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WO2014124988A1 - Pyridine derivatives and their use as herbicides - Google Patents

Pyridine derivatives and their use as herbicides Download PDF

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Publication number
WO2014124988A1
WO2014124988A1 PCT/EP2014/052755 EP2014052755W WO2014124988A1 WO 2014124988 A1 WO2014124988 A1 WO 2014124988A1 EP 2014052755 W EP2014052755 W EP 2014052755W WO 2014124988 A1 WO2014124988 A1 WO 2014124988A1
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WO
WIPO (PCT)
Prior art keywords
compound
formula
fluoro
pyridine
carboxamide
Prior art date
Application number
PCT/EP2014/052755
Other languages
French (fr)
Inventor
Matthew Murdoch Woodhead Mclachlan
Paul John De Fraine
John Finney
Melloney MORRIS
Matthew Brian Hotson
Original Assignee
Syngenta Limited
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Priority claimed from GB201313885A external-priority patent/GB201313885D0/en
Application filed by Syngenta Limited filed Critical Syngenta Limited
Publication of WO2014124988A1 publication Critical patent/WO2014124988A1/en

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Classifications

    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/34—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one nitrogen atom as the only ring hetero atom
    • A01N43/40—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one nitrogen atom as the only ring hetero atom six-membered rings
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/34—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one nitrogen atom as the only ring hetero atom
    • A01N43/44—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one nitrogen atom as the only ring hetero atom three- or four-membered rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C07D213/81—Amides; Imides
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C07D213/83—Thioacids; Thioesters; Thioamides; Thioimides

Definitions

  • the present invention relates to the use of certain substituted amide derivatives as herbicides. It also relates to certain novel substituted amide derivatives, to processes for their preparation, herbicidal compositions comprising them, and their use in controlling plants or inhibiting plant growth.
  • X 1 and X 2 are, inter alia, fluorine, Z is, inter alia, oxygen and E is, inter alia, a C 3 -C 6 cycloalkyi group which may be joined directly to the nitrogen atom or via a linker, are described in EP 2 174 931 A1 as having fungicidal activity.
  • the invention provides the use of a compound of formula (I):
  • X 1 , X 2 , X 3 and X 4 are, independently, H, CI, F, trifluoromethyl, cyano, C1-C3 alkyl, d-C 3 -alkenyl, - S-C1-C3 alkyl or C1-C3 alkoxy provided that at least one of X 1 , X 2 , X 3 and X 4 is not H;
  • Z is oxygen or sulphur;
  • R is H or C1-C3 alkyl, allyl, arylmethyl or heteroarylmethyl;
  • W is -CR 2 R 3 - or a direct bond and R 2 and R 3 are, independently, selected from H, -CH 3 or cyclopropyl;
  • the preferred groups for X 1 , X 2 , X 3 , X 4 , R , R 4 , m, n, W, Y, Z and A, in any combination thereof, are as set out below.
  • X 1 , X 2 , X 3 and X 4 are, independently, H, CI or F provided that at least one of X , X 2 , X 3 and X 4 is not H.
  • X 1 is F or CI and X 2 , X 3 and X 4 are H, or (ii) X 1 and X 2 are F or CI and X 3 and X 4 are H or (iii) X 1 and X 3 are F or CI and X 2 and X 4 are H.
  • X 1 is F or CI and X 2 , X 3 and X 4 are H or (ii) X 1 and X 2 are F or CI and X 3 and X 4 are H. More preferably, X 1 is F and X 2 is F or H. Most preferably, X 1 is F and X 2 is H. Preferably Z is oxygen.
  • Y is
  • n 1 or 2.
  • Y is
  • R is H, methyl, ethyl or allyl. More preferably, R is H.
  • W is a direct bond or -CH 2 -. More preferably, W is a direct bond.
  • A examples include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl and cycloheptyl as well as cyclopentenyl and cyclohexenyl, all of which may be substituted by one or more groups R 4 .
  • A is optionally substituted cyclopentyl or optionally substituted cyclohexyl. More preferably, A is optionally substituted cyclohexyl.
  • m is 1 or 2 or 3 and R 4 is as defined above or, preferably, each R 4 is independently selected from halo, hydroxyl, cyano, methyl, trifluoromethyl, azido or methoxy. More preferably, each R 4 is independently selected from chloro, bromo, iodo, fluoro, methyl, cyano, or trifluoromethyl. Even more preferably, each R 4 is chloro, bromo, cyano or methyl.
  • the R 4 group is present on at least the 2 or 3 positions or both the 2 and 3 positions on the cycloalkyi ring, for example, the substitution pattern may be 2-cycloalkyl, 3- cycloalkyl, 2,2-cycloalkyl, 2,3-cycloalkyl or 3,3-cycloalkyl wherein, when more than one substituent is present, each of the substituents may be the same or different. It is noted that it is possible that two R 4 groups may be present in each position of the cycloalkyi ring systems.
  • substitution patterns for the cycloalkyi ring are unsubstituted, 1-hydroxy-, 2- chloro-, 2-bromo-, 2-iodo-, 2-fluoro-, 2-cyano-, 2-methyl-, 2-trifluoromethyl-, 2-methoxy-, 3-chloro- , 3-bromo-, 2-iodo-, 3-fluoro-, 3-cyano-, 3-methyl-, 3-trifluoromethyl-, 3-methoxy-, 4-chloro-, 4- bromo-, 4-fluoro-, 4-cyano-, 4-methyl-, 4-trifluoromethyl- , 4-methoxy-, 2,2-dichloro-, 2,2-dibromo- , 2,2-difluoro-, 2,2-dicyano-, 2,2-dimethyl-, 2,2-dimethoxy-, 2,3-dichloro-, 2,3-dibromo-, 2,3- difluoro-, 2,3-dicyano-, 2,3-di
  • Preferred substitution patterns for the cycloalkyl rings are 1-hydroxy-, 2-methyl-, 3- methyl-, 2,3-dimethyl-, 2,2-dimethyl-, 3,3-dimethyl-, 2-chloro-, 2-bromo-, 2-iodo-, 2-fluoro-, 2- cyano-, 2-trifluoromethyl-, 2-azido-, 3-chloro-, 3-bromo-, 3-fluoro-, 3-trifluoromethyl-, 2,3-dichloro-, 2,3-dibromo-,2-methyl-3-trifluoronriethyl-, 2-methyl-3-cyano, 2-chloro-2-methyl-, 2-chloro-3- methyl-, 2,2-dichloro-, 2,2-difluoro-, and 3,3-difluoro-.
  • substitution patterns are 2-methyl-, 2,3-dimethyl-, 2-chloro-, 2- bromo-, 2-iodo-, 2-fluoro-, 2-trifluoromethyl-, 2-cyano-, 2-azido-, 2,2-difluoro- and 3,3-difluoro-, Preferably, these substitution patterns are found on cyclopentyl or cyclohexyl rings and, most preferably, on cyclohexyl rings.
  • A is 2-methylcyclohexyl, 2,3- dimethylcyclohexyl, 2-chlorocyclohexyl, 2-bromocyclohexyl, 2-iodocyclohexyl, 2-fluorocyclohexyl, 2-trifluoromethylcyclohexyl, 2-cyanocyclohexyl, 2-azidocyclohexyl, 2,2-difluorocyclohexyl and 3,3- difluorocyclohexyl.
  • the invention provides the use of a compound of formula (II),
  • X 1 is F or CI and X 2
  • X 3 and X 4 are H or X 1 and X 2 are F or CI and X 3 and X 4 are H or X 1 and X 3 are F or CI and X 2 and X 4 are H
  • Z is O;
  • R is H
  • W is a direct bond or -CH 2 -;
  • A is a cyclohexyl ring, m is from 0 to 3 and each R 4 is independently selected from methyl, chloro, bromo, iodo, fluoro, trifluoromethyl, cyano and azido.
  • A is 2-methylcyclohexyl, 2,3-dimethylcyclohexyl, 2-chlorocyclohexyl, 2-bromocyclohexyl, 2-iodocyclohexyl, 2- fluorocyclohexyl, 2-trifluoromethylcyclohexyl, 2-cyanocyclohexyl, 2-azidocyclohexyl, 2,2- difluorocyclohexyl or 3,3-difluorocyclohexyl.
  • the invention provides the use of a compound of formula (III):
  • X 1 , X 2 , X 3 and X 4 are, independently, H, CI or F provided that at least one of X 1 , X 2 , X 3 and X 4 is not H;
  • R is H or C1-C3 alkyl, allyl, arylmethyl or heteroarylmethyl;
  • W is -CR 2 R 3 - or a direct bond and R 2 and R 3 are, independently, selected from H, -CH 3 or cyclopropyl;
  • Z is sulphur or oxygen;
  • A is a 3 to 7 membered cycloalkyi ring which is optionally substituted by one or more substituents selected independently from methyl and trifluoromethyl; or a salt or N-oxide form thereof, as a herbicide.
  • X 1 is H or F, more preferably, X 1 is F.
  • X 2 is H or F; more preferably, X 2 is F.
  • X 3 is H or F.
  • X 4 is H or F.
  • X 1 is F and X 2 , X 3 and X 4 are H. In another embodiment, X 1 and X 3 are F and X 2 and X 4 are H. In another embodiment, X 2 and X 4 are F and X 1 and X 3 are H.
  • R is H, methyl, ethyl or allyl, more preferably, R is H.
  • W is a direct bond or -CH 2 -.
  • Z is oxygen
  • A examples include optionally substituted cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl and cycloheptyl.
  • A is optionally substituted cyclopentyl or cyclohexyl. More preferably, A is optionally substituted cyclohexyl.
  • A is optionally substituted by one or more methyl or trifluoromethyl groups on at least the 2 or 3 positions on the cycloalkyl ring. More preferably, A is optionally substituted by one or more methyl groups on at least the 2 or 3 positions on the cycloalkyl ring. This includes situations where methyl and/or trifluoromethyl replace both hydrogen atoms at a particular ring position as well as situations where only one ring hydrogen is replaced at each position.
  • substitution patterns for A are 2-methyl-, 3-methyl-, 4-methyl-, 2,2-dimethyl-, 2,3-dimethyl-, 2,4-dimethyl-, 2,5-dimethyl-, 2,6-dimethyl-, 3,3-dimethyl-, 3,4-dimethyl-, 3,5- dimethyl-, 3,6-dimethyl-, 2,2,3-trimethyl-, 2,3,3-trimethyl-, 2,2,3,3-tetramethyl-, 3,3,5,5- tetramethyl-, 2-trifluoromethyl-, 3-trifluoromethyl-, 4-trifluoromethyl- and 2,3-bis(trifluoromethyl)-.
  • Preferred substitution patterns for A are 2-methyl-, 3-methyl- and 2,3-dimethyl-.
  • A is 2-methylcyclohexyl, 3-methylcyclohexyl, 2,3- dimethylcyclohexyl, 2-methylcyclopentyl, 3-methylcyclopentyl and 2,3-dimethylcyclopentyl. More preferred examples of A are 2-methylcyclohexyl, 3-methylcyclohexyl and 2,3-dimethylcyclohexyl An even more preferred example of A is, 2,3-dimethylcyclohexyl.
  • the invention provides the use of a compound of formula (I):
  • X 1 , X 2 , X 3 and X 4 are, independently, H, CI or F provided that at least one of X 1 , X 2 , X 3 and X 4 is not H;
  • Z is sulphur or oxygen
  • R is H or C1-C3 alkyl, allyl, arylmethyl or heteroarylmethyl; W is -CR 2 R 3 - or a direct bond and R 2 and R 3 are, independently, selected from H, -CH 3 or cyclopropyl;
  • A is a 3 to 7 membered cycloalkyl ring; each R 4 is selected independently from halo, hydroxyl, methyl, trifluoromethyl, methoxy and cyano; m is an integer between 0 and 5; n is an integer between 1 and 3; or a salt of N-oxide form thereof, as a herbicide.
  • X is H or F, more preferably, X is F.
  • X 2 is H or F; more preferably, X 2 is F.
  • X 3 is H or F.
  • X 4 is H or F.
  • X 1 is F and X 2 , X 3 and X 4 are H. In another embodiment, X 1 and X 3 are F and X 2 and X 4 are H. In another embodiment, X 2 and X 4 are F and X 1 and X 3 are H.
  • Z is oxygen
  • Y is
  • R is H, methyl, ethyl or allyl, more preferably, R is H.
  • W is a direct bond or -CH 2 -.
  • A include optionally substituted cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl and cycloheptyl.
  • A is optionally substituted cyclopentyl or cyclohexyl. More preferably, A is optionally substituted cyclohexyl.
  • Y is
  • n is 1 or 2.
  • R 4 is as defined above or, preferably, each R 4 is independently selected from chloro, bromo or fluoro, methyl or trifluoromethyl. More preferably, each R 4 is chloro or bromo.
  • the R 4 group is present on at least the 2 or 3 positions or both the 2 and 3 positions on the cycloalkyl ring. It is noted that it is possible that two R 4 groups may be present in each position of the cycloalkyl ring systems.
  • substitution patterns for the cycloalkyl rings in either embodiment of Y are 2- chloro-, 2-bromo-, 2-fluoro-, 2-cyano-, 2-methyl-, 2-trifluoromethyl-, 2-methoxy-, 3-chloro-, 3- bromo-, 3-fluoro-, 3-cyano-, 3-methyl-, 3-trifluoromethyl-, 3-methoxy-, 4-chloro-, 4-bromo-, 4- fluoro-, 4-cyano-, 4-methyl-, 4-trifluoromethyl- , 4-methoxy-, 2,2-dichloro-.
  • Preferred substitution patterns for the cycloalkyl rings are 2-chloro-, 3-chloro- 2,3 dichloro-, 2-chloro-2-methyl-, 2-chloro-3-methyl and 3,3-difluoro.
  • A particularly preferred examples of A are 2-chlorocyclohexyl, 2-bromocyclohexyl 3- chlorocyclohexyl, 3-bromocyclohexyl, 2,3 dichlorocyclohexyl, 2,3-dibromocyclohexyl, 2- chlorocyclopentyl, 2-bromocyclopentyl, 3-chlorocyclopentyl, 3-bromocyclopentyl, 2,3
  • the invention provides a compound selected from the list consisting of 2-fluoro-N-(2-bromocyclohexyl)pyridine-4-carboxamide, 2-fluoro-N-(2-iodocyclohexyl)pyridine- 4-carboxamide, 2-fluoro-N-(2-fluorocyclohexyl)pyridine-4-carboxamide, 2-fluoro-N-(2- cyanocyclohexyl)pyridine-4-carboxamide, 2-fluoro-N-(2-azidocyclohexyl)pyridine-4-carboxamide, 2-fluoro-N-(2,2-dimethylcyclohexyl)pyridine-4-carboxamide, 2-fluoro-N-(2,2- difluorocyclohexyl)pyridine-4-carboxamide, 2-fluoro-N-(3,3-difluorocyclohexyl)pyridine-4- carboxamide, 2-fluoro-N-(2-methyl-3-cyan
  • the invention provides a compound selected from the list consisting of 2-fluoro-N-(2-bromocyclohexyl)pyridine-4-carboxamide, 2-fluoro-N-(2- iodocyclohexyl)pyridine-4-carboxamide, 2-fluoro-N-(2-fluorocyclohexyl)pyridine-4-carboxamide, 2-fluoro-N-(2-cyanocyclohexyl)pyridine-4-carboxamide, 2-fluoro-N-(2-azidocyclohexyl)pyridine-4- carboxamide, 2-fluoro-N-(2,2-dimethylcyclohexyl)pyridine-4-carboxamide, 2-fluoro-N-(2,2- difluorocyclohexyl)pyridine-4-carboxamide, 2-fluoro-N-(3,3-difluorocyclohexyl)pyridine-4- carboxamide, 2-fluoro-N-(2-methyl-3-cyan
  • the invention provides the compound 2-fluoro-N-(2- bromocyclohexyl )pyrid i ne-4-carboxam ide.
  • the invention provides the compound 2-fluoro-N-(2- iodocyclohexyl)pyridine-4-carboxamide. In another embodiment, the invention provides the compound 2-fluoro-N-(2- fluorocyclohexyl)pyridine-4-carboxamide. In another embodiment, the invention provides the compound 2-fluoro-N-(2- cyanocyclohexyl)pyridine-4-carboxamide.
  • the invention provides the compound 2-fluoro-N-(2- azidocyclohexyl)pyridine-4-carboxamide. In another embodiment, the invention provides the compound 2-fluoro-N-(2,2- dimethylcyclohexyl)pyridine-4-carboxamide.
  • the invention provides the compound 2-fluoro-N-(2,2- difluorocyclohexyl)pyridine-4-carboxamide.
  • the invention provides the compound 2-fluoro-N-(3,3- difluorocyclohexyl)pyridine-4-carboxamide.
  • the invention provides the compound 2-fluoro-N-(2-methyl-3- cyanocyclohexyl)pyridine-4-carboxamide.
  • the invention provides the compound 2,6-difluoro-N-(2- chlorocyclohexyl)pyridine-4-carboxamide. In another embodiment, the invention provides the compound 2,6-difluoro-N-(2,3- dimethylcyclohexyl)pyridine-4-carboxamide.
  • the invention provides the compounds 2-fluoro-N-(2- methylcyclohexyl)pyridine-4-carbothioamide
  • the invention provides the compound 23. In another embodiment, the invention provides the compound 27.
  • the invention provides the compound 30.
  • the invention provides the compound 31.
  • the invention provides the compound 37. In another embodiment, the invention provides the compound 47.
  • the invention provides the compound 48.
  • the invention provides the compound 49.
  • the invention provides the compound 50. In another embodiment, the invention provides the compound 54.
  • the invention provides the compound 55.
  • the invention provides the compound 56.
  • the invention provides the compound 68.
  • the invention provides the compound 1 10. In another embodiment, the invention provides the compound 129.
  • the invention provides the compound 137.
  • the invention provides the compound 147.
  • the invention provides the compound 163.
  • the invention provides the compound 168. In another embodiment, the invention provides the compound 169.
  • the invention provides the compound 170.
  • the compounds of formula (I) may exist as different geometric isomers, or in different tautomeric forms. This invention covers all such isomers and tautomers, and mixtures thereof in all proportions, as well as isotopic forms such as deuterated compounds.
  • the compounds of this invention may contain an asymmetric carbon atom and some of the compounds of this invention may contain one or more asymmetric centers and may thus give rise to optical isomers and diastereomers. While shown without respect to stereochemistry, the present invention includes such optical isomers and diastereomers as well as the racemic and resolved, enantiomerically pure R and S stereoisomers and, in addition, other mixtures of the R and S stereoisomers and agrochemically acceptable salts thereof. It is recognized that one stereoisomer, including diastereomer and enantiomer, may have favorable properties over the other. Thus when disclosing and claiming the invention, when one racemic mixture is disclosed, it is clearly contemplated that both optical isomers, including diastereomers and enantiomers, or stereoisomers substantially free of the other are disclosed and claimed as well.
  • Procides of the compounds of the invention may also be use as herbicides.
  • the procide contains an additional or alternative substituent to those disclosed above in relation to the compound of the invention, such substituent being removed on application of the procide to the plant (e.g. by metabolism in the plant) to give the active compound of the invention. All such procides are also covered by the invention.
  • Alkyl refers to an aliphatic hydrocarbon chain and includes straight and branched chains e. g. of 1 to 6 carbon atoms such as methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, t-butyl, n-pentyl, isopentyl, neo-pentyl, n-hexyl, and isohexyl.
  • Cycloalkyl refers to a cyclic, saturated hydrocarbon group having from 3 to 7 ring carbon atoms. Examples of cycloalkyl groups are cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl and cycloheptyl.
  • Cycloalkenyl refers to a cyclic hydrocarbon group having from 3 to 7 ring carbon atoms and containing at least one double bond.
  • Examples of cycloalkenyl groups are cyclopropenyl, cyclobutenyl, cyclopentenyl, cyclohexenyl and cycloheptenyl.
  • Preferred cycloalkenyl groups are cyclohexenyl groups with the double bond between the 2 and 3 positions of the ring system.
  • Halo, or halogen refers to chloro, bromo, fluoro or iodo.
  • Aryl refers to an aromatic carbocyclic group of from 6 to 10 carbon atoms having a single ring (e.g., phenyl) or multiple condensed (fused) rings, at least one of which is aromatic (e.g., indanyl, naphthyl).
  • Preferred aryl groups include phenyl, naphthyl and the like. Most preferably, an aryl group is a phenyl group.
  • Heteroaryl refers to a ring system containing 5 to 10 ring atoms, 1 to 4 ring heteroatoms and consisting either of a single aromatic ring or of two or more fused rings, at least one of which is aromatic.
  • single rings will contain up to three and bicyclic systems up to four heteroatoms which will preferably be independently chosen from nitrogen, oxygen and sulfur.
  • Examples of such groups include pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl, triazinyl, furanyl, thiophenyl, oxazolyl, isoxazolyl, oxadiazolyl, thiazolyl, isothiazolyl, thiadiazolyl, pyrrolyl, pyrazolyl, imidazolyl, triazolyl and tetrazolyl.
  • Examples of bicyclic groups are examples of bicyclic groups.
  • heteroaryl groups are pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl and thiophenyl.
  • "Optionally substituted" as used herein means the group referred to can be substituted at one or more positions by any one or any combination of the radicals listed thereafter. For most groups, one or more hydrogen atoms are replaced by the radicals listed thereafter.
  • Suitable salts can be formed from organic and inorganic acids, for example, acetic, propionic, lactic, citric, tartaric, succinic, fumaric, maleic, malonic, mandelic, malic, phthalic, hydrochloric, hydrobromic, phosphoric, nitric, sulfuric, methanesulfonic, naphthalenesulfonic, benzenesulfonic, toluenesulfonic, or camphorsulfonic acid, and similarly known acceptable acids when a compound of this invention contains a basic moiety.
  • organic and inorganic acids for example, acetic, propionic, lactic, citric, tartaric, succinic, fumaric, maleic, malonic, mandelic, malic, phthalic, hydrochloric, hydrobromic, phosphoric, nitric, sulfuric, methanesulfonic, naphthalenesulfonic, benzenesulfonic, tolu
  • suitable salts also include those derived from alkali or alkaline earth metals and those derived from ammonia and amines.
  • Preferred cations include sodium, potassium, magnesium, and ammonium cations of the formula N + (R 9 R 20 R 2 R 22 ) wherein R 9 , R 20 , R 2 and R 22 are independently selected from hydrogen, Ci-C 6 alkyl and Ci-C 6 hydroxyalkyl.
  • Salts of the compounds of Formula I can be prepared by treatment of compounds of formula (I) with a metal hydroxide, such as sodium hydroxide, or an amine, such as ammonia, trimethylamine, diethanolamine, 2- methylthiopropylamine, bisallylamine, 2-butoxyethylamine, morpholine, cyclododecylamine, or benzylamine.
