Classifications

• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07D—HETEROCYCLIC COMPOUNDS
  • C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
  • C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
  • C07D487/04—Ortho-condensed systems

Definitions

• This invention relates to certain benzodipyrazoles, their tautomers, their N-oxides, salts and compositions, and methods of their use as fungicides.
• This invention is directed to compounds of Formula 1 (including all stereoisomers), tautomers, N-oxides, and salts thereof, agricultural compositions containing them and their use as fungicides:
• R 1 and R 2 are each independently H, C ⁇ -C alkyl, C j -Cg haloalkyl, C 2 -C 8 alkenyl,
• each W is independently a phenyl ring optionally substituted with up to 3 substituents independently selected from halogen and C1-C3 alkyl;
• R 3 , R 4 , R 5 and R 6 are each independently H, cyano, hydroxy, halogen, C1-C3 alkyl,
• C1-C3 haloalkyl C2-C4 cyanoalkyl, C2-C4 alkenyl, C2-C4 alkynyl, C ⁇ -C ⁇ cycloalkyl, C3-C6 halocycloalkyl, C1-C3 alkoxy, Q-C3 haloalkoxy, C2-C4 alkoxyalkyl or C2-C4 haloalkoxyalkyl;
• R 7 and R 8 are each independently H, C ⁇ -C 6 alkyl, C3-C5 cycloalkyl, C4-C8
• cycloalkylalkyl C4-C8 alkylcycloalkyl, C2-Cg alkoxyalkyl, C2-Cg alkylcarbonyl,
• n 1 or 2;
• this invention pertains to a compound selected from compounds of Formula 1 (including all stereoisomers), tautomers and N-oxides and salts thereof.
• This invention also relates to a fungicidal composition
• a fungicidal composition comprising (a) a compound of the invention (i.e. in a fungicidally effective amount) or a compound selected from 2,4,6,8- tetrahydro-2,6-dimethylbenzo[l,2-c:4,5-c']dipyrazole-3,7-diol, 2,4,6, 8-tetrahydrobenzo[ 1 ,2- c:4,5-c']dipyrazole-3,7-diol, 2,3a,4,6,7a,8-hexahydro-2,6-bis(2-hydroxyethyl)benzo[l ,2- c:4,5-c']dipyrazole-3,7-dione, 3,7-dihydroxybenzo[l ,2-c:4,5-c']dipyrazole-2,6(4H,8H)- diethanol and 2,4,6,8-tetrahydro-3,7-dimeth
• This invention also relates to a fungicidal composition
• a fungicidal composition comprising (a) a compound of the invention or a compound selected from 2,4,6,8-tetrahydro-2,6-dimethylbenzo[l ,2-c:4,5- c']dipyrazole-3,7-diol, 2,4,6, 8-tetrahydrobenzo[l ,2-c:4,5-c']dipyrazole-3,7-diol,
• This invention further 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) or a compound selected from 2,4,6, 8-tetrahydro-2,6-dimethylbenzo[ 1 ,2- c:4,5-c']dipyrazole-3,7-diol, 2,4,6, 8-tetrahydrobenzo[l ,2-c:4,5-c']dipyrazole-3,7-diol,
• a compound of the invention e.g., as a composition described herein
• This invention also relates to a composition
• a composition comprising a compound of Formula 1, an N-oxide, or a salt thereof, and at least one invertebrate pest control compound or agent.
• compositions, mixture, 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, mixture, process, method, article, or apparatus.
• transitional phrase consisting essentially of is used to define a composition, method or apparatus that includes materials, steps, features, components, or elements, in addition to those literally disclosed, provided that these additional materials, steps, features, components, or elements do not materially affect the basic and novel characteristic(s) of the claimed invention.
• plant includes members of Kingdom Plantae, particularly seed plants (Spermatopsida), at all life stages, including young plants (e.g., germinating seeds developing into seedlings) and mature, reproductive stages (e.g., plants producing flowers and seeds).
• Portions of plants include geotropic members typically growing beneath the surface of the growing medium (e.g., soil), such as roots, tubers, bulbs and corms, and also members growing above the growing medium, such as foliage (including stems and leaves), flowers, fruits and seeds.
• 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.
• the terms “fungal pathogen” and “fungal plant pathogen” include pathogens in the Ascomycota, Basidiomycota and Zygomycota phyla classes, and the fungal-like Oomycota class that are the causal agents of a broad spectrum of plant diseases of economic importance, affecting ornamental, turf, vegetable, field, cereal and fruit crops.
• “protecting a plant from disease” or “control of a plant disease” includes preventative action (interruption of the fungal cycle of infection, colonization, symptom development and spore production) and/or curative action (inhibition of colonization of plant host tissues).
• mode of action is as define by the Fungicide Resistance Action Committee (FRAC), and is used to distinguish fungicides according to their biochemical mode of action in the biosynthetic pathways of plant pathogens.
• FRAC-defined mode of actions include (A) nucleic acid synthesis, (B) mitosis and cell division, (C) respiration, (D) amino acid and protein synthesis, (E) signal transduction, (F) lipid synthesis and membrane integrity, (G) sterol biosynthesis in membranes, (H) cell wall biosynthesis, (I) melanin synthesis in cell wall, (P) host plant defense induction, (U) unknown mode of action, (NC) not classified and (M) multi-site contact activity.
• Each MOA (i.e. letters A through M) contain one or more subgroups (e.g., A includes subgroups Al, A2, A3 and A4) based either on individual validated target sites of action, or in cases where the precise target site is unknown, based on cross resistance profiles within a group or in relation to other groups.
• Each of these subgroups (e.g., Al, A2, A3 and A4) is assigned a FRAC code (a number and/or letter).
• the FRAC code for subgroup Al is 4. Additional information on target sites and FRAC codes can be obtained from publicly available databases maintained, for example, by FRAC.
• cross resistance refers to the phenomenon that occurs when a pathogen develops resistance to one fungicide and simultaneously becomes resistant to other fungicides. These other fungicides are typically, but not always, in the same chemical class or have the same target site of action, or can be detoxified by the same mechanism.
• alkylating agent refers to a chemical compound in which a carbon-containing radical is bound through a carbon atom to a leaving group such as halide or sulfonate, which is displaceable by bonding of a nucleophile to said carbon atom. Unless otherwise indicated, the term “alkylating agent” or “alkylating reagent” does not limit the carbon-containing radical to alkyl.
• a molecular fragment i.e. radical
• a series of atom symbols e.g., C, H, N, O and S
• the point or points of attachment may be explicitly indicated by a hyphen ("-").
• -SCN indicates that the point of attachment is the sulfur atom (i.e. thiocyanato, not isothiocyanato).
• alkyl used either alone or in compound words such as “alkylthio” or “haloalkyl” includes straight-chain or branched alkyl such as methyl, ethyl, ⁇ -propyl, z ' -propyl, or the different butyl, pentyl or hexyl isomers.
• Alkenyl includes straight-chain or branched alkenes such as ethenyl, 1-propenyl, 2-propenyl, and the different butenyl, pentenyl and hexenyl isomers.
• Alkenyl also includes polyenes such as 1 ,2-propadienyl and 2,4-hexadienyl.
• Alkynyl includes straight-chain or branched alkynes such as ethynyl, 1-propynyl, 2-propynyl and the different butynyl, pentynyl and hexynyl isomers.
• Alkynyl also includes moieties comprised of multiple triple bonds such as 2,5-hexadiynyl.
• Alkylamino includes an NH radical substituted with straight-chain or branched alkyl.
• alkylamino examples include CH 3 CH 2 NH, CH 3 CH 2 CH 2 NH and (CH 3 ) 2 CHNH.
• dialkylamino examples include (CH 3 ) 2 N, (CH 3 CH 2 ) 2 N and CH 3 CH 2 (CH 3 )N.
• Alkylaminoalkyl denotes alkylamino substitution on alkyl.
• alkylaminoalkyl examples include CH 3 NHCH 2 , CH 3 NHCH 2 CH 2 and CH 3 CH 2 NHCH 2 .
• dialkylaminoalkyl examples include (CH 3 ) 2 NCH 2 , CH 3 CH 2 (CH 3 )NCH 2 and (CH 3 ) 2 NCH 2 CH 2 .
• Alkoxy includes, for example, methoxy, ethoxy, «-propyloxy, z ' -propyloxy and the different butoxy, pentoxy and hexyloxy isomers.
• Alkoxyalkyl denotes alkoxy substitution on alkyl. Examples of “alkoxyalkyl” include CH 3 OCH 2 , CH 3 OCH 2 CH 2 , CH 3 CH 2 OCH 2 , CH 3 CH 2 CH 2 CH 2 OCH 2 and CH 3 CH 2 OCH 2 CH 2 .
• Alkylthio includes branched or straight-chain alkylthio moieties such as methylthio, ethylthio, and the different propylthio isomers.
• Alkylthioalkyl denotes alkylthio substitution on alkyl.
• alkylthioalkyl examples include CH3SCH 2 , CH 3 SCH 2 CH 2 , CH 3 CH 2 SCH 2 , CH 3 CH 2 CH 2 CH 2 SCH 2 and CH 3 CH 2 SCH 2 CH 2 ;
• alkylsulfmylalkyl and “alkylsulfonylalkyl” include the corresponding sulfoxides and sulfones, respectively.
• cycloalkyl denotes a saturated carbocyclic ring consisting of between 3 to 8 carbon atoms linked to one another by single bonds.
• examples of “cycloalkyl” include cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl.
• cycloalkylalkyl denotes cycloalkyl substitution on an alkyl group.
• Examples of “cycloalkylalkyl” include cyclopropylmethyl, cyclopentylethyl, and other cycloalkyl moieties bonded to straight-chain or branched alkyl groups.
• Alkylcycloalkyl denotes alkyl substitution on a cycloalkyl moiety. Examples include 4-methylcyclohexyl and 3-ethylcyclopentyl.
• cycloalkoxy denotes cycloalkyl attached to and linked through an oxygen atom such as cyclopentyloxy and cyclohexyloxy.
• Cyanoalkyl denotes an alkyl group substituted with one cyano group.
• Examples of “cyanoalkyl” include NCCH 2 , NCCH 2 CH 2 and CH 3 CH(CN)CH 2 .
• “Hydroxyalkyl” denotes an alkyl group substituted with one hydroxy group. Examples of “hydroxyalkyl” include HOCH 2 , HOCH 2 CH 2 and CH 3 CH 2 (OH)CH.
• haloalkyl includes fluorine, chlorine, bromine or iodine. Further, when used in compound words such as “haloalkyl”, said alkyl may be partially or fully substituted with halogen atoms which may be the same or different. Examples of “haloalkyl” include F 3 C, C1CH 2 , CF 3 CH 2 and CF 3 CC1 2 .
• haloalkoxy include F 3 C, C1CH 2 , CF 3 CH 2 and CF 3 CC1 2 .
• haloalkoxy “haloalkylthio”
• haloalkylsulfinyl haloalkylsulfonyl
• halocycloalkyl and the like are defined analogously to the term “haloalkyl”.
• haloalkoxy examples include CF 3 0, CC1 3 CH 2 0, F 2 CHCH 2 CH 2 0 and CF 3 CH 2 0.
