Fungicidal nitroanilino-substituted pyrazoles

Abstract

To provide a valuable synthetic intermediate for 5-aminopyrazole compounds that function as fungicides.SOLUTION: For example, compounds of the formula 12 below and salts thereof are illustrated. [R2 is methyl; R3 is Cl; R4 is Cl or F; m is 2, where one R4 is at 4-position and the other is at 6-position].SELECTED DRAWING: None

Description

Technical Field

[0001] The present invention relates to certain pyrazoles, their N-oxides, salts and compositions, and methods of their use as fungicides.

Background Art

[0002] The control of plant diseases caused by fungal plant pathogens is extremely important in achieving high crop efficiency. Plant diseases in flowers, vegetables, fields, grains, and fruit crops can cause a significant decrease in productivity, which may increase the burden on consumers. Although many products are commercially available for these purposes, there is still a continuing need for new compounds that are more effective, low-cost, low-toxicity, safer from an environmental point of view, or have different modes of action.

[0003] Patent Documents 1, 2, 3, and 4 disclose fungicidal pyrazoles and their use in agriculture. Patent Document 5 discloses pyrazole, isothiazole, and isoxazole derivatives and their use in agriculture.

Prior Art Documents

Patent Documents

[0004]

Patent Document 1

Patent Document 2

Patent Document 3

Patent Document 4

Patent Document 5

Summary of the Invention

Means for Solving the Problems

[0005] The present invention relates to formula 1 (including all stereoisomers): [Chemical formula] [wherein, R 1 is C 1~ C2 alkyl; R 2 is cyano, halogen, C1-C2 alkyl or C1-C2 haloalkyl; R 3 is halogen or methyl; each R 4 is independently halogen, cyano, nitro, C1-C3 alkyl, C1-C3 alkoxy, C1-C3 haloalkoxy, C2-C6 alkenyloxy, C2-C6 alkynyloxy, C2-C6 cyanoalkoxy, C2-C6 alkoxyalkyl or C2-C6 alkoxyalkoxy; each R 5 is independently halogen, C1-C3 alkyl, C2-C6 alkoxyalkyl, C1-C3 alkoxy, C1-C3 haloalkoxy, C2-C6 alkenyloxy, C2-C6 alkynyloxy, C2-C6 cyanoalkoxy or C2-C6 alkoxyalkoxy; m and n are each independently 0, 1, 2 or 3; R 6 is H; or C1-C3 alkyl or C1-C3 haloalkyl, optionally substituted with up to two substituents independently selected from R 6a ; or amino, C2-C4 alkenyl, C2-C4 alkynyl, C3-C6 cycloalkyl, CH(=O), S(=O)2OM, S(=O) u R 7 , (C=W)R 8 or OR 9 ; each R 6ais, independently, cyano, C3-C6 cycloalkyl, C1-C3 alkoxy, C1-C3 haloalkoxy, C1-C3 alkylthio, C1-C3 alkylsulfinyl or C1-C3 alkylsulfonyl; M is K or Na; u is 0, 1 or 2; R 7 is C1-C3 alkyl or C1-C3 haloalkyl; W is O or S; R 8 is C1-C3 alkyl, C2-C4 alkoxyalkyl, C2-C4 alkylaminoalkyl, C3-C6 dialkylaminoalkyl, C1-C3 alkoxy, C1-C3 alkylthio or C2-C4 alkylthioalkyl; R 9 is H; or is C1-C3 alkyl or C1-C3 haloalkyl, and is optionally substituted by up to two substituents independently selected from R 9a ; or is CH(=O), C3-C6 cycloalkyl, S(=O)2OM or (C=W)R 10 ; Each R 9a is, independently, cyano, C3-C6 cycloalkyl, C1-C3 alkoxy, C1-C3 haloalkoxy, C1-C3 alkylthio, C1-C3 alkylsulfinyl or C1-C3 alkylsulfonyl; R 10 is C1-C3 alkyl, C2-C4 alkoxyalkyl, C2-C4 alkylaminoalkyl, C3-C6 dialkylaminoalkyl, C1-C3 alkoxy, C1-C3 alkylthio or C2-C4 alkylthioalkyl; However, the compound of formula 1 is 4-(2,6-difluoro-4-methoxyphenyl)-N-(2,4-difluoro-6-nitrophenyl)-1,3-dimethyl-1H-pyrazole-5-amine; 4-(2-chloro-4-fluorophenyl)-1,3-dimethyl-N-(2-nitrophenyl)-1H-pyrazole-5-amine; 4-(2-Chloro-4-fluorophenyl)-N-(2,4-difluoro-6-nitrophenyl)-1,3-dimethyl-1H-pyrazole-5-amine; 4-(2-Chloro-4-fluorophenyl)-3-ethyl-1-methyl-N-(2-nitrophenyl)-1H-pyrazole-5-amine; 4-(2-Chloro-4-fluorophenyl)-1-methyl-N-(2-nitrophenyl)-3-(trifluoromethyl)-1H-pyrazole-5-amine; 4-(2,6-Difluoro-4-methoxyphenyl)-N-(2-methoxy-6-nitrophenyl)-1,3-dimethyl-1H-pyrazole-5-amine; 4-(2-Chloro-4-fluorophenyl)-N-(2-methoxy-6-nitrophenyl)-1,3-dimethyl-1H-pyrazole-5-amine; N-(2-Chloro-6-nitrophenyl)-4-(2,6-difluoro-4-methoxyphenyl)-1,3-dimethyl-1H-pyrazole-5-amine; N-(2-Chloro-3-fluoro-6-nitrophenyl)-4-(2,6-difluoro-4-methoxyphenyl)-1,3-dimethyl-1H-pyrazole-5-amine; 4-(2-Chloro-4-fluorophenyl)-1,3-dimethyl-N-(2-methyl- 6-nitrophenyl)-1H-pyrazole-5-amine; N-(2-Bromo-4-fluoro-6-nitrophenyl)-4-(2-chloro-4-fluorophenyl)-1,3-dimethyl-1H-pyrazole-5-amine; 4-(2-Chloro-4-fluorophenyl)-N-(4-methoxy-2-nitrophenyl)-1,3-dimethyl-1H-pyrazole-5-amine; 4-(2,6-Difluoro-4-methoxyphenyl)-N-(4-fluoro-2-nitrophenyl)-1,3-dimethyl-1H-pyrazole-5-amine; 4-(2,6-Difluoro-4-methoxyphenyl)-N-(4-methoxy-2-nitrophenyl)-1,3-dimethyl-1H-pyrazole-5-amine; N-(4-Chloro-2-nitrophenyl)-4-(2,6-difluoro-4-methoxyphenyl)-1,3-dimethyl-1H-pyrazole-5-amine; 4-(2,6-Difluoro-4-methoxyphenyl)-1,3-dimethyl-N-[2-nitro-4-(prop-2-yn-1-yloxy)phenyl]-1H-pyrazole-5-amine; 4-(2,6-Difluoro-4-methoxyphenyl)-1,3-dimethyl-N-[2-nitro-4-(prop-1-en-1-yloxy)phenyl]-1H-pyrazole-5-amine; N-(4-Bromo-2-nitrophenyl)-4-(2,6-difluoro-4-methoxyphenyl)-1,3-dimethyl-1H-pyrazole-5-amine; N-(4-Chloro-2-fluoro-6-nitrophenyl)-4-(2,6-difluoro-4-methoxyphenyl)-1,3-dimethyl-1H-pyrazole-5-amine; 3-Chloro-4-(2-chloro-4-fluorophenyl)-N-(2,4-difluoro-6-nitrophenyl)-1-methyl-1H-pyrazole-5-amine; 4-(2,6-Difluoro-4-methoxyphenyl)-1,3-dimethyl-N-[4-methyl-2-nitrophenyl]-1H-pyrazole-5-amine; 4-(2-Chloro-4-fluorophenyl)-1,3-dimethyl-N-(4-methyl-2-nitrophenyl)-1H-pyrazole-5-amine; and N-(4-Bromo-2-fluoro-6-nitrophenyl)-4-(2,6-difluoro-4-methoxyphenyl)-1,3-dimethyl-1H-pyrazole-5-amine compounds other than], N-oxides, and salts thereof, agricultural compositions containing them and their use as fungicides.

[0006] More particularly, the present invention relates to compounds of formula 1 (including all stereoisomers), N-oxides or salts thereof.

[0007] The present invention also relates to a fungicidal composition comprising (a) a compound of the present invention (i.e., in an amount effective as a fungicide); and (b) at least one additional component selected from the group consisting of a surfactant, a solid excipient, and a liquid excipient.

[0008] The present invention also relates to a fungicidal composition comprising (a) a compound of the present invention; and (b) at least one other fungicide (e.g., at least one other fungicide having a different site of action).

[0009] The present invention further relates to a method for controlling a plant disease caused by a fungal plant pathogen, which comprises applying an amount of the compound of the present invention effective as a fungicide (e.g., as the composition described herein) to a plant or a part thereof, or to a plant seed.

[0010] The present invention also relates to a composition comprising a compound of formula 1, an N-oxide, or a salt thereof, and at least one compound or agent for controlling invertebrate pests.

DETAILED DESCRIPTION OF THE INVENTION

[0011] As used herein, the terms “comprises,” “comprising,” “includes,” “including,” “has,” “having,” “contains,” “containing,” “characterized by,” or any other variation thereof are intended to include non-exclusive incorporation, subject to any explicitly stated limitations. For example, a composition, mixture, process, method, article, or apparatus that includes 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.

[0012] The transitional phrase "consisting of" excludes any element, step, or ingredient not specified. In the case of a claim, such a phrase should close the claim to include materials other than those recited, usually excluding any associated impurities. When the phrase "consisting of" appears in the body of the claim rather than immediately following the preamble, this phrase limits only the elements recited in that body; other elements are not excluded from the claim as a whole.

[0013] The 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 characteristics(s) of the invention claimed herein. The term "consisting essentially of" takes a position neutral between "comprising" and "consisting of".

[0014] It should be readily understood that where the applicant defines an invention or a part thereof using an open-ended term such as "comprising", the description (absent any contrary indication) should be construed as also describing such invention using the terms "consisting essentially of" or "consisting of".

[0015] Furthermore, unless expressly indicated to the contrary, "or" means inclusive or and not exclusive or. For example, the condition A or B is satisfied by any one of the following: A is true (or present) and B is false (or absent), A is false (or absent) and B is true (or present), A and B are both true (or present).

[0016] Also, as used herein, the indefinite articles "a" and "an" preceding an element or component of the present invention are intended to be non - limiting with respect to the number of instances (i.e., occurrences) of the element or component. Thus, "a" or "an" should be read to include one or at least one, and the singular form of a word for an element or component also includes the plural unless the number clearly means singular.

[0017] As described in this disclosure and the claims, "plant" includes all life cycles of plants in the plant kingdom, particularly members of the spermatophytes (Spermatopsida), including young plants (e.g., germinating seeds becoming seedlings) and mature, reproductive growth stages (e.g., plants bearing flowers and seeds). Parts of a plant include geotropic members that typically grow below the surface of a growth medium (e.g., soil), such as roots, tubers, bulbs, and corms, and members that grow above the growth medium, such as foliage (including stems and leaves), flowers, fruits, and seeds.

[0018] As described herein, the term "seedling", used alone or in combination with words, means a young plant that develops from the embryo of a seed.

[0019] As described herein, the term "broad - leaf", used alone or in multiple words such as "broad - leaf crop", means dicotyledonous plants or dicots, which is a term used to describe a group of angiosperms characterized by an embryo having two cotyledons.

[0020] As described herein, the terms "fungal pathogen" and "fungal plant pathogen" include pathogens in the phyla Ascomycota, Basidiomycota, and Zygomycota, and the fungal-like Oomycota class, which are causative agents of a wide range of economically important plant diseases that affect floral, turf, vegetable, field, cereal, and fruit crops. In the context of the present disclosure, "protecting a plant from disease" or "controlling a plant disease" includes prophylactic treatments (interfering with the fungal cycle of infection, colonization, symptom expression, and spore production) and / or curative treatments (inhibiting colonization of the plant host tissue).

[0021] As used herein, the term "mode of action" (MOA) is defined by the Fungicide Resistance Action Committee (FRAC) and is used to identify fungicides according to their biochemical modes of action in the biosynthetic pathways of plant pathogens and their resistance risks. The modes of action defined by FRAC 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 walls, (P) host plant defense induction, (U) unknown mode of action, (NC) not classified, (M) multi-site contact activity, and (BM) biological agents with multiple modes of action. Each mode of action (i.e., from letter A to BM) includes one or more subgroups (e.g., A includes subgroups A1, A2, A3, and A4) based on individual verified target sites or, when the exact target site is unknown, on cross-resistance profiles within a group or against other groups. Each of these subgroups (e.g., A1, A2, A3, and A4) is assigned an FRAC code (numbers and / or letters). For example, the FRAC code for subgroup A1 is 4. Additional information regarding target sites and FRAC codes can be obtained, for example, from publicly available databases maintained by FRAC.

[0022] As used herein, the term "cross-resistance" means the phenomenon that occurs when a pathogen becomes resistant to one fungicide and simultaneously becomes resistant to one or more other fungicides. These other fungicides are usually, but not necessarily, not in the same chemical class, do not have the same target site, or cannot be detoxified by the same mechanism.

[0023] As used herein, the term "cross-resistance" means the phenomenon that occurs when a pathogen develops resistance to one biocide and simultaneously becomes resistant to one or more other biocides. These other biocides are usually, but not necessarily, not in the same chemical class, do not have the same target site of action, or cannot be detoxified by the same mechanism.

[0024] Generally, when a molecular fragment (i.e., a group) is represented by a series of atomic symbols (e.g., C, H, N, O, and S), one or more potential bonding sites are more readily recognizable to those skilled in the art. In some cases herein, particularly when alternative bonding sites may exist, one or more bonding sites can be explicitly indicated by a hyphen ("-"). For example, "-NCS" indicates that the bonding site is at the nitrogen atom (i.e., not isothiocyanato or thiocyanato).

[0025] As used herein, the term "alkylating agent" means a chemical substance in which a carbon-containing group is bonded through a carbon atom to a leaving group such as a halide or a sulfonate, which can be substituted by bonding a nucleophile to the carbon atom. Unless otherwise indicated, the term "alkylate" is not limited to alkyl for the carbon-containing group; the carbon-containing groups in alkylating agents include, for example, various carbon-bonded substituents designated as R 5 and include various carbon-bonded substituents.

[0026] In the above detailed description, the term "alkyl", as used alone or in combination, such as "alkylthio" or "haloalkyl", includes linear or branched alkyl such as methyl, ethyl, n-propyl and i-propyl, or different butyl, pentyl or hexyl isomers. "Alkenyl" includes linear or branched alkenes such as ethenyl, 1-propenyl, 2-propenyl and different butenyl, pentenyl and hexenyl isomers. "Alkenyl" also includes polyenes such as 1,2-propadienyl and 2,4-hexadienyl. "Alkynyl" includes linear or branched alkynes such as 1-propynyl, 2-propynyl and different butynyl, pentynyl and hexynyl isomers. "Alkynyl" can also include a portion consisting of multiple triple bonds, for example, 2,5-hexadiynyl.

[0027] "Alkoxy" includes, for example, methoxy, ethoxy, n-propyloxy, i-propyloxy and different butoxy, pentyloxy and hexyloxy isomers. "Alkoxyalkyl" indicates alkoxy substitution on alkyl. Examples of "alkoxyalkyl" include CH3OCH2, CH3OCH2CH2, CH3CH2OCH2, CH3CH2CH2CH2OCH2 and CH3CH2OCH2CH2. "Alkenyloxy" includes linear or branched alkenyl bonded to and linked by an oxygen atom. Examples of "alkenyloxy" include H2C=CHCH2O, (CH3)2C=CHCH2O, CH3CH=CHCH2O, CH3CH=C(CH3)CH2O and CH2=CHCH2CH2O. "Alkynyloxy" includes linear or branched alkynyl bonded to and linked by an oxygen atom. Examples of "alkynyloxy" include HC≡CCH2O, CH3C≡CCH2O and CH3C≡CCH2CH2O. "Alkoxyalkoxy" indicates alkoxy substitution on another alkoxy moiety. Examples of "alkoxyalkoxy" include CH3OCH2O, CH3OCH2O and CH3CH2OCH2O.

[0028] "Alkylthio" includes branched or straight-chain alkylthio moieties such as methylthio, ethylthio, and different propylthio isomers. "Alkylthioalkyl" indicates alkylthio substitution in alkyl. Examples of "alkylthioalkyl" include CH3SCH2, CH3SCH2CH2, CH3CH2SCH2, and CH3CH2SCH2CH2. "Alkylsulfinyl" includes both enantiomers of the alkylsulfinyl group. Examples of "alkylsulfinyl" include CH3S(=O), CH3CH2S(=O), CH3CH2CH2S(=O), and (CH3)2CHS(=O). Examples of "alkylsulfonyl" include CH3S(=O)2, CH3CH2S(=O)2, CH3CH2CH2S(=O)2, and (CH3)2CHS(=O)2.

[0029] "Alkylaminoalkyl" indicates alkylamino substitution in alkyl. Examples of "alkylaminoalkyl" include CH3NHCH2, CH3NHCH2CH2, CH3C H2NHCH2, CH3CH2CH2CH2NHCH2, and CH3CH2NHCH2CH2. Examples of "dialkylaminoalkyl" include (CH3)2NCH2, (CH3CH2)2NCH2CH2, and CH3CH2(CH3)NCH2CH2.

[0030] The term "cycloalkyl" refers to a saturated carbon ring consisting of 3 to 6 carbon atoms linked to each other by single bonds. Examples of "cycloalkyl" include cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl. The term "cycloalkylalkyl" indicates cycloalkyl substitution in an alkyl group. Examples of "cycloalkylalkyl" include cyclopropylmethyl, cyclopentylethyl, and other cycloalkyl moieties bonded to a straight-chain or branched alkyl group.

[0031] When used alone or in a compound word such as "haloalkyl" or in a description such as "alkyl substituted with halogen", the term "halogen" includes fluorine, chlorine, bromine or iodine. Further, when used in a compound word such as "haloalkyl" or in a description such as "alkyl substituted with halogen", the alkyl can be partially or completely substituted with halogen atoms, which may be the same or different. Examples of "haloalkyl" or "alkyl substituted with halogen" include F3C, ClCH2, CF3CH2 and CF3CCl2. Terms such as "haloalkoxy" are defined in the same manner as the term "haloalkyl". Examples of "haloalkoxy" include CF3O, CCl3CH2O, F2CHCH2CH2O and CF3CH2O.

[0032] "Cyanoalkoxy" refers to an alkyloxy group substituted with one cyano group. Examples of "cyanoalkoxy" include NCCH2O, NCCH2CH2O and CH3CH(CN)CH2O.

[0033] The total number of carbon atoms in the substituent is indicated by the prefix "C i ~C j ", where i and j are numbers from 1 to 6. For example, C1-C3 alkylsulfonyl designates from methylsulfonyl to propylsulfonyl; C2 alkoxyalkyl designates CH3OCH2; C3 alkoxyalkyl designates, for example, CH3OCH2CH2 or CH3CH2OCH2; C4 alkoxyalkyl designates various isomers of an alkyl group substituted with an alkoxy group containing a total of 4 carbon atoms, including, by way of example, CH3CH2CH2OCH2 and CH3CH2OCH2CH2.

[0034] In connection with a ring-like group, the term "unsubstituted" means that the group has no substituents other than one or more of its bonds to the residue of Formula 1. The term "optionally substituted" means that the number of substituents can be zero. Unless otherwise indicated, an optionally substituted group can be substituted with an optional number of substituents that can be adjusted by replacing non-hydrogen substituents and hydrogen atoms at any available carbon or nitrogen atom. Generally, the optional number of substituents (if present) ranges from 1 to 3. As used herein, the term "optionally substituted" is used synonymously with the phrase "substituted or unsubstituted" or the term "(un)substituted".

[0035] The optional number of substituents can be limited by the stated limits. For example, the phrase "optionally substituted with up to two substituents independently selected from R 6a " means that 0, 1, or 2 substituents can be present.

[0036] When a compound is substituted with a substituent having a subscript indicating the number of said substituents, it may vary (e.g., (R 4 ) m (wherein m is from 0 to 3)), in which case, the substituents are independently selected from the defined group of substituents unless otherwise indicated. When a variable group is shown to be optionally attached at a position, e.g., (R 4 ) m (wherein m can be 0), in that case, hydrogen can be at that position even if not listed in the definition of the variable group.

[0037] The substituent designations in this disclosure use generally recognized terminology and provide brevity in accurately communicating the chemical structure to those skilled in the art. For the sake of brevity, the description of position numbers may be omitted. In some cases herein, substituents (e.g., R 4 and R 5) One or more of the attachment points are indicated by the numbers of the position numbers, which may differ from the Chemical Abstracts nomenclature system where the difference does not affect the meaning.

[0038] The compounds of the present invention may exist as one or more stereoisomers. Stereoisomers are isomers that have the same structure but differ in the arrangement of their atoms in space and include enantiomers, diastereomers, cis- and trans-isomers (also known as geometric isomers), and atropisomers. Atropisomers result from restricted rotation about a single bond when the rotational barrier is high enough to allow isolation of the isomeric species. Those skilled in the art understand that a particular stereoisomer may exhibit beneficial effects if it is more active and / or enriched relative to other stereoisomers(s) or separated from other stereoisomers(s). Further, those skilled in the art know methods for separating, enriching, and / or selectively producing said stereoisomers. For a comprehensive discussion of all aspects of stereoisomerism, see Ernest L. Eliel and Samuel H. Wilen, Stereochemistry of Organic Compounds, John Wiley & Sons, 1994.

[0039] The compounds of the present invention can exist as one or more conformational isomers due to restricted rotation about the amide bond (e.g., C(=O)-N) in Formula 1. The present invention includes mixtures of conformational isomers. Further, the present invention includes compounds enriched in one conformational isomer relative to the other.

[0040] The present invention includes, in all proportions, all stereoisomers, conformational isomers, and mixtures thereof, as well as isotopic forms such as deuterated compounds.

[0041] Those skilled in the art understand that not all nitrogen-containing heterocycles can form N-oxides because nitrogen requires available lone pairs to be oxidized to oxides; those skilled in the art recognize those nitrogen-containing heterocycles that can form N-oxides. Those skilled in the art also recognize that tertiary amines can also form N-oxides. Synthetic methods for the preparation of N-oxides of heterocycles and tertiary amines are very well known to those skilled in the art, including the oxidation of heterocycles and tertiary amines with peroxyacids such as peracetic acid and m-chloroperbenzoic acid (MCPBA), hydrogen peroxide, alkyl hydroperoxides such as t-butyl hydroperoxide, sodium perborate, and dioxiranes such as dimethyldioxirane. These methods for the preparation of N-oxides are widely described in the literature and there are reviews thereof, for example: T.L. Gilchrist in Comprehensive Organic Synthesis, Volume 7, pp748 - 750, edited by S.V. Ley, Pergamon Press; M. Tisler and B. Stanovnik in Comprehensive Heterocyclic Chemistry, Volume 3, pp18 - 20, edited by A.J. Boulton and A. McKillop, Pergamon Press; M.R. Grimmett and B.R.T. Keene in Advances in Heterocyclic Chemistry, Volume 43, pp149 - 161, edited by A.R. Katritzky, Academic Press; M. Tisle r and B. Stanovnik in Advances in Heterocyclic Chemistry, Volume 9, pp285 - 291, edited by A.R. Katritzky and A.J. Boulton, Academic Press; and see G.W.H. Cheeseman and E.S.G. Werstiuk in Advances in Heterocyclic Chemistry, Volume 22, pp390 - 392, edited by A.R. Katritzky and A.J. Boulton, Academic Press.