  • a metal hydroxide such as sodium hydroxide
  • an amine such as ammonia, trimethylamine, diethanolamine, 2- methylthiopropylamine, bisallylamine, 2-butoxyethylamine, morpholine, cyclododecylamine, or benzylamine.
  • Amine salts are often preferred forms of the compounds of Formula I because they are water-soluble and lend themselves to the preparation of desirable aqueous based herbicidal compositions.
  • the compounds of this invention contain one or more asymmetric centers, as indicated above, this may give rise to optical isomers and diastereomers.
  • These isomers may be separated using several techniques, such as crystallisation, enzymatic resolution and High Performance Liquid Chromatography (HPLC) using either normal phase solvents or reverse phase solvents as the mobile phase eluant.
  • the stationary phase may be silica gel or a chiral material that allows the asymmetrical compounds to be resolved into the enantiomers. Examples of some of these techniques are outlined in "Stereochemistry of Organic Compounds", Wiley Interscience, Chapter 7, from page 297.
  • compounds of formula (I) may also be prepared by treating the compound of formula (V) wherein X 1 , X 2 , X 3 and X 4 are defined above with an amine of formula (Y) or a salt thereof (for example a hydrochloride salt) in the presence of a base:
  • the reaction is usually carried out in the presence of a solvent.
  • solvents used in the reaction include a haloalkane such as dichloromethane (DCM) or an ether such as tetrahydrofuran (THF).
  • the base used in such reactions include a nitrogen- containing aromatic compound such as pyridine, or a tertiary amine such as triethylamine or N,N- Diisopropylethylamine or an inorganic base such as a metal carbonate, for example, potassium carbonate.
  • the amine of formula (Y) may contain one or more asymmetric centers and hence give optical isomers or diastereomers of compounds of formula (I).
  • an amine of formula (Y) containing one asymmetric center can result in the compound of formula (I) and a compound of formula (Y) with the opposite asymmetric center can result in the isomer of compound of formula (I) itself with the opposite asymmetric center.
  • Intermediate amines of formula (Y) can be obtained commercially or be prepared by techniques known to the person skilled in the art of organic chemistry. Where amines of formula (Y) have an asymmetric center these may be obtained commercially, from resolution of the racemic amine or by synthesis of the asymmetric amine from suitable starting materials, by techniques known to the person skilled in the art of organic chemistry.
  • compounds of formula (I) may also be prepared by treating the compound of formula (VI) wherein X 1 , X 2 , X 3 and X 4 are defined above with an amine of formula (Y) or a salt thereof (for example an hydrochloride salt) in the presence of a base and suitable amide coupling reagents (for example 1-hydroxybenzotriazole/3-(ethyliminomethyleneamino)-N,N-dimethyl- propan-1 -amine hydrochloride or 2,4,6-tripropyl-1 ,3,5-trioxa-2,4,6-triphosphinane-2,4,6-trioxide or 0-(7-azabenzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate): wherein R , W and A are defined above.
  • compounds of formula (VIII) may also be prepared by treating the compound of formula (VII) wherein X 1 , X 2 , X 3 , X 4 m, n and R 4 are defined above with a suitable nucleophile (for example trimethylsilylcyanide or zinc bromide or tetrabutylammonium fluoride or sodium methoxide):
  • a suitable nucleophile for example trimethylsilylcyanide or zinc bromide or tetrabutylammonium fluoride or sodium methoxide
  • the compounds of formula (I) according to the invention can be used as herbicides in unmodified form, as obtained in the synthesis, but they are generally formulated into herbicidal compositions in various ways using formulation adjuvants, such as carriers, solvents and surface- active substances. Therefore, the invention also relates to a herbicidal composition which comprises a herbicidally effective amount of a compound of formula (I) in addition to formulation adjuvants.
  • the formulations can be in various physical forms, e.g.
  • the formulations can be prepared e.g. by mixing the active ingredient with the formulation adjuvants in order to obtain compositions in the form of finely divided solids, granules, solutions, dispersions or emulsions.
  • the active ingredients can also be formulated with other adjuvants, such as finely divided solids, mineral oils, oils of vegetable or animal origin, modified oils of vegetable or animal origin, organic solvents, water, surface-active substances or combinations thereof.
  • the active ingredients can also be contained in very fine microcapsules consisting of a polymer. Microcapsules contain the active ingredients in a porous carrier. This enables the active ingredients to be released into the environment in controlled amounts (e.g. slow-release). Microcapsules usually have a diameter of from 0.1 to 500 microns.
  • the active ingredients contain active ingredients in an amount of about from 25 to 95 % by weight of the capsule weight.
  • the active ingredients can be in the form of a monolithic solid, in the form of fine particles in solid or liquid dispersion or in the form of a suitable solution.
  • the encapsulating membranes comprise, for example, natural or synthetic rubbers, cellulose, styrene/butadiene copolymers, polyacrylonitrile, polyacrylate, polyesters, polyamides, polyureas, polyurethane or chemically modified polymers and starch xanthates or other polymers that are known to the person skilled in the art in this connection.
  • very fine microcapsules can be formed in which the active ingredient is contained in the form of finely divided particles in a solid matrix of base substance, but the microcapsules are not themselves encapsulated.
  • liquid carriers there may be used: water, toluene, xylene, petroleum ether, vegetable oils, acetone, methyl ethyl ketone, cyclohexanone, acid anhydrides, acetonitrile, acetophenone, amyl acetate, 2-butanone, butylene carbonate, chlorobenzene, cyclohexane, cyclohexanol, alkyl esters of acetic acid, diacetone alcohol, 1 ,2- dichloropropane, diethanolamine, p-diethylbenzene, diethylene glycol, diethylene glycol abietate, diethylene glycol butyl ether, diethylene glycol ethyl ether, diethylene glycol methyl ether, N,N- dimethylformamide, dimethyl sulfoxide, 1 ,4-dioxane, dipropylene
  • Water is generally the carrier of choice for diluting the concentrates.
  • suitable solid carriers are, for example, talc, titanium dioxide, pyrophyllite clay, silica, attapulgite clay, kieselguhr, limestone, calcium carbonate, bentonite, calcium montmorillonite, cottonseed husks, wheat flour, soybean flour, pumice, wood flour, ground walnut shells, lignin and similar substances, as described, for example, in CFR 180.1001.
  • a large number of surface-active substances can advantageously be used in both solid and liquid formulations, especially in those formulations which can be diluted with a carrier prior to use.
  • Surface-active substances may be anionic, cationic, non-ionic or polymeric and they can be used as emulsifiers, wetting agents or suspending agents or for other purposes.
  • Typical surface-active substances include, for example, salts of alkyl sulfates, such as
  • alkylarylsulfonates such as calcium dodecyl- benzenesulfonate
  • alkylphenol/alkylene oxide addition products such as nonylphenol ethoxylate
  • alcohol/alkylene oxide addition products such as tridecylalcohol ethoxylate
  • soaps such as sodium stearate
  • salts of alkylnaphthalenesulfonat.es such as sodium
  • dibutylnaphthalenesulfonate dialkyl esters of sulfosuccinate salts, such as sodium di(2- ethylhexyl)sulfosuccinate; sorbitol esters, such as sorbitol oleate; quaternary amines, such as lauryltrimethylammonium chloride, polyethylene glycol esters of fatty acids, such as polyethylene glycol stearate; block copolymers of ethylene oxide and propylene oxide; and salts of mono- and di-alkylphosphate esters; and also further substances described e.g. in "McCutcheon's
  • crystallization inhibitors such as crystallization inhibitors, viscosity modifiers, suspending agents, dyes, anti-oxidants, foaming agents, light absorbers, mixing auxiliaries, antifoams, complexing agents, neutralizing or pH- modifying substances and buffers, corrosion inhibitors, fragrances, wetting agents, take-up enhancers, micronutrients, plasticisers, glidants, lubricants, dispersants, thickeners, antifreezes, microbicides, and also liquid and solid fertilizers.
  • compositions according to the invention can additionally include an additive comprising an oil of vegetable or animal origin, a mineral oil, alkyl esters of such oils or mixtures of such oils and oil derivatives.
  • the amount of oil additive in the composition according to the invention is generally from 0.01 to 10 %, based on the spray mixture.
  • the oil additive can be added to the spray tank in the desired concentration after the spray mixture has been prepared.
  • Preferred oil additives comprise mineral oils or an oil of vegetable origin, for example rapeseed oil, olive oil or sunflower oil, emulsified vegetable oil, such as AMIGO® (Rhone-Poulenc Canada Inc.), alkyl esters of oils of vegetable origin, for example the methyl derivatives, or an oil of animal origin, such as fish oil or beef tallow.
  • a preferred additive contains, for example, as active components essentially 80 % by weight alkyl esters of fish oils and 15 % by weight methylated rapeseed oil, and also 5 % by weight of customary emulsifiers and pH modifiers.
  • Especially preferred oil additives comprise alkyl esters of C 8 -C 2 2 fatty acids, especially the methyl derivatives of Ci 2 -Ci 8 fatty acids, for example the methyl esters of lauric acid, palmitic acid and oleic acid, being of importance.
  • Those esters are known as methyl laurate (CAS-1 1 1- 82-0), methyl palmitate (CAS-1 12-39-0) and methyl oleate (CAS-1 12-62-9).
  • a preferred fatty acid methyl ester derivative is Emery® 2230 and 2231 (Cognis GmbH).
  • Those and other oil derivatives are also known from the Compendium of Herbicide Adjuvants, 5th Edition, Southern Illinois University, 2000.
  • the application and action of the oil additives can be further improved by combination with surface-active substances, such as non-ionic, anionic or cationic surfactants.
  • surface-active substances such as non-ionic, anionic or cationic surfactants.
  • suitable anionic, non-ionic and cationic surfactants are listed on pages 7 and 8 of WO 97/34485.
  • Preferred surface-active substances are anionic surfactants of the dodecylbenzylsulfonate type, especially the calcium salts thereof, and also non-ionic surfactants of the fatty alcohol ethoxylate type. Special preference is given to ethoxylated C12-C22 fatty alcohols having a degree of ethoxylation of from 5 to 40.
  • Examples of commercially available surfactants are the Genapol types (Clariant AG).
  • silicone surfactants especially polyalkyl-oxide-modified heptamethyltriloxanes which are commercially available e.g. as Silwet L-77®, and also perfluorinated surfactants.
  • concentration of the surface-active substances in relation to the total additive is generally from 1 to 30 % by weight.
  • oil additives consisting of mixtures of oil or mineral oils or derivatives thereof with surfactants are Edenor ME SU®, Turbocharge® (Syngenta AG, CH) or ActipronC (BP Oil UK Limited, GB).
  • an organic solvent may contribute to an additional enhancement of action.
  • Suitable solvents are, for example, Solvesso® (ESSO) or Aromatic Solvent® (Exxon Corporation). The concentration of such solvents can be from 10 to 80 % by weight of the total weight.
  • Oil additives that are present in admixture with solvents are described, for example, in US-A-4,834,908.
  • a commercially available oil additive disclosed therein is known by the name MERGE® (BASF Corporation).
  • a further oil additive that is preferred according to the invention is SCORE® (Syngenta Crop Protection Canada).
  • compositions according to the invention for the purpose of enhancing the action of the compositions according to the invention it is also possible for formulations of alkylpyrrolidones (e.g. Agrimax®) to be added to the spray mixture.
  • alkylpyrrolidones e.g. Agrimax®
  • synthetic lattices e.g.
  • polyacrylamide, polyvinyl compounds or poly-1-p-menthene may also be used. It is also possible for solutions that contain propionic acid, for example Eurogkem Pen-e-trate®, to be added to the spray mixture as action-enhancing agent.
  • propionic acid for example Eurogkem Pen-e-trate®
  • the herbicidal compositions generally comprise from 0.1 to 99 % by weight, especially from 0.1 to 95 % by weight, compounds of formula (I) and from 1 to 99.9 % by weight of a formulation adjuvant which preferably includes from 0 to 25 % by weight of a surface-active substance.
  • a formulation adjuvant which preferably includes from 0 to 25 % by weight of a surface-active substance.
  • commercial products will preferably be formulated as concentrates, the end user will normally employ dilute formulations.
  • the rates of application of compounds of formula (I) may vary within wide limits and depend on the nature of the soil, the method of application (pre- or post-emergence; seed dressing; application to the seed furrow; no tillage application etc.), the crop plant, the grass or weed to be controlled, the prevailing climatic conditions, and other factors governed by the method of application, the time of application and the target crop.
  • the compounds of formula (I) according to the invention are generally applied at a rate of from 10 to 2000 g/ha, especially from 50 to 1000 g/ha.
  • Emulsifiable concentrates are:
  • active ingredient 1 to 95 %, preferably 60 to 90 %
  • surface-active agent 1 to 30 %, preferably 5 to 20 %
  • liquid carrier 1 to 80 %, preferably 1 to 35 % Dusts:
  • active ingredient 0.1 to 10 %, preferably 0.1 to 5 %
  • solid carrier 99.9 to 90 %, preferably 99.9 to 99 %
  • active ingredient 5 to 75 %, preferably 10 to 50 %
  • surface-active agent 1 to 40 %, preferably 2 to 30 %
  • active ingredient 0.5 to 90 %, preferably 1 to 80 %
  • surface-active agent 0.5 to 20 %, preferably 1 to 15 %
  • solid carrier 5 to 95 %, preferably 15 to 90 %
  • active ingredient 0.1 to 30 %, preferably 0.1 to 15 %
  • solid carrier 99.5 to 70 %, preferably 97 to 85 %
  • Emulsifiable concentrates a) b) c) d) active ingredient 5 % 10 % 25 % 50 % calcium dodecylbenzenesulfonate 6 % 8 % 6 % 8 % castor oil polyglycol ether 4 % 4 % 4 % (36 mol of ethylene oxide)
  • NMP 20 % arom. hydrocarbon mixture 85 % 78 % 16 % Emulsions of any desired concentration can be obtained from such concentrates by dilution with water.
  • the solutions are suitable for use in the form of microdrops.
  • Wettable powders a) b) c) d) active ingredient 5 % 25 % 50 % 80 % sodium lignosulfonate 4 % 3 %
  • the active ingredient is mixed thoroughly with the adjuvants and the mixture is thoroughly ground in a suitable mill, affording wettable powders which can be diluted with water to give suspensions of any desired concentration.
  • the active ingredient is dissolved in methylene chloride and applied to the carrier by spraying, and the solvent is then evaporated off in vacuo.
  • active ingredient 0.1 % 5 % 15 % polyethylene glycol MW 200 1.0 % 2 % 3 % highly dispersed silicic acid 0.9 % 1 % 2 % inorganic carrier 98.0 % 92 % 80 % (diameter 0.1 - 1 mm)
  • the finely ground active ingredient is uniformly applied, in a mixer, to the carrier moistened with polyethylene glycol.
  • Non-dusty coated granules are obtained in this manner.
  • the active ingredient is mixed and ground with the adjuvants, and the mixture is moistened with water.
  • the mixture is extruded and then dried in a stream of air.
  • Ready-to-use dusts are obtained by mixing the active ingredient with the carriers and grinding the mixture in a suitable mill.
  • Suspension concentrates a) b) c) d) active ingredient 3 % 10 % 25 % 50 % ethylene glycol 5 % 5 % 5 % 5 % nonylphenol polyglycol ether 1 % 2 %
  • the finely ground active ingredient is intimately mixed with the adjuvants, giving a suspension concentrate from which suspensions of any desired concentration can be obtained by dilution with water.
  • the invention also provides a method of controlling plants which comprises applying to the plants or to the locus thereof a herbicidally effective amount of a compound of formula (I).
  • the invention also provides a method of inhibiting plant growth which comprises applying to the plants or to the locus thereof a herbicidally effective amount of a compound of formula (I).
  • the invention also provides a method of controlling weeds in crops of useful plants, comprising applying to said weeds or to the locus of said weeds, or to said useful plants or to the locus of said useful plants, a compound or a composition of the invention.
  • the invention also provides a method of selectively controlling grasses and/or weeds in crops of useful plants which comprises applying to the useful plants or locus thereof or to the area of cultivation a herbicidally effective amount of a compound of formula (I).
  • herbicide as used herein means a compound that controls or modifies the growth of plants.
  • herbicidally effective amount means the quantity of such a compound or combination of such compounds that is capable of producing a controlling or modifying effect on the growth of plants. Controlling or modifying effects include all deviation from natural development, for example: killing, retardation, leaf burn, albinism, dwarfing and the like.
  • plants refers to all physical parts of a plant, including seeds, seedlings, saplings, roots, tubers, stems, stalks, foliage, and fruits.
  • locus is intended to include soil, seeds, and seedlings, as well as established vegetation and includes not only areas where weeds may already be growing, but also areas where weeds have yet to emerge, and also to areas under cultivation with respect to crops of useful plants.
  • “Areas under cultivation” include land on which the crop plants are already growing and land intended for cultivation with such crop plants.
  • weeds as used herein means any undesired plant, and thus includes not only
  • agronomically important weeds as described below, but also volunteer crop plants.
  • the compounds for use in the invention can be applied before or after planting of the crops, before weeds emerge (pre-emergence application) or after weeds emerge (post- emergence application).
  • Crops of useful plants in which the composition according to the invention can be used include, but are not limited to, perennial crops, such as citrus fruit, grapevines, nuts, oil palms, olives, pome fruit, stone fruit and rubber, and annual arable crops, such as cereals, for example barley and wheat, cotton, oilseed rape, maize, rice, soy beans, sugar beet, sugar cane, sunflowers, ornamentals, switchgrass, turf and vegetables, especially cereals, maize and soy beans.
  • perennial crops such as citrus fruit, grapevines, nuts, oil palms, olives, pome fruit, stone fruit and rubber
  • annual arable crops such as cereals, for example barley and wheat, cotton, oilseed rape, maize, rice, soy beans, sugar beet, sugar cane, sunflowers, ornamentals, switchgrass, turf and vegetables, especially cereals, maize and soy beans.
  • the grasses and weeds to be controlled may be both monocotyledonous species, for example Agrostis, Alopecurus, Avena, Brachiaria, Bromus, Cenchrus, Cyperus, Digitaria, Echinochloa, Eriochloa, Lolium, Monochoria, Panicum, Poa, Rottboellia, Sagittaria, Scirpus, Setaria, Sida and Sorghum, and dicotyledonous species, for example Abutilon, Amaranthus, Chenopodium, Chrysanthemum, Euphorbia, Galium, Ipomoea, Kochia, Nasturtium, Polygonum, Sida, Sinapis, Solanum, Stellaria, Veronica, Viola and Xanthium.
  • Agrostis Alopecurus
  • Avena Brachiaria
  • Bromus Cenchrus
  • Cyperus Digitaria
  • Echinochloa Eriochloa
  • Lolium Monochori
  • Crops are to be understood as also including those crops which have been rendered tolerant to herbicides or classes of herbicides (e.g. auxins or ALS-, EPSPS-, PPO- and HPPD- inhibitors) by conventional methods of breeding or by genetic engineering.
  • herbicides or classes of herbicides e.g. auxins or ALS-, EPSPS-, PPO- and HPPD- inhibitors
  • An example of a crop that has been rendered tolerant to imidazolinones, e.g. imazamox, by conventional methods of breeding is Clearfield® summer rape (canola).
  • crops that have been rendered tolerant to herbicides by genetic engineering methods include e.g. glyphosate- and glufosinate- resistant maize varieties commercially available under the trade names RoundupReady® and LibertyLink®, respectively.
  • Crops are also to be understood as being those which have been rendered resistant to harmful insects by genetic engineering methods, for example Bt maize (resistant to European corn borer), Bt cotton (resistant to cotton boll weevil) and also Bt potatoes (resistant to Colorado beetle).
  • Bt maize are the Bt 176 maize hybrids of NK® (Syngenta Seeds).
  • the Bt toxin is a protein that is formed naturally by Bacillus thuringiensis soil bacteria.
  • Examples of toxins, or transgenic plants able to synthesize such toxins are described in EP-A-451 878, EP-A- 374 753, WO 93/07278, WO 95/34656, WO 03/052073 and EP-A-427 529.
  • transgenic plants comprising one or more genes that code for an insecticidal resistance and express one or more toxins are KnockOut® (maize), Yield Gard® (maize), NuCOTIN33B® (cotton), Bollgard® (cotton), NewLeaf® (potatoes), NatureGard® and Protexcta®.
  • Plant crops or seed material thereof can be both resistant to herbicides and, at the same time, resistant to insect feeding ("stacked" transgenic events).
  • seed can have the ability to express an insecticidal Cry3 protein while at the same time being tolerant to glyphosate.
  • Crops are also to be understood as being those which are obtained by conventional methods of breeding or genetic engineering and contain so-called output traits (e.g. improved storage stability, higher nutritional value and improved flavor).
  • output traits e.g. improved storage stability, higher nutritional value and improved flavor.
  • Any method of application to weeds/crop of useful plant, or locus thereof, which is routinely used in agriculture may be used, for example application by spray or broadcast method typically after suitable dilution of a compound of formula (I) (whether said compound is formulated and/or in combination with one or more further active ingredients and/or safeners, as described herein).
  • the compounds of formula (I) according to the invention can also be used in combination with other active ingredients, e.g. other herbicides, and/or insecticides, and/or acaricides, and/or nematocides, and/or molluscicides, and/or fungicides, and/or plant growth regulators.
  • other active ingredients e.g. other herbicides, and/or insecticides, and/or acaricides, and/or nematocides, and/or molluscicides, and/or fungicides, and/or plant growth regulators.
  • mixtures of invention also include mixtures of two or more different compounds of formula (I).
  • the present invention also provides a composition which comprises at least one further herbicide in addition to the compound of formula (I).
  • the present invention provides a composition comprising a compound of formula (I) + ametryn, a compound of formula (I) + atrazine, a compound of formula (I) + bicyclopyrone, a compound of formula (I) + cinosulfuron, a compound of formula (I) + clodinafop-propargyl, a compound of formula (I) + clomazone, a compound of formula (I) + dicamba, a compound of formula (I) + dimethachlor, a compound of formula (I) + diquat, a compound of formula (I) + fluazifop-p-butyl, a compound of formula (I) + fomesafen, a compound of formula (I) + glyphosate, a compound of formula (I) + mesotrione, a compound of formula (I) + molinate, a compound of formula (I) + napropamide, a compound of formula (
  • the mixing partners of the compound of formula (I) may also be in the form of esters or salts, as mentioned e.g. in The Pesticide Manual, 14th Edition (BCPC), 2006.
  • the reference to acifluorfen-sodium also applies to acifluorfen
  • the reference to dimethenamid also applies to dimethenamid-P
  • the reference to glufosinate-ammonium also applies to glufosinate
  • the reference to bensulfuron-methyl also applies to bensulfuron
  • the reference to cloransulam-methyl also applies to cloransulam
  • the reference to flamprop-M also applies to flamprop
  • the reference to pyrithiobac-sodium also applies to pyrithiobac, etc.
  • the mixing ratio of the compound of formula (I) to the mixing partner is preferably from 1 : 100 to 1000: 1.
