metofluthrin, metolcarb, metoxadiazone, mevinphos, mexacarbate,
• the compounds described herein may be combined with herbicides that are compatible with the compounds of the present disclosure in the medium selected for application, and not antagonistic to the activity of the present compounds to form pesticidal mixtures and synergistic mixtures thereof.
• the fungicidal compounds of the present disclosure may be applied in conjunction with one or more herbicides to control a wide variety of undesirable plants.
• the presently claimed compounds may be formulated with the herbicide(s), tank-mixed with the herbicide(s) or applied sequentially with the herbicide(s).
• Typical herbicides include, but are not limited to: 4-CPA; 4-CPB; 4-CPP; 2,4-D; 3,4-DA; 2,4-DB; 3,4-DB; 2,4-DEB; 2,4-DEP; 3,4-DP; 2,3,6-TBA; 2,4,5-T; 2,4,5-TB; acetochlor, acifluorfen, aclonifen, acrolein, alachlor, allidochlor, alloxydim, allyl alcohol, alorac, ametridione, ametryn, amibuzin, amicarbazone, amidosulfuron, aminocyclopyrachlor, aminopyralid, amiprofos-methyl, amitrole, ammonium sulfamate, anilofos, anisuron, asulam, atraton, atrazine, azafenidin, azimsulfuron, aziprotryne, barban, BCPC, beflubutamid, benazolin, ben
• Another embodiment of the present disclosure is a method for the control or prevention of fungal attack.
• This method comprises applying to the soil, plant, roots, foliage, or locus of the fungus, or to a locus in which the infestation is to be prevented (for example applying to cereal or grape plants), a fungicidally effective amount of one or more of the compounds of Formula I.
• the compounds are suitable for treatment of various plants at fungicidal levels, while exhibiting low phytotoxicity.
• the compounds may be useful both in a protectant and/or an eradicant fashion.
• the compounds have been found to have significant fungicidal effect particularly for agricultural use. Many of the compounds are particularly effective for use with agricultural crops and horticultural plants.
• the compounds have broad ranges of activity against fungal pathogens.
• exemplary pathogens may include, but are not limited to, causing agent of wheat leaf blotch (Zymoseptoria tritici), wheat brown rust (Puccinia triticina), wheat stripe rust (Puccinia striiformis), scab of apple (Venturia inaequalis), powdery mildew of grapevine (Uncinula necator), barley scald
• the compounds are effective in use with plants in a disease-inhibiting and
• phytologically acceptable amount refers to an amount of a compound that kills or inhibits the plant disease for which control is desired, but is not significantly toxic to the plant. This amount will generally be from about 0.1 to about 1000 ppm (parts per million), with 1 to 500 ppm being preferred. The exact concentration of compound required varies with the fungal disease to be controlled, the type of formulation employed, the method of application, the particular plant species, climate conditions, and the like. A suitable application rate is typically in the range from about 0.10 to about 4 pounds/acre (about 0.01 to 0.45 grams per square meter, g/m 2 ).
• the compounds of Formula I may be made using well-known chemical procedures. Intermediates not specifically mentioned in this disclosure are either commercially available, may be made by routes disclosed in the chemical literature, or may be readily synthesized from commercial starting materials utilizing standard procedures.
• Compounds of Formula 1.5 and 1.6 wherein R 3 and R 4 are as originally defined may be prepared by the methods shown in Scheme 1, steps a– d.
• Compounds of Formula 1.1 may be prepared by treatment of compounds of Formula 1.0, first under standard Grignard conditions, using magnesium metal and an alkali base, such as lithium chloride, in a polar, aprotic solvent such as tetrahydrofuran (THF) or diethyl ether (Et2O), at a temperature of about 0 ° C to about 70 ° C, to generate the Grignard intermediate.
• a polar, aprotic solvent such as tetrahydrofuran (THF) or diethyl ether (Et2O)
• the solution is then treated with a metal catalyst, such as iron (III) acetylacetonate, followed by allyl chloride, in a polar aprotic solvent, such as THF, at a temperature of about 0 o C to about 70 o C, to give compounds of Formula 1.1, wherein R 3 is as previously defined, and shown in step a.
• a metal catalyst such as iron (III) acetylacetonate
• allyl chloride in a polar aprotic solvent, such as THF
• Compounds of Formula 1.1, wherein R 3 is as previously defined, can be isomerized to compounds of Formula 1.2 by treating with a catalyst system, such as bis(dibenzylideneactone)palladium (0), a phosphine coordinating reagent, such as tri-tert-butylphosphine, and an acid chloride, such as isobutyryl chloride, in an aromatic hydrocarbon solvent such as toluene, at a temperature of about 25 o C to 100 o C, to generate compounds of formula 1.2, wherein R3 is as previously described, and shown in step b.
