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WO2020161248A1 - Herbicidal compounds - Google Patents

Herbicidal compounds Download PDF

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Publication number
WO2020161248A1
WO2020161248A1 PCT/EP2020/053008 EP2020053008W WO2020161248A1 WO 2020161248 A1 WO2020161248 A1 WO 2020161248A1 EP 2020053008 W EP2020053008 W EP 2020053008W WO 2020161248 A1 WO2020161248 A1 WO 2020161248A1
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WO
WIPO (PCT)
Prior art keywords
group
c6alkyl
phenyl
hydrogen
methyl
Prior art date
Legal status (The legal status 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 status listed.)
Ceased
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PCT/EP2020/053008
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French (fr)
Inventor
James Nicholas Scutt
Nigel James Willetts
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Syngenta Crop Protection AG Switzerland
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Syngenta Crop Protection AG Switzerland
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Publication of WO2020161248A1 publication Critical patent/WO2020161248A1/en
Anticipated expiration legal-status Critical
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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D237/00—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings
    • C07D237/02—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings not condensed with other rings
    • C07D237/06—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members
    • C07D237/10—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members 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
    • C07D237/24—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
    • 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
    • A01N43/48—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with two nitrogen atoms as the only ring hetero atoms
    • A01N43/58—1,2-Diazines; Hydrogenated 1,2-diazines
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
    • C07D403/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02—Phosphorus compounds
    • C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
    • C07F9/645—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having two nitrogen atoms as the only ring hetero atoms
    • C07F9/6509—Six-membered rings
    • C07F9/650905—Six-membered rings having the nitrogen atoms in the positions 1 and 2

Definitions

  • the present invention relates to herbicidally active pyridazine derivatives, as well as to processes and intermediates used for the preparation of such derivatives.
  • the invention further extends to herbicidal compositions comprising such derivatives, as well as to the use of such compounds and compositions for controlling undesirable plant growth: in particular the use for controlling weeds, in crops of useful plants.
  • the present invention is based on the finding that pyridazine derivatives of formula (I) as defined herein, exhibit surprisingly good herbicidal activity.
  • R 1 is selected from the group consisting of hydrogen, halogen, Ci-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, Cs-Cecycloalkyl, Ci-C 6 haloalkyl, -OR 7 , -OR 15a , -N(R 6 )S(0) 2 R 15 , -N(R 6 )C(0)R 15 , -N(R 6 )C(0)0R 15 , - N(R 6 )C(0)NR 16 R 17 , -N(R 6 )CHO, -N(R 7a ) 2 and -S(0) r R 15 ;
  • R 2 is selected from the group consisting of hydrogen, halogen, Ci-C6alkyl and Ci-C6haloalkyl;
  • R 1 is selected from the group consisting of -OR 7 , -OR 15a , -N(R 6 )S(0) 2 R 15 , - N(R 6 )C(0)R 15 , -N(R 6 )C(0)0R 15 , -N(R 6 )C(0)NR 16 R 17 , -N(R 6 )CHO, -N(R 7a ) 2 and -S(0) r R 15 , R 2 is selected from the group consisting of hydrogen and Ci-C6alkyl; or
  • R 1 and R 2 together with the carbon atom to which they are attached form a C3-C6cycloalkyl ring or a 3- to 6- membered heterocyclyl, which comprises 1 or 2 heteroatoms individually selected from N and O;
  • Q is (CR 1a R 2b ) m ;
  • n 0, 1 , 2 or 3;
  • each R 1a and R 2b are independently selected from the group consisting of hydrogen, halogen, Ci-C6alkyl, Ci-Cehaloalkyl, -OH, -OR 7 , -OR 15a , -NH 2 , -NHR 7 , -NHR 15a , -N(R 6 )CHO, -NR 7b R 7c and -S(0) r R 15 ; or each R 1a and R 2b together with the carbon atom to which they are attached form a C3-C6cycloalkyl ring or a 3- to 6- membered heterocyclyl, which comprises 1 or 2 heteroatoms individually selected from N and O;
  • R 3 , R 4 and R 5 are independently selected from the group consisting of hydrogen, halogen, nitro, cyano, -NH 2 , -NR 6 R 7 , -OH, -OR 7 , -S(0)rR 12 , -NR 6 S(0) r R 12 , Ci-C 6 alkyl, Ci-Cehaloalkyl, Cs-Cecycloalkyl, C 3 - Cehalocycloalkyl, C3-C6cycloalkoxy, C2-C6alkenyl, C2-C6haloalkenyl, C2-C6alkynyl, Ci-C3alkoxyCi- C3alkyl-, hydroxyCi-Cealkyl-, Ci-C6haloalkoxy, Ci-C3haloalkoxyCi-C3alkyl-, Ci-C6alkoxycarbonyl, C3- Cealkenyloxy, C3-C6alkynyloxy, Ci-C6
  • each R 6 is independently selected from hydrogen and Ci-C6alkyl
  • each R 7 is independently selected from the group consisting of Ci-C6alkyl, -S(0) 2 R 15 , -C(0)R 15 , - C(0)0R 15 and -C(0)NR 16 R 17 ;
  • each R 7a is independently selected from the group consisting of -S(0) 2 R 15 , -C(0)R 15 , -C(0)0R 15 - C(0)NR 16 R 17 and -C(0)NR 6 R 15a ;
  • R 7b and R 7c are independently selected from the group consisting of Ci-C6alkyl, -S(0) 2 R 15 , -C(0)R 15 , - C(0)0R 15 , -C(0)NR 16 R 17 and phenyl, and wherein said phenyl is optionally substituted by 1 , 2 or 3 R 9 substituents, which may be the same or different; or
  • R 7b and R 7c together with the nitrogen atom to which they are attached form a 4- to 6-membered heterocyclyl ring which optionally comprises one additional heteroatom individually selected from N, O and S; and
  • each R 9 is independently selected from the group consisting of halogen, cyano, -OH, -N(R 6 )2, Ci-C 4 alkyl, Ci-C 4 alkoxy, Ci-C 4 haloalkyl and Ci-C 4 haloalkoxy;
  • E is selected from the group consisting of of -C(0)OR 10 , -CHO, -C(0)R 24 , -C(0)NH0R 11 , -C(0)NHCN, -C(0)NHR 25 , -S(0) 2 NHR 25 , -C(0)NR 6 (CR 6 2 )qC(0)(0R 1 °), -C(0)NR 6 (CR 6 2 )qS(0) 2 (0R 10 ),
  • X is selected from the group consisting of C3-C6cycloalkyl, phenyl, a 5- or 6- membered heteroaryl, which comprises 1 , 2, 3 or 4 heteroatoms individually selected from N, O and S, and a 4- to 6- membered heterocyclyl, which comprises 1 , 2 or 3 heteroatoms individually selected from N, O and S, and wherein said cycloalkyl, phenyl, heteroaryl or heterocyclyl moieties are optionally substituted by 1 or 2 substituents, which may be the same or different, selected from R 9 , and wherein the aforementioned CR 1 R 2 , Q and Z moieties may be attached at any position of said cycloalkyl, phenyl, heteroaryl or heterocyclyl moieties;
  • n is 0 or 1 ;
  • Z is selected from the group consisting of hydrogen, Ci-C6alkyl, Ci-C6haloalkyl, Ci-C6hydroxyalkyl, Ci- CealkoxyCi-Cealkyl, nitro, halo, haloalkoxy, cyano, -NH 2 , -OH, -OR 7 , -C(0)R 15 , -C(0)NR 16 R 17 , - C(0)OR 10 , -CHO, -C(0)NH0R 11 , -C(0)NHCN, -0C(0)NH0R 11 , -0C(0)NHCN, -NR 6 C(0)NH0R 11 , - NR 6 C(0)NHCN, -C(0)NHS(0) 2 R 12 , -0C(0)NHS(0) 2 R 12 , -NHR 7 , -N(R 7 ) 2 , -NR 6 C(0)NHS(0) 2 R 12 , -NHR 7 , -N(
  • R 10 is selected from the group consisting of hydrogen, Ci-C6alkyl, phenyl and benzyl, and wherein said phenyl or benzyl are optionally substituted by 1 , 2 or 3 R 9 substituents, which may be the same or different;
  • R 11 is selected from the group consisting of hydrogen, Ci-C6alkyl and phenyl, and wherein said phenyl is optionally substituted by 1 , 2 or 3 R 9 substituents, which may be the same or different;
  • R 12 is selected from the group consisting of Ci-C6alkyl, Ci-C6haloalkyl, Ci-C6alkoxy, -OH, -N(R 6 ) 2 and phenyl, and wherein said phenyl is optionally substituted by 1 , 2 or 3 R 9 substituents, which may be the same or different;
  • R 13 is selected from the group consisting of -OH, Ci-C6alkyl, Ci-C6alkoxy, Ci-C6haloalkoxy, -O- propargyl, -O-allyl and phenyl;
  • R 14 is Ci-Cehaloalkyl
  • R 15 is selected from the group consisting of Ci-C6alkyl and phenyl, and wherein said phenyl is optionally substituted by 1 , 2 or 3 R 9 substituents, which may be the same or different;
  • R 15a is phenyl, wherein said phenyl is optionally substituted by 1 , 2 or 3 R 9 substituents, which may be the same or different;
  • R 16 and R 17 are independently selected from the group consisting of hydrogen and Ci-C6alkyl; or
  • R 16 and R 17 together with the nitrogen atom to which they are attached form a 4- to 6-membered heterocyclyl ring which optionally comprises one additional heteroatom individually selected from N, O and S;
  • R 18 is selected from the group consisting of hydrogen, Ci-C6alkyl, Ci-C6haloalkyl, Ci-C6alkoxy, -N(R 6 ) 2 and phenyl, and wherein said phenyl is optionally substituted by 1 , 2 or 3 R 9 substituents, which may be the same or different;
  • R 24 is a peptide moiety comprising one, two or three amino acid moieties independently selected from the group consisting of Ala, Cys, Asp, Glu, Phe, Gly, His, lie, Lys, Leu, Met, Asn, Pro, Gin, Arg, Ser, Thr, Val, Trp and Tyr, wherein said peptide moiety is bonded to the rest of the molecule via a nitrogen atom in the amino acid moiety;
  • R 25 is selected from the group consisting of 5- or 6- membered heteroaromatic moieties, optionally substituted with one or more groups independently selected from R 2 or; R 25 is selected from the group consisting of 5- or 6- membered heteroaromatic moieties, containing at least two N atoms, optionally substituted with one or more groups independently selected from R 9 ; and
  • r 0, 1 or 2;
  • an agrochemical composition comprising a herbicidally effective amount of a compound of formula (I) and an agrochemically-acceptable diluent or carrier.
  • Such an agricultural composition may further comprise at least one additional active ingredient.
  • a method of controlling or preventing undesirable plant growth wherein a herbicidally effective amount of a compound of formula (I), or a composition comprising this compound as active ingredient, is applied to the plants, to parts thereof or the locus thereof.
  • halogen refers to fluorine (fluoro), chlorine (chloro), bromine (bromo) or iodine (iodo), preferably fluorine, chlorine or bromine.
  • cyano means a -CN group.
  • hydroxy means an -OH group.
  • nitro means an -NO2 group.
  • Ci-C6alkyl refers to a straight or branched hydrocarbon chain radical consisting solely of carbon and hydrogen atoms, containing no unsaturation, having from one to six carbon atoms, and which is attached to the rest of the molecule by a single bond.
  • Ci-C 4 alkyl and Ci- C2alkyl are to be construed accordingly.
  • Examples of Ci-C6alkyl include, but are not limited to, methyl (Me), ethyl (Et), n-propyl, 1 -methylethyl (iso-propyl), n-butyl, and 1 -dimethylethyl (f-butyl).
  • Ci-C6alkoxy refers to a radical of the formula -OR a where R a is a Ci-C6alkyl radical as generally defined above. Ci-C 4 alkoxy is to be construed accordingly. Examples of Ci- 4 alkoxy include, but are not limited to, methoxy, ethoxy, propoxy, iso-propoxy and f-butoxy.
  • Ci-C6haloalkyl refers to a Ci-C6alkyl radical as generally defined above substituted by one or more of the same or different halogen atoms. Ci-C 4 haloalkyl is to be construed accordingly. Examples of Ci-C6haloalkyl include, but are not limited to chloromethyl, fluoromethyl, fluoroethyl, difluoromethyl, trifluoromethyl and 2,2,2-trifluoroethyl.
  • C 2 -C6alkenyl refers to a straight or branched hydrocarbon chain radical group consisting solely of carbon and hydrogen atoms, containing at least one double bond that can be of either the (E)- or ( ⁇ -configuration, having from two to six carbon atoms, which is attached to the rest of the molecule by a single bond.
  • C 2 -C 4 alkenyl is to be construed accordingly.
  • Examples of C 2 -C6alkenyl include, but are not limited to, prop-1 -enyl, allyl (prop-2-enyl) and but-1 -enyl.