[0042] Those skilled in the art recognize that salts of chemical substances are in equilibrium with their corresponding salt-free forms under environmental and physiological conditions, and thus the salts share the biological utility of the salt-free forms. Accordingly, a wide range of salts of the compounds of Formula 1 are useful for the control of plant diseases caused by fungal plant pathogens (i.e., are agriculturally suitable). Salts of the compounds of Formula 1 include acid-addition salts with inorganic or organic acids such as hydrobromic acid, hydrochloric acid, nitric acid, phosphoric acid, sulfuric acid, acetic acid, butyric acid, fumaric acid, lactic acid, maleic acid, malonic acid, oxalic acid, propionic acid, salicylic acid, tartaric acid, 4-toluenesulfonic acid or valeric acid. When the compound of Formula 1 contains an acidic moiety such as a carboxylic acid, 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 includes compounds selected from Formula 1, N-oxides and their agriculturally suitable salts.

[0043] Compounds, stereoisomers, N-oxides, and salts thereof selected from Formula 1 usually exist in more than one form. Thus, Formula 1 includes all crystalline and amorphous forms of the compounds represented by Formula 1. Amorphous forms include embodiments that are solids such as waxes and rubbers as well as embodiments that are liquids such as solutions and melts. Crystalline forms include embodiments that essentially represent single crystal types and embodiments that represent mixtures of polymorphs (i.e., different crystalline types). The term "polymorph" means a specific crystalline form of a chemical substance that can crystallize in different crystalline forms, and these forms have different arrangements and / or conformations of molecules in the crystal lattice. Polymorphs can have the same chemical composition, but they can also differ from the composition due to the presence or absence of co-crystallized water or other molecules that can bind weakly or strongly to the crystal 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 bioavailability. Those skilled in the art understand that polymorphs of the compounds represented by Formula 1 can exhibit beneficial effects (e.g., suitability for the manufacture of useful formulations, improvement of biological performance) relative to another polymorph or a mixture of polymorphs of the same compound represented by Formula 1. The production and isolation of specific polymorphs of the compounds represented by Formula 1 can be achieved by methods known to those skilled in the art, including, for example, crystallization using a selected solvent and temperature.

[0044] Embodiments of the invention described in the summary of the invention include those described below. In the following embodiments, Formula 1 includes stereoisomers, N-oxides, and salts thereof, and references to "compounds of Formula 1" include the definitions of the substituents specified in the summary of the invention unless further defined in this embodiment.

[0045] Embodiment 1. R 1 is methyl, a compound of Formula 1.

[0046] Embodiment 2. R 1 is ethyl, a compound of Formula 1.

[0047] Embodiment 3.R 2 The compound of formula 1 or Embodiment 1 or 2, wherein is cyano, halogen or C1-C2 alkyl.

[0048] Embodiment 4.R 2 The compound of formula 1 or Embodiment 1 or 2, wherein is cyano, Br, Cl, F, C1-C2 alkyl or C1-C2 haloalkyl.

[0049] Embodiment 5.R 2 The compound of Embodiment 4, wherein is cyano, Br, Cl, F, C1-C2 alkyl or halomethyl.

[0050] Embodiment 6.R 2 The compound of Embodiment 5, wherein is cyano, Br, Cl, F, C1-C2 alkyl or CF3.

[0051] Embodiment 7.R 2 The compound of Embodiment 6, wherein is cyano, Br, Cl, F or C1-C2 alkyl.

[0052] Embodiment 8.R 2 The compound of Embodiment 7, wherein is cyano or C1-C2 alkyl.

[0053] Embodiment 9.R 2 The compound of Embodiment 8, wherein is C1-C2 alkyl.

[0054] Embodiment 10.R 2 The compound of Embodiment 8, wherein is cyano or methyl.

[0055] Embodiment 11.R 2 The compound of Embodiment 10, wherein is methyl.

[0056] Embodiment 12.R 2 The compound of Embodiment 7, wherein is Br, Cl or methyl.

[0057] Embodiment 13.R 3The compound of formula 1 or any one of embodiments 1 to 12, wherein R is halogen or methyl.

[0058] Embodiment 13a. R 3 The compound of embodiment 13, wherein R is halogen.

[0059] Embodiment 13b. R 3 The compound of embodiment 13, wherein R is Br, Cl, F or methyl.

[0060] Embodiment 14. R 3 The compound of embodiment 13, wherein R is Br, Cl or F.

[0061] Embodiment 15. R 3 The compound of embodiment 14, wherein R is Cl or F.

[0062] Embodiment 16. R 3 The compound of embodiment 15, wherein R is Cl.

[0063] Embodiment 17. R 3 The compound of embodiment 15, wherein R is F.

[0064] Embodiment 18. R 3 The compound of embodiment 13, wherein R is Cl, F or methyl.

[0065] Embodiment 19. R 3 The compound of embodiment 18, wherein R is Cl or methyl.

[0066] Embodiment 20. R 3 The compound of embodiment 19, wherein R is methyl.

[0067] Embodiment 21. Each R 4is, independently, halogen, cyano, C1-C2 alkyl, C1-C2 alkoxy, C1-C2 haloalkoxy, C2-C4 alkenyloxy, C2-C4 alkynyloxy, C2-C4 cyanoalkoxy, C2-C4 alkoxyalkyl or C2-C4 alkoxyalkoxy, a compound of formula 1 or any one of embodiments 1 to 20.

[0068] Embodiment 22. Each R 4 is, independently, halogen, cyano, methyl, methoxy, halomethoxy, C2-C4 alkenyloxy, C2-C4 alkynyloxy, C2-C4 cyanoalkoxy, C2-C4 alkoxyalkyl or C2-C4 alkoxyalkoxy, the compound of embodiment 21.

[0069] Embodiment 23. Each R 4 is, independently, halogen, cyano, methyl, methoxy, halomethoxy, C2-C4 alkenyloxy, C2-C4 alkynyloxy or C2-C4 cyanoalkoxy, the compound of embodiment 22.

[0070] Embodiment 24. Each R 4 is, independently, halogen, cyano, methyl, methoxy, halomethoxy or C2-C4 cyanoalkoxy, the compound of embodiment 23.

[0071] Embodiment 25. Each R 4 is, independently, halogen, cyano, methyl or methoxy, the compound of embodiment 24.

[0072] Embodiment 25a. Each R 4 is, independently, halogen, cyano or methoxy, the compound of embodiment 25.

[0073] Embodiment 25b. Each R 4 is, independently, halogen, cyano or methyl, the compound of embodiment 25.

[0074] Embodiment 26. Each R 4The compound of embodiment 25, wherein each is independently Br, Cl, F, cyano, methyl or methoxy.

[0075] Embodiment 27. Each R 4 The compound of embodiment 26, wherein each is independently Br, Cl, F, cyano or methoxy.

[0076] Embodiment 28. Each R 4 The compound of embodiment 27, wherein each is independently Cl, F, cyano or methoxy.

[0077] Embodiment 29. Each R 4 The compound of embodiment 27, wherein each is independently Br, Cl or F.

[0078] Embodiment 30. Each R 4 The compound of embodiment 29, wherein each is independently Cl or F.

[0079] Embodiment 31. Each R 4 The compound of embodiment 30, wherein each is Cl.

[0080] Embodiment 32. Each R 4 The compound of embodiment 30, wherein each is F.

[0081] Embodiment 33. Each R 4 The compound of formula 1 or any one of embodiments 1 to 32, wherein each is independently halogen, cyano or C1-C2 alkoxy.

[0082] Embodiment 34. Each R 4 The compound of embodiment 33, wherein each is independently halogen.

[0083] Embodiment 35. Each R 4 The compound of embodiment 33, wherein each is independently Br, Cl, F or cyano.

[0084] Embodiment 36. The compound of formula 1 or any one of embodiments 1 to 35, wherein m is 0, 1 or 2.

[0085] Embodiment 37. A compound of embodiment 36, wherein m is 1 or 2.

[0086] Embodiment 38. The compound of embodiment 37, wherein m is 1.

[0087] Embodiment 39. The compound of embodiment 38, wherein m is 2.

[0088] Embodiment 40. Each R 5 is independently halogen, C1-C2 alkyl, C2-C4 alkoxyalkyl, C1-C2 alkoxy, C1-C2 haloalkoxy, C2-C4 alkenyloxy, C2-C4 alkynyloxy, C2-C4 cyanoalkoxy, or C2-C4 alkoxyalkoxy.

[0089] Embodiment 41. Each R 5 is independently halogen, methyl, methoxy, halomethoxy, C2-C4 alkenyloxy, C2-C4 alkynyloxy, or C2-C4 cyanoalkoxy.

[0090] Embodiment 42. Each R 5 is independently halogen, methyl, methoxy, halomethoxy, C2-C4 alkenyloxy, or C2-C4 cyanoalkoxy.

[0091] Embodiment 43. Each R 5 is independently halogen, methyl, methoxy, halomethoxy, or C2-C4 cyanoalkoxy.

[0092] Embodiment 44. Each R 5 The compound of embodiment 43, wherein is independently halogen, methyl or methoxy.

[0093] Embodiment 45. Each R 5 The compound of embodiment 44, wherein is independently Br, Cl, F, methyl or methoxy.

[0094] Embodiment 46. Each R 5 is independently Br, Cl, F or methoxy, the compound of Embodiment 45.

[0095] Embodiment 46a. Each R 5 is independently Br, Cl or F, the compound of Embodiment 46.

[0096] Embodiment 47. Each R 5 is independently Cl, F or methoxy, the compound of Embodiment 46.

[0097] Embodiment 48. Each R 5 is independently Cl or F, the compound of Embodiment 47.

[0098] Embodiment 49. Each R 5 is independently Br, Cl, F or methyl, the compound of Embodiment 45.

[0099] Embodiment 50. Each R 5 is independently F or methyl, the compound of Embodiment 49.

[0100] Embodiment 51. Each R 5 is F, the compound of Embodiment 50.

[0101] Embodiment 52. n is 0, 1 or 2, the compound of Formula 1 or any one of Embodiments 1 to 51.

[0102] Embodiment 53. n is 1 or 2, the compound of Embodiment 52.

[0103] Embodiment 54. n is 1, the compound of Embodiment 53.

[0104] Embodiment 55. n is 2, the compound of Embodiment 53.

[0105] Embodiment 56. R 6is H; or is C1-C3 alkyl or C1-C3 haloalkyl, each optionally substituted with up to one substituent selected from R 6a ; or is amino, C2-C3 alkenyl, C2-C3 alkynyl, cyclopropyl, CH(=O), S(=O)2OM, S(=O) u R 7 , (C=W)R 8 or OR 9 ; a compound of formula 1 or any one of embodiments 1 to 55.

[0106] Embodiment 57. R 6 is H; or is C1-C3 alkyl or C1-C3 haloalkyl, each optionally substituted with up to one substituent selected from R 6a ; or is cyclopropyl, S(=O)2OM, S(=O) u R 7 , (C=W)R 8 or OR 9 ; a compound of embodiment 56.

[0107] Embodiment 58. R 6 is H; or is C1-C2 alkyl or C1-C2 haloalkyl, each optionally substituted with up to one substituent selected from R 6a ; or is S(=O) u R 7 or OR 9 ; a compound of embodiment 57.

[0108] Embodiment 59. R 6 is H; or is C1-C2 alkyl or C1-C2 haloalkyl, each optionally substituted with up to one substituent selected from R 6a ; a compound of embodiment 58.

[0109] Embodiment 60. R 6 is H, C1-C2 alkyl or C1-C2 haloalkyl; a compound of embodiment 59.

[0110] Embodiment 61. R6 The compound of embodiment 60, wherein R is H, methyl or halomethyl.

[0111] Embodiment 62. R 6 The compound of embodiment 61, wherein R is H, methyl or trifluoromethyl.

[0112] Embodiment 63. R 6 The compound of embodiment 62, wherein R is H or methyl.

[0113] Embodiment 64. R 6 The compound of embodiment 63, wherein R is H.

[0114] Embodiment 65. Each R 6a The compound of formula 1 or any one of embodiments 1 to 64, wherein each R is independently cyano, C3-C6 cycloalkyl or C1-C3 alkoxy.

[0115] Embodiment 66. Each R 6a The compound of embodiment 65, wherein each R is independently cyano, cyclopropyl or methoxy.

[0116] Embodiment 67. Each R 6a The compound of embodiment 66, wherein each R is independently cyano or cyclopropyl.

[0117] Embodiment 68. The compound of formula 1 or any one of embodiments 1 to 58, wherein u is 0.

[0118] Embodiment 69. R 7 The compound of formula 1 or any one of embodiments 1 to 58, wherein R is methyl or halomethyl.

[0119] Embodiment 70. The compound of formula 1 or any one of embodiments 1 to 57, wherein W is O.

[0120] Embodiment 71. R 8The compound of formula 1 or any one of embodiments 1 to 57, wherein is C1-C3 alkyl, C1-C3 alkoxy or C1-C3 alkylthio.

[0121] Embodiment 72. R 8 The compound of embodiment 71, wherein is methyl, ethyl, methoxy, ethoxy, methylthio or ethylthio.

[0122] Embodiment 73. R 8 The compound of embodiment 72, wherein is methyl, methoxy or methylthio.

[0123] Embodiment 74. R 9 is H; or is C1-C3 alkyl or C1-C3 haloalkyl, and each is optionally substituted with up to one substituent selected from R 9a ; or is CH(=O), cyclopropyl, S(=O)2OM or (C=W)R 10 The compound of formula 1 or any one of embodiments 1 to 58.

[0124] Embodiment 75. R 9 is H; or is C1-C2 alkyl or C1-C2 haloalkyl, and each is optionally substituted with up to one substituent selected from R 9a The compound of embodiment 74.

[0125] Embodiment 76. Each R 9a is independently cyano, C3-C6 cycloalkyl or C1-C3 alkoxy, the compound of formula 1 or any one of embodiments 1 to 75.

[0126] Embodiment 77. Each R 9a is independently cyano, cyclopropyl or methoxy, the compound of embodiment 76.

[0127] Embodiment 78. Each R 9a is independently cyano or cyclopropyl, the compound of embodiment 77.

[0128] Embodiment 79.R 10 is C1-C3 alkyl, C1-C3 alkoxy or C1-C3 alkylthio, a compound of formula 1 or any one of Embodiments 1 to 78.

[0129] Embodiment 80.R 10 is methyl, ethyl, methoxy, ethoxy, methylthio or ethylthio, the compound of Embodiment 79.

[0130] Embodiment 81.R 10 is methyl, methoxy or methylthio, the compound of Embodiment 80.

[0131] Embodiment 82. m is 1, and R 4 is at the 4-position (or para-position) with respect to the connection of the phenyl ring to the residue of formula 1, a compound of formula 1 or any one of Embodiments 1 to 81.

[0132] Embodiment 83. m is 1, and R 4 is at the 6-position (or ortho-position) with respect to the connection of the phenyl ring to the residue of formula 1, a compound of formula 1 or any one of Embodiments 1 to 81 any one.

[0133] Embodiment 84. m is 1, and R 4 is at the 4-position (or para-position); or m is 1, and R 4 is at the 6-position (or ortho-position) with respect to the connection of the phenyl ring to the residue of formula 1, a compound of formula 1 or any one of Embodiments 1 to 81.

[0134] Embodiment 85. m is 2, and with respect to the connection of the phenyl ring to the residue of formula 1, one R 4 is at the 4-position (or para-position) and the other is at the 6-position (or ortho-position), a compound of formula 1 or any one of Embodiments 1 to 81.

[0135] Embodiment 86. m is 1, and R 4is at the 4-position (or para-position); or m is 1, and R 4 is at the 6-position (or ortho-position); or m is 2, and for the connection of the phenyl ring to the residue of formula 1, one R 4 is at the 4-position (or para-position) and the other is at the 6-position (or ortho-position), a compound of formula 1 or any one of embodiments 1 to 81.

[0136] Embodiment 86a. m is 1, and R 4 is at the 4-position (or para-position); or m is 2, and for the connection of the phenyl ring to the residue of formula 1, one R 4 is at the 4-position (or para-position) and the other is at the 6-position (or ortho-position), a compound of embodiment 86.

[0137] Embodiment 87. n is 1, and R 5 is at the 4-position (or para-position) with respect to the connection of the nitroanilino ring to the residue of formula 1, a compound of formula 1 or any one of embodiments 1 to 86a.

[0138] Embodiment 88. n is 1, and R 5 is at the 6-position (or ortho-position) with respect to the connection of the nitroanilino ring to the residue of formula 1, a compound of formula 1 or any one of embodiments 1 to 86a.

[0139] Embodiment 89. n is 2, and for the connection of the nitroanilino ring to the residue of formula 1, one R 5 is at the 4-position (or para-position) and the other is at the 6-position (or ortho-position), a compound of formula 1 or any one of embodiments 1 to 86a.

[0140] Embodiment 90. n is 1, and R 5 is at the 4-position (or para-position); or n is 1, and R 5 is at the 6-position (or ortho-position); or n is 2, and for the connection of the nitroanilino ring to the residue of formula 1, one R5 a compound of formula 1 or any one of embodiments 1 to 86a, wherein one is at the 4-position (or para-position) and the other is at the 6-position (or ortho-position).

[0141] Embodiment 91. m and n are each 1, and R 4 is at the 4-position (or para-position), and R 5 is at the 6-position (or ortho-position); or m is 1, R 4 is at the 4-position (or para-position), n is 2, one R 5 is at the 4-position (or para-position) and the other is at the 6-position (or ortho-position); or m and n are each 1, R 4 is at the 4-position (or para-position), and R 5 is at the 4-position (or para-position); or m is 2, one R 4 is at the 4-position (or para-position) and the other is at the 6-position (or ortho-position), n is 1, and R5 is at the 6-position (or ortho-position) with respect to the connection of the phenyl and nitroanilino rings to the residue of formula 1, a compound of formula 1 or any one of embodiments 1 to 90.

[0142] Embodiment 92. m and n are each 1, and R 4 is at the 4-position (or para-position), and R 5 is at the 6-position (or ortho-position); or m is 1, R 4 is at the 4- position (or para-position), n is 2, one R 5 is at the 4-position (or para-position) and the other is at the 6-position (or ortho-position); m is 2, one R 4 is at the 4-position (or para-position) and the other is at the 6-position (or ortho-position), n is 1, and R 5 is at the 6-position (or ortho-position) with respect to the connection of the phenyl and nitroanilino rings to the residue of formula 1, a compound of embodiment 91.

[0143] Embodiment 93. m and n are each 1, and R 4is at the 4-position (or para-position), R 5 is at the 6-position (or ortho-position); or m is 1, R 4 is at the 4-position (or para-position), n is 2, and for the connection of the phenyl and nitroanilino rings to the residue of Formula 1, one R 5 is at the 4-position (or para-position) and the other is at the 6-position (or ortho-position), the compound of Embodiment 92.

[0144] Embodiment 94. m and n are each 1, R 4 is at the 4-position (or para-position), R 5 is at the 6-position (or ortho-position), the compound of Embodiment 93.

[0145] Embodiment 95. m is 1, R 4 is at the 4-position (or para-position), n is 2, and one R 5 is at the 4-position (or para-position) and the other is at the 6-position (or ortho-position), the compound of Embodiment 93.

[0146] Embodiments of the present invention, including the above-described Embodiments 1 to 95 and any other embodiments described herein, can be combined in any manner, and the description of the variables in the embodiments relates 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. Further, embodiments of the present invention, including the above-described Embodiments 1 to 95 and any other embodiments described herein and any combination thereof, relate to the compositions and methods of the present invention.

[0147] The combinations of Embodiments 1 to 95 are illustrated as follows: Embodiment A. R 1 is methyl; R 2 is cyano, halogen or C1-C2 alkyl; R 3 is halogen; Each R 4is independently halogen, cyano, methyl, methoxy, halomethoxy, C2-C4 alkenyloxy, C2-C4 alkynyloxy or C2-C4 cyanoalkoxy; each R 5 is independently halogen, methyl, methoxy, halomethoxy, C2-C4 alkenyloxy, C2-C4 alkynyloxy or C2-C4 cyanoalkoxy; R 6 is H; or C1-C2 alkyl or C1-C2 haloalkyl, optionally substituted with up to one substituent selected from R 6a ; or S(=O) u R 7 or OR 9 ; R 6a is cyano, C3-C6 cycloalkyl or C1-C3 alkoxy; R 7 is methyl or halomethyl; R 9 is H; or C1-C2 alkyl or C1-C2 haloalkyl, optionally substituted with up to one substituent selected from R 9a ; R 9a is cyano, C3-C6 cycloalkyl or C1-C3 alkoxy, a compound of formula 1.

[0148] Embodiment B. R 2 is methyl or ethyl; R 3 is Br, Cl or F; each R 4 is independently halogen, cyano, methyl or methoxy; m is 1 and R 4 is at the 4-position (or para-position); or m is 1 and R 4 is at the 6-position (or ortho-position); or m is 2 and one R 4 is at the 4-position (or para-position) and the other is at the 6-position (or ortho-position); each R5 is independently halogen, methyl or methoxy; n is 1, and R 5 is at the 4-position (or para-position); or n is 1, and R 5 is at the 6-position (or ortho-position); or n is 2, and one R 5 is at the 4-position (or para-position) and the other is at the 6-position (or ortho-position); R 6 is H or methyl, a compound of Embodiment A.

[0149] Embodiment C. R 2 is methyl; each R 4 is independently Br, Cl, F, cyano or methoxy; each R 5 is independently Br, Cl, F, methyl or methoxy; R 6 is H, a compound of Embodiment B.

[0150] Embodiment D. each R 4 is independently Br, Cl or F; each R 5 is independently Br, Cl, F or methoxy; m and n are each 1, and R 4 is at the 4-position (or para-position), and R 5 is at the 6-position (or ortho-position); or m is 1, and R 4 is at the 4-position (or para-position), n is 2, and one R 5 is at the 4-position (or para-position) and the other is at the 6-position (or ortho-position); or m is 2, and one R 4 is at the 4-position (or para-position) and the other is at the 6-position (or ortho-position), n is 1, and R 5 is at the 6-position (or ortho-position), a compound of Embodiment C.

[0151] Embodiment E. R4 is Cl or F; each R 5 is independently Cl, F or methoxy; m and n are each 1, R 4 is at the 4-position (or para-position), R 5 is at the 6-position (or ortho-position); or m is 1, R 4 is at the 4-position (or para-position), n is 2, and one R 5 is at the 4-position (or para-position) and the other is at the 6-position (or ortho-position), a compound of Embodiment D.

[0152] Embodiment F. R 1 is C1-C2 alkyl; R 2 is cyano, halogen, C1-C2 alkyl or C1-C2 haloalkyl; R 3 is halogen or methyl; each R 4 is independently halogen, cyano, nitro, C1-C3 alkyl, C1-C3 haloalkoxy, C2-C6 alkenyloxy, C2-C6 alkynyloxy, C2-C6 cyanoalkoxy, C2-C6 alkoxyalkyl or C2-C6 alkoxyalkoxy; each R 5 is independently halogen, C1-C3 alkyl, C2-C6 alkoxyalkyl, C1-C3 alkoxy, C1-C3 haloalkoxy, C2-C6 alkenyloxy, C2-C6 alkynyloxy, C2-C6 cyanoalkoxy or C2-C6 alkoxyalkoxy; provided that at least one R 5 is selected from halogen; m and n are each independently 1, 2 or 3; R 6 is H; or C1-C3 alkyl or C1-C3 haloalkyl, R 6aOptionally substituted with up to two substituents independently selected therefrom; or amino, C2-C4 alkenyl, C2-C4 alkynyl, C3-C6 cycloalkyl, CH(=O), S(=O)2OM, S(=O) u R 7 , (C=W)R 8 or OR 9 ; Each R 6a is independently cyano, C3-C6 cycloalkyl, C1-C3 alkoxy, C1-C3 haloalkoxy, C1-C3 alkylthio, C1-C3 alkylsulfinyl or C1-C3 alkylsulfonyl; M is K or Na; u is 0, 1 or 2; R 7 is C1-C3 alkyl or C1-C3 haloalkyl; W is O or S; R 8 is C1-C3 alkyl, C2-C4 alkoxyalkyl, C2-C4 alkylaminoalkyl, C3-C6 dialkylaminoalkyl, C1-C3 alkoxy, C1-C3 alkylthio or C2-C4 alkylthioalkyl; R 9 is H; or C1-C3 alkyl or C1-C3 haloalkyl, and R 9a is optionally substituted with up to two substituents independently selected therefrom; or CH(=O), C3-C6 cycloalkyl, S(=O)2OM or (C=W)R 10 ; Each R 9a is independently cyano, C3-C6 cycloalkyl, C1-C3 alkoxy, C1-C3 haloalkoxy, C1-C3 alkylthio, C1-C3 alkylsulfinyl or C1-C3 alkylsulfonyl; R 10 is C1-C3 alkyl, C2-C4 alkoxyalkyl, C2-C4 alkylaminoalkyl, C3-C6 dialkylaminoalkyl, C1-C3 alkoxy, C1-C3 alkylthio or C2-C4 alkylthioalkyl; However, N-(2-bromo-4-fluoro-6-nitrophenyl)-4-(2-chloro-4-fluorophenyl)-1,3-dimethyl-1H-pyrazole-5-amine; or a compound of formula 1 that is not 3-chloro-4-(2-chloro-4-fluorophenyl)-N-(2,4-difluoro-6-nitrophenyl)-1-methyl-1H-pyrazole-5-amine.