• haloalkylthio examples include CC1 3 S, CF 3 S, CC1 3 CH 2 S and C1CH 2 CH 2 CH 2 S.
• halocycloalkyl examples include chlorocyclopropyl, fluorocyclobutyl and chlorocyclohexyl.
• C ⁇ -C 3 alkylsulfonyl designates methylsulfonyl through propylsulfonyl
• C2 alkoxyalkyl designates CH 3 OCH 2
• C3 alkoxyalkyl designates, for example, CH3OCH2CH2 or CH3CH2OCH2
• C4 alkoxyalkyl designates the various isomers of an alkyl group substituted with an alkoxy group containing a total of four carbon atoms, examples including CH3CH2CH2OCH2 and CH 3 CH 2 OCH 2 CH2.
• substituents may be restricted by an expressed limitation.
• phrase "optionally substituted with up to 3 substituents independently selected from halogen and C 1 -C 3 alkyl" means that 0, 1, 2 or 3 substituents can be present.
• Carbocyclic ring or “carbocycle” denote a ring wherein the atoms forming the ring backbone are selected only from carbon. When a fully unsaturated carbocyclic ring satisfies Huckel's rule, then said ring is also called an "aromatic carbocyclic ring".
• saturated carbocyclic ring refers to a ring having a backbone consisting of carbon atoms linked to one another by single bonds; unless otherwise specified, the remaining carbon valences are occupied by hydrogen atoms.
• Stereoisomers are isomers of identical constitution but differing in the arrangement of their atoms in space and include enantiomers, diastereomers, cis- and irans-isomers (also known as geometric isomers) and atropisomers. Atropisomers result from restricted rotation about single bonds where the rotational barrier is high enough to permit isolation of the isomeric species.
• one stereoisomer may be more active and/or may exhibit beneficial effects when enriched relative to the other stereoisomer(s) or when separated from the other stereoisomer(s). Additionally, the skilled artisan knows how to separate, enrich, and/or to selectively prepare said stereoisomers.
• the compounds of the invention may be present as a mixture of stereoisomers, individual stereoisomers or as an optically active form.
• stereoisomerism see Ernest L. Eliel and Samuel H. Wilen, Stereochemistry of Organic Compounds, John Wiley & Sons, 1994.
• Tautomers are structurally distinct isomers that interconvert by tautomerization.
• Tautomerization is a form of isomerization and includes prototropic or proton-shift tautomerization, which is considered a subset of acid-base chemistry.
• Prototropic tautomerization or proton-shift tautomerization involves the migration of a proton accompanied by changes in bond order, often the interchange of a single bond with an adjacent double bond. Where tautomerization is possible (e.g. in solution), a chemical equilibrium of tautomers can be reached.
• keto-enol tautomerization is keto-enol tautomerization.
• Compounds of Formula 1 are known to equilibrate with their keto tautomer forms. Unless otherwise indicated, reference to a compound by one tautomer description (such as enolic form) is to be considered to include all tautomers. For example, when R 7 and R 8 are hydrogen, then reference to the enol tautomeric form depicted by Formula l 1 also includes the keto tautomic form depicted by F
• the equilibrium constant for the above-mentioned tautomeric equilibrium is dependent upon factors such as temperature, the groups attached Formula 1 (e.g., R 7 and R 8 ), the type of solvent, and the like.
• This invention comprises mixtures of conformational isomers.
• this invention includes compounds that are enriched in one conformer relative to others.
• This invention comprises all stereoisomers, conformational isomers and mixtures thereof in all proportions as well as isotopic forms such as deuterated compounds.
• nitrogen containing heterocycles can form N-oxides since the nitrogen requires an available lone pair for oxidation to the oxide; one skilled in the art will recognize those nitrogen-containing heterocycles which can form N-oxides.
• nitrogen-containing heterocycles which can form N-oxides.
• tertiary amines can form N-oxides.
• N-oxides of heterocycles and tertiary amines are very well known by one skilled in the art including the oxidation of heterocycles and tertiary amines with peroxy acids such as peracetic and m-chloroperbenzoic acid (MCPBA), hydrogen peroxide, alkyl hydroperoxides such as i-butyl hydroperoxide, sodium perborate, and dioxiranes such as dimethyldioxirane.
• MCPBA peroxy acids
• alkyl hydroperoxides such as i-butyl hydroperoxide
• sodium perborate sodium perborate
• dioxiranes such as dimethyldioxirane
• salts of chemical compounds are in equilibrium with their corresponding nonsalt forms, salts share the biological utility of the nonsalt forms.
• 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.
• salts also include those formed with organic or inorganic bases such as pyridine, triethylamine or ammonia, or amides, hydrides, hydroxides or carbonates of sodium, potassium, lithium, calcium, magnesium or barium. Accordingly, the present invention comprises compounds selected from Formula 1, N-oxides and agriculturally suitable salts thereof.
• Formula 1 includes all crystalline and non-crystalline forms of the compounds that Formula 1 represents.
• Non-crystalline forms include embodiments which are solids such as waxes and gums as well as embodiments which are liquids such as solutions and melts.
• Crystalline forms include embodiments which represent essentially a single crystal type and embodiments which represent a mixture of polymorphs (i.e. different crystalline types).
• polymorph refers to a particular crystalline form of a chemical compound that can crystallize in different crystalline forms, these forms having different arrangements and/or conformations of the molecules in the crystal lattice.
• polymorphs can have the same chemical composition, they can also differ in composition due to the presence or absence of co- crystallized water or other molecules, which can be weakly or strongly bound in the lattice. Polymorphs can differ in such chemical, physical and biological properties as crystal shape, density, hardness, color, chemical stability, melting point, hygroscopicity, suspensibility, dissolution rate and biological availability.
• beneficial effects e.g., suitability for preparation of useful formulations, improved biological performance
• Embodiments of the present invention as described in the Summary of the Invention include those described below.
• Formula 1 includes stereoisomers, tautomers, N-oxides and salts thereof, and reference to "a compound of Formula 1" includes the definitions of substituents specified in the Summary of the Invention unless further defined in the Embodiments.
• Embodiment 1 A compound of Formula 1 wherein R 1 and R 2 are each independently H, C r C 6 alkyl, C r C 6 haloalkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 2 -C 6 cyanoalkyl, C 2 -Cg hydroxyalkyl, C3-C6 cycloalkyl, C3-C6 halocycloalkyl, C4-C6 cycloalkylalkyl, ⁇ - ⁇ alkylcycloalkyl, C ⁇ -Cg alkylthio, C Cg haloalkylthio, C j -Cg alkylsulfmyl, C j -Cg haloalkylsulfinyl, C j -Cg alkylsulfonyl, C ⁇ -Cg haloalkylsulfonyl, C 2 -C 6 alkylthioalkyl
• Embodiment 2 A compound of Embodiment 1 wherein R 1 and R 2 are each
• Cj-Cg alkyl independently H, Cj-Cg alkyl, Cj-Cg haloalkyl, C 2 -Cg alkenyl, C 2 -Cg alkynyl, C 2 -Cg hydroxyalkyl, C3-C 6 cycloalkyl, C4-C5 cycloalkylalkyl, C4-Cg alkylcycloalkyl, C 2 -Cg alkylthioalkyl or C 2 -Cg alkoxyalkyl; or -(CH 2 ) n W.
• Embodiment 3 A compound of Embodiment 2 wherein R 1 and R 2 are each
• Cj-Cg alkyl independently H, Cj-Cg alkyl, Cj-Cg haloalkyl, C 2 -Cg alkenyl, C 2 -Cg alkynyl, C 2 -Cg hydroxyalkyl, C3-C 6 cycloalkyl, C4-Cg cycloalkylalkyl, C4-C 6 alkylcycloalkyl or C 2 -C 6 alkoxyalkyl; or -(CH 2 ) n W.
• Embodiment 4 A compound of Embodiment 3 wherein R 1 and R 2 are each
• Embodiment A compound of Embodiment 4 wherein R 1 and R 2 are each
• Embodiment 6 A compound of Embodiment 5 wherein R 1 and R 2 are each
• Embodiment 7 A compound of Embodiment 6 wherein R 1 and R 2 are each
• Embodiment 8 A compound of Formula 1 or any one of Embodiments 1 through 7 wherein each W is phenyl optionally substituted with up to 3 substituents independently selected from halogen and C1-C3 alkyl.
• Embodiment 9 A compound of Embodiment 7 wherein each W is phenyl.
• Embodiment 10 A compound of Formula 1 or any one of Embodiments 1 through 9 wherein R 3 , R 4 , R 5 and R 6 are each independently H, cyano, hydroxy, halogen,
• Embodiment 11 A compound of Embodiment 10 wherein R 3 , R 4 , R 5 and R 6 are each independently H, halogen or C1-C3 alkyl.
• Embodiment 12 A compound of Embodiment 11 wherein R 3 , R 4 , R 5 and R 6 are each independently H or methyl.
• Embodiment 13 A compound of Embodiment 12 wherein R 3 , R 4 , R 5 and R 6 are each H.
• Embodiment 14 A compound of Formula 1 or any one of Embodiments 1 through 13 wherein R 7 and R 8 are each independently H, C Cg alkyl, C3-C 6 cycloalkyl, C 4 -Cg cycloalkylalkyl, C2-Cg alkylcarbonyl, C4-C8 cycloalkylcarbonyl or C2-Cg alkoxycarbonyl.
• Embodiment 15 A compound of Embodiment 14 wherein R 7 and R 8 are each
• Embodiment 16 A compound of Embodiment 15 wherein R 7 and R 8 are each
• Embodiment 17 A compound of Embodiment 16 wherein R 7 and R 8 are each
• Embodiment 18 A compound of Embodiment 16 wherein R 7 and R 8 are each
• Embodiment 19 A compound of Embodiment 18 wherein R 7 and R 8 are each
• Embodiments of this invention can be combined in any manner, and the descriptions of variables in the embodiments pertain not only to the compounds of Formula 1 but also to the starting compounds and intermediate compounds useful for preparing the compounds of Formula 1.
• embodiments of this invention including Embodiments 1-19 above as well as any other embodiments described herein, and any combination thereof, pertain to the compositions and methods of the present invention.
• Embodiment A A compound of Formula 1 wherein
• R 1 and R 2 are each independently H, C j -Cg alkyl, C j -Cg haloalkyl, C2-Q alkenyl, C2-C 6 alkynyl, C -C ⁇ hydroxyalkyl, C3-C 6 cycloalkyl, C4-C6 cycloalkylalkyl, C4-C 6 alkylcycloalkyl, C2-Cg alkylthioalkyl or C2-Cg alkoxyalkyl; or -(CH 2 ) n W;
• each W is phenyl optionally substituted with up to 3 substituents independently selected from halogen and C1-C3 alkyl;
• R 3 , R 4 , R 5 and R 6 are each independently H, cyano, hydroxy, halogen, C1-C3 alkyl, C1-C3 haloalkyl or C1-C3 alkoxy;
• R 7 and R 8 are each independently H, C j -Cg alkyl, C3-C6 cycloalkyl, C4-C8 cycloalkylalkyl, C2-C 6 alkylcarbonyl, rCg cycloalkylcarbonyl or C2-C5 alkoxycarbonyl.