  • C 2 -C6haloalkenyl refers to a C 2 -C6alkenyl radical as generally defined above substituted by one or more of the same or different halogen atoms.
  • Examples of C 2 -C6haloalkenyl include, but are not limited to chloroethylene, fluoroethylene, 1 ,1 -difluoroethylene, 1 ,1 -dichloroethylene and 1 ,1 ,2-trichloroethylene.
  • C 2 -C6alkynyl refers to a straight or branched hydrocarbon chain radical group consisting solely of carbon and hydrogen atoms, containing at least one triple bond, having from two to six carbon atoms, and which is attached to the rest of the molecule by a single bond.
  • C 2 -C 4 alkynyl is to be construed accordingly.
  • Examples of C 2 -C6alkynyl include, but are not limited to, prop-1 -ynyl, propargyl (prop-2-ynyl) and but-1 -ynyl.
  • Ci-C6haloalkoxy refers to a Ci-C6alkoxy group as defined above substituted by one or more of the same or different halogen atoms. Ci-C 4 haloalkoxy is to be construed accordingly. Examples of Ci-C6haloalkoxy include, but are not limited to, fluoromethoxy, difluoromethoxy, fluoroethoxy, trifluoromethoxy and trifluoroethoxy.
  • Ci-C3haloalkoxyCi-C3alkyl refers to a radical of the formula Rb-O-Ra- where Rb is a Ci-C3haloalkyl radical as generally defined above, and R a is a Ci-C3alkylene radical as generally defined above.
  • Ci-C3alkoxyCi-C3alkyl refers to a radical of the formula Rb-0-R a - where Rb is a Ci-C3alkyl radical as generally defined above, and R a is a Ci-C3alkylene radical as generally defined above.
  • Ci-C3alkoxyCi-C3alkoxy- refers to a radical of the formula Rb-0-R a -0- where Rb is a Ci-C3alkyl radical as generally defined above, and R a is a Ci-C3alkylene radical as generally defined above.
  • C3-C6alkenyloxy refers to a radical of the formula -OR a where R a is a C3- Cealkenyl radical as generally defined above.
  • C3-C6alkynyloxy refers to a radical of the formula -OR a where R a is a C3- Cealkynyl radical as generally defined above.
  • hydroxyCi-Cealkyl refers to a Ci-C6alkyl radical as generally defined above substituted by one or more hydroxy groups.
  • Ci-C6alkylcarbonyl refers to a radical of the formula -C(0)R a where R a is a Ci-C6alkyl radical as generally defined above.
  • Ci-C6alkoxycarbonyl refers to a radical of the formula -C(0)0R a where R a is a Ci-C6alkyl radical as generally defined above.
  • aminocarbonyl refers to a radical of the formula -C(0)NH 2 .
  • C3-C6cycloalkyl refers to a stable, monocyclic ring radical which is saturated or partially unsaturated and contains 3 to 6 carbon atoms.
  • C3-C 4 cycloalkyl is to be construed accordingly.
  • Examples of C3-C6cycloalkyl include, but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl.
  • C3-C6halocycloalkyl refers to a C3-C6cycloalkyl radical as generally defined above substituted by one or more of the same or different halogen atoms.
  • C3-C 4 halocycloalkyl is to be construed accordingly.
  • C3-C6cycloalkoxy refers to a radical of the formula -OR a where R a is a C3- C6cycloalkyl radical as generally defined above.
  • N-C3-C6cycloalkylamino refers to a radical of the formula -NHR a where R a is a C3-C6cycloalkyl radical as generally defined above.
  • heteroaryl refers to a 5- or 6- membered monocyclic aromatic ring which comprises 1 , 2, 3 or 4 heteroatoms individually selected from nitrogen, oxygen and sulfur.
  • the heteroaryl radical may be bonded to the rest of the molecule via a carbon atom or heteroatom.
  • heteroaryl include, furyl, pyrrolyl, imidazolyl, thienyl, pyrazolyl, thiazolyl, isothiazolyl, oxazolyl, isoxazolyl, triazolyl, tetrazolyl, pyrazinyl, pyridazinyl, pyrimidyl or pyridyl.
  • heterocyclyl refers to a stable 4- to 6-membered non-aromatic monocyclic ring radical which comprises 1 , 2, or 3 heteroatoms individually selected from nitrogen, oxygen and sulfur.
  • the heterocyclyl radical may be bonded to the rest of the molecule via a carbon atom or heteroatom.
  • heterocyclyl examples include, but are not limited to, pyrrolinyl, pyrrolidyl, tetrahydrofuryl, tetrahydrothienyl, tetrahydrothiopyranyl, piperidyl, piperazinyl, tetrahydropyranyl, dihydroisoxazolyl, dioxolanyl, morpholinyl or d-lactamyl.
  • asymmetric carbon atoms in a compound of formula (I) means that the compounds may occur in chiral isomeric forms, i.e., enantiomeric or diastereomeric forms. Also atropisomers may occur as a result of restricted rotation about a single bond.
  • Formula (I) is intended to include all those possible isomeric forms and mixtures thereof.
  • the present invention includes all those possible isomeric forms and mixtures thereof for a compound of formula (I).
  • formula (I) is intended to include all possible tautomers (including lactam-lactim tautomerism and keto-enol tautomerism) where present.
  • the present invention includes all possible tautomeric forms for a compound of formula (I).
  • where there are di-substituted alkenes these may be present in E or Z form or as mixtures of both in any proportion.
  • the present invention includes all these possible isomeric forms and mixtures thereof for a compound of formula (I).
  • the compounds of formula (I) will typically be provided in the form of an agronomically acceptable salt, a zwitterion or an agronomically acceptable salt of a zwitterion.
  • This invention covers all such agronomically acceptable salts, zwitterions and mixtures thereof in all proportions.
  • a compound of formula (I) wherein E or Z comprises an acidic proton may exist as a zwitterion, a compound of formula (l-l) or formula (l-V), or as an agronomically acceptable salt, a compound of formula (l-ll) or formula (l-VI)as shown below:
  • Y represents an agronomically acceptable anion and j and k represent integers that may be selected from 1 , 2 or 3, dependent upon the charge of the respective anion Y.
  • a compound of formula (I) may also exist as an agronomically acceptable salt of a zwitterion, a compound of formula (l-lll) or formula (l-VII) as shown below:
  • Y represents an agronomically acceptable anion
  • M represents an agronomically acceptable cation (in addition to the pyridazinium cation) and the integers j, k and q may be selected from 1 , 2 or 3, dependent upon the charge of the respective anion Y and respective cation M.
  • a compound of formula (I) is drawn in protonated form herein, the skilled person would appreciate that it could equally be represented in unprotonated or salt form with one or more relevant counter ions.
  • a nitrogen atom comprised in R 1 , R 2 , R 3 , R 4 , R 5 , E, Q, Z or X may be protonated.
  • Suitable agronomically acceptable salts of the present invention include but are not limited chloride, bromide, iodide, fluoride, 2-naphthalenesulfonate, acetate, adipate, methoxide, ethoxide, propoxide, butoxide, aspartate, benzenesulfonate, benzoate, bicarbonate, bisulfate, bitartrate, butylsulfate, butylsulfonate, butyrate, camphorate, camsylate, caprate, caproate, caprylate, carbonate, citrate, diphosphate, edetate, edisylate, enanthate, ethanedisulfonate, ethanesulfonate, ethylsulfate, formate, fumarate, gluceptate, gluconate, glucoronate, glutamate, glycerophosphate, hepta
  • Suitable cations represented by M include, but are not limited to, metals, conjugate acids of amines and organic cations.
  • suitable metals include aluminium, calcium, cesium, copper, lithium, magnesium, manganese, potassium, sodium, iron and zinc.
  • Suitable amines include allylamine, ammonia, amylamine, arginine, benethamine, benzathine, butenyl-2-amine, butylamine, butylethanolamine, cyclohexylamine, decylamine, diamylamine, dibutylamine, diethanolamine, diethylamine, diethylenetriamine, diheptylamine, dihexylamine, diisoamylamine, diisopropylamine, dimethylamine, dioctylamine, dipropanolamine, dipropargylamine, dipropylamine, dodecylamine, ethanolamine, ethylamine, ethylbutylamine, ethylenediamine, ethylheptylamine, ethyloctylamine, ethylpropanolamine, heptadecylamine, heptylamine, hexadecylamine, he
  • Suitable organic cations include benzyltributylammonium, benzyltrimethylammonium, benzyltriphenylphosphonium, choline, tetrabutylammonium, tetrabutylphosphonium, tetraethylammonium, tetraethylphosphonium, tetramethylammonium, tetramethylphosphonium, tetrapropylammonium, tetrapropylphosphonium, tributylsulfonium, tributylsulfoxonium, triethylsulfonium, triethylsulfoxonium, trimethylsulfonium, trimethylsulfoxonium, tripropylsulfonium and tripropylsulfoxonium.
  • Preferred compounds of formula (I), wherein E or Z comprises an acidic proton can be represented as either (l-l), (l-V), (l-ll) or (l-VI).
  • E or Z comprises an acidic proton
  • Y is chloride, bromide, iodide, hydroxide, bicarbonate, acetate, pentafluoropropionate, triflate, trifluoroacetate, methylsulfate, tosylate and nitrate, wherein j and k are 1.
  • Y is chloride, bromide, iodide, hydroxide, bicarbonate, acetate, trifluoroacetate, methylsulfate, tosylate and nitrate, wherein j and k are 1.
  • j and k are 1.
  • compounds of formula (l-ll) or (l-VI) emphasis is also given to salts when Y is carbonate and sulfate, wherein j is 2 and k is 1 , and when Y is phosphate, wherein j is 3 and k is 1.
  • R 1 , R 2 , R 3 , R 4 , R 5 , E and Z are as defined for compounds of formula (I).
  • R 1 , R 2 , R 1a , R 2b , R 3 , R 4 , R 5 , E and Z are as defined for compounds of formula (I).
  • R 1 , R 2 , R 1a , R 2b , R 3 , R 4 , R 5 , E and Z are as defined for compounds of formula (I).
  • Pyridazocidin which is specifically excluded from compounds of the present invention is a compound of formula (I) in which R 1 , R 2 , R 3 , R 4 and R 5 are hydrogen, E is -C(0)0H, Q is -CH 2 CH 2 CH(NH 2 )- and Z is -C(0)0H.
  • R 1 , R 2 , R 3 , R 4 and R 5 are hydrogen
  • E is -C(0)0H
  • Q is -CH 2 CH 2 CH(NH 2 )-
  • Z is -C(0)0H.
  • agrochemically acceptable salts of pyridazocidin Preferably also excluded are also excluded.
  • R 1 is selected from the group consisting of hydrogen, halogen, Ci-C6alkyl, Ci-C6fluoroalkyl, -OR 7 , -NHS(0) 2 R 15 , -NHC(0)R 15 , -NHC(0)0R 15 , -NHC(0)NR 16 R 17 , -N(R 7a ) 2 and -S(0) r R 15 . More preferably, R 1 is selected from the group consisting of hydrogen, halogen, Ci-C6alkyl, Ci-C6fluoroalkyl, -OR 7 and -N(R 7a ) 2 .
  • R 1 is selected from the group consisting of hydrogen, Ci- Cealkyl, -OR 7 and -N(R 7a ) 2 . Even more preferably still, R 1 is hydrogen or Ci-C6alkyl. Yet even more preferably still, R 1 is hydrogen or methyl. Most preferably R 1 is hydrogen.
  • R 2 is selected from the group consisting of hydrogen, halogen, Ci-C6alkyl and Ci-C6haloalkyl.
  • R 2 is selected from the group consisting of hydrogen, halogen, Ci-C6alkyl and Ci- C6fluoroalkyl. More preferably, R 2 is hydrogen or Ci-C6alkyl. Even more preferably, R 2 is hydrogen or methyl. Most preferably R 2 is hydrogen.
  • R 1 is selected from the group consisting of -OR 7 , -OR 15a , -N(R 6 )S(0) 2 R 15 , -N(R 6 )C(0)R 15 , -N(R 6 )C(0)0R 15 , -N(R 6 )C(0)NR 16 R 17 , -N(R 6 )CHO, -N(R 7a ) 2 and -S(0) r R 15
  • R 2 is selected from the group consisting of hydrogen and Ci-C6alkyl.
  • R 1 is selected from the group consisting of -OR 7 , -NHS(0) 2 R 15 , -NHC(0)R 15 , -NHC(0)0R 15 , -NHC(0)NR 16 R 17 , -N(R 7a ) 2 and -S(0) r R 15
  • R 2 is selected from the group consisting of hydrogen and methyl.
  • R 1 and R 2 together with the carbon atom to which they are attached form a C3-C6cycloalkyl ring or a 3- to 6- membered heterocyclyl, which comprises 1 or 2 heteroatoms individually selected from N and O.
