[go: up one dir, main page]
More Web Proxy on the site http://driver.im/

WO2007061966A2 - Amidinylphenyl compounds and their use as fungicides - Google Patents

Amidinylphenyl compounds and their use as fungicides Download PDF

Info

Publication number
WO2007061966A2
WO2007061966A2 PCT/US2006/044924 US2006044924W WO2007061966A2 WO 2007061966 A2 WO2007061966 A2 WO 2007061966A2 US 2006044924 W US2006044924 W US 2006044924W WO 2007061966 A2 WO2007061966 A2 WO 2007061966A2
Authority
WO
WIPO (PCT)
Prior art keywords
compound
alkyl
plant
caused
disease
Prior art date
Application number
PCT/US2006/044924
Other languages
French (fr)
Other versions
WO2007061966A3 (en
Inventor
Chi-Ping Tseng
Michael Caldwell Klapproth
Original Assignee
E. I. Du Pont De Nemours And Company
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by E. I. Du Pont De Nemours And Company filed Critical E. I. Du Pont De Nemours And Company
Publication of WO2007061966A2 publication Critical patent/WO2007061966A2/en
Publication of WO2007061966A3 publication Critical patent/WO2007061966A3/en

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C257/00—Compounds containing carboxyl groups, the doubly-bound oxygen atom of a carboxyl group being replaced by a doubly-bound nitrogen atom, this nitrogen atom not being further bound to an oxygen atom, e.g. imino-ethers, amidines
    • C07C257/10—Compounds containing carboxyl groups, the doubly-bound oxygen atom of a carboxyl group being replaced by a doubly-bound nitrogen atom, this nitrogen atom not being further bound to an oxygen atom, e.g. imino-ethers, amidines with replacement of the other oxygen atom of the carboxyl group by nitrogen atoms, e.g. amidines
    • C07C257/12—Compounds containing carboxyl groups, the doubly-bound oxygen atom of a carboxyl group being replaced by a doubly-bound nitrogen atom, this nitrogen atom not being further bound to an oxygen atom, e.g. imino-ethers, amidines with replacement of the other oxygen atom of the carboxyl group by nitrogen atoms, e.g. amidines having carbon atoms of amidino groups bound to hydrogen atoms
    • 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
    • A01N37/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom having three bonds to hetero atoms with at the most two bonds to halogen, e.g. carboxylic acids
    • A01N37/52—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom having three bonds to hetero atoms with at the most two bonds to halogen, e.g. carboxylic acids containing groups, e.g. carboxylic acid amidines
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F7/00—Compounds containing elements of Groups 4 or 14 of the Periodic Table
    • C07F7/02—Silicon compounds
    • C07F7/08—Compounds having one or more C—Si linkages
    • C07F7/0803—Compounds with Si-C or Si-Si linkages
    • C07F7/081—Compounds with Si-C or Si-Si linkages comprising at least one atom selected from the elements N, O, halogen, S, Se or Te