• Embodiment B A compound of Embodiment A wherein
• R 1 and R 2 are each independently H, C1-C4 alkyl, C1-C4 haloalkyl, C2-Cg alkenyl, C2-C5 alkynyl, C2-C4 hydroxyalkyl, C3-C4 cycloalkyl, C4-C6 cycloalkylalkyl, C4-C 6 alkylcycloalkyl or C2-C4 alkoxyalkyl; or -(CH 2 ) n W;
• R 3 , R 4 , R 5 and R 6 are each independently H, halogen or C1-C3 alkyl; and R 7 and R 8 are each independently H, C1-C3 alkyl, cyclopropyl, C2-C4
• alkylcarbonyl or C2-C4 alkoxycarbonyl are examples of alkylcarbonyl or C2-C4 alkoxycarbonyl.
• Embodiment C A compound of Embodiment B wherein
• R1 and R 2 are each independently H, methyl or ethyl
• R 3 , R 4 , R 5 and R 6 are each independently H or methyl
• R 7 and R 8 are each independently H, methyl, ⁇ 4 alkylcarbonyl or C2-C4 alkoxycarbonyl.
• Specific embodiments include compounds of Formula 1 selected from the group consisting of:
• Compounds of Formula la can be prepared by first condensing a compound of Formula 2 with a hydrazine of Formula 3 followed by a second hydrazine of Formula 4.
• the compound of Formula 2 can be contacted with compounds of Formula 3 and 4 either sequentially or a mixture Formula 3 and 4 can be used.
• two or more equivalents of a single hydrazine can be used.
• Acid salts of hydrazines of Formula 3 and 4 can also be used in this reaction, provided that at least 2 equivalents of an acid scavenger is present, as known to one skilled in the art.
• Typical acids used to form salts with amines include hydrochloric acid, oxalic acid and trifluoroacetic acid.
• General procedures for this type of reaction are documented in the chemical literature; see, for example, Journal fuer Praktician Chemie 1978, 320(6), 991-998 and Dyes and Pigments 1991, 17(2), 113-121. Also, the method of Scheme 1 is illustrated in Example 1.
• R a is lower alkyl
• Certain compounds of Formula 2 are known and can be obtained from commercial sources. Compounds of Formula 2 can also be synthesized by methods documented in the chemical literature (see, e.g., Chemistry - A European Journal 2009, 15(9), 2200-2209, Journal fuer Praktician Chemie 1978, 320(6), 991-998 and Synthesis 2007, 19, 3061-3067).
• compounds of Formula 2a can be prepared by reacting dialkyl succinates of Formula 4 with a base such as sodium hydride, triethyl amine or potassium carbonate in an aprotic solvent such as benzene, tetrahydrofuran or dioxane at a temperature between 25° C and the boiling point of the solvent.
• a base such as sodium hydride, triethyl amine or potassium carbonate
• an aprotic solvent such as benzene, tetrahydrofuran or dioxane
• a mixture of two different compounds of Formula 4 can be used in the method of Scheme 2.
• reactions using two different compounds of Formula 2 result in a mixture of products, which can be purified by chromatography or recrystallization methods, or it can be reacted without purification, and purified at a later stage.
• R is lower alkyl
• R is lower alkyl
• compounds of Formula 1 wherein R 7 and R 8 are other than H can be prepared from compounds of Formula la by standard alkylation or acylation methods, as illustrated in Example 2.
• compounds of Formula la wherein R 1 and/or R 2 are hydrogen can undergo alkylation to provide compounds of Formula 1 wherein R 1 and/or R 2 are alkyl.
• Typical reaction conditions involve treating a compound of Formula la wherein R 1 R 2 , R 7 and/or R 8 are hydrogen with an alkylating agent, in amount ranging from about 1 to about 10 molar equivalents relative to the compound of Formula la.
• the reaction is preferably run in the presence of a base such as potassium carbonate, sodium hydride or potassium tert- butoxide typically in an amount ranging from about 1 to 10 molar equivalents.
• a base such as potassium carbonate, sodium hydride or potassium tert- butoxide typically in an amount ranging from about 1 to 10 molar equivalents.
• Optimum results are usually obtained when the reaction is run in a polar solvent such as N,N- dimethylformamide, tetrahydrofuran, acetone or dimethyl sulfoxide, at temperatures ranging from about 0 °C to 150 °C (depending on the solvent).
• a polar solvent such as N,N- dimethylformamide, tetrahydrofuran, acetone or dimethyl sulfoxide
• a compound of this invention will generally be used as a fungicidal active ingredient in a composition, i.e. formulation, with at least one additional component selected from the group consisting of surfactants, solid diluents and liquid diluents, which serve as a carrier.
• a composition i.e. formulation
• additional component selected from the group consisting of surfactants, solid diluents and liquid diluents, which serve as a carrier.
• the formulation or composition ingredients are selected to be consistent with the physical properties of the active ingredient, mode of application and environmental factors such as soil type, moisture and temperature.
• Liquid compositions include solutions (including emulsifiable concentrates), suspensions, emulsions (including microemulsions and/or suspoemulsions) and the like, which optionally can be thickened into gels.
• aqueous liquid compositions are soluble concentrate, suspension concentrate, capsule suspension, concentrated emulsion, microemulsion and suspo-emulsion.
• nonaqueous liquid compositions are emulsifiable concentrate, microemulsifiable concentrate, dispersible concentrate and oil dispersion.
• compositions are dusts, powders, granules, pellets, prills, pastilles, tablets, filled films (including seed coatings) and the like, which can be water-dispersible ("wettable") or water-soluble. Films and coatings formed from film- forming solutions or flowable suspensions are particularly useful for seed treatment.
• Active ingredient can be (micro)encapsulated and further formed into a suspension or solid formulation; alternatively the entire formulation of active ingredient can be encapsulated (or "overcoated”). Encapsulation can control or delay release of the active ingredient.
• An emulsifiable granule combines the advantages of both an emulsifiable concentrate formulation and a dry granular formulation. High-strength compositions are primarily used as intermediates for further formulation.
• Sprayable formulations are typically extended in a suitable medium before spraying. Such liquid and solid formulations are formulated to be readily diluted in the spray medium, usually water. Spray volumes can range from about one to several thousand liters per hectare, but more typically are in the range from about ten to several hundred liters per hectare. Sprayable formulations can be tank mixed with water or another suitable medium for foliar treatment by aerial or ground application, or for application to the growing medium of the plant. Liquid and dry formulations can be metered directly into drip irrigation systems or metered into the furrow during planting. Liquid and solid formulations can be applied onto seeds of crops and other desirable vegetation as seed treatments before planting to protect developing roots and other subterranean plant parts and/or foliage through systemic uptake.
• the formulations will typically contain effective amounts of active ingredient, diluent and surfactant within the following approximate ranges which add up to 100 percent by weight.
• Solid diluents include, for example, clays such as bentonite, montmorillonite, attapulgite and kaolin, gypsum, cellulose, titanium dioxide, zinc oxide, starch, dextrin, sugars (e.g., lactose, sucrose), silica, talc, mica, diatomaceous earth, urea, calcium carbonate, sodium carbonate and bicarbonate, and sodium sulfate.
• Typical solid diluents are described in Watkins et al., Handbook of Insecticide Dust Diluents and Carriers, 2nd Ed., Dorland Books, Caldwell, New Jersey.
• Liquid diluents include, for example, water, N,N-dimethylalkanamides (e.g., N,N-dimethylformamide), limonene, dimethyl sulfoxide, N-alkylpyrrolidones (e.g., N-methylpyrrolidinone), ethylene glycol, triethylene glycol, propylene glycol, dipropylene glycol, polypropylene glycol, propylene carbonate, butylene carbonate, paraffins (e.g., white mineral oils, normal paraffins, isoparaffins), alkylbenzenes, alkylnaphthalenes, glycerine, glycerol triacetate, sorbitol, aromatic hydrocarbons, dearomatized aliphatics, alkylbenzenes, alkylnaphthalenes, ketones such as cyclohexanone, 2-heptanone, isophorone and 4-hydroxy- 4-methyl-2-pentan
• Liquid diluents also include glycerol esters of saturated and unsaturated fatty acids (typically Cg-C22), such as plant seed and fruit oils (e.g., oils of olive, castor, linseed, sesame, corn (maize), peanut, sunflower, grapeseed, saffiower, cottonseed, soybean, rapeseed, coconut and palm kernel), animal-sourced fats (e.g., beef tallow, pork tallow, lard, cod liver oil, fish oil), and mixtures thereof.
• plant seed and fruit oils e.g., oils of olive, castor, linseed, sesame, corn (maize), peanut, sunflower, grapeseed, saffiower, cottonseed, soybean, rapeseed, coconut and palm kernel
• animal-sourced fats e.g., beef tallow, pork tallow, lard, cod liver oil, fish oil
• Liquid diluents also include alkylated fatty acids (e.g., methylated, ethylated, butylated) wherein the fatty acids may be obtained by hydrolysis of glycerol esters from plant and animal sources, and can be purified by distillation.
• alkylated fatty acids e.g., methylated, ethylated, butylated
• Typical liquid diluents are described in Marsden, Solvents Guide, 2nd Ed., Interscience, New York, 1950.
• the solid and liquid compositions of the present invention often include one or more surfactants.
• surfactants also known as “surface-active agents”
• surface-active agents generally modify, most often reduce, the surface tension of the liquid.
• surfactants can be useful as wetting agents, dispersants, emulsifiers or defoaming agents.
• Nonionic surfactants useful for the present compositions include, but are not limited to: alcohol alkoxylates such as alcohol alkoxylates based on natural and synthetic alcohols (which may be branched or linear) and prepared from the alcohols and ethylene oxide, propylene oxide, butylene oxide or mixtures thereof; amine ethoxylates, alkanolamides and ethoxylated alkanolamides; alkoxylated triglycerides such as ethoxylated soybean, castor and rapeseed oils; alkylphenol alkoxylates such as octylphenol ethoxylates, nonylphenol ethoxylates, dinonyl phenol ethoxylates and dodecyl phenol ethoxylates (prepared from the phenols and ethylene oxide, propylene oxide, butylene oxide or mixtures thereof); block polymers prepared from ethylene oxide or propylene
• Useful anionic surfactants include, but are not limited to: alkylaryl sulfonic acids and their salts; carboxylated alcohol or alkylphenol ethoxylates; diphenyl sulfonate derivatives; lignin and lignin derivatives such as lignosulfonates; maleic or succinic acids or their anhydrides; olefin sulfonates; phosphate esters such as phosphate esters of alcohol alkoxylates, phosphate esters of alkylphenol alkoxylates and phosphate esters of styryl phenol ethoxylates; protein-based surfactants; sarcosine derivatives; styryl phenol ether sulfate; sulfates and sulfonates of oils and fatty acids; sulfates and sulfonates of ethoxylated alkylphenols; sulfates of alcohols; sulfates of e
• Useful cationic surfactants include, but are not limited to: amides and ethoxylated amides; amines such as N-alkyl propanediamines, tripropylenetriamines and dipropylenetetramines, and ethoxylated amines, ethoxylated diamines and propoxylated amines (prepared from the amines and ethylene oxide, propylene oxide, butylene oxide or mixtures thereof); amine salts such as amine acetates and diamine salts; quaternary ammonium salts such as quaternary salts, ethoxylated quaternary salts and diquaternary salts; and amine oxides such as alkyldimethylamine oxides and bis-(2-hydroxyethyl)-alkylamine oxides.