  • R 1 and R 2 together with the carbon atom to which they are attached form a C3- C6cycloalkyl ring.
  • R 1 and R 2 together with the carbon atom to which they are attached form a cyclopropyl ring.
  • R 1 is methyl and R 2 is hydrogen. In another embodiment R 1 is methyl and R 2 is methyl.
  • R 1 and R 2 are hydrogen
  • n 0, 1 , 2 or 3.
  • m is 0,1 or 2. More preferably, m is 1 or 2. Most preferably, m is 0.
  • Each R 1a and R 2b are independently selected from the group consisting of hydrogen, halogen, Ci- Cealkyl, Ci-C 6 haloalkyl, -OH, -OR 7 , -OR 15a , -NH 2 , -NHR 7 , -NHR 15a , -N(R 6 )CHO, -NR 7b R 7c and -S(0) r R 15 .
  • each R 1a and R 2b are independently selected from the group consisting of hydrogen, halogen, Ci-C6alkyl, Ci-C6fluoroalkyl, -OH, -NH 2 and -NHR 7 .
  • each R 1a and R 2b are independently selected from the group consisting of hydrogen, Ci-C6alkyl, -OH and -NH 2 . Even more preferably, each R 1a and R 2b are independently selected from the group consisting of hydrogen, methyl, -OH and -NH 2 . Even more preferably still, each R 1a and R 2b are independently selected from the group consisting of hydrogen and methyl. Most preferably R 1a and R 2b are hydrogen.
  • each R 1a and R 2b are independently selected from the group consisting of hydrogen and Ci-C6alkyl.
  • each R 1a and R 2b together with the carbon atom to which they are attached form a C3- C6cycloalkyl ring or a 3- to 6- membered heterocyclyl, which comprises 1 or 2 heteroatoms individually selected from N and O.
  • each R 1a and R 2b together with the carbon atom to which they are attached form a C3-C6cycloalkyl ring.
  • each R 1a and R 2b together with the carbon atom to which they are attached form a cyclopropyl ring.
  • R 3 , R 4 , and R 5 are preferably independently hydrogen, Ci-C6alkyl, or Ci-C6alkoxy, most preferably hydrogen or methyl.
  • Each R 6 is independently selected from hydrogen and Ci-C6alkyl. Preferably, each R 6 is independently selected from hydrogen and methyl.
  • Each R 7 is independently selected from the group consisting of Ci-C6alkyl, -S(0) 2 R 15 , -C(0)R 15 , - C(0)0R 15 and -C(0)NR 16 R 17 .
  • each R 7 is independently selected from the group consisting of Ci-C6alkyl, -C(0)R 15 and -C(0)NR 16 R 17 . More preferably, each R 7 is Ci-C6alkyl. Most preferably, each R 7 is methyl.
  • Each R 7a is independently selected from the group consisting of -S(0) 2 R 15 , -C(0)R 15 , -C(0)0R 15 - C(0)NR 16 R 17 and -C(0)NR 6 R 15a .
  • each R 7a is independently -C(0)R 15 or -C(0)NR 16 R 17 .
  • R 7b and R 7c are independently selected from the group consisting of Ci-C6alkyl, -S(0) 2 R 15 , -C(0)R 15 , - C(0)0R 15 , -C(0)NR 16 R 17 and phenyl, and wherein said phenyl is optionally substituted by 1 , 2 or 3 R 9 substituents, which may be the same or different.
  • R 7b and R 7c are independently selected from the group consisting of Ci-C6alkyl, -C(0)R 15 and -C(0)NR 16 R 17 . More preferably, R 7b and R 7c are Ci-C6alkyl. Most preferably, R 7b and R 7c are methyl.
  • R 7b and R 7c together with the nitrogen atom to which they are attached form a 4- to 6- membered heterocyclyl ring which optionally comprises one additional heteroatom individually selected from N, O and S.
  • R 7b and R 7c together with the nitrogen atom to which they are attached form a 5- to 6-membered heterocyclyl ring which optionally comprises one additional heteroatom individually selected from N and O.
  • R 7b and R 7c together with the nitrogen atom to which they are attached form an pyrrolidyl, oxazolidinyl, imidazolidinyl, piperidyl, piperazinyl or morpholinyl group.
  • Each R 9 is independently selected from the group consisting of halogen, cyano, -OH, -N(R 6 )2, Ci-C 4 alkyl, Ci-C 4 alkoxy, Ci-C 4 haloalkyl and Ci-C 4 haloalkoxy.
  • each R 9 is independently selected from the group consisting of halogen, cyano, -N(R 6 )2, Ci-C 4 alkyl, Ci-C 4 alkoxy, Ci-C 4 haloalkyl and Ci- C 4 haloalkoxy. More preferably, each R 9 is independently selected from the group consisting of halogen, Ci-C 4 alkyl, Ci-C 4 alkoxy and Ci-C 4 haloalkyl. Even more preferably, each R 9 is independently selected from the group consisting of halogen and Ci-C 4 alkyl.
  • E is -C(0)OR 10 , -C(0)NHS(0) 2 R 12 , -C(0)R 24 , -P(0)(R 13 )(OR 10 ); or
  • X is selected from the group consisting of C3-C6cycloalkyl, phenyl, a 5- or 6- membered heteroaryl, which comprises 1 , 2, 3 or 4 heteroatoms individually selected from N, O and S, and a 4- to 6- membered heterocyclyl, which comprises 1 , 2 or 3 heteroatoms individually selected from N, O and S, and wherein said cycloalkyl, phenyl, heteroaryl or heterocyclyl moieties are optionally substituted by 1 or 2 substituents, which may be the same or different, selected from R 9 , and wherein the aforementioned CR 1 R 2 , Q and Z moieties may be attached at any position of said cycloalkyl, phenyl, heteroaryl or heterocyclyl moieties.
  • X is selected from the group consisting of phenyl and a 4- to 6- membered heterocyclyl, which comprises 1 or 2 heteroatoms individually selected from N and O, and wherein said phenyl or heterocyclyl moieties are optionally substituted by 1 or 2 substituents, which may be the same or different, selected from R 9 , and wherein the aforementioned CR 1 R 2 , Q and Z moieties may be attached at any position of said phenyl or heterocyclyl moieties.
  • X is a 4- to 6- membered heterocyclyl, which comprises 1 or 2 heteroatoms individually selected from N and O, and wherein said heterocyclyl moieties is optionally substituted by 1 or 2 substituents, which may be the same or different, selected from R 9 , and wherein the aforementioned CR 1 R 2 , Q and Z moieties may be attached at any position of said heterocyclyl moiety.
  • X is a 5-membered heterocyclyl, which comprises 1 heteroatom, wherein said heteroatom is N, and wherein the aforementioned CR 1 R 2 , Q and Z moieties may be attached at any position of said heterocyclyl moiety.
  • X is a 5-membered heterocyclyl, which comprises 1 heteroatom, wherein said heteroatom is N, and wherein the aforementioned CR 1 R 2 and Q moieties are attached adjacent to the N atom and the Z moiety is attached to the N atom
  • X is phenyl optionally substituted by 1 or 2 substituents, which may be the same or different, selected from R 9 , and wherein the aforementioned CR 1 R 2 , Q and Z moieties may be attached at any position of said phenyl moiety.
  • X is phenyl and the aforementioned CR 1 R 2 and Q moieties are attached in a postion para to the Z moiety.
  • n is 0 or 1 .
  • Z is selected from the group consisting of hydrogen, OH, Ci-C6alkyl, Ci-C6haloalkyl, Ci- Cehydroxyalkyl, -C(0)OR 10 , -C(0)NH0R 11 , -0C(0)NH0R 11 , -NR 6 C(0)NH0R 11 , -C(0)NHS(0) 2 R 12 , - 0C(0)NHS(0) 2 R 12 , -NR 6 C(0)NHS(0) 2 R 12 , -S(0) 2 0R 10 , -0S(0) 2 0R 10 , -NR 6 S(0) 2 0R 10 , -NR 6 S(0)OR 10 , -NHS(0) 2 R 14 , -S(0)OR 10 , -OS(0)OR 10 , -S(0) 2 NHC(0)R 18 , -S(0) 2 NHS(0) 2 R 12 , -0S(0) 2 NHS(0) 2 R 12 , -0S(0) 2 NHS(0) 2 R 12 ,
  • Z is selected from the group consisting of hydrogen, Ci-C6alkyl, Ci-C6haloalkyl, Ci- Cehydroxyalkyl, Ci-C 6 alkoxy, -C(0)OR 10 , -C(0)NH0R 11 , -C(0)NHS(0) 2 R 12 , -S(0) 2 OR 10 , -OS(0) 2 OR 10 , -NR 6 S(0) 2 0R 10 , -NHS(0) 2 R 14 , -S(0)OR 10 and -P(0)(R 13 )(OR 10 ).
  • Z is selected from the group consisting of hydrogen, Ci-C6alkyl, Ci-C6haloalkyl, Ci-Cehydroxyalkyl, Ci-C 6 alkoxy, -C(0)OR 10 , -C(0)NHS(0) 2 R 12 , -S(0) 2 OR 10 , and -P(0)(R 13 )(OR 10 ).
  • Z is selected from the group consisting of hydrogen, Ci-C6alkyl, Ci- C6haloalkyl, Ci-C6hydroxyalkyl and Ci-C6alkoxy,.
  • Z is hydrogen, Ci-C6alkyl or Ci-C6hydroxyalkyl, especially hydrogen, methyl or CH 2 OH.
  • R 10 is selected from the group consisting of hydrogen, Ci-C6alkyl, phenyl and benzyl, and wherein said phenyl or benzyl are optionally substituted by 1 , 2 or 3 R 9 substituents, which may be the same or different.
  • R 10 is selected from the group consisting of hydrogen, Ci-C6alkyl, phenyl and benzyl. More preferably, R 10 is selected from the group consisting of hydrogen and Ci-C6alkyl. Most preferably, R 10 is hydrogen.
  • R 11 is selected from the group consisting of hydrogen, Ci-C6alkyl and phenyl, and wherein said phenyl is optionally substituted by 1 , 2 or 3 R 9 substituents, which may be the same or different.
  • R 11 is selected from the group consisting of hydrogen, Ci-C6alkyl and phenyl. More preferably, R 11 is selected from the group consisting of hydrogen and Ci-C6alkyl. Even more preferably, R 11 is Ci-C6alkyl. Most preferably, R 11 is methyl.
  • R 12 is selected from the group consisting of Ci-C6alkyl, Ci-C6haloalkyl, Ci-C6alkoxy, -OH, -N(R 6 ) 2 and phenyl, and wherein said phenyl is optionally substituted by 1 , 2 or 3 R 9 substituents, which may be the same or different.
  • R 12 is selected from the group consisting of Ci-C6alkyl, Ci-C6haloalkyl, Ci- C6alkoxy, -OH, -N(R 6 ) 2 and phenyl. More preferably, R 12 is selected from the group consisting of Ci- Cealkyl, Ci-C6haloalkyl and -N(R 6 ) 2 . Even more preferably, R 12 is selected from the group consisting of methyl, -N(Me) 2 and trifluoromethyl. Most preferably, R 12 is methyl.
  • R 13 is selected from the group consisting of -OH, Ci-C6alkyl, Ci-C6alkoxy, Ci-C6haloalkoxy, -O- propargyl, -O-allyl and phenyl.
  • R 13 is selected from the group consisting of Ci-C6alkyl, Ci- C6alkoxy, Ci-C6haloalkoxy, -O-propargyl or -O-allyl. More preferably, R 13 is selected from the group consisting of -OH and Ci-C6alkoxy. Even more preferably, R 13 is selected from the group consisting of methyl, ethyl, propyl, isopropyl, isobutyl, -O propargyl and -O-allyl.
  • R 14 is Ci-C6haloalkyl. Preferably, R 14 is trifluoromethyl.
  • R 15 is selected from the group consisting of Ci-C6alkyl and phenyl, and wherein said phenyl is optionally substituted by 1 , 2 or 3 R 9 substituents, which may be the same or different.
  • R 15 is selected from the group consisting of Ci-C6alkyl and phenyl. More preferably, R 15 is Ci-C6alkyl. Most preferably R 15 is methyl.
  • R 15a is phenyl, wherein said phenyl is optionally substituted by 1 , 2 or 3 R 9 substituents, which may be the same or different.
  • R 15a is phenyl optionally substituted by 1 R 9 substituent. More preferably, R 15a is phenyl.
  • R 16 and R 17 are independently selected from the group consisting of hydrogen and Ci-C6alkyl. Preferably, R 16 and R 17 are independently selected from the group consisting of hydrogen and methyl.
  • R 16 and R 17 together with the nitrogen atom to which they are attached form a 4- to 6- membered heterocyclyl ring which optionally comprises one additional heteroatom individually selected from N, O and S.
  • R 16 and R 17 together with the nitrogen atom to which they are attached form a 5- to 6-membered heterocyclyl ring which optionally comprises one additional heteroatom individually selected from N and O.