Definitions

  • This invention relates to certain amidinylphenyl compounds, their iV-oxides, agriculturally suitable salts and compositions, and methods of their use as fungicides.
  • One area of need is for compounds that are useful for controlling plant disease caused by Ascomycete fungal plant pathogens, such as powdery mildew disease of cereals and/or broadleaf crops.
  • Another area of need is for compounds that are useful for controlling plant disease caused by Basidiomycete fungal plant pathogens, such as rust disease of cereals and/or broadleaf crops.
  • World Patent Application- Publication WO 2003/093224 discloses certain phenylamidines of Formula i as new fungicidal active ingredients.
  • R 1 , R 2 , R 3 , R 4 , R 5 , R 6 and A are broadly defined, m is 0, 1, 2 or 3.
  • This invention is directed to compounds of Formula 1 (including all geometric and stereoisomers), jV-oxides, and agriculturally suitable salts thereof, agricultural compositions containing them and their use as fungicides:
  • R 1 is C 1 -C 4 alkyl or C 3 -C 4 cycloalkyl
  • R 2 is C 1 -C 3 alkyl
  • R 3 is Br, Cl or I
  • R 4 is Cl; or C 1 -C 2 alkyl or C 1 -C 2 alkoxy, each optionally substituted with one to three substituents independently selected from halogen;
  • A is C or Si;
  • each R 5 is independently C 1 -C 2 alkyl optionally substituted with one to three substituents independently selected from halogen; and
  • R 5a is H or Cj-C 2 alkyl; provided that when A is Si, then R 5a is C 1 - C 2 alkyl.
  • This invention provides a method of controlling plant diseases caused by Ascomycete plant pathogens (e.g., powdery mildew diseases caused by Erysiphe spp., Uncinula necatur, Sphaerotheca fuligena and Podosphaera leucotrichd) and diseases caused by Helminthosporium, Pyrenophora teres and Rhyncosporiwn secalis.
  • This method comprises applying to the plant (e.g., a cereal or broadleaf crop) or portion thereof, or to the plant seed or seedling, a fungicidally effective amount of a compound selected from the compounds of Formula 1, ⁇ T-oxides, and agriculturally suitable salts thereof.
  • This invention also provides a method of controlling plant diseases caused by Ascomycete plant pathogens (e.g., powdery mildew diseases caused by Erysiphe spp., Uncinula necatur, Sphaerotheca fuligena and Pod
  • Basidiomycete plant pathogens e.g., rust diseases caused by Puccinia spp., Hemileia vastatrix, Uromyces appendiculatus, Phakopsora pachyrhizi and Phakopsora meibomiae.
  • This method comprises applying to the plant (e.g., a cereal or broadleaf crop) or portion thereof, or to the plant seed or seedling, a fungicidally effective amount of a compound selected from the compounds of Formula 1, .V-oxides, and agriculturally suitable salts thereof.
  • This invention also provides a method of controlling plant diseases caused by plant pathogens other than Ascomycete plant pathogens and Basidiomycete plant pathogens (e.g., Deuteromycetes plant pathogens).
  • This method comprises applying to the plant (e.g., a cereal or broadleaf crop) or portion thereof, or to the plant seed or seedling, a fungicidally effective amount of a compound selected from the compounds of Formula 1, JV-oxides, and agriculturally suitable salts thereof.
  • compositions comprising, “comprising,” “includes,” “including,” “has,” “having” or any other variation thereof, are intended to cover a non-exclusive inclusion.
  • a composition, process, method, article, or apparatus that comprises a list of elements is not necessarily limited to only those elements but may include other elements not expressly listed or inherent to such composition, process, method, article, or apparatus.
  • “or” refers to an inclusive or and not to an exclusive or. For example, a condition A or B is satisfied by any one of the following: A is true (or present) and B is false (or not present), A is false (or not present) and B is true (or present), and both A and B are true (or present).
  • compositions of the present invention comprises a biologically effective amount of "a" compound of Formula 1 which should be read that the composition includes one or at least one compound of Formula 1.
  • seedling used either alone or in a combination of words means a young plant developing from the embryo of a seed.
  • the term “broadleaf used either alone or in words such as “broadleaf crop” means dicot or dicotyledon, a term used to describe a group of angiosperms characterized by embryos having two cotyledons.
  • alkyl includes straight-chain or branched alkyl, such as, methyl, ethyl, n-propyl, /-propyl, or the different butyl isomers.
  • Alkoxy includes, for example, methoxy and ethoxy.
  • Cycloalkyl includes, for example, cyclopropyl and cyclobutyl.
  • halogen includes fluorine, chlorine, bromine or iodine.
  • the total number of carbon atoms in a substituent group is indicated by the "Cj-C j " prefix where i and j are numbers from 1 to 4.
  • C 2 alkyl designates CH 3 CH 2 ;
  • C 3 alkyl designates, for example, CH 3 CH 2 CH 2 or (CH 3 ) 2 CH.
  • tertiary amines can form iV-oxides.
  • Synthetic methods for the preparation of iV-oxides of tertiary amines are very well known by one skilled in the art including the oxidation of tertiary amines with peroxy acids such as peracetic and m-chloroperbenzoic acid (MCPBA), hydrogen peroxide, alkyl hydroperoxides such as *-butyl hydroperoxide, sodium perborate, and dioxiranes such as dimethyldioxirane.
  • MCPBA peroxy acids
  • alkyl hydroperoxides such as *-butyl hydroperoxide
  • sodium perborate sodium perborate
  • dioxiranes such as dimethyldioxirane.
  • Compounds of this invention can exist as one or more stereoisomers.
  • the various stereoisomers include enantiomers, diastereomers, atropisomers and geometric isomers.
  • one stereoisomer may be more active and/or may exhibit beneficial effects when enriched relative to the other stereoisomer(s) or when separated from the other stereoisomers). Additionally, the skilled artisan knows how to separate, enrich, and/or to selectively prepare said stereoisomers.
  • the compounds of the invention may be present as a mixture of stereoisomers, individual stereoisomers, or as an optically active form.
  • salts of the compounds of Formula 1 are useful for control of fungal plant diseases (i.e. are agriculturally suitable).
  • the salts of the compounds of Formula 1 include acid-addition salts with inorganic or organic acids such as hydrobromic, hydrochloric, nitric, phosphoric, sulfuric, acetic, butyric, fumaric, lactic maleic, malonic, oxalic, propionic, salicylic, tartaric, 4-toluenesulfonic or valeric acids.
  • the present invention comprises compounds selected from Formula 1, iV-oxides and agriculturally suitable salts thereof.
  • Embodiments of the present invention include: Embodiment Al.
  • Embodiment A2 A compound of Embodiment Al wherein R 1 is C 1 -C 2 alkyl.
  • Embodiment A3. A compound of Embodiment A2 wherein R 1 is ethyl.
  • Embodiment A4 A compound of Formula 1 wherein R 2 is C 1 -C 2 alkyl- Embodiment A5.
  • Embodiment A6 A compound of Formula 1 wherein R 3 is Br or Cl.
  • Embodiment A7 A compound of Embodiment A6 wherein R 3 is Br. .
  • Embodiment A8 A compound of Formula 1 wherein R 4 is Cl; or C]-C 2 alkyl or C 1 -
  • Embodiment A 12 A compound of Embodiment Al 1 wherein each R 5 is independently C 1 -C 2 alkyl optionally substituted with one to three Cl. Embodiment A13. A compound of Embodiment A12 wherein each R 5 is independently Cj alkyl optionally substituted with one to three Cl. Embodiment A 14. A compound of Formula 1 wherein A is C and R 5a is H. Embodiment Bl .
  • a method of controlling at least one plant fungal disease in cereal or broadleaf crops selected from the group consisting of powdery mildew disease caused by Erysiphe spp., Uncinula necatur, Sphaerothecafuligena and
  • Embodiment B2 A method of Embodiment Bl wherein at least one powdery mildew disease is controlled.
  • Embodiment B3. A method of Embodiment B2 wherein the plant disease is caused by
  • Embodiment B4 A method of Embodiment B2 wherein the plant disease is caused by
  • Embodiment B5. A method of Embodiment B2 wherein the plant disease is caused by Uncinula necatur.
  • Embodiment B6 A method of Embodiment B2 wherein the plant disease is caused by
  • Embodiment B7 A method of Embodiment Bl wherein at least one rust disease is controlled. .
  • Embodiment B8. A method of Embodiment B7 wherein the plant disease is caused by
  • Embodiment B9 A method of Embodiment B7 wherein the plant disease is caused by Puccinia striiformis.
  • Embodiment BlO A method of Embodiment B7 wherein the plant disease is caused by Puccinia graminis.
  • Embodiment BIl A method of Embodiment B7 wherein the plant disease is caused by Hemileia vastatrix.
  • Embodiment B 12. A method of Embodiment B7 wherein the plant disease is caused by Uromyces appendiculatus.
  • Embodiment B 13 A method of Embodiment B7 wherein the plant disease is caused by Phakopsora pachyrhizi.
  • Embodiment B 14 A method of any one of Embodiments Bl to Bl 3 wherein the plant is a dicot crop.
  • Embodiment B 15 A method of Embodiment Bl 4 wherein the dicot crop is selected from soybean, grape and cucurbit.
  • Embodiment B 16 A method of Embodiment Bl 5 wherein the dicot crop is soybean.
  • Embodiment B17 A method of Embodiment Bl 5 wherein the dicot crop is grape.
  • Embodiment B 18. A method of Embodiment Bl 5 wherein the dicot crop is cucurbit.
  • Embodiment Cl A compound of Formula 1 wherein R 1 is C 1 -C 3 alkyl or C 3 -C 4 cycloalkyl; R 2 is C 1 -C 2 alkyl; R3 is Br or Cl;
  • R 4 is Cl; or C 1 - C 2 alkyl or C 1 - C 2 alkoxy, each optionally substituted with one to three substituents independently selected from F and Cl; and each R 5 is independently C 1 -C 2 alkyl optionally substituted with one to three substituents independently selected from F and Cl.
  • Embodiment C2. A compound of Embodiment Cl wherein
  • R l is C 1 -C 2 alkyl; R 2 is methyl; R 3 is Br;
  • R 4 is Cl; or C 1 -C 2 alkyl or C 1 -C 2 alkoxy, each optionally substituted with one to three F; and each R 5 is independently C 1 -C 2 alkyl optionally substituted with one to three
  • R 1 is ethyl; R 2 is methyl; R 4 is C 1 alkyl or C 1 alkoxy, each optionally substituted with one to three F; and each R 5 is independently Cj alkyl optionally substituted with one to three
  • Embodiment C4 A compound of Embodiment C3 selected from the group consisting of: iV'-[2-bromo-4-[(4-methylpentyl)oxy]-5-(trifluoromethyl)phenyl]-iV-ethyl-iV- methyknethanimidamide;
  • This invention also relates to a fungicidal composition
  • a fungicidal composition comprising a fungicidally effective amount of a compounds of the invention and at least one of a surfactant, a solid diluent or a liquid diluent.
  • a surfactant e.g., sodium bicarbonate
  • a solid diluent e.g., sodium bicarbonate
  • a liquid diluent e.g., sodium bicarbonate, sodium bicarbonate
  • the compounds of Formula 1 can be prepared by one or more of the following methods and variations as described in Schemes 1-5.
  • the definitions of R 1 , R 2 , R 3 , R 4 , R 5 , R 5a and A in the compounds of Formulae 1-8 below are as defined above in the Summary of the Invention.
  • a compound of Formula 1 can be prepared by reaction of a compound of Formula 2 with a halogenating agent such as JV-chlorosuccinimide, N- bromosuccinimide, iV-iodosuccinimide or their equivalent in an inert solvent such as dichloromethane or carbon tetrachloride.
  • a halogenating agent such as JV-chlorosuccinimide, N- bromosuccinimide, iV-iodosuccinimide or their equivalent in an inert solvent such as dichloromethane or carbon tetrachloride.
  • the reaction can be carried out at temperatures ranging from 0 to 110 0 C for a period of time between 1 and 48 h.
  • the reaction mixture is then allowed to come to room temperature and filtered.
  • the filtrate is washed with dilute aqueous sodium hydroxide solution, dried over a drying agent such as magnesium sulfate and then concentrated to give the compound of Formula
  • Compounds of Formula 2 can be prepared from anilines of Formula 3 as shown in Scheme 2.. A variety of methods can be used for this transformation. The following five methods are especially useful.
  • Method 1 Treatment of an aniline of Formula 3 with an acetal of formula R 1 R 2 NCH(OR 6 ⁇ 5 wherein R 6 is an alkyl. This type of transformation can be found in Toste et al., Synth. Commun., 1994, 24(11), 1617-1624.
  • a halogenating reagent such as, but not limited to, POCI 3 or SOCI 2 . This type of transformation can be found in Bergman et al., Tetrahedron, 1990, 46(17), 6058-6112.
  • Method 3 Treatment of an aniline of Formula 3 with an orthoester of formula HC(OR 6 > 3 , wherein R 6 is an alkyl, to form a corresponding iminoether, followed by heating the iminoether with an amine of formula HNR 1 R 2 .
  • This type of transformation can be found in Pissiotas et al., U.S. Patent 4,209,319.
  • This type of transformation can be found in Charles et al., World Patent Application Publication WO 2000/46184.
  • This type of transformation can be found in Charles et al., World Patent Application Publication WO 2000/46184. This method is illustrated in Step C and D of Example I, Step C and D of Example 2 and Step E and F of Example 3.
  • Compounds of Formula 3 can be prepared by reduction of the nitro group in compounds of Formula 4 as shown in Scheme 3. Many methods can be used for this reduction. Preferred methods include stannous chloride reduction in concentrated hydrochloric acid (see, for example, J. Med. Chem., 1984, 24(12), 1705-1710), iron powder reduction in a solution of acetic acid and water (see, for example, J. Org. Chem., 2001,
  • compounds of Formula 4 can be prepared by alkylation of a compound of Formula 5 with an alkylating agent of Formula 6 in the presence of a base.
  • X is a nucleophilic reaction leaving group such as, for example, bromide or iodide.
  • the reaction is conducted in the presence of at least 1 equivalent of a base, preferably from 1 to 2 equivalents.
  • Suitable bases include inorganic bases such as alkali metal hydrides (e.g., lithium hydride, sodium hydride or potassium hydride), alkali metal carbonates or alkali metal hydroxides, and organic bases such as 1,8- diazabicyclo[5.4.0]undec-7-ene.
  • a wide variety of solvents are suitable for the reaction, including, for example, but are not limited to benzene, toluene, tetrahydrofuran, dimethoxyethane, acetonitrile, i ⁇ yV-dimethylformamide as well as mixtures of these solvents.
  • the reaction is generally conducted between about -20 and 150 0 C, and preferably between 20 and 140 0 C.
  • the reaction time can range from 1 h to 7 days.
  • compounds of Formula 4 can also be prepared from compounds of Formula 7 by reacting with an appropriate alcohol of Formula 8 in the presence of a base.
  • the reaction is conducted by first treating 1 to 2 equivalents of the appropriate alcohol of Formula 8, preferably from 1 to 1.4 equivalents, with at least 1 equivalent of a base, preferably from 1 to 1.2 equivalents, for a period of time ranging from 3 minutes to 5 h followed by the addition of a compound of Formula 7.
  • Suitable bases include inorganic bases such as alkali metal hydrides (e.g., lithium hydride, sodium hydride or potassium hydride), alkali metal carbonates or alkali metal hydroxides, and organic bases such as l,8-diazabicyclo[5.4.0]undec-7-ene.
  • a phase transfer reagent such as tetrabutylammonium chloride may be employed as a catalyst for the reaction.
  • a wide variety of solvents are suitable for the reaction, such as for example, benzene, toluene, tetrahydrofuran, dimethoxyethane, acetonitrile, iV,7V-dimethylformamide, as well as mixtures of these solvents.
  • the reaction is generally conducted between about -20 and 150 0 C, and preferably between 20 and 140 0 C.
  • the reaction time can range from 1 h to 7 days. Further experimental details for the method of Scheme 5 are illustrated in Step A of Example 1.
  • compounds of Formula 4 can also be prepared from compounds of Formula 5 through a Mitsunobu reaction, which involves reaction of a compound of Formula 5 with an appropriate alcohol of Formula 8.
  • the Mitsunobu Reaction has been the subject of a number of reviews. For conditions and variations of this reaction, see the following reference and references cited therein: Hughes, Org. React., 1992, 42, 335-656. Further experimental details for the Mitsunobu reaction are illustrated in Step A of Example 2 and Step A of Example 3.
  • Step A Preparation of 1 -r(4-methylpentv ⁇ oxy1-4-nitro-2-('trifluoromethyl " )benzene To a solution of 4-methyl-l-pentanol (5.85 g, 57.2 mmol) in 1,2-dimethoxyethane
  • Step C Preparation of iV-cvano-JV-[4-[(4-methylpentyl > )oxy1-3-( ' trifluoromethyl)- phenyl]methanimidamide
  • the precipitate was collected by filtration, air dried and then dried in oven to give 1.89 g of the title compound as a white solid melting at 138-140 0 C.
  • the filtrate was concentrated, and the residue was triturated with a solution of 10 % ethyl acetate in hexanes (20 mL).
  • the precipitate was collected by filtration, air dried and then dried in oven to give an additional 0.47 g of the title compound as a white solid.
  • Step D Preparation of iV-ethyl-iV " -methyl-N " '-f4-r( r 4-methylpentyl)oxy1-3-(trifluoro- memvDphenylimethanimidamide
  • iV-cyano-iV r '-[4-[(4-methylpentyl)oxy]-3-(trifluoromethyl)phenyl]- methanimidamide (Le. the product from Step C) (2.34 g, 7.48 mmol) in acetonitrile (65 mL) at room temperature was added 7V-ethylmethylamine (3.22 mL, 37.4 mmol) dropwise.
  • Step E Preparation of N'-[2-bromo-4-f(4-methyl ⁇ entyl)oxy]-5-(trifluoromethyr)- phenyli- ⁇ -ethyl-JV ' -methylmethanirnidarnide f Compound 7)
  • Step A Preparation of r3-(2-methoxy-4-m ' trophenoxy)propyl1trimethylsilane
  • Step B Preparation of 3 -methoxy-4- [3 -(trimethylsil vDpropoxyibenzenamine
  • Step C Preparation of iV-cyano-N J -
  • iV-cyanomethanimidate 9.9 g, 101.8 mmol
  • absolute ethanol 50 mL
  • 3-methoxy-4-[3- (trimetiiylsilyl) ⁇ ropoxy]benzenamine i.e. the product from Step B
  • the reaction mixture was stirred at room temperature overnight and then concentrated.
  • Step D Preparation of iV ; -ethyl-iv 'J -
  • JV-methylmethanimidamide A mixture of iV-cyano-iV'-[3-methoxy-4-[3-(trimethylsilyl)pro ⁇ oxy]phenyl]methan- imidamide (i.e. the product from Step C) (5 g, 16.4 mmol), iV-ethylmethylamine (7 mL, 81.97 mmol) and acetonitrile (20 mL) in a Fisher-Porter bottle was heated at 130 0 C for 4 h. The resulting mixture was cooled to room temperature and then concentrated.
  • Step E Preparation of JV'-r2-bromo-5-methoxy-4-f3-( ' trimethylsilyl)propoxy1phenvn-