• amines such as N-alkyl propanediamines, tripropylenetriamines and dipropylenetetramines, and ethoxylated amine
• Nonionic, anionic and cationic surfactants and their recommended uses are disclosed in a variety of published references including McCutcheon 's Emulsifiers and Detergents, annual American and International Editions published by McCutcheon's Division, The Manufacturing Confectioner Publishing Co.; Sisely and Wood, Encyclopedia of Surface Active Agents, Chemical Publ. Co., Inc., New York, 1964; and A. S. Davidson and B. Milwidsky, Synthetic Detergents, Seventh Edition, John Wiley and Sons, New York, 1987.
• compositions of this invention may also contain formulation auxiliaries and additives, known to those skilled in the art as formulation aids (some of which may be considered to also function as solid diluents, liquid diluents or surfactants).
• formulation auxiliaries and additives may control: pH (buffers), foaming during processing (antifoams such polyorganosiloxanes), sedimentation of active ingredients (suspending agents), viscosity (thixotropic thickeners), in-container microbial growth (antimicrobials), product freezing (antifreezes), color (dyes/pigment dispersions), wash-off (film formers or stickers), evaporation (evaporation retardants), and other formulation attributes.
• Film formers include, for example, polyvinyl acetates, polyvinyl acetate copolymers, polyvinylpyrrolidone-vinyl acetate copolymer, polyvinyl alcohols, polyvinyl alcohol copolymers and waxes.
• formulation auxiliaries and additives include those listed in McCutcheon 's Volume 2: Functional Materials, annual International and North American editions published by McCutcheon's Division, The Manufacturing Confectioner Publishing Co.; and PCT Publication WO 03/024222.
• the compound of Formula 1 and any other active ingredients are typically incorporated into the present compositions by dissolving the active ingredient in a solvent or by grinding in a liquid or dry diluent.
• Solutions, including emulsifiable concentrates can be prepared by simply mixing the ingredients. If the solvent of a liquid composition intended for use as an emulsifiable concentrate is water-immiscible, an emulsifier is typically added to emulsify the active-containing solvent upon dilution with water.
• Active ingredient slurries, with particle diameters of up to 2,000 ⁇ can be wet milled using media mills to obtain particles with average diameters below 3 ⁇ .
• Aqueous slurries can be made into finished suspension concentrates (see, for example, U.S. 3,060,084) or further processed by spray drying to form water-dispersible granules. Dry formulations usually require dry milling processes, which produce average particle diameters in the 2 to 10 um range. Dusts and powders can be prepared by blending and usually grinding (such as with a hammer mill or fluid-energy mill). Granules and pellets can be prepared by spraying the active material upon preformed granular carriers or by agglomeration techniques.
• 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.
• One embodiment of the present invention relates to a method for controlling fungal pathogens, comprising diluting the fungicidal composition of the present invention (a compound of Formula 1 formulated with surfactants, solid diluents and liquid diluents or a formulated mixture of a compound of Formula 1 and at least one other fungicide) with water, and optionally adding an adjuvant to form a diluted composition, and contacting the fungal pathogen or its environment with an effective amount of said diluted composition.
• the fungicidal composition of the present invention a compound of Formula 1 formulated with surfactants, solid diluents and liquid diluents or a formulated mixture of a compound of Formula 1 and at least one other fungicide
• a spray composition formed by diluting with water a sufficient concentration of the present fungicidal composition can provide sufficient efficacy for controlling fungal pathogens
• adjuvant products can also be added to spray tank mixtures.
• additional adjuvants are commonly known as “spray adjuvants” or “tank- mix adjuvants”, and include any substance mixed in a spray tank to improve the performance of a pesticide or alter the physical properties of the spray mixture.
• Adjuvants can be anionic or nonionic surfactants, emulsifying agents, petroleum-based crop oils, crop-derived seed oils, acidifiers, buffers, thickeners or defoaming agents.
• Adjuvants are used to enhancing efficacy (e.g., biological availability, adhesion, penetration, uniformity of coverage and durability of protection), or minimizing or eliminating spray application problems associated with incompatibility, foaming, drift, evaporation, volatilization and degradation.
• adjuvants are selected with regard to the properties of the active ingredient, formulation and target (e.g., crops, insect pests).
• the amount of adjuvants added to spray mixtures is generally in the range of about 2.5% to 0.1 % by volume.
• the application rates of adjuvants added to spray mixtures are typically between about 1 to 5 L per hectare.
• Representative examples of spray adjuvants include: Adigor® (Syngenta) 47% methylated rapeseed oil in liquid hydrocarbons, Silwet® (Helena Chemical Company) polyalkyleneoxide modified heptamethyltrisiloxane and Assist® (BASF) 17% surfactant blend in 83% paraffin based mineral oil.
• compositions formulated for seed treatment generally comprise a film former or adhesive agent. Therefore typically a seed coating composition of the present invention comprises a biologically effective amount of a compound of Formula 1 and a film former or adhesive agent. Seeds can be coated by spraying a flowable suspension concentrate directly into a tumbling bed of seeds and then drying the seeds. Alternatively, other formulation types such as wetted powders, solutions, suspoemulsions, emulsifiable concentrates and emulsions in water can be sprayed on the seed. This process is particularly useful for applying film coatings on seeds. Various coating machines and processes are available to one skilled in the art. Suitable processes include those listed in P. Kosters et al., Seed Treatment: Progress and Prospects, 1994 BCPC Mongraph No. 57, and references listed therein.
• Compound 1 10.0% attapulgite granules (low volatile matter, 0.71/0.30 mm; 90.0% U.S.S. No. 25-50 sieves)
• Compound 10 25.0% anhydrous sodium sulfate 10.0% crude calcium ligninsulfonate 5.0% sodium alkylnaphthalenesulfonate 1.0% calcium/magnesium bentonite 59.0%
• Compound 9 10.0% polyoxyethylene sorbitol hexoleate 20.0% Cg-Qo fatty acid methyl ester 70.0%
• Compound 14 20.00% polyvinylpyrrolidone -vinyl acetate copolymer 5.00%) montan acid wax 5.00%) calcium ligninsulfonate 1.00%) polyoxyethylene/polyoxypropylene block copolymers 1.00% stearyl alcohol (POE 20) 2.00% polyorganosilane 0.20% colorant red dye 0.05% water 65.75%
• butyl polyoxyethylene/polypropylene block copolymer 4.0%> stearic acid/polyethylene glycol copolymer 1.0% styrene acrylic polymer 1.0% xanthan gum 0.1% propylene glycol 5.0%> silicone based defoamer 0.1%
• compound 11 10.0% butyl polyoxyethylene/polypropylene block copolymer 4.0% stearic acid/polyethylene glycol copolymer 1.0% styrene acrylic polymer 1.0% xanthan gum 0.1%) propylene glycol 5.0% silicone based defoamer 0.1%
• compound 13 10.0% imidacloprid 5.0% butyl polyoxyethylene/polypropylene block copolymer 4.0% stearic acid/polyethylene glycol copolymer 1.0% styrene acrylic polymer 1.0% xanthan gum 0.1% propylene glycol 5.0% silicone based defoamer 0.1%
• Water-soluble and water-dispersible formulations are typically diluted with water to form aqueous compositions before application.
• Aqueous compositions for direct applications to the plant or portion thereof typically at least about 1 ppm or more (e.g., from 1 ppm to 100 ppm) of the compound(s) of this invention.
• a flowable suspension formulated for seed treatment typically comprises from about 0.5 to about 70% of the active ingredient, from about 0.5 to about 30% of a film- forming adhesive, from about 0.5 to about 20% of a dispersing agent, from 0 to about 5% of a thickener, from 0 to about 5% of a pigment and/or dye, from 0 to about 2% of an antifoaming agent, from 0 to about 1% of a preservative, and from 0 to about 75% of a volatile liquid diluent.
• the compounds of this invention are useful as plant disease control agents.
• the present invention therefore further comprises a method for controlling plant diseases caused by fungal plant pathogens comprising applying to the plant or portion thereof to be protected, or to the plant seed to be protected, an effective amount of a compound of the invention or a fungicidal composition containing said compound.
• the compounds and/or compositions of this invention provide control of diseases caused by a broad spectrum of fungal plant pathogens in the Ascomycete, Basidiomycota, Zygomycota phyla, and the fungal-like Oomycete and Deuteromycete classes. They are effective in controlling a broad spectrum of plant diseases, particularly foliar pathogens of ornamental, turf, vegetable, field, cereal, and fruit crops.
• pathogens include but are not limited to those listed in Table 1-1.
• names for both the sexual/teleomorph/perfect stage as well as names for the asexual/anamorph/imperfect stage (in parentheses) are listed where known. Synonymous names for pathogens are indicated by an equal sign.
• the sexual/teleomorph/perfect stage name Phaeosphaeria nodorum is followed by the corresponding asexual/anamorph/imperfect stage name Stagnospora nodorum and the synonymous older name Septoria nodorum.
• Botryotinia fuckeliana Botrytis cinerea
• Oculimacula yallundae Tapesia yallundae
• anamorph Helgardia herpotrichoides Pseudocercosporella herpetrichoides), Monilinia fructicola, Sclerotinia sclerotiorum, Sclerotinia minor, and Sclerotinia homoeocarpa;
• Rhynchosporium secalis and anthracnose pathogens such as Glomerella acutata (Colletotrichum acutatum), G. graminicola (C. graminicola) and G. lagenaria (C. orbicular e);
• Basidiomycetes in the order Urediniales including Puccinia recondita, P. striiformis, Puccinia hordei, P. graminis and P. arachidis), Hemileia vastatrix and Phakopsora pachyrhizi; Basidiomycetes in the order Ceratobasidiales such as Thanatophorum cucumeris (Rhizoctonia solani) and Ceratobasidium oryzae-sativae (Rhizoctonia oryzae);
• Basidiomycetes in the order Polyporales such as Athelia rolfsii (Sclerotium rolfsii);
• Oomycetes in the order Pythiales including Phytophthora infestans, P. megasperma, P. parasitica, P. sojae, P. cinnamomi and P. capsici, and Pythium pathogens such as Pythium aphanidermatum, P. graminicola, P. irregulare, P. ultimum and P. dissoticum;
• compositions or combinations also have activity against bacteria such as Erwinia amylovora, Xanthomonas campestris, Pseudomonas syringae, and other related species.
• bacteria such as Erwinia amylovora, Xanthomonas campestris, Pseudomonas syringae, and other related species.
• the compounds of the invention are useful for improving (i.e. increasing) the ratio of beneficial to harmful microorganisms in contact with crop plants or their propagules (e.g., seeds, corms, bulbs, tubers, cuttings) or in the agronomic environment of the crop plants or their propagules.
• Plant and seed varieties and cultivars can be obtained by conventional propagation and breeding methods or by genetic engineering methods. Genetically modified plants or seeds (transgenic plants or seeds) are those in which a heterologous gene (transgene) has been stably integrated into the plant's or seed's genome. A transgene that is defined by its particular location in the plant genome is called a transformation or transgenic event.