  • R 16 and R 17 together with the nitrogen atom to which they are attached form an pyrrolidyl, oxazolidinyl, imidazolidinyl, piperidyl, piperazinyl or morpholinyl group.
  • R 18 is selected from the group consisting of hydrogen, Ci-C6alkyl, Ci-C6haloalkyl, Ci-C6alkoxy, -N(R 6 )2 and phenyl, and wherein said phenyl is optionally substituted by 1 , 2 or 3 R 9 substituents, which may be the same or different.
  • R 18 is selected from the group consisting of hydrogen, Ci-C6alkyl, Ci-C6haloalkyl, Ci-C6alkoxy, -N(R 6 )2 and phenyl. More preferably, R 18 is selected from the group consisting of hydrogen, Ci-C6alkyl and Ci-C6haloalkyl.
  • R 18 is selected from the group consisting of Ci-C6alkyl and Ci-C6haloalkyl. Most preferably, R 18 is methyl or trifluoromethyl. r is 0, 1 or 2. Preferably, r is 0 or 2.
  • compounds of formula (I) may exist/be manufactured in‘procidal form’, wherein they comprise a group‘G’. Such compounds are referred to herein as compounds of formula (l-IV).
  • G is a group which may be removed in a plant by any appropriate mechanism including, but not limited to, metabolism and chemical degradation to give a compound of formula (l-l), (l-V) or (l-VI) wherein E contains an acidic proton, for example see the scheme below: Whilst such G groups may be considered as‘procidal’, and thus yield active herbicidal compounds once removed, compounds comprising such groups may also exhibit herbicidal activity in their own right. In such cases in a compound of formula (l-IV), E-G may include but is not limited to, any one of (G1) to (G7) below and J indicates the point of attachment to the remaining part of a compound of formula (I):
  • G, R 19 , R 20 , R 21 , R 22 and R 23 are defined as follows:
  • G is Ci-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, -C(R 21 R 22 )0C(0)R 19 , phenyl or phenyl-Ci-C 4 alkyl-, wherein said phenyl moiety is optionally substituted by 1 to 5 substituents independently selected from halo, cyano, nitro, Ci-C6alkyl, Ci-C6haloalkyl or Ci-C6alkoxy.
  • R 19 is Ci-C6alkyl or phenyl
  • R 20 is hydroxy, Ci-C6alkyl, Ci-C6alkoxy or phenyl,
  • R 21 is hydrogen or methyl
  • R 22 is hydrogen or methyl
  • R 23 is hydrogen or Ci-C6alkyl.
  • Tables 1 to 9 illustrate the compounds of the invention. The skilled person would understand that the compounds of formula (I) may exist as an agronomically acceptable salt, a zwitterion or an agronomically acceptable salt of a zwitterion as described hereinbefore. Table 1 :
  • the compounds of formula (I) may be prepared by the alkylation of compounds of formula (X), wherein R 3 , R 4 , R 5 and E are as defined for compounds of formula (I), with a suitable alkylating agent of formula (W), wherein R 1 , R 2 , Q, X, n and Z are as defined for compounds of formula (I) and LG is a suitable leaving group, for example, halide or pseudohalide such as triflate, mesylate or tosylate, in a suitable solvent at a suitable temperature, as described in reaction scheme 1 .
  • Example conditions include stirring a compound of formula (X) with an alkylating agent of formula (W) in a solvent, or mixture of solvents, such as acetone, dichloromethane, dichloroethane, A/,A/-dimethylformamide, acetonitrile, 1 ,4-dioxane, water, acetic acid or trifluoroacetic acid at a temperature between -78°C and 150°C.
  • solvent such as acetone, dichloromethane, dichloroethane, A/,A/-dimethylformamide, acetonitrile, 1 ,4-dioxane, water, acetic acid or trifluoroacetic acid at a temperature between -78°C and 150°C.
  • Alkylating agents of formula (W) are commercially avaialable or are known in the literature and may include, but are not limited to, iodomethane, bromomethane, chloromethane, dimethylsulfate, iodoethane, bromoethane, chloroethane, diethylsulfate, 2-methoxyethyl trifluoromethanesulfonate, 2-bromoethyl methyl ether, 2- iodoethyl methyl ether, benzyl bromide, benzyl chloride, benzyl iodide, 2-bromoethanol, 2-iodoethanol, 2,2-difluoroethyl trifluoromethanesulfonate, 2-bromoethylamine hydrobromide, bromoacetic acid, methyl bromoacetate, 3-bromopropionoic acid, methyl 3-bromopropionate, 2-bromo-
  • esters of /V-alkyl acids which include, but are not limited to, esters of carboxylic acids, phosphonic acids, phosphinic acids, sulfonic acids and sulfinic acids, may optionally be subsequently partially or fully hydrolysed by treament with a suitable reagent, for example, aqueous hydrochloric acid or trimethylsilyl bromide, in a suitable solvent at a suitable temperature between 0°C and 100°C.
  • compounds of formula (I) may be prepared by reacting compounds of formula (X), wherein R 3 , R 4 , R 5 and E are as defined for compounds of formula (I), with a suitably activated electrophilic alkene of formula (B), wherein Z is -C(0)R 15 , -C(0)NR 16 R 17 , -C(0)OR 10 , -CHO, nitro, cyano, - S(0) 2 0R 10 , -S(0) 2 NR 16 R 17 , -S(0) r R 15 , -P(0)(R 13 )(OR 10 ) and R 1 , R 2 , R 1a , R 10 , R 13 , R 15 , R 16 and R 17 are as defined for compounds of formula (I), in a suitable solvent at a suitable temperature.
  • a suitably activated electrophilic alkene of formula (B) wherein Z is -C(0)R 15 , -C(0)NR 16 R 17 , -C(0)OR 10 , -CHO,
  • Example reagents include, but are not limited to, acrylic acid, methacrylic acid, crotonic acid, 3,3-dimethylacrylic acid, methyl acrylate, ethene sulfonic acid, isopropyl ethylenesulfonate, 2,2-dimethylpropyl ethenesulfonate and dimethyl vinylphosphonate.
  • esters of N-alkyl acids which include, but are not limited to, esters of carboxylic acids, phosphonic acids, phosphinic acids, sulfonic acids and sulfinic acids, may optionally be subsequently partially or fully hydrolysed by treament with a suitable reagent in a suitable solvent at a suitable temperature, as described in reaction scheme 2.
  • An alkylating agent of formula (E) or (F) may include, but is not limited to, 1 ,3-propanesultone, 1 ,4-butanesultone, ethylenesulfate, 1 ,3-propylene sulfate and 1 ,2,3-oxathiazolidine 2,2-dioxide.
  • Such alkylating agents and related compounds are either known in the literature or may be prepared by known literature methods.
  • R R S0 3 H, OSOJH or
  • a compound of formula (I), wherein m is 0, n is 0 and Z is -S(0) 2 0H, may be prepared from a compound of formula (I), wherein m is 0, n is 0 and Z is C(0)OR 10 , by treatment with trimethylsilylchlorosulfonate in a suitable solvent at a suitable temperature, as described in reaction scheme 4.
  • Preferred conditions include heating the carboxylate precursor in neat trimethylsilylchlorosulfonate at a temperature between 25°C and 150°C.
  • compounds of formula (I) may be prepared by reacting compounds of formula (X), wherein R 3 , R 4 , R 5 and E are as defined for compounds of formula (I), with a suitable alcohol of formula (WW), wherein R 1 , R 2 , Q, X, n and Z are as defined for compounds of formula (I), under Mitsunobu-type conditions such as those reported by Petit et al, Tet. Lett. 2008, 49 (22), 3663.
  • Suitable phosphines include triphenylphosphine
  • suitable azodicarboxylates include diisopropylazodicarboxylate
  • suitable acids include fluoroboric acid, triflic acid and bis(trifluoromethylsulfonyl)amine, as described in reaction scheme 5.
  • Alcohols of formula (WW) are either known in the literature or may be prepared by known literature methods.
  • Compounds of formula (I) may also be prepared by reacting compounds of formula (C), wherein R 3 , R 4 , R 5 and E are as defined for compounds of formula (I), with a hydrazine of formula (D), wherein R 1 , R 2 , Q, X, n and Z are as defined for compounds of formula (I), in a suitable solvent or mixture of solvents, in the presence of a suitable acid at a suitable temperature, between -78°C and 150°C, as described in reaction scheme 6.
  • Suitable solvents include, but are not limited to, alcohols, such as methanol, ethanol and isopropanol, water, aqueous hydrochloric acid, aqueous sulfuric acid, acetic acid and trifluoroacetic acid.
  • Alcohols such as methanol, ethanol and isopropanol
  • water aqueous hydrochloric acid
  • aqueous sulfuric acid aqueous sulfuric acid
  • acetic acid trifluoroacetic acid.
  • Hydrazine compounds of formula (D) for example 2,2-dimethylpropyl 2- hydrazinoethanesulfonate, are either known in the literature or may be prepared by known literature procedures.
  • Compounds of formula (C) may be prepared by reacting compounds of formula (G), wherein R 3 , R 4 , R 5 and E are as defined for compounds of formula (I), with an oxidising agent in a suitable solvent at a suitable temperature, between -78°C and 150°C, optionally in the presence of a suitable base, as described in reaction scheme 7.
  • Suitable oxidising agents include, but are not limited to, bromine and suitable solvents include, but are not limited to alcohols such as methanol, ethanol and isopropanol.
  • Suitable bases include, but are not limited to, sodium bicarbonate, sodium carbonate, potassium bicarbonate, potassium carbonate and potassium acetate. Similar reactions are known in the literature (for example Hufford, D. L; Tarbell, D. S.; Koszalka, T. R. J. Amer. Chem. Soc., 1952, 3014).
  • Furans of formula (G) are known in the literature or may be prepared using literature methods.
  • R' H, C C 4 alkyl
  • Suitable bases include, but are not limited to, triethylamine, pyridine, N,N- diisopropylethylamine, an alkali metal carbonate, such as sodium carbonate, potassium carbonate or cesium carbonate, or an alkali metal alkoxide, such as sodium methoxide.
  • Suitable solvents include, but are not limited to, dichloromethane, A/,A/-dimethylformamide, THF ortoluene.
  • Compounds of formula (J) are either known in the literature or may be prepared by known literature methods or may be commercially available.
  • Such reactions include, but are not limited to, reacting a carboxylic acid of formula (L) with an amine, for example, of formula -R 24 , NH2OR 11 , NH2CN, NHR 6 (CR 6 2)qZ or NH 2 S(0) 2 R 12 , wherein R 6 , R 11 , R 12 , R 24 , q and Z are as defined for compounds of formula (I), in the presence of a suitable coupling agent in a suitable solvent or mixture of solvents, at a suitable temperature between -78°C and 200°C, and optionally in the presence of a suitable base.
  • an amine for example, of formula -R 24 , NH2OR 11 , NH2CN, NHR 6 (CR 6 2)qZ or NH 2 S(0) 2 R 12 , wherein R 6 , R 11 , R 12 , R 24 , q and Z are as defined for compounds of formula (I), in the presence of a suitable coupling agent in a suitable solvent or mixture of solvents, at
  • Suitable coupling reagents include, but are not limited to, a carbodiimide, for example dicyclohexylcarbodiimide or 1 -ethyl-3-[3-dimethylaminopropyl]carbodiimide hydrochloride, a phosphonic anhydride, for example 2,4,6-tripropyM ,3,5,2,4,6-trioxatriphosphorinane-2,4,6-trioxide, or a phosphonium salt, for example benzotriazol-1 -yloxy(tripyrrolidin-1 -yl)phosphonium hexafluorophosphate.
  • a carbodiimide for example dicyclohexylcarbodiimide or 1 -ethyl-3-[3-dimethylaminopropyl]carbodiimide hydrochloride
  • a phosphonic anhydride for example 2,4,6-tripropyM ,3,5,2,4,6-trioxatriphosphor
  • Suitable solvents include, but are not limited to, dichloromethane, N,N- dimethylformamide, THF or toluene, and suitable bases include, but are not limited to, triethylamine, pyridine and A/,A/-diisopropylethylamine.
  • suitable bases include, but are not limited to, triethylamine, pyridine and A/,A/-diisopropylethylamine.
  • Compounds of formula (L) are either known in the literature or may be prepared by known literature methods or may be commercially available.
  • the direct product of this reaction may then be oxidised to a compound of formula (N) and, optionally, subsequently or partially hydrolysed to afford compounds of formula (X).
  • Example oxidants include, but are not limited to, 2,3-dichloro-5,6-dicyano-1 ,4- benzoquinone, tetrachloro-p-benzoquinone, potassium permanganate, manganese dioxide, 2, 2,6,6- tetramethyl-1 -piperidinyloxy and bromine, and example hydrolysis conditions include treatment with aqueous hydrochloric acid or trimethylsilyl bromide, in a suitable solvent at a suitable temperature between 0°C and 100°C.