[0153] Embodiment G. R 1 is methyl; R 2 is cyano, halogen or C1-C2 alkyl; R 3 is halogen; each R 4 is independently halogen, cyano, methyl, C1-C2 alkoxy or C1-C2 haloalkoxy; m is 1 and R 4 is at the 4-position (or para-position); or m is 1 and R 4 is at the 6-position (or ortho-position); or m is 2, one R 4 is at the 4-position (or para-position) and the other is at the 6-position (or ortho-position); each R 5 is independently halogen, methyl, methoxy, halomethyl, C2-C4 alkenyloxy or C2-C4 cyanoalkoxy; n is 1 and R 5 is at the 4-position (or para-position); or n is 1 and R 5 is at the 6-position (or ortho-position); or n is 2, one R 5 is at the 4-position (or para-position) and the other is at the 6-position (or ortho-position); R 6 is H or methyl, a compound of Embodiment F.

[0154] Embodiment H. R 2 is methyl; each R4 is independently Br, Cl, F, cyano or methoxy; each R 5 is independently Br, Cl, F, methyl or methoxy; R 6 is H, a compound of embodiment G.

[0155] Embodiment I. R 4 is Br, Cl or F; each R 5 is independently Br, Cl, F or methoxy; m and n are each 1, R 4 is at the 4-position, R 5 is at the 6-position; or m is 1, R 4 is at the 4-position, n is 2, one R 5 is at the 4-position and the other is at the 6-position, a compound of embodiment H.

[0156] Embodiment J. R 4 is Cl or F; each R 5 is independently Cl, F or methoxy, a compound of embodiment I.

[0157] Certain embodiments include 4-(2-bromo-4,6-difluorophenyl)-N-(2-fluoro-6-nitrophenyl)-1,3-dimethyl-1H-pyrazol-5-amine (Compound 1), 3-chloro-4-[5-[(2-chloro-4-fluoro-6-nitrophenyl)amino]-1,3-dimethyl-1H-pyrazol-4-yl]benzonitrile (Compound 18), N-(2-chloro-4-fluoro-6-nitrophenyl)-4-(2-chloro-4-fluorophenyl)-1,3-dimethyl-1H-pyrazol-5-amine (Compound 19), 4-(2-chloro-6-fluorophenyl)-N-(2-fluoro-4-methoxy-6-nitrophenyl)-1,3-dimethyl-1H-pyrazol-5-amine (Compound 23), 4-(2,4-Difluorophenyl)-N-(2-fluoro-4-methoxy-6-nitrophenyl)-1,3-dimethyl-1H-pyrazole-5-amine (Compound 57), 4-(2-Bromo-4-fluorophenyl)-N-(2-fluoro-6-nitrophenyl)-1,3-dimethyl-1H-pyrazole-5-amine (Compound 60), 4-(2-Chloro-4,6-difluorophenyl)-N-(2-fluoro-6-nitrophenyl)-1,3-dimethyl-1H-pyrazole-5-amine (Compound 68), 4-(2-Chloro-4-fluorophenyl)-N-(2-fluoro-6-nitrophenyl)-3-ethyl-1-methyl-1H-pyrazole-5-amine (Compound 72), N-(2-Chloro-4-fluoro-6-nitrophenyl)-4-(2-chloro-4-methoxyphenyl)-1,3-dimethyl-1H-pyrazole-5-amine (Compound 73), 4-(2-Chloro-4-fluorophenyl)-N-(2-fluoro-4-methyl-6-nitrophenyl)-1,3-dimethyl-1H-pyrazole-5-amine (Compound 93), 4-(2-Chloro-4-fluorophenyl)-N-(4-fluoro-2-nitrophenyl)-1,3-dimethyl-1H-pyrazole-5-amine (Compound 111), 4-(2-Chloro-4-fluorophenyl)-N-(2-fluoro-6-nitrophenyl)-1,3-dimethyl-1H-pyrazole-5-amine (Compound 112), 4-(2,4-Difluorophenyl)-N-(2-fluoro-6-nitrophenyl)-1,3-dimethyl-1H-pyrazole-5-amine (Compound 118), N-(4-Chloro-2-fluoro-6-nitrophenyl)-4-(2-chloro-4-fluorophenyl)-1,3-dimethyl-1H-pyrazole-5-amine (Compound 121) and A compound of formula 1 selected from the group consisting of 3-chloro-4-[5-[(2-fluoro-4-methyl-6-nitrophenyl)amino]-1,3-dimethyl-1H-pyrazol-4-yl]benzonitrile (Compound 127) is included.

[0158] The present invention provides a fungicidal composition comprising a compound of formula 1 (including all stereoisomers, N-oxides, and salts thereof), and at least one other fungicide. Of note as an embodiment of such a composition is a composition comprising a compound corresponding to any of the embodiments of the compounds described above.

[0159] The present invention provides a fungicidal composition comprising a compound of formula 1 (including all stereoisomers, N-oxides, and salts thereof) in an amount effective as a fungicide, and at least one additional component selected from the group consisting of surfactants, solid excipients, and liquid excipients. Of note as an embodiment of such a composition is a composition comprising a compound corresponding to any of the embodiments of the compounds described above.

[0160] The present invention provides a method for controlling plant diseases caused by fungal plant pathogens, which comprises applying an amount effective as a fungicide of a compound of formula 1 (including all stereoisomers, N-oxides, and salts thereof) to a plant or a part thereof, or to the seeds of a plant. Of note as an embodiment of such a method is a method comprising applying an amount effective as a fungicide of a compound corresponding to any of the embodiments of the compounds described above. Of particular note is the embodiment in which the present compound is applied as the composition of the present invention.

[0161] Of note are the compounds of formula 1A (including all geometric and stereoisomers), the compounds of formula 1 which are N-oxides, hydrates and salts thereof, and their use as agricultural compositions and fungicides containing them,

Chemical formula

[0162] Embodiment A1. R 2 is methyl or ethyl; R 3 is Br, Cl or F; R 4a and R 4b each independently is H, Br, Cl or F; R 5a and R 5b each independently is H, Br, Cl, F or methyl, a compound of formula 1A.

[0163] Embodiment B1. R 2 is methyl; R 4a is Cl or F; R 4b is H, Cl or F; R 5a is H, Cl, F or methyl; R 5b is H or F, a compound of Embodiment A1.

[0164] Also worthy of note is a fungicidal composition comprising an effective amount of a compound of formula 1A (including all geometric and stereoisomers, N-oxides, and salts thereof), or any one of the corresponding embodiments of embodiments 1 to 95 and embodiments A to J, and at least one additional component selected from the group consisting of a surfactant, a solid excipient, and a liquid excipient. Further worthy of note is a method for controlling a plant disease caused by a fungal plant pathogen, comprising the step of applying an effective amount of a compound of formula 1A (including all geometric and stereoisomers, N-oxides, and salts thereof), or any one of the said corresponding embodiments, to a plant or a part thereof, or to a plant seed. Particularly worthy of note is the embodiment in which the compound of formula 1A is applied as the composition of the present invention.

[0165] One or more of the following methods and modified methods described in Schemes 1 to 12 can be used to produce the compound of formula 1. R in the following compounds of formulae 1 to 21 1 、R 2 、R 3 、R 4 、R 5 、m, n and R 6 are defined as defined above in the summary of the invention, unless otherwise indicated. Formulae 1a and 1b are subsets of formula 1. Substituents for the subset formulae are as defined for their parent formulae, unless otherwise indicated.

[0166] As shown in Scheme 1, the compound of formula 1 can be prepared by reacting a 5-aminopyrazole of formula 2 with a nitrophenyl compound of formula 3, L 1is, optionally, in the presence of a metal catalyst, generally in the presence of a base such as potassium tert-butoxide, triethylamine or potassium carbonate and a solvent such as tetrahydrofuran, N,N-dimethylformamide, 1,4-dioxane, toluene, ethanol, methanol or dimethyl sulfoxide, a leaving group such as a halogen (e.g., F, Cl, Br, I) or a sulfonate (e.g., mesylate, triflate or p-toluenesulfonate). In certain cases, the desired reaction can be facilitated by using a metal catalyst in an amount from a catalytic amount to a stoichiometric excess. Typical reaction conditions include, for example, in the presence of a metal catalyst such as a copper salt complex (e.g., CuI with N,N'-dimethylethylenediamine, proline or bipyridyl), a palladium complex (e.g., tris(dibenzylideneacetone)dipalladium(0)) or a palladium salt (e.g., palladium acetate), a ligand such as 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene, 2-dicyclohexylphosphino-2',4',6'-triisopropylbiphenyl or 2,2'-bis(diphenylphosphino)1,1'-binaphthalene, a base such as potassium carbonate, cesium carbonate, potassium phosphate, sodium phenoxide or sodium tert-butoxide and a solvent such as N,N-dimethylformamide, 1,2-dimethoxyethane, dimethyl sulfoxide, 1,4-dioxane or toluene, a solvent optionally containing an alcohol such as ethanol. For related references, see PCT Patent Publication WO2013 / 126283, Synthesis Example 1, Step C; and WO2010 / 020363, Example 2A. Also, the method of Scheme 1 is illustrated in this Example 1, Step C; Example 5, Step C; and Example 3. Compounds of Formula 3 are commercially available or their preparation is known in the art.

[0167]

Chemical formula

[0168] General methods useful for preparing the 5-aminopyrazoles of formula 2 are well known in the art; see, for example, Journal fur Praktische Chemie (Leipzig) 1911, 83, 171 and J. Am. Chem. Soc. 1954, 76, 501. One such method is illustrated in Scheme 2 below, and the 5-aminopyrazoles of formula 2 are prepared by condensing a hydrazine of formula 5 (e.g., methylhydrazine or ethylhydrazine) with a compound of formula 4 in a solvent such as ethanol or methanol and optionally in the presence of an acid such as acetic acid according to general procedures known in the art; see, for example, PCT Patent Publication WO2012 / 031061, Synthesis Example 1, Step A; and Synthesis Example 2, Step C. Also, the method of Scheme 2 is illustrated in Example 1, Step B herein.

[0169]

Chem.

[0170] Alternatively, as shown in Scheme 3, the 5-aminopyrazoles of formula 2 can also be prepared by reacting a 4-bromo or 4-iodopyrazole of formula 6 with a boronic acid compound of formula 7 using cross-coupling reaction conditions catalyzed by a well-known transition metal.

[0171]

Chem.

[0172] Methods useful for preparing the compounds of formula 6 are known in the art.

[0173] The compound of formula 1a (i.e., R 6wherein it is H, Formula 1) can be produced as shown in Scheme 4. In this method, the compound of Formula 8 is condensed with hydrazine of Formula 5 (e.g., methylhydrazine or ethylhydrazine) in a solvent such as ethanol or methanol and optionally in the presence of an acid or base catalyst such as acetic acid, piperidine or sodium methoxide according to general procedures known in the art. For reaction conditions, refer to PCT Patent Publication WO2013 / 116251, Synthesis Example 1, Step C and Example 2, Step B. Also, R a The method of Scheme 4 using a compound of Formula 8 wherein R is methyl is exemplified in Step C of Example 2 of the present invention.

[0174]

Chemical formula

[0175] As shown in Scheme 5, the compound of Formula 8 can be produced by reacting a ketene dithioacetal derivative of Formula 9 with a compound of Formula 10 in a solvent such as toluene, tetrahydrofuran or dimethoxymethane in the presence of a base such as sodium hydride or ethylmagnesium chloride, at a temperature from about -10 °C to the boiling point of the solvent. For related references, see, for example, J. Heterocycl. Chem. 1975, 12(1), 139. Methods useful for preparing the compound of Formula 9 are known in the art.

[0176]

Chemical formula

[0177] Furthermore, as shown in Scheme 6, R a wherein Formula 8 and Formula 8a are lower alkyl (e.g., methyl, ethyl, n-propyl) (i.e., R aWhen it is H, the tautomer of the compound of formula 8) can be prepared by the condensation reaction of the isothiocyanate compound of formula 11 with the carbonyl compound of formula 12 to obtain an intermediate compound of formula 13, which is a salt of the thioamide of formula 8a. The intermediate compound of formula 13 can be used in situ (as illustrated in WO2013 / 116251, Synthesis Example 1, Step C; and this Example 2, Step C) or in isolated form (as illustrated in WO2013 / 116251, Example 2, Step A). Bases useful for preparing the compound of formula 13 include hydrides, alkoxides, hydroxides or carbonates of sodium or potassium such as sodium hydride, potassium tert-butoxide, sodium ethoxide, potassium hydroxide, sodium hydroxide or potassium carbonate. The condensation of the compounds of formulas 11 and 12 to the compound of formula 13 can be carried out using an amine base (e.g., triethylamine or N,N-diisopropylethylamine). Various solvents are useful, such as tetrahydrofuran, diethyl ether, toluene, N,N-dimethylformamide, alcohols (e.g., ethanol), esters (e.g., ethyl acetate or isopropyl acetate), or mixtures thereof. The solvent is selected for compatibility with the base, as will be understood by those skilled in the art. The reaction temperature can range from -78 °C to the boiling point of the solvent. One useful mixture of base and solvent is potassium tert-butoxide or potassium tert-pentoxide in tetrahydrofuran, to which a solution of the isothiocyanate of formula 11 and the carbonyl compound of formula 12 can be added, which can be combined in one solution or, preferably, added separately by adding the carbonyl compound first and then the isothiocyanate. Usually, this reaction is carried out at -70 to 0 °C. The salt of formula 13 can be acidified to form the keto-thioamide compound of formula 8a, or R a X 1 (Formula 14)[wherein R a is lower alkyl (e.g., methyl, ethyl, n-propyl), X 1is a nucleophilic leaving group (i.e., a nucleophilic reaction leaving group such as Br, I, OS(O)2CH3), and can be alkylated to form the corresponding compound of formula 8. This general method is known in the chemical literature; see, for example, Zhurnal Organicheskoi Khimii 1982, Vol. 18 (No. 12), page 2501. R a is methyl obtained from the intermediate compound of formula 13, and the method of Scheme 6 for producing the compound of formula 8 without isolation of this is illustrated in PCT Patent Publication WO2013 / 116251, Synthesis Example 1, Step C. Also, this Example 2, Step C illustrates the production of the compound of formula 8.

[0178] [Chemical formula]

[0179] The keto-thioamide of formula 8a can also be produced by reacting the corresponding ketoamide with a sulfurizing agent such as Lawesson's reagent or P2S5; see, for example, Helv. Chim. Acta 1998, Vol. 81 (No. 7), page 1207.

[0180] As shown in Scheme 7, the compound of formula 1 is preferably in the presence of a base such as 1,8-diazabicyclo[5.4.0]undec-7-ene, potassium carbonate or potassium hydroxide, and a solvent such as N,N-dimethylformamide, tetrahydrofuran, toluene or water, and the 1H-pyrazole compound of formula 15 is reacted with the formula R 1 -L 2 [wherein R 1 is methyl or ethyl, and L 2It can also be produced by reacting with a methylating agent which is a leaving group such as a halogen (e.g., Cl, Br, I), a sulfonate (e.g., mesylate, triflate or p-toluenesulfonate) or a phosphate (e.g., dimethyl phosphate). General procedures for this type of methylation are well known in the art and can be easily adapted to produce the compounds of the present invention. Particularly useful methylating agents include diazomethane and iodomethane using general procedures known in the art, such as those described in Canada Journal of Chemistry, 1986, Vol. 64, pp. 2211-2219 and Heterocycles, 2000, Vol. 53(12), pp. 2775-2780.

[0181]

Chemical formula

[0182] The compound of formula 15 can be produced by condensing the compound of formula 8 with hydrazine in a manner similar to the method of Scheme 4. This method is described in Chemistry of Heterocyclic Compounds, 2005, Vol. 41(1), pp. 105-110.

[0183] In an alternative method, as shown in Scheme 8, the compound of formula 1 can be produced by reacting a 4-bromo or 4-iodopyrazole of formula 16 with an organometallic compound of formula 17 under cross-coupling reaction conditions catalyzed by a transition metal, in the presence of a suitable palladium, copper or nickel catalyst. In this method, the compound of formula 17 is an organoboronic acid (e.g., M 1 is B(OH)2), an organoboronic acid ester (e.g., M 1 is B(-OC(CH2)3O-), an organotrifluoroborate (e.g., M 1 is BF3K), an organotin reagent (e.g., M 1 is Sn(n-Bu)3, Sn(Me)3), a Grignard reagent (e.g., M 1is MgBr or MgCl) or an organozinc reagent (e.g., M 1 is ZnBr or ZnCl). Suitable metal catalysts include, but are not limited to, palladium(II) acetate, palladium(II) chloride, tetrakis(triphenylphosphine)palladium(0), bis(triphenylphosphine)palladium(II) dichloride, dichloro[1,1'-bis(diphenylphosphino)ferrocene]palladium(II), bis(triphenylphosphine)dichloronickel(II), and copper(I) salts (e.g., copper(I) iodide, copper(I) bromide, copper(I) chloride, copper(I) cyanide, or copper(I) triflate). Optimal conditions, as will be understood by those skilled in the art, depend on the catalyst and the counterion attached to the coupling reagent (i.e., M 1 ). In some cases, the addition of a ligand such as a substituted phosphine or a substituted bisphosphinoalkane enhances the reactivity. Also, the presence of a base such as an alkali carbonate, a tertiary amine, or an alkali fluoride may be required for some reactions using the organoboron reagent of formula 17. For a review of this type of reaction, see: E. Negishi, Handbook of Organopalladium Chemistry for Organic Synthesis, John Wiley and Sons, Inc., New York, 2002; N. Miyaura, Cross-Coupling Reactions: A Practical Guide, Springer, New York, 2002; H.C. Brown et al., Organic Synthesis via Boranes, Vol. 3, Aldrich Chemical Co., Milwaukee, WI, 2002; Suzuki et al., Chemical Review 1995, 95, 2457 - 2483, and Molander et al., Accounts of Chemical Research 2007, 40, 275 - 286. Also, the method of Scheme 8 is described in PCT Patent Publications WO2010 / 101973 and WO2012 It is exemplified in / 031061.

[0184]

Chemical formula

[0185] As shown in Scheme 9, the pyrazole intermediate of Formula 16 is readily prepared from the corresponding pyrazole of Formula 18 by treatment with a halogenating reagent. Suitable halogenating reagents for this method include N-bromosuccinimide (NBS), N-iodosuccinimide (NIS), bromine, sodium bromite, thionyl chloride, oxalyl chloride, phenylphosphonic dichloride or phosgene. Particularly useful are N-bromosuccinimide (NBS) and N-iodosuccinimide (NIS). Suitable solvents for this reaction include, for example, N,N-dimethylformamide, N,N-dimethylacetamide, dichloromethane, chloroform, chlorobutane, benzene, xylene, chlorobenzene, tetrahydrofuran, p-dioxane, acetonitrile and the like. Optionally, organic bases such as triethylamine, pyridine, N,N-dimethylaniline and the like can be added. The typical reaction temperature ranges from about ambient temperature to 200 °C. For representative procedures, see Synthesis 2006, Vol. 17, pp. 2855 - 2864; Journal of Medicinal Chemistry 2005, Vol. 48, pp. 6843 - 6854; Journal of Medicinal Chemistry 2007, Vol. 50, pp. 3086 - 3100 and Journal of Medicinal Chemistry 2005, Vol. 48, pp. 4420 - 4431.

[0186]

Chemical formula

[0187] As shown in Scheme 10, the compound of Formula 18 can be prepared from the corresponding compound of Formula 19 by a procedure similar to that used for the method of Scheme 1. The compound can be commercially available or prepared by methods known in the art.

[0188]

Chemical formula

[0189] The compounds of Formula 1 and their intermediates described herein can be subjected to various electrophilic, nucleophilic, organometallic, oxidation and reduction reactions to add substituents or modify existing substituents, thus providing other functionalized compounds of Formula 1. For example, as shown in Scheme 11, the compound of Formula 1b (i.e., (R 5 ) n is CH3, Formula 1) is preferably in the presence of a catalyst such as [1,1'-bis(diphenylphosphino)ferrocene]palladium(II) chloride dichloromethane adduct, in the presence of a base such as 1,8-diazabicyclo[5.4.0]undec-7-ene, cesium carbonate or potassium hydroxide and in a solvent such as N,N-dimethylformamide, tetrahydrofuran, 1,4-dioxane, ethanol, toluene or water, L 3 is a leaving group such as halogen (e.g., Br, I) or sulfonate (e.g., mesylate, triflate, p-toluenesulfonate), and can be prepared by reaction with a reagent such as 2,4,6-trimethylboroxine or tetramethylstannane of the compound of Formula 20. The method of Scheme 11 is illustrated in PCT Patent Publication WO2013 / 192126 Example 4, Step A, and this Example 4, Step B.

[0190] The compound of formula 20 can be prepared by the methods described in PCT Patent Publications WO2010 / 101973 and WO2012 / 031061. Those skilled in the art will recognize that in some cases, the preparation of the N-protected compound of formula 20 prior to the interconversion of functional groups will aid in obtaining the desired product. The selection and use of appropriate N-protecting groups will be apparent to those skilled in the art; for representative examples, see T.W. Greene and P.G.M. Wuts, Protective Groups in Organic Synthesis, 2nd ed.; Wiley: New York, 1991. Again, Step A of Example 4 illustrates the preparation of the compound protected by N-Boc of formula 20.

[0191] [Chemical formula]

[0192] Similar to the method of Scheme 11, the compound of formula 20 can be treated with potassium (trifluoromethyl) trimethoxyborate to provide the trifluoromethyl analog of formula 1b.

[0193] In another example, as shown in Scheme 12, for a compound of formula 1 where R 6 is other than H, it can be prepared from the corresponding compound of formula 1 where R 6 is H by reaction with an electrophilic reagent containing R 6 (i.e., formula 21). Usually, the reaction is carried out in the presence of a base such as sodium hydride and in a polar solvent such as N,N-dimethylformamide. In this context, the expression "electrophilic reagent containing R 6 " means a chemical substance capable of transferring the R 6 moiety to a nucleophile (i.e., the nitrogen atom in formula 1 when R 6 is H). Often, the electrophilic reagent containing R 6 has the formula R 6 X 2 [wherein X 2has a leaving group (i.e., a leaving group in a nucleophilic reaction). Typical leaving groups include halides (e.g., Br, Cl, I) or sulfonates (e.g., mesylate, triflate, p - toluenesulfonate). However, some electrophiles containing R 6 do not involve a leaving group; one example is sulfur trioxide (SO3), which, when R 6 is H, can bond to the nitrogen atom in formula 1 as the -SO3M substituent after deprotonation (such as by a base of formula M + H - [wherein M + is a cation).

[0194]

Chemical formula

[0195] It is recognized that some of the reagents and reaction conditions described above for preparing the compounds of formula 1 may not be compatible with certain functional groups present in the intermediates. In these cases, a protecting / deprotecting sequence or a combination of functional group interconversions in the synthesis can help obtain the desired product. The use and selection of protecting groups are apparent to those skilled in chemical synthesis (see, for example, T.W. Greene and P.G.M. Wuts, Protective Groups in Organic Synthesis, 2nd ed.; Wiley: New York, 1991). Those skilled in the art recognize that in some cases, as illustrated in any individual scheme, after the introduction of a given reagent, additional routine synthetic steps not described in detail may be required to complete the synthesis of the compounds of formula 1. Those skilled in the art also recognize that they may need to perform combinations of the steps exemplified in the above schemes in an order other than that indicated by the specific sequences presented for preparing the compounds of formula 1.