  • reaction mixture was then concentrated, and the residue was purified by silica gel chromatography using 50 % ethyl acetate in hexane as eluant to give 1.42 g of the title product, a compound of the present invention as a brown oil.
  • Step A Preparation of 5-nitro-2-[ " 3-rtrlmethylsilyl)propoxy1benzaldeliyde
  • diisopropyl azodicarboxylate 26 mL, 132 mmol
  • anhydrous tetrahydrofura ⁇ 500 mL
  • 2-hydroxy-5-nitrobenzaldehyde 20 g, 119.7 mmol
  • triphenylphosphine 37.7 g, 143.3 mmol
  • reaction mixture was then concentrated under reduced pressure, and the resulting precipitate was removed by filtration.
  • the filtrate was concentrated, and the residue was purified by silica gel chromatography using 10 to 20 % ethyl acetate in hexane as eluant to give 12.4 g of the title product as an oil.
  • reaction mixture was stirred at room temperature for 2 h, and an additional amount of Freon ® 22, chlorodifluoromethane (12 mL) was then added through a dry ice condenser.
  • the reaction mixture was stirred at room temperature for another 3 h, and dichloromethane (500 mL) was then added.
  • the reaction mixture was washed with water (3 x 300 mL), dried (MgSC ⁇ ), and concentrated.
  • the residue was purified by silica gel chromatography using 5 to 10 % ethyl acetate in hexane as eluant to give 7.26 g of the title product as an oil.
  • Step D Preparation of 3-rdifluoromethoxyV4-f3-trimethylsilyl]propoxy]ben2amine
  • Step E Preparation of JV-cyano-N'-f3-( ' difluoromethoxy)-4-r3-( ' trimethylsilyl)- propoxylphenyllmethanimidamide
  • Step F Preparation of Jv "> -f3-fdifluoromethoxy)-4-f3-('trimethylsilyl ' )propoxy1phenyl1-
  • n means normal, i means iso, . c means cyclo,
  • OMe means methoxy
  • OEt means ethoxy
  • the compound numbers of Tables 1 to 4 refer to compounds in Index Table A.
  • Compounds of this invention will generally be used as a formulation or composition with an agriculturally suitable carrier comprising at least one of a liquid diluent, a solid diluent or a surfactant.
  • the formulation or composition ingredients are selected to be consistent with the physical properties of the active ingredient, mode of application and environmental factors such as soil type, moisture and temperature.
  • Useful formulations include 'liquids such as solutions (including emulsifiable concentrates), suspensions, emulsions (including microemulsions and/or suspoemulsions) and the like which optionally can be thickened into gels.
  • Useful formulations further include solids such as dusts, powders, granules, pellets, tablets, films (including seed coatings), and the like which can be water-dispersible (“wettable”) or water-soluble.
  • Active ingredient can be
  • 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.
  • AU formulations can contain minor amounts of additives to reduce foam, caking, corrosion, microbiological growth and the like, or thickeners to increase viscosity.
  • Surfactants include, for example, polyethoxylated alcohols, polyethoxylated alkylphenols, polyethoxylated sorbitan fatty acid esters, dialkyl sulfosuccinates, alkyl sulfates, alkylbenzene sulfonates, organosilicones, ⁇ iV-dialkyltaurates, lignin sulfonates, naphthalene sulfonate formaldehyde condensates, polycarboxylates, glycerol esters, poly- oxyethylene/polyoxypropylene block copolymers, and alkylpolyglycosides where the number of glucose units, referred to as degree of polymerization (D.P.), can range from 1 to 3 and the alkyl units can range from C 6 to C 14 (see Pure and Applied Chemistry 72, 1255—
  • degree of polymerization D.P.
  • Solid diluents include, for example, clays such as bentonite, montmorillonite, attapulgite and kaolin, starch, sugar, silica, talc, diatomaceous earth, urea, calcium carbonate, sodium carbonate and bicarbonate, and sodium sulfate.
  • Liquid diluents include, for example, water, ⁇ yV-dimethylformamide, dimethyl sulfoxide, JV-alkylpyrrolidone, ethylene glycol, polypropylene glycol, propylene carbonate, dibasic esters, paraffins, alkylbenzenes, alkylnaphthalenes, glycerine, triacetine, oils of olive, castor, linseed, tung, sesame, corn, peanut, cotton-seed, soybean, rape-seed and coconut, fatty acid esters, ketones such as cyclohexanone, 2-heptanone, isophorone and 4-hydroxy-4-methyl-2-pentanone, acetates such as hexyl acetate, heptyl acetate and octyl acetate, and alcohols such as methanol, cyclohexanol, decanol, benzyl and tetrahydrofurfur
  • Useful formulations of this invention may also contain materials well known to those skilled in the art as formulation aids such as antifoams, film formers and dyes.
  • Antifoams can include water dispersible liquids comprising polyorganosiloxanes like Rhodorsil® 416.
  • the film formers can include polyvinyl acetates, polyvinyl acetate copolymers, polyvinylpyrrolidone-vinyl acetate copolymer, polyvinyl alcohols, polyvinyl alcohol copolymers and waxes.
  • Dyes can include water dispersible liquid colorant compositions like Pro-lzed® Colorant Red.
  • formulation aids include those listed herein and those listed in McCutcheon 's 2001, Volume 2: Functional Materials published by MC Publishing Company and PCT Publication WO 03/024222.
  • Dusts and powders can be prepared by blending and, usually, grinding as in a hammer mill or fluid-energy mill.
  • Suspensions are usually prepared by wet-milling; see, for example, U.S. 3,060,084.
  • Granules and pellets can be prepared by spraying the active material upon preformed granular carriers or by agglomeration techniques. See Browning, "Agglomeration", Chemical Engineering, December 4, 1967, pp ⁇ A1-A%, Perry's Chemical Engineer's Handbook, 4th Ed., McGraw-Hill, New York, 1963, pages 8-57 and following, and WO 91/13546.
  • Pellets can be prepared as described in U.S. 4,172,714. Water-dispersible and water-soluble granules can be prepared as taught in U.S. 4,144,050, U.S. 3,920,442 and DE 3,246,493. Tablets can be prepared as taught in U.S. 5,180,587, U.S. 5,232,701 and U.S. 5,208,030. Films can be prepared as taught in GB 2,095,558 and U.S. 3,299,566. For further information regarding the art of formulation, see T. S. Woods, "The art of formulation, see T. S. Woods,
  • Example B Wettable Powder Compound 7 65.0% dodecylphenol polyethylene glycol ether 2.0% sodium ligninsulfonate 4.0% sodium silicoaluminate 6.0% montmorillonite (calcined) 23.0%.
  • Example C Wettable Powder Compound 7 65.0% dodecylphenol polyethylene glycol ether 2.0% sodium ligninsulfonate 4.0% sodium silicoaluminate 6.0% montmorillonite (calcined) 23.0%.
  • Example C Wettable Powder Compound 7 65.0% dodecylphenol polyethylene glycol ether 2.0% sodium ligninsulfonate 4.0% sodium silicoaluminate 6.0% montmorillonite (calcined) 23.0%.
  • Compound 7 25.0% hydrated attapulgite 3.0% crude calcium ligninsulfonate 10.0% sodium dihydrogen phosphate 0.5% water 61.5%.
  • Compound 7 25.0% anhydrous sodium sulfate 10.0% crude calcium ligninsulfonate 5.0% sodium alkylnaphthalenesulfonate 1.0% calcium/magnesium bentonite 59.0%.
  • the compounds of this invention are useful as plant disease control agents.
  • the present invention therefore further relates to a method for controlling plant diseases caused by plant pathogens comprising applying to the plant or portion thereof to be protected, or to the plant seed or seedling to be protected, an effective amount of a compound of the invention or a fungicidal composition containing said compound.
  • the compounds of Formula 1 are considered to be particularly advantageous for use on dicot (i.e., broadleaf) plants. Accordingly, the compounds of Formula 1 can be used to provide effective fungal disease control for dicot plants.
  • the compounds of Formula 1 and their fungicidal compositions are useful for controlling fungal plant disease, such as powdery mildews and rusts, caused by fungal plant pathogens in the Ascomycete, Basidiomycete and Deuteromycete classes and afflicting a wide range of ornamental, vegetable, field, cereal and fruit crops.
  • fungal plant disease such as powdery mildews and rusts
  • pathogens include: Ascomycetes, including powdery mildew diseases of cereals and broadleaf crops caused by Erysiphe spp. (including Erysiphe graminis f. sp. tritici, Erysiphe graminis f. sp.
  • hordei and Erysiphe poly gon ⁇ Uncinula necatur, Sphaerotheca fuligena, Podosphaera leucotricha and diseases caused by Helminthosporium spp. such as Helminthosporium tritici repentis, Pyren ⁇ phora teres and Rhyncosporium secalis;
  • Basidiomycetes including rust diseases of cereals and broadleaf crops caused by Puccinia spp. (such as Puccinia recondita, Puccinia striiformis, Puccinia hordei, Puccinia graminis and Puccinia arachidis), Hemileia vastatrix, Uromyces appendiculatus, Phakopsora pachyrhizi and Phakopsora meibomiae; and other genera and species related to these pathogens, including those classified in Deuteromycetes.
  • Puccinia recondita Puccinia striiformis, Puccinia hordei, Puccinia graminis and Puccinia arachidis
  • Hemileia vastatrix Uromyces appendiculatus
  • Phakopsora pachyrhizi and Phakopsora meibomiae and other genera and species related to these pathogens, including those classified in De
  • Compounds of Formula 1 can be used to control fungal diseases of a wide range of economic plants such as alfalfa, barley, cotton, wheat, rape, sugarbeets, corn (maize), sorghum, soybeans, rice, oats, peanuts, vegetables including lettuce, garden beets, peas, beans, carrots, cole crops, curcurbit crops, tomato and pepper, potato, perennial plantation crops including coffee, cocoa, oil palm, rubber, sugarcane, grapes, citrus (e.g., orange, tangerine, lemon, lime, grapefruit), apple, cherry, pear, peach, apricot and other fruit trees, nut trees, banana, plantain, pineapple, hops, tea and forests such as eucalyptus and conifers (e.g., loblolly pine), and turf species (e.g., Kentucky bluegrass, St. Augustine grass, Kentucky fescue and Bermuda grass).
  • turf species e.g., Kentucky bluegrass, St. August
  • Compounds of this invention can also be mixed with one or more other insecticides, fungicides, nematocides, bactericides, acaricides, growth regulators, chemosterilants, semiochemicals, repellents, attractants, pheromones, feeding stimulants or other biologically active compounds to form a multi-component pesticide giving an even broader spectrum of agricultural protection.
  • insecticides such as abamectin, acephate, azinphos-methyl, bifenthrin, 3-bromo-l-(3-chloro-2 ⁇ pyridmyl)-N-[4-cyano-2-methyl- 6-[(methylamino)carbonyl] ⁇ henyl]-lH-pyrazole-5-carboxamide, buprofezin, ⁇ carbofuran, chlorfenapyr, chlorantraniliprole, chlorpyrifos, chlorpyrifos-methyl, cyflumetofen, cyfluthrin, beta-cyfluthrin, cyhalothrin, lambda-cyhalothrin, deltamethrin, diafenthiuron, diazinon, difiubenzuron, dimefluthrin, dimethoate, dinotefuran, esfenvaler
  • insecticides such as abamectin, acep
  • fungicides such as acibenzolar, aldimorph, amisulbrom, azaconazole, azoxystrobin, benalaxyl, benomyl, benthiavalicarb, benthiavalicarb-isopropyl, binomial, biphenyl, bitertanol, blasticidin-S, Bordeaux mixture (tribasic copper sulfate), boscalid/nicobifen, bromuconazole, bupirimate, buthiobate, carboxin, carpropamid,
  • the weight ratios of these various mixing partners to compounds of this invention typically are between 100:1 and 1:100, preferably between 30:1 and 1:30, more preferably between 10:1 and 1:10, and most preferably between 4:1 and 1:4.
  • a compound of Formula 1 e.g., Compound 15
  • azoxystrobin kresoxim-methyl
  • trifloxystrobin pyraclostrobin
  • picoxystrobin dimoxystrobin, metominostrobin/fenominostrobin, carbendazim, chlorothalonil, quinoxyfen, metrafenone, cyflufenamid, fam ⁇ xadone, fenpropidin, fenpropimorph, fluoxastrobin, bromuconazole, cyproconazole, difenoconazole, epoxiconazole, fenbuconazole, flusilazole, hexaconazole, ipconazole, metconazole, penconazole, propiconazole, proquinazid, prothioconazole, tebuconazole, triticonazole, prochloraz or boscalid/nicobifen.
  • Preferred for better control of plant diseases caused by fungal plant pathogens are mixtures of a compound of Formula 1 with a fungicide selected from the group: azoxystrobin, fluoxastrobin, kresoxim-methyl, trifloxystrobin, pyraclostrobin, picoxystrobin, dimoxystrobin, metominostrobin/fenominostrobin, quinoxyfen, metrafenone, cyflufenamid, fenpropidin, fenpropimorph, cyproconazole, epoxiconazole, flusilazole, metconazole, propiconazole, famoxadone, proquinazid, prothioconazole, tebuconazole and triticonazole.
  • azoxystrobin fluoxastrobin, kresoxim-methyl, trifloxystrobin, pyraclostrobin, picoxystrobin, dimoxystrobin, metomin
  • Specifically preferred mixtures are selected from the group: the combinations of Compound 7, Compound 8, Compound 15, Compound 22 or Compound 25 with azoxystrobin, the combinations of Compound 7, Compound 8, Compound 15, Compound 22 or Compound 25 with fluoxastrobin, the combinations of Compound 7, Compound 8, Compound 15, Compound 22 or Compound 25 with kresoxim-methyl, the combinations of Compound 7, Compound 8, Compound 15, Compound 22 or Compound 25 with trifloxystrobin, the combinations of
  • Phakopsora pachyrhizi which comprise applying a combination of a compound of Formula 1 (e.g., Compound 7, 8, 15, 22 or 25) with at least one compound selected from triazole fungicides that inhibit demethylase in sterol biosynthesis (e.g., cyproconazole, flusilazole and/or tebuconazole).
  • fungicidal compositions comprising a compound of Formula 1 (e.g., Compound 7, 8, 15, 22 or 25) and at least one compound selected from triazole fungicides that inhibit demethylase in sterol biosynthesis (e.g., cyproconazole, flusilazole and/or tebuconazole).
  • Plant disease control preventatively and curatively, is ordinarily accomplished by applying an effective amount of a compound of this invention either pre- or post-infection, to the portion of the plant to be protected such as the roots, stems, foliage, fruit, seeds, tubers or bulbs, or to the media (soil or sand) in which the plants to be protected are growing.
  • the compounds can also be applied to the seed to protect the seed and seedling.
  • Rates of application for these compounds can be influenced by many factors of the environment and should be determined under actual use conditions. Foliage can normally be protected when treated at a rate of from less than 1 g/ha to 5,000 g/ha of active ingredient. Seed and seedlings can normally be protected when seed is treated at a rate of from 0.1 to 1O g per kilogram of seed.
  • TESTS demonstrate the control efficacy of compounds of this invention on specific pathogens.
  • the pathogen control protection afforded by the compounds is not limited, however, to these species. See Index Tables A-B for compound descriptions. The following abbreviations are used in the Index Tables which follow: Me means methyl, Et means ethyl, Pr means propyl, ra-Pr means normal propyl, i-P ⁇ means isopropyl, OMe means methoxy, OEt means ethoxy.
  • the abbreviation "Ex.” stands for "Example” and is followed by a number indicating in which example the compound is prepared.
  • Test compounds were first dissolved in acetone in an amount equal to 3 % of the final volume and then suspended at the desired concentration (in ppm) in acetone and purified water (50/50 mix) containing 250 ppm of the surfactant Trem® 014 (polyhydric alcohol esters). The resulting test suspensions were then used in the following tests.
  • test suspension was sprayed at 40 ppm (equivalent to a rate of 120 g/ha) to the point of run-off on wheat seedlings.
  • seedlings were inoculated with a spore suspension of Puccinia recondita (the causal agent of wheat brown rust) and incubated in a saturated atmosphere at 20 0 C for 24 h, and then moved to a growth chamber at 20 0 C for 6 days, after which time disease ratings were made.
  • test suspension was sprayed at 40 ppm (equivalent to a rate of 120 g/ha) to the point of run-off on wheat seedlings.
  • seedlings were inoculated with a spore dust of Erysiphe graminis f. sp. tritid, (the causal agent of wheat powdery mildew) and incubated in a growth chamber at 20 0 C for 7 days, after which time disease ratings were made.
  • test suspension was sprayed at 20 g/ha (in an application volume of 1000 L/ha) on grape seedlings. The following day the seedlings were inoculated with a spore suspension of Uncinula necatur (the causal agent of grape powdery mildew) and incubated in a greenhouse at 20 0 C for 14 days, after which time disease ratings were made.
  • test suspension was sprayed at 100 g/ha (in an application volume of 1000 L/ha) on soybean seedlings. The following day the seedlings were incubated in a saturated atmosphere at 20 0 C for 48 h and then moved to a growth chamber at 22 0 C for 14 days, after which time crop safety ratings were made.
  • test suspension was sprayed at 20 g/ha (in an application volume of 1000 L/ha) on soybean seedlings. The following day the seedlings were incubated in a saturated atmosphere at 20 0 C for 48 h and then moved to a growth chamber at 22 0 C for 14 days, after which time crop safety ratings were made.
  • Results for Tests A-E are given in Table A.
  • disease efficacy ratings are based on the percent leaf area with no visible symptoms, expressed as a percent (0 to 100 %) of total leaf area — e.g., a rating of 100 indicates 100 % disease control and a rating of 0 indicates no disease control (relative to the controls).
  • a dash (-) indicates no test results.
  • crop safety ratings are based on the percent leaf area showing injury, expressed as a percent (0 to 100 %) of total leaf area — e.g., a rating of 100 indicates 100 % crop injury and a rating of 0 indicates no crop injury.
  • Tests A-E show compounds that are effective at controlling rust and powdery mildew diseases of cereal and broadleaf crops, and are advantageous for use on broadleaved crops.
  • the compound numbers of Table A refer to compounds in Index Table A. Table A
  • Results are given in Table B. Disease efficacy ratings are expressed as a percent (0 to 100 %) of total leaf area - e.g., a rating of 100 indicates 100 % disease control and a rating of 0 indicates no disease control (relative to the controls). "DATl" refers to the number of days after the first spray application (Tl). The compound numbers of Table B refer to compounds in Index Table A.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Agronomy & Crop Science (AREA)
  • Pest Control & Pesticides (AREA)
  • Plant Pathology (AREA)
  • Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Dentistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Wood Science & Technology (AREA)
  • Zoology (AREA)
  • Environmental Sciences (AREA)
  • Agricultural Chemicals And Associated Chemicals (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