• a catalyst system such as bis(dibenzylideneactone)palladium (0), a phosphine coordinating reagent, such as tri-tert-butylphosphine, and an acid chloride, such as isobutyryl chloride
• an aromatic hydrocarbon solvent such as toluene
• Epoxides of Formulas 1.3 and 1.4, wherein R 3 is as previously defined can be obtained by a catalytic asymmetric epoxidation method using oxone as oxidant and a fructose derived ketone as described by Wang, Z-X; Tu, Y.; Frohn, M.; Zhang, J-R.; Shi, Y. J. Am. Chem. Soc.1997, 119, 11224 - 11235, and depicted in step c.
• epoxides of Formulae 1.3 and 1.4, wherein R3 is as previously defined can be prepared by other catalytic asymmetric epoxidation methods, including, but not limited to, dioxiranes derived from other
• chiral ketones catalytic metal salen complexes using an oxidant, such as dioxygen or sodium hypochlorite; chiral iminium salts using oxone as the oxidizing species; chiral organic oxaziridine salts; and enzymatic epoxidation biocatalysts, such as monooxygenases and hydrolases.
• an oxidant such as dioxygen or sodium hypochlorite
• chiral iminium salts using oxone as the oxidizing species chiral organic oxaziridine salts
• enzymatic epoxidation biocatalysts such as monooxygenases and hydrolases.
• Compounds of Formulas 1.5 and 1.6, wherein R 3 and R 4 are as previously defined, can be prepared by treating epoxides of Formulas 1.3 and 1.4, with a sulfur nucleophile, such as benzenethiol, in the presence of an alkali base, such as sodium hydroxide, in a polar biphasic solvent system, such as 1,4-dioxane and water, in a ratio of about 10:1, at a temperature of about 25 o C to 70 o C, as described by Caldentey, X.; Pericas, M.A. J. Org. Chem.2010, 75, 2628– 2644, and shown in step d.
• a sulfur nucleophile such as benzenethiol
• an alkali base such as sodium hydroxide
• a polar biphasic solvent system such as 1,4-dioxane and water
• Compounds of Formula 2.2 may be prepared according to the method outlined in Scheme 2, step a.
• Alcohols of Formula 2.0 wherein R 2 , R 3 , R 4 , and R 12 , are as originally defined, can be treated with compounds of Formula 2.1, wherein R1 and R11 are as originally defined, a coupling reagent, such as 3- (ethyliminomethyleneamino)-N,N-dimethylpropan-1-amine hydrochloride (EDC) or a polymer- supported carbodiimide (PS-CDI), and a catalyst, such as N,N-dimethylpyridin-4-amine (DMAP), in a halogenated solvent, such as CH2Cl2, to generate compounds of Formula 2.2, wherein R1, R2, R3, R4, R11, and R12 are as previously defined, as shown in step a.
• Scheme 2
• Compounds of Formula 3.4 wherein R1, R2, R3, R4, R6, R11, and R12 are as originally defined, may be prepared according to the methods outlined in Scheme 3, steps a– d.
• Compounds of Formula 2.2 wherein R 1 , R 2 , R 3 , R 4 , R 11 , and R 12 are as originally defined, but not alkenyl, may be treated with an acid, such as a 4 N solution of HCl in dioxane, with or without a halogenated solvent such as CH 2 Cl 2 to generate compounds of Formula 3.1, wherein R 1 , R 2 , R 3 , R 4 , R 11 , and R 12 , are as originally defined, but not alkenyl, as shown in step a.
• Compounds of Formula 3.2 wherein R1, R2, R3, R4, R11, and R12 are as originally defined, can be prepared by treating compounds of Formula 2.2, wherein R 1 , R 2 , R 3 , R 4 , R 11 , and R 12 are as originally defined, with an acid, such as 2,2,2-trifluoroacetic acid, in a halogenated solvent such as CH2Cl2, as shown in step c.
• an acid such as 2,2,2-trifluoroacetic acid
• Compounds of Formulas 3.1 and 3.2, wherein R1, R2, R3, R4, R11, and R12 are as originally defined, can be treated with compounds of Formula 3.3, wherein R 6 is as originally defined, in the presence of a base, such as diisopropylethylamine, and a peptide coupling reagent, such as benzotriazol-1-yl- oxytripyrrolidinophosphonium hexafluorophosphate (PyBOP) or O-(7-azabenzo-triazol-1-yl)- N,N,N′,N′-tetramethyluronium hexafluorophosphate (HATU), in an halogenated solvent such as CH 2 Cl 2 , to generate compounds of Formula 3.4, wherein R 1 , R 2 , R 3 , R 4 , R 6 , R 11 , and R 12 are as previously defined, as shown in step b and d.