• Genetically modified plant cultivars which can be treated according to the invention include those that are resistant against one or more biotic stresses (pests such as nematodes, insects, mites, fungi, etc.) or abiotic stresses (drought, cold temperature, soil salinity, etc.), or that contain other desirable characteristics. Plants can be genetically modified to exhibit traits of, for example, herbicide tolerance, insect-resistance, modified oil profiles or drought tolerance. Useful genetically modified plants containing single gene transformation events or combinations of transformation events are listed in Table 2- 1. Additional information for the genetic modifications listed in Table 2-1 can be obtained from publicly available databases maintained, for example, by the U.S. Department of Agriculture.
• Potato cry3A plrv orfl; plrv orf2; cp4 epsps (aroA:CP4)
• Potato cry A plrv orfl; plrv orf2; cp4 epsps (aroA:CP4)
• Treatment of genetically modified plants and seeds with compounds of the invention may result in super-additive or synergistic effects. For example, reduction in application rates, broadening of the activity spectrum, increased tolerance to biotic/abiotic stresses or enhanced storage stability may be greater than expected from just simple additive effects of the application of compounds of the invention on genetically modified plants and seeds.
• treating a seed means contacting the seed with a biologically effective amount of a compound of this invention, which is typically formulated as a composition of the invention.
• This seed treatment protects the seed from soil-borne disease pathogens and generally can also protect roots and other plant parts in contact with the soil of the seedling developing from the germinating seed.
• the seed treatment may also provide protection of foliage by translocation of the compound of this invention or a second active ingredient within the developing plant. Seed treatments can be applied to all types of seeds, including those from which plants genetically transformed to express specialized traits will germinate.
• Representative examples include those expressing proteins toxic to invertebrate pests, such as Bacillus thuringiensis toxin or those expressing herbicide resistance such as glyphosate acetyltransferase, which provides resistance to glyphosate.
• Seed treatments with compounds of this invention can also increase vigor of plants growing from the seed.
• Compounds of this invention and their compositions, both alone and in combination with other fungicides, nematicides and insecticides, are particularly useful in seed treatment for crops including, but not limited to, maize or corn, soybeans, cotton, cereal (e.g., wheat, oats, barley, rye and rice), potatoes, vegetables and oilseed rape.
• the compounds of this invention are useful in treating postharvest diseases of fruits and vegetables caused by fungi and bacteria. These infections can occur before, during and after harvest. For example, infections can occur before harvest and then remain dormant until some point during ripening (e.g., host begins tissue changes in such a way that infection can progress); also infections can arise from surface wounds created by mechanical or insect injury.
• the compounds of this invention can reduce losses (i.e. losses resulting from quantity and quality) due to postharvest diseases which may occur at any time from harvest to consumption.
• Treatment of postharvest diseases with compounds of the invention can increase the period of time during which perishable edible plant parts (e.g, fruits, seeds, foliage, stems, bulbs, tubers) can be stored refrigerated or un- refrigerated after harvest, and remain edible and free from noticeable or harmful degradation or contamination by fungi or other microorganisms.
• Treatment of edible plant parts before or after harvest with compounds of the invention can also decrease the formation of toxic metabolites of fungi or other microorganisms, for example, mycotoxins such as aflatoxins.
• Plant disease control 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, fruits, 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 seeds to protect the seeds and seedlings developing from the seeds.
• the compounds can also be applied through irrigation water to treat plants. Control of postharvest pathogens which infect the produce before harvest is typically accomplished by field application of a compound of this invention, and in cases where infection occurs after harvest the compounds can be applied to the harvested crop as dips, sprays, fumigants, treated wraps and box liners.
• Rates of application for these compounds can be influenced by factors such as the plant diseases to be controlled, the plant species to be protected, ambient moisture and temperature and should be determined under actual use conditions.
• a fungicidally effective amount can be influenced by factors such as the plant diseases to be controlled, the plant species to be protected, ambient moisture and temperature and should be determined under actual use conditions.
• One skilled in the art can easily determine through simple experimentation the fungicidally effective amount necessary for the desired level of plant disease control.
• Foliage can normally be protected when treated at a rate of from less than about 1 g/ha to about 5,000 g/ha of active ingredient.
• Seed and seedlings can normally be protected when seed is treated at a rate of from about 0.1 to about 10 g per kilogram of seed.
• Compounds of this invention can also be mixed with one or more other biologically active compounds or agents including fungicides, insecticides, nematocides, bactericides, acaricides, herbicides, herbicide safeners, growth regulators such as insect molting inhibitors and rooting stimulants, chemosterilants, semiochemicals, repellents, attractants, pheromones, feeding stimulants, plant nutrients, other biologically active compounds or entomopathogenic bacteria, virus or fungi to form a multi-component pesticide giving an even broader spectrum of agricultural protection.
• fungicides insecticides, nematocides, bactericides, acaricides, herbicides, herbicide safeners
• growth regulators such as insect molting inhibitors and rooting stimulants, chemosterilants, semiochemicals, repellents, attractants, pheromones, feeding stimulants, plant nutrients, other biologically active compounds or entomopathogenic bacteria, virus
• the present invention also pertains to a composition
• a composition comprising a compound of Formula 1 (in a fungicidally effective amount) and at least one additional biologically active compound or agent (in a biologically effective amount) and can further comprise at least one of a surfactant, a solid diluent or a liquid diluent.
• the other biologically active compounds or agents can be formulated in compositions comprising at least one of a surfactant, solid or liquid diluent.
• one or more other biologically active compounds or agents can be formulated together with a compound of Formula 1, to form a premix, or one or more other biologically active compounds or agents can be formulated separately from the compound of Formula 1, and the formulations combined together before application (e.g., in a spray tank) or, alternatively, applied in succession.
• one aspect of the present invention is a fungicidal composition
• a fungicidal composition comprising (i.e. a mixture or combination of) a compound of Formula 1, an N-oxide, or a salt thereof (i.e. component a), and at least one other fungicide (i.e. component b).
• a combination where the other fungicidal active ingredient has different site of action from the compound of Formula 1.
• a combination with at least one other fungicidal active ingredient having a similar spectrum of control but a different site of action will be particularly advantageous for resistance management.
• a composition of the present invention can further comprise a fungicidally effective amount of at least one additional fungicidal active ingredient having a similar spectrum of control but a different site of action.
• composition which in addition to the Formula 1 compound of component (a), includes as component (b) at least one fungicidal compound selected from the group consisting of the FRAC-defmed mode of action (MOA) classes (A) nucleic acid synthesis, (B) mitosis and cell division, (C) respiration, (D) amino acid and protein synthesis, (E) signal transduction, (F) lipid synthesis and membrane integrity, (G) sterol biosynthesis in membranes, (H) cell wall biosynthesis in membranes, (I) melanin synthesis in cell wall, (P) host plant defense induction, multi-site contact activity and unknown mode of action.
• MOA FRAC-defmed mode of action
• A nucleic acid synthesis
• B mitosis and cell division
• C respiration
• D amino acid and protein synthesis
• E signal transduction
• F lipid synthesis and membrane integrity
• G sterol biosynthesis in membranes
• H cell wall biosynthesis in membranes
• I melanin synthesis in cell
• FRAC-recognized or proposed target sites of action along with their FRAC target site codes belonging to the above MOA classes are (Al) RNA polymerase I, (A2) adenosine deaminase, (A3) DNA RNA synthesis (proposed), (A4) DNA topoisomerase, (B1-B3) B- tubulin assembly in mitosis, (B4) cell division (proposed), (B5) derealization of spectrin- like proteins, (CI) complex I NADH odxido-reductase, (C2) complex II: succinate dehydrogenase, (C3) complex III: cytochrome bcl (ubiquinol oxidase) at Qo site, (C4) complex III: cytochrome bcl (ubiquinone reductase) at Qi site, (C5) uncouplers of oxidative phosphorylation, (C6) inhibitors of oxidative phosphorylation, ATP synthase, (
• composition which in addition to the Formula 1 compound of component (a), includes as component (b) at least one fungicidal compound selected from the group consisting of the classes (bl) methyl benzimidazole carbamate (MBC) fungicides; (b2) dicarboximide fungicides; (b3) demethylation inhibitor (DMI) fungicides; (b4) phenylamide fungicides; (b5) amine/morpholine fungicides; (b6) phospholipid biosynthesis inhibitor fungicides; (bl) succinate dehydrogenase inhibitor fungicides; (b8) hydroxy(2- amino-)pyrimidine fungicides; (b9) anilinopyrimidine fungicides; (blO) N-phenyl carbamate fungicides; (bl 1) quinone outside inhibitor (Qol) fungicides; (bl2) phenylpyrrole fungicides; (bl3) azanaphthalene fung
• Methyl benzimidazole carbamate (MBC) fungicides inhibit mitosis by binding to ⁇ -tubulin during microtubule assembly. Inhibition of microtubule assembly can disrupt cell division, transport within the cell and cell structure.
• Methyl benzimidazole carbamate fungicides include benzimidazole and thiophanate fungicides.
• the benzimidazoles include benomyl, carbendazim, fuberidazole and thiabendazole.
• the thiophanates include thiophanate and thiophanate-methyl.
• b2 "Dicarboximide fungicides" (FRAC code 2) inhibit a MAP/histidine kinase in osmotic signal transduction.
• Examples include chlozolinate, iprodione, procymidone and vinclozolin.
• DMI Demethylation inhibitor
• FRAC code 3 Step 3
• SBI Sterol Biosynthesis Inhibitors (SBI): Class I) inhibit C14-demethylase, which plays a role in sterol production.
• Sterols such as ergosterol, are needed for membrane structure and function, making them essential for the development of functional cell walls. Therefore, exposure to these fungicides results in abnormal growth and eventually death of sensitive fungi.
• DMI fungicides are divided between several chemical classes: azoles (including triazoles and imidazoles), pyrimidines, piperazines, pyridines and triazolinthiones.
• the triazoles include azaconazole, bitertanol, bromuconazole, cyproconazole, difenoconazole, diniconazole (including diniconazole-M), epoxiconazole, etaconazole, fenbuconazole, fluquinconazole, flusilazole, flutriafol, hexaconazole, imibenconazole, ipconazole, metconazole, myclobutanil, penconazole, propiconazole, , quinconazole, simeconazole, tebuconazole, tetraconazole, triadimefon, triadimenol, triticonazole, uniconazole, uniconazole-P, a-(l- ch j orocyciopropyl)-a-[2-(2,2-dichlorocyclopropyl)ethyl]-l
• the imidazoles include econazole, imazalil, oxpoconazole, prochloraz, pefurazoate and triflumizole.
• the pyrimidines include fenarimol, nuarimol and triarimol.
• the piperazines include triforine.
• the pyridines include buthiobate, pyrifenox, pyrisoxazole (3-[(3R)-5-(4-chlorophenyl)-2,3- dimethyl-3-isoxazolidinyl]pyridine, mixture of 3R,5R- and S i ⁇ -isomers) and ( 5)-[3-(4- chloro-2-fluorophenyl)-5-(2,4-difluorophenyl)-4-isoxazolyl]-3-pyridinemethanol.
• the triazolinthiones include prothioconazole and 2-[2-(l-chlorocyclopropyl)-4-(2,2- dichlorocyclopropyl)-2-hydroxybutyl]-l,2-dihydro-3H-l,2,4-triazole-3-thione.