[0196] Those skilled in the art will also recognize that the compounds and intermediates of Formula 1 described herein can be subjected to various electrophilic, nucleophilic, radical, organometallic, oxidation, and reduction reactions to add substituents or modify existing substituents.

[0197] Without further elaboration, it is believed that one skilled in the art can, using the preceding description, utilize the present invention to its fullest extent. Accordingly, the following examples are to be construed as merely illustrative, and any of them are not to be construed as limiting the disclosure in any way. The steps in the following examples illustrate the procedures for each step in the overall synthetic transformation, and the starting materials for each step need not necessarily be produced by a specific preparative run as described in other examples or steps of the procedure. Percentages are by weight unless otherwise indicated, except for solvent mixtures for chromatography or where otherwise noted. Parts and percentages for solvent mixtures for chromatography are by volume unless otherwise indicated. 1 1H NMR spectra are reported as low-field shifts relative to tetramethylsilane at 0 ppm; "s" means singlet, "d" means doublet, "t" means triplet, "m" means multiplet, "br s" means broad singlet, and "dd" means doublet of doublets.

Examples

[0198] Preparation of 4-(2-chloro-4-fluorophenyl)-N-(2-fluoro-6-nitrophenyl)-1,3-dimethyl-1H-pyrazole-5-amine (Compound 112) Step A: Preparation of α-acetyl-2-chloro-4-fluorobenzeneacetonitrile A mixture of a sodium methoxide solution (30% in methanol, 85 mL, 0.47 mol) in toluene (400 mL) was heated to 120 °C using a Dean - Stark trap for azeotropic removal of methanol. After cooling to 90 °C, 2 - chloro - 4 - fluorobenzeneacetonitrile (40.0 g, 0.24 mol) in ethyl acetate (200 mL) was added dropwise to the reaction mixture. The reaction mixture was stirred at 90 °C for 1 h and then hydrochloric acid (1 N, 30 mL) was added. The resulting mixture was extracted with ethyl acetate (3 × 250 mL), and the combined organic extracts were dried over sodium sulfate, filtered, and concentrated under reduced pressure. The resulting material was purified by silica gel column chromatography (using ethyl acetate - petroleum ether 3:7 as the eluent) to give the title compound as a white solid (35 g). 1 1H NMR (CDCl3): δ 7.49 (dd, 1H), 7.24 (dd, 1H), 7.14 - 7.09 (m, 1H), 5.13 (s, 1H), 2.36 (s, 3H).

[0199] Step B: Preparation of 4 - (2 - chloro - 4 - fluorophenyl) - 1,3 - dimethyl - 1H - pyrazol - 5 - amine To a mixture of α - acetyl - 2 - chloro - 4 - fluorobenzeneacetonitrile (i.e., the product of Step A) (28 g, 0.13 mol) in ethanol (400 mL) were added methylhydrazine sulfate (28.6 g, 0.20 mol) and sodium acetate (21.7 g, 0.27 mol). The reaction mixture was heated at 120 °C for 12 h and then concentrated under reduced pressure to remove the solvent. The resulting mixture was poured into ice - water (500 mL) and filtered to collect a white solid. The solid was washed with water and pentane and then dried to give the title compound as an off - white solid (24 g). 1 1H NMR (CDCl3): δ 7.45 (dd, 1H), 7.27 (t, 1H), 7.23 - 7.12 (m, 1H), 4.89 (s, 2H), 3.49 (s, 3H).

[0200] Step C: Preparation of 4-(2-chloro-4-fluorophenyl)-N-(2-fluoro-6-nitrophenyl)-1,3-dimethyl-1H-pyrazole-5-amine To a mixture of 4-(2-chloro-4-fluorophenyl)-1,3-dimethyl-1H-pyrazole-5-amine (i.e., the product of Step B) (1.2 g, 5.0 mmol) in tetrahydrofuran (40 mL) at 0 °C was added potassium tert-butoxide (1 M in THF, 10 mL, 10 mmol) portionwise. The reaction mixture was stirred at 0 °C for 1 h and then 1,2-difluoro-3-nitrobenzene (0.85 g, 5.3 mmol) was added dropwise. After 30 min at 0 °C, saturated aqueous ammonium chloride solution was added to the reaction mixture and the resulting mixture was extracted with ethyl acetate (100 mL). The aqueous layer was further extracted with ethyl acetate (2 × 40 mL), and the combined organic extracts were washed with saturated sodium chloride solution, dried over sodium sulfate, filtered, and concentrated under reduced pressure. The resulting material was purified by silica gel column chromatography (using 40% ethyl acetate in petroleum ether as the eluent) to give the title compound, a yellow solid (1.1 g), which is the compound of the present invention. 1 H NMR (CDCl3): δ 8.59 (s, 1H), 7.59 (d, 1H), 7.31 (d, 1H), 7.2 (d, 1H), 7.09 (t, 1H), 7.04 - 7.01 (m, 1H), 6.82 - 6.86 (m, 1H), 3.74 (s, 3H), 1.97 (s, 3H).

Example

[0201] Preparation of 3-chloro-4-[5-[(2-fluoro-6-nitrophenyl)amino]-1,3-dimethyl-1H-pyrazol-4-yl]benzonitrile (Compound 113) Step A: Preparation of 3-chloro-4-(2-oxopropyl)benzonitrile To a mixture of 4-amino-3-chlorobenzonitrile (50.0 g, 0.33 mol) in diethyl ether (500 mL) at -10 °C was added boron trifluoride diethyl etherate (61 mL, 0.50 mol). The reaction mixture was stirred at -10 °C for 10 minutes, then tert-butyl nitrite (48 mL, 0.4 mol) was added. After 20 minutes at -10 °C, the reaction mixture was allowed to warm to room temperature and stirred for 2 h, then filtered to collect the white solid. The white solid was triturated with diethyl ether and pentane (1:1, 300 mL), filtered, and dried to give the intermediate compound 2-chloro-4-cyanobenzenediazonium tetrafluoroborate as an off-white solid (72 g).

[0202] To a mixture of 2-chloro-4-cyanobenzenediazonium tetrafluoroborate (72 g, 0.33 mol) in dimethylformamide (500 mL) at -10 °C was added isopropenyl acetate (354 mL, 3.2 mol). The reaction mixture was stirred at -10 °C for 20 minutes, then 4-aminomorpholine (1.0 mL) in dimethyl sulfoxide (40 mL) was added. After 1 h, ice-cold water (1000 mL) was added and the resulting mixture was extracted with ethyl acetate (3 × 250 mL). The combined organic extracts were dried over sodium sulfate, filtered, and concentrated under reduced pressure. The resulting material was purified by silica gel column chromatography (using ethyl acetate - petroleum ether 1:4 as the eluent) to give the title compound as a solid (52 g). 1 H NMR (CDCl3): δ 7.69 (s, 1H), 7.53 (d, 1H), 7.32 (d, 1H), 3.93 (s, 2H), 2.28 (s, 3H).

[0203] Step B: Preparation of 1-fluoro-2-isothiocyanato-3-nitrobenzene To a mixture of 2-fluoro-6-nitroaniline (1.0 g, 6.4 mmol) in 1,2-dichlorobenzene (10 mL) at 0 °C were added 2 drops of dimethylformamide, then thiophosgene (1.46 mL, 19 mmol). The reaction mixture was heated at 160 °C for 1 h It was heated, cooled to room temperature, and concentrated under reduced pressure. The obtained material was purified by silica gel column chromatography (using ethyl acetate - petroleum ether 1:9 as the eluent) to give the title compound as an oily substance (0.91 g). 1 H NMR (CDCl3) δ 7.88 (d, 1H), 7.46 (t, 1H), 7.36 (m,1H).

[0204] Step C: Preparation of 3-chloro-4-[5-[(2-fluoro-6-nitrophenyl)amino]-1,3-dimethyl-1H-pyrazol-4-yl]benzonitrile To a mixture of 3-chloro-4-(2-oxopropyl)benzonitrile (i.e., the product of Step A) (1.0 g, 5.2 mmol) in tetrahydrofuran (20 mL) at -10 °C was added potassium tert-butoxide (0.7 g, 6.2 mmol). After 30 minutes at -10 °C, 1-fluoro-2-isothiocyanato-3-nitrobenzene (i.e., the product of Step B) (0.99 g, 5.0 mmol) in tetrahydrofuran (10 mL) was added to the reaction mixture, and stirring was continued for about 15 minutes to produce a reaction mixture containing the potassium salt of the intermediate compound 4-[1-[[(2-chloro-6-nitrophenyl)amino]methylenethio]-2-oxopropyl]-3-chloro-benzonitrile, which is the potassium salt of α-acetyl-N-(2-chloro-6-nitrophenyl)-2-chloro-4-cyano-benzene-ethanethioamide. Iodomethane (1.2 mL, 19 mmol) was added to the reaction mixture. After 20 minutes at -10 °C, the reaction temperature was brought to 0 °C, and acetic acid (5.0 mL) and methylhydrazine (85% in water, 0.5 g, 10 mmol) were added. The reaction mixture was allowed to warm to room temperature and heated under reflux for 2 h, then poured into ice-cold water (30 mL) and ethyl acetate (20 mL). The organic layer was separated, and the aqueous layer was extracted with ethyl acetate (2 × 10 mL). The combined organic extracts were washed with saturated sodium chloride solution (20 mL), dried over sodium sulfate, filtered, and concentrated under reduced pressure. The resulting material was purified by silica gel column chromatography (using ethyl acetate - petroleum ether 2:3 as the eluent) to produce the title compound, which is a compound of the present invention, as a pale yellow solid (0.850 g). 1 H NMR (CDCl3) δ 8.71 (d, 1H), 7.85 (d, 1H), 7.64 - 7.58 (m, 2H), 7.34 - 7.25 (m, 2H), 6.87 - 6.81 (m, 1H), 3.75 (s, 3H), 1.99 (s, 3H).

Example

[0205] Production of N-(4-Bromo-2-fluoro-6-nitrophenyl)-4-(2-chloro-4-fluorophenyl)-1,3-dimethyl-1H-pyrazol-5-amine (Compound 61) To a mixture of 4-(2-chloro-4-fluorophenyl)-1,3-dimethyl-1H-pyrazol-5-amine (i.e., the product of Step B of Example 1) (0.5 g, 2.1 mmol) in tetrahydrofuran (30 mL) at 0 °C was added potassium tert-butoxide (1 M in THF, 4.2 mL, 4.2 mmol) portionwise. The reaction mixture was stirred at 0 °C for 1 h and then 5-bromo-1,2-difluoro-3-nitrobenzene (0.54 g, 2.3 mmol) was added dropwise. After 30 minutes at 0 °C, saturated aqueous ammonium chloride was added to the reaction mixture and the resulting mixture was extracted with ethyl acetate (100 mL). The aqueous layer was further extracted with ethyl acetate (2 × 40 mL), and the combined organic extracts were washed with saturated sodium chloride solution, dried over sodium sulfate, filtered, and concentrated under reduced pressure. The resulting material was purified by silica gel column chromatography (using 40% ethyl acetate in petroleum ether as the eluent) to give the title compound, which is a compound of the present invention, as a yellow solid (0.45 g). 1 H NMR (CDCl3): δ 8.69 (br s, 1H), 7.77 (t, 1H), 7.66 (dd, 1H), 7.27 (dd, 2.0 Hz, 1H), 7.09-7.06 (m, 2H), 3.73 (s, 3H), 1.97 (s, 3H).

Example

[0206] Production of 4-(2-Chloro-4-fluorophenyl)-N-(2-fluoro-4-methyl-6-nitrophenyl)-1,3-dimethyl-1H-pyrazol-5-amine (Compound 93) Step A: Production of tert-butyl N-(4-bromo-2-fluoro-6-nitrophenyl)-N-[4-(2-chloro-4-fluorophenyl)-1,3-dimethyl-1H-pyrazol-5-yl]carbamate A mixture of N-(4-bromo-2-fluoro-6-nitrophenyl)-4-(2-chloro-4-fluorophenyl)-1,3-dimethyl-1H-pyrazol-5-amine (i.e., the product of Example 3) (1 g, 2.2 mmol) and triethylamine (1.24 mL, 8.9 mmol) in dichloromethane (20 mL) at 0 °C was treated with di-tert-butyl dicarbonate (1.46 g, 6.7 mmol). The reaction mixture was allowed to warm to room temperature and stirred overnight, then diluted with water (20 mL) and extracted with dichloromethane (2 × 20 mL). The combined organic extracts were washed with saturated sodium chloride solution, dried over sodium sulfate, filtered, and concentrated under reduced pressure. The resulting material was purified by silica gel column chromatography (using 40% ethyl acetate in petroleum ether as the eluent) to give the title compound as a yellow solid (750 mg). 1 1H NMR (CDCl3): δ 7.85 (s, 1H), 7.78 (s, 1H), 7.52 - 7.47 (m, 1H), 7.17 - 7.19 (m, 1H), 6.97 - 6.88 (m, 1H), 3.8 (s, 3H), 1.96 (s, 3H), 1.49 (s, 9H).

[0207] Step B: Preparation of 4-(2-chloro-4-fluorophenyl)-N-(2-fluoro-4-methyl-6-nitrophenyl)-1,3-dimethyl-1H-pyrazol-5-amine A mixture of N-tert-butyl-N-(4-bromo-2-fluoro-6-nitrophenyl)-N-[4-(2-chloro-4-fluorophenyl)-1,3-dimethyl-1H-pyrazol-5-yl]carbamate (i.e., the product of Step A) (600 mg, 1.07 mmol), potassium carbonate (372 mg, 2.7 mmol), dichloro[1,1'-bis(diphenylphosphino)ferrocene]palladium(II) dichloromethane complex (1:1) (40 mg, 0.05 mmol) and trimethylboroxine (0.54 mL, 3.9 mmol) in 1,4-dioxane (20 mL) was heated under reflux for 3 h. The reaction mixture was diluted with water (15 mL) and extracted with ethyl acetate (2 × 10 mL). The combined organic extracts were washed with saturated aqueous sodium chloride solution (3 × 5 mL), dried over sodium sulfate, filtered and concentrated under reduced pressure. The resulting material was dissolved in dichloromethane and trifluoroacetic acid (3:1; 4 mL) and stirred at room temperature for 16 h. The reaction mixture was concentrated under reduced pressure and the resulting material was dissolved in dichloromethane (5 mL) and washed with saturated aqueous sodium hydrogen carbonate solution (2 mL). The aqueous layer was further extracted with dichloromethane (3 × 10 mL). The combined organic extracts were washed with saturated sodium chloride solution, dried over sodium sulfate, filtered and concentrated under reduced pressure. The resulting material was purified by silica gel column chromatography (using 40% ethyl acetate in petroleum ether as the eluent) to give the title compound, a yellow solid (210 mg), which is the compound of the present invention. 1 H NMR (CDCl3) δ 8.41 (s, 1H), 7.45 (s, 1H), 7.24 - 7.15 (m, 2H), 7.1 - 7.01 (m, 2H), 3.72 (s, 3H), 2.15 (s, 3H), 1.95 (s, 3H).

Example

[0208] Alternative preparation of 3-chloro-4-[5-[(2-fluoro-6-nitrophenyl)amino]-1,3-dimethyl-1H-pyrazol-4-yl]benzonitrile (Compound 113) Step A: Preparation of 1-methyl-hydrazinecarbonitrile A solution of cyanogen bromide (13.5 g, 127.5 mmol) and dichloromethane (250 mL) was cooled to 0 °C, and then a mixture of methylhydrazine (85% aqueous solution, 6.0 g, 127.5 mmol), sodium carbonate (7.5 g, 63.9 mmol) and water (60 mL) was added dropwise with vigorous stirring. After the obvious signs of gas generation ceased, the aqueous layer was separated and extracted with dichloromethane (3×). The combined organic layers were dried over magnesium sulfate, filtered, and the filtrate was concentrated under reduced pressure to give the title compound as an oil (6.0 g).

[0209] Step B: Preparation of 4-(5-amino-1,3-dimethyl-1H-pyrazol-4-yl)-3-chloro-benzonitrile A mixture of 3-chloro-4-(2-oxopropyl)benzonitrile (13.7 g, 71.4 mmol) and 1-methylhydrazinecarbonitrile (i.e., the product of Step A) (6.0 g, 86 mmol) was heated at 60 °C with stirring. After 48 h, the reaction mixture was dissolved in dichloromethane (100 mL) and water (100 mL), the layers were separated, and the aqueous layer was extracted with dichloromethane (3×). The combined organic layers were dried over magnesium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The resulting material was purified by silica gel column chromatography (using 60% ethyl acetate in petroleum ether as the eluent) to give the title compound as a pale yellow solid (8.1 g). LCMS: 247 (M+1)

[0210] Step C: Preparation of 3-chloro-4-[5-[(2-fluoro-6-nitrophenyl)amino]-1,3-dimethyl-1H-pyrazol-4-yl]benzonitrile A mixture of 4-(5-amino-1,3-dimethyl-1H-pyrazol-4-yl)-3-chlorobenzonitrile (i.e., the product of Step B) (1.2 g, 4.8 mmol) in tetrahydrofuran (40 mL) at 0 °C was added dropwise with potassium tert-butoxide (9.7 mL, 1 M in tetrahydrofuran). The reaction mixture was stirred at 0 °C for 1 h, then 1,2-difluoro-3-nitrobenzene (0.85 g, 5.3 mmol) was added dropwise and stirring was continued at 0 °C for an additional 30 min. The reaction mixture was diluted with saturated aqueous ammonium chloride and ethyl acetate (100 mL), and these layers were separated. The aqueous layer was extracted with ethyl acetate (40 mL × 2), the combined organic extracts were washed with saturated aqueous sodium chloride, dried over magnesium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The resulting material was purified by silica gel column chromatography (using 40% ethyl acetate in petroleum ether as the eluent) to yield a yellow solid. The yellow solid was crystallized from ethanol to produce the title compound, which is a compound of the present invention, as a light yellow solid (560 mg). 1 H NMR (CDCl3) δ 8.71 (d, 1H), 7.85 (d, 1H), 7.63 - 7.58 (m, 2H), 7.33 - 7.25 (m, 2H), 6.86 - 6.82 (m, 1H), 3.75 (s, 3H), 1.99 (s, 3H). LCMS: 386 (M+1).

[0211] By the procedures described herein together with methods known in the art, the compounds disclosed in the following table can be prepared. The following abbreviations are used in the table shown below. Me means methyl, MeO means methoxy, EtO means ethoxy, and CN means cyano.

[0212]

Table 1

[0213] The present disclosure also includes Tables 1A to 46A, and the column headings in Table 1 (i.e., "R2 is CH3, and R 3 is Cl, and (R 4 ) m is 4-F”) is replaced with the respective headings of the respective columns shown below, and each of them is composed of the same as Table 1 above.

[0214]

Table 2

Table 3

[0215]

Table 4

[0216] Complex / Usefulness (Including N-oxides, hydrates, and salts thereof) The compounds of formula 1 of the present invention are generally used as a fungicidally active ingredient in a composition, i.e., a formulation, together with at least one additional component selected from the group consisting of surfactants, solid excipients, and liquid excipients that act as carriers. The formulation or composition components are selected to be compatible with the physical properties of the active ingredient, the mode of application as well as environmental factors such as soil type, moisture, and temperature.

[0217] Useful formulations include liquid compositions and solid compositions. Liquid compositions include solutions (including emulsions), suspensions, emulsions (including microemulsions and / or suspoemulsions), etc., which can optionally be concentrated into gels. Common types of aqueous liquid compositions are soluble concentrates, suspension concentrates, capsule suspensions, concentrated emulsions, microemulsions, and suspoemulsions. Common types of non-aqueous liquid compositions are emulsions, microemulsions, dispersible concentrates, and oil dispersions.

[0218] Common types of solid compositions are powders, dusts, granules, pellets, pills, aromatic tablets, tablets, filled films (including seed film coatings), etc., which may be water-dispersible ("wettable") or water-soluble. Films and coatings formed from film-forming liquids or flowable suspensions are particularly useful for seed treatment. The active ingredient can be placed in (micro)capsules and further formed into suspensions or solid formulations; alternatively, the entire formulation of the active ingredient can be placed in (or "coated with") capsules. Capsule filling can control or delay the release of the active ingredient. Emulsifiable granules combine the advantages of both emulsion formulations and dry granular formulations. High-strength compositions are mainly used as intermediates for further formulations.

[0219] Sprayable formulations are usually diluted in a suitable medium before spraying. Such liquid and solid formulations are formulated to be easily diluted in the spraying medium, which is usually water, but sometimes another suitable medium such as an aromatic or paraffinic hydrocarbon or vegetable oil. The application rate can range from about 1 to several thousand liters per hectare, but more commonly within the range of about 10 to several hundred liters per hectare. Sprayable formulations can be in a tank mixed with water or another suitable medium for foliar treatment by aerial or ground application, or for application to the plant growth medium. Liquid and dry formulations can be supplied directly while metering into a drip irrigation system or metered into the furrows during planting. Liquid and solid formulations can be applied to crop seeds and pre-planting seeds for other desired vegetation to protect the growth of roots and other underground plant parts and / or foliage through uptake of the systemic pesticide.

[0220] The present formulation usually contains effective amounts of the active ingredient, excipients and surfactants within the following approximate ranges, which add up to 100 weight percent.

[0221] [Table 5]

[0222] Examples of solid excipients include clays such as bentonite, montmorillonite, attapulgite and kaolin, gypsum, cellulose, titanium dioxide, zinc oxide, starch, dextrin, saccharides (e.g., lactose, sucrose), silica, talc, mica, diatomaceous earth, urea, calcium carbonate, sodium carbonate, sodium hydrogen carbonate, and sodium sulfate. Typical solid excipients are described in Watkins et al., Handbook of Insecticide Dust Diluents and Carriers, 2nd Edition, Dorland Books, Caldwell, New Jersey.

[0223] Liquid excipients include, for example, water, N,N-dimethylalkanamide (e.g., N,N-dimethylformamide), limonene, dimethyl sulfoxide, N-alkylpyrrolidone (e.g., N-methylpyrrolidinone), alkyl phosphate (e.g., triethyl phosphate), ethylene glycol, triethylene glycol, propylene glycol, dipropylene glycol, polypropylene glycol, propylene carbonate, butylene carbonate, paraffin (e.g., white mineral oil, normal paraffin, isoparaffin), alkylbenzene, alkylnaphthalene, glycerin, glyceryl triacetate, sorbitol, aromatic hydrocarbons, de-aromatized aliphatic compounds, alkylbenzene, alkylnaphthalene, ketones such as cyclohexanone, 2-heptanone, isophorone and 4-hydroxy-4-methyl-2-pentanone, acetates such as isoamyl acetate, hexyl acetate, heptyl acetate, octyl acetate, nonyl acetate, tridecyl acetate and isobornyl acetate, other esters such as alkylated lactate ester, dibasic acid esters, alkyl benzoate, aryl benzoate and γ-butyrolactone, and alcohols which can be straight-chain, branched, saturated or unsaturated, such as methanol, ethanol, n-propanol, isopropyl alcohol, n-butanol, isobutyl alcohol, n-hexanol, 2-ethylhexanol, n-octanol, decanol, isodecyl alcohol, isooctadecanol, cetyl alcohol, lauryl alcohol, tridecyl alcohol, oleyl alcohol, cyclohexanol, tetrahydrofurfuryl alcohol, diacetone alcohol, cresol and benzyl alcohol. Liquid excipients include saturated and unsaturated fatty acids (usually C6~C 22) also includes glycerin esters. The liquid excipients include alkylated fatty acids (e.g., methylated, ethylated, butylated), and the fatty acids can be obtained by hydrolysis of glycerin esters derived from plant and animal sources and can be purified by distillation. Typical liquid excipients are described in Marsden, Solvents Guide, 2nd Edition, Interscience, New York, 1950.