  • mixtures can advantageously be used in the above-mentioned formulations (in which case "active ingredient” relates to the respective mixture of compound of formula (I) with the mixing partner).
  • the compounds of formula (I) according to the invention can also be used in combination with one or more safeners.
  • mixtures of a compound of formula (I) according to the invention with one or more further active ingredients, in particular with one or more further herbicides can also be used in combination with one or more safeners.
  • safener as used herein means a chemical that when used in combination with a herbicide reduces the undesirable effects of the herbicide on non-target organisms, for example, a safener protects crops from injury by herbicides but does not prevent the herbicide from killing the weeds.
  • a compound of formula (I) is combined with a safener, the following combinations of the compound of formula (I) and the safener are particularly preferred.
  • the safeners of the compound of formula (I) may also be in the form of esters or salts, as mentioned e.g. in The Pesticide Manual, 14th Edition (BCPC), 2006.
  • the reference to cloquintocet-mexyl also applies to cloquintocet and to a lithium, sodium, potassium, calcium, magnesium, aluminium, iron, ammonium, quaternary ammonium, sulfonium or phosphonium salt thereof as disclosed in WO02/34048 and the reference to fenchlorazole-ethyl also applies to fenchlorazole, etc.
  • the mixing ratio of compound of formula (I) to safener is from 100: 1 to 1 : 10, especially from 20: 1 to 1 : 1.
  • the mixtures can advantageously be used in the above-mentioned formulations (in which case "active ingredient” relates to the respective mixture of compound of formula (I) and any further active ingredient, in particular a further herbicide, with the safener).
  • active ingredient relates to the respective mixture of compound of formula (I) and any further active ingredient, in particular a further herbicide, with the safener.
  • the safener and a compound of formula (I) and one or more additional herbicide(s), if any are applied simultaneously.
  • the safener, a compound of formula (I) and one or more additional herbicide(s), if any might be applied to the locus pre-emergence or might be applied to the crop post-emergence.
  • the safener and a compound of formula (I) and one or more additional herbicide(s), if any are applied sequentially.
  • the safener might be applied before sowing the seeds as a seed treatment and a compound of formula (I) and one or more additional herbicides, if any, might be applied to the locus pre-
  • A/-(2,3-Dimethylcyclohexyl)-2-fluoro-pyridine-4-carboxamide is commercially available as a mixture of stereoisomers and was separated into four pairs of enantiomers using mass directed reverse phase and then normal phase chromatography, as detailed in the following sentences.
  • An initial separation was made by mass directed preparative HPLC using a mixed trigger of UV with ES+ on a Waters Fraction Lynx system comprising a 2767 injector/collector with a 2545 gradient pump, two 515 isocratic pumps, SFO, 2998 photodiode array, 2424 ELSD and 3100 mass spectrometer.
  • a Waters XBridge dC18 5micron 19x10mm guard column was used with an ACE c!C18-Ar 5micron 30x1 OOmm prep column.
  • the preparative HPLC was conducted using a 20 minute run time using 'at column dilution ' , according to the following gradient table.
  • Solvent B CH 3 CN with 0.05% TFA
  • Characterising data for the compound are as follows: 1H NMR (400 MHz, CD30D) ⁇ ppm 8.33 (m, 1H), 7.66 (m, 1H), 7.43 (m, 1H), 4.04 (m, 1H), 2.20-2.11 (m, 1H), 1.89-1.70 (m, 1H), 1.70- 1.53 (m, 1H), 1.53-1.35 (m, 1H), 1.30-1.17 (m, 1H), 1.04-0.94 (m, 1H), 0.95 (d, 3H), 0.85 (m, 1H).
  • Characterising data for the compound are as follows: 1H NMR (400 MHz, CD30D) ⁇ ppm 8.33 (m, 1H), 7.66 (m,1H), 7.42 (m, 1H), 3.67 (m, 1H), 1.96-1.87 (m, 1H), 1.83-1.74 (m,1H), 1.74-1.65 (m, 1H), 1.52-1.30 (m, 2H), 1.27-1.13 (m, 2H), 1.13-1.00 (m, 1H), 0.98 (m, 6H).
  • the yellow gum was purified by mass directed preparative HPLC using a mixed trigger of UV with ES+ on a Waters Fraction Lynx system comprising a 2767 injector/collector with a 2545 gradient pump, two 515 isocratic pumps, SFO, 2998 photodiode array, 2424 ELSD and 3100 mass spectrometer.
  • a Waters XBridge dC18 5micron 19x10mm guard column was used with an ACE dC18-Ar 5micron 30x100mm prep column.
  • the preparative HPLC was conducted using a 1 1.4 minute run time using 'at column dilution ' , according to the following gradient table:
  • reaction mixture was concentrated in vacuo to leave an orange oil which was adsorbed onto silica gel and purified using silica gel (80g column) chromatography with gradient elution (0-50% EtOAc in isohexane) to give compounds Nos. 37 and 38.
  • Characterising data for the compound are as follows: 1 H NMR (400 MHz, CDCI3) ⁇ ppm 8.23 (d, 1 H), 8.13 (d, 1 H), 7.40 (d, 1 H), 7.13 (s, 1 H), 4.32 (dd, 1 H), 2.18-2.24 (m, 1 H) 1.70-1.89 (m, 3H), 1.52-1.67 (m, 1 H), 1.41 (d, 1 H), 1.28-1.17 (m, 3H), 1 .02 (d, 3H).
  • Compound No. 38 cis-2-fluoro-N-(2-methylcyclohexyl)pyridine-4-carbothioamide (158mgs, 14.1 %). Characterising data for the compound are as follows: 1 H NMR (400 MHz, CDCI3) ⁇ ppm 8.23 (d, 1 H), 7.64 (br s, 1 H), 7.38 (d, 1 H), 7.14 (s, 1 H), 4.71-4.82 (m, 1 H), 2.19 (dd, 1 H), 1.95 (td, 1 H), 1.28-1.76 (m, 7H), 0.99 (d, 3H).
  • reaction mass was diluted with dichloromethane (50ml) and washed with water (2x 50ml), dried over anhydrous sodium sulfate and the solvents were evaporated under reduced pressure.
  • the crude product was purified by Combiflash chromatography to give 7-azabicyclo[4.1 .0]heptan-7-yl-(2- fluoro-4-pyridyl)methanone (2.7g, 49.6%) as an off-white solid.
  • Characterising data for the compound are as follows: 1 H NMR (400 MHz, CDCI3) ⁇ ppm 8.33 (m, 1 H), 7.47 (m, 1 H), 7.26 (m, 1 H), 6.10 (br, 1 H), 4.43 (m, 0.5H), 4.33 (m, 0.5H), 4.08 (m, 1 H),2.23 (m, 1 H), 1.84 (m, 1 H), 1.71 (m, 1 H),1.62-1.24 (m, 4H).
  • 2-Fluoropyridine-4-carboxylic acid (0.34 g, 2.4 mmol), 1-hydroxybenzotriazole (0.69g, 4.9 mmol), 3-(ethyliminomethyleneamino)-N,N-dimethyl-propan-1-amine hydrochloride (0.93 g, 4.9 mmol) and pyridine (0.24 mL, 2.9 mmol) were added to a stirring solution of 2,2- difluorocyclohexylamine hydrochloride (500 mg, 2.9 mmol) in N,N-dimethylformamide (7 mL) at room temperature. The reaction mixture was stirred overnight. Sodium bicarbonate (sat.
  • 170 1000 100 100 70 60 90 100
  • SOLNI Solanum nigrum
  • AMARE Amaranthus retroflexus
  • SETFA Setaria faberi
  • ALOMY Alopecurus myosuroides
  • ECHCG Echinochloa crus-galli
  • IPOHE Ipomea hederaceae
  • ABUTH Abuthilon theophrasti.
  • AMARE Amaranthus retroflexus
  • STEME Stellaria media
  • LOLPE Lolium perenne
  • DIGSA Digitaria sanguinalis Herbicidal Action - Test 3
  • Seeds of a variety of test species were sown in standard soil in pots. After cultivation for one day (pre-emergence) or after 12 days cultivation (post-emergence) under controlled conditions in a glasshouse (warm climate species at 24/18°C, cool climate species at 20/16°C, both at day/night; 16 hours light; 65 % humidity), the plants were sprayed with an aqueous spray solution derived from the formulation of the technical active ingredient dissolved in acetone plus IF50 containing 10.56 wt% Emulsogen EL, 42.22 wt% N-MethylPyrrolidon, 2.22 wt% DPG-Monoethyl ether at a 1 :20 ratio (technical active ingredient : IF50.
  • the adjuvant X-77 is added to form a 0.2% v/v solution.

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Abstract

The invention relates to the use of amide derivatives of the formula (I) wherein X1, X2, X3, X4, Z1 and Y are as defined in the specification as herbicides. Furthermore, the present invention relates to certain novel substituted amide derivatives, to processes for their preparation, herbicidal compositions comprising them, and their use in controlling plants or inhibiting plant growth.

Description

PYRIDINE DERIVATIVES AND THEIR USE AS HERBICIDES
The present invention relates to the use of certain substituted amide derivatives as herbicides. It also relates to certain novel substituted amide derivatives, to processes for their preparation, herbicidal compositions comprising them, and their use in controlling plants or inhibiting plant growth.
Amide derivatives of the formula:
Figure imgf000002_0001
wherein X1 and X2 are, inter alia, fluorine, Z is, inter alia, oxygen and E is, inter alia, a C3-C6 cycloalkyi group which may be joined directly to the nitrogen atom or via a linker, are described in EP 2 174 931 A1 as having fungicidal activity.
However, it has now been found that some amide derivatives are also active as herbicides.
Accordingly, in a first aspect, the invention provides the use of a compound of formula (I):
Figure imgf000002_0002
(I)
wherein:
X1 , X2, X3 and X4 are, independently, H, CI, F, trifluoromethyl, cyano, C1-C3 alkyl, d-C3-alkenyl, - S-C1-C3 alkyl or C1-C3 alkoxy provided that at least one of X1 , X2, X3 and X4 is not H; Z is oxygen or sulphur;
Y is
Figure imgf000003_0001
R is H or C1-C3 alkyl, allyl, arylmethyl or heteroarylmethyl;
W is -CR2R3- or a direct bond and R2 and R3 are, independently, selected from H, -CH3 or cyclopropyl;
A is a 3 to 7 membered cycloalkyl ring or a 3-7 membered cycloalkenyl ring; each R4 is selected independently from halo, hydroxyl, cyano, C1-C4 alkyl, C1-C3 haloalkyi , C1-C3 hydroxyalkyl, C1-C3 alkoxy -S-C1-C3 alkyl, azido or the group =0; m is an integer between 0 and 5; n is an integer between 1 and 3; or a salt or N-oxide form thereof, as a herbicide.
In particularly preferred embodiments of the invention, the preferred groups for X1 , X2, X3, X4, R , R4, m, n, W, Y, Z and A, in any combination thereof, are as set out below.
Preferably, X1 , X2, X3 and X4 are, independently, H, CI or F provided that at least one of X , X2, X3 and X4 is not H.
Preferably, (i) X1 is F or CI and X2, X3 and X4 are H, or (ii) X1 and X2 are F or CI and X3 and X4 are H or (iii) X1 and X3 are F or CI and X2 and X4 are H.
More preferably, (i) X1 is F or CI and X2, X3 and X4 are H or (ii) X1 and X2 are F or CI and X3 and X4 are H. More preferably, X1 is F and X2 is F or H. Most preferably, X1 is F and X2 is H. Preferably Z is oxygen.
In one embodiment, Y is
Figure imgf000003_0002
and R4 is as described above. Preferably n is 1 or 2. In a preferred embodiment, Y is
Figure imgf000004_0001
Preferably R is H, methyl, ethyl or allyl. More preferably, R is H.
Preferably W is a direct bond or -CH2-. More preferably, W is a direct bond.
Examples of A include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl and cycloheptyl as well as cyclopentenyl and cyclohexenyl, all of which may be substituted by one or more groups R4. Preferably, A is optionally substituted cyclopentyl or optionally substituted cyclohexyl. More preferably, A is optionally substituted cyclohexyl.
Preferably, m is 1 or 2 or 3 and R4 is as defined above or, preferably, each R4 is independently selected from halo, hydroxyl, cyano, methyl, trifluoromethyl, azido or methoxy. More preferably, each R4 is independently selected from chloro, bromo, iodo, fluoro, methyl, cyano, or trifluoromethyl. Even more preferably, each R4 is chloro, bromo, cyano or methyl.
Preferably, the R4 group is present on at least the 2 or 3 positions or both the 2 and 3 positions on the cycloalkyi ring, for example, the substitution pattern may be 2-cycloalkyl, 3- cycloalkyl, 2,2-cycloalkyl, 2,3-cycloalkyl or 3,3-cycloalkyl wherein, when more than one substituent is present, each of the substituents may be the same or different. It is noted that it is possible that two R4 groups may be present in each position of the cycloalkyi ring systems.
Examples of substitution patterns for the cycloalkyi ring are unsubstituted, 1-hydroxy-, 2- chloro-, 2-bromo-, 2-iodo-, 2-fluoro-, 2-cyano-, 2-methyl-, 2-trifluoromethyl-, 2-methoxy-, 3-chloro- , 3-bromo-, 2-iodo-, 3-fluoro-, 3-cyano-, 3-methyl-, 3-trifluoromethyl-, 3-methoxy-, 4-chloro-, 4- bromo-, 4-fluoro-, 4-cyano-, 4-methyl-, 4-trifluoromethyl- , 4-methoxy-, 2,2-dichloro-, 2,2-dibromo- , 2,2-difluoro-, 2,2-dicyano-, 2,2-dimethyl-, 2,2-dimethoxy-, 2,3-dichloro-, 2,3-dibromo-, 2,3- difluoro-, 2,3-dicyano-, 2,3-dimethyl-, 2,3-bis(trifluoromethyl)-, 2,3-dimethoxy-, 2,4-dichloro-, 2,4- dibromo-, 2,4-difluoro-, 2,4-dicyano-, 2,4-dimethyl-, 2,4-dimethoxy-, 2,5-dichloro-, 2,5-dibromo-, 2,5-difluoro-, 2,5-dicyano-, 2,5-dimethyl-, 2, 5-di methoxy-, 2,6-dichloro-, 2,6-dibromo-, 2,6- difluoro-, 2,6-dicyano-, 2,6-dimethyl-, 2,6-dimethoxy-, 3,3-dichloro-, 3,3-dibromo-, 3,3-difluoro-, 3,3-dicyano-, 3,3-dimethyl-, 3,3-dimethoxy-, 3,4-dichloro-, 3,4-dibromo-, 3,4-difluoro-, 3,4- dicyano-, 3,4-dimethyl-, 3,4-dimethoxy-, 3,5-dichloro-, 3,5-dibromo-, 3,5-difluoro-, 3,5-dicyano-, 3,5-dimethyl-, 3,5-dimethoxy-, 3,6-dichloro-, 3,6-dibromo-, 3,6-difluoro-, 3,6-dicyano-, 3,6- dimethyl-, 3,6-dimethoxy-, 2,2,3-trimethyl-, 2,3,3-trimethyl-, 2,2,3,3-tetramethyl-, 3,3,5,5- tetramethyl, 2-methyl-3-trifluoromethyl-, 2-methyl-3-cyano, 2-chloro-2-methyl-, 2-bromo-2-methyl- , 2-fluoro-2-methyl-, 2-chloro-3-methyl-, 2-bromo-3-methyl-, 2-fluoro-3-methyl-, 2-chloro-3- trifluoromethyl-, 2-bromo-3-trifluoromethyl-, 2-fluoro-3-trifluoromethyl-, 2,3-dichloro-3-methyl, 2,3- dibromo-3-m ethyl- and 2,3-difluoro-3-methyl-. Preferred substitution patterns for the cycloalkyl rings are 1-hydroxy-, 2-methyl-, 3- methyl-, 2,3-dimethyl-, 2,2-dimethyl-, 3,3-dimethyl-, 2-chloro-, 2-bromo-, 2-iodo-, 2-fluoro-, 2- cyano-, 2-trifluoromethyl-, 2-azido-, 3-chloro-, 3-bromo-, 3-fluoro-, 3-trifluoromethyl-, 2,3-dichloro-, 2,3-dibromo-,2-methyl-3-trifluoronriethyl-, 2-methyl-3-cyano, 2-chloro-2-methyl-, 2-chloro-3- methyl-, 2,2-dichloro-, 2,2-difluoro-, and 3,3-difluoro-.
More preferably, the substitution patterns are 2-methyl-, 2,3-dimethyl-, 2-chloro-, 2- bromo-, 2-iodo-, 2-fluoro-, 2-trifluoromethyl-, 2-cyano-, 2-azido-, 2,2-difluoro- and 3,3-difluoro-, Preferably, these substitution patterns are found on cyclopentyl or cyclohexyl rings and, most preferably, on cyclohexyl rings. Thus, particularly preferred examples of A are 2-methylcyclohexyl, 2,3- dimethylcyclohexyl, 2-chlorocyclohexyl, 2-bromocyclohexyl, 2-iodocyclohexyl, 2-fluorocyclohexyl, 2-trifluoromethylcyclohexyl, 2-cyanocyclohexyl, 2-azidocyclohexyl, 2,2-difluorocyclohexyl and 3,3- difluorocyclohexyl.
In one embodiment, the invention provides the use of a compound of formula (II),
Figure imgf000005_0001
wherein
X1 is F or CI and X2, X3 and X4 are H or X1 and X2 are F or CI and X3 and X4 are H or X1 and X3 are F or CI and X2 and X4 are H; Z is O;
R is H;
W is a direct bond or -CH2-;
A is a cyclohexyl ring, m is from 0 to 3 and each R4 is independently selected from methyl, chloro, bromo, iodo, fluoro, trifluoromethyl, cyano and azido. Preferably, A is 2-methylcyclohexyl, 2,3-dimethylcyclohexyl, 2-chlorocyclohexyl, 2-bromocyclohexyl, 2-iodocyclohexyl, 2- fluorocyclohexyl, 2-trifluoromethylcyclohexyl, 2-cyanocyclohexyl, 2-azidocyclohexyl, 2,2- difluorocyclohexyl or 3,3-difluorocyclohexyl.
In another embodiment, the invention provides the use of a compound of formula (III):
Figure imgf000006_0001
wherein:
X1 , X2, X3 and X4 are, independently, H, CI or F provided that at least one of X1 , X2, X3 and X4 is not H;
R is H or C1-C3 alkyl, allyl, arylmethyl or heteroarylmethyl;
W is -CR2R3- or a direct bond and R2 and R3 are, independently, selected from H, -CH3 or cyclopropyl;
Z is sulphur or oxygen; A is a 3 to 7 membered cycloalkyi ring which is optionally substituted by one or more substituents selected independently from methyl and trifluoromethyl; or a salt or N-oxide form thereof, as a herbicide.
Preferably X1 is H or F, more preferably, X1 is F.
Preferably X2 is H or F; more preferably, X2 is F. Preferably X3 is H or F.
Preferably X4 is H or F.
In one embodiment, X1 is F and X2, X3 and X4 are H. In another embodiment, X1 and X3 are F and X2 and X4 are H. In another embodiment, X2 and X4 are F and X1 and X3 are H.
Preferably R is H, methyl, ethyl or allyl, more preferably, R is H. Preferably W is a direct bond or -CH2-.
Preferably Z is oxygen.
Examples of A include optionally substituted cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl and cycloheptyl. Preferably, A is optionally substituted cyclopentyl or cyclohexyl. More preferably, A is optionally substituted cyclohexyl. Preferably, A is optionally substituted by one or more methyl or trifluoromethyl groups on at least the 2 or 3 positions on the cycloalkyl ring. More preferably, A is optionally substituted by one or more methyl groups on at least the 2 or 3 positions on the cycloalkyl ring. This includes situations where methyl and/or trifluoromethyl replace both hydrogen atoms at a particular ring position as well as situations where only one ring hydrogen is replaced at each position.
Examples of substitution patterns for A are 2-methyl-, 3-methyl-, 4-methyl-, 2,2-dimethyl-, 2,3-dimethyl-, 2,4-dimethyl-, 2,5-dimethyl-, 2,6-dimethyl-, 3,3-dimethyl-, 3,4-dimethyl-, 3,5- dimethyl-, 3,6-dimethyl-, 2,2,3-trimethyl-, 2,3,3-trimethyl-, 2,2,3,3-tetramethyl-, 3,3,5,5- tetramethyl-, 2-trifluoromethyl-, 3-trifluoromethyl-, 4-trifluoromethyl- and 2,3-bis(trifluoromethyl)-. Preferred substitution patterns for A are 2-methyl-, 3-methyl- and 2,3-dimethyl-.
Particularly preferred examples of A are 2-methylcyclohexyl, 3-methylcyclohexyl, 2,3- dimethylcyclohexyl, 2-methylcyclopentyl, 3-methylcyclopentyl and 2,3-dimethylcyclopentyl. More preferred examples of A are 2-methylcyclohexyl, 3-methylcyclohexyl and 2,3-dimethylcyclohexyl An even more preferred example of A is, 2,3-dimethylcyclohexyl.
In a further embodiment, the invention provides the use of a compound of formula (I):
Figure imgf000007_0001
(I)
wherein:
X1 , X2, X3 and X4 are, independently, H, CI or F provided that at least one of X1 , X2, X3 and X4 is not H;
Z is sulphur or oxygen;
Y is
Figure imgf000007_0002
and R is H or C1-C3 alkyl, allyl, arylmethyl or heteroarylmethyl; W is -CR2R3- or a direct bond and R2 and R3 are, independently, selected from H, -CH3 or cyclopropyl;
A is a 3 to 7 membered cycloalkyl ring; each R4 is selected independently from halo, hydroxyl, methyl, trifluoromethyl, methoxy and cyano; m is an integer between 0 and 5; n is an integer between 1 and 3; or a salt of N-oxide form thereof, as a herbicide.
Preferably X is H or F, more preferably, X is F.
Preferably X2 is H or F; more preferably, X2 is F.
Preferably X3 is H or F. Preferably X4 is H or F.
In one embodiment, X1 is F and X2, X3 and X4 are H. In another embodiment, X1 and X3 are F and X2 and X4 are H. In another embodiment, X2 and X4 are F and X1 and X3 are H.
Preferably Z is oxygen.
In one embodiment, Y is
Figure imgf000008_0001
Preferably R is H, methyl, ethyl or allyl, more preferably, R is H.
Preferably W is a direct bond or -CH2-. Examples of A include optionally substituted cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl and cycloheptyl. Preferably, A is optionally substituted cyclopentyl or cyclohexyl. More preferably, A is optionally substituted cyclohexyl.
In another embodiment, Y is
Figure imgf000008_0002
Preferably, m is 1 or 2. Preferably n is 1 or 2.