Abstract

Compounds of Formula 1, and their N-oxides and agriculturally suitable salts, are disclosed as useful as fungicides (Formula 1) here wherein R1 is C1-C4 alkyl or C3-C4 cycloalkyl; R2 is C1-C3 alkyl; R3 is Br, Cl or I; R4 is Cl; or C1-C2 alkyl or C1-C2 alkoxy, each optionally substituted with one to three substituents independently selected from halogen; A is C or Si; each R5 is independently C1-C2 alkyl optionally substituted with one to three substituents independently selected from halogen; and R5a is H or C1-C2 alkyl; provided that when A is Si, then R5a is C1-C2 alkyl. Also disclosed are compositions comprising the compounds of Formula 1 and methods for controlling plant diseases caused by fungal plant pathogens which involve applying an effective amount of a compound of Formula 1.

Description

[ U AMIDINYLPHENYL COMPOUNDS AND THEIR USE AS FUNGICIDES
FIELD OF THE INVENTION
This invention relates to certain amidinylphenyl compounds, their iV-oxides, agriculturally suitable salts and compositions, and methods of their use as fungicides.
BACKGROUND OF THE INVENTION
The control of plant diseases caused by fungal plant pathogens is extremely important in achieving high crop efficiency. Plant disease damage to ornamental, vegetable, field, cereal, and fruit crops can cause significant reduction in productivity and thereby result in increased costs to the consumer. Many products are commercially available for these purposes, but the need continues for new compounds which are more effective, less costly, less toxic, environmentally safer or have different modes of action.
One area of need is for compounds that are useful for controlling plant disease caused by Ascomycete fungal plant pathogens, such as powdery mildew disease of cereals and/or broadleaf crops. Another area of need is for compounds that are useful for controlling plant disease caused by Basidiomycete fungal plant pathogens, such as rust disease of cereals and/or broadleaf crops.
World Patent Application- Publication WO 2003/093224 discloses certain phenylamidines of Formula i as new fungicidal active ingredients.
Figure imgf000002_0001
i .
R1, R2, R3, R4, R5, R6 and A are broadly defined, m is 0, 1, 2 or 3.
SUMMARY OF THE INVENTION
This invention is directed to compounds of Formula 1 (including all geometric and stereoisomers), jV-oxides, and agriculturally suitable salts thereof, agricultural compositions containing them and their use as fungicides:
Figure imgf000003_0001
1 wherein
R1 is C1-C4 alkyl or C3-C4 cycloalkyl; R2 is C1-C3 alkyl; R3 is Br, Cl or I;
R4 is Cl; or C1-C2 alkyl or C1-C2 alkoxy, each optionally substituted with one to three substituents independently selected from halogen; A is C or Si; each R5 is independently C1-C2 alkyl optionally substituted with one to three substituents independently selected from halogen; and
R5a is H or Cj-C2 alkyl; provided that when A is Si, then R5a is C1- C2 alkyl.
This invention provides a method of controlling plant diseases caused by Ascomycete plant pathogens (e.g., powdery mildew diseases caused by Erysiphe spp., Uncinula necatur, Sphaerotheca fuligena and Podosphaera leucotrichd) and diseases caused by Helminthosporium, Pyrenophora teres and Rhyncosporiwn secalis. This method comprises applying to the plant (e.g., a cereal or broadleaf crop) or portion thereof, or to the plant seed or seedling, a fungicidally effective amount of a compound selected from the compounds of Formula 1, ΛT-oxides, and agriculturally suitable salts thereof. This invention also provides a method of controlling plant diseases caused by
Basidiomycete plant pathogens (e.g., rust diseases caused by Puccinia spp., Hemileia vastatrix, Uromyces appendiculatus, Phakopsora pachyrhizi and Phakopsora meibomiae). This method comprises applying to the plant (e.g., a cereal or broadleaf crop) or portion thereof, or to the plant seed or seedling, a fungicidally effective amount of a compound selected from the compounds of Formula 1, .V-oxides, and agriculturally suitable salts thereof.
This invention also provides a method of controlling plant diseases caused by plant pathogens other than Ascomycete plant pathogens and Basidiomycete plant pathogens (e.g., Deuteromycetes plant pathogens). This method comprises applying to the plant (e.g., a cereal or broadleaf crop) or portion thereof, or to the plant seed or seedling, a fungicidally effective amount of a compound selected from the compounds of Formula 1, JV-oxides, and agriculturally suitable salts thereof. DETAILS OF THE INVENTION
As used herein, the terms "comprises," "comprising," "includes," "including," "has," "having" or any other variation thereof, are intended to cover a non-exclusive inclusion. For example, a composition, process, method, article, or apparatus that comprises a list of elements is not necessarily limited to only those elements but may include other elements not expressly listed or inherent to such composition, process, method, article, or apparatus. Further, unless expressly stated to the contrary, "or" refers to an inclusive or and not to an exclusive or. For example, a condition A or B is satisfied by any one of the following: A is true (or present) and B is false (or not present), A is false (or not present) and B is true (or present), and both A and B are true (or present).
Also, the indefinite articles "a" and "an" preceding an element or component of the invention are intended to be nonrestrictive regarding the number of instances (i.e. occurrences) of the element or component. Therefore "a" or "an" should be read to include one or at least one, and the singular word form of the element or component also includes the plural unless the number is obviously meant to be singular. For example, a composition of the present invention comprises a biologically effective amount of "a" compound of Formula 1 which should be read that the composition includes one or at least one compound of Formula 1.
As referred to herein, the term "seedling", used either alone or in a combination of words means a young plant developing from the embryo of a seed.
As referred to herein, the term "broadleaf used either alone or in words such as "broadleaf crop" means dicot or dicotyledon, a term used to describe a group of angiosperms characterized by embryos having two cotyledons.
In the above recitations, the term "alkyl" includes straight-chain or branched alkyl, such as, methyl, ethyl, n-propyl, /-propyl, or the different butyl isomers. "Alkoxy" includes, for example, methoxy and ethoxy. "Cycloalkyl" includes, for example, cyclopropyl and cyclobutyl. The term "halogen" includes fluorine, chlorine, bromine or iodine. The total number of carbon atoms in a substituent group is indicated by the "Cj-Cj" prefix where i and j are numbers from 1 to 4. For example, C2 alkyl designates CH3CH2; C3 alkyl designates, for example, CH3CH2CH2 or (CH3)2CH.
One skilled in the art will also recognize that tertiary amines can form iV-oxides. Synthetic methods for the preparation of iV-oxides of tertiary amines are very well known by one skilled in the art including the oxidation of tertiary amines with peroxy acids such as peracetic and m-chloroperbenzoic acid (MCPBA), hydrogen peroxide, alkyl hydroperoxides such as *-butyl hydroperoxide, sodium perborate, and dioxiranes such as dimethyldioxirane. These methods for the preparation of iV-oxides have been extensively described and reviewed in the literature, see for example: T. L. Gilchrist in Comprehensive Organic Synthesis, vol. 7, pp 748-750, S. V. Ley, Ed., Pergamon Press; M. Tisler and B. Stanovnik in Comprehensive Heterocyclic Chemistry, vol. 3, pp 18-20, A. J. Boulton and A. McKillop, Eds., Pergamon Press; M. R. Grimmett and B. R. T. Keene in Advances in Heterocyclic Chemistry, vol. 43, pp 149-161, A. R. Katritzky, Ed., Academic Press; M. Tisler and B. Stanovnik in Advances in Heterocyclic Chemistry, vol. 9, pp 285-291, A. R. Katritzky and A. J. Boulton, Eds., Academic Press; and G. W. H. Cheeseman and E. S. G. Werstiuk in Advances in Heterocyclic Chemistry, vol. 22, pp 390-392, A. R. Katritzky and A. J. Boulton, Eds., Academic Press.
Compounds of this invention can exist as one or more stereoisomers. The various stereoisomers include enantiomers, diastereomers, atropisomers and geometric isomers. One skilled in the art will appreciate that one stereoisomer may be more active and/or may exhibit beneficial effects when enriched relative to the other stereoisomer(s) or when separated from the other stereoisomers). Additionally, the skilled artisan knows how to separate, enrich, and/or to selectively prepare said stereoisomers. The compounds of the invention may be present as a mixture of stereoisomers, individual stereoisomers, or as an optically active form.
One skilled in the art recognizes that because in the environment and under physiological conditions salts of chemical compounds are in equilibrium with their corresponding nonsalt forms, salts share the biological utility of the nonsalt forms. Thus a wide variety of salts of the compounds of Formula 1 are useful for control of fungal plant diseases (i.e. are agriculturally suitable). The salts of the compounds of Formula 1 include acid-addition salts with inorganic or organic acids such as hydrobromic, hydrochloric, nitric, phosphoric, sulfuric, acetic, butyric, fumaric, lactic maleic, malonic, oxalic, propionic, salicylic, tartaric, 4-toluenesulfonic or valeric acids. Accordingly, the present invention comprises compounds selected from Formula 1, iV-oxides and agriculturally suitable salts thereof.
Embodiments of the present invention include: Embodiment Al. A compound of Formula 1 wherein R1 is C]- C3 alkyl or C3— C4 cycloalkyl.
Embodiment A2. A compound of Embodiment Al wherein R1 is C1-C2 alkyl. Embodiment A3. A compound of Embodiment A2 wherein R1 is ethyl.
Embodiment A4. A compound of Formula 1 wherein R2 is C1-C2 alkyl- Embodiment A5. A compound of Embodiment A4 wherein R2 is methyl. Embodiment A6. A compound of Formula 1 wherein R3 is Br or Cl. Embodiment A7. A compound of Embodiment A6 wherein R3 is Br. . Embodiment A8. A compound of Formula 1 wherein R4 is Cl; or C]-C2 alkyl or C1-
C2 alkoxy, each optionally substituted with one to three substituents independently selected from F and CL Embodiment A9. A compound of Embodiment A8 wherein R4 is Cl; or Cj- C2 alkyl or Cj-C2 alkoxy, each optionally substituted with one to three F. Embodiment AlO. A compound of Embodiment A9 wherein R4 is C^ alkyl or C^ alkoxy. each optionally substituted with one to three F. Embodiment Al l. A compound of Formula 1 wherein each R5 is independently C]-
C2 alkyl optionally substituted with one to three substituents independently selected from F and Cl. Embodiment A 12. A compound of Embodiment Al 1 wherein each R5 is independently C1-C2 alkyl optionally substituted with one to three Cl. Embodiment A13. A compound of Embodiment A12 wherein each R5 is independently Cj alkyl optionally substituted with one to three Cl. Embodiment A 14. A compound of Formula 1 wherein A is C and R5a is H. Embodiment Bl . A method of controlling at least one plant fungal disease in cereal or broadleaf crops selected from the group consisting of powdery mildew disease caused by Erysiphe spp., Uncinula necatur, Sphaerothecafuligena and
Podosphaera leucotricha, diseases caused by Helminthosporium spp., Pyrenophora teres and Rhyncosporium secalis, and rust disease caused by Puccinia spp., Hemileia vastatrix, Uromyces appendiculatus, Phakopsora pachyrhizi and Phakopsora meibomiae, comprising applying to the plant or portion thereof, or to the plant seed or seedling, a fungicidally effective amount of a compound selected from the compounds of Formula 1, N-oxides, and agriculturally suitable salts thereof. Embodiment B2. A method of Embodiment Bl wherein at least one powdery mildew disease is controlled. Embodiment B3. A method of Embodiment B2 wherein the plant disease is caused by
Erysiphe graminis f. sp. tritid. Embodiment B4. A method of Embodiment B2 wherein the plant disease is caused by
Erysiphe graminis f. sp. hordei.
Embodiment B5. A method of Embodiment B2 wherein the plant disease is caused by Uncinula necatur.
Embodiment B6. A method of Embodiment B2 wherein the plant disease is caused by
Podosphaera leucotricha.. Embodiment B7. A method of Embodiment Bl wherein at least one rust disease is controlled. . Embodiment B8. A method of Embodiment B7 wherein the plant disease is caused by
Puccinia recondita.
Embodiment B9. A method of Embodiment B7 wherein the plant disease is caused by Puccinia striiformis. Embodiment BlO. A method of Embodiment B7 wherein the plant disease is caused by Puccinia graminis. Embodiment BIl. A method of Embodiment B7 wherein the plant disease is caused by Hemileia vastatrix. Embodiment B 12. A method of Embodiment B7 wherein the plant disease is caused by Uromyces appendiculatus. Embodiment B 13. A method of Embodiment B7 wherein the plant disease is caused by Phakopsora pachyrhizi.
Embodiment B 14. A method of any one of Embodiments Bl to Bl 3 wherein the plant is a dicot crop.
Embodiment B 15. A method of Embodiment Bl 4 wherein the dicot crop is selected from soybean, grape and cucurbit.
Embodiment B 16. A method of Embodiment Bl 5 wherein the dicot crop is soybean. Embodiment B17. A method of Embodiment Bl 5 wherein the dicot crop is grape. Embodiment B 18. A method of Embodiment Bl 5 wherein the dicot crop is cucurbit.
Combinations of Embodiments A1-A14 are illustrated by: Embodiment Cl. A compound of Formula 1 wherein R1 is C1-C3 alkyl or C3-C4 cycloalkyl; R2 is C1-C2 alkyl; R3 is Br or Cl;
R4 is Cl; or C1- C2 alkyl or C1- C2 alkoxy, each optionally substituted with one to three substituents independently selected from F and Cl; and each R5 is independently C1-C2 alkyl optionally substituted with one to three substituents independently selected from F and Cl. Embodiment C2. A compound of Embodiment Cl wherein
Rl is C1-C2 alkyl; R2 is methyl; R3 is Br;
R4 is Cl; or C1-C2 alkyl or C1-C2 alkoxy, each optionally substituted with one to three F; and each R5 is independently C1-C2 alkyl optionally substituted with one to three
Cl.
Of note are compounds of Formula 1 (e.g., compounds of Embodiment Cl or Embodiment C2) wherein R4 is Cl. Embodiment C3. A compound of Embodiment C2 wherein
R1 is ethyl; R2 is methyl; R4 is C1 alkyl or C1 alkoxy, each optionally substituted with one to three F; and each R5 is independently Cj alkyl optionally substituted with one to three
Cl.
Embodiment C4. A compound of Embodiment C3 selected from the group consisting of: iV'-[2-bromo-4-[(4-methylpentyl)oxy]-5-(trifluoromethyl)phenyl]-iV-ethyl-iV- methyknethanimidamide;
7/'-[2-bromo-5-methoxy-4-[3-(trimethylsilyl)propoxy]phenyl]-iV-ethyl]-iVr- methylmethanimidamide; iV'-[2-bromo-5-(difluoromethoxy)-4-[3-(trimethylsilyl)propoxy]phenyl]-iV-ethyl- iV-methylmethanimidamide;
Λr'-[2-bromo-5-(difluoromethyl)-4-[(4-methylpentyl)oxy]phenyl]-iV-ethyl-iV- methylmethanimidamide; and iV'-[2-bromo-5-methoxy-4-[(4-methylpentyl)oxy]phenyl]-iV-ethyl-iV- methylmethanimidamide.
This invention also relates to a fungicidal composition comprising a fungicidally effective amount of a compounds of the invention and at least one of a surfactant, a solid diluent or a liquid diluent. Noteworthy as embodiments of fungicidal compositions of the present invention are those comprising the compounds of the embodiments described above. This invention also relates to a method for controlling plant diseases caused by fungal plant pathogens comprising applying to the plant or portion thereof, or to the plant seed, a fungicidally effective amount of a compound of the invention (e.g., as a composition described herein). Methods of use of note are those involving the compounds of the embodiments described above. The compounds of Formula 1 can be prepared by one or more of the following methods and variations as described in Schemes 1-5. The definitions of R1, R2, R3, R4, R5, R5a and A in the compounds of Formulae 1-8 below are as defined above in the Summary of the Invention.
As illustrated in Scheme 1, a compound of Formula 1 can be prepared by reaction of a compound of Formula 2 with a halogenating agent such as JV-chlorosuccinimide, N- bromosuccinimide, iV-iodosuccinimide or their equivalent in an inert solvent such as dichloromethane or carbon tetrachloride. The reaction can be carried out at temperatures ranging from 0 to 110 0C for a period of time between 1 and 48 h. The reaction mixture is then allowed to come to room temperature and filtered. The filtrate is washed with dilute aqueous sodium hydroxide solution, dried over a drying agent such as magnesium sulfate and then concentrated to give the compound of Formula 1. This method is illustrated in Step
E of Example 1 , Step E of Example 2 and Step G of Example 3. Scheme 1
Figure imgf000009_0001
Compounds of Formula 2 can be prepared from anilines of Formula 3 as shown in Scheme 2.. A variety of methods can be used for this transformation. The following five methods are especially useful.
Scheme 2
Figure imgf000009_0002
Method 1: Treatment of an aniline of Formula 3 with an acetal of formula R1R2NCH(OR6^5 wherein R6 is an alkyl. This type of transformation can be found in Toste et al., Synth. Commun., 1994, 24(11), 1617-1624.
Method 2: Treatment of an aniline of Formula 3 with a formamide of formula HC(=O)NR1R2 in the presence of a halogenating reagent such as, but not limited to, POCI3 or SOCI2. This type of transformation can be found in Bergman et al., Tetrahedron, 1990, 46(17), 6058-6112.
Method 3: Treatment of an aniline of Formula 3 with an orthoester of formula HC(OR6>3, wherein R6 is an alkyl, to form a corresponding iminoether, followed by heating the iminoether with an amine of formula HNR1R2. This type of transformation can be found in Pissiotas et al., U.S. Patent 4,209,319.
Method 4: Treatment of an aniline of Formula 3 with phosgene to form an isocyanate followed by reaction of the isocyanate with an amide of formula HCC=O)NR1R2. This type of transformation can be found in Charles et al., World Patent Application Publication WO 2000/46184.
Method 5: Treatment of an aniline of Formula 3 with C2H5OCH=NCN to form an N- cyanoamidine followed by a reaction of the resulting iV-cyanoamidine with an amine of formula HNR' R2. This type of transformation can be found in Charles et al., World Patent Application Publication WO 2000/46184. This method is illustrated in Step C and D of Example I, Step C and D of Example 2 and Step E and F of Example 3.
Compounds of Formula 3 can be prepared by reduction of the nitro group in compounds of Formula 4 as shown in Scheme 3. Many methods can be used for this reduction. Preferred methods include stannous chloride reduction in concentrated hydrochloric acid (see, for example, J. Med. Chem., 1984, 24(12), 1705-1710), iron powder reduction in a solution of acetic acid and water (see, for example, J. Org. Chem., 2001,