• a base such as diisopropylethy
• Compounds of Formula 4.1 wherein R1, R2, R3, R4, R6, R7, R11, and R12 are as originally defined, may be prepared according to the method outlined in Scheme 4, steps a or b.
• Compounds of Formula 3.4 wherein R 1 , R 2 , R 3 , R 4 , R 6 , R 11 , and R 12 are as previously defined, may be treated with an appropriate alkyl halide with or without a reagent such as sodium iodide (NaI) and an alkali carbonate base, such as Na 2 CO 3 or potassium carbonate (K 2 CO 3 ), in a solvent such as acetone, as shown in step a.
• NaI sodium iodide
• K 2 CO 3 potassium carbonate
• Compounds of Formula 3.4 may be treated with a thionating reagent such as phosphorus pentasulfide, an additive, such as hexamethyldisiloxane, optionally in a polar aprotic solvent such as acetonitrile (CH 3 CN), at a temperature of about 0 °C to 80 °C to generate compounds of Formula 5.0, wherein R1, R2, R3, R4, R6, R11, and R12 are as originally defined, and shown in step a.
• a thionating reagent such as phosphorus pentasulfide
• an additive such as hexamethyldisiloxane
• a polar aprotic solvent such as acetonitrile (CH 3 CN)
• compounds such as Formula 1.1 may also be prepared using other thionating agents including, but not limited to: sulfur, sulfhydric acid, sodium sulfide, sodium hydrosulfide, boron trisulfide, bis(diethylaluminum)sulfide, ammonium sulfide, Lawesson’s reagent, ammonium O,O'- diethyl dithiophosphate, rhodanine, or a polymer supported thionating reagent.
• thionating agents including, but not limited to: sulfur, sulfhydric acid, sodium sulfide, sodium hydrosulfide, boron trisulfide, bis(diethylaluminum)sulfide, ammonium sulfide, Lawesson’s reagent, ammonium O,O'- diethyl dithiophosphate, rhodanine, or a polymer supported thionating reagent.
• Additives can include, but not limited to, aluminum oxide (Al2O3); inorganic bases, such as potassium carbonate and sodium bicarbonate; organic bases, such as triethylamine, diethylaniline, pyridine and morpholine.
• Al2O3 aluminum oxide
• inorganic bases such as potassium carbonate and sodium bicarbonate
• organic bases such as triethylamine, diethylaniline, pyridine and morpholine.
• Optional solvents can include, but not limited to, aliphatic, alicyclic or aromatic hydrocarbons, such as hexane, cyclohexane or toluene; halogenated hydrocarbons, such as dichloromethane, 1,2-dichloroethane and chlorobenzene; ethers, such as diethyl ether, 1,4-dioxane, THF and 1,2-dimethoxyethane; and other polar aprotic solvents such as pyridine and
• HMPA hexamethylphosphoramide
• Compounds of Formula 3.4 may be treated with an oxidizing reagent, such as sodium perborate tetrahydrate, in a solvent, such as acetic acid, at a temperature of about 25 o C to 60 o C, to give compounds of Formula 6.0 and 6.1, wherein R1, R2, R3, R4, R6, R11, and R12 are as originally defined, and shown in Scheme 6, step a.
• an oxidizing reagent such as sodium perborate tetrahydrate
• a solvent such as acetic acid
• compounds of Formula 4.1 wherein R1, R2, R3, R4, R6, R7, R11, and R12 are as originally defined, can be subjected to an excess (3-5 equivalents) of an oxidizing reagent, such as sodium perborate tetrahydrate, in a solvent, such as acetic acid, at a temperature of about 25 o C to 60 o C, to generate compounds of Formulae 6.1, 7.0 and 7.1, wherein R1, R2, R3, R4, R6, R7, R11, and R12 are as originally defined, and shown in Scheme 7, step b.
• Scheme 7
• Example 1A Preparation of (E)-1-methyl-4-(prop-1-en-1-yl)benzene.
• Step 1 Preparation of (E,Z)-4-fluoro-2-methoxy-1-(prop-1-en-1-yl)benzene.
• allyl chloride (1.33 mL, 16.26 mmol) was added and the reaction was stirred at 0 °C for 30 min. The mixture was warmed to room temperature over 1 hr and was heated at 70 °C overnight. The reaction was cooled and diluted with petroleum ether (100 mL). The reaction was then quenched by the addition of a saturated NH4Cl solution (100 mL). The mixture was filtered through a Celite ® pad and the layers were separated. The aqueous layer was extracted with petroleum ether (2 x 100 mL) and the combined organic phases were dried over Na2SO4 and carefully concentrated (25 °C, 250 mbar).