In either of the embodiments of Y, R4 is as defined above or, preferably, each R4 is independently selected from chloro, bromo or fluoro, methyl or trifluoromethyl. More preferably, each R4 is chloro or bromo. Preferably, the R4 group is present on at least the 2 or 3 positions or both the 2 and 3 positions on the cycloalkyl ring. It is noted that it is possible that two R4 groups may be present in each position of the cycloalkyl ring systems.
Examples of substitution patterns for the cycloalkyl rings in either embodiment of Y are 2- chloro-, 2-bromo-, 2-fluoro-, 2-cyano-, 2-methyl-, 2-trifluoromethyl-, 2-methoxy-, 3-chloro-, 3- bromo-, 3-fluoro-, 3-cyano-, 3-methyl-, 3-trifluoromethyl-, 3-methoxy-, 4-chloro-, 4-bromo-, 4- fluoro-, 4-cyano-, 4-methyl-, 4-trifluoromethyl- , 4-methoxy-, 2,2-dichloro-. 2,2-dibromo-, 2,2- difluoro-, 2,2-dicyano-, 2,2-dimethyl-, 2,2-dimethoxy, 2,3-dichloro-, 2,3-dibromo-, 2,3-difluoro-,
2.3- dicyano-, 2,3dimethyl-, 2,3-bis(trifluoromethyl)-, 2,3-dimethoxy-, 2,4-dichloro-, 2,4-dibromo,
2.4- difluoro-, 2,4-dicyano-, 2,4-dimethyl-, 2,4-dimethoxy-, 2,5-dichloro-, 2,5-dibromo-, 2,5- difluoro-, 2,5-dicyano-, 2,5-dimethyl-, 2,5-dimethoxy-, 2,6-dichloro-, 2,6-dibromo-, 2,6-difluoro-, 2,6-dicyano-, 2,6-dimethyl-, 2,6-dimethoxy-, 3,3-dichloro-, 3,3-dibromo-, 3,3-difluoro-, 3,3- dicyano-, 3,3-dimethyl-, 3,3-dimethoxy-, 3,4-dichloro-, 3,4-dibromo, 3,4-difluoro-, 3,4-dicyano-, 3,4-dimethyl-, 3,4-dimethoxy-, 3,5-dichloro-, 3,5-dibromo-, 3,5-difluoro-, 3,5-dicyano-, 3,5- dimethyl-, 3,5-dimethoxy-, 3,6-dichloro-, 3,6-dibromo-, 3,6-difluoro-, 3,6-dicyano-, 3,6-dimethyl-, 3,6-dimethoxy-, 2,2,3-trimethyl-, 2,3,3-trimethyl-, 2,2,3,3-tetramethyl-, 3,3,5,5-tetramethyl, 2- chloro-2-methyl-, 2-bromo-2-methyl-, 2-fluoro-2-methyl-, 2-chloro-3-methyl, 2-bromo-3-methyl-, 2- fluoro-3-methyl-, 2-chloro-3-trifluoromethyl-, 2-bromo-3-trifluoromethyl-, 2-fluoro-3-trifluoromethyl- , 2,3-dichloro-3-methyl, 2,3-dibromo-3-methyl- and 2,3-difluoro-3methyl.
Preferred substitution patterns for the cycloalkyl rings are 2-chloro-, 3-chloro- 2,3 dichloro-, 2-chloro-2-methyl-, 2-chloro-3-methyl and 3,3-difluoro.
When Y is
Figure imgf000009_0001
particularly preferred examples of A are 2-chlorocyclohexyl, 2-bromocyclohexyl 3- chlorocyclohexyl, 3-bromocyclohexyl, 2,3 dichlorocyclohexyl, 2,3-dibromocyclohexyl, 2- chlorocyclopentyl, 2-bromocyclopentyl, 3-chlorocyclopentyl, 3-bromocyclopentyl, 2,3
dichlorocyclopentyl and 2,3-dibromocyclopentyl.
In a second aspect, the invention provides a compound selected from the list consisting of 2-fluoro-N-(2-bromocyclohexyl)pyridine-4-carboxamide, 2-fluoro-N-(2-iodocyclohexyl)pyridine- 4-carboxamide, 2-fluoro-N-(2-fluorocyclohexyl)pyridine-4-carboxamide, 2-fluoro-N-(2- cyanocyclohexyl)pyridine-4-carboxamide, 2-fluoro-N-(2-azidocyclohexyl)pyridine-4-carboxamide, 2-fluoro-N-(2,2-dimethylcyclohexyl)pyridine-4-carboxamide, 2-fluoro-N-(2,2- difluorocyclohexyl)pyridine-4-carboxamide, 2-fluoro-N-(3,3-difluorocyclohexyl)pyridine-4- carboxamide, 2-fluoro-N-(2-methyl-3-cyanocyclohexyl)pyridine-4-carboxamide, 2,6-difluoro-N-(2- chlorocyclohexyl)pyridine-4-carboxamide, 2,6-difluoro-N-(2,3-dimethylcyclohexyl)pyridine-4- carboxamide, 2-fluoro-N-(2,2-dimethylcyclohexyl)pyridine-4-carboxamide, 2-fluoro-N-(3- trifluoromethyl-chlorocyclohexyl)pyridine-4-carboxanriide, 2-fluoro-N-(1- hyd roxycyclohexyl)pyrid ine-4-carboxam id e, 2-f I uoro-N-(2-m ethyl-3- trifluoromethylcyclohexyl)pyridine-4-carboxanriide, 2,6-difluoro-N-(2-cyanocyclohexyl)pyridine-4- carboxamide, 2-fluoro-N-(2-methylcyclohexyl)pyridine-4-carbothioamide, compound 23, compound 24, compound 27, compound 30, compound 31 , compound 32, compound 36, compound 37, compound 43, compound 44, compound 47, compound 48, compound 49, compound 50, compound 54, compound 55, compound 56, compound 67, compound 68, compound 1 10, compound 129, compound 131 , compound 137, compound 147, compound 148, compound 152, compound 163, compound 167, compound 168, compound 169, compound 170 and compound 186.
In a preferred embodiment, the invention provides a compound selected from the list consisting of 2-fluoro-N-(2-bromocyclohexyl)pyridine-4-carboxamide, 2-fluoro-N-(2- iodocyclohexyl)pyridine-4-carboxamide, 2-fluoro-N-(2-fluorocyclohexyl)pyridine-4-carboxamide, 2-fluoro-N-(2-cyanocyclohexyl)pyridine-4-carboxamide, 2-fluoro-N-(2-azidocyclohexyl)pyridine-4- carboxamide, 2-fluoro-N-(2,2-dimethylcyclohexyl)pyridine-4-carboxamide, 2-fluoro-N-(2,2- difluorocyclohexyl)pyridine-4-carboxamide, 2-fluoro-N-(3,3-difluorocyclohexyl)pyridine-4- carboxamide, 2-fluoro-N-(2-methyl-3-cyanocyclohexyl)pyridine-4-carboxamide, 2,6-difluoro-N-(2- chlorocyclohexyl)pyridine-4-carboxamide, 2,6-difluoro-N-(2,3-dimethylcyclohexyl)pyridine-4- carboxamide, 2-fluoro-N-(2-methylcyclohexyl)pyridine-4-carbothioamide, compound 23, compound 27, compound 30, compound 31 , compound 37, compound 47, compound 48, compound 49, compound 50, compound 54, compound 55, compound 56, compound 68, compound 1 10, compound 129, compound 137, compound 147, compound 163, compound 168, compound 170 and compound 169.
In another embodiment, the invention provides the compound 2-fluoro-N-(2- bromocyclohexyl )pyrid i ne-4-carboxam ide.
In another embodiment, the invention provides the compound 2-fluoro-N-(2- iodocyclohexyl)pyridine-4-carboxamide. In another embodiment, the invention provides the compound 2-fluoro-N-(2- fluorocyclohexyl)pyridine-4-carboxamide. In another embodiment, the invention provides the compound 2-fluoro-N-(2- cyanocyclohexyl)pyridine-4-carboxamide.
In another embodiment, the invention provides the compound 2-fluoro-N-(2- azidocyclohexyl)pyridine-4-carboxamide. In another embodiment, the invention provides the compound 2-fluoro-N-(2,2- dimethylcyclohexyl)pyridine-4-carboxamide.
In another embodiment, the invention provides the compound 2-fluoro-N-(2,2- difluorocyclohexyl)pyridine-4-carboxamide.
In another embodiment, the invention provides the compound 2-fluoro-N-(3,3- difluorocyclohexyl)pyridine-4-carboxamide.
In another embodiment, the invention provides the compound 2-fluoro-N-(2-methyl-3- cyanocyclohexyl)pyridine-4-carboxamide.
In another embodiment, the invention provides the compound 2,6-difluoro-N-(2- chlorocyclohexyl)pyridine-4-carboxamide. In another embodiment, the invention provides the compound 2,6-difluoro-N-(2,3- dimethylcyclohexyl)pyridine-4-carboxamide.
In another embodiment, the invention provides the compounds 2-fluoro-N-(2- methylcyclohexyl)pyridine-4-carbothioamide
In another embodiment, the invention provides the compound 23. In another embodiment, the invention provides the compound 27.
In another embodiment, the invention provides the compound 30.
In another embodiment, the invention provides the compound 31.
In another embodiment, the invention provides the compound 37. In another embodiment, the invention provides the compound 47.
In another embodiment, the invention provides the compound 48.
In another embodiment, the invention provides the compound 49.
In another embodiment, the invention provides the compound 50. In another embodiment, the invention provides the compound 54.
In another embodiment, the invention provides the compound 55.
In another embodiment, the invention provides the compound 56.
In another embodiment, the invention provides the compound 68.
In another embodiment, the invention provides the compound 1 10. In another embodiment, the invention provides the compound 129.
In another embodiment, the invention provides the compound 137.
In another embodiment, the invention provides the compound 147.
In another embodiment, the invention provides the compound 163.
In another embodiment, the invention provides the compound 168. In another embodiment, the invention provides the compound 169.
In another embodiment, the invention provides the compound 170. The compounds of formula (I) may exist as different geometric isomers, or in different tautomeric forms. This invention covers all such isomers and tautomers, and mixtures thereof in all proportions, as well as isotopic forms such as deuterated compounds.
The compounds of this invention may contain an asymmetric carbon atom and some of the compounds of this invention may contain one or more asymmetric centers and may thus give rise to optical isomers and diastereomers. While shown without respect to stereochemistry, the present invention includes such optical isomers and diastereomers as well as the racemic and resolved, enantiomerically pure R and S stereoisomers and, in addition, other mixtures of the R and S stereoisomers and agrochemically acceptable salts thereof. It is recognized that one stereoisomer, including diastereomer and enantiomer, may have favorable properties over the other. Thus when disclosing and claiming the invention, when one racemic mixture is disclosed, it is clearly contemplated that both optical isomers, including diastereomers and enantiomers, or stereoisomers substantially free of the other are disclosed and claimed as well.
For example, the compound: 2-fluoro-N-(2-methylcyclohexyl)pyridine-4-carboxamide
Figure imgf000013_0001
may exist in one of four isomeric forms as shown below a) 2-fluoro-N-[(1 R,2R)-2-methylcyclohexyl]pyridine-4-carboxamide
b) 2-fluoro-N-[(1 R,2S)-2-methylcyclohexyl]pyridine-4-carboxamide
c) 2-fluoro-N-[(1 S,2R)-2-methylcyclohexyl]pyridine-4-carboxamide
d) 2-fluoro-N-[(1 S,2S)-2-methylcyclohexyl]pyridine-4-carboxamide
Figure imgf000014_0001
As a further example, the compound: N-(2,3-dimethylcyclohexyl)-2-fluoro-pyridine-4- carboxamide
Figure imgf000014_0002
may exist in one of ei ht isomeric forms as shown below:
Figure imgf000014_0003
Figure imgf000014_0004
a) N-[(1 R,2R,3S)-2,3-dimethylcyclohexyl]-2-fluoro-pyridine-4-carboxamide b) N-[(1 R,2R,3R)-2,3-dimethylcyclohexyl]-2-fluoro-pyridine-4-carboxamide c) N-[(1 S,2R,3S)-2,3-dimethylcyclohexyl]-2-fluoro-pyridine-4-carboxamide d) N-[(1 S,2R,3R)-2,3-dimethylcyclohexyl]-2-fluoro-pyridine-4-carboxamide e) N-[(1 S,2S,3S)-2,3-dimethylcyclohexyl]-2-fluoro-pyridine-4-carboxamide
f) N-[(1 R,2S,3R)-2,3-dimethylcyclohexyl]-2-fluoro-pyridine-4-carboxamide
g) N-[(1 R,2S,3S)-2,3-dimethylcyclohexyl]-2-fluoro-pyridine-4-carboxamide
h) N-[(1 S,2S,3R)-2,3-dimethylcyclohexyl]-2-fluoro-pyridine-4-carboxamide
As indicated above, all of these isomeric forms are covered by the present invention.
Procides of the compounds of the invention may also be use as herbicides. In such cases, the procide contains an additional or alternative substituent to those disclosed above in relation to the compound of the invention, such substituent being removed on application of the procide to the plant (e.g. by metabolism in the plant) to give the active compound of the invention. All such procides are also covered by the invention.
Alkyl, as used herein refers to an aliphatic hydrocarbon chain and includes straight and branched chains e. g. of 1 to 6 carbon atoms such as methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, t-butyl, n-pentyl, isopentyl, neo-pentyl, n-hexyl, and isohexyl. Cycloalkyl, as used herein, refers to a cyclic, saturated hydrocarbon group having from 3 to 7 ring carbon atoms. Examples of cycloalkyl groups are cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl and cycloheptyl.
Cycloalkenyl, as used herein, refers to a cyclic hydrocarbon group having from 3 to 7 ring carbon atoms and containing at least one double bond. Examples of cycloalkenyl groups are cyclopropenyl, cyclobutenyl, cyclopentenyl, cyclohexenyl and cycloheptenyl. Preferred cycloalkenyl groups are cyclohexenyl groups with the double bond between the 2 and 3 positions of the ring system.
Halo, or halogen, as used herein, refers to chloro, bromo, fluoro or iodo.
Aryl, as used herein, refers to an aromatic carbocyclic group of from 6 to 10 carbon atoms having a single ring (e.g., phenyl) or multiple condensed (fused) rings, at least one of which is aromatic (e.g., indanyl, naphthyl). Preferred aryl groups include phenyl, naphthyl and the like. Most preferably, an aryl group is a phenyl group.
Heteroaryl, as used herein, refers to a ring system containing 5 to 10 ring atoms, 1 to 4 ring heteroatoms and consisting either of a single aromatic ring or of two or more fused rings, at least one of which is aromatic. Preferably, single rings will contain up to three and bicyclic systems up to four heteroatoms which will preferably be independently chosen from nitrogen, oxygen and sulfur. Examples of such groups include pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl, triazinyl, furanyl, thiophenyl, oxazolyl, isoxazolyl, oxadiazolyl, thiazolyl, isothiazolyl, thiadiazolyl, pyrrolyl, pyrazolyl, imidazolyl, triazolyl and tetrazolyl. Examples of bicyclic groups are
benzothiophenyl, benzimidazolyl, benzothiadiazolyl, quinolinyl, cinnolinyl, quinoxalinyl and pyrazolo[1 ,5-a]pyrimidinyl. Preferably heteroaryl groups are pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl and thiophenyl. "Optionally substituted" as used herein means the group referred to can be substituted at one or more positions by any one or any combination of the radicals listed thereafter. For most groups, one or more hydrogen atoms are replaced by the radicals listed thereafter.
Suitable salts can be formed from organic and inorganic acids, for example, acetic, propionic, lactic, citric, tartaric, succinic, fumaric, maleic, malonic, mandelic, malic, phthalic, hydrochloric, hydrobromic, phosphoric, nitric, sulfuric, methanesulfonic, naphthalenesulfonic, benzenesulfonic, toluenesulfonic, or camphorsulfonic acid, and similarly known acceptable acids when a compound of this invention contains a basic moiety.
If the compound of the invention contains a suitable acidic moiety, suitable salts also include those derived from alkali or alkaline earth metals and those derived from ammonia and amines. Preferred cations include sodium, potassium, magnesium, and ammonium cations of the formula N+(R 9R20R2 R22) wherein R 9, R20, R2 and R22 are independently selected from hydrogen, Ci-C6 alkyl and Ci-C6 hydroxyalkyl. Salts of the compounds of Formula I can be prepared by treatment of compounds of formula (I) with a metal hydroxide, such as sodium hydroxide, or an amine, such as ammonia, trimethylamine, diethanolamine, 2- methylthiopropylamine, bisallylamine, 2-butoxyethylamine, morpholine, cyclododecylamine, or benzylamine. Amine salts are often preferred forms of the compounds of Formula I because they are water-soluble and lend themselves to the preparation of desirable aqueous based herbicidal compositions.
Compounds of the invention may be prepared by techniques known to the person skilled in the art of organic chemistry. General methods for the production of compounds of formula (I) are described below. Unless otherwise stated in the text, the substituents X1 , X2, X3, X4, Z , Y, R , R4, m, n, W and A are as defined hereinbefore. The starting materials used for the preparation of the compounds of the invention may be purchased from the usual commercial suppliers or may be prepared by known methods. The starting materials as well as the intermediates may be purified before use in the next step by state of the art methodologies such as chromatography, crystallization, distillation and filtration.
Compounds of the invention may be purchased from commercial suppliers such as Enamine Ltd, Ryan Scientific Inc or Aurora Fine Chemicals LLC. In addition, compounds of the invention may be made as described herein in the Examples, or, as the skilled man will appreciate, by applying and/or adapting as appropriate, the methods described in EP 2 174 931 A1.
Where the compounds of this invention contain one or more asymmetric centers, as indicated above, this may give rise to optical isomers and diastereomers. These isomers may be separated using several techniques, such as crystallisation, enzymatic resolution and High Performance Liquid Chromatography (HPLC) using either normal phase solvents or reverse phase solvents as the mobile phase eluant. The stationary phase may be silica gel or a chiral material that allows the asymmetrical compounds to be resolved into the enantiomers. Examples of some of these techniques are outlined in "Stereochemistry of Organic Compounds", Wiley Interscience, Chapter 7, from page 297.
In particular, compounds of formula (I) may also be prepared by treating the compound of formula (V) wherein X1 , X2, X3 and X4 are defined above with an amine of formula (Y) or a salt thereof (for example a hydrochloride salt) in the presence of a base:
Figure imgf000017_0001
wherein R , W and A are defined above.
The reaction is usually carried out in the presence of a solvent. Examples of solvents used in the reaction include a haloalkane such as dichloromethane (DCM) or an ether such as tetrahydrofuran (THF). Examples of the base used in such reactions include a nitrogen- containing aromatic compound such as pyridine, or a tertiary amine such as triethylamine or N,N- Diisopropylethylamine or an inorganic base such as a metal carbonate, for example, potassium carbonate. The amine of formula (Y) may contain one or more asymmetric centers and hence give optical isomers or diastereomers of compounds of formula (I). For example, an amine of formula (Y) containing one asymmetric center can result in the compound of formula (I) and a compound of formula (Y) with the opposite asymmetric center can result in the isomer of compound of formula (I) itself with the opposite asymmetric center. Intermediate amines of formula (Y) can be obtained commercially or be prepared by techniques known to the person skilled in the art of organic chemistry. Where amines of formula (Y) have an asymmetric center these may be obtained commercially, from resolution of the racemic amine or by synthesis of the asymmetric amine from suitable starting materials, by techniques known to the person skilled in the art of organic chemistry. In addition, compounds of formula (I) may also be prepared by treating the compound of formula (VI) wherein X1 , X2, X3 and X4 are defined above with an amine of formula (Y) or a salt thereof (for example an hydrochloride salt) in the presence of a base and suitable amide coupling reagents (for example 1-hydroxybenzotriazole/3-(ethyliminomethyleneamino)-N,N-dimethyl- propan-1 -amine hydrochloride or 2,4,6-tripropyl-1 ,3,5-trioxa-2,4,6-triphosphinane-2,4,6-trioxide or 0-(7-azabenzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate):
Figure imgf000018_0001
wherein R , W and A are defined above.
In addition, compounds of formula (VIII) may also be prepared by treating the compound of formula (VII) wherein X1 , X2, X3, X4 m, n and R4 are defined above with a suitable nucleophile (for example trimethylsilylcyanide or zinc bromide or tetrabutylammonium fluoride or sodium methoxide):
Figure imgf000018_0002
wherein A is defined above.
The compounds of formula (I) according to the invention can be used as herbicides in unmodified form, as obtained in the synthesis, but they are generally formulated into herbicidal compositions in various ways using formulation adjuvants, such as carriers, solvents and surface- active substances. Therefore, the invention also relates to a herbicidal composition which comprises a herbicidally effective amount of a compound of formula (I) in addition to formulation adjuvants. The formulations can be in various physical forms, e.g. in the form of dusting powders, gels, wettable powders, water-dispersible granules, water-dispersible tablets, effervescent pellets, emulsifiable concentrates, microemulsifiable concentrates, oil-in-water emulsions, oil- flowables, aqueous dispersions, oily dispersions, suspo-emulsions, capsule suspensions, emulsifiable granules, soluble liquids, water-soluble concentrates (with water or a water-miscible organic solvent as carrier), impregnated polymer films or in other forms known e.g. from the Manual on Development and Use of FAO Specifications for Plant Protection Products, 5th Edition, 1999. Such formulations can either be used directly or they are diluted prior to use. The dilutions can be made, for example, with water, liquid fertilizers, micronutrients, biological organisms, oil or solvents.
The formulations can be prepared e.g. by mixing the active ingredient with the formulation adjuvants in order to obtain compositions in the form of finely divided solids, granules, solutions, dispersions or emulsions. The active ingredients can also be formulated with other adjuvants, such as finely divided solids, mineral oils, oils of vegetable or animal origin, modified oils of vegetable or animal origin, organic solvents, water, surface-active substances or combinations thereof. The active ingredients can also be contained in very fine microcapsules consisting of a polymer. Microcapsules contain the active ingredients in a porous carrier. This enables the active ingredients to be released into the environment in controlled amounts (e.g. slow-release). Microcapsules usually have a diameter of from 0.1 to 500 microns. They contain active ingredients in an amount of about from 25 to 95 % by weight of the capsule weight. The active ingredients can be in the form of a monolithic solid, in the form of fine particles in solid or liquid dispersion or in the form of a suitable solution. The encapsulating membranes comprise, for example, natural or synthetic rubbers, cellulose, styrene/butadiene copolymers, polyacrylonitrile, polyacrylate, polyesters, polyamides, polyureas, polyurethane or chemically modified polymers and starch xanthates or other polymers that are known to the person skilled in the art in this connection. Alternatively, very fine microcapsules can be formed in which the active ingredient is contained in the form of finely divided particles in a solid matrix of base substance, but the microcapsules are not themselves encapsulated.