66(13), 4563-4575), catalytic hydrogenation using hydrogen and a catalyst such as platinum oxide (see, for example, Egyptian Journal of Chemistry, 1991, 32(3), 359-66) or palladium on carbon (see, for example, U.S. Patent 6,150,343). This method is illustrated in Step B of
Example I5 Step B of Example 2 and Step D of Example 3.
Scheme 3
Figure imgf000010_0001
4 3 As illustrated in Scheme 4, compounds of Formula 4 can be prepared by alkylation of a compound of Formula 5 with an alkylating agent of Formula 6 in the presence of a base. In the alkylating agent of Formula 6, X is a nucleophilic reaction leaving group such as, for example, bromide or iodide. The reaction is conducted in the presence of at least 1 equivalent of a base, preferably from 1 to 2 equivalents. Suitable bases include inorganic bases such as alkali metal hydrides (e.g., lithium hydride, sodium hydride or potassium hydride), alkali metal carbonates or alkali metal hydroxides, and organic bases such as 1,8- diazabicyclo[5.4.0]undec-7-ene. A wide variety of solvents are suitable for the reaction, including, for example, but are not limited to benzene, toluene, tetrahydrofuran, dimethoxyethane, acetonitrile, i\yV-dimethylformamide as well as mixtures of these solvents. The reaction is generally conducted between about -20 and 150 0C, and preferably between 20 and 1400C. The reaction time can range from 1 h to 7 days. Scheme 4
Figure imgf000011_0001
wherein X is a leaving group.
As shown in Scheme 5, compounds of Formula 4 can also be prepared from compounds of Formula 7 by reacting with an appropriate alcohol of Formula 8 in the presence of a base. The reaction is conducted by first treating 1 to 2 equivalents of the appropriate alcohol of Formula 8, preferably from 1 to 1.4 equivalents, with at least 1 equivalent of a base, preferably from 1 to 1.2 equivalents, for a period of time ranging from 3 minutes to 5 h followed by the addition of a compound of Formula 7. Suitable bases include inorganic bases such as alkali metal hydrides (e.g., lithium hydride, sodium hydride or potassium hydride), alkali metal carbonates or alkali metal hydroxides, and organic bases such as l,8-diazabicyclo[5.4.0]undec-7-ene. A phase transfer reagent such as tetrabutylammonium chloride may be employed as a catalyst for the reaction. A wide variety of solvents are suitable for the reaction, such as for example, benzene, toluene, tetrahydrofuran, dimethoxyethane, acetonitrile, iV,7V-dimethylformamide, as well as mixtures of these solvents. The reaction is generally conducted between about -20 and 150 0C, and preferably between 20 and 140 0C. The reaction time can range from 1 h to 7 days. Further experimental details for the method of Scheme 5 are illustrated in Step A of Example 1.
Scheme 5
Figure imgf000011_0002
7 8 4
Alternatively, compounds of Formula 4 can also be prepared from compounds of Formula 5 through a Mitsunobu reaction, which involves reaction of a compound of Formula 5 with an appropriate alcohol of Formula 8. The Mitsunobu Reaction has been the subject of a number of reviews. For conditions and variations of this reaction, see the following reference and references cited therein: Hughes, Org. React., 1992, 42, 335-656. Further experimental details for the Mitsunobu reaction are illustrated in Step A of Example 2 and Step A of Example 3.
Compounds of Formulae 5, 6, 7 and 8 are either commercially available or can be prepared by methods taught in the literature or by slight modification of these literature methods.
It is recognized that some reagents and reaction conditions described above for preparing compounds of Formula 1 may not be compatible with certain functionalities present in the intermediates. In these instances, the incorporation of protection/deprotection sequences or functional group interconversions into the synthesis will aid in obtaining the desired products. The use and choice of the protecting groups will be apparent to one skilled in chemical synthesis (see, for example, Greene, T. W.; Wuts, P. G. M. Protective Groups in Organic Synthesis, 2nd ed.; Wiley: New York, 1991). One skilled in the art will recognize that, in some cases, after the introduction of a given reagent as it is depicted in any individual scheme, it may be necessary to perform additional routine synthetic steps not described in detail to complete the synthesis of compounds of Formula 1. One skilled in the art will also recognize that it may be necessary to perform a combination of the steps illustrated in the above schemes in an order other than that implied by the particular sequence presented to prepare the compounds of Formula 1.
One skilled in the art will also recognize that compounds of Formula 1 and the intermediates described herein can be subjected to various electrophilic, nucleophilic, radical, organometallic, oxidation, and reduction reactions to add substituents or modify existing substituents.
Without further elaboration, it is believed that one skilled in the art using the preceding description can utilize the present invention to its fullest extent. The following Examples are, therefore, to be construed as merely illustrative, and not limiting of the disclosure in any way whatsoever. Percentages are by weight except for chromatographic solvent mixtures or where otherwise indicated. Parts and percentages for chromatographic solvent mixtures are by volume unless otherwise indicated. 1H NMR spectra are reported in ppm downfield from tetramethylsilane; s means singlet, d means doublet, t means triplet, m means multiplet, br means broad singlet.
EXAMPLE 1
Preparation of iV'-[2-bromo-4-[(4-methylpentyl)oxy]-5-(trifluoromethyl)phenyl]-iV-ethyl-N- methyknethanimidamide (Compound 7)
Step A: Preparation of 1 -r(4-methylpentvπoxy1-4-nitro-2-('trifluoromethyl")benzene To a solution of 4-methyl-l-pentanol (5.85 g, 57.2 mmol) in 1,2-dimethoxyethane
(120 DiL) at room temperature under nitrogen was added portionwise sodium hydride (60 % dispersion in mineral oil; 1.96 g, 49 mmol). After the addition, the reaction mixture was stirred at ambient temperature for about 20 minutes until the evolution of hydrogen stopped. Then 2-chloro-5-nitrobenzotrifluoride (9.93 g, 44 mmol) was added. The reaction mixture was heated to reflux and stirred at reflux overnight. The mixture was then cooled to room temperature, and ethyl acetate (300 mL) was added. The organic layer was washed with brine (3 x 200 mL), dried (MgSO^ and concentrated to give 13.5 g of crude product as an oil. The crude product was purified by silica gel flash column chromatography using a gradient of ethyl acetate/hexanes (1:100 to 1:20) to give 5.67 g of the title compound as an oil. 1H NMR (CDCl3) δ 8.5 (d, IH), 8.4 (dd, IH), 7.07 (d, IH), 4.16 (t, 2H), 1.34-1.92 (m, 5H), 0.93 (d, 6H).
Step B: Preparation of 4-[(4-methylpentvDoxyl-3-(trifluoromethyl)benzenamine
A mixture of l-[(4-methylpentyl)oxy]-4-nitro-2-(trifluoromethyl)benzene (i.e. the product from Step A) (3.38 g, 11.62 mmol), platinum oxide (0.80 g, 3.54 mmol) and anhydrous tetrahydrofuran (30 mL) was hydrogenated under hydrogen gas (331 kPa) in a Parr apparatus for 6 h. The reaction mixture was then filtered through Celite®, diatomaceous filter aid. The filtrate was then concentrated to give 3 g of the title compound as an oil.
1H NMR (CDCl3) δ 6.75-7.92 (m, 3H), 3.93 (t, 2H), 1.22-1.82 (m, 5H), 0.91 (d, 6H). Step C: Preparation of iV-cvano-JV-[4-[(4-methylpentyl>)oxy1-3-('trifluoromethyl)- phenyl]methanimidamide
To a solution of ethyl iV-cyanomethanimidate (1.3 g, 13.3 mmol) in absolute ethanol (40 mL) at room temperature was added dropwise a solution of 4-[(4-methylpentyl)oxy]-3- (trifluoromethyl)benzenamine (i.e. the product from Step B) (3.03 g, 11.6 mmol) in absolute ethanol (40 mL). After the addition, the reaction mixture was stirred at room temperature overnight and was then concentrated. The residue was triturated with a solution of 20 % ethyl acetate in hexanes (20 mL). The precipitate was collected by filtration, air dried and then dried in oven to give 1.89 g of the title compound as a white solid melting at 138-140 0C. The filtrate was concentrated, and the residue was triturated with a solution of 10 % ethyl acetate in hexanes (20 mL). The precipitate was collected by filtration, air dried and then dried in oven to give an additional 0.47 g of the title compound as a white solid.
1H NMR (CDCl3) δ 6.9-8.5 (m, 5H), 4.01 (m, 2H), 1.82 (m, 2H), 1.6 (m, IH), 1.35 (m, 2H), 0.92 (d, 6H).
Step D: Preparation of iV-ethyl-iV"-methyl-N"'-f4-r(r4-methylpentyl)oxy1-3-(trifluoro- memvDphenylimethanimidamide To a mixture of iV-cyano-iVr'-[4-[(4-methylpentyl)oxy]-3-(trifluoromethyl)phenyl]- methanimidamide (Le. the product from Step C) (2.34 g, 7.48 mmol) in acetonitrile (65 mL) at room temperature was added 7V-ethylmethylamine (3.22 mL, 37.4 mmol) dropwise. After the addition, the reaction mixture was stirred at room temperature overnight. Ethyl acetate (250 mL) was then added to the reaction mixture. The resulting mixture was washed with water (200 mL) and then brine (200 mL). The organic layer was separated, dried (MgSC^), and concentrated to give 2.25 g of the title compound as a semi-solid.
1H NMR (CDCl3) δ 6.78-7.58 (m, 4H)5 3.98 (m, 2H), 3.2-3.5 (br, 2H), 3.01 (s, 3H), 1.78 (m, 2H), 1.6 (m, IH), 1.35 (m, 2H), 1.21 (t, 3H), 0.91 (d, 6H).
Step E: Preparation of N'-[2-bromo-4-f(4-methylρentyl)oxy]-5-(trifluoromethyr)- phenyli-Λ^-ethyl-JV'-methylmethanirnidarnide f Compound 7)
To a solution of iV-ethyl-Λ'r-methyl-Λ^'-[4-[(4-methylpentyl)oxy]-3-(trifluoromethyl)- phenyljmethanimidamide (i.e. the product from Step D) (1.3 g, 3.94 mmol) in carbon tetrachloride (35 mL) at room temperature was added iV-bromosuccinimide (0.7 g, 3.94 mmol). After the addition, the reaction mixture was heated to reflux and was stirred at reflux for about 4 h. The reaction mixture was then cooled to room temperature and filtered. To the filtrate was added additional carbon tetrachloride until the volume reached about 240 mL. The organic solution was then washed with aqueous 1 N sodium hydroxide solution (2 x 240 mL), dried (MgSO^, and concentrated to give 1.1 g of the title product, a compound of the present invention as a brown oil.
1H NMR (CDCl3) δ 7-7.5 (m, 3H), 3.96 (t, 2H), 3.2-3.6 (br, 2H), 3.03 (s, 3H), 1.8 (m, 2H), 1.6 (m, IH), 1.35 (m, 2H), 1.24 (t, 3H), 0.91 (d, 6H).
EXAMPLE 2 Preparation ofiV'-[2-bromo-5-methoxy-4-[3-(trimethylsilyl)propoxy]phenyl]-iV-ethyl]-iV- methylmethanimidamide (Compound 15)
Step A: Preparation of r3-(2-methoxy-4-m'trophenoxy)propyl1trimethylsilane
Diisopropyl azodicarboxylate (19.6 mL, 99.6 mmol), triphenylphosphine (28.5 g, 109 mmol) and 3-(trimethylsilyl)-l-propanol (14.4 mL, 91 mmol) were added to a solution of 4- nitroguaiacol (15.3 g, 91 mmol) in tetrahydrofuran (400 mL) at about -10 0C. The reaction mixture was then warmed to room temperature and stirred overnight. The excess solvent was removed under reduced pressure, and the residue was purified by silica gel chromatography using 50-100 % of 1 -chlorobutane in hexane as eluant to give 22 g of the title product as a yellow solid melting at 40-43 0C. 1H NMR (CDCl3) δ 7.9 (dd, IH), 7.75 (d, IH), 6.89 (d, IH), 4.06 (t, 2H), 3.96 (s, 3H), 1.89
(m, 2H), 0.6 (m, 2H), 0.04 (s, 9 H).
Step B : Preparation of 3 -methoxy-4- [3 -(trimethylsil vDpropoxyibenzenamine
A mixture of [3-(2-methoxy-4-nitrophenoxy)propyl]trimethylsilane (i.e. the product from Step A) (10 g, 35.2 mmol) and platinum oxide (1 g, 4.41 mmol) in anhydrous tetrahydrofuran (25 mL) was hydrogenated under hydrogen gas (331 kPa) in a Parr apparatus for 7 h. The reaction mixture was then filtered through Celite®, diatomaceous filter aid. The filtrate was concentrated to give 8.6 g of the title compound as a brown oil. 1H NMR (CDCl3) δ 6.71 (d, IH)5 6.3 (d, IH), 6.2 (dd, IH), 3.81-3.9 (m, 5H)5 3.42 (br, 2H), 1.8 (m, 2H), 0.58 (m, 2H), 0.01 (s, 9H).
Step C: Preparation of iV-cyano-NJ-|'3-methoxy-4-|'3-('trimethylsilyl)propoxy]phenyll- methanimidamide To a solution of iV-cyanomethanimidate (9.9 g, 101.8 mmol) in absolute ethanol (50 mL) at room temperature was added dropwise a solution of 3-methoxy-4-[3- (trimetiiylsilyl)ρropoxy]benzenamine (i.e. the product from Step B) (8.6 g, 33.7 mmol) in absolute ethanol (50 mL). The reaction mixture was stirred at room temperature overnight and then concentrated. The residue was triturated with a solution of 20 % ethyl acetate in hexanes. The precipitate was collected by filtration, air dried, and then dried in oven to give 10 g of crude product as a purple solid. The crude product was further triturated with a solution of 10 % ethyl acetate in hexanes. The precipitate was collected by filtration, air dried, and then dried in oven to give 7.8 g of the title compound as a solid melting at 142- 144 °C. 1H NMR (CDCl3) δ 6.6-9.2 (m, 5H), 3.85-4 (m, 5H), 1.82 (m, 2H), 0.58 (m, 2H), 0.02 (s, 9H).
Step D: Preparation of iV;-ethyl-iv'J-|'3-methoxy-4-[3-('trirnethylsilyl)propoxy]phenyl]-
JV-methylmethanimidamide A mixture of iV-cyano-iV'-[3-methoxy-4-[3-(trimethylsilyl)proρoxy]phenyl]methan- imidamide (i.e. the product from Step C) (5 g, 16.4 mmol), iV-ethylmethylamine (7 mL, 81.97 mmol) and acetonitrile (20 mL) in a Fisher-Porter bottle was heated at 130 0C for 4 h. The resulting mixture was cooled to room temperature and then concentrated. The residue was purified by silica gel chromatography using 50-100 % ethyl acetate in hexane as eluant to give 3.1 g of the title product as an oil. 1H NMR (CDCl3) δ 7.54 (s, IH), 6.77 (d, IH), 6.58 (d, IH)5 6.42 (dd, IH), 3.91 (t, 2H), 3.85 (s, 3H), 3.2-3.5 (br, 2H), 2.98 (s, 3H), 1.82 (m, 2H), 1.2 (t, 3H), 0.58 (m, 2H), 0.02 (s, 9H).
Step E: Preparation of JV'-r2-bromo-5-methoxy-4-f3-('trimethylsilyl)propoxy1phenvn-
JVr-emyl1-iV-methylm.ethaniniidarnide (Compound 15) To a solution of JV1-ethyl-N'-[3-methoxy-4-[3-(trimethylsilyl)propoxy]phenyl]-iV"- methylmethanimidamide (i.e. the product from Step D) (1.5 g, 4.66 mmol) in carbon tetrachloride (30 mL) at room temperature was added iV-bromosuccinimide (0.91 g, 5.12 mmol). The reaction mixture was stirred at room temperature for about 3.5 h. The reaction mixture was then concentrated, and the residue was purified by silica gel chromatography using 50 % ethyl acetate in hexane as eluant to give 1.42 g of the title product, a compound of the present invention as a brown oil.
1H NMR (CDCl3) δ 7.27-7.56 (br, IH)5 7.03 (s, IH), 6.46 (s, IH)5 3.9 (t, 2H), 3.84 (s, 3H), 3.2-3.6 (br, 2H), 3.02 (s, 3H)5 1.82 (m, 2H)5 1.23 (t5 3H)5 0.58 (m, 2H), 0.01 (s, 9H). EXAMPLE 3
Preparation ofiV''-[2-bromo-5-(difluoromethoxy)-4-[3-(triπiethylsilyl)propoxy]phenyl]-iV- ethyl-iV-methylmethanimidamide (Compound 22)
Step A: Preparation of 5-nitro-2-["3-rtrlmethylsilyl)propoxy1benzaldeliyde To a solution of diisopropyl azodicarboxylate (26 mL, 132 mmol) in anhydrous tetrahydrofuraή (500 mL) at -10 0C was added 3-(trimethylsilyl)-l-propanol (19 mL, 119.5 mmol), 2-hydroxy-5-nitrobenzaldehyde (20 g, 119.7 mmol) and triphenylphosphine (37.7 g, 143.3 mmol). The reaction mixture was warmed to room temperature and stirred overnight. The reaction mixture was then concentrated under reduced pressure, and the resulting precipitate was removed by filtration. The filtrate was concentrated, and the residue was purified by silica gel chromatography using 10 to 20 % ethyl acetate in hexane as eluant to give 12.4 g of the title product as an oil.
1H NMR (CDCl3) δ 10.48 (s, IH)3 8.7 (d, IH), 8.4 (dd, IH)5 7.09 (d, IH), 4.18 (t, 2H), 1.9 (m, 2H), 0.65 (m.2H), 0.05 (s, 9H). Step B: Preparation of 5-nitro-2-[3-(trimethylsilyl)propoxy]phenol
To a solution of 5-nitro-2-[3-(trimethylsilyl)propoxy]benzaldehyde (i.e. the product from Step A) (12.4 g, 44.3 mmol) in chloroform (120 mL) at room temperature was added 3- chloroperbenzoic acid (about 53% pure, 14.1 g, 53.1 mmol). The reaction mixture was stirred at room temperature overnight and then filtered. The filtrate was washed with saturated sodium bisulfite aqueous solution (2 x 200 mL), followed by saturated sodium bicarbonate aqueous solution (3 x 200 mL), dried (MgSC^), and concentrated to give 14 g of an oil. The oil was then added to a solution of concentrated hydrochloric acid (15 drops) in methanol (60 mL) at room temperature, and the reaction mixture was stirred overnight. The reaction mixture was then concentrated, and the residue was purified by silica gel chromatography using 10 to 20 % ethyl acetate in hexane as eluant to give 8.78 g of the title product as an oil.
1H NMR (CDCl3) δ 7.8-7.84 (m, 2H), 6.87 (d, IH), 5.84 (s, IH), 4.11 (t, 2H), 1.85 (m, 2H), 0.6 (m, 2H), 0.04 (s, 9 H). Step C: Preparation of f3-[2-(difluoromethoxy)-4-nitrophenoxylpropyl'|trimethyl- silane
To a solution of 5-nitro-2-[3-(trimethylsilyl)propoxy]phenol (i.e. the product from Step B) (8.77 g, 32.6 mmol) in/?-dioxane (140 mL) was added tetrabutylammonium bromide (10.5 g, 32.6 mmol) and aqueous 50 % sodium hydroxide solution (28 mL) while the temperature was maintained between 20 and 30 0C using an acetone bath. Freon® 22, chlorodifluoromethane (43 mL) was then added to the reaction mixture through a dry ice condenser. The reaction mixture was stirred at room temperature for 2 h, and an additional amount of Freon® 22, chlorodifluoromethane (12 mL) was then added through a dry ice condenser. The reaction mixture was stirred at room temperature for another 3 h, and dichloromethane (500 mL) was then added. The reaction mixture was washed with water (3 x 300 mL), dried (MgSC^), and concentrated. The residue was purified by silica gel chromatography using 5 to 10 % ethyl acetate in hexane as eluant to give 7.26 g of the title product as an oil. 1H NMR (CDCl3) δ 8.05-8.16 (m, 2H)3 7 (d, IH), 6.6 (t, IH), 4.08 (t, 2H), 1.85 (m, 2H), 0.6 (m, 2H), 0.04 (s, 9H).
Step D: Preparation of 3-rdifluoromethoxyV4-f3-trimethylsilyl]propoxy]ben2amine
A mixture of [3-[2-difluoromethoxy)-4-nitrophenoxy]propyl]trimethylsilane (i.e. the product from Step C) (7.24 g, 22.7 mmol), platinum oxide (3.58 g, 15.76 mmol) and anhydrous tetrahydrofuran (70 mL) was hydrogenated under hydrogen gas (48 psi, 331 kPa) in a Parr apparatus overnight. The reaction mixture was then filtered through Celite®, diatomaceous filter aid. The filtrate was concentrated to give 6.6 g of the title compound as a brown oil. IH NMR (CDCl3) δ 6.3-7.81 (m, 4H), 3.87 (t, 2H), 3.45 (br, 2H), 1.77 (m, 2H), 0.58 (m, 2H), 0.01 (s, 9H).
Step E: Preparation of JV-cyano-N'-f3-('difluoromethoxy)-4-r3-('trimethylsilyl)- propoxylphenyllmethanimidamide
To a solution of i^cyanomethanimidate (2.55 g, 26.0 mmol) in absolute ethanol (90 mL) at room temperature was added dropwise a solution of 3-(difluoromethoxy)-4-[3- trimethylsilyl]propoxy]benzarnine (i.e. the product from Step D) (6.58 g, 22.8 mmol) in absolute ethanol (90 mL). After the addition, the reaction solution was stirred at room temperature overnight and was then concentrated. The residue was triturated with a solution of 20 % ethyl acetate in hexanes. The precipitate was collected by filtration, air dried and then dried in oven to give 5 g of the title compound as a solid melting at 154-155 0C. IH NMR (CDCl3) δ 6.25-8.9 (m, 6H), 3.97 (t, 2H), 1.8 (m, 2H), 0.6 (m, 2H), 0.03 (s, 9H).