• Step 2 Preparation of (E)-4-fluoro-2-methoxy-1-(prop-1-en-1-yl)benzene.
• reaction mixture was cooled to 0 o C with an ice bath.
• a solution of oxone (6.53 g, 10.61 mmol) in aqueous Na 2 (EDTA) (4 x 10 -4 M, 50 mL) and a solution of potassium carbonate (6.17 g, 44.6 mmol) in water (50 mL) were added dropwise through two syring pumps over a period of 1.5 h (under these conditions, the reaction pH is around 10.5; it is recommended that both oxone and K 2 CO 3 be added uniformly over 1.5 h).
• the reaction was immediately quenched by the addition of 100 mL each of petroleum ether and water.
• Example 3 Preparation of (1R,2S)-1-(phenylthio)-1-(p-tolyl)propan-2-ol.
• Example 4 Preparation of (1R,2S)-1-(phenylthio)-1-(p-tolyl)propan-2-yl (tert-butoxycarbonyl)- L - alaninate.
• Example 4A Preparation of erythro-1-(methylsulfonyl)-1-phenylpropan-2-yl (tert- butoxycarbonyl)-L-alaninate.
• Example 6B Preparation of 4-methoxy-2-(((S)-1-oxo-1-(((1R,2S)-1-phenyl-1- (phenylthio)propan-2-yl)oxy)propan-2-yl)carbamoyl)pyridin-3-yl isobutyrate.
• reaction mixture was loaded directly onto an Isco column (0 to 50% Acetone in hexanes) to provide 4-methoxy-2-(((S)-1-oxo-1- (((1R,2S)-1-phenyl-1-(phenylthio)propan-2-yl)oxy)propan-2-yl)carbamoyl)pyridin-3-yl isobutyrate (109 mg, 0.193 mmol, 90 % yield) as a colorless oil.
• Example 6C Preparation of (1R,2S)-1-phenyl-1-(phenylthio)propan-2-yl-(3- (acetoxymethoxy)-4-methoxypicolinoyl)-L-alaninate.
• Example 6D Preparation of ((4-methoxy-2-(((S)-1-oxo-1-(((1R,2S)-1-phenyl-1- (phenylthio)propan-2-yl)oxy)propan-2-yl)carbamoyl)pyridin-3-yl)oxy)methyl isobutyrate.
• Example 7 Preparation of (1R,2S)-1-(4-fluorophenyl)-1-(phenylthio)propan-2-yl-(3- hydroxy-4-methoxypyridine-2-carbonothioyl)-L-alaninate.
• Example 8 Preparation of (1R,2S)-1-((R)-(4-fluorophenyl)sulfinyl)-1-phenylpropan- 2-yl (3-hydroxy-4-methoxypicolinoyl)-L-alaninate and (1R,2S)-1-((4-fluorophenyl)sulfonyl)-1- phenylpropan-2-yl-(3-hydroxy-4-methoxypicolinoyl)-L-alaninate.
• Example 9 Preparation of (1R,2S)-1-(benzylsulfonyl)-1-phenylpropan-2-yl-(3- hydroxy-4-methoxypicolinoyl)-L-alaninate, (1R,2S)-1-(benzylsulfonyl)-1-phenylpropan-2-yl-(3- acetoxy-4-methoxypicolinoyl)-L-alaninate, and (1R,2S)-1-((S)-benzylsulfinyl)-1-phenylpropan-2- yl-(3-acetoxy-4-methoxypicolinoyl)- L -alaninate.
• Example A Evaluation of Fungicidal Activity: Leaf Blotch of Wheat (Zymoseptoria tritici; Bayer code SEPTTR):
• Wheat plants (variety Yuma) were grown from seed in a greenhouse in 50% mineral soil/50% soil-less Metro mix until the first leaf was fully emerged, with 7-10 seedlings per pot. These plants were inoculated with an aqueous spore suspension of Zymoseptoria tritici either prior to or after fungicide treatments. After inoculation the plants were kept in 100% relative humidity (one day in a dark dew chamber followed by two to three days in a lighted dew chamber at 20 oC) to permit spores to germinate and infect the leaf. The plants were then transferred to a greenhouse set at 20 oC for disease to develop.
• Example B Evaluation of Fungicidal Activity: Wheat Brown Rust (Puccinia triticina; Synonym: Puccinia recondita f. sp. tritici; Bayer code PUCCRT):

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