• Biochemical investigations have shown that all of the above mentioned fungicides are DMI fungicides as described by . H. Kuck et al. in Modern Selective Fungicides - Properties, Applications and Mechanisms of Action, H. Lyr (Ed.), Gustav Fischer Verlag: New York, 1995, 205-258.
• Phenylamide fungicides are specific inhibitors of RNA polymerase in Oomycete fungi. Sensitive fungi exposed to these fungicides show a reduced capacity to incorporate uridine into rRNA. Growth and development in sensitive fungi is prevented by exposure to this class of fungicide.
• Phenylamide fungicides include acylalanine, oxazolidinone and butyrolactone fungicides.
• the acylalanines include benalaxyl, benalaxyl-M (also known as kiralaxyl), furalaxyl, metalaxyl and metalaxyl-M (also known as mefenoxam).
• the oxazolidinones include oxadixyl.
• the butyrolactones include ofurace.
• Amine/morpholine fungicides include morpholine, piperidine and spiroketal-amine fungicides.
• the morpho lines include aldimorph, dodemorph, fenpropimorph, tridemorph and trimorphamide.
• the piperidines include fenpropidin and piperalin.
• the spiroketal-amines include spiroxamine.
• Phospholipid biosynthesis inhibitor fungicides inhibit growth of fungi by affecting phospholipid biosynthesis.
• Phospholipid biosynthesis fungicides include phophorothiolate and dithiolane fungicides.
• the phosphorothiolates include edifenphos, iprobenfos and pyrazophos.
• the dithiolanes include isoprothiolane.
• SDHI fungicides include phenylbenzamide, furan carboxamide, oxathiin carboxamide, thiazole carboxamide, pyrazole-4-carboxamide, pyridine carboxamide,, phenyl oxoethyl thiophene amides and pyridinylethyl benzamides
• the benzamides include benodanil, flutolanil and mepronil.
• the furan carboxamides include fenfuram.
• the oxathiin carboxamides include carboxin and oxycarboxin.
• the thiazole carboxamides include thifluzamide.
• the pyrazole-4-carboxamides include benzovindiflupyr (N-[9-(dichloromethylene)- 1 ,2,3 ,4-tetrahydro- 1 ,4- methanonaphthalen-5 -yl]-3 -(difluoromethyl)- 1 -methyl- 1 H-pyrazole-4-carboxamide), bixafen, fluxapyroxad (3-(difluoromethyl)-l-methyl-N-(3',4',5'-trifluoro[l, -biphenyl]-2- yl)-lH-pyrazole-4-carboxamide), furametpyr, isopyrazam (3 -(difluoromethyl)- 1- methyl-N- [l,2,3,4- ⁇ .etrahydro ⁇ 9-(l -meihyiei
• the pyridine carboxamides include boscalid.
• the phenyl oxoethyl thiophene amides include isofetamid (N-[l,l-dimethyl-2-[2- methyl-4-( 1 -methylethoxy)phenyl]-2-oxoethyl] -3 -methyl-2-thiophenecarboxamide) .
• the pyridinylethyl benzamides include fluopyram.
• Anilinopyrimidine fungicides (FRAC code 9) are proposed to inhibit biosynthesis of the amino acid methionine and to disrupt the secretion of hydro lytic enzymes that lyse plant cells during infection. Examples include cyprodinil, mepanipyrim and pyrimethanil.
• N-Phenyl carbamate fungicides (FRAC code 10) inhibit mitosis by binding to ⁇ -tubulin and disrupting microtubule assembly. Inhibition of microtubule assembly can disrupt cell division, transport within the cell and cell structure. Examples include diethofencarb.
• Quinone outside inhibitor fungicides include methoxyacrylate, methoxycarbamate, oximinoacetate, oximinoacetamide and dihydrodioxazine fungicides (collectively also known as strobilurin fungicides), and oxazolidinedione, imidazolinone and benzylcarbamate fungicides.
• the methoxyacrylates include azoxystrobin, coumoxystrobin (methyl (a£)-2-[[(3-butyl-4-methyl-2-oxo-2H-l- benzopyran-7-yl)oxy]methyl] -a-(methoxymethylene)benzeneacetate), enoxastrobin (methyl (a£ -2-[[[(£T)-[(2£')-3-(4-chlorophenyl)-l-methyl-2-propen-l-ylidene]amino]oxy]methyl]-a- (methoxymethylene)benzeneaceate) (also known as enestrobunn), flufenoxystrobin (methyl (a£ -2-[[2-chloro-4-(trifluoromethyl)phenoxy]methyl]-a- (methoxymethylene)benzeneacetate), picoxystrobin, and pyraoxystrobin (methyl (a£')-2- [[[3-(4-chlorophenyl
• the methoxycarbamates include pyraclostrobin ,pyrametostrobin (methyl N-[2-[[(l ,4-dimethyl-3 -phenyl- lH-pyrazol-5- yl)oxy]methyl]phenyl]-N-methoxycarbamate) and triclopyricarb (methyl N-methoxy-N-[2- [[(3,5,6-trichloro-2-pyridinyl)oxy]methyl]phenyl]carbamate).
• the oximinoacetates include kresoxim-methyl, and trifloxystrobin.
• the oximinoacetamides include dimoxystrobin, fenaminstrobin ((aii)-2-[[[(£)-[(2£)-3-(2,6-dichlorophenyl)-l-methyl-2-propen-l- ylidene]amino]oxy]methyl]-a-(methoxyimino)-N-methylbenzeneacetamide),
• the dihydrodioxazines include fluoxastrobin.
• the oxazolidinediones include famoxadone.
• the imidazolinones include fenamidone.
• the benzylcarbamates include pyribencarb. Class (bl l) also includes mandestrobin (2-[(2,5-dimethylphenoxy)methyl]-a-methoxy-N-benzeneacetamide).
• Azanaphthalene fungicides (FRAC code 13) are proposed to inhibit signal transduction by a mechanism which is as yet unknown. They have been shown to interfere with germination and/or appressorium formation in fungi that cause powdery mildew diseases.
• Azanaphthalene fungicides include aryloxyquinolines and quinazolinones.
• the aryloxyquinolines include quinoxyfen.
• the quinazolinones include proquinazid.
• Lipid peroxidation inhibitor fungicides are proposed to inhibit lipid peroxidation which affects membrane synthesis in fungi. Members of this class, such as etndiazole, may also affect other biological processes such as respiration and melanin biosynthesis.
• Lipid peroxidation fungicides include aromatic hydrocarbon and 1 ,2,4-thiadiazole fungicides.
• the aromatic hydrocarboncarbon fungicides include biphenyl, chloroneb, dicloran, quintozene, tecnazene and tolclofos-methyl.
• the 1 ,2,4-thiadiazoles include etridiazole.
• Melanin biosynthesis inhibitors-reductase fungicides include isobenzofuranone, pyrroloquinolmone and triazolobenzothiazole fungicides.
• the isobenzofuranones include fthalide.
• the pyrroloquinolinones include pyroquilon.
• the triazolobenzothiazoles include tricyclazole.
• Melanin biosynthesis inhibitors-dehydratase fungicides include cyclopropanecarboxamide, carboxamide and propionamide fungicides.
• the cyclopropanecarboxamides include carpropamid.
• the carboxamides include diclocymet.
• the propionamides include fenoxanil. (bl7) "Sterol Biosynthesis Inhibitor (SBI): Class III fungicides (FRAC code 17) inhibit 3-ketoreductase during C4-demethylation in sterol production.
• Class III inhibitors include hydroxyanilide fungicides and amino-pyrazolinone fungicides. Hydroxyanilides include fenhexamid. Amino-pyrazolinones include fenpyrazamine (5-2- propen- 1 -yl 5 -amino-2,3 -dihydro-2-( 1 -methylethyl)-4-(2-methylphenyl)-3 -oxo- lH-pyrazole- 1-carbothioate).
• Squalene-epoxidase inhibitor fungicides include thiocarbamate and allylamine fungicides.
• the thiocarbamates include pyributicarb.
• the allylamines include naftifme and terbinafme.
• Quinone inside inhibitor (Qil) fungicides inhibit Complex III mitochondrial respiration in fungi by affecting ubiquinone reductase. Reduction of ubiquinone is blocked at the "quinone inside" ( ⁇ 3 ⁇ 4) site of the cytochrome bc ⁇ complex, which is located in the inner mitochondrial membrane of fungi. Inhibiting mitochondrial respiration prevents normal fungal growth and development.
• Quinone inside inhibitor fungicides include cyanoimidazole and sulfamoyltriazole fungicides.
• the cyanoimidazoles include cyazofamid.
• the sulfamoyltriazoles include amisulbrom.
• Benzamide and thiazole carboxamide fungicides inhibit mitosis by binding to ⁇ -tubulin and disrupting microtubule assembly. Inhibition of microtubule assembly can disrupt cell division, transport within the cell and cell structure.
• the benzamides include zoxamide.
• the thiazole carboxamides include ethaboxam.
• Glucopyranosyl antibiotic protein synthesis fungicides
• FRAC code 25 "Glucopyranosyl antibiotic: protein synthesis fungicides” inhibit growth of fungi by affecting protein biosynthesis. Examples include streptomycin.
• FRAC code 26 inhibit trehalase and inositol biosynthesis. Examples include validamycin.
• Cyanoacetamideoxime fungicides include cymoxanil.
• b28 “Carbamate fungicides” (FRAC code 28) are considered multi-site inhibitors of fungal growth. They are proposed to interfere with the synthesis of fatty acids in cell membranes, which then disrupts cell membrane permeability. Propamacarb, iodocarb, and prothiocarb are examples of this fungicide class.
• Carboxylic acid fungicides inhibit growth of fungi by affecting deoxyribonucleic acid (DNA) topoisomerase type II (gyrase). Examples include oxolinic acid.
• Heteroaromatic fungicides include isoxazoles and isothiazolones.
• the isoxazoles include hymexazole and the isothiazolones include octhilinone.
• Phosphonate fungicides include phosphorous acid and its various salts, including fosetyl-aluminum.
• Examples include silthiofam.
• Carboxylic acid amide (CAA) fungicides inhibit cellulose synthase which prevents growth and leads to death of the target fungus.
• Carboxylic acid amide fungicides include cinnamic acid amide, valinamide and other carbamate, and mandelic acid amide fungicides.
• the cinnamic acid amides include dimethomorph, flumorph and pyrimorph (3-(2-chloro-4-pyridinyl)-3-[4-(l ,l-dimethylethyl)phenyl]-l -(4- morpholinyl)-2-propene-l-one).
• valinamide and other carbamates include benthiavalicarb, benthiavalicarb-isopropyl, iprovalicarb, tolprocarb (2,2,2-trifluoroethyl N- [( 1 iS)-2-methyl- 1 - [ [(4-methylbenzoyl)amino]methyl]propyl]carbamate) and valifenalate (methyl N-[(l-methylethoxy)carbonyl]-L-valyl-3-(4-chlorophenyl)- -alaninate) (also known as valiphenal).
• the mandelic acid amides include mandipropamid, N-[2-[4-[[3-(4- chlorophenyl)-2-propyn-l-yl]oxy]-3-methoxyphenyl]ethyl]-3-methyl-2-[(methylsulfonyl)- amino]butanamide and N-[2-[4-[[3-(4-chlorophenyl)-2-propyn-l-yl]oxy]-3-methoxyphenyl]- ethyl] -3 -methyl-2- [(ethylsulfonyl)amino]butanamide.