Step F: Preparation of Jv">-f3-fdifluoromethoxy)-4-f3-('trimethylsilyl')propoxy1phenyl1-
JV-ethyl-JV-methyhnethanimidamide
To a suspension of iV-cyano-7V'-[3-(difiuoromethoxy)-4-[3-(trimethylsilyl)- propoxy]phenyl]methanimidamide (i.e. the product from Step E) (3.38 g, 10 mmol) in acetonitrile (40 mL) at room temperature was added dropwise N-ethylmethylamine (4.3 mL, 50 mmol). The resulting mixture was stirred at room temperature overnight, and ethyl acetate (200 mL) was then added. The organic solution was washed with water (2 x 200 mL) followed by brine (200 mL), dried (MgSC^), and concentrated to give 3.65 g of the title compound as an oil. *H NMR (CDCl3) δ 7.48 (br, IH), 6.3-6.9 (m, 4H), 3.9 (t, 2H), 3.2-3.5 (br, 2H), 2.98 (s, 3H), 1.78 (m, 2H), 1.2 (t, 3H), 0.58 (m, 2H), 0.01 (s, 9H). Step G: Preparation of 7^>-r2-bromo-5-(difluoromethoxy)-4-r3-rtrimethylsilyl)-
. propoxy1phenyl]-iV'-ethyl-iV'-methykπeihanimidamide (Compound 22)
To a solution of iV'-[3-(difluoromethoxy)-4-[3-(trimethylsilyl)propoxy]phenyl]-iV- ethyl-iV-methylmethanimidaniide (i.e. the product from Step F) (0.55 g, 1.52 mrnol) in carbon tetrachloride (7 mL) at room temperature was added iV^bromosuccinimide (0.30 g,
1.68 mmol). After the addition, the reaction mixture was stirred at room temperature overnight, and dichloromethane (100 mL) was then added. The organic mixture was washed with aqueous 1 N sodium hydroxide solution (2 x 100 mL), dried (MgSO^), and concentrated. The residue was purified by silica gel chromatography using 20 % ethyl acetate in hexane as ehiant to give 0.5 g of the title product, a compound of the present invention as a brown oil.
1H NMR (CDCl3) δ 7.27-7.5 (br, IH), 7.15 (s, IH), 6.7 (s, IH), 6.54 (t, IH), 3.9 (t, 2H), 3.2- 3.6 (br, 2H), 3.02 (s, 3H), 1.78 (m, 2H), 1.23 (t, 3H), 0.6 (m, 2H), 0.02 (s, 9H).
By the procedures described herein together with methods known in the art, the following compounds of Tables 1 to 6 can be prepared. The following abbreviations are used in the Tables which follow: n means normal, i means iso, . c means cyclo,
OMe means methoxy, OEt means ethoxy. The compound numbers of Tables 1 to 4 refer to compounds in Index Table A.
Table 1
Figure imgf000018_0001
Cmpd No. R1 R2 R3 R4 Cmpd No. R1 R2 R3 R4
CH3 CH3 Br CH3 C2H5 C2H5 Cl Cl
C2H5 CH3 Br CH3 /-C3H7 CH3 Cl Cl
C2H5 C2H5 Br CH3 C-C3H5 CH3 Cl Cl
/-C3H7 CH3 Br CH3 W-C3H7 CH3 Br CF3
C-C3H5 CH3 Br CH3 H-C3H7 CH3 Br CH3
CH3 CH3 Br OMe M-C3H7 CH3 Br OCHF2
15 C2H5 CH3 Br OMe W-C3H7 CH3 Br OMe
C2H5 C2H5 Br OMe W-C3H7 CH3 Br Cl
18 ■ /-C3H7 CH3 Br OMe 10 CH3 CH3 Cl CF3
C-C3H5 CH3 Br OMe 3 C2H5 CH3 Cl CF3 Cmpd No. R2 R3 R4 Cmpd No. Rl . R2 R3 R4
CH3 CH3 Br OEt CH3 CH3 Cl OEt
42 C2H5 CH3 Br OEt 43 C2H5 CH3 , Cl OEt
C2H5 C2H5 Br OEt C2H5 C2H5 Cl OEt
H-C3H7 CH3 Br OEt 44 M-C3H7 CH3 Cl OEt
/-C3H7 CH3 Br OEt /-C3H7 CH3 Cl OEt
C-C3H5 CH3 Br OEt C-C3H5 CH3 Cl OEt
CH3 CH3 Br OCHF2 C2H5 C2H5 Cl CF3
22 C2H5 CH3 Br OCHF2 35 /-C3H7 CH3 Cl CF3
C2H5 CH3 Br OCHF2 C-C3H5 CH3 Cl CF3
'-C3H7 CH3 Br OCHF2 CH3 CH3 Cl CHF2
C-C3H5 CH3 Br OCHF2 6 C2H5 CH3 Cl CHF2
C2H5 CH3 Br C2H5 C2H5 C2H5 Cl CHF2
C2H5 CH3 Br CH2CF3 /-C3H7 CH3 Cl CHF2
C2H5 CH3 Br CHFCHF2 C-C3H5 CH3 Cl CHF2
C2H5 CH3 Br CHCl2 29 CH3 CH3 Br CF3
C2H5 CH3 Br CCl3 2 C2H5 CH3 Br CF3
CH3 CH3 Br OCF3 C2H5 C2H5 Br CF3
C2H5 CH3 Br OCF3 34 /-C3H7 CH3 Br CF3
C2H5 C2H5 Br OCF3 C-C3H5 CH3 Br CF3
Z-C3H7 CH3 Br OCF3 CH3 CH3 Br CHF2
C-C3H5 CH3 Br OCF3 5 C2H5 CH3 Br CHF2
CH3 CH3 Cl OMe C2H5 C2H5 Br CHF2
16 C2H5 CH3 Cl OMe /-C3H7 CH3 Br CHF2
C2H5 C2H5 Cl OMe C-C3H5 CH3 Br CHF2
«-C3H7 CH3 Cl OMe W-C3H7 CH3 Br OMe
17 '-C3H7 CH3 Cl OMe C2H5 CH3 I CF3
C-C3H5 CH3 Cl OMe CH3 Br CF3
C2H5 CH3 I OMe C2H5 CH3 I CHF2
C2H5 CH3 1 OCF3 /1-C4H9 CH3 Br CHF2
C2H5 CH3 I CH3 23 C2H5 CH3 Cl OCHF2
C2H5 CH3 I OCHF2 H-C4H9 CH3 Br OCHF2
C2H5 CH3 I Cl /-C3H7 CH3 Cl OCHF2
CH3 CH3 Cl Cl C-C3H5 CH3 Cl OCHF2
C2H5 CH3 Cl Cl CH3 CH3 Cl OCHF2 Table 2
Figure imgf000020_0001
Cmpd No. R1 R2 R3 R4 Cmpd No. Rl R2 R3 R4
CH3 CH3 Br CH3 C2H5 C2H5 Cl Cl
C2H5 CH3 Br ■ CH3 /-C3H7 CH3 Cl Cl
C2H5 C2H5 Br CH3 C-C3H5 CH3 Cl Cl
' /-C3H7 CH3 Br CH3 M-C3H7 CH3 Br CF3
C-C3H5 CH3 Br CH3 «-C3H7 CH3 Br CH3
CH3 CH3 Br OMe H-C3H7 CH3 Br OCHF2
C2H5 CH3 Br OMe Ti-C3H7 CH3 Br OMe
C2H5 C2H5 Br OMe «-C3H7 CH3 Br Cl
/-C3H7 CH3 Br OMe CH3 CH3 Cl CF3
C-C3H5 CH3 . Br OMe 1 1 C2H5 CH3 Cl CF3
CH3 CH3 Br OEt CH3 CH3 Cl OEt
C2H5 CH3 Br OEt C2H5 CH3 Cl OEt
C2H5 C2H5 Br OEt C2H5 C2H5 Cl OEt
M-C3H7 CH3 Br OEt W-C3H7 CH3 Cl OEt
/-C3H7 CH3 Br OEt /-C3H7 CH3 Cl OEt
C-C3H5 CH3 Br OEt C-C3H5 CH3 Cl OEt
CH3 CH3 Br OCHF2 C2H5 C2H5 Cl CF3
C2H5 CH3 Br OCHF2 /-C3H7 CH3 Cl CF3
C2H5 CH3 Br OCHF2 C-C3H5 CH3 Cl CF3
/-C3H7 CH3 Br OCHF2 CH3 CH3 Cl CHF2
0C3H5 CH3 Br OCHF2 C2H5 CH3 Cl CHF2
C2H5 CH3 Br C2H5 C2H5 C2H5 Cl CHF2
C2H5 CH3 Br CH2CF3 /-C3H7 CH3 Cl CHF2
C2H5 CH3 Br CHFCHF2 C-C3H5 CH3 Cl CHF2
C2H5 CH3 Br CHCl2 CH3 CH3 Br CF3
C2H5 CH3 Br CCl3 I2 C2H5 CH3 Br CF3
CH3 CH3 Br OCF3 C2H5 C2H5 Br CF3
C2H5 CH3 Br OCF3 /-C3H7 CH3 Br CF3 Cmpd No. R1 R2 R3 R4 Cmpd No. R1 R2 R3 R4
C2H5 C2H5 Br OCF3 C-C3H5 CH3 Br CF3
J-C3H7 CH3 Br OCF3 CH3 CH3 Br CHF2
C-C3H5 CH3 Br OCF3 C2H5 CH3 Br CHF2
CH3 CH3 Cl OMe C2H5 C2H5 Br CHF2
C2H5 CH3 Cl OMe /-C3H7 CH3 Br CHF2
C2H5 C2H5 CI OMe C-C3H5 CH3 Br CHF2
W-C3H7 CH3 Cl OMe /Z-C3H7 CH3 Br OMe
'-C3H7 CH3 Cl OMe C2H5 CH3 I CF3
C-C3H5 CH3 Cl OMe W-C4Hp CH3 Br CF3
C2H5 CH3 I OMe C2H5 CH3 I CHF2
C2H5 CH3 I OCF3 W-C4H9 CH3 Br CHF2
C2H5 CH3 I CH3 C2H5 CH3 Cl OCHF2
C2H5 CH3 I OCHF2 M-C4H9 CH3 Br OCHF2
C2H5 CH3 I Cl /-C3H7 CH3 Cl OCHF2
CH3 CH3 Cl Cl C-C3H5 CH3 Cl OCHF2
C2H5 CH3 Cl Cl CH3 CH3 Cl OCHF2
Table 3
Figure imgf000021_0001
Cmpd No. R2 Rl R3 R4 Cmpd No. R2 Rl R3 R4
CH3 CH3 Br CH3 C2H5 C2H5 Cl Cl
C2H5 CH3 Br CH3 /-C3H7 CH3 Cl Cl
C2H5 C2H5 Br CH3 C-C3H5 CH3 Cl Cl
/-C3H7 CH3 Br CH3 «-C3H7 CH3 Br CF3
C-C3H5 CH3 Br CH3 W-C3H7 CH3 Br CH3
CH3 CH3 Br OMe W-C3H7 CH3 Br OCHF2
25 C2H5 CH3 Br OMe W-C3H7 CH3 Br. OMe
C2H5 C2H5 Br OMe W-C3H7 CH3 Br Cl
30 '-C3H7 CH3 Br OMe CH3 CH3 Cl CF3
C-C3H5 CH3 Br OMe 4 C2H5 CH3 Cl CF3
CH3 CH3 Br OEt CH3 CH3 Cl OEt CmpdNo. R2 Rl R3 R4 Cmpd No. R2 Rl R3 R4
36 C2H5 CH3 Br OEt 37 C2H5 CH3 Cl OEt
C2H5 C2H5 Br OEt C2H5 C2H5 Cl OEt
38 W-C3H7 CH3 Br OEt 39 M-C3H7 CH3 Cl OEt
40 Z-C3H7 CH3 Br OEt 41 /-C3H7 CH3 Cl OEt
C-C3H5 CH3 Br OEt C-C3H5 CH3 Cl OEt
CH3 CH3 Br OCHF2 C2H5 C2H5 Cl CF3
C2H5 CH3 Br OCHF2 /-C3H7 CH3 Cl CF3
27 C2H5 CH3 Br OCHF2 C-C3H5 CH3 Cl CF3
J-C3H7 CH3 Br OCHF2 CH3 CH3 Cl CHF2
C-C3H5 CH3 Br OCHF2 9 C2H5 CH3 Cl CHF2
C2H5 CH3 Br C2H5 C2H5 C2H5 Cl CHF2
C2H5 CH3 BT CH2CF3 /-C3H7 CH3 CI CHF2
C2H5 CH3 Br CHFCHF2 C-C3H5 CH3 Cl CHF2
C2H5 CH3 Br CHCl2 CH3 CH3 Br CF3
C2H5 CH3 Br CCl3 7 C2H5 CH3 Br CF3
CH3 CH3 Br OCF3 C2H5 C2H5 Br CF3
C2H5 CH3 Br OCF3 /-C3H7 CH3 Br CF3
C2H5 C2H5 Br OCF3 C-C3H5 CH3 Br CF3
/-C3H7 CH3 Br OCF3 CH3 CH3 Br CHF2
C-C3H5 CH3 Br OCF3 8 C2H5 CH3 Br CHF2
CH3 CH3 CI OMe C2H5 C2H5 Br CHF2
26 C2H5 CH3 Cl OMe /-C3H7 CH3 Br CHF2
C2H5 C2H5 Cl OMe C-C3H5 CH3 Br CHF2
33 /J-C3H7 CH3 Cl OMe 31 M-C3H7 CH3 Br OMe
32 t-C3H7 CH3 Cl OMe C2H5 CH3 I CF3
C-C3H5 CH3 Cl OMe M-C4H9 CH3 Br CF3
C2H5 CH3 I OMe C2H5 CH3 I CHF2
C2H5 CH3 I OCF3 H-C4H9 CH3 Br CHF2
C2H5 CH3 I CH3 28 C2H5 CH3 Cl OCHF2
C2H5 CH3 I OCHF2 M-C4H9 CH3 Br OCHF2
C2H5 CH3 I Cl /-C3H7 CH3 Cl OCHF2
1 CH3 CH3 Cl Cl C-C3H5 CH3 Cl OCHF2
C2H5 CH3 Cl Cl CH3 CH3 Cl OCHF2
Figure imgf000023_0001
Cmpd No. R1 R2 R3 R4 Cmpd No. Rl R2 R3 R4
CH3 CH3 Br CH3 C2H5 C2H5 Cl Cl
C2H5 CH3 Br CH3 /-C3H7 CH3 Cl Cl
C2H5 C2H5 Br ' CH3 C-C3H5 CH3 Cl CI
Z-C3H7 CH3 Br CH3 W-C3H7 CH3 Br CF3
C-C3H5 CH3 Br CH3 M-C3H7 CH3 Br CH3
CH3 CH3 Br OMe «-C3H7 CH3 Br OCHF2
24 C2H5 CH3 Br OMe «-C3H7 CH3 Br OMe
C2H5 C2H5 Br OMe W-C3H7 CH3 Br Cl
Z-C3H7 CH3 Br OMe CH3 CH3 Cl CF3
C-C3H5 CH3 Br OMe 13 C2H5 CH3 Cl CF3
CH3 CH3 Br OEt CH3 CH3 Cl OEt
C2H5 CH3 Br OEt C2H5 CH3 Cl OEt
C2H5 C2H5 Br OEt C2H5 C2H5 Cl OEt
K-C3H7 CH3 Br OEt W-C3H7 CH3 Cl OEt
/-C3H7 CH3 Br OEt /-C3H7 CH3 Cl OEt
C-C3H5 CH3 Br OEt C-C3H5 CH3 Cl OEt
CH3 CH3 Br OCHF2 C2H5 C2H5 Cl CF3
C2H5 CH3 Br OCHF2 /-C3H7 CH3 Cl CF3
C2H5 CH3 Br OCHF2 C-C3H5 CH3 Cl CF3
Z-C3H7 CH3 Br OCHF2 CH3 CH3 Cl CHF2
C-C3H5 CH3 Br OCHF2 19 C2H5 CH3 Cl CHF2
C2H5 CH3 Br C2H5 C2H5 C2H5 Cl CHF2
C2H5 CH3 Br CH2CF3 Z-C3H7 CH3 Cl CHF2
C2H5 CH3 Br CHFCHF2 C-C3H5 CH3 Cl CHF2
C2H5 CH3 Br CHCl2 CH3 CH3 Br CF3
C2H5 CH3 Br CCl3 14 C2H5 CH3 Br - CF3
CH3 CH3 Br OCF3 C2H5 C2H5 Br CF3
C2H5 CH3 Br OCF3 Z-C3H7 CH3 Br CF3
C2H5 C2H5 Br OCF3 C-C3H5 CH3 Br CF3 Cmpd No. RI R2 R3 R4 Cmpd No. R1 R2 R3 R4
J-C3H7 CH3 Br OCF3 CH3 CH3 Br CHF2
C-C3H5 CH3 Br OCF3 20 C2H5 CH3 Br CHF2
CH3 CH3 Cl OMe C2H5 C2H5 Br CHF2
21 C2H5 CH3 Cl OMe /-C3H7 CH3 Br CHF2
C2H5 C2H5 Cl OMe C-C3H5 CH3 . Br CHF2
W-C3Hy CH3 Cl OMe W-C3H7 CH3 Br OMe
/-C3H7 CH3 Cl OMe C2H5 CH3 I CF3
C-C3H5 CH3 Cl OMe W-C-JHa CH3 Br CF3
C2H5 CH3 1 OMe C2H5 CH3 I CHF2
C2H5 CH3 I OCF3 W-C4H9 CH3 Br CHF2
C2H5 CH3 I CH3 C2H5 CH3 Cl OCHF2
C2H5 CH3 I OCHF2 W-C4H9 CH3 Br OCHF2
C2H5 CH3 I Cl ,-C3H7 CH3 Cl OCHF2
CH3 CH3 Cl Cl C-C3H5 CH3 Cl OCHF2
C2H5 CH3 Cl CI CH3 CH3 Cl OCHF2
Table 5
Figure imgf000024_0001
Rl R2 R3 R4 Rl R2 R3 R4
CH3 CH3 Br CH3 C2H5 C2H5 Cl Cl
C2H5 CH3 Br CH3 /-C3H7 CH3 Cl Cl
C2H5 C2H5 Br CH3 C-C3H5 CH3 Cl Cl
/-C3H7 CH3 Br CH3 W-C3H7 CH3 Br CF3
C-C3H5 CH3 Br CH3 W-C3H7 CH3 Br CH3
CH3 CH3 Br OMe W-C3H7 CH3 Br OCHF2
C2H3 CH3 Br OMe W-C3H7 CH3 Br OMe
C2H5 C2H5 Br OMe W-C3H7 CH3 Br Cl .
J-C3H7 CH3 Br OMe CH3 CH3 Cl CF3
C-C3H5 CH3 Br OMe C2H5 CH3 Cl CF3
CH3 CH3 Br OEt CH3 " CH3 Cl OEt
C2H5 CH3 Br OEt C2H5 CH3 Cl OEt Rl R3 R4 Rl R2 R3 R4
C2H5 C2H5 Br OEt C2H5 C2H5 Cl OEt
W-C3H7 CH3 Br OEt W-C3H7 CH3 Cl OEt
/-C3H7 CH3 Br OEt /-C3H7 CH3 Cl OEt
C-C3H5 CH3 Br OEt C-C3H5 CH3 Cl OEt
CH3 CH3 Br OCHP2 C2H5 C2H5 Cl CF3
C2H5 CH3 Br OCHF2 1-C3H7 CH3 Cl CF3
C2H5 CH3 Br OCHF2 C-C3H5 CH3 Cl CF3
J-C3H7 CH3 Br OCHF2 CH3 CH3 Cl CHF2
C-C3H5 CH3 Br OCHF2 C2H5 CH3 Cl CHF2
C2H5 CH3 Br C2H5 C2H5 C2H5 Cl CHF2
C2H5 CH3 Br CH2CF3 /-C3H7 CH3 Cl CHF2
C2H5 CH3 Br .CHFCHF2 C-C3H5 CH3 Cl CHF2
C2H5 CH3 Br CHCl2 CH3 CH3 Br CF3
C2H5 CH3 Br CCl3 C2H5 CH3 Br CF3
CH3 CH3 Br OCF3 C2H5 C2H5 Br CF3
C2H5 CH3 Br OCF3 /-C3H7 CH3 Br CF3
C2H5 C2H5 Br OCF3 C-C3H5 CH3 Br CF3
/-C3H7 CH3 Br OCF3 CH3 CH3 Br CHF2
C-C3H5 CH3 Br OCF3 C2H5 CH3 Br CHF2
CH3 CH3 Cl OMe C2H5 C2H5 Br CHF2
C2H5 CH3 Cl OMe /-C3H7 CH3 Br CHF2 C2H5 C2H5 Cl OMe C-C3H5 CH3 Br CHF2
W-C3H7 CH3 Cl OMe M-C3H7 CH3 Br OMe
;-C3H7 CH3 Cl OMe C2H5 CH3 I CF3
C-C3H5 CH3 Cl OMe H-C4H9 CH3 Br CF3
C2H5 CH3 I OMe C2H5 CH3 I CHF2
C2H5 CH3 I OCF3 W-C4H9 CH3 Br CHF2
C2H5 CH3 r CH3 C2H5 CH3 Cl . OCHF2
C2H5 CH3 I OCHF2 Λ-C4H9 CH3 Br OCHF2
C2H5 CH3 1 Cl /-C3H7 CH3 Cl OCHF2
CH3 CH3 Cl Cl C-C3H5 CH3 Cl OCHF2
C2H5 CH3 Cl Cl CH3 CH3 Cl OCHF2 Table 6
Figure imgf000026_0001
(R^) CR5)2A R3 R4
BrCH2(CH3)2Si Br CF3
FCH2(CH3)2Si Br CF3
ICH2(CH3)2Si Br CF3
BrCH2(CH3)2Si Br CHF2
FCH2(CH3)2Si Br CHF2
ICH2(CH3)2Si Br CHF2
C2H5(CH3)2Si Br CF3
(C1CH2)2(CH3)SJ Br CF3
(C2H5)2(CH3)Si Br CF3
BrCH2(CH3)2Si Cl CF3
ICH2(CH3)2Si Br Cl
BrCH2(CH3)2Si Br Cl
FCH2(CH3)2Si Br Cl
BrCH2(CH3)2Si Br OCH3
BrCH2(CH3)2Si Cl OCH3
C2H5(CH3)2Si Br OCH3
(C2H5)2(CH3)Si Br OCH3
C2H5(CH3)2Si Br OCHF2
ICH2(CH3)2Si Br OCHF2
BrCH2(CH3)2Si Br OCHF2
FCH2(CH3)2Si Br OCHF2
BrCH2(CH3)2Si Cl OCHF2
(CH3)2CH Br CH2F
(CH3)3C Br CH2F
(CH3)3Si Br CH2F
(CH3)2CH Cl CH2F
ClCH2(CH3)2Si Br CH2F
(CH3)3C Cl CH2F
(CH3)3Si Cl CH2F
(ClCH2)2(CH3)Si Cl CH2F Formulation/Utility
Compounds of this invention will generally be used as a formulation or composition with an agriculturally suitable carrier comprising at least one of a liquid diluent, a solid diluent or a surfactant. The formulation or composition ingredients are selected to be consistent with the physical properties of the active ingredient, mode of application and environmental factors such as soil type, moisture and temperature. Useful formulations include 'liquids such as solutions (including emulsifiable concentrates), suspensions, emulsions (including microemulsions and/or suspoemulsions) and the like which optionally can be thickened into gels. Useful formulations further include solids such as dusts, powders, granules, pellets, tablets, films (including seed coatings), and the like which can be water-dispersible ("wettable") or water-soluble. 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. 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 to 100 percent by weight.
Weight Percent
Active Ingredient Diluent Surfactant
Water-Dispersible and Water- 0.001-90 0-99.999 0-15 soluble Granules, Tablets and Powders.
Suspensions, Emulsions, 1-50 40-99 0-50 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
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 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. AU formulations can contain minor amounts of additives to reduce foam, caking, corrosion, microbiological growth and the like, or thickeners to increase viscosity.
Surfactants include, for example, polyethoxylated alcohols, polyethoxylated alkylphenols, polyethoxylated sorbitan fatty acid esters, dialkyl sulfosuccinates, alkyl sulfates, alkylbenzene sulfonates, organosilicones, ΛζiV-dialkyltaurates, lignin sulfonates, naphthalene sulfonate formaldehyde condensates, polycarboxylates, glycerol esters, poly- oxyethylene/polyoxypropylene block copolymers, and alkylpolyglycosides where the number of glucose units, referred to as degree of polymerization (D.P.), can range from 1 to 3 and the alkyl units can range from C6 to C14 (see Pure and Applied Chemistry 72, 1255—
1264). Solid diluents include, for example, clays such as bentonite, montmorillonite, attapulgite and kaolin, starch, sugar, silica, talc, diatomaceous earth, urea, calcium carbonate, sodium carbonate and bicarbonate, and sodium sulfate. Liquid diluents include, for example, water, ΛyV-dimethylformamide, dimethyl sulfoxide, JV-alkylpyrrolidone, ethylene glycol, polypropylene glycol, propylene carbonate, dibasic esters, paraffins, alkylbenzenes, alkylnaphthalenes, glycerine, triacetine, oils of olive, castor, linseed, tung, sesame, corn, peanut, cotton-seed, soybean, rape-seed and coconut, fatty acid esters, ketones such as cyclohexanone, 2-heptanone, isophorone and 4-hydroxy-4-methyl-2-pentanone, acetates such as hexyl acetate, heptyl acetate and octyl acetate, and alcohols such as methanol, cyclohexanol, decanol, benzyl and tetrahydrofurfuryl alcohol.
Useful formulations of this invention may also contain materials well known to those skilled in the art as formulation aids such as antifoams, film formers and dyes. Antifoams can include water dispersible liquids comprising polyorganosiloxanes like Rhodorsil® 416. The film formers can include polyvinyl acetates, polyvinyl acetate copolymers, polyvinylpyrrolidone-vinyl acetate copolymer, polyvinyl alcohols, polyvinyl alcohol copolymers and waxes. Dyes can include water dispersible liquid colorant compositions like Pro-lzed® Colorant Red. One skilled in the art will appreciate that this is a non-exhaustive list of formulation aids. Suitable examples of formulation aids include those listed herein and those listed in McCutcheon 's 2001, Volume 2: Functional Materials published by MC Publishing Company and PCT Publication WO 03/024222.
Solutions, including emulsifiable concentrates, can be prepared by simply mixing the ingredients. Dusts and powders can be prepared by blending and, usually, grinding as in a hammer mill or fluid-energy mill. Suspensions are usually prepared by wet-milling; see, for example, U.S. 3,060,084. Granules and pellets can be prepared by spraying the active material upon preformed granular carriers or by agglomeration techniques. See Browning, "Agglomeration", Chemical Engineering, December 4, 1967, pp \A1-A%, Perry's Chemical Engineer's Handbook, 4th Ed., McGraw-Hill, New York, 1963, pages 8-57 and following, and WO 91/13546. Pellets can be prepared as described in U.S. 4,172,714. Water-dispersible and water-soluble granules can be prepared as taught in U.S. 4,144,050, U.S. 3,920,442 and DE 3,246,493. Tablets can be prepared as taught in U.S. 5,180,587, U.S. 5,232,701 and U.S. 5,208,030. Films can be prepared as taught in GB 2,095,558 and U.S. 3,299,566. For further information regarding the art of formulation, see T. S. Woods, "The
Formulator's Toolbox — Product Forms for Modern Agriculture" in Pesticide Chemistry and Bioscience, The Food— Environment Challenge, T. Brooks and T. R. Roberts, Eds., Proceedings of the 9th International Congress on Pesticide Chemistry, The Royal Society of Chemistry, Cambridge, 1999, pp. 120-133. See also U.S. 3,235,361, Col. 6, line 16 through Col. 7, line 19 and Examples 10-41; U.S. 3,309,192, Col. 5, line 43 through Col. 7, line 62 and Examples 8, 12, 15, 39, 41, 52, 53, 58, 132, 138-140, 162-164, 166, 167 and 169-182; U.S.2,891,855, Col. 3, line 66 through Col. 5, line 17 and Examples \-A; 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, UK, 2000.
In the following Examples, all percentages are by weight and all formulations are prepared in conventional ways. Compound numbers refer to compounds in Index Table A.
Example A
High Strength Concentrate Compound 7 98.5% silica aerogel 0.5% synthetic amorphous fine silica 1.0%.
Example B Wettable Powder Compound 7 65.0% dodecylphenol polyethylene glycol ether 2.0% sodium ligninsulfonate 4.0% sodium silicoaluminate 6.0% montmorillonite (calcined) 23.0%. Example C
Granule
Compound 7 10.0% attapulgite granules (low volatile matter,
0.71/0.30 mm; U.S.S. No. 25-50 sieves) 90.0%. Example D
Aqueous Suspension
Compound 7 25.0% hydrated attapulgite 3.0% crude calcium ligninsulfonate 10.0% sodium dihydrogen phosphate 0.5% water 61.5%.
Example E
Extruded Pellet
Compound 7 25.0% anhydrous sodium sulfate 10.0% crude calcium ligninsulfonate 5.0% sodium alkylnaphthalenesulfonate 1.0% calcium/magnesium bentonite 59.0%.
Example F
Microemulsion
Compound 7 1.0% triacetine 30.0%
Cg-C JO alkylpolyglycoside 30.0% glyceryl monooleate 19.0% water 20.0%.
The compounds of this invention are useful as plant disease control agents. The present invention therefore further relates to a method for controlling plant diseases caused by plant pathogens comprising applying to the plant or portion thereof to be protected, or to the plant seed or seedling to be protected, an effective amount of a compound of the invention or a fungicidal composition containing said compound.
Because of their relatively low phytotoxicity, the compounds of Formula 1 are considered to be particularly advantageous for use on dicot (i.e., broadleaf) plants. Accordingly, the compounds of Formula 1 can be used to provide effective fungal disease control for dicot plants.
The compounds of Formula 1 and their fungicidal compositions are useful for controlling fungal plant disease, such as powdery mildews and rusts, caused by fungal plant pathogens in the Ascomycete, Basidiomycete and Deuteromycete classes and afflicting a wide range of ornamental, vegetable, field, cereal and fruit crops. These pathogens include: Ascomycetes, including powdery mildew diseases of cereals and broadleaf crops caused by Erysiphe spp. (including Erysiphe graminis f. sp. tritici, Erysiphe graminis f. sp. hordei and Erysiphe poly gonϊ), Uncinula necatur, Sphaerotheca fuligena, Podosphaera leucotricha and diseases caused by Helminthosporium spp. such as Helminthosporium tritici repentis, Pyrenσphora teres and Rhyncosporium secalis;