The formulation adjuvants that are suitable for the preparation of the compositions according to the invention are known per se. As liquid carriers there may be used: water, toluene, xylene, petroleum ether, vegetable oils, acetone, methyl ethyl ketone, cyclohexanone, acid anhydrides, acetonitrile, acetophenone, amyl acetate, 2-butanone, butylene carbonate, chlorobenzene, cyclohexane, cyclohexanol, alkyl esters of acetic acid, diacetone alcohol, 1 ,2- dichloropropane, diethanolamine, p-diethylbenzene, diethylene glycol, diethylene glycol abietate, diethylene glycol butyl ether, diethylene glycol ethyl ether, diethylene glycol methyl ether, N,N- dimethylformamide, dimethyl sulfoxide, 1 ,4-dioxane, dipropylene glycol, dipropylene glycol methyl ether, dipropylene glycol dibenzoate, diproxitol, alkylpyrrolidone, ethyl acetate, 2-ethylhexanol, ethylene carbonate, 1 ,1 , 1-trichloroethane, 2-heptanone, alpha-pinene, d-limonene, ethyl lactate, ethylene glycol, ethylene glycol butyl ether, ethylene glycol methyl ether, gamma-butyrolactone, glycerol, glycerol acetate, glycerol diacetate, glycerol triacetate, hexadecane, hexylene glycol, isoamyl acetate, isobornyl acetate, isooctane, isophorone, isopropylbenzene, isopropyl myristate, lactic acid, laurylamine, mesityl oxide, methoxypropanol, methyl isoamyl ketone, methyl isobutyl ketone, methyl laurate, methyl octanoate, methyl oleate, methylene chloride, m-xylene, n-hexane, n-octylamine, octadecanoic acid, octylamine acetate, oleic acid, oleylamine, o-xylene, phenol, polyethylene glycol (PEG400), propionic acid, propyl lactate, propylene carbonate, propylene glycol, propylene glycol methyl ether, p-xylene, toluene, triethyl phosphate, triethylene glycol, xylenesulfonic acid, paraffin, mineral oil, trichloroethylene, perchloroethylene, ethyl acetate, amyl acetate, butyl acetate, propylene glycol methyl ether, diethylene glycol methyl ether, methanol, ethanol, isopropanol, and alcohols of higher molecular weight, such as amyl alcohol, tetrahydro- furfuryl alcohol, hexanol, octanol, ethylene glycol, propylene glycol, glycerol, N-methyl-2- pyrrolidone and the like. Water is generally the carrier of choice for diluting the concentrates. Suitable solid carriers are, for example, talc, titanium dioxide, pyrophyllite clay, silica, attapulgite clay, kieselguhr, limestone, calcium carbonate, bentonite, calcium montmorillonite, cottonseed husks, wheat flour, soybean flour, pumice, wood flour, ground walnut shells, lignin and similar substances, as described, for example, in CFR 180.1001. (c) & (d). A large number of surface-active substances can advantageously be used in both solid and liquid formulations, especially in those formulations which can be diluted with a carrier prior to use. Surface-active substances may be anionic, cationic, non-ionic or polymeric and they can be used as emulsifiers, wetting agents or suspending agents or for other purposes. Typical surface-active substances include, for example, salts of alkyl sulfates, such as
diethanolammonium lauryl sulfate; salts of alkylarylsulfonates, such as calcium dodecyl- benzenesulfonate; alkylphenol/alkylene oxide addition products, such as nonylphenol ethoxylate; alcohol/alkylene oxide addition products, such as tridecylalcohol ethoxylate; soaps, such as sodium stearate; salts of alkylnaphthalenesulfonat.es, such as sodium
dibutylnaphthalenesulfonate; dialkyl esters of sulfosuccinate salts, such as sodium di(2- ethylhexyl)sulfosuccinate; sorbitol esters, such as sorbitol oleate; quaternary amines, such as lauryltrimethylammonium chloride, polyethylene glycol esters of fatty acids, such as polyethylene glycol stearate; block copolymers of ethylene oxide and propylene oxide; and salts of mono- and di-alkylphosphate esters; and also further substances described e.g. in "McCutcheon's
Detergents and Emulsifiers Annual" MC Publishing Corp., Ridgewood New Jersey, 1981.
Further adjuvants that can usually be used in pesticidal formulations include
crystallization inhibitors, viscosity modifiers, suspending agents, dyes, anti-oxidants, foaming agents, light absorbers, mixing auxiliaries, antifoams, complexing agents, neutralizing or pH- modifying substances and buffers, corrosion inhibitors, fragrances, wetting agents, take-up enhancers, micronutrients, plasticisers, glidants, lubricants, dispersants, thickeners, antifreezes, microbicides, and also liquid and solid fertilizers.
The compositions according to the invention can additionally include an additive comprising an oil of vegetable or animal origin, a mineral oil, alkyl esters of such oils or mixtures of such oils and oil derivatives. The amount of oil additive in the composition according to the invention is generally from 0.01 to 10 %, based on the spray mixture. For example, the oil additive can be added to the spray tank in the desired concentration after the spray mixture has been prepared. Preferred oil additives comprise mineral oils or an oil of vegetable origin, for example rapeseed oil, olive oil or sunflower oil, emulsified vegetable oil, such as AMIGO® (Rhone-Poulenc Canada Inc.), alkyl esters of oils of vegetable origin, for example the methyl derivatives, or an oil of animal origin, such as fish oil or beef tallow. A preferred additive contains, for example, as active components essentially 80 % by weight alkyl esters of fish oils and 15 % by weight methylated rapeseed oil, and also 5 % by weight of customary emulsifiers and pH modifiers. Especially preferred oil additives comprise alkyl esters of C8-C22 fatty acids, especially the methyl derivatives of Ci2-Ci8 fatty acids, for example the methyl esters of lauric acid, palmitic acid and oleic acid, being of importance. Those esters are known as methyl laurate (CAS-1 1 1- 82-0), methyl palmitate (CAS-1 12-39-0) and methyl oleate (CAS-1 12-62-9). A preferred fatty acid methyl ester derivative is Emery® 2230 and 2231 (Cognis GmbH). Those and other oil derivatives are also known from the Compendium of Herbicide Adjuvants, 5th Edition, Southern Illinois University, 2000. The application and action of the oil additives can be further improved by combination with surface-active substances, such as non-ionic, anionic or cationic surfactants. Examples of suitable anionic, non-ionic and cationic surfactants are listed on pages 7 and 8 of WO 97/34485. Preferred surface-active substances are anionic surfactants of the dodecylbenzylsulfonate type, especially the calcium salts thereof, and also non-ionic surfactants of the fatty alcohol ethoxylate type. Special preference is given to ethoxylated C12-C22 fatty alcohols having a degree of ethoxylation of from 5 to 40. Examples of commercially available surfactants are the Genapol types (Clariant AG). Also preferred are silicone surfactants, especially polyalkyl-oxide-modified heptamethyltriloxanes which are commercially available e.g. as Silwet L-77®, and also perfluorinated surfactants. The concentration of the surface-active substances in relation to the total additive is generally from 1 to 30 % by weight. Examples of oil additives consisting of mixtures of oil or mineral oils or derivatives thereof with surfactants are Edenor ME SU®, Turbocharge® (Syngenta AG, CH) or ActipronC (BP Oil UK Limited, GB).
If desired, it is also possible for the mentioned surface-active substances to be used in the formulations on their own, that is to say, without oil additives.
Furthermore, the addition of an organic solvent to the oil additive/surfactant mixture may contribute to an additional enhancement of action. Suitable solvents are, for example, Solvesso® (ESSO) or Aromatic Solvent® (Exxon Corporation). The concentration of such solvents can be from 10 to 80 % by weight of the total weight. Oil additives that are present in admixture with solvents are described, for example, in US-A-4,834,908. A commercially available oil additive disclosed therein is known by the name MERGE® (BASF Corporation). A further oil additive that is preferred according to the invention is SCORE® (Syngenta Crop Protection Canada).
In addition to the oil additives listed above, for the purpose of enhancing the action of the compositions according to the invention it is also possible for formulations of alkylpyrrolidones (e.g. Agrimax®) to be added to the spray mixture. Formulations of synthetic lattices, e.g.
polyacrylamide, polyvinyl compounds or poly-1-p-menthene (e.g. Bond®, Courier® or Emerald®) may also be used. It is also possible for solutions that contain propionic acid, for example Eurogkem Pen-e-trate®, to be added to the spray mixture as action-enhancing agent.
The herbicidal compositions generally comprise from 0.1 to 99 % by weight, especially from 0.1 to 95 % by weight, compounds of formula (I) and from 1 to 99.9 % by weight of a formulation adjuvant which preferably includes from 0 to 25 % by weight of a surface-active substance. Whereas commercial products will preferably be formulated as concentrates, the end user will normally employ dilute formulations.
The rates of application of compounds of formula (I) may vary within wide limits and depend on the nature of the soil, the method of application (pre- or post-emergence; seed dressing; application to the seed furrow; no tillage application etc.), the crop plant, the grass or weed to be controlled, the prevailing climatic conditions, and other factors governed by the method of application, the time of application and the target crop. The compounds of formula (I) according to the invention are generally applied at a rate of from 10 to 2000 g/ha, especially from 50 to 1000 g/ha.
Preferred formulations have especially the following compositions (% = percent by weight):
Emulsifiable concentrates:
active ingredient: 1 to 95 %, preferably 60 to 90 %
surface-active agent: 1 to 30 %, preferably 5 to 20 %
liquid carrier: 1 to 80 %, preferably 1 to 35 % Dusts:
active ingredient: 0.1 to 10 %, preferably 0.1 to 5 %
solid carrier: 99.9 to 90 %, preferably 99.9 to 99 %
Suspension concentrates:
active ingredient: 5 to 75 %, preferably 10 to 50 %
water: 94 to 24 %, preferably 88 to 30 %
surface-active agent: 1 to 40 %, preferably 2 to 30 %
Wettable powders:
active ingredient: 0.5 to 90 %, preferably 1 to 80 %
surface-active agent: 0.5 to 20 %, preferably 1 to 15 %
solid carrier: 5 to 95 %, preferably 15 to 90 %
Granules:
active ingredient: 0.1 to 30 %, preferably 0.1 to 15 %
solid carrier: 99.5 to 70 %, preferably 97 to 85 %
The following Examples further illustrate, but do not limit, the invention. Formulation Examples for herbicides of formula (I) (% = % by weight)
F1. Emulsifiable concentrates a) b) c) d) active ingredient 5 % 10 % 25 % 50 % calcium dodecylbenzenesulfonate 6 % 8 % 6 % 8 % castor oil polyglycol ether 4 % 4 % 4 % (36 mol of ethylene oxide)
octylphenol polyglycol ether 4 % 2 % (7-8 mol of ethylene oxide)
NMP 20 % arom. hydrocarbon mixture 85 % 78 % 16 % Emulsions of any desired concentration can be obtained from such concentrates by dilution with water.
F2. Solutions
active ingredient
Figure imgf000023_0001
1-methoxy-3-(3-methoxy- propoxy)-propane 20 % 20 %
polyethylene glycol MW 400 20 % 10 %
NMP 30 % 10 % arom. hydrocarbon mixture 75 % 60 %
The solutions are suitable for use in the form of microdrops.
F3. Wettable powders a) b) c) d) active ingredient 5 % 25 % 50 % 80 % sodium lignosulfonate 4 % 3 %
sodium lauryl sulfate 2 % 3 % 4 % sodium diisobutylnaphthalene- sulfonate 6 % 5 % 6 % octylphenol polyglycol ether 1 % 2 %
(7-8 mol of ethylene oxide)
highly dispersed silicic acid 3 % 5 % 10 % kaolin
Figure imgf000023_0002
62 % 35 %
The active ingredient is mixed thoroughly with the adjuvants and the mixture is thoroughly ground in a suitable mill, affording wettable powders which can be diluted with water to give suspensions of any desired concentration.
F4. Coated granules a) b) c)
active ingredient 0.1 % 5 % 15 %
highly dispersed silicic acid 0.9 % 2 % 2 %
inorganic carrier 99.0 % 93 % 83 %
(diameter 0.1 - 1 mm)
e.g. CaC03 or Si02
The active ingredient is dissolved in methylene chloride and applied to the carrier by spraying, and the solvent is then evaporated off in vacuo.
F5. Coated granules a) b) c)
active ingredient 0.1 % 5 % 15 % polyethylene glycol MW 200 1.0 % 2 % 3 % highly dispersed silicic acid 0.9 % 1 % 2 % inorganic carrier 98.0 % 92 % 80 % (diameter 0.1 - 1 mm)
e.g. CaC03 or Si02
The finely ground active ingredient is uniformly applied, in a mixer, to the carrier moistened with polyethylene glycol. Non-dusty coated granules are obtained in this manner.
F6. Extruder granules a) b) c) d) active ingredient 0.1 % 3 % 5 % 15 % sodium lignosulfonate 1.5 % 2 % 3 % 4 % carboxymethylcellulose 1.4 % 2 % 2 % 2 % kaolin 97.0 % 93 % 90 % 79 %
The active ingredient is mixed and ground with the adjuvants, and the mixture is moistened with water. The mixture is extruded and then dried in a stream of air.
F7. Dusts a) b) c)
active ingredient 0.1 % 1 % 5 %
talcum 39.9 % 49 % 35 %
kaolin 60.0 % 50 % 60 %
Ready-to-use dusts are obtained by mixing the active ingredient with the carriers and grinding the mixture in a suitable mill.
F8. Suspension concentrates a) b) c) d) active ingredient 3 % 10 % 25 % 50 % ethylene glycol 5 % 5 % 5 % 5 % nonylphenol polyglycol ether 1 % 2 %
(15 mol of ethylene oxide)
sodium lignosulfonate 3 % 3 % 4 % 5 % carboxymethylcellulose 1 % 1 % 1 % 1 % 37 % aqueous formaldehyde 0.2 % 0.2 % 0.2 % 0.2 % solution
silicone oil emulsion 0.8 % 0.8 % 0.8 % 0.8 % water 87 % 79 % 62 % 38 %
The finely ground active ingredient is intimately mixed with the adjuvants, giving a suspension concentrate from which suspensions of any desired concentration can be obtained by dilution with water.
The invention also provides a method of controlling plants which comprises applying to the plants or to the locus thereof a herbicidally effective amount of a compound of formula (I).
The invention also provides a method of inhibiting plant growth which comprises applying to the plants or to the locus thereof a herbicidally effective amount of a compound of formula (I). The invention also provides a method of controlling weeds in crops of useful plants, comprising applying to said weeds or to the locus of said weeds, or to said useful plants or to the locus of said useful plants, a compound or a composition of the invention.
The invention also provides a method of selectively controlling grasses and/or weeds in crops of useful plants which comprises applying to the useful plants or locus thereof or to the area of cultivation a herbicidally effective amount of a compound of formula (I).
The term "herbicide" as used herein means a compound that controls or modifies the growth of plants. The term "herbicidally effective amount" means the quantity of such a compound or combination of such compounds that is capable of producing a controlling or modifying effect on the growth of plants. Controlling or modifying effects include all deviation from natural development, for example: killing, retardation, leaf burn, albinism, dwarfing and the like. The term "plants" refers to all physical parts of a plant, including seeds, seedlings, saplings, roots, tubers, stems, stalks, foliage, and fruits. The term "locus" is intended to include soil, seeds, and seedlings, as well as established vegetation and includes not only areas where weeds may already be growing, but also areas where weeds have yet to emerge, and also to areas under cultivation with respect to crops of useful plants. "Areas under cultivation" include land on which the crop plants are already growing and land intended for cultivation with such crop plants. The term "weeds" as used herein means any undesired plant, and thus includes not only
agronomically important weeds as described below, but also volunteer crop plants. The compounds for use in the invention can be applied before or after planting of the crops, before weeds emerge (pre-emergence application) or after weeds emerge (post- emergence application).
Crops of useful plants in which the composition according to the invention can be used include, but are not limited to, perennial crops, such as citrus fruit, grapevines, nuts, oil palms, olives, pome fruit, stone fruit and rubber, and annual arable crops, such as cereals, for example barley and wheat, cotton, oilseed rape, maize, rice, soy beans, sugar beet, sugar cane, sunflowers, ornamentals, switchgrass, turf and vegetables, especially cereals, maize and soy beans.
The grasses and weeds to be controlled may be both monocotyledonous species, for example Agrostis, Alopecurus, Avena, Brachiaria, Bromus, Cenchrus, Cyperus, Digitaria, Echinochloa, Eriochloa, Lolium, Monochoria, Panicum, Poa, Rottboellia, Sagittaria, Scirpus, Setaria, Sida and Sorghum, and dicotyledonous species, for example Abutilon, Amaranthus, Chenopodium, Chrysanthemum, Euphorbia, Galium, Ipomoea, Kochia, Nasturtium, Polygonum, Sida, Sinapis, Solanum, Stellaria, Veronica, Viola and Xanthium. Crops are to be understood as also including those crops which have been rendered tolerant to herbicides or classes of herbicides (e.g. auxins or ALS-, EPSPS-, PPO- and HPPD- inhibitors) by conventional methods of breeding or by genetic engineering. An example of a crop that has been rendered tolerant to imidazolinones, e.g. imazamox, by conventional methods of breeding is Clearfield® summer rape (canola). Examples of crops that have been rendered tolerant to herbicides by genetic engineering methods include e.g. glyphosate- and glufosinate- resistant maize varieties commercially available under the trade names RoundupReady® and LibertyLink®, respectively.
Crops are also to be understood as being those which have been rendered resistant to harmful insects by genetic engineering methods, for example Bt maize (resistant to European corn borer), Bt cotton (resistant to cotton boll weevil) and also Bt potatoes (resistant to Colorado beetle). Examples of Bt maize are the Bt 176 maize hybrids of NK® (Syngenta Seeds). The Bt toxin is a protein that is formed naturally by Bacillus thuringiensis soil bacteria. Examples of toxins, or transgenic plants able to synthesize such toxins, are described in EP-A-451 878, EP-A- 374 753, WO 93/07278, WO 95/34656, WO 03/052073 and EP-A-427 529. Examples of transgenic plants comprising one or more genes that code for an insecticidal resistance and express one or more toxins are KnockOut® (maize), Yield Gard® (maize), NuCOTIN33B® (cotton), Bollgard® (cotton), NewLeaf® (potatoes), NatureGard® and Protexcta®. Plant crops or seed material thereof can be both resistant to herbicides and, at the same time, resistant to insect feeding ("stacked" transgenic events). For example, seed can have the ability to express an insecticidal Cry3 protein while at the same time being tolerant to glyphosate.
Crops are also to be understood as being those which are obtained by conventional methods of breeding or genetic engineering and contain so-called output traits (e.g. improved storage stability, higher nutritional value and improved flavor).
Any method of application to weeds/crop of useful plant, or locus thereof, which is routinely used in agriculture may be used, for example application by spray or broadcast method typically after suitable dilution of a compound of formula (I) (whether said compound is formulated and/or in combination with one or more further active ingredients and/or safeners, as described herein).