• Tetracycline antibiotic fungicides (FRAC code 41) inhibit growth of fungi by affecting protein synthesis. Examples include oxytetracycline.
• Benzamide fungicides inhibit growth of fungi by derealization of spectrin-like proteins.
• Examples include pyridinylmethyl benzamide fungicides such as fluopicolide (now FRAC code 7, pyridinylethyl benzamides).
• Microbial fungicides disrupt fungal pathogen cell membranes.
• Microbial fungicides include Bacillus species such as Bacillus amyloliquefaciens strains QST 713, FZB24, MB 1600, D747 and the fungicidal lipopeptides which they produce.
• Q X I fungicides inhibit Complex III mitochondrial respiration in fungi by affecting ubiquinone reductase at an unknown (Q x ) site of the cytochrome bc ⁇ complex. Inhibiting mitochondrial respiration prevents normal fungal growth and development.
• Q X I fungicides include triazolopyrimidylamines such as ametoctradin (5- ethyl-6-octyl[ 1 ,2,4]triazolo[ 1 ,5-a]pyrimidin-7-amine).
• Plant extract fungicides include terpene hydrocarbons and terpene alcohols such as the extract from Melaleuca alternifolia (tea tree).
• Host plant defense induction fungicides include benzothiadiazoles, benzisothiazole and thiadiazole-carboxamide fungicides.
• the benzothiadiazoles include acibenzolar-S-methyl.
• the benzisothiazoles include probenazole.
• the thiadiazole- carboxamides include tiadinil and isotianil.
• (b48) Multi-site contact fungicides” inhibit fungal growth through multiple sites of action and have contact/preventive activity.
• This class of fungicides includes: (b48.1) “copper fungicides” (FRAC code Ml)", (b48.2) “sulfur fungicides” (FRAC code M2), (b48.3) “dithiocarbamate fungicides” (FRAC code M3), (b48.4) "phthalimide fungicides” (FRAC code M4), (b48.5) “chloronitrile fungicides” (FRAC code M5), (b48.6) “sulfamide fungicides” (FRAC code M6), (b48.7) multi-site contact “guanidine fungicides” (FRAC code M7), (b48.8) “triazine fungicides” (FRAC code M8), (b48.9) “quinone fungicides” (FRAC code M9), (b48.10) "quinoxaline
• Copper fungicides are inorganic compounds containing copper, typically in the copper(II) oxidation state; examples include copper oxychloride, copper sulfate and copper hydroxide, including compositions such as Bordeaux mixture (tribasic copper sulfate).
• Sulfur fungicides are inorganic chemicals containing rings or chains of sulfur atoms; examples include elemental sulfur.
• Dithiocarbamate fungicides contain a dithiocarbamate molecular moiety; examples include mancozeb, metiram, propineb, ferbam, maneb, thiram, zineb and ziram.
• Phthalimide fungicides contain a phthalimide molecular moiety; examples include folpet, captan and captafol.
• Chloronitrile fungicides contain an aromatic ring substituted with chloro and cyano; examples include chlorothalonil.
• Sulfamide fungicides include dichlofluanid and tolyfluanid.
• Multi-site contact “guanidine fungicides” include, guazatine, iminoctadine albesilate and iminoctadine triacetate.
• Triazine fungicides include anilazine.
• Quinone fungicides include dithianon.
• Quinoxaline fungicides include quinomethionate (also known as chinomethionate).
• Meleimide fungicides include fiuoroimide.
• the phenyl-acetamides include cyflufenamid and N- [[(cyclopropylmethoxy)amino][6-(difluoromethoxy)-2,3-difluorophenyl]-methylene]- benzeneacetamide.
• the aryl-phenyl ketones include benzophenones such as metrafenone, and benzoylpyridines such as pynofenone (5-chloro-2-methoxy-4-methyl-3-pyridinyl)(2,3,4- trimethoxy-6-methylphenyl)methanone).
• the quanidines include dodine.
• the thiazolidines include flutianil ((2 )-2-[[2-fluoro-5-(trifluoromethyl)phenyl]thio]-2-[3-(2-methoxyphenyl)-
• the pyrimidinonehydrazones include ferimzone.
• the (b49.6) class includes oxathiapiprolin (l -[4-[4-[5-(2,6-difluorophenyl)-4,5-dihydro-3- isoxazolyl]-2-thiazolyl]-l-piperidinyl]-2-[5-methyl-3-(trifluoromethyl)-lH-pyrazol-l- yl]ethanone) and its R-enantiomer which is l-[4-[4-[5i?-(2,6-difluorophenyl)-4,5-dihydro-
• the (b49) class also includes bethoxazin, flometoquin (2-ethyl-3,7-dimefhyl-6-[4- (trifluoromethoxy)phenoxy]-4-quinolinyl methyl carbonate), fiuoroimide, neo-asozin (ferric methanearsonate), picarbutrazox (1 ,1-dimethylethyl N-[6-[[[[[[((Z)-l-methyl-lH-tetrazol- 5-yl)phenylmethylene]amino]oxy]methyl]-2-pyridinyl]carbamate), pyrrolnitrin, quinomethionate, tebufloquin (6-( 1 , 1 -dimethylethyl)-8-fluoro-2,3-dimethyl-4-quinolinyl acetate), tolnifanide (N-(4-chloro-2-nitrophenyl)-N-
• Additional "Fungicides other than fungicides of classes (1) through (46)" whose mode of action may be unknown, or may not yet be classified include a fungicidal compound selected from components (b49.7) through (b49.12), as shown below.
• Component (b49.7) relates to a compound of Formula b49.7
• Examples of a compound of Formula b49.7 include (b49.7a) (2-chloro-6-fluorophenyl)- methyl 2-[l-[2-[3,5-bis(difluoromethyl)-lH-pyrazol-l-yl]acetyl]-4-piperidinyl]-4-thiazole- carboxylate (Registry Number 1299409-40-7) and (b49.7b) (1R)- 1 ,2,3, 4-tetrahydro- 1-naphthalenyl 2-[l-[2-[3,5-bis(difluoromethyl)-lH-pyrazol-l-yl]acetyl]-4-piperidinyl]- 4-thiazolecarboxylate (Registry Number 1299409-42-9).
• Methods for preparing compounds of Formula b46.2 are described in PCT Patent Publications WO 2009/132785 and WO 201 1/051243.
• Component (b49.8) relates to a compound of Formula b49.8
• R b2 is CH 3 , CF 3 or CHF 2 ;
• R b3 is CH 3 , CF 3 or CHF 2 ;
• R b4 is halogen or
• n 0, 1, 2 or 3.
• Examples of a compound of Formula b49.8 include (b49.8a) l-[4-[4-[5-[(2,6- difluorophenoxy)methyl]-4,5-dihydro-3-isoxazolyl]-2-thiazolyl]-l-piperdinyl]-2-[5-methyl- 3-(trifluoromethyl)-lH-pyrazol-l-yl]ethanone.
• Methods for preparing compounds of Formula b49.8 are described in PCT Patent Application PCT US11/64324.
• Component (b4799) relates to a compound of Formula b49.9
• Examples of a compound of Formula b49.9 include (b49.9a) [[4-methoxy-2- [[[(3 1 S',7R,8R,9 1 S)-9-methyl-8-(2-methyl-l-oxopropoxy)-2,6-dioxo-7-(phenylmethyl)-l,5- dioxonan-3 -yl] amino]carbonyl] -3 -pyridinyl]oxy]methyl 2-methylpropanoate (Registry Number 517875-34-2), (b49.9b) (35,65,7R,8i?)-3-[[[3-(acetyloxy)-4-methoxy-2-pyridinyl]- carbonyl]amino]-6-methyl-4,9-dioxo-8-(phenylmethyl)-l,5-dioxonan-7-yl 2-methyl- propanoate (Registry Number 234112-93-7), (b49.9c) (S.S ⁇ .
• Component (b49.10) relates to a com ound of Formula b49.10
• R b6 is H or F
• R b7 is -CF2CHFCF3 or -CF2CF2H.
• Examples of a compound of Formula b49.10 are (b49.10a) 3-(difluoromethyl)-N-[4-fiuoro-2-(l ,l,2,3,3,3-hexafluoro- propoxy)phenyl]-l -methyl- lH-pyrazole-4-carboxamide (Registry Number 1 172611-40-3) and (b49.10b) 3-(difluoromethyl)-l-methyl-N-[2-(l,l,2,2-tetrafluoroethoxy)phenyl]-lH- pyrazole-4-carboxamide (Registry Number 923953-98-4).
• Compounds of Formula 49.10 can be prepared by methods described in PCT Patent Publication WO 2007/017450.
• Component b49.11 relates a compound of Formula b49.1 1
• R b8 is halogen, C1-C4 alkoxy or C2-C4 alkynyl
• R b9 is ⁇ , halogen or C!-C 4 alkyl
• R bl ° is C!-C 12 alkyl, C j -C 12 haloalkyl, C l -C l2 alkoxy, C 2 -C 12 alkoxyalkyl, C 2 - C 2 alkenyl, C2-C12 alkynyl, C4-C12 alkoxyalkenyl, C4-C12 alkoxyalkynyl, C - C ⁇ 2 alkylthio or C2- 2 alkylthioalkyl;
• R bl 1 is methyl or -Ybl3.
• R bl2 is Q-C2 alkyl
• Y bl 3 is CH 2 , O or S.
• Examples of compounds of Formula b49.11 include (b49.1 1a) 2-[(3-bromo-6- quinolinyl)oxy]-N-(l,l-dimethyl-2-butyn-l-yl)-2-(methylthio)acetamide, (b49.1 lb) 2-[(3- ethynyl-6-quinolinyl)oxy]-N-[l-(hydroxymethyl)-l-methyl-2-propyn-l-yl]-2-(methylthio)- acetamide, (b49.1 1c) N-( 1 , 1 -dimethyl-2-butyn- 1 -yl)-2- [(3 -ethynyl-6-quinolinyl)oxy] -2- (methylthio)acetamide, (b49.1 Id) 2-[(3-bromo-8-methyl-6-quinolinyl)oxy]-N-(l ,l-dimethyl- 2-propyn-l
• Component 49.12 relates to iV-[4-[[3-[(4-chlorophenyl)methyl]-l,2,4-thiadiazol-5- yl]oxy]-2,5-dimethylphenyl]-N-ethyl-N-methylmethanimidamide, which is believed to inhibit C24-methyl transferase involved in the biosynthesis of sterols.
• a mixture comprising a compound of Formula 1 and at least one fungicidal compound selected from the group consisting of the aforedescribed classes (1) through (49).
• a composition comprising said mixture (in fungicidally effective amount) and further comprising at least one additional component selected from the group consisting of surfactants, solid diluents and liquid diluents.
• a mixture comprising a compound of Formula 1 and at least one fungicidal compound selected from the group of specific compounds listed above in connection with classes (1) through (49).
• a composition comprising said mixture (in fungicidally effective amount) and further comprising at least one additional surfactant selected from the group consisting of surfactants, solid diluents and liquid diluents.