Basidiomycetes, including rust diseases of cereals and broadleaf crops caused by Puccinia spp. (such as Puccinia recondita, Puccinia striiformis, Puccinia hordei, Puccinia graminis and Puccinia arachidis), Hemileia vastatrix, Uromyces appendiculatus, Phakopsora pachyrhizi and Phakopsora meibomiae; and other genera and species related to these pathogens, including those classified in Deuteromycetes.
Of note is the use of compounds of this invention to control powdery mildew disease caused by the Erysiphaceae family of fungi (e.g., Erysiphe sp.). Also of note is the use of compounds of this invention to control rust disease caused by the Pucciniaceae family of fungi (e.g., Puccinia sp.).
Compounds of Formula 1 can be used to control fungal diseases of a wide range of economic plants such as alfalfa, barley, cotton, wheat, rape, sugarbeets, corn (maize), sorghum, soybeans, rice, oats, peanuts, vegetables including lettuce, garden beets, peas, beans, carrots, cole crops, curcurbit crops, tomato and pepper, potato, perennial plantation crops including coffee, cocoa, oil palm, rubber, sugarcane, grapes, citrus (e.g., orange, tangerine, lemon, lime, grapefruit), apple, cherry, pear, peach, apricot and other fruit trees, nut trees, banana, plantain, pineapple, hops, tea and forests such as eucalyptus and conifers (e.g., loblolly pine), and turf species (e.g., Kentucky bluegrass, St. Augustine grass, Kentucky fescue and Bermuda grass). Of particular note is the utility of the compounds of Formula 1 for controlling fungal diseases in the following dicot crops: soybean, grape and cucurbit.
Compounds of this invention can also be mixed with one or more other insecticides, fungicides, nematocides, bactericides, acaricides, growth regulators, chemosterilants, semiochemicals, repellents, 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 such agricultural protectants with which compounds of this invention can be formulated are: insecticides such as abamectin, acephate, azinphos-methyl, bifenthrin, 3-bromo-l-(3-chloro-2~pyridmyl)-N-[4-cyano-2-methyl- 6-[(methylamino)carbonyl]ρhenyl]-lH-pyrazole-5-carboxamide, buprofezin, ■ carbofuran, chlorfenapyr, chlorantraniliprole, chlorpyrifos, chlorpyrifos-methyl, cyflumetofen, cyfluthrin, beta-cyfluthrin, cyhalothrin, lambda-cyhalothrin, deltamethrin, diafenthiuron, diazinon, difiubenzuron, dimefluthrin, dimethoate, dinotefuran, esfenvalerate, fenoxycarb, fenpropathrin, fenvalerate, fipronil, flonicamid, fiubendiamide, flucythrinate, tau-fluvalinate, fonophos, imidacloprid, indoxacarb, isofenphos, malathion, metaflumizone, metaldehyde, methamidophos, methidathion, methomyl, methoprene, methoxychlor, metofluthrin, monocrotophos, novifiumuron, oxamyl, parathion, parathion-methyl, permethrin, phorate, phosalone, phosmet, phosphatnidon, pirimicarb, profenofos, profluthrin, pyrafluprole, pyridalyl, pyrifluquinazon. pyriprole, rotenone, spirodiclofen, spiromesifen, spirotetramat, sulprofos, tebufenozide, tefluthrin, terbufos, tetrachlorvinphos, thiamethoxam, thiodicarb, tralomethrin, trichlorfon and triflumtiron; fungicides such as acibenzolar, aldimorph, amisulbrom, azaconazole, azoxystrobin, benalaxyl, benomyl, benthiavalicarb, benthiavalicarb-isopropyl, binomial, biphenyl, bitertanol, blasticidin-S, Bordeaux mixture (tribasic copper sulfate), boscalid/nicobifen, bromuconazole, bupirimate, buthiobate, carboxin, carpropamid, captafol, captan, carbendazim, chloroneb, chlorothalonil, chlozolinate, clotrimazole, copper oxychloride, copper salts such as copper sulfate and copper hydroxide, cyazofamid, cyflufenamid, cymoxanil, cyproconazole, cyprodinil, dichlofluanid, diclocymet, diclomezine, dicloran, diethofencarb, difenoconazole, dimethomorph, dimoxystrobin, diniconazole, diniconazole-M, dinocap, discostrobin, dithianon, dodemorph, dodine, econazole, etaconazole, edifenphos, epoxiconazole, ethaboxam, ethirimol, ethridiazole, famoxadone, fenamidone, fenarimol, fenbuconazole, fencaramid, fenfuram, fenhexamide, fenoxanil, fenpiclonil, fenpropidin, fenpropimorph, fentin acetate, fentin hydroxide, ferbam, ferfurazoate, ferimzone, fluazinam, fludioxonil, flumetover, fluopicolide, fluoxastrobin, fluquinconazole, fluquinconazole, flusilazole, flusulfamide, flutolanil, flutriafol, folpet, fosetyl-alurninum, fuberidazole, furalaxyl, furametapyr, hexaconazole, hymexazole, guazatine, imazalil, imibenconazole, iminoctadine, iodicarb, ipconazole, iprobenfos, iprodione, iprovalicarb, isoconazole, isoprothiolane, isotianil, kasugamycin, kresoxim-methyl, mancozeb, mandipropamid, maneb, mapanipyrin, mefenoxam, mepronil, metalaxyl, metconazole, methasulfocarb, metiram, metominostrobin, mepanipyrim, metiram, metrafenone, miconazole, myclobutanil, neo-asozin (ferric tnethanearsonate), nuarimol, octhilinone, ofurace, orysastrobin, oxadixyl, oxolinic acid, oxpoconazole, oxycarboxin, paclobutrazol, penconazole, pencycuron, penthiopyrad, perfurazoate, ' phosphonic acid, phthalide, picobenzamid, picoxystrobin, polyoxin, probenazole, prochloraz, procymidone, propamocarb, propamocarb-hydrochloride, propiconazole, propineb, proquinazid, prothioconazole, pyraclostrobin, pryazophos, pyrifenox, pyrimethanil, pyrifenox, pyroLtiitrine, pyroquilon, quinconazole, quinoxyfen, quintozene, silthiofam, simeconazole, spiroxamine, streptomycin, sulfur, tebuconazole, techrazene, tecloftalam, tecnazene, tetraconazole, thiabendazole, thifiuzamide,' thiophanate, thiophanate-methyl, thiram, tiadinil, tolclofos-methyl, tolyfluanid, triadimefon, triaditnenol, triarimol, triazoxide, tridemorph, trimoprhamide tricyclazole, trifloxystrobin, triforine, triticonazole, uniconazole, validamycin, vinclozolin, zineb, ziram, and zoxamide, nematocides such as aldoxycarb and fenamiphos; bactericides such as streptomycin; acaricides such as amitraz, chinomethionat, chlorobenzilate, cyhexatin, dicofol, dienochlor, etoxazole, fenazaquin, fenbutatin oxide, fenpropathrin, fenpyroximate, hexythiazox, propargitei pyridaben and tebufenpyrad; and biological agents such as Bacillus thuringiensis, Bacillus thuringiensis delta endotoxin, baculovirus, and entomopathogenic bacteria, virus and fungi. The weight ratios of these various mixing partners to compounds of this invention typically are between 100:1 and 1:100, preferably between 30:1 and 1:30, more preferably between 10:1 and 1:10, and most preferably between 4:1 and 1:4. Of note are combinations of a compound of Formula 1 (e.g., Compound 15) with azoxystrobin, kresoxim-methyl, trifloxystrobin, pyraclostrobin, . picoxystrobin, dimoxystrobin, metominostrobin/fenominostrobin, carbendazim, chlorothalonil, quinoxyfen, metrafenone, cyflufenamid, famόxadone, fenpropidin, fenpropimorph, fluoxastrobin, bromuconazole, cyproconazole, difenoconazole, epoxiconazole, fenbuconazole, flusilazole, hexaconazole, ipconazole, metconazole, penconazole, propiconazole, proquinazid, prothioconazole, tebuconazole, triticonazole, prochloraz or boscalid/nicobifen.
Preferred for better control of plant diseases caused by fungal plant pathogens (e.g., lower use rate or broader spectrum of plant pathogens controlled) or resistance management are mixtures of a compound of Formula 1 with a fungicide selected from the group: azoxystrobin, fluoxastrobin, kresoxim-methyl, trifloxystrobin, pyraclostrobin, picoxystrobin, dimoxystrobin, metominostrobin/fenominostrobin, quinoxyfen, metrafenone, cyflufenamid, fenpropidin, fenpropimorph, cyproconazole, epoxiconazole, flusilazole, metconazole, propiconazole, famoxadone, proquinazid, prothioconazole, tebuconazole and triticonazole.
Specifically preferred mixtures (compound numbers refer to compounds in Index Table A) are selected from the group: the combinations of Compound 7, Compound 8, Compound 15, Compound 22 or Compound 25 with azoxystrobin, the combinations of Compound 7, Compound 8, Compound 15, Compound 22 or Compound 25 with fluoxastrobin, the combinations of Compound 7, Compound 8, Compound 15, Compound 22 or Compound 25 with kresoxim-methyl, the combinations of Compound 7, Compound 8, Compound 15, Compound 22 or Compound 25 with trifloxystrobin, the combinations of
Compound 7, Compound 8, Compound 15, Compound 22 or Compound 25 with pyraclostrobin, the combinations of Compound 7, Compound 8, Compound 15, Compound 22 or Compound 25 with picoxystrobin, the combinations of Compound 7, Compound 8,
Compound 15, Compound 22 or Compound 25 with dimoxystrobin, the combinations of Compound 7, Compound 8, Compound 15, Compound 22 or Compound 25 with metominostrobin/fenominostrobin, the combinations of Compound 7, Compound 8, Compound 15, Compound 22 or Compound 25 with quinoxyfen, the combinations of Compound 7, Compound 8, Compound 15, Compound 22 or Compound 25 with metrafenone, the combinations of Compound 7, Compound 8, Compound 15, Compound 22 or Compound 25 with cyflufenamid, the combinations of Compound 7, Compound 8, Compound 15, Compound 22 or Compound 25 with fenpropidin, the combinations of Compound 7, Compound 8, Compound 15, Compound 22 or Compound 25 with fenpropirnorph, the combinations of Compound 7, Compound 8, Compound 15, Compound 22 or Compound 25 with cyproconazole, the combinations of Compound 7, Compound 8, Compound 15, Compound 22 or Compound 25 with epoxiconazole, the combinations of Compound 7, Compound 8, Compound 15, Compound 22 or Compound 25 with flusilazole, the combinations of Compound 7, Compound 8, Compound 15, Compound 22 or Compound 25 with metconazole, the combinations of Compound 7, Compound 8, Compound 15, Compound 22 or Compound 25 with propiconazole, the combinations of Compound 7, Compound 8, Compound 15, Compound 22 or Compound 25 with famoxadone, the combinations of Compound 7, Compound 8, Compound 15, Compound 22 or Compound 25 with propiconazole, the combinations of Compound .7, Compound 8, Compound 15, Compound 22 or Compound 25 with proquinazid, the combinations of Compound 7, Compound 8, Compound 15, Compound 22 or Compound 25 with prothioconazole, the combinations of Compound 7, Compound 8, Compound 15, Compound 22 or Compound 25 with tebuconazole, the combinations of Compound 7, Compound 8, Compounds 15, Compound 22 or Compound 25 with triticonazole. Of note are methods of controlling fungal plant disease in soybean plants caused by
Phakopsora pachyrhizi which comprise applying a combination of a compound of Formula 1 (e.g., Compound 7, 8, 15, 22 or 25) with at least one compound selected from triazole fungicides that inhibit demethylase in sterol biosynthesis (e.g., cyproconazole, flusilazole and/or tebuconazole). Also of note are fungicidal compositions comprising a compound of Formula 1 (e.g., Compound 7, 8, 15, 22 or 25) and at least one compound selected from triazole fungicides that inhibit demethylase in sterol biosynthesis (e.g., cyproconazole, flusilazole and/or tebuconazole).
Plant disease control, preventatively and curatively, is ordinarily accomplished by applying an effective amount of a compound of this invention either pre- or post-infection, to the portion of the plant to be protected such as the roots, stems, foliage, fruit, seeds, tubers or bulbs, or to the media (soil or sand) in which the plants to be protected are growing. The compounds can also be applied to the seed to protect the seed and seedling.
Rates of application for these compounds can be influenced by many factors of the environment and should be determined under actual use conditions. Foliage can normally be protected when treated at a rate of from less than 1 g/ha to 5,000 g/ha of active ingredient. Seed and seedlings can normally be protected when seed is treated at a rate of from 0.1 to 1O g per kilogram of seed.
The following TESTS demonstrate the control efficacy of compounds of this invention on specific pathogens. The pathogen control protection afforded by the compounds is not limited, however, to these species. See Index Tables A-B for compound descriptions. The following abbreviations are used in the Index Tables which follow: Me means methyl, Et means ethyl, Pr means propyl, ra-Pr means normal propyl, i-Pτ means isopropyl, OMe means methoxy, OEt means ethoxy. The abbreviation "Ex." stands for "Example" and is followed by a number indicating in which example the compound is prepared.
INDEX TABLE A
Figure imgf000035_0001
Compound CR.5a)(R5)nA El R3 El m.o. (°O
1 (CH3)2CH . Me Cl Cl *
2 (CH3)3Si Et Br CF3 *
3 (CH3)3Si Et Cl CF3 *
4 (CH3)2CH Et Cl CF3 *
5 (CH3)3Si Et Br CHF2 *
6 (CH3)3Si Et Cl CHF2 *
7 (Ex. 1) (CH3J2CH Et Br CF3 **
8 (CH3)2CH Et Br CHF2 *
9 (CH3)2CH Et Cl CHF2 *
10 (CH3)3Si Me Cl CF3 *
11 (CH3)3C Et Cl CF3 *
12 (CH3J3C Et Br CF3 *
13 ClCH2(CH3)2Si Et Cl CF3 *
14 ClCH2(CH3)2Si Et Br CF3 *
15 (Ex. 2) (CH3J3Si Et Br OMe **
16 (CH3J3Si Et Cl OMe
17 (CH3J3Si i-Pr Cl OMe *
18 (CH3J3Si i-Pr Br OMe *
19 ClCH2(CH3J2Si Et Cl CHF2 *
20 ClCH2(CH3J2Si Et Br CHF2 *
21 ClCH2(CH3J2Si Et CI OMe *
22 (Ex. 3) (CH3J3Si Et Br OCHF2 **
23 (CH3J3Si Et Cl OCHF2 ♦
24 ClCH2(CH3J2Si Et Br OMe *
25 (CH3J2CH Et Br • OMe * Compound rR5aϊra5^A Ei R3 El m.D. f°CΪ
26 (CH3)2CH Et Cl OMe *
27 (CH3)2CH Et Br OCHF2
28 (CH3)2CH Et Cl OCHF2 *
29 (CH3)3Si Me Br CF3 *
30 (CH3)2CH /-Pr Br OMe *
31 (CH3)2CH H-Pr Br OMe *
32 (CH3)2CH /-Pr Cl OMe
33 (CH3)2CH n-Pr Cl OMe *
34 (CH3)3Si /-Pr Br CF3 *
35 (CH3)3Si /-Pr Cl CF3 *
36 (CH3)2CH Et Br OEt *
37 (CH3)2CH Et Cl OEt *
38 (CH3)2CH «-Pr Br OEt *
39 (CH3)2CH «-Pr Cl OEt *
40 (CH3)2CH /-Pr Br OEt *
41 (CH3)2CH /-Pr Cl OEt *
42 (CH3)3Si Et Br OEt *
43 (CH3)3Si Et Cl OEt *
* See Index Table B for 1H NMR data.
** See synthesis example for 1H NMR data.
INDEX TABLE B
Figure imgf000036_0002
Figure imgf000037_0001
Figure imgf000038_0001
Cmpd ^H NMR Data (CDCI3 solution unless indicated otherwise)a No. δ 7.27-7.56 (br, IH), 6.88 (s, IH), 6.48 (s, IH), 4.05 (q, 2H), 3.9 (t, 2H), 3.2-3.6 (br, 2H), 3.02 (s,
43 3H), 1.8 (m, 2H), 1.42 (t, 3H), 1.22 (t, 3H), 0.58 (m, 2H), 0.01 (s, 9H). δ 7.3-7.56 (br, IH), 6.87 (s, IH), 6.46 (s, IH), 4.04 (q, 2H), 3.89 (t, 2H), 3.1-3.5 (br, 2H), 3.01 (s,
44 3H), 1.8 (m, 2H), 1.62 (m, 2H), 1.41 (t, 3H), 0.92 (m, 3H), 0.58 (m, 2H) , 0.01 (s , 9H).
a *H NMR data are in ppm downfield from tetramethylsilane. Couplings are designated by (s)-singlet, (d)-doublet, (t)-triplet, (q)-quartet, (m)-multiρlet, (br)-broad singlet.
BIOLOGICAL EXAMPLES OF THE INVENTION
General protocol for preparing test suspensions: Test compounds were first dissolved in acetone in an amount equal to 3 % of the final volume and then suspended at the desired concentration (in ppm) in acetone and purified water (50/50 mix) containing 250 ppm of the surfactant Trem® 014 (polyhydric alcohol esters). The resulting test suspensions were then used in the following tests.
TEST A
The test suspension was sprayed at 40 ppm (equivalent to a rate of 120 g/ha) to the point of run-off on wheat seedlings. The following day the seedlings were inoculated with a spore suspension of Puccinia recondita (the causal agent of wheat brown rust) and incubated in a saturated atmosphere at 20 0C for 24 h, and then moved to a growth chamber at 20 0C for 6 days, after which time disease ratings were made.
TEST B
The test suspension was sprayed at 40 ppm (equivalent to a rate of 120 g/ha) to the point of run-off on wheat seedlings. The following day the seedlings were inoculated with a spore dust of Erysiphe graminis f. sp. tritid, (the causal agent of wheat powdery mildew) and incubated in a growth chamber at 20 0C for 7 days, after which time disease ratings were made.
TEST C
The test suspension was sprayed at 20 g/ha (in an application volume of 1000 L/ha) on grape seedlings. The following day the seedlings were inoculated with a spore suspension of Uncinula necatur (the causal agent of grape powdery mildew) and incubated in a greenhouse at 20 0C for 14 days, after which time disease ratings were made. TEST D
The test suspension was sprayed at 100 g/ha (in an application volume of 1000 L/ha) on soybean seedlings. The following day the seedlings were incubated in a saturated atmosphere at 20 0C for 48 h and then moved to a growth chamber at 22 0C for 14 days, after which time crop safety ratings were made.
TEST E
The test suspension was sprayed at 20 g/ha (in an application volume of 1000 L/ha) on soybean seedlings. The following day the seedlings were incubated in a saturated atmosphere at 20 0C for 48 h and then moved to a growth chamber at 22 0C for 14 days, after which time crop safety ratings were made.
Results for Tests A-E are given in Table A. For Tests A-C, disease efficacy ratings are based on the percent leaf area with no visible symptoms, expressed as a percent (0 to 100 %) of total leaf area — e.g., a rating of 100 indicates 100 % disease control and a rating of 0 indicates no disease control (relative to the controls). A dash (-) indicates no test results. For Tests D-E, crop safety ratings are based on the percent leaf area showing injury, expressed as a percent (0 to 100 %) of total leaf area — e.g., a rating of 100 indicates 100 % crop injury and a rating of 0 indicates no crop injury. A letter code following the percent rating indicates the type of symptom observed; a "B" indicates necrosis and an "H" indicates hormonal effects. A dash (-) indicates no test results. Results of Tests A-E show compounds that are effective at controlling rust and powdery mildew diseases of cereal and broadleaf crops, and are advantageous for use on broadleaved crops. The compound numbers of Table A refer to compounds in Index Table A. Table A
Figure imgf000040_0001
Figure imgf000041_0001
Three compounds were evaluated in a replicated soybean field trial for the control of Asian soybean rust, caused by the pathogen Phakopsora pachyrhizi. Each compound was formulated as an emulsifiable concentrate, dispersed in water, and then applied with a field sprayer at 200 liters/Ha. Each compound was applied at three rates (50, 100, and 200 grams active/Ha) and at two application timings — at the Rl stage (first flower buds visible) and at the R5 stage (end of flowering). Two commercial standards were included for comparison. Treatments were then evaluated for percent disease (percent of leaf area with visible symptoms) in the lower canopy for each of four replicates and expressed as percent control relative to the untreated control. No plant injury was observed with any of the compounds.
Results are given in Table B. Disease efficacy ratings are expressed as a percent (0 to 100 %) of total leaf area - e.g., a rating of 100 indicates 100 % disease control and a rating of 0 indicates no disease control (relative to the controls). "DATl" refers to the number of days after the first spray application (Tl). The compound numbers of Table B refer to compounds in Index Table A.
Table B
Figure imgf000042_0001