The compounds of formula (I) according to the invention can also be used in combination with other active ingredients, e.g. other herbicides, and/or insecticides, and/or acaricides, and/or nematocides, and/or molluscicides, and/or fungicides, and/or plant growth regulators. Such mixtures, and the use of such mixtures to control weeds and/or undesired plant growth, form yet further aspects of the invention. For the avoidance of doubt, mixtures of invention also include mixtures of two or more different compounds of formula (I). In particular, the present invention also provides a composition which comprises at least one further herbicide in addition to the compound of formula (I). When a compound of formula (I) is combined with at least one additional herbicide, the following mixtures of the compound of formula (I) are preferred. Compound of formula (I) + acetochlor, compound of formula (I) + acifluorfen, compound of formula (I) + acifluorfen-sodium, compound of formula (I) + aclonifen, compound of formula (I) + acrolein, compound of formula (I) + alachlor, compound of formula (I) + alloxydim, compound of formula (I) + allyl alcohol, compound of formula (I) + ametryn, compound of formula (I) + amicarbazone, compound of formula (I) + amidosulfuron, compound of formula (I) + aminocyclopyrachlor, compound of formula (I) + aminopyralid, compound of formula (I) + amitrole, compound of formula (I) + ammonium sulfamate, compound of formula (I) + anilofos, compound of formula (I) + asulam, compound of formula (I) + atrazine, formula (I) + aviglycine, formula (I) + azafenidin, compound of formula (I) + azimsulfuron, compound of formula (I) + BCPC, compound of formula (I) + beflubutamid, compound of formula (I) + benazolin, formula (I) + bencarbazone, compound of formula (I) + benfluralin, compound of formula (I) + benfuresate, compound of formula (I) + bensulfuron, compound of formula (I) + bensulfuron-methyl, compound of formula (I) + bensulide, compound of formula (I) + bentazone, compound of formula (I) + benzfendizone, compound of formula (I) + benzobicyclon, compound of formula (I) + benzofenap, compound of formula (I) and bicyclopyrone, compound of formula (I) + bifenox, compound of formula (I) + bilanafos, compound of formula (I) + bispyribac, compound of formula (I) + bispyribac-sodium, compound of formula (I) + borax, compound of formula (I) + bromacil, compound of formula (I) + bromobutide, formula (I) + bromophenoxim, compound of formula (I) + bromoxynil, compound of formula (I) + butachlor, compound of formula (I) + butafenacil, compound of formula (I) + butamifos, compound of formula (I) + butralin, compound of formula (I) + butroxydim, compound of formula (I) + butylate, compound of formula (I) + cacodylic acid, compound of formula (I) + calcium chlorate, compound of formula (I) + cafenstrole, compound of formula (I) + carbetamide, compound of formula (I) + carfentrazone, compound of formula (I) + carfentrazone-ethyl, compound of formula (I) + CDEA, compound of formula (I) + CEPC, compound of formula (I) + chlorflurenol, compound of formula (I) + chlorflurenol-methyl, compound of formula (I) + chloridazon, compound of formula (I) + chlorimuron, compound of formula (I) + chlorimuron-ethyl, compound of formula (I) + chloroacetic acid, compound of formula (I) + chlorotoluron, compound of formula (I) + chlorpropham, compound of formula (I) + chlorsulfuron, compound of formula (I) + chlorthal, compound of formula (I) + chlorthal-dimethyl, compound of formula (I) + cinidon-ethyl, compound of formula (I) + cinmethylin, compound of formula (I) + cinosulfuron, compound of formula (I) + cisanilide, compound of formula (I) + clethodim, compound of formula (I) + clodinafop, compound of formula (I) + clodinafop-propargyl, compound of formula (I) + clomazone, compound of formula (I) + clomeprop, compound of formula (I) + clopyralid, compound of formula (I) + cloransulam, compound of formula (I) + cloransulam-methyl, compound of formula (I) + CMA, compound of formula (I) + 4-CPB, compound of formula (I) + CPMF, compound of formula (I) + 4-CPP, compound of formula (I) + CPPC, compound of formula (I) + cresol, compound of formula (I) + cumyluron, compound of formula (I) + cyanamide, compound of formula (I) + cyanazine, compound of formula (I) + cycloate, compound of formula (I) + cyclosulfamuron, compound of formula (I) + cycloxydim, compound of formula (I) + cyhalofop, compound of formula (I) + cyhalofop-butyl, compound of formula (I) + 2,4-D, compound of formula (I) + 3,4-DA, compound of formula (I) + daimuron, compound of formula (I) + dalapon, compound of formula (I) + dazomet, compound of formula (I) + 2,4-DB, compound of formula (I) + 3,4-DB, compound of formula (I) + 2,4-DEB, compound of formula (I) + desmedipham, formula (I) + desmetryn, compound of formula (I) + dicamba, compound of formula (I) + dichlobenil, compound of formula (I) + ortho-dichlorobenzene, compound of formula (I) + para-dichlorobenzene, compound of formula (I) + dichlorprop, compound of formula (I) + dichlorprop-P, compound of formula (I) + diclofop, compound of formula (I) + diclofop-methyl, compound of formula (I) + diclosulam, compound of formula (I) + difenzoquat, compound of formula (I) + difenzoquat metilsulfate, compound of formula (I) + diflufenican, compound of formula (I) + diflufenzopyr, compound of formula (I) + dimefuron, compound of formula (I) + dimepiperate, compound of formula (I) + dimethachlor, compound of formula (I) + dimethametryn, compound of formula (I) + dimethenamid, compound of formula (I) + dimethenamid-P, compound of formula (I) + dimethipin, compound of formula (I) + dimethylarsinic acid, compound of formula (I) + dinitramine, compound of formula (I) + dinoterb, compound of formula (I) + diphenamid, formula (I) + dipropetryn, compound of formula (I) + diquat, compound of formula (I) + diquat dibromide, compound of formula (I) + dithiopyr, compound of formula (I) + diuron, compound of formula (I) + DNOC, compound of formula (I) + 3,4-DP, compound of formula (I) + DSMA, compound of formula (I) + EBEP, compound of formula (I) + endothal, compound of formula (I) + EPTC, compound of formula (I) + esprocarb, compound of formula (I) + ethalfluralin, compound of formula (I) + ethametsulfuron, compound of formula (I) + ethametsulfuron-methyl, formula (I) + ethephon, compound of formula (I) + ethofumesate, compound of formula (I) + ethoxyfen, compound of formula (I) + ethoxysulfuron, compound of formula (I) + etobenzanid, compound of formual (I) + fenoxaprop, compound of formula (I) + fenoxaprop-P, compound of formula (I) + fenoxaprop-ethyl, compound of formula (I) + fenoxaprop-P-ethyl, compound of formula (I) + fentrazamide, compound of formula (I) + ferrous sulfate, compound of formula (I) + flamprop-M, compound of formula (I) + flazasulfuron, compound of formula (I) + florasulam, compound of formula (I) + fluazifop, compound of formula (I) + fluazifop-butyl, compound of formula (I) + fluazifop-P, compound of formula (I) + fluazifop-P-butyl, formula (I) + fluazolate, compound of formula (I) + flucarbazone, compound of formula (I) + flucarbazone-sodium, compound of formula (I) + flucetosulfuron, compound of formula (I) + fluchloralin, compound of formula (I) + flufenacet, compound of formula (I) + flufenpyr, compound of formula (I) + flufenpyr-ethyl, formula (I) + flumetralin, compound of formula (I) + flumetsulam, compound of formula (I) + flumiclorac, compound of formula (I) + flumiclorac-pentyl, compound of formula (I) + flumioxazin, formula (I) + flumipropin, compound of formula (I) + fluometuron, compound of formula (I) + fluoroglycofen, compound of formula (I) + fluoroglycofen-ethyl, formula (I) + fluoxaprop, formula (I) + flupoxam, formula (I) + flupropacil, compound of formula (I) + flupropanate, compound of formula (I) + flupyrsulfuron, compound of formula (I) + flupyrsulfuron-methyl-sodium, compound of formula (I) + flurenol, compound of formula (I) + fluridone, compound of formula (I) + flurochloridone, compound of formula (I) + fluroxypyr, compound of formula (I) + flurtamone, compound of formula (I) + fluthiacet, compound of formula (I) + fluthiacet-m ethyl, compound of formula (I) + fomesafen, compound of formula (I) + foramsulfuron, compound of formula (I) + fosamine, compound of formula (I) + glufosinate, compound of formula (I) + glufosinate-ammonium, compound of formula (I) + glyphosate, compound formula (I) and halauxifen, compound of formula (I) and halauxifen- methyl, compound of formula (I) + halosulfuron, compound of formula (I) + halosulfuron-methyl, compound of formula (I) + haloxyfop, compound of formula (I) + haloxyfop-P, compound of formula (I) + HC-252, compound of formula (I) + hexazinone, compound of formula (I) + imazamethabenz, compound of formula (I) + imazamethabenz-methyl, compound of formula (I) + imazamox, compound of formula (I) + imazapic, compound of formula (I) + imazapyr, compound of formula (I) + imazaquin, compound of formula (I) + imazethapyr, compound of formula (I) + imazosulfuron, compound of formula (I) + indanofan, compound of formula (I) and indaziflam, compound of formula (I) + iodomethane, compound of formula (I) + iodosulfuron, compound of formula (I) + iodosulfuron-methyl-sodium, compound of formula (I) + ioxynil, compound of formula (I) and ipfencarbazone, compound of formula (I) + isoproturon, compound of formula (I) + isouron, compound of formula (I) + isoxaben, compound of formula (I) + isoxachlortole, compound of formula (I) + isoxaflutole, formula (I) + isoxapyrifop, compound of formula (I) + karbutilate, compound of formula (I) + lactofen, compound of formula (I) + lenacil, compound of formula (I) + linuron, compound of formula (I) + MAA, compound of formula (I) + MAMA, compound of formula (I) + MCPA, compound of formula (I) + MCPA-thioethyl, compound of formula (I) + MCPB, compound of formula (I) + mecoprop, compound of formula (I) + mecoprop- P, compound of formula (I) + mefenacet, compound of formula (I) + mefluidide, compound of formula (I) + mesosulfuron, compound of formula (I) + mesosulfuron-methyl, compound of formula (I) + mesotrione, compound of formula (I) + metam, compound of formula (I) + metamifop, compound of formula (I) + metamitron, compound of formula (I) + metazachlor, compound of formula (I) and metazosulfuron, compound of formula (I) + methabenzthiazuron, formula (I) + methazole, a compound of formula (I) and methiozolin, compound of formula (I) + methylarsonic acid, compound of formula (I) + methyldymron, compound of formula (I) + methyl isothiocyanate, compound of formula (I) + metobenzuron, formula (I) + metobromuron, compound of formula (I) + metolachlor, compound of formula (I) + S-metolachlor, compound of formula (I) + metosulam, compound of formula (I) + metoxuron, compound of formula (I) + metribuzin, compound of formula (I) + metsulfuron, compound of formula (I) + metsulfuron-methyl, compound of formula (I) + MK-616, compound of formula (I) + molinate, compound of formula (I) + monolinuron, a compound of formula (I) and monosulfuron, a compound of formula (I) and monosulfuron-ester compound of formula (I) + MSMA, compound of formula (I) + naproanilide, compound of formula (I) + napropamide, compound of formula (I) + naptalam, formula (I) + NDA- 402989, compound of formula (I) + neburon, compound of formula (I) + nicosulfuron, formula (I) + nipyraclofen, formula (I) + n-methyl glyphosate, compound of formula (I) + nonanoic acid, compound of formula (I) + norflurazon, compound of formula (I) + oleic acid (fatty acids), compound of formula (I) + orbencarb, compound of formula (I) + orthosulfamuron, compound of formula (I) + oryzalin, compound of formula (I) + oxadiargyl, compound of formula (I) + oxadiazon, compound of formula (I) + oxasulfuron, compound of formula (I) + oxaziclomefone, compound of formula (I) + oxyfluorfen, compound of formula (I) + paraquat, compound of formula (I) + paraquat dichloride, compound of formula (I) + pebulate, compound of formula (I) + pendimethalin, compound of formula (I) + penoxsulam, compound of formula (I) +
pentachlorophenol, compound of formula (I) + pentanochlor, compound of formula (I) + pentoxazone, compound of formula (I) + pethoxamid, compound of formula (I) + petrolium oils, compound of formula (I) + phenmedipham, compound of formula (I) + phenmedipham-ethyl, compound of formula (I) + picloram, compound of formula (I) + picolinafen, compound of formula (I) + pinoxaden, compound of formula (I) + piperophos, compound of formula (I) + potassium arsenite, compound of formula (I) + potassium azide, compound of formula (I) + pretilachlor, compound of formula (I) + primisulfuron, compound of formula (I) + primisulfuron-methyl, compound of formula (I) + prodiamine, compound of formula (I) + profluazol, compound of formula (I) + profoxydim, formula (I) + prohexadione-calcium, compound of formula (I) + prometon, compound of formula (I) + prometryn, compound of formula (I) + propachlor, compound of formula (I) + propanil, compound of formula (I) + propaquizafop, compound of formula (I) + propazine, compound of formula (I) + propham, compound of formula (I) + propisochlor, compound of formula (I) + propoxycarbazone, compound of formula (I) + propoxycarbazone-sodium, compound of formula (I) + propyzamide, compound of formula (I) + prosulfocarb, compound of formula (I) + prosulfuron, compound of formula (I) + pyraclonil, compound of formula (I) + pyraflufen, compound of formula (I) + pyraflufen-ethyl, formula (I) + pyrasulfotole, compound of formula (I) + pyrazolynate, compound of formula (I) + pyrazosulfuron, compound of formula (I) + pyrazosulfuron-ethyl, compound of formula (I) + pyrazoxyfen, compound of formula (I) + pyribenzoxim, compound of formula (I) + pyributicarb, compound of formula (I) + pyridafol, compound of formula (I) + pyridate, compound of formula (I) + pyriftalid, compound of formula (I) + pyriminobac, compound of formula (I) + pyriminobac-methyl, compound of formula (I) + pyrimisulfan, compound of formula (I) + pyrithiobac, compound of formula (I) + pyrithiobac-sodium, formula (I) + pyroxasulfone, formula (I) + pyroxulam, compound of formula (I) + quinclorac, compound of formula (I) + quinmerac, compound of formula (I) + quinoclamine, compound of formula (I) + quizalofop, compound of formula (I) + quizalofop-P, compound of formula (I) + quizalofop-ethyl, compound of formula (I) + quizalofop-P-ethyl, compound of formula (I) + rimsulfuron, compound of formula (I) + saflufenacil, compound of formula (I) + sethoxydim, compound of formula (I) + siduron, compound of formula (I) + simazine, compound of formula (I) + simetryn, compound of formula (I) + SMA, compound of formula (I) + sodium arsenite, compound of formula (I) + sodium azide, compound of formula (I) + sodium chlorate, compound of formula (I) + sulcotrione, compound of formula (I) + sulfentrazone, compound of formula (I) + sulfometuron, compound of formula (I) + sulfometuron-methyl, compound of formula (I) + sulfosate, compound of formula (I) + sulfosulfuron, compound of formula (I) + sulfuric acid, compound of formula (I) + tar oils, compound of formula (I) + 2,3,6- TBA, compound of formula (I) + TCA, compound of formula (I) + TCA-sodium, formula (I) + tebutam, compound of formula (I) + tebuthiuron, formula (I) + tefuryltrione, compound of formula 1 + tembotrione, compound of formula (I) + tepraloxydim, compound of formula (I) + terbacil, compound of formula (I) + terbumeton, compound of formula (I) + terbuthylazine, compound of formula (I) + terbutryn, compound of formula (I) + thenylchlor, compound of formula (I) + thiazafluron, compound of formula (I) + thiazopyr, compound of formula (I) + thifensulfuron, compound of formula (I) + thiencarbazone, compound of formula (I) + thifensulfuron-methyl, compound of formula (I) + thiobencarb, compound of formula (I) + tiocarbazil, compound of formula (I) + topramezone, compound of formula (I) + tralkoxydim, a compound of formula (I) and triafamone compound of formula (I) + tri-allate, compound of formula (I) + triasulfuron, compound of formula (I) + triaziflam, compound of formula (I) + tribenuron, compound of formula (I) + tribenuron-methyl, compound of formula (I) + tricamba, compound of formula (I) + triclopyr, compound of formula (I) + trietazine, compound of formula (I) + trifloxysulfuron, compound of formula (I) + trifloxysulfuron-sodium, compound of formula (I) + trifluralin, compound of formula (I) + triflusulfuron, compound of formula (I) + triflusulfuron-methyl, compound of formula (I) + trifop, compound of formula (I) + trifop-methyl, compound of formula (I) + trihydroxytriazine, compound of formula (I) + trinexapac-ethyl, compound of formula (I) + tritosulfuron, compound of formula (I) + [3-[2-chloro-4-fluoro-5-(1-methyl-6-trifluoromethyl-2,4-dioxo-1 ,2,3,4-tetrahydropyrimidin-3- yl)phenoxy]-2-pyridyloxy]acetic acid ethyl ester (CAS RN 353292-31-6), compound of formula (I) + 2-[[8-chloro-3,4-dihydro-4-(4-methoxyphenyl)-3-oxo-2-quinoxalinyl]carbonyl]1 ,3- cyclohexanedione and the compound of formula (I) + VX-573.
In particular, the following mixtures are important and, accordingly, the present invention provides a composition comprising a compound of formula (I) + ametryn, a compound of formula (I) + atrazine, a compound of formula (I) + bicyclopyrone, a compound of formula (I) + cinosulfuron, a compound of formula (I) + clodinafop-propargyl, a compound of formula (I) + clomazone, a compound of formula (I) + dicamba, a compound of formula (I) + dimethachlor, a compound of formula (I) + diquat, a compound of formula (I) + fluazifop-p-butyl, a compound of formula (I) + fomesafen, a compound of formula (I) + glyphosate, a compound of formula (I) + mesotrione, a compound of formula (I) + molinate, a compound of formula (I) + napropamide, a compound of formula (I) + S-metolachlor, a compound of formula (I) + nicosulfuron, a compound of formula (I) + paraquat, a compound of formula (I) + pinoxaden, a compound of formula (I) + pretilachlor, a compound of formula (I) + primisulfuron, a compound of formula (I) + prometryn, a compound of formula (I) + prosulfocarb, a compound of formula (I) + prosulfuron, a compound of formula (I) + pyridate, a compound of formula (I) + pyriftalid, a compound of formula (I) + tralkoxydim, a compound of formula (I) + triasulfuron or a compound of formula (I) +
trif loxysu If u ron-sod iu m .
Whilst two-way mixtures of a compound of formula (I) and another herbicide are explicitly disclosed above, the skilled man will appreciate that the invention extends to three-way, and further multiple combinations comprising the above two-way mixtures.
The mixing partners of the compound of formula (I) may also be in the form of esters or salts, as mentioned e.g. in The Pesticide Manual, 14th Edition (BCPC), 2006. The reference to acifluorfen-sodium also applies to acifluorfen, the reference to dimethenamid also applies to dimethenamid-P, the reference to glufosinate-ammonium also applies to glufosinate, the reference to bensulfuron-methyl also applies to bensulfuron, the reference to cloransulam-methyl also applies to cloransulam, the reference to flamprop-M also applies to flamprop, and the reference to pyrithiobac-sodium also applies to pyrithiobac, etc. The mixing ratio of the compound of formula (I) to the mixing partner is preferably from 1 : 100 to 1000: 1.
The mixtures can advantageously be used in the above-mentioned formulations (in which case "active ingredient" relates to the respective mixture of compound of formula (I) with the mixing partner).
The compounds of formula (I) according to the invention can also be used in combination with one or more safeners. Likewise, mixtures of a compound of formula (I) according to the invention with one or more further active ingredients, in particular with one or more further herbicides, can also be used in combination with one or more safeners. The term "safener" as used herein means a chemical that when used in combination with a herbicide reduces the undesirable effects of the herbicide on non-target organisms, for example, a safener protects crops from injury by herbicides but does not prevent the herbicide from killing the weeds. Where a compound of formula (I) is combined with a safener, the following combinations of the compound of formula (I) and the safener are particularly preferred. Compound of formula (I) + AD 67 (MON 4660), compound of formula (I) + benoxacor, compound of formula (I) + cloquintocet- mexyl, compound of formula (I) + cyometrinil and a compound of formula (I) + the corresponding (Z) isomer of cyometrinil, compound of formula (I) + cyprosulfamide (CAS RN 221667-31-8), compound of formula (I) + dichlormid, compound of formula (I) and dicyclonon, compound of formula (I) and dietholate, compound of formula (I) + fenchlorazole-ethyl, compound of formula (I) + fenclorim, compound of formula (I) + flurazole, compound of formula (I) + fluxofenim, compound of formula (I) + furilazole and a compound of formula (I) + the corresponding R isomer or furilazome, compound of formula (I) + isoxad if en-ethyl, compound of formula (I) + mefenpyr- diethyl, compound of formula (I) and mephenate, compound of formula (I) + oxabetrinil, compound of formula (I) + naphthalic anhydride (CAS RN 81-84-5), compound of formula (I) and TI-35, compound of formula (I) + N-isopropyl-4-(2-methoxy-benzoylsulfamoyl)-benzamide (CAS RN 221668-34-4) and a compound of formula (I) + N-(2-methoxybenzoyl)-4- [(methylaminocarbonyl)amino]benzenesulfonamide.
The safeners of the compound of formula (I) may also be in the form of esters or salts, as mentioned e.g. in The Pesticide Manual, 14th Edition (BCPC), 2006. The reference to cloquintocet-mexyl also applies to cloquintocet and to a lithium, sodium, potassium, calcium, magnesium, aluminium, iron, ammonium, quaternary ammonium, sulfonium or phosphonium salt thereof as disclosed in WO02/34048 and the reference to fenchlorazole-ethyl also applies to fenchlorazole, etc.
Preferably the mixing ratio of compound of formula (I) to safener is from 100: 1 to 1 : 10, especially from 20: 1 to 1 : 1.
The mixtures can advantageously be used in the above-mentioned formulations (in which case "active ingredient" relates to the respective mixture of compound of formula (I) and any further active ingredient, in particular a further herbicide, with the safener). It is possible that the safener and a compound of formula (I) and one or more additional herbicide(s), if any, are applied simultaneously. For example, the safener, a compound of formula (I) and one or more additional herbicide(s), if any, might be applied to the locus pre-emergence or might be applied to the crop post-emergence. It is also possible that the safener and a compound of formula (I) and one or more additional herbicide(s), if any, are applied sequentially. For example, the safener might be applied before sowing the seeds as a seed treatment and a compound of formula (I) and one or more additional herbicides, if any, might be applied to the locus pre-emergence or might be applied to the crop post-emergence.
Various aspects and embodiments of the present invention will now be illustrated in more detail by way of example. It will be appreciated that modification of detail may be made without departing from the scope of the invention.
Examples
Preparation Examples
Example 1 (Compound No. 7)
Synthesis of 2-fluoro-N-(3-methylcyclohexyl)pyridine-4-carboxamide.
Figure imgf000033_0001
2-Fluoropyridine-4-carboxylic acid (500 mg, 3.54 mmol) was stirred with toluene (5 ml) and thionyl chloride (1 ml) was added. The resulting mixture was heated at reflux for 40 minutes. The reaction mixture was cooled and concentrated in vacuo to give 2-fluoropyridine-4-carbonyl chloride. This was dissolved in dichloromethane (10 ml) and added dropwise to a stirred solution of 3-methylcyclohexylamine (392 mg, 3.46 mmol) and pyridine (0.28 ml, 3.5 mmol) in
dichloromethane (10 ml) with cooling in an ice/water bath. After 3 hours the reaction mixture was poured into water and the organic layer was separated and dried (MgS04), and then
concentrated in vacuo and purified by silica gel chromatography (gradient elution 0-40% EtOAc in isohexane) to give 2-fluoro-N-(3-methylcyclohexyl)pyridine-4-carboxamide (328 mg, 39%) as an oil which crystallised on standing.
Characterising data for the compound are as follows: 1 H NMR (400 MHz, CDCI3) δ ppm 8.33 (m, 1 H), 7.46 (m, 1 H), 7.25 (m, 1 H), 6.18 (br s, 1 H), 5.91 (br s, 1 H), 4.33 (m, 1 H), 3.97 (m, 1 H), 2.08- 1.35 (m, 7H) and 1.15-0.70 (m, 5H).
Example 2 (Compound No. 22) Synthesis of 2,5-difluoro-N-(2-methylcyclohexyl)pyridine-4-carboxamide
Figure imgf000034_0001
2,5-Difluoro-N-(2-methylcyclohexyl)pyridine-4-carboxamide was prepared in a similar manner to the method described in example 1.
Characterising data for the compound are as follows: 1 H NMR (400 MHz, CDCI3) δ ppm 8.17 (m, 1 H), 7.59 (m, 1 H), 6.76 (m, 1 H), 4.32-4.28 (m, 1 H), 3.74-3.68 (m, 1 H), 2.10-1.57 (m, 5H) and 1.50-0.93 (m, 7H).
Example 3 (Compound Nos. 29 - 34)
Separation of isomers of N-(2,3-dimethylcyclohexyl)-2-fluoro-pyridine-4-carboxamide
Figure imgf000034_0002
A/-(2,3-Dimethylcyclohexyl)-2-fluoro-pyridine-4-carboxamide is commercially available as a mixture of stereoisomers and was separated into four pairs of enantiomers using mass directed reverse phase and then normal phase chromatography, as detailed in the following sentences. An initial separation was made by mass directed preparative HPLC using a mixed trigger of UV with ES+ on a Waters Fraction Lynx system comprising a 2767 injector/collector with a 2545 gradient pump, two 515 isocratic pumps, SFO, 2998 photodiode array, 2424 ELSD and 3100 mass spectrometer. A Waters XBridge dC18 5micron 19x10mm guard column was used with an ACE c!C18-Ar 5micron 30x1 OOmm prep column. The preparative HPLC was conducted using a 20 minute run time using 'at column dilution', according to the following gradient table.
Figure imgf000035_0001
515 pump 2ml/min CH3CN with 0.05% TFA
515 pump 1 ml/min 90% MeOH/10% H20 (make up pump)
Solvent A: H20 with 0.05% TFA
Solvent B: CH3CN with 0.05% TFA
This was followed by normal phase chromatography (gradient elution of 15-60% EtOAc in isohexane) to give the following stereoisomeric compounds.: Compound No 31: cis/cis-N-(2,3-dimethylcyclohexyl)-2-fluoro-pyridine-4-carboxamide
Characterising data for the compound are as follows: 1H NMR (400 MHz, CD30D) δ ppm 8.33 (m, 1H), 7.66 (m, 1H), 7.43 (m, 1H), 4.04 (m, 1H), 2.20-2.11 (m, 1H), 1.89-1.70 (m, 1H), 1.70- 1.53 (m, 1H), 1.53-1.35 (m, 1H), 1.30-1.17 (m, 1H), 1.04-0.94 (m, 1H), 0.95 (d, 3H), 0.85 (m, 1H).