[0224] The solid and liquid compositions of the present invention often include one or more surfactants. When added to a liquid, a surfactant (also known as a "surface-active agent") generally modifies and often reduces the surface tension of the liquid. Depending on the nature of the hydrophilic and lipophilic groups in the surfactant molecule, the surfactant can be useful as a wetting agent, dispersing agent, emulsifying agent or defoaming agent.

[0225] Surfactants can be classified as nonionic, anionic or cationic. Useful nonionic surfactants for the present compositions include, but are not limited to, alcohol alkoxylates based on natural and synthetic alcohols (branched or straight-chain) and alcohol alkoxylates made from alcohols and ethylene oxide, propylene oxide, butylene oxide or mixtures thereof; amine ethoxylates, alkanolamides and ethoxylated alkanolamides; ethoxylated soybean oil, h Alkoxylated triglycerides such as machine oil and rapeseed oil; alkylphenol alkoxylates such as octylphenol ethoxylate, nonylphenol ethoxylate, dinonylphenol ethoxylate and dodecylphenol ethoxylate (produced from phenol and ethylene oxide, propylene oxide, butylene oxide or mixtures thereof); block polymers produced from ethylene oxide or propylene oxide and reverse block polymers with terminal blocks produced from propylene oxide; ethoxylated fatty acids; ethoxylated fatty esters and oils; ethoxylated methyl esters; ethoxylated tristyrylphenol (including those produced from ethylene oxide, propylene oxide, butylene oxide or mixtures thereof); polyethoxylated esters such as fatty acid esters, glycerin esters, lanolin-based derivatives, polyethoxylated sorbitan fatty acid esters, polyethoxylated sorbitol fatty acid esters and polyethoxylated glycerin fatty acid esters; other sorbitan derivatives such as sorbitan esters; polymer surfactants such as random copolymers, block copolymers, alkyl peg (polyethylene glycol) resins, graft polymers or comb polymers and star polymers; polyethylene glycols (pegs); polyethylene glycol fatty acid esters; silicone-based surfactants; and sugar-derivatives such as sucrose esters, alkyl polyglycosides and alkyl polysaccharides are included.

[0226] Useful anionic surfactants include, but are not limited to, alkylaryl sulfonic acids and their salts; carboxylated alcohols or alkylphenol ethoxylates; diphenyl sulfonate derivatives; lignin derivatives such as lignin and lignosulfonates; maleic acid or succinic acid or their anhydrides; olefin sulfonates; phosphate esters of alcohol alkoxylates, phosphate esters of alkylphenol alkoxylates and phosphate esters of styrylphenol ethoxylates; protein-based surfactants; sarcosine derivatives; styrylphenol ether sulfates; sulfates and sulfonates of oils and fatty acids; sulfates and sulfonates of ethoxylated alkylphenols; sulfates of alcohols; sulfates of ethoxylated alcohols; amine sulfonates and amide sulfonates such as N,N-alkyltaurine salts; benzenesulfonates, cumenesulfonates, toluenesulfonates, xylenesulfonates, and dodecylsulfonic acid and tridecylbenzenesulfonic acid; condensed naphthalenesulfonates; naphthalenesulfonates and alkylnaphthalenesulfonates; fractionated petroleum sulfonates; sulfosuccinamates; and their derivatives such as sulfosuccinates and dialkylsulfosuccinates.

[0227] Useful cationic surfactants include, but are not limited to, amides and ethoxylated amides; amines such as N-alkylpropanediamine, tripropylenetriamine and dipropylenetetraamine, and ethoxylated amines, ethoxylated diamines and propoxylated amines (produced from 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 oxide and bis-(2-hydroxyethyl)-alkylamine oxide.

[0228] Also useful for this composition are mixtures of nonionic and anionic surfactants or mixtures of nonionic and cationic surfactants. Nonionic, anionic and cationic surfactants and their recommended uses are disclosed in various 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, 7th Edition, John Wiley and Sons, New York, 1987, among other published references.

[0229] The composition of the present invention can also contain formulation aids and additives known to those skilled in the art as formulation adjuvants. Such formulation aids and additives include pH (buffers), foaming during processing (antifoaming, such as Rhodorsil® 416), sedimentation of the active ingredient (suspending agents), viscosity (thixotropic thickeners), growth of microorganisms in the container (antimicrobial agents), freezing of the product (antifreeze), color (pigment / dye dispersion, such as Pro-lzed® red colorant), wash-off (film-forming agents or stickers), evaporation (evaporation retardants), and other formulation properties can be controlled. Film-forming agents include, for example, polyvinyl acetate, polyvinyl acetate copolymers, polyvinylpyrrolidone-vinyl acetate copolymers, polyvinyl alcohol, polyvinyl alcohol copolymers, and waxes. Examples of formulation aids and additives include those shown in McCutcheon’s Division, McCutcheon’s Volume 2: Functional Materials, published by The Manufacturing Confectioner Publishing Co., annual International and North American editions; and those shown in PCT International Publication WO03 / 024222.

[0230] The compound of formula 1 and any other active ingredient are usually incorporated into the composition by dissolving the active ingredient in a solvent or by grinding in a liquid or dry excipient. Solutions, including emulsions, can be prepared by simply mixing these components. If the solvent of the liquid composition intended for use as an emulsion is water-insoluble, an emulsifier is usually added and after dilution with water, the active ingredient-containing solvent is emulsified. An active ingredient slurry with a particle size up to 2,000 μm can be wet-milled using a media mill to obtain particles with an average diameter of less than 3 μm. The aqueous slurry may become the final suspension concentrate (see, for example, U.S. 3,060,084) or can be further processed by spray drying to form water-dispersible granules. Dry formulations usually require a dry grinding process, which produces in the range of an average particle size of 2 - 10 μm. Powders and dusts can be manufactured by blending (such as by a hammer mill or a fluid energy mill) and usually grinding. Granules and pellets can be manufactured by spraying the active substance onto a preformed granular carrier or by agglomeration techniques. Browning, "Agglomeration", Chemical Engineering, December 4, 1967, pp147 - 48, Perry’s Chemical Engineer’s Handbook, 4th Edition, McGraw-Hill, New York, 1963, pp8 - 57 and the following, and see WO91 / 13546. Pellets can be manufactured as described in U.S. 4,172,714. Water-dispersible and water-soluble granules can be manufactured as taught in U.S. 4,144,050, U.S. 3,920,442 and DE3,246,493. Tablets can be manufactured as taught in U.S. 5,180,587, U.S. 5,232,701 and U.S. 5,208,030. Films can be manufactured as taught in GB2,095,558 and U.S. 3,299,566.

[0231] One embodiment of the present invention relates to a method for controlling a fungal pathogen, comprising the steps of diluting a fungicidal composition of the present invention (a compound of formula 1 or a mixture of a compound of formula 1 and at least one other fungicide formulated with a surfactant, a solid excipient and a liquid excipient) with water, optionally adding an adjuvant to form a diluted composition, and contacting a fungal pathogen or its environment with an effective amount of said diluted composition. The spray composition is formed by dilution with water, but a sufficient concentration of the fungicidal composition can exhibit sufficient efficacy to control the fungal pathogen, and separately formulated adjuvant products can also be added to the spray tank mixture. These additional adjuvants are commonly known as "spray adjuvants" or "tank mix adjuvants" and include any substances mixed in the spray tank to improve the performance of the pesticide or to modify the physical properties of the spray mixture. The adjuvant can be an anionic or non-ionic surfactant, an emulsifier, a petroleum-based crop oil, a crop-derived seed oil, an acidifying agent, a buffering agent, a thickening agent or an antifoaming agent. The adjuvant is used to enhance efficacy (e.g., bioavailability, adhesion, penetration, coating uniformity and protection persistence) or to minimize or eliminate problems associated with spray application such as incompatibility, foaming, drift, evaporation, volatilization and decomposition. To obtain optimal performance, the adjuvant is selected based on the properties of the active ingredient, formulation and target (e.g., crop, pest).

[0232]

[0233] ​The amount of adjuvant added to the spray mixture generally ranges from about 2.5% to 0.1% by volume. The application rate of the adjuvant added to the spray mixture is usually between about 1 and 5 L per hectare. Representative examples of spray adjuvants include: Adigor® (Syngenta) 47% methylated rapeseed oil in liquid hydrocarbons, Silwet® (Helena Chemical Company) polyalkylene oxide-modified heptamethyltrisiloxane, and Assist® (BASF) 17% surfactant blend in 83% paraffinic mineral oil.

[0234] One method of seed treatment is by spraying or dusting the seeds with the compounds of the present invention (i.e., as the formulated composition) prior to sowing. The composition formulated for seed treatment generally contains a film-forming agent or an adhesive. Thus, the seed dressing composition of the present invention usually contains a biologically effective amount of the compound of formula 1 and a film-forming agent or an adhesive. The seeds can be coated by directly spraying a flowable suspension concentrate onto a tumbling bed of seeds and then drying the seeds. Alternatively, other formulation types such as wet powders, solutions, suspoemulsions, emulsions, and emulsions in water can be sprayed onto the seeds. This method is particularly useful for applying a film coating to seeds. A variety of coating machines and methods are available to those skilled in the art. Suitable methods include those shown in P. Kosters et al., Seed Treatment: Progress and Prospects, 1994 BCPC Mongraph No. 57, and references cited therein.

[0235] For further information on the field of formulations, 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, column 6, lines 16 to column 7, line 19 and Examples 10-41; U.S. 3,309,192, column 5, line 43 to column 7, line 62 and Examples 8, 12, 15, 39, 41, 52, 53, 58, 132, 138-140, 16 2-164, 166, 167 and 169-182; U.S. 2,891,855, column 3, line 66 to column 5, line 17 and Examples 1-4; Klingman, Weed Control as a Science, John Wiley and Sons, Inc., New York, 1961, pp81-96; Hance et al., Weed Control Handbook, 8th Edition, Blackwell Scientific Publications, Oxford, 1989; and Developments in formulation technology, PJB Publications, Richmond, UK, 2000.

[0236] In the following examples, all percentages are by weight and all formulations are prepared in a conventional manner. Compound numbers refer to the compounds in Index Tables A - B. 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. Accordingly, the following examples are to be construed as merely illustrative and not limitative of the disclosure in any way whatsoever.

[0237] Example A [Table 6]

[0238] Example B

Table 7

[0239] Example C

Table 8

[0240] Example D

Table 9

[0241] Example E

Table 10

[0242] Example F

Table 11

[0243] Example G

Table 12

[0244] Example H

Table 13

[0245] Example I

Table 14

[0246] Example J

Table 15

[0247] Example K [Table 16]

[0248] Example L [Table 17]

[0249] Water-soluble and water-dispersible formulations are usually diluted with water to form an aqueous composition prior to application. An aqueous composition (e.g., a spray tank composition) for direct application to a plant or a part thereof usually contains at least about 1 ppm or more (e.g., 1 ppm to 100 ppm) of the compound(s) of the present invention.

[0250] Seeds are usually treated at a rate of about 0.001 g (more generally, about 0.1 g) to about 10 g (i.e., about 0.0001 to 1 wt% of the seed before treatment) per kilogram of seeds. The flowable suspension formulated for seed treatment usually contains about 0.5 to about 70% of the active ingredient, about 0.5 to about 30% of the film-forming adhesive, about 0.5 to about 20% of the dispersing agent, 0 to about 5% of the thickening agent, 0 to about 5% of the pigment and / or dye, 0 to about 2% of the antifoaming agent, 0 to about 1% of the preservative, and 0 to about 75% of the volatile liquid excipient.

[0251] The compounds of the present invention are useful as plant disease control agents. Accordingly, the present invention further includes a method for controlling plant diseases caused by fungal plant pathogens, which comprises applying an effective amount of the compound of the present invention or a fungicidal composition containing the compound to a plant to be protected or a part thereof, or to the seeds of the plant to be protected. The compounds and / or compositions of the present invention provide control of diseases caused by a wide range of fungal plant pathogens in the Ascomycota, Basidiomycota, Zygomycota, and oomycete classes of fungus-like organisms. They are effective in controlling a wide range of plant diseases, particularly leaf pathogens of flowers, turf, vegetables, field crops, grains, and fruit crops. These pathogens include, but are not limited to, those shown in Table 1-1. For Ascomycetes and Basidiomycetes, the names for the sexual / perfect stage / teleomorph and the asexual / imperfect stage / anamorph (in parentheses) are shown where known. Synonymous names for pathogens are indicated by an equal sign. For example, the sexual / perfect stage / teleomorph name Phaeosphaeria nodorum is followed by the corresponding asexual / imperfect stage / anamorph name Stagnospora nodorum and the synonymous older name Septoria nodorum.

[0252] [Table 18] [Table 19]

[0253] In addition to their fungicidal activity, the compositions or combinations also have activity against bacteria such as Erwinia amylovora, Xanthomonas campestris, Pseudomonas syringae, and other related species. To control harmful microorganisms By doing so, the compounds of the present invention are useful for improving (i.e., increasing) the ratio of beneficial microorganisms to harmful microorganisms upon contact with crop plants or their vegetative propagules (e.g., seeds, bulbs, corms, tubers, cuttings) or in the agronomic environment of crop plants or their vegetative propagules.

[0254] The compounds of the present invention are useful for treating all plants, plant parts and seeds. Varieties and cultivars of plants and seeds can be obtained by conventional breeding and breeding methods or genetic engineering methods. Genetically modified plants or seeds (transgenic plants or seeds) are those in which a heterologous gene (transgene) is stably integrated into the genome of the plant or seed. The transgene, defined by its specific position in the plant genome, is called a transformation or transgene event.

[0255] Genetically modified plant varieties that can be treated according to the present invention include those that are resistant to one or more biotic stresses (pests such as nematodes, insects, mites, fungi, etc.) or abiotic stresses (drought, low temperature, soil salinity, etc.), or those that include other desired characteristics. The plant can be genetically modified to exhibit traits such as herbicide tolerance, insect resistance, modified oil profile or drought tolerance.

[0256] Treatment of genetically modified plants and seeds with the compounds of the present invention can result in supra-additive or enhanced effects. For example, a decrease in application rate, broadening of the activity spectrum, increase in resistance to biotic / abiotic stresses or enhancement of storage stability can exceed the prediction from mere additive effects of the application of the compounds of the present invention to genetically modified plants and seeds.

[0257] The compounds of the present invention are useful for the treatment of seeds to protect them from plant diseases. In the context of the present disclosure and claims, treating a seed means bringing into contact the seed with a biologically effective amount of a compound of the present invention, which is usually formulated as a composition of the present invention. This treatment of the seeds protects the seeds from soil-borne pathogen and can generally also protect the roots and other plant parts by contacting the soil of the seedlings growing from the germinated seeds. The treatment of the seeds can also protect the foliage by translocation of the compound of the present invention or a second active ingredient within the growing plant. The treatment of the seeds can be applied to all types of seeds, including those of plants genetically transformed to express a differentiated trait, including those that germinate. Representative examples include those that express a protein toxic to invertebrate pests such as the Bacillus thuringiensis toxin or those that express herbicide resistance such as glyphosate acetyltransferase that exhibits resistance to glyphosate. Treatment of seeds with the compounds of the present invention can also enhance the vigor of plants growing from the seeds.

[0258] The compounds of the present invention and their compositions are particularly useful in the treatment of crop seeds, including but not limited to, maize or corn, soybeans, cotton, cereals (e.g., wheat, rye, barley, oats and rice), potatoes, vegetables and oilseed rape, alone and in combination with other fungicides, nematicides and insecticides.

[0259] Furthermore, the compounds of the present invention are useful for treating storage diseases of fruits and vegetables caused by fungi and bacteria. These infections can occur before, during, and after harvest. For example, an infection can occur before harvest and then remain dormant until a certain point during ripening (e.g., the host begins to undergo tissue changes in such a way that the infection can progress); also, an infection can result from surface wounds created by mechanical or insect damage. In this regard, the compounds of the present invention can reduce losses (i.e., losses due to quantity and quality) caused by storage diseases that can occur during any period from harvest to consumption. By treating storage diseases with the compounds of the present invention, perishable edible plant parts (e.g., fruits, seeds, foliage, stems, bulbs, tubers) can have an increased period of storage, either refrigerated or unrefrigerated after harvest, remain edible, and have no notable or harmful decomposition or contamination by fungi or other microorganisms. By treating edible plant parts before or after harvest with the compounds of the present invention, the formation of toxic metabolites of fungi or other microorganisms, such as mycotoxins like aflatoxin, can also be reduced.

[0260] Plant disease control is generally achieved by applying an effective amount of the compounds of the present invention to the parts of the plant to be protected, such as roots, stems, foliage, fruits, seeds, tubers, or bulbs, or to the medium (soil or sand) in which the plant to be protected is growing, either before or after infection. The compound can also be applied to seeds to protect the seeds and the seedlings growing from the seeds. The compound can also be applied by irrigation water for treating plants. Control of post-harvest pathogens that infect pre-harvest products is usually achieved by field application of the compounds of the present invention, and when the infection occurs post-harvest, the compound can be applied to the harvested crop as a dip, spray, fumigant, treated wrap, and box liner.

[0261] The compound can also be applied using an unmanned aerial vehicle (UAV) for the dispension of the compositions disclosed herein onto the cropped area. In some embodiments, the cropped area is an area containing crops. In some embodiments, the crops are selected from monocotyledonous or dicotyledonous plants. In some embodiments, the crops are selected from rice, corn, wheat, soybean, barley, vegetables, tobacco, tea trees, fruit trees, and sugarcane. In some embodiments, the compositions disclosed herein are formulated for ultra-low volume spraying. The product applied by the drone may use water or oil as a spraying carrier. Typical application rates (including the product) are used in the case of drone application on a global scale. 5.0 liters per hectare to 100 liters per hectare (approximately 0.5 to 10 gpa). This includes the range from ultra-low volume (ULV) to low volume (LV) application rates. Although not common, there may be situations where even lower application rates can be used, up to 1.0 liter per hectare (0.1 gpa).

[0262] The application rates (i.e., the amount effective as a fungicide) for these compounds may be affected by factors such as the plant disease to be controlled, the plant species to be protected, and the ambient moisture and temperature, and should be determined under actual use conditions. A person skilled in the art can easily determine the amount effective as a fungicide required for the desired level of plant disease control by simple experiments. The foliage can usually be protected when treated at a rate of less than about 1 g per hectare to about 5,000 g per hectare of the active ingredient. The seeds and seedlings can usually be protected when the seeds are treated at a rate of about 0.001 g (more typically, about 0.1 g) to about 10 g per kilogram of seeds.

[0263] The compounds of the present invention can be mixed with one or more other bioactive compounds or agents such as fungicides, insecticides, nematicides, bactericides, acaricides, herbicides, herbicide safeners, insect growth regulators such as insect molting inhibitors and root growth stimulants, chemosterilants, semiochemicals, repellents, attractants, pheromones, feeding stimulants, plant nutrients, other bioactive compounds or entomopathogenic bacteria, viruses or fungi, in order to form multi-component pesticides that provide an even broader range of agricultural protection. Accordingly, the present invention also relates to a composition comprising a compound of formula 1 in an amount effective as a fungicide and at least one additional bioactive compound or agent in a biologically effective amount, which may further comprise at least one of a surfactant, a solid excipient or a liquid excipient. The other bioactive compound or agent can be formulated in a composition comprising at least one of a surfactant, a solid or a liquid excipient. In the case of the mixtures of the present invention, one or more other bioactive compounds or agents can be formulated together with the compound of formula 1 to form a premix, or one or more other bioactive compounds or agents can be formulated separately from the compound of formula 1 and the formulations are combined together (e.g., in a spray tank) prior to application or applied sequentially. As mentioned in the summary of the invention, one aspect of the present invention is a fungicidal composition comprising 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) (i.e., a mixture or combination thereof). It is noted that such combinations are when the other fungicidal active ingredients have a different site of action than the compound of formula 1. In certain cases, combinations with at least one other fungicidal active ingredient having a similar spectrum of control but a different site of action are particularly advantageous for resistance management. Accordingly, the composition of the present invention can further comprise an effective amount of a fungicide of at least one additional fungicidal active ingredient having a similar spectrum of control but a different site of action.

[0264] As set forth in the summary of the invention, one aspect of the present invention is a fungicidal composition comprising 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) (i.e., a mixture or combination thereof). It is noted that such combinations are when the other fungicidal active ingredients have a different site of action than the compound of formula 1. In certain cases, combinations with at least one other fungicidal active ingredient having a similar spectrum of control but a different site of action are particularly advantageous for resistance management. Accordingly, the composition of the present invention can further comprise an effective amount of a fungicide of at least one additional fungicidal active ingredient having a similar spectrum of control but a different site of action.

[0265] It should be noted that, in addition to the compound of formula 1 of component (a), as component (b), at least one fungicidal compound selected from the group consisting of the 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 walls, (P) host plant defense induction, multi-site contact activity and unknown mode of action defined by FRAC is included in the composition.

[0266] Together with those FRAC target site codes belonging to the above MOA class, the target sites recognized or proposed by FRAC are: (A1) RNA polymerase I, (A2) adenosine deaminase, (A3) DNA / RNA synthesis (proposed), (A4) DNA topoisomerase, (B1 - B3) β-tubulin aggregates during mitosis, (B4) cell division (proposed), (B5) delocalization of spectrin-like proteins, (C1) complex I NADH oxidoreductase, (C2) complex II: succinate dehydrogenase, (C3) complex III: cytochrome bc1 (ubiquinol oxidase) at the Qo site, (C4) complex III: cytochrome bc1 (ubiquinone reductase) at the Qi site, (C5) uncoupler of oxidative phosphorylation, (C6) inhibitor of oxidative phosphorylation, ATP synthase, (C7) ATP production (proposed), (C8) complex III: cytochrome bc1 (ubiquinone reductase) at the Qx (unknown) site, (D1) methionine biosynthesis (proposed), (D2 - D5) protein synthesis, (E1) signal transduction (unknown mechanism), (E2 - E3) MAP / histidine kinase in osmoregulatory signal transduction, (F2) phospholipid biosynthesis, methyltransferase, (F3) lipid peroxidation (proposed), (F4) cell membrane permeability, fatty acids (proposed), (F6) microbial disrupter of the pathogen cell membrane, (F7) cell membrane disruption (proposed), (G1) C14-demethylase in sterol biosynthesis, (G2) Δ14-reductase and Δ8→Δ7-isomerase in sterol biosynthesis, (G3) 3-ketoreductase, C4-demethylation, (G4) squalene epoxidase in sterol biosynthesis, (H3) trehalase and inositol biosynthesis, (H4) chitin synthase, (H5) cellulose synthase, (I1) reductase in melanin biosynthesis and (I2) dehydratase in melanin biosynthesis.

[0267] Particularly noteworthy is that in addition to the compound of Formula 1 of Component (a), as Component (b), (b1) 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; (b7) succinate dehydrogenase inhibitor fungicides; (b8) hydroxy(2-amino- (b9) Anilinopyrimidine fungicides; (b10) Phenyl N-carbamate fungicides; (b11) Quinone outside inhibitors (QoI) fungicides; (b12) Phenylpyrrole fungicides; (b13) Azanaphthalene fungicides; (b14) Lipid peroxidation inhibitor fungicides; (b15) Melanin biosynthesis inhibitor - reductase (MBI-R) fungicides; (b16) Melanin biosynthesis inhibitor - dehydratase (MBI-D) fungicides; (b17) Sterol biosynthesis inhibitors (SBI): Class III fungicides; (b18) Squalene - epoxidase inhibitor fungicides; (b19) Polyoxins fungicides; (b20) Phenylurea fungicides; (b21) Quinone inside inhibitors (QiI) fungicides; (b22) Benzamide and thiazole carboxamide fungicides; (b23) Enopyranuronic acid antibiotic fungicides; (b24) Hexopyranosyl antibiotic fungicides; (b25) Glucopyranosyl antibiotics: Protein synthesis fungicides; (b26) Glucopyranosyl antibiotics: Trehalase and inositol biosynthesis fungicides; (b27) Cyanoacetamide oxime fungicides; (b28) Carbamate fungicides; (b29) Oxidative phosphorylation uncoupling fungicides; (b30) Organotin fungicides; (b31) Carboxylic acid fungicides; (b32) Heteroaromatic fungicides; (b33) Phosphate fungicides; (b34) Phthalamic acid fungicides; (b35) Benzotriazine fungicides; (b36) Benzene - sulfonamide fungicides; (b37) Pyridazinone fungicides; (b38) Thiophene - carboxamide fungicides; (b39) Complex I NADH oxidoreductase inhibitor fungicides; (b40) Carboxylic acid amide (CAA) fungicides; (b41) Tetracycline antibiotic fungicides; (b42) Thiocarbamate fungicides; (b43) Benzamide fungicides; (b44) Microbial fungicides; (b45) QxI fungicides; (b46) Plant extract fungicides; (b47) Host plant defense induction fungicides; (b48) Multi-site contact active fungicides; and at least one fungicidal compound selected from the group consisting of fungicides other than those of classes (b1) to (b48) and salts of compounds of classes (b1) to (b48).