  • the compounds according to the invention can be used as herbicidal agents in unmodified form, but they are generally formulated into compositions in various ways using formulation adjuvants, such as carriers, solvents and surface-active substances.
  • formulation adjuvants such as carriers, solvents and surface-active substances.
  • the formulations can be in various physical forms, e.g.
  • soluble liquids soluble liquids, water-soluble concentrates or water soluble granules are preferred.
  • Such formulations can either be used directly or diluted prior to use.
  • the dilutions can be made, for example, with water, liquid fertilisers, 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.
  • 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 can 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.
  • 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, A/,A/-dimethylformamide, dimethyl sulfoxide, 1 ,4- dioxane, di
  • 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.
  • 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 dodecylbenzenesulfonate; 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 alkylnaphthalenesulfonates, such as sodium dibutylnaphthalenesulfonate; dialkyl esters of sulfosu coin ate salts, such as sodium di(2- ethylhexyl)sulfosuccinate; sorbitol esters, such as sorbitol oleate; quaternary amines, such as lauryltrimethylammonium chloride, polyethylene glycol esters
  • Further adjuvants that can be used in pesticidal formulations include crystallisation inhibitors, viscosity modifiers, suspending agents, dyes, anti-oxidants, foaming agents, light absorbers, mixing auxiliaries, antifoams, complexing agents, neutralising or pH-modifying substances and buffers, corrosion inhibitors, fragrances, wetting agents, take-up enhancers, micronutrients, plasticisers, glidants, lubricants, dispersants, thickeners, antifreezes, microbicides, and liquid and solid fertilisers.
  • compositions according to the invention can 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 mixture to be applied.
  • the oil additive can be added to a spray tank in the desired concentration after a 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, 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.
  • Preferred oil additives comprise alkyl esters of C8-C22 fatty acids, especially the methyl derivatives of C12-C18 fatty acids, for example the methyl esters of lauric acid, palmitic acid and oleic acid (methyl laurate, methyl palmitate and methyl oleate, respectively).
  • Many oil derivatives are known from the Compendium of Herbicide Adjuvants, 10 th Edition, Southern Illinois University, 2010.
  • 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.
  • the inventive compositions generally comprise from 0.1 to 99 % by weight, especially from 0.1 to 95 % by weight, of compounds of the present invention 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 may preferably be formulated as concentrates, the end user will normally employ dilute formulations.
  • the rates of application vary within wide limits and depend on the nature of the soil, the method of application, the crop plant, the pest to be controlled, the prevailing climatic conditions, and other factors governed by the method of application, the time of application and the target crop.
  • a general guideline compounds may be applied at a rate of from 1 to 2000 l/ha, especially from 10 to 1000 l/ha.
  • Preferred formulations can have the following compositions (weight %):
  • 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 %
  • 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 %
  • composition of the present may further comprise at least one additional pesticide.
  • additional pesticide is a herbicide and/or herbicide safener.
  • compounds of formula (I) can be used in combination with one or more other herbicides to provide various herbicidal mixtures.
  • specific examples of such mixtures include (wherein “I” represents a compound of formula (I)):- 1 + acetochlor; I + acifluorfen (including acifluorfen-sodium); I + aclonifen; I + alachlor; I + alloxydim; I + ametryn; I + amicarbazone; I + amidosulfuron; I + aminocyclopyrachlor ; I + aminopyralid; I + amitrole; I + asulam; I + atrazine; I + bensulfuron (including bensulfuron-methyl); I + bentazone; I + bicyclopyrone; I + bilanafos; I + bifenox; I + bispyribac-sodium; I + bixlozone; I + bromacil; I + bromoxynil; I + butachlor; I
  • 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, Fourteenth Edition, British Crop Protection Council, 2006.
  • the compound of formula (I) can also be used in mixtures with other agrochemicals such as fungicides, nematicides or insecticides, examples of which are given in The Pesticide Manual.
  • 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).
  • T represents a compound of formula (I)
  • Preferred combinations include:- I + benoxacor, I + cloquintocet (including cloquintocet-mexyl); I + cyprosulfamide; I + dichlormid; I + fenchlorazole (including fenchlorazole-ethyl); I + fenclorim; I + fluxofenim; l+ furilazole I + isoxadifen (including isoxadifen-ethyl); I + mefenpyr (including mefenpyr-diethyl); I + metcamifen; I + N-(2-methoxybenzoyl)- 4-[(methylaminocarbonyl)amino] benzenesulfonamide and I + oxabetrinil.
  • 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, 14 th Edition (BCPC), 2006.
  • the reference to cloquintocet-mexyl also applies to a lithium, sodium, potassium, calcium, magnesium, aluminium, iron, ammonium, quaternary ammonium, sulfonium or phosphonium salt thereof as disclosed in WO 02/34048, 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 .
  • 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 safener).
  • the compounds of formula (I) of this invention are useful as herbicides.
  • the present invention therefore further comprises a method for controlling unwanted plants comprising applying to the said plants or a locus comprising them, an effective amount of a compound of the invention or a herbicidal composition containing said compound.
  • Controlling means killing, reducing or retarding growth or preventing or reducing germination.
  • weeds unwanted plants
  • Locus means the area in which the plants are growing or will grow.
  • 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-emergence; post-emergence; application to the seed furrow; no tillage application etc.), the crop plant, the weed(s) 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.
  • the application is generally made by spraying the composition, typically by tractor mounted sprayer for large areas, but other methods such as dusting (for powders), drip or drench can also be used.
  • composition according to the invention can be used include crops such as cereals, for example barley and wheat, cotton, oilseed rape, sunflower, maize, rice, soybeans, sugar beet, sugar cane and turf.
  • crops such as cereals, for example barley and wheat, cotton, oilseed rape, sunflower, maize, rice, soybeans, sugar beet, sugar cane and turf.
  • Crop plants can also include trees, such as fruit trees, palm trees, coconut trees or other nuts. Also included are vines such as grapes, fruit bushes, fruit plants and vegetables.
  • Crops are to be understood as also including those crops which have been rendered tolerant to herbicides or classes of herbicides (e.g. ALS-, GS-, EPSPS-, PPO-, ACCase- and HPPD-inhibitors) by conventional methods of breeding or by genetic engineering.
  • herbicides or classes of herbicides e.g. ALS-, GS-, EPSPS-, PPO-, ACCase- 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®.
  • 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 synthesise 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 to include 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 flavour).
  • output traits e.g. improved storage stability, higher nutritional value and improved flavour.
  • turf grass for example in golf-courses, lawns, parks and roadsides, or grown commercially for sod
  • ornamental plants such as flowers or bushes.
  • Compounds of formula (I) and compositions of the invention can typically be used to control a wide variety of monocotyledonous and dicotyledonous weed species.
  • monocotyledonous species that can typically be controlled include Alopecurus myosuroides, Avena fatua, Brachiaria plantaginea, Bromus tectorum, Cyperus esculentus, Digitaria sanguinalis, Echinochloa crus-galli, Lolium perenne, Lolium multiflorum, Panicum miliaceum, Poa annua, Setaria viridis, Setaria faberi and Sorghum bicolor.
  • dicotyledonous species that can be controlled include Abutilon theophrasti, Amaranthus retroflexus, Bidens pilosa, Chenopodium album, Euphorbia heterophylla, Galium aparine, Ipomoea hederacea, Kochia scoparia, Polygonum convolvulus, Sida spinosa, Sinapis arvensis, Solanum nigrum, Stellaria media, Veronica persica and Xanthium strumarium.
  • the compounds of formula (I) are also useful for pre-harvest desiccation in crops, for example, but not limited to, potatoes, soybean, sunflowers and cotton.
  • Pre-harvest desiccation is used to desiccate crop foliage without significant damage to the crop itself to aid harvesting.
  • Compounds/compositions of the invention are particularly useful in non-selective burn-down applications, and as such may also be used to control volunteer or escape crop plants.
  • the combination is thoroughly mixed with the adjuvants and the mixture is thoroughly ground in a suitable mill, affording wettable powders that can be diluted with waterto give suspensions of the desired concentration.
  • Emulsions of any required dilution which can be used in plant protection, can be obtained from this concentrate by dilution with water.
  • Ready-for-use dusts are obtained by mixing the combination with the carrier and grinding the mixture in a suitable mill.
  • the combination 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.
  • polyethylene glycol (mol. wt. 200) 3 %
  • the finely ground combination is uniformly applied, in a mixer, to the kaolin moistened with polyethylene glycol.
  • Non-dusty coated granules are obtained in this manner.
  • nonylphenol polyethylene glycol ether (15 mol of ethylene oxide) 6 %
  • silicone oil (in the form of a 75 % emulsion in water) 1 %
  • the finely ground combination is intimately mixed with the adjuvants, giving a suspension concentrate from which suspensions of any desired dilution can be obtained by dilution with water.
  • 28 parts of the combination are mixed with 2 parts of an aromatic solvent and 7 parts of toluene diisocyanate/polymethylene-polyphenylisocyanate-mixture (8:1).
  • This mixture is emulsified in a mixture of 1 .2 parts of polyvinylalcohol, 0.05 parts of a defoamer and 51 .6 parts of water until the desired particle size is achieved.
  • a mixture of 2.8 parts 1 ,6-diaminohexane in 5.3 parts of water is added. The mixture is agitated until the polymerization reaction is completed.
  • the obtained capsule suspension is stabilized by adding 0.25 parts of a thickener and 3 parts of a dispersing agent.
  • the capsule suspension formulation contains 28% of the active ingredients.
  • the medium capsule diameter is 8-15 microns.
  • the resulting formulation is applied to seeds as an aqueous suspension in an apparatus suitable for that purpose.
  • Boc fe/ -butyloxycarbonyl
  • HPLC high-performance liquid chromatography (description of the apparatus and the methods used for HPLC are given below)
  • Preparative Reverse Phase HPLC Method Compounds purified by mass directed preparative HPLC using ES+/ES- on a Waters FractionLynx Autopurification system comprising a 2767 injector/collector with a 2545 gradient pump, two 515 isocratic pumps, SFO, 2998 photodiode array (Wavelength range (nm): 210 to 400), 2424 ELSD and QDa mass spectrometer.
  • a Waters Atlantis T3 5micron 19x10mm guard column was used with a Waters Atlantis T3 OBD, 5micron 30x100mm prep column.
  • Electrospray positive and negative Cone (V) 20.00, Source Temperature (°C) 120, Cone Gas Flow (L/Hr.) 50
  • the preparative HPLC was conducted using an 11.4 minute run time (not using at column dilution, bypassed with the column selector), according to the following gradient table:
  • Solvent A Water with 0.05% Trifluoroacetic Acid
  • Solvent B Acetonitrile with 0.05% Trifluoroacetic Acid
  • Methyl iodide (2.33 mL) was added drop wise over 30 minutes to pyridazine (2 g) and stirred at room temperature for 1 hour. The resulting solid was filtered off and washed with iso-hexane to give 1- methylpyridazin-1-ium iodide as a hygroscopic orange solid.
  • Step 2 Preparation of (1 -methylpyridazin-1 -ium-4-yl)phosphonic acid bromide A2
  • the reaction mixture was slowly warmed to room temperature, concentrated and purified by preparative reverse phase HPLC to afford a 5:1 mixture of (1 - methylpyridazin-1 -ium-4-yl)phosphonic acid and methoxy-(1 -methylpyridazin-1 -ium-4-yl)phosphinate which was used directly in the next step.
  • the 5:1 mixture of (1 -methylpyridazin-1 -ium-4-yl)phosphonic acid and methoxy-(1 -methylpyridazin-1 -ium-4-yl)phosphinate (0.2 g) was dissolved in dichloromethane (2 mL) and bromotrimethylsilane (0.43 mL) was added drop wise at room temperature. The reaction mixture was stirred for a further 3 hours at this temperature then concentrated to afford (1 - methylpyridazin-1 -ium-4-yl)phosphonic acid bromide as an orange gum.
  • Step 2 Preparation of 4-[ethoxy(methyl)phosphoryl]-1 -methyl-pyridazin-1 -ium bromide A63
  • Step 3 Preparation of methyl-(1 -methylpyridazin-1 -ium-4-yl)phosphinate A10
  • Step 2 Preparation of fe/ -butyl 2-[(1 -methylpyridazin-1 -ium-4-carbonyl)amino]propanoate A65
  • Step 3 Preparation of 2-[(1 -methylpyridazin-1 -ium-4-carbonyl)amino]propanoate A19 A solution of fe/ -butyl 2-[(1 -methylpyridazin-1 -ium-4-carbonyl)amino]propanoate (0.104 g) in formic acid (5 mL) was stirred at room temperature for 48 hours. The reaction mixture was concentrated to afford 2-[(1 -methylpyridazin-1 -ium-4-carbonyl)amino]propanoate.