Compound No 32: trans/cis-N-(2,3-dimethylcyclohexyl)-2-fluoro-pyridine-4-carboxamide Characterising data for the compound are as follows: 1H NMR (400 MHz, CD30D) δ ppm 8.33 (m, 1H), 7.66 (m, 1H), 7.41 (m, 1H), 3.94 (m, 1H), 2.02-1.83 (m 2H), 1.80-1.70 (m, 1H), 1.68-1.50 (m, 4H), 1.45-1.30 (m, 1H), 0.97 (m, 6H).
Compound No 33: trans/trans-N-(2,3-dimethylcyclohexyl)-2-fluoro-pyridine-4-carboxamide
Characterising data for the compound are as follows: 1H NMR (400 MHz, CD30D) δ ppm 8.33 (m, 1H), 7.66 (m,1H), 7.42 (m, 1H), 3.67 (m, 1H), 1.96-1.87 (m, 1H), 1.83-1.74 (m,1H), 1.74-1.65 (m, 1H), 1.52-1.30 (m, 2H), 1.27-1.13 (m, 2H), 1.13-1.00 (m, 1H), 0.98 (m, 6H).
Compound No 34: cis/trans-N-(2,3-dimethylcyclohexyl)-2-fluoro-pyridine-4-carboxamide
Characterising data for the compound are as follows: 1H NMR (400 MHz, CD30D) δ ppm 8.33 (m, 1H), 7.46 (m, 1H), 7.24 (m, 1H), 4.32 (m, 1H), 1.93-1.84 (m, 1H), 1.76-1.52 (m, 1H), 1.52- 1.34 (m,3H), 1.34 -1.20 (m, 2H), 1.16-1.01 (m, 1H), 0.95 (m, 6H). Example 4 (Compound Nos. 39-40)
Synthesis of 2-fluoro-N-[(4-methylcyclohexyl)methyl]pyridine-4-carboxamide nantiomer
Figure imgf000036_0001
A solution of 2-fluoropyridine-4-carbonyl chloride (301 mg, 1.89 mmol), prepared using the method detailed in example 1 , in dichloromethane (5ml) was added dropwise to a solution of (4- methylcyclohexyl)methylamine (200 mg, 1.57 mmol) and pyridine (149 mg, 1.89 mmol) stirred in dichloromethane (5ml) under nitrogen and cooled to 0°C. The stirred reaction mixture was allowed to warm to room temperature over 16 hours and then poured into water (10ml) and the organic layer was separated and concentrated in vacuo to give the crude product (500mg) as a yellow gum.
The yellow gum was purified by mass directed preparative HPLC using a mixed trigger of UV with ES+ on a Waters Fraction Lynx system comprising a 2767 injector/collector with a 2545 gradient pump, two 515 isocratic pumps, SFO, 2998 photodiode array, 2424 ELSD and 3100 mass spectrometer. A Waters XBridge dC18 5micron 19x10mm guard column was used with an ACE dC18-Ar 5micron 30x100mm prep column. The preparative HPLC was conducted using a 1 1.4 minute run time using 'at column dilution' , according to the following gradient table:
Figure imgf000036_0002
515 pump 2ml/min CH3CN with 0.05% TFA
515 pump 1 ml/min 90% MeOH/10% H20 (make up pump)
Solvent A: H20 with 0.05% TFA
Solvent B: CH3CN with 0.05% TFA Fraction 1 , compound No. 39: 170mgs of a white solid is a mixture of major trans, minor cis isomer with a ratio of 1 : 0.9.
Characterising data for the compound are as follows: 1 H NMR (400 MHz, CDCI3) δ ppm 8.33 (d, 1 H), 7.48 (d, 1 H), 7.27 (s, 1 H), 6.20-6.36 (m, 1 H), 3.42 (dd, 1 H), 3.32 (t, 1 H), 1.24-1.82 (m, 8H), 0.85-1.09 (m, 5 H).
Fraction 2, compound No. 40: 180mgs of a white solid is also a mixture of major trans, minor cis isomer with a ratio of 2 : 1.
Characterising data for the compound are as follows: 1 H NMR (400 MHz, CDCI3) δ ppm 8.33 (d, 1 H), 7.46-7.50 (m, 1 H), 7.27 (s, 1 H), 6.17-6.30 (br d, 1 H), 3.43 (dd, 0.65H), 3.32 (t, 1 H), 0.84 - 1.84 (m, 13H).
Example 5 (Compound Nos. 37 - 38)
Synthesis of 2-fluoro-N-(2-methylcyclohexyl)pyridine-4-carbothioamide nan nantiomer
Figure imgf000037_0001
2,4-Bis[(4-methylphenyl)sulfanyl]-1 ,3,2,4-dithiadiphosphetane 2,4-disulfide (1.03g, 2.37mmol) was added to a stirring solution of 2-fluoro-N-(2-methylcyclohexyl)pyridine-4-carboxamide (1.12 g, 4.74 mmol) in toluene (70 ml) under nitrogen at room temperature. The resultant yellow mixture was then heated to reflux and as it was heating the colour changed to dark orange. The reaction mixture was heated for an hour and then allowed to cool. LCMS analysis showed that the theoretical mass was present. The reaction mixture was concentrated in vacuo to leave an orange oil which was adsorbed onto silica gel and purified using silica gel (80g column) chromatography with gradient elution (0-50% EtOAc in isohexane) to give compounds Nos. 37 and 38.
Compound No. 37: trans-2-fluoro-N-(2-methylcyclohexyl)pyridine-4-carbothioamide (578mgs. 51.6%).
Characterising data for the compound are as follows: 1 H NMR (400 MHz, CDCI3) δ ppm 8.23 (d, 1 H), 8.13 (d, 1 H), 7.40 (d, 1 H), 7.13 (s, 1 H), 4.32 (dd, 1 H), 2.18-2.24 (m, 1 H) 1.70-1.89 (m, 3H), 1.52-1.67 (m, 1 H), 1.41 (d, 1 H), 1.28-1.17 (m, 3H), 1 .02 (d, 3H).
Compound No. 38: cis-2-fluoro-N-(2-methylcyclohexyl)pyridine-4-carbothioamide (158mgs, 14.1 %). Characterising data for the compound are as follows: 1 H NMR (400 MHz, CDCI3) δ ppm 8.23 (d, 1 H), 7.64 (br s, 1 H), 7.38 (d, 1 H), 7.14 (s, 1 H), 4.71-4.82 (m, 1 H), 2.19 (dd, 1 H), 1.95 (td, 1 H), 1.28-1.76 (m, 7H), 0.99 (d, 3H).
In addition, a mixed cis/trans fraction (294mg, 26.3%) was obtained. Example 6 (Compound No. 64)
Synthesis of 7-azabicyclo[4.1 .0]heptan-7-yl-(2-fluoro-4-pyridyl)methanone
Figure imgf000038_0001
To a solution of 7-azabicyclo[4.1.0]heptane (2.4g, 24.6mmol) and 2-fluoropyridine-4-carboxylic acid (2.9g, 20.5mmol) in anhydrous dichloromethane (55ml) was added anhydrous triethylamine (8.5ml, 61.6mmol) at 0 °C under nitrogen. A 50% solution of 2,4,6-tripropyl-1 ,3,5-trioxa-2,4,6- triphosphinane-2,4,6-trioxide (T3P) in ethyl acetate (26ml, 41.1 mmol, 2.0 equiv) was added dropwise at 0 °C and the resulting mixture was stirred at room temperature for 3h. The reaction mass was diluted with dichloromethane (50ml) and washed with water (2x 50ml), dried over anhydrous sodium sulfate and the solvents were evaporated under reduced pressure. The crude product was purified by Combiflash chromatography to give 7-azabicyclo[4.1 .0]heptan-7-yl-(2- fluoro-4-pyridyl)methanone (2.7g, 49.6%) as an off-white solid.
Characterising data for the compound are as follows: 1 H NMR (400 MHz, CDCI3) δ ppm 8.35 (m, 1 H), 7.65 (m, 1 H), 7.40 (m, 1 H), 2.81 (m, 2H), 2.05 (m, 2H), 1.93 (m, 2H), 1 .54 (m, 2H), 1.37 (m, 2H)
Example 7 (Compound No. 47)
Synthesis of 2-fluoro-N-(2-fluorocyclohexyl)pyridine-4-carboxamide
Figure imgf000038_0002
To an argon-degassed solution of 7-azabicyclo[4.1 .0]heptan-7-yl-(2-fluoro-4-pyridyl)methanone (600mg, 2.7mmol) in anhydrous tetrahydrofuran (30ml) was added TBAF (1 M solution in THF) (3.2ml, 3.2mmol) and the reaction mixture was stirred at room temperature for 5h. TLC analysis showed complete conversion (TLC system: 30% EtOAc in hexanes, Rf~0.2). The solvents were removed under vacuum and the crude product was purified by Combiflash chromatography (product eluted with 19-25% EtOAc in hexanes) to give pure 2-fluoro-N-(2- fluorocyclohexyl)pyridine-4-carboxamide (420mg, 64.9%) as a white solid.
Characterising data for the compound are as follows: 1 H NMR (400 MHz, CDCI3) δ ppm 8.33 (m, 1 H), 7.47 (m, 1 H), 7.26 (m, 1 H), 6.10 (br, 1 H), 4.43 (m, 0.5H), 4.33 (m, 0.5H), 4.08 (m, 1 H),2.23 (m, 1 H), 1.84 (m, 1 H), 1.71 (m, 1 H),1.62-1.24 (m, 4H).
Example 8 (Compound No. 48)
Synthesis of 2-fluoro-N-(2-chlorocyclohexyl)pyridine-4-carboxamide
Figure imgf000039_0001
To a solution of the crude 2-fluoropyridine-4-carbonyl chloride (3.1 mmol), prepared as described in example 1 , was added dropwise diisopropylethylamine (1.1 ml, 6.4mmol) at 0°C under nitrogen. A solution of 7-azabicyclo[4.1.0] heptane (250mg, 2.5mmol) in anhydrous dichloromethane (3ml) was added dropwise at 0°C and the reaction mixture was stirred at 0°C for 1 hr. The solvents were removed under vacuum and the crude product was purified by flash column
chromatography, eluting with 20-25% EtOAc in hexanes, to give pure 2-fluoro-N-(2- chlorocyclohexyl)pyridine-4-carboxamide (350mg, 53%) as a white solid.
Characterising data for the compound are as follows: 1 H NMR (400 MHz, CDCI3) δ ppm 8.34 (d, 1 H) 7.49 (d, 1 H) 7.25 - 7.30 (m, 1 H) 6.52 (br. s., 1 H) 4.59 (d, 1 H) 4.25 - 4.34 (m, 1 H) 2.08 - 2.18 (m, 1 H) 1.67 - 1.96 (m, 5 H) 1.55-1.58 (m, 1 H) 1.37 - 1.52 (m, 1 H)
Example 9 (Compound No. 54)
Synthesis of 2-fluoro-N-(2-cyanocyclohexyl)pyridine-4-carboxamide
Figure imgf000039_0002
To an argon-degassed solution of 7-azabicyclo[4.1 .0]heptan-7-yl-(2-fluoro-4-pyridyl)methanone (600mg, 2.7mmol) in anhydrous tetrahydrofuran (30ml) was sequentially added TMSCN (0.4ml, 2.72mmol) and TBAF (1 M solution in THF) (0.15ml. 0.15mmol) and the reaction mixture was heated at 40 °C (bath temperature) for 4h. TLC analysis showed complete conversion (TLC system: 1 : 1 EtOAc in hexanes, Rf~0.3). Solvents were removed under vacuum and the crude product was purified by Combiflash chromatography (product eluted with 25-28% EtOAc in hexanes) to give pure 2-fluoro-N-(2-cyanocyclohexyl)pyridine-4-carboxamide (600mg, 89%) as white solid.
Example 10 (Compound No. 49)
Synthesis of 2-fluoro-N-(2-bromocyclohexyl)pyridine-4-carboxamide
Figure imgf000040_0001
To a turbid solution of zinc bromide (51 1 mg, 2.3mmol) in chloroform (3ml) was added dropwise solution of 7-azabicyclo[4.1.0]heptan-7-yl-(2-fluoro-4-pyridyl)methanone (250mg, 1 .13mmol) in chloroform (3ml) at ambient temperature and stirred for 4h. Saturated aqueous ammonium chloride solution was added and the resulting mixture was extracted with chloroform (15ml x 2).
The combined organic layers were washed with brine, dried over anhydrous sodium sulfate and the solvents were removed to give the crude product which was purified by Combiflash chromatography (product eluted with 25-50% EtOAc in hexanes, TLC system: 30% EtOAc in hexanes, Rf~0.3) to give pure 2-fluoro-N-(2-bromocyclohexyl)pyridine-4-carboxamide (225mg,
65.8%) as a white solid.
Example 11 (Compound No. 65)
Synthesis of 2-fluoro-N-(2- methylsulfanylcyclohexyl)pyridine-4-carboxamide
Figure imgf000040_0002
To a solution of 7-azabicyclo[4.1.0]heptan-7-yl-(2-fluoro-4-pyridyl)methanone (600mg, 2.7mmol) in anhydrous Ν,Ν-dimethylformamide (17ml) was added a solution of sodium thiomethoxide (230mg, 3.2 mmol) in anhydrous Ν,Ν-dimethylformamide (3ml) at room temperature. The resulting mixture was stirred at room temperature for 2h. TLC analysis showed complete conversion (TLC system: 30% EtOAc in hexanes, Rf~0.3). The reaction mass was poured into saturated aqueous ammonium chloride solution (30ml) and was extracted with ethyl acetate (2x 50ml). The combined organic layers were washed successively with water (4 x 50ml) and brine (100ml), and then dried over anhydrous sodium sulfate. The solvents were removed under vacuum to give the crude product which was purified by trituration in 10% ethyl acetate in hexanes (15ml) to give pure 2-fluoro-N-(2- methylsulfanylcyclohexyl)pyridine-4-carboxamide (570mg, 78%) as a white solid. Example 12 (Compound No. 53)
Synthesis of 2-fluoro-N-(2-methoxycyclohexyl)pyridine-4-carboxamide
Figure imgf000041_0001
7-Azabicyclo[4.1.0]heptan-7-yl-(2-fluoro-4-pyridyl)methanone (750mg, 3.47mmol) and phenyl phosphonic acid (241 mg, 1 Jmmol) were put into a two-neck round bottom flask and thrice evacuated under vacuum, the vacuum being replaced each time with argon. Anhydrous methanol (654mg, 0.8ml, 20.4mmol, 6.0 equiv) was added, followed by anhydrous dichloromethane (12ml) and the reaction mass was stirred at room temperature for 4h (TLC system 1 :1 EtOAc in hexanes, Rf~0.3) The reaction mass was concentrated under reduced pressure and the crude product was purified by silica gel column chromatography (100-200 mesh silica gel, product eluted with 25-35% EtOAc in hexanes) to give pure 2-fluoro-N-(2-methoxycyclohexyl)pyridine-4- carboxamide (500mg, 58.8%) as a white solid.
Example 13 (Compound No. 56)
Synthesis of N-(2,2-difluorocyclohexyl)-2-fluoro-pyridine-4-carboxamide:
Figure imgf000041_0002
2-Fluoropyridine-4-carboxylic acid (0.34 g, 2.4 mmol), 1-hydroxybenzotriazole (0.69g, 4.9 mmol), 3-(ethyliminomethyleneamino)-N,N-dimethyl-propan-1-amine hydrochloride (0.93 g, 4.9 mmol) and pyridine (0.24 mL, 2.9 mmol) were added to a stirring solution of 2,2- difluorocyclohexylamine hydrochloride (500 mg, 2.9 mmol) in N,N-dimethylformamide (7 mL) at room temperature. The reaction mixture was stirred overnight. Sodium bicarbonate (sat.
aqueous, 5 mL) was then added and the mixture was extracted with ethyl acetate (3 x 10 mL). The combined organics were washed with water (10 mL) and brine (10 mL), then dried (MgS04) and concentrated in vacuo to give a yellow oil. The crude material was purified using column chromatography (24g silica cartridge) to afford N-(2,2-difluorocyclohexyl)-2-fluoro-pyridine-4- carboxamide as a white solid (598 mg, 2.3 mmol, 79%).
Additional compounds in Table 1 below were prepared by similar methods using appropriate starting materials. Unless otherwise stated, NMR spectra were run in deuterated chloroform and on an instrument operating at 400 MHz.
Table 1
Figure imgf000042_0001
Figure imgf000043_0001
Figure imgf000044_0001
Figure imgf000045_0001
Figure imgf000046_0001
Figure imgf000047_0001
Figure imgf000048_0001
Figure imgf000049_0001
Figure imgf000050_0001
Figure imgf000051_0001
Figure imgf000052_0001
Figure imgf000053_0001
Figure imgf000054_0001
Figure imgf000055_0001
Figure imgf000056_0001
Figure imgf000057_0001
Figure imgf000058_0001
Figure imgf000059_0001
Figure imgf000060_0001
Figure imgf000061_0001
Figure imgf000062_0001
Figure imgf000063_0001
Figure imgf000064_0001
Figure imgf000065_0001
Figure imgf000066_0001
n on 0.3H), 3.92 - 4.03 (m, yi cyclohexa 0.7H), 2.07 (m, 2H), ne. 1.91 - 1.95 (m, 3H), 1.63
- 1.87 (m, 3H), 1.39 - 1.49 (m, 1 H), 1.01 - 1.13 (m, 1 H), 0.93 - 0.98 (m, 3H), 0.77 - 0.90 (m, 2H).
185 Or enantiomer cis-2- methylcyc As reported for lohexyl, compound 24
F H H H H - 0 enantiom (racemate)
er A
186 Or enantiomer cis-2- methylcyc As reported for lohexyl, compound 24
F H H H H - 0 enantiom (racemate)
er B
187 cis-2- 8.35 (d, 1 H), 7.50-7.68 cyano (m, 1 H), 7.32 (s, 1 H), cyclohexy 6.67 (d, 1 H), 4.12 (ddt, I 1 H), 3.36-3.52 (m, 1 H),
F H H H H - 0 2.78 (br.s., 1 H), 2.01- 2.13 (m, 1 H), 1.94-1.92 (m, 2H), 1.65-1.82 (m, 3H), 1.34-1.62 (m, 2H).
188 2,3- No NMR data (prepared dimethylc by multiparallel yclohexyl synthesis). Pure by
H H F H H - 0 HPLC.