[0268] Further explanations of these classes of fungicidal compounds are shown below.

[0269] (b1) The "methyl benzimidazole carbamate (MBC) fungicide" (FRAC code 1) inhibits mitosis by binding to β-tubulin in microtubule assembly. By inhibiting microtubule assembly, it can interfere with cell division and be transported into cells and cell structures. Methyl benzimidazole carbamate fungicides include benzimidazole and thiophanate fungicides. Benzimidazoles include benomyl, carbendazim, fuberidazole, and thiabendazole. Thiophanates include thiophanate and thiophanate-methyl.

[0270] (b2) The "dicarboximide fungicide" (FRAC code 2) inhibits MAP / histidine kinase in osmotic signal transduction. Examples include chlozolinate, iprodione, procymidone, and vinclozolin.

[0271] (b3) The "demethylation inhibitor (DMI) fungicide" (FRAC code 3) (sterol biosynthesis inhibitor (SBI): class I) inhibits C14-demethylase, which plays a role in sterol production. Sterols such as ergosterol are necessary for membrane structures and functions that are essential for the growth of a functional cell wall. Therefore, exposure to these fungicides leads to abnormal growth and ultimately kills susceptible fungi. DMI fungicides are divided among several chemical classes: azoles (including triazoles and imidazoles), pyrimidines, piperazines, pyridines, and triazolylthiones. Triazoles include azaconazole, bitertanol, bromoconazole, cyproconazole, difenoconazole, diniconazole (including diniconazole-M), epoxiconazole, etaconazole, fenbuconazole, fluquinconazole, flusilazole, flutriafol, hexaconazole, imibenconazole, ipconazole, metcon It includes nazole, microbutanil, penconazole, propiconazole, quinconazole, simconazole, tebuconazole, tetraconazole, triadimefon, triadimenol, triticonazole, uniconazole, uniconazole-P, α-(1-chlorocyclopropyl)-α-[2-(2,2-dichlorocyclopropyl)ethyl]-1H-1,2,4-triazole-1-ethanol, rel-1-[[(2R,3S)-3-(2-chlorophenyl)-2-(2,4-difluorophenyl)-2-oxiranyl]methyl]-1H-1,2,4-triazole, rel-2-[[(2R,3S)-3-(2-chlorophenyl)-2-(2,4-difluorophenyl)-2-oxiranyl]methyl]-1,2-dihydro-3H-1,2,4-triazole-3-thione, and rel-1-[[(2R,3S)-3-(2-chlorophenyl)-2-(2,4-difluorophenyl)-2-oxiranyl]methyl]-5-(2-propen-1-ylthio)-1H-1,2,4-triazole. Imidazoles include econazole, imazalil, oxpoconazole, prochloraz, pefurazoate, and triflumizole. Pyrimidines include fenarimol, nuarimol, and triarimol. Piperazines include triforine. Pyridines include buthiobate, pyrifenox, pyrisoctazole (3-[(3R)-5-(4-chlorophenyl)-2,3-dimethyl-3-isoxazolidinyl]pyridine, a mixture of 3R,5R- and 3R,5S-isomers), and (αS)-[3-(4-chloro-2-fluorophenyl)-5-(2,4-difluorophenyl)-4-isoxazolyl]-3-pyridinemethanol. Triazolinethiones include prothioconazole and 2-[2-(1-chlorocyclopropyl)-4-(2,2-dichlorocyclopropyl)-2-hydroxybutyl]-1,2-dihydro-3H-1,2,4-triazole-3-thione.In biochemical investigations, all of the above-mentioned fungicides have been shown to be DMI fungicides as described by K.H. Kuck et al. in Modern Selective Fungicides - Properties, Applications and Mechanisms of Action, H. Lyr (ed.), Gustav Fischer Verlag: New York, 1995, pages 205 - 258.

[0272] (b4) "Phenylamide fungicides" (FRAC code 4) are specific inhibitors of RNA polymerase in oomycete fungi. Susceptible fungi exposed to these fungicides show a reduced ability to incorporate uridine into rRNA. The growth and development of susceptible fungi are prevented by exposure to this class of fungicides. Phenylamide fungicides include acylalanine, oxazolidinone, and butyrolactone fungicides. Acylalanine includes benalaxyl, benalaxyl-M (also known as kiralaxyl), furalaxyl, metalaxyl, and metalaxyl-M (also known as mefenoxam). Oxazolidinone includes oxadixyl. Butyrolactone includes ofurace.

[0273] (b5) "Amine / morpholine fungicides" (FRAC code 5) (SBI: class II) inhibit two target sites within the sterol biosynthesis pathway, Δ8→Δ7 isomerase and Δ14 reductase. Sterols such as ergosterol are required for membrane structures and functions that are essential for the growth of a functional cell wall. Therefore, exposure to these fungicides results in abnormal growth and ultimately kills susceptible fungi. Amine / morpholine fungicides (also known as non-DMI sterol biosynthesis inhibitors) include morpholine, piperidine, and spiroketal-amine fungicides. Morpholine includes aldimorph, dodemorph, fenpropimorph, tridemorph, and trimorphamide. Piperidine includes fenpropidin and piperalin. Spiroketal-amine includes spiroxamine.

[0274] (b6) "Phospholipid biosynthesis inhibitor fungicide" (FRAC code 6) inhibits the growth of fungi by acting on phospholipid biosynthesis. Phospholipid biosynthesis fungicides include phosphorothiolate and dithiolane fungicides. Phosphorothiolates include edifenphos, iprobenfos, and pyrazophos. Dithiolanes include isoprothiolane. By acting on it, the growth of fungi is suppressed. Phospholipid biosynthesis fungicides include phosphorothiolate and dithiolane fungicides. Phosphorothiolates include edifenphos, iprobenfos, and pyrazophos. Dithiolanes include isoprothiolane.

[0275] (b7) "Succinate dehydrogenase inhibitor (SDHI) fungicides" (FRAC code 7) inhibit the respiration of complex II fungi by interfering with the most important enzyme in the Krebs cycle (TCA cycle), named succinate dehydrogenase. By inhibiting respiration, the fungi are prevented from producing ATP and thus their growth and reproduction are suppressed. SDHI fungicides include phenylbenzamides, furancarboxamides, oxathiin carboxamides, thiazole carboxamides, pyrazole-4-carboxamides, pyridine carboxamides, phenyloxoethylthiophenamides and pyridinylethylbenzamides. Benzamides include benodanil, flutolanil and mepronil. Furancarboxamides include fenfuram. Oxathiin carboxamides include carboxin and oxycarboxin. Thiazole carboxamides include thifluzamide.Pyrazole-4-carboxamides include benzovindiflupyr (N-[9-(dichloromethylene)-1,2,3,4-tetrahydro-1,4-methanonaphthalen-5-yl]-3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxamide), bixafen, fluindapyr, fluxapyroxad (3-(difluoromethyl)-1-methyl-N-(3’,4’,5’-trifluoro[1,1’-biphenyl]-2-yl)-1H-pyrazole-4-carboxamide), flutolanil, isopyrazam (3-(difluoromethyl)-1-methyl-N-[1,2,3,4-tetrahydro-9-(1-methylethyl)-1,4-methanonaphthalen-5-yl]-1H-pyrazole-4-carboxamide), penflufen (N-[2-(1,3-dimethylbutyl)phenyl]-5-fluoro-1,3-dimethyl-1H-pyrazole-4-carboxamide), penthiopyrad, pidiflumetofen, sedaxane (N-[2-[1,1’-bicyclopropyl]-2-ylphenyl]-3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxamide), N-[2-(1S,2R)-[1,1’-bicyclopropyl]-2-ylphenyl]-3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxamide, 3-(difluoromethyl)-N-(2,3-dihydro-1,1,3-trimethyl-1H-inden-4-yl)-1-methyl-1H-pyrazole-4-carboxamide, N-[2-(2,4-dichlorophenyl)2-methoxy-1-methylethyl]-3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxamide and N-cyclopropyl-3-(difluoromethyl)-5-fluoro-1-methyl-N-[[2-(1-methylethyl)phenyl]methyl]-1H-pyrazole-4-carboxamide. Pyridinecarboxamides include boscalid. Phenyloxoethylthiopheneamides include isophentamid (N-[1,1-dimethyl-2-[2-methyl-4-(1-methylethoxy)phenyl]-2-oxoethyl]-3-methyl-2-thiophenecarboxamide). Pyridinylethylbenzamides include fluopyram.

[0276] (b8) "Hydroxy-(2-amino-)pyrimidine fungicides" (FRAC code 8) inhibit nucleic acid synthesis by interfering with adenosine deaminase. Examples include bupirimate, dimethirimol, and ethirimol.

[0277] (b9) "Anilinopyrimidine fungicides" (FRAC code 9) are proposed to inhibit the biosynthesis of the amino acid methionine and interfere with the secretion of hydrolases that lyse plant cells during infection. Examples include cyprodinil, mepanipyrim, and pyrimethanil.

[0278] (b10) "Phenyl N-carbamate fungicides" (FRAC code 10) inhibit mitosis by binding to β-tub ulin and disrupting microtubule assembly. By inhibiting microtubule assembly, cell division can be interfered with and it can be transported within cells and cell structures. Examples include diethofencarb.

[0279] (b11) The "quinone outside inhibitor (QoI) fungicide" (FRAC code 11) suppresses complex III mitochondrial respiration in fungi by acting on ubiquinol oxidase. The oxidation of ubiquinol is blocked at the "quinone outside" (Qo) site of the cytochrome bc1 complex, which is located in the inner mitochondrial membrane of fungi. By suppressing mitochondrial respiration, it prevents the normal growth and proliferation of fungi. Quinone outside inhibitor fungicides include methoxyacrylates, methoxycarbamates, oximinoacetates, oximinoacetamides, and dihydrodioxazine fungicides (collectively also known as strobilurin fungicides), as well as oxazolidinediones, imidazolinones, and benzylcarbamate fungicides. Methoxyacrylates include azoxystrobin, coumoxystrobin (methyl (αE)-2-[[(3-butyl-4-methyl-2-oxo-2H-1-benzopyran-7-yl)oxy]methyl]-α-(methoxymethylene)benzeneacetate), enoxastrobin (methyl (αE)-2-[[[(E)-[(2E)-3-(4-chlorophenyl)-1-methyl-2-propen-1-ylidene]amino]oxy]methyl]-α-(methoxymethylene)benzeneacetate) (also known as enestrobin), fluopicoxystrobin (methyl (αE)-2-[[2-chloro-4-(trifluoromethyl)phenoxy]methyl]-α-(methoxymethylene)benzeneacetate), picoxystrobin, and pyraoxystrobin (methyl (αE)-2-[[[3-(4-chlorophenyl)-1-methyl-1H-pyrazol-5-yl]oxy]methyl]-α-(methoxymethylene)benzeneacetate).Methoxycarbamates include pyraclostrobin, pyrametostrobin (methyl N-[2-[[(1,4-dimethyl-3-phenyl-1H-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). Oximinoacetates include kresoxim-methyl and trifloxystrobin. Oximinoacetamides include dimoxystrobin, fenaminstrobin ((αE)-2-[[[(E)-[(2E)-3-(2,6-dichlorophenyl)-1-methyl-2-propen-1-ylidene]amino]oxy]methyl]-α-(methoxyimino)-N-methylbenzeneacetamide), metominostrobin, orysastrobin, and α-[methoxyimino]-N-methyl-2-[[[1-[3-(trifluoromethyl)phenyl]ethoxy]imino]methyl]benzeneacetamide. Dihydrodioxazines include fluoxastrobin. Oxazolidinediones include famoxadone. Imidazolinones include fenamidone. Benzylcarbamates include pyribencarb. Class (b11) also includes mandestrobin (2-[(2,5-dimethylphenoxy)methyl]-α-methoxy-N-benzeneacetamide).

[0280] (b12) "Phenylpyrrole fungicides" (FRAC code 12) inhibit MAP / histidine kinases related to osmotic signal transduction in fungi. Fenpiclonil and fludioxonil are examples of this fungicide class.

[0281] (b13) The "azanaphthalene fungicides" (FRAC code 13) are proposed to inhibit signal transduction by an unknown mechanism. They have been shown to interfere with germination and / or appressorium formation in the fungi that cause powdery mildew. Azanaphthalene fungicides include aryloxyquinolines and quinazolinones. Arylo xyquinolines include quinoxyfen. Quinazolinones include proquinazid.

[0282] (b14) The "lipid peroxidation inhibitor fungicides" (FRAC code 14) are proposed to inhibit lipid peroxidation, which acts on membrane synthesis in fungi. Members of this class, such as etridiazole, can also act on other biological processes such as respiration and melanin biosynthesis. Lipid peroxidation fungicides include aromatic hydrocarbons and 1,2,4-thiadiazole fungicides. Aromatic hydrocarbon fungicides include biphenyl, chloroneb, dichloran, quintozene, tecnazene and tolclofos-methyl. 1,2,4-Thiadiazole includes etridiazole.

[0283] (b15) The "melanin biosynthesis inhibitor - reductase (MBI-R) fungicides" (FRAC code 16.1) inhibit the naphthalene reduction step in melanin biosynthesis. Melanin is required for host plant infection by some fungi. Melanin biosynthesis inhibitor - reductase fungicides include isobenzofuranone, pyrroloquinolinone and triazolobenzothiazole fungicides. Isobenzofuranone includes fthalide. Pyrroloquinolinone includes pyroquilon. Triazolobenzothiazole includes tricyclazole.

[0284] (b16) The "Melanin biosynthesis inhibitor - dehydratase (MBI-D) fungicide" (FRAC code 16.2) inhibits citral dehydratase in melanin biosynthesis. Melanin is necessary for host plant infections by some fungi. Melanin biosynthesis inhibitor - dehydratase fungicides include cyclopropanecarboxamides, carboxamides, and propionamide fungicides. Cyclopropanecarboxamides include carpropamid. Carboxamides include diclocymet. Propionamides include fenoxanil.

[0285] (b17) The "Sterol biosynthesis inhibitor (SBI): Class III fungicide" (FRAC code 17) inhibits 3-ketoreductase during C4-demethylation in sterol production. SBI: Class III inhibitors include hydroxyanilide fungicides and amino-pyrazolinone fungicides. Hydroxyanilides include fenhexamid. Amino-pyrazolinones include fenpyrazamine (S-2-propen-1-yl 5-amino-2,3-dihydro-2-(1-methylethyl)-4-(2-methylphenyl)-3-oxo-1H-pyrazole-1-carbothioate).

[0286] (b18) The "Squalene-epoxidase inhibitor fungicide" (FRAC code 18) (SBI: Class IV) inhibits squalene-epoxidase in the sterol biosynthesis pathway. Sterols such as ergosterol are necessary for membrane structures and functions that are essential for the growth of functional cell walls. Therefore, exposure to these fungicides results in abnormal growth and ultimately kills susceptible fungi. Squalene-epoxidase inhibitor fungicides include thiocarbamate and allylamine fungicides. Thiocarbamates include pyributicarb. Allylamines include naftifine and terbinafine.

[0287] (b19) The "Polyoxin fungicide" (FRAC code 19) inhibits chitin synthase. Examples include polyoxin.

[0288] (b20) The "phenylurea fungicide" (FRAC code 20) is proposed to act on cell division. Examples include pencycuron.

[0289] (b21) The "quinone inner inhibitor (QiI) fungicide" (FRAC code 21) suppresses complex III mitochondrial respiration in fungi by acting on ubiquinone reductase. The reduction of ubiquinone is blocked at the "quinone inner" (Q i ) site of the cytochrome bc1 complex, which is located in the inner mitochondrial membrane of fungi. By suppressing mitochondrial respiration, normal fungal growth and proliferation are prevented. Quinone inner inhibitor fungicides include cyanoimidazoles and sulfamoyl triazole fungicides. Cyanoimidazoles include cyazofamid. Sulfamoyl triazoles include amisulbrom.

[0290] (b22) The "benzamide and thiazole carboxamide fungicides" (FRAC code 22) inhibit mitosis by binding to β-tubulin and disrupting microtubule assembly. By inhibiting microtubule assembly, cell division is disrupted and can be transported into cells and cell structures. Benzamides include zoxamide. Thiazole carboxamides include ethaboxam.

[0291] (b23) The "enopyranuronic acid antibiotic fungicide" (FRAC code 23) suppresses fungal growth by acting on protein biosynthesis. Examples include blasticidin-S.

[0292] (b24) The "hexopyranosyl antibiotic fungicide" (FRAC code 24) suppresses fungal growth by acting on protein biosynthesis. Examples include kasugamycin.

[0293] (b25) "Glucopyranosyl antibiotics: Protein synthesis bactericides" (FRAC code 25) inhibits fungal growth by acting on protein biosynthesis. Examples include streptomycin.

[0294] (b26) "Glucopyranosyl antibiotics: Trehalase and inositol biosynthesis bactericides" (FRAC code 26) inhibits trehalase and inositol biosynthesis. Examples include validamycin.

[0295] (b27) "Cyanoacetamide oxime bactericides (FRAC code 27) include cymoxanil.

[0296] (b28) "Carbamate bactericides" (FRAC code 28) are considered multi-site inhibitors of fungal growth. These are proposed to interfere with the synthesis of fatty acids in the cell membrane and then prevent the permeability of the cell membrane. Propamacarb, iodocarb, and prothiocarb are examples of this class of bactericides.

[0297] (b29) "Oxidative phosphorylation uncoupling bactericides" (FRAC code 29) inhibits fungal respiration by uncoupling oxidative phosphorylation. By inhibiting respiration, normal fungal growth and development are prevented. This class includes 2,6-dinitroanilines such as fluazinam, and dinitrophenyl crotonates such as dinocap, meptyldinocap, and binapacryl.

[0298] (b30) "Organotin bactericides" (FRAC code 30) inhibits adenosine triphosphate (ATP) synthase in the oxidative phosphorylation pathway. Examples include fentin acetate, fentin chloride, and fentin hydroxide.

[0299] (b31) "Carboxylic acid fungicide" (FRAC code 31) suppresses the growth of fungi by acting on DNA type II topoisomerase (gyrase). Examples include oxolinic acid.

[0300] (b32) "Heteroaromatic fungicide" (Fungicide Resistance Action Committee (FRAC) code 32) is proposed to act on DNA / ribonucleic acid (RNA) synthesis. Heteroaromatic fungicides include isoxazole and isothiazolone. Isoxazole includes hymexazole, and isothiazolone includes octhilinone.

[0301] (b33) "Phosphonate fungicides" (FRAC code 33) include various salts including phosphorous acid and fosetyl-aluminum.

[0302] (b34) "Phthalic acid fungicides" (FRAC code 34) include teclofthalam.

[0303] (b35) "Benzotriazine fungicides" (FRAC code 35) include triazoxide.

[0304] (b36) "Benzene-sulfonamide fungicides" (FRAC code 36) include flusulfamide.

[0305] (b37) "Pyridazinone fungicides" (FRAC code 37) include dichomedine.

[0306] (b38) "Thiophene-carboxamide fungicides" (FRAC code 38) are proposed to act on ATP production. Examples include silthiopham.

[0307] (b39) "Complex I NADH oxidoreductase inhibitor fungicide" (FRAC code 39) inhibits electron transport in mitochondria and includes pyrimidine amines such as diflumetorim and pyrazole-5-carboxamides such as tolfenpyrad.

[0308] (b40) "Carboxylic acid amide (CAA) fungicide" (FRAC code 40) inhibits cellulose synthase, which prevents growth and leads to the death of the target fungus. Carboxylic acid amide fungicides include cinnamic acid amides, valine amides and other carbamates, as well as mandelic acid amide fungicides. Cinnamic acid amides include dimethomorph, flumorph and pyrimorph (3-(2-chloro-4-pyridinyl)-3-[4-(1,1-dimethylethyl)phenyl]-1-(4-morpholinyl)-2-propen-1-one). Valine amides and other carbamates include benzov alicarb, benzov alicarb-isopropyl, iprovalicarb, tolprocarb (2,2,2-trifluoroethyl N-[(1S)-2-methyl-1-[[(4-methylbenzoyl)amino]methyl]propyl]carbamate) and valifenalate (methyl N-[(1-methylethoxy)carbonyl]-L-valyl-3-(4-chlorophenyl)-β-alaninate) (also known as valiphenal). Mandelic acid amides include mandipropamid, N-[2-[4-[[3-(4-chlorophenyl)-2-propyn-1-yl]oxy]-3-methoxyphenyl]ethyl]-3-methyl-2-[(methylsulfonyl)amino]butanamide and N-[2-[4-[[3-(4-chlorophenyl)-2-propyn-1-yl]oxy]-3-methoxyphenyl]ethyl]-3-methyl-2-[(ethylsulfonyl)amino]butanamide.

[0309] (b41) "Tetracycline antibiotic fungicide" (FRAC code 41) inhibits fungal growth by acting on protein synthesis. Examples include oxytetracycline.

[0310] (b42) The "thiocarbamate fungicide" (FRAC code 42) includes methiocarb.

[0311] (b43) The "benzamide fungicide" (FRAC code 43) inhibits fungal growth by the delocalization of spectrin-like proteins. Examples include pyridinylmethylbenzamide fungicides such as fluopicolide (currently FRAC code 7, pyridinylethylbenzamide).

[0312] (b44) The "microbial fungicide" (FRAC code 44) interferes with the fungal pathogen cell membrane. Microbial fungicides include Bacillus species such as Bacillus amyloliquefaciens strains QST 713, FZB24, MB1600, D747 and the fungicidal lipopeptides they produce.

[0313] (b45) The "QxI fungicide" (FRAC code 45) suppresses complex III mitochondrial respiration in fungi by acting on ubiquinol reductase at an unknown (Q x ) site of the cytochrome bc1 complex. By suppressing mitochondrial respiration, it 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).

[0314] (b46) The "plant extract fungicide" is proposed to act by disrupting the cell membrane. Plant extract fungicides include terpene hydrocarbons and terpene alcohols such as extracts obtained from Melaleuca alternifolia (tea tree).

[0315] (b47) The "host plant defense-inducing fungicide" (FRAC code P) induces the host plant defense mechanism. Host plant defense-inducing fungicides include benzothiadiazole, benzisothiazole, and thiadiazole-carboxamide fungicides. Benzothiadiazole includes acibenzolar-S-methyl. Benzisothiazole includes probenazole. Thiadiazole-carboxamide includes thiadinyl and isothianyl.

[0316] (b48) The "multi-site contact fungicide" suppresses the growth of fungi by multiple sites of action and has contact / preventive activity. This class of fungicides includes the following: (b48.1) "copper fungicide" (FRAC code M1)", (b48.2) "sulfur fungicide" (FRAC code M2), (b48.3) "dithiocarbamate fungicide" (FRAC code M3), (b48.4) "phthalimide fungicide" (FRAC code M4), (b48.5) "chloronitrile fungicide" (FRAC code M5), (b48.6) "sulfamide fungicide" (FRAC code M6), (b48.7) multi-site contact "guanidine fungicide" (FRAC code M7), (b48.8) "triazine fungicide" (FRAC code M8), (b48.9) "quinone fungicide" (FRAC code M9), (b48.10) "quinoxaline fungicide" (FRAC code M10) and (b48.11) "maleimide fungicide" (FRAC code M11). The "copper fungicide" is usually an inorganic compound containing copper in the copper(II) oxidation state; examples include copper oxychloride, copper sulfate, and copper hydroxide, including compositions such as Bordeaux mixture (tribasic copper sulfate). The "sulfur fungicide" contains a ring or chain of sulfur atoms It is an inorganic chemical; for example, elemental sulfur is included. The "dithiocarbamate fungicide" contains a dithiocarbamate molecular moiety; for example, mancozeb, metiram, propineb, ferbam, maneb, thiram, zineb and ziram are included. The "phthalimide fungicide" contains a phthalimide molecular moiety; for example, folpet, captan and captafol are included. The "chloronitrile fungicide" contains an aromatic ring substituted with chloro and cyano; for example, chlorothalonil is included. The "sulfamide fungicide" includes dichlofluanid and tolylfluanid. The multi-site contact "guanidine fungicide" includes guazatine, iminoctadine albesilate and iminoctadine triacetate. The "triazine fungicide" includes anilazine. The "quinone fungicide" includes dithianon. The "quinoxaline fungicide" includes quinomethionate (also known as chinomethionate). The "maleimide fungicide" includes fluoroimide.