  • Step 2 Preparation of 1 -methyl-/V-methylsulfonyl-pyridazin-1 -ium-4-carboxamide iodide A28
  • Step 1 Preparation of methyl 1 -butylpyridazin-1 -ium-4-carboxylate iodide A64
  • Step 2 Preparation of 1 -butylpyridazin-1 -ium-4-carboxylic acid chloride A33
  • Step 1 Preparation of methyl 1 -[(4-cyanophenyl)methyl]pyridazin-1 -ium-4-carboxylate bromide
  • acetone 15 mL
  • 4- bromomethylbenzonitrile 1 .95 g
  • the reaction mixture was concentrated and partitioned between water (20 mL) and dichloromethane (20 mL).
  • the aqueous phase was concentrated and purified by preparative reverse phase HPLC to afford methyl 1 -[(4-cyanophenyl)methyl]pyridazin-1 -ium-4-carboxylate bromide as a white solid.
  • Step 2 Preparation of 1 -[(4-cyanophenyl)methyl]pyridazin-1 -ium-4-carboxylic acid bromide A38 To a suspension of 1 -[(4-cyanophenyl)methyl]pyridazin-1 -ium-4-carboxylate bromide (0.3 g) in acetonitrile (3 mL) was added bromotrimethylsilane (0.41 g) drop wise at room temperature. The reaction mixture was stirred for 4 days at this temperature and concentrated. The crude product was purified by preparative reverse phase HPLC to afford 1 -[(4-cyanophenyl)methyl]pyridazin-1 -ium-4- carboxylic acid bromide as brown solid.
  • Step 1 Preparation of methyl 3-bromopyridazine-4-carboxylate
  • Step 3 Preparation of methyl 1 -methyl-3-pyrimidin-2-yl-pyridazin-1 -ium-4-carboxylate iodide A48
  • Step 4 Preparation of 1 -methyl-3-pyrimidin-2-yl-pyridazin-1 -ium-4-carboxylate A43
  • Step 1 Preparation of A/,A/-dimethylpyridazine-4-carboxamide
  • Step 4 Preparation of methyl 1 -methyl-5-phenyl-pyridazin-1 -ium-4-carboxylate iodide
  • Step 5 Preparation of 1 -methyl-5-phenyl-pyridazin-1 -ium-4-carboxylic acid 2,2,2-trifluoroacetate
  • A44 A solution of methyl 1 -methyl-5-phenyl-pyridazin-1 -ium-4-carboxylate iodide (0.34 g) in 2M aqueous hydrochloric acid (6.8 mL) was heated at 80°C for 40 hours. The reaction mixture was concentrated and purified by preparative reverse phase HPLC (trifluoroacetic acid is present in the eluent) to afford 1 -methyl-5-phenyl-pyridazin-1 -ium-4-carboxylic acid 2,2,2-trifluoroacetate.
  • Step 1 Preparation of methyl 2-(pyridazine-4-carbonylamino)acetate
  • Step 2 Preparation of methyl 2-[(1 -methylpyridazin-1 -ium-4-carbonyl)amino]acetate 2,2,2- trifluoroacetate A45
  • Step 3 Preparation of 2-[(1 -methylpyridazin-1 -ium-4-carbonyl)amino]acetic acid 2,2,2-trifluoroacetate A46
  • Step 2 Preparation of methyl 1 -(2-methoxyethyl)pyridazin-1 -ium-4-carboxylate
  • Step 3 Preparation of 1 -(2-methoxyethyl)pyridazin-1 -ium-4-carboxylate trifluoromethanesulfonate A5
  • a mixture of methyl 1 -(2-methoxyethyl)pyridazin-1 -ium-4-carboxylate trifluoromethanesulfonate (0.04 g) and concentrated hydrochloric acid (2 ml_) was heated at 80°C for 4 hours. The mixture was concentrated to give 1 -(2-methoxyethyl)pyridazin-1 -ium-4-carboxylate trifluoromethanesulfonate.
  • Step 2 Preparation of 1 -(2-hydroxyethyl)pyridazin-1 -ium-4-carboxylate A9
  • Step 1 Preparation of methyl 3-(trifluoromethylsulfonyloxy)propanoate
  • Step 2 Preparation of methyl 1 -(3-methoxy-3-oxo-propyl)pyridazin-1 -ium-4-carboxylate 2,2,2- trifluoroacetate A23 To a solution of methyl pyridazine-4-carboxylate (0.43 g) in dichloromethane (1 mL) was added methyl
  • Methyl 1 -(3-methoxy-3-oxo-propyl)pyridazin-1 -ium-4-carboxylate 2,2,2-trifluoroacetate (0.06 g) was heated at 80°C in 2M aqueous hydrochloric acid (2 mL) for 4 hours. The reaction was concentrated to give 1 -(2-carboxyethyl)pyridazin-1 -ium-4-carboxylic acid chloride.
  • Step 1 Preparation of methyl 2-(pyridazine-4-carbonylamino)propanoate
  • Step 2 Preparation of 3-[4-[(2-methoxy-1 -methyl-2-oxo-ethyl)carbamoyl]pyridazin-1 -ium-1 - yljpropanoic acid 2,2,2-trifluoroacetate A51
  • Step 3 Preparation of 2-[[1 -(2-carboxyethyl)pyridazin-1 -ium-4-carbonyl]amino]propanoic acid chloride A50
  • Step 2 Preparation of 1 -[3-(methylamino)-3-oxo-propyl]pyridazin-1 -ium-4-carboxylic acid 2,2,2- trifluoroacetate A56
  • reaction was concentrated, triturated with methyl te/ -butyl ether and purified by preparative reverse phase HPLC (trifluoroacetic acid is present in the eluent) to give 1 -[3-(methylamino)-3-oxo-propyl]pyridazin-1 -ium-4-carboxylic acid 2,2,2- trifluoroacetate.
  • Step 2 Preparation of 1 -[2-(methylsulfamoyl)ethyl]pyridazin-1 -ium-4-carboxylic acid 2,2,2- trifluoroacetate A55
  • Step 1 Preparation of 2-bromo-N-methylsulfonyl-acetamide To a solution of methanesulfonamide (1 g) in toluene (63 ml_) was added 2-bromoacetyl bromide (3.7 ml_) drop wise at room temperature. The reaction mixture was then heated at 1 10°C for 5 hours.
  • Step 2 Preparation of methyl 1 -[2-(methanesulfonamido)-2-oxo-ethyl]pyridazin-1 -ium-4-carboxylate 2,2,2-trifluoroacetate A25
  • Ipomoea hederacea IPHE
  • Euphorbia heterophylla EPHHL
  • Chenopodium album CHEAL
  • Amaranthus palmeri AMAPA
  • Lolium perenne LLOLPE
  • Digitaria sanguinalis DIGSA
  • Eleusine indica ELEIN
  • Echinochloa crus-galli EHCG
  • Setaria faberi SETFA

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Abstract

Compounds of the formula (I) wherein the substituents are as defined in claim 1, useful as a pesticides, especially as herbicides.

Description

Herbicidal Compounds
The present invention relates to herbicidally active pyridazine derivatives, as well as to processes and intermediates used for the preparation of such derivatives. The invention further extends to herbicidal compositions comprising such derivatives, as well as to the use of such compounds and compositions for controlling undesirable plant growth: in particular the use for controlling weeds, in crops of useful plants.
The present invention is based on the finding that pyridazine derivatives of formula (I) as defined herein, exhibit surprisingly good herbicidal activity. Thus, according to the present invention there is provided use as a herbicide of a compound of formula (I) or an agronomically acceptable salt or zwitterionic species thereof:
Figure imgf000002_0001
wherein
R1 is selected from the group consisting of hydrogen, halogen, Ci-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, Cs-Cecycloalkyl, Ci-C6haloalkyl, -OR7, -OR15a, -N(R6)S(0)2R15, -N(R6)C(0)R15, -N(R6)C(0)0R15, - N(R6)C(0)NR16R17, -N(R6)CHO, -N(R7a)2 and -S(0)rR15;
R2 is selected from the group consisting of hydrogen, halogen, Ci-C6alkyl and Ci-C6haloalkyl;
and wherein when R1 is selected from the group consisting of -OR7, -OR15a, -N(R6)S(0)2R15, - N(R6)C(0)R15, -N(R6)C(0)0R15, -N(R6)C(0)NR16R17, -N(R6)CHO, -N(R7a)2 and -S(0)rR15, R2 is selected from the group consisting of hydrogen and Ci-C6alkyl; or
R1 and R2 together with the carbon atom to which they are attached form a C3-C6cycloalkyl ring or a 3- to 6- membered heterocyclyl, which comprises 1 or 2 heteroatoms individually selected from N and O;
Q is (CR1aR2b)m;
m is 0, 1 , 2 or 3;
each R1a and R2b are independently selected from the group consisting of hydrogen, halogen, Ci-C6alkyl, Ci-Cehaloalkyl, -OH, -OR7, -OR15a, -NH2, -NHR7, -NHR15a, -N(R6)CHO, -NR7bR7c and -S(0)rR15; or each R1a and R2b together with the carbon atom to which they are attached form a C3-C6cycloalkyl ring or a 3- to 6- membered heterocyclyl, which comprises 1 or 2 heteroatoms individually selected from N and O;
R3, R4 and R5 are independently selected from the group consisting of hydrogen, halogen, nitro, cyano, -NH2, -NR6R7, -OH, -OR7, -S(0)rR12, -NR6S(0)rR12, Ci-C6alkyl, Ci-Cehaloalkyl, Cs-Cecycloalkyl, C3- Cehalocycloalkyl, C3-C6cycloalkoxy, C2-C6alkenyl, C2-C6haloalkenyl, C2-C6alkynyl, Ci-C3alkoxyCi- C3alkyl-, hydroxyCi-Cealkyl-, Ci-C6haloalkoxy, Ci-C3haloalkoxyCi-C3alkyl-, Ci-C6alkoxycarbonyl, C3- Cealkenyloxy, C3-C6alkynyloxy, Ci-C6alkylcarbonyl, Ci-C6alkylaminocarbonyl, di-Ci- Cealkylaminocarbonyl, -C(R8)=NOR8, phenyl and heteroaryl, wherein the heteroaryl moiety is a 5- or 6- membered monocyclic aromatic ring which comprises 1 , 2, 3 or 4 heteroatoms individually selected from N, O and S, and wherein any of said phenyl or heteroaryl moieties are optionally substituted by 1 , 2 or 3 substituents R9, which may be the same or different;
each R6 is independently selected from hydrogen and Ci-C6alkyl;
each R7 is independently selected from the group consisting of Ci-C6alkyl, -S(0)2R15, -C(0)R15, - C(0)0R15 and -C(0)NR16R17;
each R7a is independently selected from the group consisting of -S(0)2R15, -C(0)R15, -C(0)0R15 - C(0)NR16R17 and -C(0)NR6R15a;
R7b and R7c are independently selected from the group consisting of Ci-C6alkyl, -S(0)2R15, -C(0)R15, - C(0)0R15, -C(0)NR16R17 and phenyl, and wherein said phenyl is optionally substituted by 1 , 2 or 3 R9 substituents, which may be the same or different; or
R7b and R7c together with the nitrogen atom to which they are attached form a 4- to 6-membered heterocyclyl ring which optionally comprises one additional heteroatom individually selected from N, O and S; and
each R9 is independently selected from the group consisting of halogen, cyano, -OH, -N(R6)2, Ci-C4alkyl, Ci-C4alkoxy, Ci-C4haloalkyl and Ci-C4haloalkoxy;
E is selected from the group consisting of of -C(0)OR10, -CHO, -C(0)R24, -C(0)NH0R11, -C(0)NHCN, -C(0)NHR25, -S(0)2NHR25, -C(0)NR6(CR6 2)qC(0)(0R1°), -C(0)NR6(CR6 2)qS(0)2(0R10),
C(0)NR6(CR6 2)qP(0)(R13)(0R1°), -(CR6 2)qC(0)OR10, -(CR6 2)qS(0)2(0R10), -(CR6 2)qP(0)(R13)(OR10), - 0C(0)NH0R11 , -0(CR6 2)qC(0)0R1°, -0C(0)NHCN, -0(CR6 2)qS(0)2(0R10), -0(CR6 2)qP(0)(R13)(0R10), -NR6C(0)NH0R11 , -NR6C(0)NHCN, -C(0)NHS(0)2R12, -0C(0)NHS(0)2R12, -NR6C(0)NHS(0)2R12, - S(0)20R10, -0S(0)20R10, -NR6S(0)20R10, -NR6S(0)OR10, -NHS(0)2R14, -S(0)OR10, -
S(CR6 2)qC(0)OR10, -S(CR6 2)qS(0)2(0R10), -S(CR6 2)qP(0)(R13)(OR10), -OS(0)OR10, -S(0)2NHCN, - S(0)2NHC(0)R18, -S(0)2NHS(0)2R12, -0S(0)2NHCN, -0S(0)2NHS(0)2R12, -0S(0)2NHC(0)R18, - NR6S(0)2NHCN, -NR6S(0)2NHC(0)R18, -N(0H)C(0)R15, -0NHC(0)R15, -NR6S(0)2NHS(0)2R12, - P(0)(R13)(OR10), -P(0)H(OR10), -0P(0)(R13)(0R1°), -NR6P(0)(R13)(OR10) and tetrazole;
q is 1 -3
X is selected from the group consisting of C3-C6cycloalkyl, phenyl, a 5- or 6- membered heteroaryl, which comprises 1 , 2, 3 or 4 heteroatoms individually selected from N, O and S, and a 4- to 6- membered heterocyclyl, which comprises 1 , 2 or 3 heteroatoms individually selected from N, O and S, and wherein said cycloalkyl, phenyl, heteroaryl or heterocyclyl moieties are optionally substituted by 1 or 2 substituents, which may be the same or different, selected from R9, and wherein the aforementioned CR1R2, Q and Z moieties may be attached at any position of said cycloalkyl, phenyl, heteroaryl or heterocyclyl moieties;