Example 14
Herbicidal action - Test 1
Seeds of a variety of test species were sown in standard soil in pots. After cultivation for one day (pre-emergence) or after 8 days cultivation (post-emergence) under controlled conditions in a glasshouse (at 24/16°C, day/night; 14 hours light; 65 % humidity), the plants were sprayed with an aqueous spray solution derived from the formulation of the technical active ingredient in acetone / water (50:50) solution containing 0.5% Tween 20 (polyoxyethelyene sorbitan monolaurate, CAS RN 9005-64-5). The test plants were then grown in a glasshouse under controlled conditions in a glasshouse (at 24/16°C, day/night; 14 hours light; 65 % humidity) and watered twice daily. After 13 days for pre and post-emergence, the test was evaluated (100 = total damage to plant; 0 = no damage to plant). Results are shown in Tables 2 and 3. Table 2: Application post-emergence
Compound Rate SOLNI AMARE SETFA ALOMY ECHCG IPOHE ABUTH Number (g/ha)
3 1000 70 70 50 40 40 80
4 1000 90 70 40 60 50 100
6 1000 100 100 70 90 80 70
7 1000 70 100 30 60 50 60
12 1000 70 100 100 80 70 80
13 1000 20 20 30 20 10 20
14 1000 0 0 10 0 0
17 1000 0 0 20 0 10
18 1000 0 0 10 0 0
19 1000 0 0 10 0 0
20 1000 0 0 20 0 0
23 1000 100 100 90 90 90 90
24 1000 40 50 50 40 20 80
25 1000 0 40 0 20 0 10
26 1000 30 30 30 10 10 20
27 1000 100 100 100 100 100 80
29 1000 20 30 30 20 20 20
30 1000 100 100 100 100 100 100
31 1000 100 100 100 100 100 90
32 1000 30 70 30 60 30 30
33 1000 0 30 0 20 10 10
34 1000 50 60 50 50 40 40
35 1000 20 60 40 50 60 70
36 1000 70 90 70 80 70 70
37 1000 80 90 70 80 80 70
38 1000 40 50 0 20 10 30
39 1000 40 70 20 20 20 60
40 1000 40 70 20 20 20 60
41 :42
1000 20 20 0 10 0 20 70%:30%
41 :42
1000 20 30 0 20 10 40 50%:50%
43:44
1000 70 70 40 50 50 60 70%:30%
43:44
1000 40 100 50 50 60 60 50%:50%
47 1000 90 90 80 80 90 90
48 1000 100 100 100 100 100 100
49 1000 90 100 90 90 90 90
50 1000 70 100 60 80 80 70
51 1000 0 0 0 10 0 10
52 1000 30 50 40 30 10 40
53 1000 20 20 20 30 0 30 Compound Rate SOLNI AMARE SETFA ALOMY ECHCG IPOHE ABUTH Number (g/ha)
54 1000 90 90 70 80 80 80
55 1000 80 95 75 80 85 85
56 1000 90 90 80 80 80 70
57 1000 35 35 40 40 15 45
58 1000 40 40 0 20 10 60
59 1000 40 40 0 20 10 60
60 1000 45 85 65 50 35 65
62 1000 10 0 20 15 0 10
63 1000 10 10 5 10 5 10
64 1000 30 40 70 70 10 30
65 1000 10 10 0 10 0 0
66 1000 90 100 90 90 90 90
67 1000 70 90 60 70 70 80
68 1000 90 100 90 90 90 90
69 1000 5 0 0 5 0 10
71 1000 5 15 15 15 5 25
72 1000 0 0 0 5 0 10
73 1000 0 0 0 0 0 0
74 1000 0 0 0 0 0 0
75 1000 0 0 0 0 0 0
76 1000 5 15 5 10 5 10
77 1000 15 5 5 0 0 20
78 1000 5 5 0 10 0 35
79 1000 0 0 10 20 0 0
80 1000 10 10 20 10 10 0
81 1000 0 0 0 0 0 0
82 1000 10 10 10 10 10 10
83 1000 30 40 20 20 20 30
84 1000 0 0 0 10 0 20
85 1000 10 0 10 10 10 10
86 1000 0 0 0 0 0 0
87 1000 0 0 0 0 0 0
88 1000 0 0 0 0 0 0
89 1000 0 0 0 0 0 0
90 1000 0 10 0 10 0 0
91 1000 0 10 0 10 0 0
92 1000 10 10 0 10 0 0
93 1000 0 0 0 10 0 10
94 1000 0 0 20 20 0 20
95 1000 10 20 0 10 0 20
96 1000 0 0 0 0 0 20
97 1000 0 0 0 10 0 10
98 1000 0 0 0 0 0 10
99 1000 40 80 60 60 30 80
100 1000 30 30 40 20 20 60 Compound Rate SOLNI AMARE SETFA ALOMY ECHCG IPOHE ABUTH Number (g/ha)
101 1000 50 50 40 50 20 60
102 1000 0 30 0 0 0 20
103 1000 60 40 10 30 0 40
104 1000 10 20 0 0 0 10
105 1000 30 60 20 20 20 70
106 1000 0 0 0 0 0 10
107 1000 10 30 0 0 0 20
108 1000 0 0 0 0 0 10
109 1000 20 40 0 0 0 40
1 10 1000 80 100 70 80 90 90
1 1 1 1000 0 0 0 0 0 0
1 12 1000 10 60 0 10 0 20
1 13 1000 10 60 0 30 0 60
1 14 1000 30 50 10 20 10 30
1 15 1000 80 20 20 20 30 30
1 16 1000 60 40 60 40 20 70
1 17 1000 60 40 60 40 20 70
1 18 1000 60 40 60 40 20 70
1 19 1000 60 20 70 30 20 60
120 1000 60 20 70 30 20 60
121 1000 80 100 80 70 70 100
122 1000 70 30 20 30 0 60
123 1000 60 30 20 40 0 70
124 1000 60 20 0 0 30 0
125 1000 40 0 0 10 0 20
126 1000 40 30 10 10 0 20
127 1000 40 50 10 10 0 30
128 1000 40 40 10 0 0 20
129 1000 90 100 100 90 90 90
130 1000 50 0 10 20 20 20
131 1000 60 40 50 40 40 70
132 1000 60 20 20 10 10 20
133 1000 50 10 10 10 20 10
134 1000 50 20 30 10 30 20
135 1000 50 10 10 10 10 10
136 1000 10 80 10 30 20 20
137 1000 90 100 100 100 100 100
138 1000 60 30 40 20 10 30
139 1000 30 20 10 10 10 30
140 1000 0 0 0 0 0 10
141 1000 0 0 0 0 0 0
142 1000 0 0 0 0 0 0
143 1000 10 10 20 20 10 20
144 1000 0 0 0 0 0 0
145 1000 10 20 10 20 10 20 Compound Rate SOLNI AMARE SETFA ALOMY ECHCG IPOHE ABUTH Number (g/ha)
146 1000 10 10 0 20 0 0
147 1000 100 100 100 100 100 100
148 1000 70 40 70 60 60 70
149 1000 10 20 20 30 20 30
150 1000 0 10 0 10 10 20
151 1000 10 10 0 20 10 40
152 10000 70 90 60 70 70 70
153 1000 30 20 20 40 20 40
154 1000 0 0 0 0 0 0
155 1000 0 0 0 0 0 0
156 1000 0 0 0 0 0 0
157 1000 30 10 0 20 0 20
158 1000 30 20 0 30 0 20
159 1000 50 30 10 40 0 30
160 1000 20 NC 20 20 0 40
161 1000 20 NC 20 20 0 NC
162 1000 30 20 10 30 0 30
163 1000 70 100 70 90 80 80
164 1000 60 80 50 40 0 50
165 1000 0 0 0 20 0 10
166 1000 30 20 0 20 20 50
167 1000 70 80 50 50 50 70
168 1000 100 100 100 100 100 100
169 1000 90 100 70 80 80 100
170 1000 100 100 70 60 90 100
171 1000 60 50 50 40 40 40
172 1000 20 30 10 10 0 0
173 1000 60 90 50 20 40 30
174 1000 30 80 10 10 20 20
177 1000 10 10 0 0 10 20
178 1000 10 0 0 20 0 50
179 1000 20 10 0 20 30 50
180 1000 0 0 0 0 0 30
181 1000 30 40 0 20 10 30
182 1000 40 80 20 40 40 30
183 1000 10 30 20 30 30 20
184 1000 30 80 20 30 40 20
185 1000 40 30 10 60 20 30
186 1000 80 80 70 70 50 90
187 1000 20 30 30 20 20 20
188 1000 20 30 30 40 20 50
Table 3: Application pre-emerqence Compound Rate SOLNI AMARE SETFA ALOMY ECHCG IPOHE ABUTH Number (g/ha)
3 1000 50 10 50 60 80 20
4 1000 60 60 40 60 60 30
6 1000 80 90 70 80 90 70
7 1000 60 80 20 70 70 70
12 1000 70 70 90 70 90 70
13 1000 40 80 70 20 20 20
14 1000 60 40 10 10 70
17 1000 10 0 0 0 0
18 1000 10 0 0 0 0
19 1000 20 0 0 0 0
20 1000 10 0 0 0 0
23 1000 100 70 100 100 100 80
24 1000 80 90 80 90 90 80
25 1000 0 60 0 10 0 0
26 1000 20 30 20 20 40 50
27 1000 100 100 100 100 100 100
29 1000 70 100 60 40 70 0
30 1000 100 100 100 100 100 90
31 1000 100 100 100 100 100 100
32 1000 70 70 90 80 90 70
33 1000 0 0 20 60 20 0
34 1000 20 50 60 60 70 80
35 1000 0 0 30 50 70 0
36 1000 70 60 70 80 90 40
37 1000 70 70 80 90 100 80
38 1000 0 0 0 0 0 20
39 1000 0 20 20 50 70 60
40 1000 0 20 20 50 70 60
40:42
1000 0 0 0 0 0 0 70%:30%
40:42
1000 10 10 0 20 40 20 50%:50%
43:44
1000 70 100 70 80 90 80 70%:30%
43:44
1000 20 50 60 80 80 80 50%:50%
47 1000 80 90 80 90 100 100
48 1000 100 100 90 100 100 100
49 1000 100 100 90 90 100 90
50 1000 60 70 70 80 80 30
51 1000 70 50 60 70 50 30
52 1000 50 70 70 70 60 70
53 1000 20 40 20 10 0 30
54 1000 80 90 80 80 90 90
55 1000 90 100 90 90 95 95
56 1000 70 80 70 80 70 80
57 1000 35 75 40 35 15 45 Compound Rate SOLNI AMARE SETFA ALOMY ECHCG IPOHE ABUTH Number (g/ha)
58 1000 0 0 0 0 0 50
59 1000 0 0 0 0 0 50
60 1000 65 75 60 50 70 65
62 1000 5 15 20 5 0 20
63 1000 5 25 0 0 0 5
64 1000 70 80 70 80 80 70
65 1000 0 0 0 0 0 0
66 1000 90 90 80 90 90 80
67 1000 70 90 70 70 30 20
68 1000 90 100 90 90 90 70
69 1000 15 30 10 10 0 0
71 1000 0 35 15 20 15 20
72 1000 0 50 0 0 0 0
73 1000 0 0 0 0 0 0
74 1000 0 0 0 0 0 0
75 1000 60 50 0 0 0 0
76 1000 10 25 10 10 15 40
77 1000 20 10 5 15 15 25
78 1000 0 0 0 0 0 0
79 1000 10 10 30 30 0 30
80 1000 0 0 0 0 0 0
81 1000 0 0 0 0 0 0
82 1000 0 0 0 0 0 0
83 1000 0 0 0 0 0 20
84 1000 0 70 10 30 0 NC
85 1000 0 0 0 0 0 0
86 1000 0 0 0 0 0 0
87 1000 0 0 0 0 0 0
88 1000 0 0 0 0 0 0
89 1000 0 0 0 0 0 0
90 1000 0 0 0 0 0 0
91 1000 0 0 0 0 0 0
92 1000 0 0 20 10 0 10
93 1000 0 0 0 10 0 20
94 1000 0 0 0 0 0 0
95 1000 0 0 0 0 0 0
96 1000 40 20 0 10 10 40
97 1000 0 0 0 0 0 0
98 1000 0 30 0 0 0 0
99 1000 40 20 10 60 10 30
100 1000 20 30 20 20 30 30
101 1000 60 60 60 50 40 60
102 1000 0 0 0 0 0 0
103 1000 0 0 0 0 0 0
104 1000 0 0 0 0 0 0 Compound Rate SOLNI AMARE SETFA ALOMY ECHCG IPOHE ABUTH Number (g/ha)
105 1000 0 0 0 0 0 0
106 1000 0 0 0 0 0 0
107 1000 0 0 0 0 0 0
108 1000 0 0 0 0 0 30
109 1000 0 0 0 0 0 0
1 10 1000 70 70 80 90 100 90
1 1 1 1000 60 20 10 50 0 20
1 12 1000 10 20 20 60 0 10
1 13 1000 30 30 40 60 0 0
1 14 1000 20 40 70 30 0 10
1 15 1000 60 20 20 20 0 0
1 16 1000 30 10 20 40 20 10
1 17 1000 30 10 20 40 20 10
1 18 1000 30 10 20 40 20 10
1 19 1000 60 50 60 50 30 50
120 1000 60 50 60 50 30 50
121 1000 60 40 50 70 70 80
122 1000 20 0 10 30 0 20
123 1000 30 40 30 30 0 40
124 1000 0 0 0 0 0 0
125 1000 0 0 0 0 0 0
126 1000 30 30 0 20 0 0
127 1000 20 10 10 20 10 NC
128 1000 30 40 0 20 0 0
129 1000 70 70 70 80 80 70
130 1000 0 0 0 0 0 0
131 1000 60 20 70 70 90 100
132 1000 0 0 0 0 0 0
133 1000 0 0 0 0 0 0
134 1000 0 0 0 0 0 0
135 1000 0 0 0 0 0 0
136 1000 30 20 10 40 10 60
137 1000 100 100 100 100 100 90
138 1000 20 30 50 20 20 100
139 1000 10 20 20 20 0 30
140 1000 0 10 0 0 0 10
141 1000 0 0 0 0 0 0
142 1000 0 0 0 0 0 0
143 1000 60 0 40 20 0 0
144 1000 0 0 0 0 0 0
145 1000 20 10 20 20 0 10
146 1000 10 40 70 30 20 10
147 1000 100 100 100 100 100 90
148 1000 70 70 60 80 80 70
149 1000 0 0 0 10 0 10 Compound Rate SOLNI AMARE SETFA ALOMY ECHCG IPOHE ABUTH Number (g/ha)
150 1000 0 0 0 10 0 10
151 1000 0 0 0 0 0 0
152 1000 60 100 60 70 80 70
153 1000 20 30 10 10 0 20
154 1000 0 0 0 0 0 0
155 1000 0 0 0 0 0 0
156 1000 0 0 0 0 0 0
157 1000 10 0 10 20 0 30
158 1000 20 20 10 10 0 10
159 1000 40 40 50 40 0 60
160 1000 20 30 30 10 0 10
161 1000 10 40 20 0 0 30
162 1000 20 50 30 30 20 30
163 1000 100 100 90 90 100 100
164 1000 70 80 30 40 30 70
165 1000 10 0 0 20 0 0
166 1000 0 0 0 0 0 0
167 1000 70 70 70 80 80 80
168 1000 100 100 100 100 100 100
169 1000 100 90 90 100 90 90
170 1000 100 90 80 80 90 100
171 1000 40 70 40 20 30 60
172 1000 10 90 0 0 0 0
173 1000 50 70 60 40 30 40
174 1000 50 100 0 10 0 10
177 1000 0 0 0 0 0 0
178 1000 0 0 0 0 0 0
179 1000 20 NC 0 0 NC NC
180 1000 0 0 0 0 0 0
181 1000 0 70 10 10 30 20
182 1000 20 60 60 40 80 0
183 1000 20 30 20 20 0 0
184 1000 0 100 0 30 0 0
185 1000 40 60 40 60 20 60
186 1000 70 70 60 60 80 70
187 1000 20 30 60 30 40 100
188 1000 20 40 50 30 40 30
SOLNI = Solanum nigrum; AMARE = Amaranthus retroflexus; SETFA = Setaria faberi; ALOMY = Alopecurus myosuroides; ECHCG = Echinochloa crus-galli; IPOHE = Ipomea hederaceae; ABUTH = Abuthilon theophrasti.
Herbicidal action - Test 2 Seeds of a variety of test species were sown in unsterilised compost in small pots. After cultivation for one day (pre-emergence) or seven days (post-emergence) in controlled conditions in the glasshouse (at 24/16°C, day/night; 14 hours light; 65 % humidity) the plants were sprayed with 0.675 mg, 1 mg or 4 mg of the active ingredient, formulated in 466μΙ acetone / water / Tween 20 (49.75:49.75:0.5) solution, which is equivalent to 1000 or 4000 g/ha, respectively. Once the foliage was dry, the pots were kept in the glasshouse (at 24/16°C, day/night; 14 hours light; 65 % humidity), and were watered twice daily. After 12 days the test was evaluated and scored (100 = total damage to plant, 0 = no damage to plant).
Table 4: Application post-emergence
Figure imgf000076_0001
Table 5: Application Pre-emergence
Compound Rate AMARE LOLPE STEME DIGSA
Number (g/ha)
1 4000 10 10 10 20
2 4000 0 0 0 0
5 675 0 20 90 20
8 4000 30 40 30 80
9 1000 0 30 30 60
10 4000 30 0 0 0
1 1 4000 0 0 0 0 Compound Rate AMARE LOLPE STEME DIGSA
Number (g/ha)
14 4000 0 0 0 0
15 4000 0 0 0 0
16 4000 0 30 20 0
17 4000 0 0 0 0
18 4000 90 80 90 80
19 4000 20 10 10 0
20 4000 0 20 0 0
21 4000 0 0 0 0
22 1000 90 80 60 90
26 4000 0 0 0 0
175 1000 0 0 0 0
176 1000 0 0 0 0
AMARE = Amaranthus retroflexus; STEME = Stellaria media; LOLPE = Lolium perenne; DIGSA = Digitaria sanguinalis Herbicidal Action - Test 3
Seeds of a variety of test species were sown in standard soil in pots. After cultivation for one day (pre-emergence) or after 12 days cultivation (post-emergence) under controlled conditions in a glasshouse (warm climate species at 24/18°C, cool climate species at 20/16°C, both at day/night; 16 hours light; 65 % humidity), the plants were sprayed with an aqueous spray solution derived from the formulation of the technical active ingredient dissolved in acetone plus IF50 containing 10.56 wt% Emulsogen EL, 42.22 wt% N-MethylPyrrolidon, 2.22 wt% DPG-Monoethyl ether at a 1 :20 ratio (technical active ingredient : IF50. The adjuvant X-77 is added to form a 0.2% v/v solution.
The test plants were grown in a glasshouse under controlled conditions (at 24/18°C or 20/16°C, day/night; 16 hours light; 65 % humidity) and watered twice daily. After 15 days for post- emergence and 20 DAA for pre-emergence the test was evaluated (100 = total damage to plant; 0 = no damage to plant).
Table 6
Compound 28; 1000 gai/ha
Species Post-emergence activity Pre-emergence activity
Alopecurus myosuroides 30 10
Lolium perenne 20 20
Setaria faberi 0 0
Digitaria sanguinalis 0 10
Echinochloa cms galli 0 0
Abutilon theophrasti 20 20
Ipomoea hederacea 10 30
Amaranthus retroflexus 0 0
Stellaria media 10 50 Although the invention has been described with reference to preferred embodiments and examples thereof, the scope of the present invention is not limited only to those described embodiments. As will be apparent to persons skilled in the art, modifications and adaptations to the above-described invention can be made without departing from the spirit and scope of the invention, which is defined and circumscribed by the appended claims. All publications cited herein are hereby incorporated by reference in their entirety for all purposes to the same extent as if each individual publication were specifically and individually indicated to be so incorporated by reference.

Claims

CLAIMS 1. Use of a compound of formula (I):
Figure imgf000079_0001
(I)
wherein:
X1, X2, X3 and X4 are, independently, H, CI, F, trifluoromethyl, cyano, C1-C3 alkyl, C1-C3- alkenyl, -S-C1-C3 alkyl or C1-C3 alkoxy provided that at least one of X1, X2, X3 and X4 is not
H;
Z is oxygen or sulphur; Y is
Figure imgf000079_0002
and
R is H or C1-C3 alkyl, allyl, arylmethyl or heteroarylmethyl;
W is -CR2R3- or a direct bond and R2 and R3 are, independently, selected from H, -CH3 or cyclopropyl;
A is a 3 to 7 membered cycloalkyl ring or a 3-7 membered cycloalkenyl ring; each R4 is selected independently from halo, hydroxyl, cyano, C1-C4 alkyl, C1-C3 haloalkyi ,
C1-C3 hydroxyalkyl, C1-C3 alkoxy -S-C1-C3 alkyl, azido or the group =0; m is an integer between 0 and 5; n is an integer between 1 and 3; or a salt or N-oxide form thereof, as a herbicide.
2. The use according to claim 1 , wherein X1 , X2, X3 and X4 are, independently, H, CI or F provided that at least one of X1 , X2, X3 and X4 is not H.
3. The use according to claim 2, wherein (i) X1 is F or CI and X2, X3 and X4 are H, or (ii) X1 and X2 are F or CI and X3 and X4 are H or (iii) X1 and X3 are F or CI and X2 and X4 are H.
4. The use according to claim 3, wherein (i) X1 is F or CI and X2, X3 and X4 are H or (ii) X1 and X2 are F or CI and X3 and X4 are H.
5. The use according to claim 4, wherein X1 is F and X2 is F or H. Most preferably, X1 is F and X2 is H.
6. The use according to any one of claims 1 to 5, wherein Z is oxygen.
7. The use according to any one of claims 1 to 6, wherein Y is
Figure imgf000080_0001
8. The use according to claim 7 wherein n is 1 or 2.
9. The use according to any one of claims 1 to 6, wherein Y is
Figure imgf000080_0002
10. The use according to claim 9, wherein R is H, methyl, ethyl or allyl.
1 1. The use according to claim 10, wherein R is H.
12. The use according to any one of claims 9 to 1 1 , wherein W is a direct bond or -CH2-.
13. The use according to claim 12, wherein W is a direct bond.
14. The use according to any one of claims 9 to 13, wherein A is optionally substituted
cyclopentyl or optionally substituted cyclohexyl.
15. The use according to claim 14, wherein A is optionally substituted cyclohexyl.
16. The use according to any one of claims 9 to 13, wherein m is 1 or 2 or 3.
17. The use according to any one of claims 9 to 13, wherein each R4 is independently selected from halo, hydroxyl, cyano, methyl, trifluoromethyl, azido or methoxy.
18. The use according to claim 17, wherein each R4 is independently selected from chloro, bromo, iodo, fluoro, methyl, cyano, or trifluoromethyl.
19. The use according to any one of claims 9 to 18, wherein A is 2-methylcyclohexyl, 2,3- dimethylcyclohexyl, 2-chlorocyclohexyl, 2-bromocyclohexyl, 2-iodocyclohexyl, 2- fluorocyclohexyl, 2-trifluoromethylcyclohexyl, 2-cyanocyclohexyl, 2-azidocyclohexyl, 2,2- difluorocyclohexyl or 3,3-difluorocyclohexyl.
20. The use according to claim 1 , wherein X1 is F or CI and X2, X3 and X4 are H or X1 and X2 are F or CI and X3 and X4 are H or X1 and X3 are F or CI and X2 and X4 are H; Z is O; R is H; W is a direct bond or -CH2-; A is a cyclohexyl ring, m is from 0 to 3 and each R4 is independently selected from methyl, chloro, bromo, iodo, fluoro, trifluoromethyl, cyano and azido.
21. A compound selected from the group consisting of 2-fluoro-N-(2-bromocyclohexyl)pyridine- 4-carboxamide, 2-fluoro-N-(2-iodocyclohexyl)pyridine-4-carboxamide, 2-fluoro-N-(2- fluorocyclohexyl)pyridine-4-carboxamide, 2-fluoro-N-(2-cyanocyclohexyl)pyridine-4- carboxamide, 2-fluoro-N-(2-azidocyclohexyl)pyridine-4-carboxamide, 2-fluoro-N-(2,2- dimethylcyclohexyl)pyridine-4-carboxamide, 2-fluoro-N-(2,2-difluorocyclohexyl)pyridine-4- carboxamide, 2-fluoro-N-(3,3-difluorocyclohexyl)pyridine-4-carboxamide, 2-fluoro-N-(2- methyl-3-cyanocyclohexyl)pyridine-4-carboxamide, 2,6-difluoro-N-(2- chlorocyclohexyl)pyridine-4-carboxamide, 2,6-difluoro-N-(2,3-dimethylcyclohexyl)pyridine- 4-carboxamide, 2-fluoro-N-(2,2-dimethylcyclohexyl)pyridine-4-carboxamide, 2-fluoro-N-(3- trifluoromethyl-chlorocyclohexyl)pyridine-4-carboxamide, 2-fluoro-N-(1- hydroxycyclohexyl)pyridine-4-carboxamide, 2-fluoro-N-(2-methyl-3- trifluoromethylcyclohexyl)pyridine-4-carboxamide, 2,6-difluoro-N-(2- cyanocyclohexyl)pyridine-4-carboxamide, 2-fluoro-N-(2-methylcyclohexyl)pyridine-4- carbothioamide, compound 23, compound 24, compound 27, compound 30, compound 31 , compound 32, compound 36, compound 37, compound 43, compound 44, compound 47, compound 48, compound 49, compound 50, compound 54, compound 55, compound 56, compound 67, compound 68, compound 1 10, compound 129, compound 131 , compound 137, compound 147, compound 148, compound 152, compound 163, compound 167, compound 168, compound 169, compound 170 and compound 186.
22. A herbicidal composition comprising a herbicidally effective amount of a compound of claim 21 in addition to formulation adjuvants.
23. A composition comprising a compound as defined in any one of claims 1 to 20 or a compound as claimed in claim 21 and a further herbicide.
24. The composition of claim 23, wherein the further herbicide is selected from the group consisting of ametryn, atrazine, bicyclopyrone, cinosulfuron, clodinafop-propargyl, clomazone, dicamba, dimethachlor, diquat, fluazifop-p-butyl, fomesafen, glyphosate, mesotrione, molinate, napropamide, S-metolachlor, nicosulfuron, paraquat, pinoxaden, pretilachlor, primisulfuron, prometryn, prosulfocarb, prosulfuron, pyridate, pyriftalid, tralkoxydim, triasulfuron and trifloxysulfuron-sodium.
25. A method of controlling plants, comprising applying to the plants or to the locus thereof a herbicidally effective amount of a compound of formula (I) as defined in any one of claims 1 to 20.
26. A method of inhibiting plant growth which comprises applying to the plants or to the locus thereof a herbicidally effective amount of a compound of formula (I) as defined in any one of claims 1 to 20 or as claimed in claim 21.
27. A method of controlling weeds in crops of useful plants, comprising applying to said weeds or to the locus of said weeds, or to said useful plants or to the locus of said useful plants a compound of formula (I) as defined in any one of claims 1 to 20 or as claimed in claim 21.
28. A method of selectively controlling grasses and/or weeds in crops of useful plants which comprises applying to the useful plants or locus thereof or to the area of cultivation a herbicidally effective amount of a compound of formula (I) as defined in any one of claims
1 to 20 or as claimed in claim 21.
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