[0317] (b49) "Fungicides other than those from class (b1) to (b48)" include certain fungicides whose mode of action may be unknown. These include the following: (b49.1), "phenyl-acetamide fungicides" (FRAC code U6), (b49.2) "aryl-phenyl-ketone fungicides" (FRAC code U8), (b49.3) "guanidine fungicides" (FRAC code U12), (b49.4) "thiazolidine fungicides" (FRAC code U13), (b49.5) "pyrimidinone-hydrazone fungicides" (FRAC code U14) and (b49.6) compounds that bind to oxysterol-binding proteins as described in PCT Patent Publication WO2013 / 009971. Phenyl-acetamides include difenoconazole and N-[[(cyclopropylmethoxy)amino][6-(difluoromethoxy)-2,3-difluorophenyl]-methylene]benzeneacetamide. Aryl-phenyl ketones include benzophenones such as metrafenone, and benzoylpyridines such as pyriofenone ((5-chloro-2-methoxy-4-methyl-3-pyridinyl)(2,3,4-trimethoxy-6-methylphenyl)methanone). Guanidine includes dodine. Thiazolidine includes flutianil ((2Z)-2-[[2-fluoro-5-(trifluoromethyl)phenyl]thio]-2-[3-(2-methoxyphenyl)-2-thiazolidinylidene]acetonitrile). Pyrimidinone hydrazone includes ferimzone. Class (b49.6) includes oxathiapiprolin (1-[4-[4-[5-(2,6-difluorophenyl)-4,5-dihydro-3-isoxazolyl]-2-thiazolyl]-1-piperidinyl]-2-[5-methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl]ethanone) and its R-enantiomer, which is 1-[4-[4-[5R-(2,6-difluorophenyl)-4,5-dihydro-3-isoxazolyl]-2-thiazolyl]-1-piperidinyl]-2-[5-methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl]ethanone (registration number 1003319-79-6).(b49) The class also includes vetoxazine, flometoquine (2-ethyl-3,7-dimethyl-6-[4-(trifluoromethoxy)phenoxy]-4-quinolinylmethyl carbonate), fluoroimide, neo-asozin (iron methanearsonate), picarbutrazox (1,1-dimethylethyl N-[6-[[[[((Z)1-methyl-1H-tetrazol-5-yl)phenylmethylene]amino]oxy]methyl]-2-pyridinyl]carbamate), pyrrolnitrin, quinomethionate, tebufloquin (6-(1,1-dimethylethyl)-8-fluoro-2,3-dimethyl-4-quinolinylacetate), torufanide (N-(4-chloro-2-nitrophenyl)-N-ethyl-4-methylbenzenesulfonamide), 2-butoxy-6-iodo-3-propyl-4H-1-benzopyran-4-one, 3-butyn-1-yl, N-[6-[[[[(1-methyl-1H-tetrazol-5-yl)phenylmethylene]amino]oxy]methyl]-2-pyridinyl]carbamate, (N-(4-chloro-2-nitrophenyl)-N-ethyl-4-methylbenzenesulfonamide), N’-[4-[4-chloro-3-(tri. [[(Fluoromethyl)phenoxy]-2,5-dimethylphenyl]-N-ethyl-N-methylmethanimidamide, N-[[(Cyclopropylmethoxy)amino][6-(difluoromethoxy)-2,3-difluorophenyl]methylene]benzeneacetamide, 2,6-dimethyl-1H,5H-[1,4]dithiino[2,3-c:5,6-c']dipyrrole-1,3,5,7(2H,6H)-tetrone, 5-fluoro-2-[(4-methylphenyl)methoxy]-4-pyrimidinamine, 5-fluoro-2-[(4-fluorophenyl)methoxy]-4-pyrimidinamine and 4-fluorophenyl N-[1-[[[(1-(4-cyanophenyl)ethyl]sulfonyl]methyl]propyl]carbamate, pentyl N-[6-[[[[(1-methyl-1H-tetrazol-5-yl)phenylmethylene]amino]oxy]methyl]-2-pyridinyl]carbamate, pentyl N-[4-[[[[(1-methyl-1H-tetrazol-5-yl)phenylmethylene]amino]oxy]methyl]-2-thiazolyl]carbamate and pentyl N-[6-[[[[(Z)-(1-methyl-1H-tetrazol-5-yl)phenylmethylene]amino]oxy]methyl]-2-pyridinyl]carbamate are included. Class (b46) includes, in addition to those of the specific classes described above (e.g., (b1), (b10) and (b22)), mitosis- and cell division-inhibiting fungicides.

[0318] Additional "fungicides other than the fungicides of classes (1) to (46)", whose mechanism of action may be unknown or not yet classifiable, include fungicidal compounds selected from constituents (b49.7) to (b49.12) as shown below.

[0319] Constituent (b49.7) relates to a compound of formula b49.7 [Chemical formula] [wherein R b1 is [Chemical formula] as defined]

[0320] Examples of the compound of formula b49.7 include (b49.7a) (2-chloro-6-fluorophenyl) methyl 2-[1-[2-[3,5-bis(difluoromethyl)-1H-pyrazol-1-yl]acetyl]-4-piperidinyl]-4-thiazolecarboxylate (registration number 1299409-40-7) and (b49.7b) (1R)-1,2,3,4-tetrahydro-1-naphthalenyl 2-[1-[2-[3,5-bis(difluoromethyl)-1H-pyrazol-1-yl]acetyl]-4-piperidinyl]-4-thiazolecarboxylate (registration number 1299409-42-9). Methods for preparing the compound of formula b46.2 are described in PCT Patent Publications WO2009 / 132785 and WO2011 / 051243.

[0321] Component (b49.8) is a compound of formula b49.8

Chemical formula

[0322] Examples of the compound of formula b49.8 include (b49.8a) 1-[4-[4-[5-[(2,6-difluorophenoxy)methyl]-4,5-dihydro-3-isoxazolyl]-2-thiazolyl]-1-piperidinyl]-2-[5-methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl]ethanone. A method for preparing the compound of formula b49.8 is described in PCT Patent Application Publication PCT / US11 / 64324.

[0323] Component (b4799) is a compound of formula b49.9

Chemical formula

Chemical formula

[0324] Examples of the compound of formula b49.9 include (b49.9a) [[4-methoxy-2-[[[(3S,7R,8R,9S)-9-methyl-8-(2-methyl-1-oxopropoxy)-2,6-dioxo-7-(phenylmethyl)-1,5-dioxonan-3-yl]amino]carbonyl]-3-pyridinyl]oxy]methyl 2-methylpropanoate (registration number 517875-34-2), (b49.9b) (3S,6S,7R,8R)-3-[[[3-(acetyloxy)-4-methoxy-2-pyridinyl]carbonyl]amino]-6-meth Chir-4,9-dioxo-8-(phenylmethyl)-1,5-dioxonan-7-yl 2-methylpropanoate (Registration No. 234112-93-7), (b49.9c) (3S,6S,7R,8R)-3[[[3[(acetyloxy)methoxy]-4-methoxy-2-pyridinyl]carbonyl]amino]-6-methyl-4,9-dioxo-8-(phenylmethyl)-1,5-dioxonan-7-yl 2-methylpropanoate (Registration No. 517875-31-9), (b49.9d) (3S,6S,7R,8R)-3-[[[4-methoxy-3-[[(2-methylpropoxy)carbonyl]oxy]-2-pyridinyl]carbonyl]amino]6-methyl-4,9-dioxo-8-(phenylmethyl)-1,5-dioxonan-7-yl 2-methylpropanoate (Registration No. 328256-72-0), and (b49.9e) N-[[3-(1,3-benzodioxol-5-ylmethoxy)-4-methoxy-2-pyridinyl]carbonyl]-O-[2,5-dideoxy-3-O-(2-methyl-1-oxopropyl)-2-(phenylmethyl)-L-arabinonoyl]-L-serine, (1→4’)-lactone (Registration No. 1285706-70-8) are included. Methods for producing the compounds of formula b49.9 are described in PCT Patent Publications WO99 / 40081, WO2001 / 014339, WO2003 / 035617 and WO2011044213.

[0325] Component (b49.10) is of formula b49.10 [Chemical formula] [wherein, R b6 is H or F, and R b7relates to a compound which is -CF2CHFCF3 or -CF2CF2H. Examples of the compound of formula b49.10 are (b49.10a) 3-(difluoromethyl)-N-[4-fluoro-2-(1,1,2,3,3,3-hexafluoropropoxy)phenyl]-1-methyl-1H-pyrazole-4-carboxamide (registration number 1172611-40-3) and (b49.10b) 3-(difluoromethyl)-1-methyl-N-[2-(1,1,2,2-tetrafluoroethoxy)phenyl]-1H-pyrazole 4-carboxamide (registration number 923953-98-4). The compound of formula 49.10 can be produced by the method described in PCT Patent Publication WO2007 / 017450.

[0326] Component b49.11 has the formula b49.11 [Chemical formula] [wherein, R b8 is halogen, C1-C4 alkoxy or C2-C4 alkynyl; R b9 is H, halogen or C1-C4 alkyl; R b10 is C1-C 12 alkyl, C1-C 12 haloalkyl, C1-C 12 alkoxy, C2-C 12 alkoxyalkyl, C2-C 12 alkenyl, C2-C 12 alkynyl, C4-C 12 alkoxyalkenyl, C4-C 12 alkoxyalkynyl, C1-C 12 alkylthio or C2-C 12 alkylthioalkyl; R b11 is methyl or -Y b13 -R b12 ; R b12 is C1-C2 alkyl; Y b13relates to a compound which is CH2, O or S.

[0327] Examples of the compound of formula b49.11 include (b49.11a) 2-[(3-bromo-6-quinolinyl)oxy]-N-(1,1-dimethyl-2-butyn-1-yl)-2-(methylthio)acetamide, (b49.11b) 2-[(3-ethynyl-6-quinolinyl)oxy]-N-[1-(hydroxymethyl)-1-methyl-2-propyn-1-yl]-2-(methylthio)acetamide, (b49.11c) N-(1,1-dimethyl-2-butyn-1-yl)-2-[(3-ethynyl-6-quinolinyl)oxy]-2-(methylthio)acetamide, (b49.11d) 2-[(3-bromo-8-methyl-6-quinolinyl)oxy]-N-(1,1-dimethyl-2-propyn-1-yl)-2-(methylthio)acetamide and (b49.11e) 2-[(3-bromo-6-quinolinyl)oxy]-N-(1,1-dimethylethyl)butanamide. The compounds of formula b49.11, their use as fungicides and methods of manufacture are generally known; see, for example, PCT patent publications WO2004 / 047538, WO2004 / 108663, WO2006 / 058699, WO2006 / 058700, WO2008 / 110355, WO2009 / 030469, WO2009 / 049716 and WO2009 / 087098.

[0328] Component 49.12 relates to N’-[4-[[3-[(4-chlorophenyl)methyl]-1,2,4-thiadiazol-5-yl]oxy]-2,5-dimethylphenyl]-N-ethyl-N-methylmethanimidamide, which is thought to inhibit the C 24 -methyltransferase involved in sterol biosynthesis.

[0329] Accordingly, of note is a mixture (i.e., composition) comprising a compound of formula 1 and at least one fungicidal compound selected from the group consisting of classes (1) to (49) above. Also of note is a composition comprising said mixture (in an amount effective as a fungicide) and further comprising at least one additional constituent selected from the group consisting of surfactants, solid excipients and liquid excipients. Of particular note is a mixture (i.e., composition) comprising a compound of formula 1 and at least one fungicidal compound selected from the group of specific compounds shown above in connection with classes (1) to (49). Also of particular note is a composition comprising said mixture (in an amount effective as a fungicide) and further comprising at least one additional surfactant selected from the group consisting of surfactants, solid excipients and liquid excipients.

[0330] Examples of component (b) fungicides include acibenzolar-S-methyl, aldimorph, ametoctradin, amisulbrom, anilazine, azaconazole, azoxystrobin, benalaxyl (including benalaxyl-M), benodanil, benomyl, benzovindiflupyr, benthiavalicarb (including benthiavalicarb-isopropyl), benzoxazin, binapacryl, biphenyl, bitertanol, bixafen, blasticidin-S, boscalid, bromoconazole, buthiobate, captan, captafol, carbendazim, carboxin, carpropamid, chloroneb, chlorothalonil, chlorozolinate, clotrimazole, copper hydroxide, copper basic chloride, copper sulfate, coumoxystrobin, cyazofamid, cyflufenamid, cymoxanil, cyproconazole, cyprodinil, dichlofluanid, dichlomezine, diclomezine, dichloran, diethofencarb B, difenoconazole, diflumezopyrim, dimethirimol, dimethomorph, dimoxystrobin, diniconazole (including diniconazole-M), dinocap, dithianon, dithiolane, dodemorph, dodine, econazole, edifenphos, enoxastrobin (also known as enestroburin), epoxiconazole, etaconazole, ethaboxam, ethirimol, etridiazole, famoxadone, fenamidone, fenarimol, fenaminstrobin, fenbuconazole, fenfluram, fenhexamid, phenoxanil, fenpiclonil, fenpropidin, fenpropimorph, fenpyrazamine, triphenyltin acetate, triphenyltin chloride, triphenyltin hydroxide, ferbam, ferimzone, flometoquin, fluazinam, fluazinilam, fluopicoxystrobin, fluindapyr, fluopyram, fluoroimide, fluoxastrobin, flutriafol, fludioxonil, flusulfamide, fluthianil, flutolanil, flutriafol, fluoxapipoxad, folpet, fthalide, fuberidazole, fluralaxyl, flupropacil, guazatine, hexaconazole, hymexazol, imazalil, imibenconazole, iminoctadine albesilate, iminoctadine triacetate, iodocarb, ipconazole, iprobenfos, iprodione, iprovalicarb, isoconazole, isofetamid, isoprothiolane, isopyrazam, isothianil, kasugamycin, kresoxim-methyl, mancozeb, mandepropamid, mandestrobin, maneb, mepanipyrim, mepronil, meptyldinocap, metalaxyl (including metalaxyl-M / mefenoxam), metconazole, methiocarb, metham, metominostrobin, metrafenone, miconazole, microbutanil, naftifine, neoasozin, nuarimol, octhilinone, ofurace, orysastrobin, oxadixyl, oxathiapiprolin, oxolinic acid, oxpoconazole, oxycarboxin, oxytetracycline, pefurazoate, penconazole, pencycuron, penflufen, penthiopyrad, phosphorous acid (including their salts, such as fosetyl-aluminum)Picarbutrazox, picoxystrobin, piperine, polyoxin, probenazole, procraz, procymidone, propamacarb, propiconazole, propineb, proquinazid, prothiocarb, prothioconazole, pyraclostrobin, pyra-metostrobin, pyraoxystrobin, pyrazophos, pyribencarb, pyributicarb, pyrifenox, pyrimethanil, pyriofenone, pyrisoctoxazole, pyroquilon, pyrrolnitrin, kinkonazole, quinomethionate, quinoxyfen, quintozene, sedaxane, silthiopham, simconazole, spiroxamine, streptomycin, sulfur, tebuconazole, tebufloquin, techlofthalam, tecnazene, terbinafine, tetraconazole, thiabendazole, diflufenzopyr, thiophanate, thiophanate-methyl, thiram, thiazinyl, tolclofos-methyl, tolylfluanid, triadimefon, triadimenol, triarimol, triticonazole, triazoxide, tribasic copper sulfate, tricyclazole, triclopyricarb, tridemorph, trifloxystrobin, triflumizole, triforine, trimorphamide, uniconazole, uniconazole-P, validamycin, valifenalate (also known as valifenal), vinclozolin, dinneb, ziram, zoxamide, (3S,6S,7R,8R)-3-[[[3-[(acetyloxy)methoxy]-4-methoxy-2-pyridinyl]carbonyl]amino]-6-methyl-4,9-dioxo-8-(phenylmethyl)-1,5-dioxonan-7-yl 2-methylpropanoate, (3S,6S,7R,8R)-3-[[[3-((acetyloxy))-4-methoxy-2-pyridinyl]carbonyl]amino]-6-methyl-4,9-dioxo-8-(phenylmethyl)-1,5-dioxonan-7-yl 2-methylpropanoate, N-[[3-(1,3-benzodioxol-5-ylmethoxy)-4-methoxy-2-pyridinyl]carbonyl]-O-[2,5-dideoxy-3-O-(2-methyl-1-oxopropyl)-2-(phenylmethyl)-L-arabinonoyl]-L-serine, (1→4’)-lactone,N-[2-(1S,2R)-[1,1'-Bicyclopropyl]-2-ylphenyl, Ru]-3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxamide, 2-[(3-bromo-6-quinolinyl)oxy]-N-(1,1-dimethyl-2-butyn-1-yl)-2-(methylthio)acetamide, 2-[(3-bromo-6-quinolinyl)oxy]-N-(1,1-dimethylethyl)butanamide, 2-[(3-bromo-8-methyl-6-quinolinyl)oxy]-N-(1,1-dimethyl-2-propyn-1-yl)-2-(methylthio)acetamide, 2-butoxy-6-iodo-3-propyl-4H-1-benzopyran-4-one, 3-butyn-1-yl N-[6-[[[[(1-methyl-1H-tetrazol-5-yl)phenylmethylene]amino]oxy]methyl]-2-pyridinyl]carbamate, α-(1-chlorocyclopropyl)-α-[2-(2,2-dichlorocyclopropyl)ethyl]-1H-1,2,4-triazole-1-ethanol, 2-[2-(1-chlorocyclopropyl)-4-(2,2-dichlorocyclopropyl)-2-hydroxybutyl]-1,2-dihydro-3H-1,2,4-triazole-3-thione, (αS)-[3-(4-chloro-2-fluorophenyl)-5-(2,4-difluorophenyl)-4-isoxazolyl]-3-pyridinemethanol, rel-1-[[(2R,3S)-3-(2-chlorophenyl)-2-(2,4-difluorophenyl)-2-oxiranyl]methyl]-1H-1,2,4-triazole, rel-2-[[(2R,3S)-3-(2-chlorophenyl)-2-(2,4-difluorophenyl)-2-oxiranyl]methyl]-1,2-dihydro-3H-1,2,4-triazole-3-thione, rel-1-[[(2R,3S)-3-(2-chlorophenyl)-2-(2,4-difluorophenyl)-2-oxiranyl]methyl]-5-(2-propen-1-ylthio)-1H-1,2,4-triazole, 3-[5-(4-chlorophenyl)-2,3-dimethyl-3-isoxazolidinyl]pyridine, (2-chloro-6-fluorophenyl)methyl 2-[1-[2-[3,5-bis(difluoromethyl)-1H-pyrazol-1-yl]acetyl]-4-piperidinyl]-4-thiazolecarboxylate, N’-[4-[[3-[(4-chlorophenyl)methyl]-1,2,[4-Thiazol-5-yl]oxy]-2,5-dimethylphenyl]-N-ethyl-N-methyl-methanimidamide, N-[2-[4-[[3-(4-chlorophenyl)-2-propyn-1-yl]oxy]-3-methoxyphenyl]ethyl]-3-methyl-2-[(methylsulfonyl)amino]butanamide, N-[2-[4-[[3-(4-chlorophenyl)-2-propyn-1-yl]oxy]-3-methoxyphenyl]ethyl]-3-methyl-2-[(ethylsulfonyl)amino]butanamide, N’-[4-[4-chloro-3-(trifluoromethyl)phenoxy]-2,5-dimethylphenyl]-N-ethyl-N-methylmethanimidamide, N-cyclopropyl-3-(difluoromethyl)-5-fluoro-1-methyl-N-[[2-(1-methylethyl)phenyl]methyl]-1H-pyrazole-4-carboxamide, N-[[(cyclopropylmethoxy)amino][6-(difluoromethoxy)-2,3-difluorophenyl]methylene]benzeneacetamide, N-[2-(2,4-dichlorophenyl)-2-methoxy-1-methylethyl]-3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxamide, N-(3’,4’-difluoro[1,1’-biphenyl]-2-yl)-3-(trifluoromethyl)-2-pyrazinecarboxamide, 3-(difluoromethyl)-N-(2,3-dihydro-1,1,3-trimethyl-1H-inden-4-yl)-1-methyl-1H-pyrazole-4-carboxamide, 3-(difluoromethyl)-N-[4-fluoro-2-(1,1,2,3,3,3-hexafluoropropoxy)phenyl]-1-methyl-1H-pyrazole-4-carboxamide, 5,8-difluoro-N-[2-[3-methoxy-4-[[4-(trifluoromethyl)-2-pyridinyl]oxy]phenyl]ethyl]-4-quinazolinamine, 3-(difluoromethyl)-1-methyl-N-[2-(1,1,2,2-tetrafluoroethoxy)phenyl]-1H-pyrazole-4-carboxamide,, 1-[4-[4-[5R-[(2,6-Difluorophenoxy)methyl]-4,5-dihydro-3-isoxazolyl]-2-thiazolyl]-1-piperidinyl]-2-[5-methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl]ethanone, N-(1 ,1-dimethyl-2-butyn-1-yl)-2-[(3-ethynyl-6-quinolinyl)oxy]-2-(methylthio)acetamide, 2,6-dimethyl-1H,5H-[1,4]dithieno[2,3-c:5,6-c’]dipyrrole-1,3,5,7(2H,6H)-tetraone, 2-[(3-ethynyl-6-quinolinyl)oxy]-N-[1-(hydroxymethyl)-1-methyl-2-propyn-1-yl]-2-(methylthio)acetamide, 4-fluorophenyl N-[1-[[[1-(4-cyanophenyl)ethyl]sulfonyl]methyl]propyl]carbamate, 5-fluoro-2-[(4-fluorophenyl)methoxy]-4-pyrimidinamine, 5-fluoro-2-[(4-methylphenyl)methoxy]-4-pyrimidinamine, (3S,6S,7R,8R)-3-[[[4-methoxy-3-[[(2-methylpropoxy)carbonyl]oxy]-2-pyridinyl]carbonyl]amino]-6-methyl-4,9-dioxo-8-(phenylmethyl)-1,5-dioxonan-7-yl-2-methylpropanoate, α-(methoxyimino)-N-methyl-2-[[[1-[3-(trifluoromethyl)phenyl]ethoxy]imino]methyl]benzeneacetamide, [[4-methoxy-2-[[[(3S,7R,8R,9S)-9-methyl-8-(2-methyl-1-oxopropoxy)-2,6-dioxo-7-(phenylmethyl)-1,5-dioxonan-3-yl]amino]carbonyl]-3-pyridinyl]oxy]methyl 2-methylpropanoate, pentyl N-[6-[[[[(1-methyl-1H-tetrazol-5-yl)phenylmethylene]amino]oxy]methyl]-2-pyridinyl]carbamate, pentyl N-[4-[[[[(1-methyl-1H-tetrazol-5-yl)phenylmethylene]amino]oxy]methyl]-2-thiazolyl]carbamate, and pentyl N-[6-[[[[(Z)-(1-methyl-1H-tetrazol-5-yl)phenylmethylene]amino]oxy]methyl]-2-pyridinyl]carbamate and (1R)-1,2,3,4-tetrahydro-1-naphthalenyl 2-[1-[2-[3,5-bis(difluoromethyl)-1H-pyrazol-1-yl]acetyl]-4-piperidinyl]-4-thiazolecarboxylate are included.Therefore, it is noted that the fungicidal composition contains, as component (a), a compound of formula 1 (or an N-oxide or a salt thereof) and, as component (b), at least one fungicide selected from the aforementioned list.