n is 0 or 1 ; Z is selected from the group consisting of hydrogen, Ci-C6alkyl, Ci-C6haloalkyl, Ci-C6hydroxyalkyl, Ci- CealkoxyCi-Cealkyl, nitro, halo, haloalkoxy, cyano, -NH2, -OH, -OR7, -C(0)R15, -C(0)NR16R17, - C(0)OR10, -CHO, -C(0)NH0R11 , -C(0)NHCN, -0C(0)NH0R11 , -0C(0)NHCN, -NR6C(0)NH0R11 , - NR6C(0)NHCN, -C(0)NHS(0)2R12, -0C(0)NHS(0)2R12, -NHR7, -N(R7)2, -NR6C(0)NHS(0)2R12, -
NR6S(0)2R15, -S(0)20R10, -0S(0)20R10, -NR6S(0)20R10, -NR6S(0)OR10, -NHS(0)2R14, -S(0)rR15, - S(0)OR10, -S(0)2NR16R17 -OS(0)OR10, -S(0)2NHCN, -S(0)2NHC(0)R18, -S(0)2NHS(0)2R12, - 0S(0)2NHCN, -0S(0)2NHS(0)2R12, -0S(0)2NHC(0)R18, -NR6S(0)2NHCN, -NR6S(0)2NHC(0)R18, - N(0H)C(0)R15, -0NHC(0)R15, -NR6S(0)2NHS(0)2R12, -P(0)(R13)(OR10), -P(0)H(OR10), -
0P(0)(R13)(0R1°), -NR6P(0)(R13)(OR10), tetrazole;
R10 is selected from the group consisting of hydrogen, Ci-C6alkyl, phenyl and benzyl, and wherein said phenyl or benzyl are optionally substituted by 1 , 2 or 3 R9 substituents, which may be the same or different;
R11 is selected from the group consisting of hydrogen, Ci-C6alkyl and phenyl, and wherein said phenyl is optionally substituted by 1 , 2 or 3 R9 substituents, which may be the same or different;
R12 is selected from the group consisting of Ci-C6alkyl, Ci-C6haloalkyl, Ci-C6alkoxy, -OH, -N(R6)2 and phenyl, and wherein said phenyl is optionally substituted by 1 , 2 or 3 R9 substituents, which may be the same or different;
R13 is selected from the group consisting of -OH, Ci-C6alkyl, Ci-C6alkoxy, Ci-C6haloalkoxy, -O- propargyl, -O-allyl and phenyl;
R14 is Ci-Cehaloalkyl;
R15 is selected from the group consisting of Ci-C6alkyl and phenyl, and wherein said phenyl is optionally substituted by 1 , 2 or 3 R9 substituents, which may be the same or different;
R15a is phenyl, wherein said phenyl is optionally substituted by 1 , 2 or 3 R9 substituents, which may be the same or different;
R16 and R17 are independently selected from the group consisting of hydrogen and Ci-C6alkyl; or
R16 and R17 together with the nitrogen atom to which they are attached form a 4- to 6-membered heterocyclyl ring which optionally comprises one additional heteroatom individually selected from N, O and S;
R18 is selected from the group consisting of hydrogen, Ci-C6alkyl, Ci-C6haloalkyl, Ci-C6alkoxy, -N(R6)2 and phenyl, and wherein said phenyl is optionally substituted by 1 , 2 or 3 R9 substituents, which may be the same or different;
R24 is a peptide moiety comprising one, two or three amino acid moieties independently selected from the group consisting of Ala, Cys, Asp, Glu, Phe, Gly, His, lie, Lys, Leu, Met, Asn, Pro, Gin, Arg, Ser, Thr, Val, Trp and Tyr, wherein said peptide moiety is bonded to the rest of the molecule via a nitrogen atom in the amino acid moiety;
R25 is selected from the group consisting of 5- or 6- membered heteroaromatic moieties, optionally substituted with one or more groups independently selected from R2 or; R25 is selected from the group consisting of 5- or 6- membered heteroaromatic moieties, containing at least two N atoms, optionally substituted with one or more groups independently selected from R9; and
r is 0, 1 or 2;
with the proviso that pyridazocidin is excluded.
According to a second aspect of the invention, there is provided a compound of formula (I) as defined above, wherein R3, R4 and R5 are each independently hydrogen, Ci-C6alkyl, or Ci-C6alkoxy, with the proviso that said compound is not pyridazocidin
According to a third aspect of the invention, there is provided an agrochemical composition comprising a herbicidally effective amount of a compound of formula (I) and an agrochemically-acceptable diluent or carrier. Such an agricultural composition may further comprise at least one additional active ingredient.
According to a fourth aspect of the invention, there is provided a method of controlling or preventing undesirable plant growth, wherein a herbicidally effective amount of a compound of formula (I), or a composition comprising this compound as active ingredient, is applied to the plants, to parts thereof or the locus thereof.
According to a fifth aspect of the invention, there is provided the use of a compound of formula (I) as a herbicide.
According to a sixth aspect of the invention, there is provided a process for the preparation of compounds of formula (I).
As used herein, the term "halogen" or“halo” refers to fluorine (fluoro), chlorine (chloro), bromine (bromo) or iodine (iodo), preferably fluorine, chlorine or bromine.
As used herein, cyano means a -CN group.
As used herein, hydroxy means an -OH group.
As used herein, nitro means an -NO2 group.
As used herein, the term "Ci-C6alkyl" refers to a straight or branched hydrocarbon chain radical consisting solely of carbon and hydrogen atoms, containing no unsaturation, having from one to six carbon atoms, and which is attached to the rest of the molecule by a single bond. Ci-C4alkyl and Ci- C2alkyl are to be construed accordingly. Examples of Ci-C6alkyl include, but are not limited to, methyl (Me), ethyl (Et), n-propyl, 1 -methylethyl (iso-propyl), n-butyl, and 1 -dimethylethyl (f-butyl).
As used herein, the term "Ci-C6alkoxy" refers to a radical of the formula -ORa where Ra is a Ci-C6alkyl radical as generally defined above. Ci-C4alkoxy is to be construed accordingly. Examples of Ci-4alkoxy include, but are not limited to, methoxy, ethoxy, propoxy, iso-propoxy and f-butoxy.
As used herein, the term "Ci-C6haloalkyl" refers to a Ci-C6alkyl radical as generally defined above substituted by one or more of the same or different halogen atoms. Ci-C4haloalkyl is to be construed accordingly. Examples of Ci-C6haloalkyl include, but are not limited to chloromethyl, fluoromethyl, fluoroethyl, difluoromethyl, trifluoromethyl and 2,2,2-trifluoroethyl.
As used herein, the term "C2-C6alkenyl" refers to a straight or branched hydrocarbon chain radical group consisting solely of carbon and hydrogen atoms, containing at least one double bond that can be of either the (E)- or (^-configuration, having from two to six carbon atoms, which is attached to the rest of the molecule by a single bond. C2-C4alkenyl is to be construed accordingly. Examples of C2-C6alkenyl include, but are not limited to, prop-1 -enyl, allyl (prop-2-enyl) and but-1 -enyl.
As used herein, the term“C2-C6haloalkenyl” refers to a C2-C6alkenyl radical as generally defined above substituted by one or more of the same or different halogen atoms. Examples of C2-C6haloalkenyl include, but are not limited to chloroethylene, fluoroethylene, 1 ,1 -difluoroethylene, 1 ,1 -dichloroethylene and 1 ,1 ,2-trichloroethylene.
As used herein, the term "C2-C6alkynyl" refers to a straight or branched hydrocarbon chain radical group consisting solely of carbon and hydrogen atoms, containing at least one triple bond, having from two to six carbon atoms, and which is attached to the rest of the molecule by a single bond. C2-C4alkynyl is to be construed accordingly. Examples of C2-C6alkynyl include, but are not limited to, prop-1 -ynyl, propargyl (prop-2-ynyl) and but-1 -ynyl.
As used herein, the term "Ci-C6haloalkoxy" refers to a Ci-C6alkoxy group as defined above substituted by one or more of the same or different halogen atoms. Ci-C4haloalkoxy is to be construed accordingly. Examples of Ci-C6haloalkoxy include, but are not limited to, fluoromethoxy, difluoromethoxy, fluoroethoxy, trifluoromethoxy and trifluoroethoxy.
As used herein, the term "Ci-C3haloalkoxyCi-C3alkyl" refers to a radical of the formula Rb-O-Ra- where Rb is a Ci-C3haloalkyl radical as generally defined above, and Ra is a Ci-C3alkylene radical as generally defined above.
As used herein, the term "Ci-C3alkoxyCi-C3alkyl" refers to a radical of the formula Rb-0-Ra- where Rb is a Ci-C3alkyl radical as generally defined above, and Ra is a Ci-C3alkylene radical as generally defined above.
As used herein, the term " Ci-C3alkoxyCi-C3alkoxy-" refers to a radical of the formula Rb-0-Ra-0- where Rb is a Ci-C3alkyl radical as generally defined above, and Ra is a Ci-C3alkylene radical as generally defined above.
As used herein, the term "C3-C6alkenyloxy" refers to a radical of the formula -ORa where Ra is a C3- Cealkenyl radical as generally defined above.
As used herein, the term "C3-C6alkynyloxy" refers to a radical of the formula -ORa where Ra is a C3- Cealkynyl radical as generally defined above.
As used herein, the term“hydroxyCi-Cealkyl” refers to a Ci-C6alkyl radical as generally defined above substituted by one or more hydroxy groups.
As used herein, the term "Ci-C6alkylcarbonyl" refers to a radical of the formula -C(0)Ra where Ra is a Ci-C6alkyl radical as generally defined above. As used herein, the term "Ci-C6alkoxycarbonyl" refers to a radical of the formula -C(0)0Ra where Ra is a Ci-C6alkyl radical as generally defined above.
As used herein, the term“aminocarbonyl” refers to a radical of the formula -C(0)NH2.
As used herein, the term "C3-C6cycloalkyl" refers to a stable, monocyclic ring radical which is saturated or partially unsaturated and contains 3 to 6 carbon atoms. C3-C4cycloalkyl is to be construed accordingly. Examples of C3-C6cycloalkyl include, but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl.
As used herein, the term "C3-C6halocycloalkyl" refers to a C3-C6cycloalkyl radical as generally defined above substituted by one or more of the same or different halogen atoms. C3-C4halocycloalkyl is to be construed accordingly.
As used herein, the term "C3-C6cycloalkoxy" refers to a radical of the formula -ORa where Ra is a C3- C6cycloalkyl radical as generally defined above.
As used herein, the term“N-C3-C6cycloalkylamino” refers to a radical of the formula -NHRa where Ra is a C3-C6cycloalkyl radical as generally defined above.
As used herein, except where explicitly stated otherwise, the term "heteroaryl" refers to a 5- or 6- membered monocyclic aromatic ring which comprises 1 , 2, 3 or 4 heteroatoms individually selected from nitrogen, oxygen and sulfur. The heteroaryl radical may be bonded to the rest of the molecule via a carbon atom or heteroatom. Examples of heteroaryl include, furyl, pyrrolyl, imidazolyl, thienyl, pyrazolyl, thiazolyl, isothiazolyl, oxazolyl, isoxazolyl, triazolyl, tetrazolyl, pyrazinyl, pyridazinyl, pyrimidyl or pyridyl.
As used herein, except where explicitly stated otherwise, the term "heterocyclyl" or "heterocyclic" refers to a stable 4- to 6-membered non-aromatic monocyclic ring radical which comprises 1 , 2, or 3 heteroatoms individually selected from nitrogen, oxygen and sulfur. The heterocyclyl radical may be bonded to the rest of the molecule via a carbon atom or heteroatom. Examples of heterocyclyl include, but are not limited to, pyrrolinyl, pyrrolidyl, tetrahydrofuryl, tetrahydrothienyl, tetrahydrothiopyranyl, piperidyl, piperazinyl, tetrahydropyranyl, dihydroisoxazolyl, dioxolanyl, morpholinyl or d-lactamyl.