Claims

CLAIMSWhat is claimed is:
1. A compound selected from Formula 1, iV-oxides and agriculturally suitable salts thereof,
Figure imgf000043_0001
wherein
R1 is C1-C4 alkyl or C3-C4 cycloalkyl; R2 is C1-C3 alkyl; R3 is Br, Cl or I; •
R4 is Cl; or Cj-C2 alkyl or C1-C2 alkoxy, each optionally substituted with one to three substituents independently selected from halogen; A is C or Si; each R5 is independently C1-C2 alkyl optionally substituted with one to three substituents independently selected from halogen; and
R5a is H or C1-C2 alkyl; provided that when A is Si, then R5a is C1-C2 alkyl.
2. A compound of Claim 1 wherein R1 is C1-C3 alkyl or C3-C4 cycloalkyl; R2 is C1-C2 alkyl;
R3 is Br or Cl;
R4 is Cl; or C1-C2 alkyl or C1-C2 alkoxy, each optionally substituted with one to three substituents independently selected from F and Cl; and each R5 is independently C1-C2 alkyl optionally substituted with one to three substituents independently selected from F and Cl.
3. A compound of Claim 2 wherein R1 is C1-C2 alkyl;
R2 is methyl; R3 is Br; R4 is Cl; or C1-C2 alkyl or C1-C2 alkoxy, each optionally substituted with one to three
F; and each R5 is independently C1-C2 alkyl optionally substituted with one to three CL
4. A compound of Claim 3 wherein R1 is ethyl;
R2 is methyl;
R4 is Ci alkyl or C1 alkoxy, each optionally substituted with one to three F; and each R5 is independently Ci alkyl optionally substituted with one to three Cl.
5. A compound of Claim 1 selected from the group consisting of: iVr'-[2-bromo-4-[(4-methylpentyl)oxy]-5-(trifluoromethyl)phenyl]-JV-ethyl-iV- methylmethanimidamide, iV'-[2-bromo-5-methoxy-4-[3-(trimethylsilyl)propoxy]phenyl]-Λr-ethyl]-Λ7- methylmethanimidamide,
JV'-[2-bromo-5-(difluoromethoxy)-4-[3-(trimethylsilyl)propoxy]phenyl]-i^-ethyl- iV-methylmethanimidamide,
Λr'-[2-bromo-5-(difluoromethyl)-4-[(4-methylpentyl)oxy]phenyl]-iV-ethyl-N- methylmethanimidamide; and iV'-[2-bromo-5-πiethoxy-4-[(4-methylpentyl)oxy]phenyl]-N-ethyl-iV- methylmethanimidamide.
6. A fungicidal composition comprising a fungicidally effective amount of a compound of Claim 1 and at least one additional component selected from the group consisting of a surfactants, a solid diluent or a liquid diluent, said composition optionally further comprising an effective amount of at least one additional biologically active compound or agent.
7. A fungicidal composition comprising (a) a compound of Claim 1 ; and (b) at least one other fungicide.
8. A fungicidal composition of Claim 7 comprising wherein the (b) component includes at least one compound selected from triazole fungicides that inhibit demethylase in sterol biosynthesis.
9. A method of controlling at least one plant fungal disease in cereal or broadleaf crops selected from the group consisting of powdery mildew disease caused by Erysiphe spp., Uncinula necatur, Sphaerotheca fuligena and Podosphaera leucotricha, diseases caused by Helminthosporium spp., Pyrenophora teres and Rhyncosporium secalis, and rust disease caused by Puccinia spp., Hemileia vastatrix, Uromyces appendiculatus, Phakopsora pachyrhizi and Phakopsora meibomiae, comprising: applying to the plant or portion thereof, or to the plant seed or seedling, a fungicidally effective amount of a compound of Claim 1.
10. The method of Claim 9 wherein at least one powdery mildew disease is controlled.
11. The method of Claim 10 wherein the fungal disease is caused by Erysiphe graminis f. sp. tritici.
12. The method of Claim 10 wherein the fungal disease is caused by Erysiphe graminis f. sp. hordei.
13. The method of Claim 10 wherein the fungal disease is caused by Uncinula necatur.
14. The method of Claim 10 wherein the fungal disease is caused by Podosphaera leucotricha.
15. The method of Claim 9 wherein at least one rust disease is controlled.
16. The method of Claim 15 wherein the fungal disease is caused by Puccinia recondita.
17. The method of Claim 15 wherein the fungal disease is caused by Puccinia striiformis.
18. The method of Claim 15 wherein the fungal disease is caused by Puccinia graminis.
19. The method of Claim 15 wherein the fungal disease is caused by Hemileia vastatrix.
20. The method of Claim 15 wherein the fungal disease is caused by Uromyces appendiculatus .
21. The method of Claim 15 wherein the fungal disease is caused by Phakopsora pachyrhizi.
22. The method of Claim 21 wherein a fungal plant disease in soybean plants caused by Phakopsora pachyrhizi is controlled; and which comprises applying a combination of compounds that includes at least one compound selected from triazole fungicides that inhibit demethylase in sterol biosynthesis.
23. The method of any one of Claims 9 to 21 wherein the plant is a dicot crop.
24. The method of Claim 23 wherein the dicot crop is selected from soybean, grape and cucurbit.
25. The method of Claim 24 wherein the dicot crop is soybean.
26. The method of Claim 24 wherein the dicot crop is grape.
27. The method of Claim 24 wherein the dicot crop is cucurbit.
28. A method of controlling plant diseases caused by Ascomycete plant pathogens, comprising: applying to the plant or portion thereof, or to the plant seed or seedling, a fungicidally effective amount of a compound of Claim 1.
29. A method of controlling plant diseases caused by Basidiomycete plant pathogens, comprising: applying to the plant or portion thereof, or to the plant seed or seedling, a fungicidally effective amount of a compound of Claim 1.
30. A method of controlling plant diseases caused by plant pathogens other than Ascomycete plant pathogens and Basidiomycete plant pathogens, comprising: applying to the plant or portion thereof, or to the plant seed or seedling, a fungicidally effective amount of a compound of Claim 1.
31. The methods of Claim 28, 29 or 30 wherein the plant is a dicot crop.
PCT/US2006/044924 2005-11-23 2006-11-20 Amidinylphenyl compounds and their use as fungicides WO2007061966A2 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US73962705P 2005-11-23 2005-11-23
US60/739,627 2005-11-23

Publications (2)

Publication Number Publication Date
WO2007061966A2 true WO2007061966A2 (en) 2007-05-31
WO2007061966A3 WO2007061966A3 (en) 2007-07-12

Family

ID=37946278

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2006/044924 WO2007061966A2 (en) 2005-11-23 2006-11-20 Amidinylphenyl compounds and their use as fungicides

Country Status (4)

Country Link
AR (1) AR057929A1 (en)
PE (1) PE20070822A1 (en)
TW (1) TW200804245A (en)
WO (1) WO2007061966A2 (en)

Cited By (13)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
ITMI20101575A1 (en) * 2010-08-26 2012-02-27 Isagro Ricerca Srl PHENYLAMIDINE WITH HIGH FUNGICIDAL ACTIVITY AND RELATED USE
WO2012060401A1 (en) 2010-11-05 2012-05-10 大塚アグリテクノ株式会社 Ethynylphenylamidine compound or salt thereof, method for producing same, and fungicide for agricultural and horticultural use
WO2016202688A1 (en) 2015-06-15 2016-12-22 Bayer Cropscience Aktiengesellschaft Halogen-substituted phenoxyphenylamidines and the use thereof as fungicides
WO2016202742A1 (en) 2015-06-15 2016-12-22 Bayer Cropscience Aktiengesellschaft Halogen-substituted phenoxyphenylamidines and the use thereof as fungicides
EP3335559A1 (en) 2016-12-14 2018-06-20 Bayer CropScience Aktiengesellschaft Active compound combinations
WO2018109002A1 (en) 2016-12-14 2018-06-21 Bayer Cropscience Aktiengesellschaft Active compound combinations
WO2018108992A2 (en) 2016-12-14 2018-06-21 Bayer Cropscience Aktiengesellschaft Phenoxyphenylamidines and the use thereof as fungicides
WO2018108998A1 (en) 2016-12-14 2018-06-21 Bayer Cropscience Aktiengesellschaft Phenylamidines and the use thereof as fungicides
WO2018193385A1 (en) 2017-04-20 2018-10-25 Pi Industries Ltd. Novel phenylamine compounds
WO2018211442A1 (en) 2017-05-18 2018-11-22 Pi Industries Ltd. Formimidamidine compounds useful against phytopathogenic microorganisms
EP3708565A1 (en) 2020-03-04 2020-09-16 Bayer AG Pyrimidinyloxyphenylamidines and the use thereof as fungicides
US10912297B2 (en) 2015-07-08 2021-02-09 Bayer Cropscience Aktiengesellschaft Phenoxyhalogenphenylamidines and the use thereof as fungicides
EP3915971A1 (en) 2020-12-16 2021-12-01 Bayer Aktiengesellschaft Phenyl-s(o)n-phenylamidines and the use thereof as fungicides

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2003093224A1 (en) * 2002-05-03 2003-11-13 E.I. Du Pont De Nemours And Company Amidinylphenyl compounds and their use as fungicides
WO2005120234A2 (en) * 2004-06-03 2005-12-22 E.I. Dupont De Nemours And Company Fungicidal mixtures of amidinylphenyl compounds

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2003093224A1 (en) * 2002-05-03 2003-11-13 E.I. Du Pont De Nemours And Company Amidinylphenyl compounds and their use as fungicides
WO2005120234A2 (en) * 2004-06-03 2005-12-22 E.I. Dupont De Nemours And Company Fungicidal mixtures of amidinylphenyl compounds

Cited By (19)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
ITMI20101575A1 (en) * 2010-08-26 2012-02-27 Isagro Ricerca Srl PHENYLAMIDINE WITH HIGH FUNGICIDAL ACTIVITY AND RELATED USE
WO2012060401A1 (en) 2010-11-05 2012-05-10 大塚アグリテクノ株式会社 Ethynylphenylamidine compound or salt thereof, method for producing same, and fungicide for agricultural and horticultural use
US8785649B2 (en) 2010-11-05 2014-07-22 Otsuka Agritechno Co., Ltd. Ethynylphenylamidine compound or salt thereof, method for producing same, and fungicide for agricultural and horticultural use
US9169276B2 (en) 2010-11-05 2015-10-27 Otsuka Agritechno Co., Ltd. Ethynylphenylamidine compound or salt thereof, method for producing same, and fungicide for agricultural and horticultural use
US10252977B2 (en) 2015-06-15 2019-04-09 Bayer Cropscience Aktiengesellschaft Halogen-substituted phenoxyphenylamidines and the use thereof as fungicides
WO2016202688A1 (en) 2015-06-15 2016-12-22 Bayer Cropscience Aktiengesellschaft Halogen-substituted phenoxyphenylamidines and the use thereof as fungicides
WO2016202742A1 (en) 2015-06-15 2016-12-22 Bayer Cropscience Aktiengesellschaft Halogen-substituted phenoxyphenylamidines and the use thereof as fungicides
US10506807B2 (en) 2015-06-15 2019-12-17 Bayer Cropscience Aktiengesellschaft Halogen-substituted phenoxyphenylamidines and the use thereof as fungicides
US10912297B2 (en) 2015-07-08 2021-02-09 Bayer Cropscience Aktiengesellschaft Phenoxyhalogenphenylamidines and the use thereof as fungicides
WO2018109002A1 (en) 2016-12-14 2018-06-21 Bayer Cropscience Aktiengesellschaft Active compound combinations
WO2018108998A1 (en) 2016-12-14 2018-06-21 Bayer Cropscience Aktiengesellschaft Phenylamidines and the use thereof as fungicides
WO2018108992A2 (en) 2016-12-14 2018-06-21 Bayer Cropscience Aktiengesellschaft Phenoxyphenylamidines and the use thereof as fungicides
WO2018108977A1 (en) 2016-12-14 2018-06-21 Bayer Cropscience Aktiengesellschaft Active compound combinations
EP3335559A1 (en) 2016-12-14 2018-06-20 Bayer CropScience Aktiengesellschaft Active compound combinations
WO2018193385A1 (en) 2017-04-20 2018-10-25 Pi Industries Ltd. Novel phenylamine compounds
US11524934B2 (en) 2017-04-20 2022-12-13 Pi Industries Ltd Phenylamine compounds
WO2018211442A1 (en) 2017-05-18 2018-11-22 Pi Industries Ltd. Formimidamidine compounds useful against phytopathogenic microorganisms
EP3708565A1 (en) 2020-03-04 2020-09-16 Bayer AG Pyrimidinyloxyphenylamidines and the use thereof as fungicides
EP3915971A1 (en) 2020-12-16 2021-12-01 Bayer Aktiengesellschaft Phenyl-s(o)n-phenylamidines and the use thereof as fungicides

Also Published As

Publication number Publication date
TW200804245A (en) 2008-01-16
WO2007061966A3 (en) 2007-07-12
AR057929A1 (en) 2007-12-26
PE20070822A1 (en) 2007-08-16

Similar Documents

Publication Publication Date Title
WO2007061966A2 (en) Amidinylphenyl compounds and their use as fungicides
JP7487364B2 (en) Fungicidal Oxadiazoles
EP2217600B1 (en) Fungicidal bicyclic pyrazoles
EP2121660B1 (en) Fungicidal amides
US20050182025A1 (en) Amidinylphenyl compounds and their use as fungicides
CN113260610A (en) Substituted tolyl fungicides
DK2427058T3 (en) nematicidal SULPHONAMIDES
EP2867228B1 (en) Fungicidal heterocyclic carboxamides
EP2521450B1 (en) Fungicidal heterocyclic compounds
US8026359B2 (en) Fungicidal heterocyclic amines
WO2005120234A2 (en) Fungicidal mixtures of amidinylphenyl compounds
TW201418223A (en) Substituted tolyl fungicides
MX2013002400A (en) Fungicidal pyrazoles.
WO2010093595A1 (en) Fungicidal 2-pyridones
US20110092544A1 (en) Fungicidal pyridines
US20150336985A1 (en) Fungicidal heterocyclic compounds
US20050020644A1 (en) Bicyclic fused pyridinyl amides and advantagesous compositons thereof for use as fungicides
WO2002091830A1 (en) Pyridinyl fused bicyclic amide as fungicides
JP2008530231A (en) Bactericidal and fungicidal pyrazine derivatives
TW201116212A (en) Heterobicycle-substituted azolyl benzene fungicides
CN105683164A (en) Fungicidal pyrazoles
US20140235689A1 (en) Fungicidal pyrazoles

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application
NENP Non-entry into the national phase in:

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 06844442

Country of ref document: EP

Kind code of ref document: A2