[0331] Particularly notable is the combination of the compound of formula 1 (or an N-oxide or a salt thereof) (i.e., component (a) in the composition) with azoxystrobin, benzovindiflupyr, bixafen, captan, carpropamid, chlorothalonil, copper hydroxide, basic copper chloride, copper sulfate, cymoxanil, cyproconazole, cyprodinil, diethofencarb, difenoconazole, dimethomorph, epoxyconazole, ethaboxam, fenarimol, fenhexamid, fluazinam, fluoxastrobin, fluopyram, fludioxonil, fluindapyr, fluopyram, flusilazole, flutianil, flutriafol, fluxapyroxad, folpet, iprodione, isofetamid, isopyrazam, kresoxim-methyl, mancozeb, mandestrobin, mepronil, metalaxyl (including metalaxyl-M / mefenoxam), metconazole, metrafenone, microbutanil, oxathiapiprolin, penflufen, penthiopyrad, phosphorous acid (including its salts, e.g., fosetyl-aluminum), picoxystrobin, propiconazole, proquinazid, prothioconazole, pyraclostrobin, pyrimethanil, sedaxane, spiroxamine, sulfur, tebuconazole, thiophanate-methyl, trifloxystrobin, zoxamide, α-(1-chlorocyclopropyl)-α-[2-(2,2-dichlorocyclopropyl)ethyl]-1H-1,2,4-triazole-1-ethanol, 2-[2-(1-chlorocyclopropyl)-4-(2,2-dichlorocyclopropyl)-2-hydroxybutyl]-1,2-dihydro-3H-1,2,4-triazole-3-thione, N-[2-(2,4-dichlorophenyl)-2-methoxy-1-methylethyl]-3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxamide, 3-(difluoromethyl)-N-(2,3-dihydro-1,1,3-trimethyl-1H-inden-4-yl)-1-methyl-1H-pyrazole- 4-Carboxamide, 1-[4-[4-[5R-(2,6-difluorophenyl)-4,5-dihydro-3-isoxazolyl]-2-thiazolyl]-1-piperidinyl]-2-[5-methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl]ethanone, 1,1-dimethylethyl N-[6-[[[[(1-methyl-1H-tetrazol-5-yl)phenylmethylene]amino]oxy]methyl]-2-pyridinyl]carbamate, 2,6-dimethyl-1H,5H-[1,4]dithieno[2,3-c:5,6-c']dipyrrole-1,3,5,7(2H,6H)-tetrone, 5-fluoro-2-[(4-fluorophenyl)methoxy]-4-pyrimidinamine, 5-fluoro-2-[(4-methylphenyl)methoxy]-4-pyrimidinamine, (αS)-[3-(4-chloro-2-fluorophenyl)-5-(2,4-difluorophenyl)-4-isoxazolyl]-3-pyridinemethanol, rel-1-[[(2R,3S)-3-(2-chlorophenyl)-2-(2,4-difluorophenyl)-2-oxiranyl]methyl]-1H-1,2,4-triazole, rel-2-[[(2R,3S)-3-(2-chlorophenyl)-2-(2,4-difluorophenyl)-2-oxiranyl]methyl]-1,2-dihydro-3H-1,2,4-triazole-3-thione, and rel-1-[[(2R,3S)-3-(2-chlorophenyl)-2-(2,4-difluorophenyl)-2-oxiranyl]methyl]-5-(2-propen-1-ylthio)-1H-1,2,4-triazole (i.e., as component (b) in the composition) in combination.

[0332] Examples of other bioactive compounds or agents with which the compounds of the present invention can be formulated are as follows: abamectin, acephate, acetamiprid, acrinathrin, afidopyropen ([[(3S,4R,4aR,6S,6aS,12R,12aS,12bS)-3-[(cyclopropylcarbonyl)oxy]-1,3,4,4a,5,6,6a,12,12a,12b-decahydro-6,12-dihydroxy-4,6a,12b-trimethyl-11-oxo-9-(3-pyridinyl)-2H,11H-naphtho[2,1-b]pyrano[3,4-e]pyran-4-yl]methyl cyclopropanecarboxylate]), amidoflumet (S-1955), avermectin, azadirachtin, azinphos-methyl, bifenthrin, bifenazate, buprofezin, carbofuran, cartap, chlorantraniliprole, chlorfenapyr, chlorfluazuron, chlorpyrifos, chlorpyrifos-methyl, chromafenozide, clothianidin, cyantraniliprole (3-bromo-1-(3-chloro-2-pyridinyl)-N-[4-cyano-2-methyl-6-[(methylamino)carbonyl]phenyl]-1H-pyrazole-5-carboxamide), cyclaniliprole (3-bromo-N-[2-bromo-4-chloro-6-[[(1-cyclopropylethyl)amino]carbonyl]phenyl]-1-(3-chloro-2-pyridinyl)-1H-pyrazole-5-carboxamide), cycloxaprid ((5S,8R)-1-[(6-chloro-3-pyridinyl)methyl]-2,3,5,6,7,8-hexahydro-9-nitro-5,8-epoxy-1H-imidazo[1,2-α]azepine), silafluofen, cyfluthrin, beta-cyfluthrin, cyhalothrin, lambda-cyhalothrin, permethrin, silafluofen, deltamethrin, diafenthiuron, diazinon, dieldrin, diflubenzuron, dimefluthrin, dimethoate, dinotefuran, diofenolan, emamectin, endosulfan, esfenvalerate, ethiprole, phenothiocarb, phenoxycarb, fenpropathrin, fenvalerate, fipronil, flonicamid, flubendiamide, flucitranate, fluoxastrobin (methyl (αE)-2-[[2-chloro-4-(trifluoromethyl)phenoxy]methyl]-α-(methoxymethylene)benzeneacetate), fluenesulfone (5-chloro-2-[(3,4,4-trifluoro-3-buten-1-yl)sulfonyl]thiazole), flupiprole (1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-5-[(2-methyl-2-propen-1-yl)amino]-4-[(trifluoromethyl)sulfinyl]-1H-pyrazole-3-carbonitrile), flupyradifurone (4-[[(6-chloro-3-pyridinyl)methyl](2,2-difluoroeth, (2,3,5,6 - tetrafluoro - 4 - (methoxymethyl)phenyl)methyl 2,2 - dimethyl - 3 - [(1Z) - 3,3,3 - trifluoro - 1 - propen - 1 - yl]cyclopropanecarboxylate), tau - fluvalinate, flufenoxuron (UR - 50701), flufenoxuron, honohos, halofenozide, heptafluthrin ([2,3,5,6 - tetrafluoro - 4 - (methoxymethyl)phenyl]methyl 2,2 - dimethyl - 3 - [(1Z) - 3,3,3 - trifluoro - 1 - propen - 1 - yl]cyclopropanecarboxylate), hexaflumuron, hydramethylnon, imidacloprid, indoxacarb, isofenphos, lufenuron, malathion, meperfluthrin ([2,3,5,6 - tetrafluoro - 4 - (methoxymethyl)phenyl]methyl (1R,3S) - 3 - (2,2 - dichloroethenyl) - 2,2 - dimethylcyclopropanecarboxylate), metaflumizone, meta - aldehyde, methamidophos, methidathion, mesomil, methoprene, methoxychlor, methoxyphenozide, metofluthrin, milbemycin oxime, monofluoro - trin ([2,3,5,6 - tetrafluoro - 4 - (methoxymethyl)phenyl]methyl - 3 - (2 - cyano - 1 - propen - 1 - yl) - 2,2 - dimethylcyclopropanecarboxylate), monocrotophos, nicotine, nitenpyram, nithiazine, novaluron, noviflumuron (XDE - 007), oxamyl, piflubumid (1,3,5 - trimethyl - N - (2 - methyl - 1 - oxopropyl) - N - [3 - (2 - methylpropyl) - 4 - [2,2,2 - trifluoro - 1 - methoxy - 1 - (trifluoromethyl)ethyl]phenyl] - 1H - pyrazole - 4 - carboxamide), parathion, parathion - methyl, permethrin, phorate, phosalone, phosmet, phosphamidon, pyrimicarb, profenofos, profluthrin, pymetrozine, pyrafluprole, pyrethrin, pyridalyl, pyrifluquinazone, pyriminostrobin (methyl (αE) - 2 - [[[2 - [(2,4-(dichlorophenyl)amino]-6-(trifluoromethyl)-4-pyrimidinyl]oxy]methyl]-α-(methoxymethylene)benzeneacetate), pyriprole, pyriproxyfen, rotenone, ryanodine, spinetoram, spinosad, spirodiclofen, spirotetramat, sulfoxaflor, sulprofos, tebufenozide, teflubenzuron, tefluthrin, terbufos, tetrachlorvinphos, tetramethylfluthrin, thiacloprid, thiamethoxam, thiodicarb, thiosultap-sodium, tolfenpyrad, tralomethrin, triazamate, trichlorfon and triflumuron; and biological agents including entomopathogenic bacteria such as Bacillus thuringiensis subsp. aizawai, Bacillus thuringiensis subsp. kurstaki, and encapsulated δ-endotoxins of Bacillus thuringiensis (e.g., Sipcap, MPV, MPVII); entomopathogenic fungi such as Beauveria bassiana; and entomopathogenic viruses including nucleopolyhedroviruses (NPV) such as baculovirus, HzNPV, AfNPV; and granulosis viruses (GV) such as CpGV.,

[0333] The compounds of the present invention and their compositions can be applied to genetically transformed plants to express proteins that are toxic to invertebrate pests (such as Bacillus thuringiensis δ-endotoxins). The effects of the fungicidal compounds of the present invention, when applied externally, can be synergistic with the expressed toxin proteins.,

[0334] General references on agricultural protectants (i.e., insecticides, fungicides, nematicides, acaricides, herbicides and biological agents) include The Pesticide Manual, 13th Edition, edited by C.D.S. Tomlin, British Crop Protection Council, Farnham, Surrey, U.K., 2003 and The BioPesticide Manual, 2nd Edition, edited by L.G. Copping, British Crop Protection Council, Farnham, Surrey, U.K., 2001.

[0335] In embodiments where one or more of these various mixing partners are used, the weight ratio of these various mixing partners to the compound of formula 1 (in total) is usually between about 1:3000 and about 3000:1. It should be noted that the weight ratio is between about 1:300 and about 300:1 (e.g., a ratio between about 1:30 and about 30:1). One of ordinary skill in the art can readily determine the biologically effective amount of the active ingredient necessary for the desired spectrum of biological activity by simple experimentation. It is clear that including these additional components may expand the spectrum of diseases controlled beyond that controlled by the compound of formula 1 alone. In certain cases, the combination of the compounds of the present invention with other bioactive (especially fungicidal) compounds or agents (i.e., active ingredients) can result in an effect that exceeds an additive (i.e., synergistic) effect. It is always desirable to reduce the amount of active ingredient released into the environment while ensuring effective pest control. Such combinations can be advantageous for reducing the cost of crop production and the environmental burden when the synergistic action of the fungicidal active ingredient occurs at an application rate that gives an agriculturally satisfactory level of fungal control.

[0336]

[0337] ​Also, in certain cases, combinations of the compounds of the present invention with other bioactive compounds or agents can result in effects that are less than additive (i.e., safening) effects on beneficial organisms in an agricultural environment. For example, the compounds of the present invention can safen herbicides in crop plants or protect beneficial insect species (e.g., insect predators, pollinators such as bees) from insecticides.

[0338] Notable fungicides for formulations containing a compound of formula 1 for providing useful mixtures in seed treatment include, but are not limited to, amisulbrom, azoxystrobin, boscalid, carbendazim, carboxin, cymoxanil, cyproconazole, difenoconazole, dimethomorph, fluazinam, fluoxastrobin, fluxapyroxad, ipconazole, iprodione, metalaxyl, mefenoxam, metconazole, microbutanil, paclobutrazol, penflufen, picoxystrobin, prothioconazole, pyraclostrobin, sedaxane, silthiopham, tebuconazole, thiabendazole, thiophanate-methyl, thiram, trifloxystrobin and triticonazole.

[0339] The compounds of formula 1 can be formulated with invertebrate pest control compounds or agents, including but 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, cyphenothrin, gamma-cyphenothrin, lambda-cyphenothrin, permethrin, alpha-permethrin, zeta-permethrin, silafluofen, deltamethrin, dieldrin, dinotefuran, diofenolan, emamectin, endosulfan, esfenvalerate, ethiprole, etofenprox, etoxazole, phenothiocarb, phenoxycarb, fenvalerate, fipronil, flonicamid, flubendiamide, flufiprole, flupyradifurone, flubalinate, formetanate, fosthiazate, heptafluthrin, hexaflumuron, hydramethylnon, imidacloprid, indoxacarb, lufenuron, meperfluthrin, metaflumizone, methiocarb, methomyl, methoprene, methoxyphenozide, monofluoroacetate, nitenpyram, nithiazine, novaluron, oxamyl, piflubutrazone, pymetrozine, pyrethrin, pyridaben, pyriminostrobin, pyridalyl, pyriproxyfen, ryanodine, spinetoram, spinosad, spirodiclofen, spirotetramat, sulfoxaflor, tebufenozide, tetramethrin, tetramethylfluthrin, thiacloprid, thiamethoxam, thiodicarb, thiosultap-sodium, tralomethrin, triazamate, triflumuron, Bacillus thuringiensis delta-endotoxin, strains of Bacillus thuringiensis and strains of Nucleo polyhydrosis virus, to provide useful mixtures in the treatment of seeds. Also included are spinosad, spirodiclofen, spirotetramat, sulfoxaflor, tebufenozide, tetramethrin, tetramethylfluthrin, thiacloprid, thiamethoxam, thiodicarb, thiosultap-sodium, tralomethrin, triazamate, triflumuron, Bacillus thuringiensis delta-endotoxin, strains of Bacillus thuringiensis and strains of Nucleo polyhydrosis virus.

[0340] Compositions containing a compound of formula 1 useful for seed treatment can further comprise bacteria and fungi having the ability to provide protection from the deleterious effects of phytopathogenic fungi or bacteria and / or soil animals such as nematodes. Bacteria exhibiting nematicidal properties can include, but are not limited to, Bacillus firmus, Bacillus cereus, Bacillius subtiliis, and Pasteuria penetrans. A suitable Bacillus firmus strain is the CNCM I-1582 (GB-126) strain marketed as BioNem™. A suitable Bacillus cereus strain is the NCMM I-1592 strain. The Bacillus strains are disclosed in US6,406,690. Other suitable bacteria exhibiting nematicidal activity are B. amyloliquefaciens IN937a and B. subtilis strain GB03. Bacteria exhibiting fungicidal properties can include, but are not limited to, the B. pumilus strain GB34. Fungal species exhibiting nematicidal properties can include, but are not limited to, Myrothecium verrucaria, Paecilomyces lilacinus, and Purpureocillium lilacinum.

[0341] Seed treatment can also include one or more nematicides of natural origin, such as elicitor proteins called harpins, isolated from certain bacterial plant pathogens such as Erwinia amylovora. An example is the harpin-N-Tek seed treatment technology available as N-Hibit™ Gold CST.

[0342] Seed treatment can also include one or more species of legume root nodule bacteria, such as the micro-symbiotic nitrogen-fixing bacterium Bradyrhizobium japonicum. These inoculation materials can optionally contain one or more lipochitin oligosaccharides (LCOs), which are nodulation (Nod) factors produced by rhizobial bacteria during the initiation of nodule formation in the roots of leguminous plants. For example, the seed treatment technology of the Optimize® brand incorporates LCO Promoter Technology™.

[0343] Seed treatment can also include one or more isoflavones that can increase the level of root colonization by mycorrhizal fungi. Mycorrhizal fungi improve plant growth by promoting the uptake of nutrients such as water, sulfates, nitrates, phosphates, and metals. Examples of isoflavones include, but are not limited to, genistein, biochanin A, formononetin, daidzein, glycitein, hesperetin, naringenin, and pratensein. Formononetin is available as an active ingredient in mycorrhizal inoculation material products such as PHC Colonize® AG.

[0344] Seed treatment can also include one or more plant activators that induce systemic acquired resistance in plants after contact with pathogens. An example of a plant activator that induces such a defense mechanism is acibenzolar-S-methyl.

[0345] The following tests demonstrate the efficacy of the compounds of the present invention against specific pathogens. However, the pathogen control protection provided by these compounds is not limited to these species. For a description of the compounds, refer to Index Tables A - B below. The following abbreviations are used in Index Table A. Me means methyl, i-Pr means iso-propyl, MeO means methoxy, and -NO2 means nitro. The abbreviation "Cmpd." represents "compound", and the abbreviation "Ex." represents "example", followed by a number indicating the example in which the compound is prepared. In Index Table A, the locant numbers shown for substituents R 4 and R 5 are as shown in the structure at the top of the table. The order in which substituents R 4 and R 5 are shown may differ from the Chemical Abstracts naming system when the difference does not affect the meaning. For example, in Compound 1 in Index Table A, substituent R 5 is at the 6-position (i.e., 6-F), and the CAS name for Compound 1 is 4-(2-bromo-4,6-difluorophenyl)-N-(2-fluoro-6-nitrophenyl)-1,3-dimethyl-1H-pyrazole-5-amine. The values reported in the "AP + (M+1)" column are the molecular weights of the observed molecular ions formed by adding H + (molecular weight 1) to the molecule with the highest isotope abundance (i.e., M); the values reported in the "AP - (M-1)" column are the molecular weights of the observed molecular ions formed by losing H + (molecular weight 1) from the molecule with the highest isotope abundance (i.e., M). The presence of molecular ions containing one or more higher atomic weight isotopes of lower abundance (e.g., 37 Cl, 81 Br) is not reported. The reported M+1 and M-1 peaks were observed by mass spectrometry using electrospray ionization (ESI) or atmospheric pressure chemical ionization (APCI).

[0346]

Table 20

Table 21

Table 22

Table 23

Table 24

Table 25

[0347]

Table 26

[0348] Biological examples of the present invention General protocol for producing test suspensions for Tests A - F: The test compound was first dissolved in acetone in an amount equal to 3% of the final volume and then suspended in pure water (50 / 50 by volume) containing acetone and 250 ppm of the surfactant PEG400 (polyhydric alcohol ester) at the desired concentration (ppm). The resulting test suspension was then used in Tests A - F.

[0349] Test A The test solution was sprayed onto wheat seedlings up to the outflow point. The next day, the seedlings were inoculated with a spore suspension of Septoria tritici (the causative agent of wheat leaf blotch), incubated at 24 °C for 48 h in a saturated atmosphere, then transferred to a growth chamber at 20 °C for 17 days, and then a time disease rating was performed.

[0350] Test B The test liquid agent was sprayed onto wheat seedlings up to the exudation point. The next day, the seedlings were inoculated with a spore suspension of Puccinia recondita f.sp. tritici (the causative agent of wheat leaf rust), incubated at 20 °C for 24 h under a saturated atmosphere, then transferred to a growth chamber at 20 °C for 7 days, and thereafter, time disease scoring was performed.

[0351] Test C The test suspension was sprayed onto wheat seedlings up to the exudation point. The next day, the seedlings were inoculated with spore powder of Blumeria graminis f.sp. tritici (also known as Erysiphe graminis f.sp. tritici, the causative agent of wheat powdery mildew), incubated at 20 °C for 8 days under a saturated atmosphere, and thereafter, time visual disease rating was performed.

[0352] Test D The test liquid agent was sprayed onto soybean seedlings up to the exudation point. The next day, the seedlings were inoculated with a spore suspension of Puccinia graminis (the causative agent of soybean rust), incubated at 22 °C for 24 h under a saturated atmosphere, then transferred to a growth chamber at 22 °C for 8 days, and thereafter, time visual disease rating was performed.

[0353] Test E The test suspension was sprayed onto tomato seedlings up to the exudation point. The next day, the seedlings were inoculated with a spore suspension of Botrytis cinerea (the causative agent of tomato botrytis), incubated at 20 °C for 48 h under a saturated atmosphere, then transferred to a growth chamber at 24 °C for 3 days, and thereafter, time visual disease rating was performed.

[0354] Test F The test suspension was sprayed onto tomato seedlings up to the outflow point. The next day, the seedlings were inoculated with a spore suspension of Alternaria solani (the causative agent of tomato target spot), incubated at 27 °C for 48 h in a saturated atmosphere, then transferred to a growth chamber at 20 °C for 3 days, and thereafter, a time-visible disease score was performed.

[0355] The results of Tests A to F are shown in Table A below. A score of 100 indicates 100% disease control, and a score of 0 indicates no disease control (against control). A dash (-) indicates that the compound was not tested.

[0356] [Table 27] [Table 28] [Table 29] [Table 30] [Table 31] [Table 32]

[0357] Biological Comparative Example General protocol for preparing the test suspension for Tests A1 to F1: The test compound was first dissolved in acetone in an amount equal to 3% of the final volume, and then suspended in pure water (50 / 50 by volume) containing acetone and 250 ppm of the surfactant PEG400 (polyhydric alcohol ester) at the desired concentration (ppm). The resulting test suspension was then used in Tests A1 to F1.

[0358] Test A1 The test liquid agent was sprayed onto wheat seedlings up to the bleeding point. The next day, the seedlings were inoculated with a spore suspension of Septoria tritici (the causative agent of wheat leaf blight), incubated at 24 °C for 48 h in a saturated atmosphere, then transferred to a growth chamber at 20 °C for 17 days, and thereafter, time disease scoring was performed.

[0359] Test B1 The test liquid agent was sprayed onto wheat seedlings up to the bleeding point. The next day, the seedlings were inoculated with a spore suspension of Puccinia recondita f.sp. tritici (the causative agent of wheat brown rust), incubated at 20 °C for 24 h in a saturated atmosphere, then transferred to a growth chamber at 20 °C for 7 days, and thereafter, time disease scoring was performed.

[0360] Test C1 The test suspension was sprayed onto wheat seedlings up to the bleeding point. The next day, the seedlings were inoculated with spore powder of Blumeria graminis f.sp. tritici (also known as Erysiphe graminis f.sp. tritici, the causative agent of wheat powdery mildew), incubated at 20 °C for 8 days, and thereafter, time visible disease scoring was performed.

[0361] Test E1 The test suspension was sprayed onto tomato seedlings up to the bleeding point. The next day, the seedlings were inoculated with a spore suspension of Botrytis cinerea (the causative agent of tomato Botrytis), incubated at 20 °C for 48 h in a saturated atmosphere, then transferred to a growth chamber at 24 °C for 3 days, and thereafter, time visible disease scoring was performed.

[0362] Test F1 The test suspension was sprayed onto tomato seedlings up to the bleeding point. The next day, the seedlings were inoculated with a spore suspension of Alternaria solani (the causative agent of tomato target spot), incubated at 27 °C for 48 h in a saturated atmosphere, then transferred to a growth chamber at 20 °C for 3 days, and thereafter time visible disease scoring was performed.

[0363] The results of Tests A1 to F1 are shown in Table B below. A score of 100 indicates 100% disease control, and a score of 0 indicates no disease control (against the control). The data are shown for the following compounds.

[0364] [Table 33]

[0365] [Table 34]

Claims

1. Formula 8 【Chemistry 1】 [In the formula, R a is CH3, CH2CH3 or (CH2)2CH3; R 2 is methyl; R 3 is Br, Cl or F; R 4 is Cl or F; R 5 is Br, Cl, F, methyl or methoxy; m is 1, R 4 is in the 4th position; and m is 1 and R 4 is in the 6th position; and m is 2 and one R 4 is in the 4-position and the other is in the 6-position; and n is 0, and n is 1, R 5 is at the 4th position; and n is 1 and R 5 is in the 6th position; and n is 2 and one R 5 is in the 4-position and the other is in the 6-position. or a salt thereof.

2. R a is CH3; R 3 is Cl or F; R 4 is F; R 5 is F or methyl.

3. R 3 is Cl; m is 1, R 4 is in the 4th position; and m is 2 and one of R 4 is in the 4-position and the other is in the 6-position; and n is 0, and n is 1, R 5 The compound of claim 2, wherein is at the 6-position.

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