• component (b) fungicides include acibenzolar-S-methyl, aldimorph, ametoctradin, amisulbrom, anilazine, azaconazole, azoxystrobin, benalaxyl (including benalaxyl-M), benodanil, benomyl, benthiavalicarb (including benthiavalicarb-isopropyl), benzovindiflupyr, bethoxazin, binapacryl, biphenyl, bitertanol, bixafen, blasticidin-S, boscalid, bromuconazole, bupirimate, buthiobate, captafol, captan, carbendazim, carboxin, carpropamid, chloroneb, chlorothalonil, chlozolinate, clotrimazole, copper hydroxide, copper oxychloride, copper sulfate, coumoxystrobin, c
• invertebrate pest control compounds or agents such as abamectin, acephate, acetamiprid, acrinathrin, afidopyropen
• cyclopropanecarboxylate amidoflumet (S-1955), avermectin, azadirachtin, azinphos-methyl, bifenthrin, bifenazate, buprofezin, carbofuran, cartap, chlorantramliprole, chlorfenapyr, chlorfluazuron, chlorpyrifos, chlorpyrifos-methyl, chromafenozide, clothianidin, cyantraniliprole (3-bromo-l-(3-chloro-2-pyridinyl)-N-[4-cyano-2-methyl-6- [(methylamino)carbonyl]phenyl]- lH-pyrazole-5-carboxamide), cyclaniliprole (3-bromo-N- [2-bromo-4-c)iloro-6-[[(i -cyciopropyieihyi)ammo]carbonyl]pheiiyl]
• Bacillus thuringiensis subsp. kurstaki and the encapsulated delta-endotoxins of Bacillus thuringiensis (e.g., Cellcap, MPV, MP VII); entomopathogenic fungi, such as green muscardine fungus; and entomopathogenic virus including baculovirus, nucleopolyhedro virus (NPV) such as HzNPV, AfNPV; and granulosis virus (GV) such as CpGV.
• NPV nucleopolyhedro virus
• GV granulosis virus
• Compounds of this invention and compositions thereof can be applied to plants genetically transformed to express proteins toxic to invertebrate pests (such as Bacillus thuringiensis delta-endotoxins).
• proteins toxic to invertebrate pests such as Bacillus thuringiensis delta-endotoxins.
• the effect of the exogenously applied fungicidal compounds of this invention may be synergistic with the expressed toxin proteins.
• the weight ratio of these various mixing partners (in total) to the compound of Formula 1 is typically between about 1 :3000 and about 3000: 1. Of note are weight ratios between about 1 :300 and about 300: 1 (for example ratios between about 1 :30 and about 30: 1).
• weight ratios between about 1 :300 and about 300: 1 for example ratios between about 1 :30 and about 30: 1).
• One skilled in the art can easily determine through simple experimentation the biologically effective amounts of active ingredients necessary for the desired spectrum of biological activity. It will be evident that including these additional components may expand the spectrum of diseases controlled beyond the spectrum controlled by the compound of Formula 1 alone.
• combinations of a compound of this invention with other biologically active (particularly fungicidal) compounds or agents can result in a greater-than-additive (i.e. synergistic) effect. Reducing the quantity of active ingredients released in the environment while ensuring effective pest control is always desirable.
• synergism of fungicidal active ingredients occurs at application rates giving agronomically satisfactory levels of fungal control, such combinations can be advantageous for reducing crop production cost and decreasing environmental load.
• a combination of a compound of Formula 1 with at least one other fungicidal active ingredient is such a combination where the other fungicidal active ingredient has different site of action from the compound of Formula 1.
• a combination with at least one other fungicidal active ingredient having a similar spectrum of control but a different site of action will be particularly advantageous for resistance management.
• a composition of the present invention can further comprise a biologically effective amount of at least one additional fungicidal active ingredient having a similar spectrum of control but a different site of action.
• combinations of a compound of the invention with other biologically active compounds or agents can result in a less-than-additive (i.e. safening) effect on organisms beneficial to the agronomic environment.
• a compound of the invention may safen a herbicide on crop plants or protect a beneficial insect species (e.g., insect predators, pollinators such as bees) from an insecticide.
• Fungicides of note for formulation with compounds of Formula 1 to provide mixtures useful in seed treatment include but are not limited to amisulbrom, azoxystrobin, boscalid, carbendazim, carboxin, cymoxanil, cyproconazole, difenoconazole, dimethomorph, fluazinam, fludioxonil, flufenoxystrobin, fluquinconazole, fluopicolide, fluoxastrobin, flutriafol, fluxapyroxad, ipconazole, iprodione, metalaxyl, mefenoxam, metconazole, myclobutanil, paclobutrazole, penflufen, picoxystrobin, prothioconazole, pyraclostrobin, sedaxane, silthiofam, tebuconazole, thiabendazole, thiophanate-methyl, thiram, trifloxystrobin and
• Invertebrate pest control compounds or agents with which compounds of Formula 1 can be formulated to provide mixtures useful in seed treatment include but are not limited to abamectin, acetamiprid, acrinathrin, afidopyropen, amitraz, avermectin, azadirachtin, bensultap, bifenthrin, buprofezin, cadusafos, carbaryl, carbofuran, cartap, chlorantraniliprole, chlorfenapyr, chlorpyrifos, clothianidin, cyantraniliprole, cyclaniliprole, cyfluthrin, beta- cyfluthrin, cyhalothrin, gamma-cyhalothrin, lambda-cyhalothrin, cypermethrin, alpha- cypermethrin, zeta-cypermethrin, cyrom
• Compositions comprising compounds of Formula 1 useful for seed treatment can further comprise bacteria and fungi that have the ability to provide protection from the harmful effects of plant pathogenic fungi or bacteria and/or soil born animals such as nematodes.
• Bacteria exhibiting nematicidal properties may include but are not limited to Bacillus firmus, Bacillus cereus, Bacillius subtiliis and Pasteuria penetrans.
• a suitable Bacillus firmus strain is strain CNCM 1-1582 (GB-126) which is commercially available as BioNemTM.
• a suitable Bacillus cereus strain is strain NCMM 1-1592. Both Bacillus strains are disclosed in US 6,406,690.
• Other suitable bacteria exhibiting nematicidal activity are B.
• Bacteria exhibiting fungicidal properties may include but are not limited to B. pumilus strain GB34.
• Fungal species exhibiting nematicidal properties may include but are not limited to Myrothecium verrucaria, Paecilomyces lilacinus and Purpureocillium lilacinum.
• Seed treatments can also include one or more nematicidal agents of natural origin such as the elicitor protein called harpin which is isolated from certain bacterial plant pathogens such as Erwinia amylovora.
• harpin elicitor protein
• An example is the Harpin-N-Tek seed treatment technology available as N-HibitTM Gold CST.
• Seed treatments can also include one or more species of legume-root nodulating bacteria such as the microsymbiotic nitrogen- fixing bacteria Bradyrhizobium japonicum.
• These inocculants can optionally include one or more lipo-chitooligosaccharides (LCOs), which are nodulation (Nod) factors produced by rhizobia bacteria during the initiation of nodule formation on the roots of legumes.
• LCOs lipo-chitooligosaccharides
• Nod nodulation
• the Optimize® brand seed treatment technology incorporates LCO Promoter TechnologyTM in combination with an inocculant.
• Seed treatments can also include one or more isoflavones which can increase the level of root colonization by mycorrhizal fungi.
• Mycorrhizal fungi improve plant growth by enhancing the root uptake of nutrients such as water, sulfates, nitrates, phosphates and metals.
• isoflavones include, but are not limited to, genistein, biochanin A, formononetin, daidzein, glycitein, hesperetin, naringenin and pratensein.
• Formononetin is available as an active ingredient in mycorrhizal inocculant products such as PHC Colonize® AG.
• Seed treatments can also include one or more plant activators that induce systemic acquired resistance in plants following contact by a pathogen.
• a plant activator which induces such protective mechanisms is acibenzolar-iS-methyl.
• NMR data are in ppm downfield from tetramethylsilane. Couplings are designated by (s)-singlet, (d)-doublet, (t)-triplet and (m)-multiplet.
• test suspensions for Tests A-G 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 by volume) containing 250 ppm of the surfactant Trem® 014 (polyhydric alcohol esters). The resulting test suspensions were then used in Tests A-G.
• Trem® 014 polyhydric alcohol esters
• test suspension was sprayed to the point of run-off on wheat seedlings.
• seedlings were inoculated with a spore suspension of Puccinia recondita f. sp. tritici (the causal agent of wheat leaf rust) and incubated in a saturated atmosphere at 20 °C for 24 h, and then moved to a growth chamber at 20 °C for 7 days, after which time visual disease ratings were made.
• test suspension was sprayed to the point of run-off on wheat seedlings.
• seedlings were inoculated with a spore suspension of Septoria tritici (the causal agent of wheat leaf blotch) and incubated in a saturated atmosphere at 24 °C for 48 h, and then moved to a growth chamber at 20 °C for 19 to 25 days, after which time visual disease ratings were made.
• test suspension was sprayed to the point of run-off on tomato seedlings.
• seedlings were inoculated with a spore suspension of Botrytis cinerea (the causal agent of tomato Botrytis) and incubated in a saturated atmosphere at 20 °C for 48 h, and then moved to a growth chamber at 27 °C for 3 days, after which time visual disease ratings were made.
• Botrytis cinerea the causal agent of tomato Botrytis
• test suspension was sprayed to the point of run-off on wheat seedlings.
• seedlings were inoculated with a spore dust of Blumeria graminis f. sp. tritici, (also known as Erysiphe graminis f. sp. tritici, the causal agent of wheat powdery mildew) and incubated in a growth chamber at 20 °C for 8 days, after which time visual disease ratings were made.
• Blumeria graminis f. sp. tritici also known as Erysiphe graminis f. sp. tritici, the causal agent of wheat powdery mildew
• Grape seedlings were inoculated with a spore suspension of Plasmopara viticola (the causal agent of grape downy mildew) and incubated in a saturated atmosphere at 20 °C for 24 h. After a short drying period, the grape seedlings were sprayed with the test suspension to the point of run-off and then moved to a growth chamber at 20 °C for 5 days, after which time the grape seedlings were placed back into a saturated atmosphere at 20 °C for 24 h. Upon removal, visual disease ratings were made.
• Plasmopara viticola the causal agent of grape downy mildew
• test suspension was sprayed to the point of run-off on wheat seedlings.
• seedlings were inoculated with a spore suspension of Septoria nodorum (the causal agent of wheat glume blotch) and incubated in a saturated atmosphere at 20 °C for 48 h, and then moved to a growth chamber at 20 °C for 5 days, after which time visual disease ratings were made.
• Septoria nodorum the causal agent of wheat glume blotch
• test suspension was sprayed to the point of run-off on tomato seedlings.
• seedlings were inoculated with a spore suspension of Phytophthora infestans (the causal agent of tomato late blight) and incubated in a saturated atmosphere at 20 °C for 24 h, and then moved to a growth chamber at 20 °C for 4 days, after which time visual disease ratings were made.
• Results for Tests A-G are given in Table A. In the Table, 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. All results are for 500 ppm except where followed by which indicates 250 ppm.

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• 2015
  • 2015-02-10 WO PCT/US2015/015183 patent/WO2015123193A1/fr active Application Filing

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