The presence of one or more possible asymmetric carbon atoms in a compound of formula (I) means that the compounds may occur in chiral isomeric forms, i.e., enantiomeric or diastereomeric forms. Also atropisomers may occur as a result of restricted rotation about a single bond. Formula (I) is intended to include all those possible isomeric forms and mixtures thereof. The present invention includes all those possible isomeric forms and mixtures thereof for a compound of formula (I). Likewise, formula (I) is intended to include all possible tautomers (including lactam-lactim tautomerism and keto-enol tautomerism) where present. The present invention includes all possible tautomeric forms for a compound of formula (I). Similarly, where there are di-substituted alkenes, these may be present in E or Z form or as mixtures of both in any proportion. The present invention includes all these possible isomeric forms and mixtures thereof for a compound of formula (I).
The compounds of formula (I) will typically be provided in the form of an agronomically acceptable salt, a zwitterion or an agronomically acceptable salt of a zwitterion. This invention covers all such agronomically acceptable salts, zwitterions and mixtures thereof in all proportions. For example a compound of formula (I) wherein E or Z comprises an acidic proton, may exist as a zwitterion, a compound of formula (l-l) or formula (l-V), or as an agronomically acceptable salt, a compound of formula (l-ll) or formula (l-VI)as shown below:
Figure imgf000008_0001
wherein, Y represents an agronomically acceptable anion and j and k represent integers that may be selected from 1 , 2 or 3, dependent upon the charge of the respective anion Y.
A compound of formula (I) may also exist as an agronomically acceptable salt of a zwitterion, a compound of formula (l-lll) or formula (l-VII) as shown below:
Figure imgf000008_0002
(l-lll) (I-VII)
wherein, Y represents an agronomically acceptable anion, M represents an agronomically acceptable cation (in addition to the pyridazinium cation) and the integers j, k and q may be selected from 1 , 2 or 3, dependent upon the charge of the respective anion Y and respective cation M.
Thus where a compound of formula (I) is drawn in protonated form herein, the skilled person would appreciate that it could equally be represented in unprotonated or salt form with one or more relevant counter ions. In one embodiment of the invention there is provided a compound of formula (l-ll) or formula (l-VI) wherein k is 2, j is 1 and Y is selected from the group consisting of halogen, trifluoroacetate and pentafluoropropionate. In this embodiment a nitrogen atom comprised in R1 , R2, R3, R4, R5, E, Q, Z or X may be protonated.
Suitable agronomically acceptable salts of the present invention, represented by an anion Y, include but are not limited chloride, bromide, iodide, fluoride, 2-naphthalenesulfonate, acetate, adipate, methoxide, ethoxide, propoxide, butoxide, aspartate, benzenesulfonate, benzoate, bicarbonate, bisulfate, bitartrate, butylsulfate, butylsulfonate, butyrate, camphorate, camsylate, caprate, caproate, caprylate, carbonate, citrate, diphosphate, edetate, edisylate, enanthate, ethanedisulfonate, ethanesulfonate, ethylsulfate, formate, fumarate, gluceptate, gluconate, glucoronate, glutamate, glycerophosphate, heptadecanoate, hexadecanoate, hydrogen sulfate, hydroxide, hydroxynaphthoate, isethionate, lactate, lactobionate, laurate, malate, maleate, mandelate, mesylate, methanedisulfonate, methylsulfate, mucate, myristate, napsylate, nitrate, nonadecanoate, octadecanoate, oxalate, pelargonate, pentadecanoate, pentafluoropropionate, perchlorate, phosphate, propionate, propylsulfate, propylsulfonate, succinate, sulfate, tartrate, tosylate, tridecylate, triflate, trifluoroacetate, undecylinate and valerate.
Suitable cations represented by M include, but are not limited to, metals, conjugate acids of amines and organic cations. Examples of suitable metals include aluminium, calcium, cesium, copper, lithium, magnesium, manganese, potassium, sodium, iron and zinc. Examples of suitable amines include allylamine, ammonia, amylamine, arginine, benethamine, benzathine, butenyl-2-amine, butylamine, butylethanolamine, cyclohexylamine, decylamine, diamylamine, dibutylamine, diethanolamine, diethylamine, diethylenetriamine, diheptylamine, dihexylamine, diisoamylamine, diisopropylamine, dimethylamine, dioctylamine, dipropanolamine, dipropargylamine, dipropylamine, dodecylamine, ethanolamine, ethylamine, ethylbutylamine, ethylenediamine, ethylheptylamine, ethyloctylamine, ethylpropanolamine, heptadecylamine, heptylamine, hexadecylamine, hexenyl-2-amine, hexylamine, hexylheptylamine, hexyloctylamine, histidine, indoline, isoamylamine, isobutanolamine, isobutylamine, isopropanolamine, isopropylamine, lysine, meglumine, methoxyethylamine, methylamine, methylbutylamine, methylethylamine, methylhexylamine, methylisopropylamine, methylnonylamine, methyloctadecylamine, methylpentadecylamine, morpholine, N,N-diethylethanolamine, N- methylpiperazine, nonylamine, octadecylamine, octylamine, oleylamine, pentadecylamine, pentenyl-2- amine, phenoxyethylamine, picoline, piperazine, piperidine, propanolamine, propylamine, propylenediamine, pyridine, pyrrolidine, sec-butylamine, stearylamine, tallowamine, tetradecylamine, tributylamine, tridecylamine, trimethylamine, triheptylamine, trihexylamine, triisobutylamine, triisodecylamine, triisopropylamine, trimethylamine, tripentylamine, tripropylamine, tris(hydroxymethyl)aminomethane, and undecylamine. Examples of suitable organic cations include benzyltributylammonium, benzyltrimethylammonium, benzyltriphenylphosphonium, choline, tetrabutylammonium, tetrabutylphosphonium, tetraethylammonium, tetraethylphosphonium, tetramethylammonium, tetramethylphosphonium, tetrapropylammonium, tetrapropylphosphonium, tributylsulfonium, tributylsulfoxonium, triethylsulfonium, triethylsulfoxonium, trimethylsulfonium, trimethylsulfoxonium, tripropylsulfonium and tripropylsulfoxonium. Preferred compounds of formula (I), wherein E or Z comprises an acidic proton, can be represented as either (l-l), (l-V), (l-ll) or (l-VI). For compounds of formula (l-ll) or (l-VI) emphasis is given to salts when Y is chloride, bromide, iodide, hydroxide, bicarbonate, acetate, pentafluoropropionate, triflate, trifluoroacetate, methylsulfate, tosylate and nitrate, wherein j and k are 1. Preferably, Y is chloride, bromide, iodide, hydroxide, bicarbonate, acetate, trifluoroacetate, methylsulfate, tosylate and nitrate, wherein j and k are 1. For compounds of formula (l-ll) or (l-VI) emphasis is also given to salts when Y is carbonate and sulfate, wherein j is 2 and k is 1 , and when Y is phosphate, wherein j is 3 and k is 1.
Where appropriate compounds of formula (I) may also be in the form of (and/or be used as) an N-oxide.
Compounds of formula (I) wherein m is 0 and n is 0 may be represented by a compound of formula (I- la) as shown below:
Figure imgf000010_0001
(l-la)
wherein R1, R2, R3, R4, R5, E and Z are as defined for compounds of formula (I).
Compounds of formula (I) wherein m is 1 and n is 0 may be represented by a compound of formula (I- lb) as shown below:
Figure imgf000010_0002
(l-lb)
wherein R1, R2, R1a, R2b, R3, R4, R5 , E and Z are as defined for compounds of formula (I).
Compounds of formula (I) wherein m is 2 and n is 0 may be represented by a compound of formula (I- lc) as shown below:
Figure imgf000010_0003
(l-lc) wherein R1 , R2, R1a, R2b, R3, R4, R5, E and Z are as defined for compounds of formula (I).
Compounds of formula (I) wherein m is 3 and n is 0 may be represented by a compound of formula (I- Id) as shown below:
Figure imgf000011_0001
(l-ld)
wherein R1 , R2, R1a, R2b, R3, R4, R5, E and Z are as defined for compounds of formula (I).
Pyridazocidin which is specifically excluded from compounds of the present invention is a compound of formula (I) in which R1 , R2, R3, R4 and R5 are hydrogen, E is -C(0)0H, Q is -CH2CH2CH(NH2)- and Z is -C(0)0H. Preferably also excluded are agrochemically acceptable salts of pyridazocidin.
The following are preferred definitions for formula (I). Any of the definitions given below may be combined with any definition of any other substituent given below or elsewhere in this document.
Preferably, R1 is selected from the group consisting of hydrogen, halogen, Ci-C6alkyl, Ci-C6fluoroalkyl, -OR7, -NHS(0)2R15, -NHC(0)R15, -NHC(0)0R15, -NHC(0)NR16R17, -N(R7a)2 and -S(0)rR15. More preferably, R1 is selected from the group consisting of hydrogen, halogen, Ci-C6alkyl, Ci-C6fluoroalkyl, -OR7 and -N(R7a)2. Even more preferably, R1 is selected from the group consisting of hydrogen, Ci- Cealkyl, -OR7 and -N(R7a)2. Even more preferably still, R1 is hydrogen or Ci-C6alkyl. Yet even more preferably still, R1 is hydrogen or methyl. Most preferably R1 is hydrogen.
R2 is selected from the group consisting of hydrogen, halogen, Ci-C6alkyl and Ci-C6haloalkyl. Preferably, R2 is selected from the group consisting of hydrogen, halogen, Ci-C6alkyl and Ci- C6fluoroalkyl. More preferably, R2 is hydrogen or Ci-C6alkyl. Even more preferably, R2 is hydrogen or methyl. Most preferably R2 is hydrogen.
Wherein when R1 is selected from the group consisting of -OR7, -OR15a, -N(R6)S(0)2R15, -N(R6)C(0)R15, -N(R6)C(0)0R15, -N(R6)C(0)NR16R17, -N(R6)CHO, -N(R7a)2 and -S(0)rR15, then R2 is selected from the group consisting of hydrogen and Ci-C6alkyl. Preferably, when R1 is selected from the group consisting of -OR7, -NHS(0)2R15, -NHC(0)R15, -NHC(0)0R15, -NHC(0)NR16R17, -N(R7a)2 and -S(0)rR15, then R2 is selected from the group consisting of hydrogen and methyl.
Alternatively, R1 and R2 together with the carbon atom to which they are attached form a C3-C6cycloalkyl ring or a 3- to 6- membered heterocyclyl, which comprises 1 or 2 heteroatoms individually selected from N and O. Preferably, R1 and R2 together with the carbon atom to which they are attached form a C3- C6cycloalkyl ring. More preferably, R1 and R2 together with the carbon atom to which they are attached form a cyclopropyl ring.
In another embodiment R1 is methyl and R2 is hydrogen. In another embodiment R1 is methyl and R2 is methyl.
In a preferred embodiment R1 and R2 are hydrogen
Q is (CR1aR2b)m.
m is 0, 1 , 2 or 3. Preferably, m is 0,1 or 2. More preferably, m is 1 or 2. Most preferably, m is 0.
Each R1a and R2b are independently selected from the group consisting of hydrogen, halogen, Ci- Cealkyl, Ci-C6haloalkyl, -OH, -OR7, -OR15a, -NH2, -NHR7, -NHR15a, -N(R6)CHO, -NR7bR7c and -S(0)rR15. Preferably, each R1a and R2b are independently selected from the group consisting of hydrogen, halogen, Ci-C6alkyl, Ci-C6fluoroalkyl, -OH, -NH2 and -NHR7. More preferably, each R1a and R2b are independently selected from the group consisting of hydrogen, Ci-C6alkyl, -OH and -NH2. Even more preferably, each R1a and R2b are independently selected from the group consisting of hydrogen, methyl, -OH and -NH2. Even more preferably still, each R1a and R2b are independently selected from the group consisting of hydrogen and methyl. Most preferably R1a and R2b are hydrogen.
In another embodiment each R1a and R2b are independently selected from the group consisting of hydrogen and Ci-C6alkyl.
Alternatively, each R1a and R2b together with the carbon atom to which they are attached form a C3- C6cycloalkyl ring or a 3- to 6- membered heterocyclyl, which comprises 1 or 2 heteroatoms individually selected from N and O. Preferably, each R1a and R2b together with the carbon atom to which they are attached form a C3-C6cycloalkyl ring. More preferably, each R1a and R2b together with the carbon atom to which they are attached form a cyclopropyl ring.
R3 , R4 , and R5 are preferably independently hydrogen, Ci-C6alkyl, or Ci-C6alkoxy, most preferably hydrogen or methyl.
Each R6 is independently selected from hydrogen and Ci-C6alkyl. Preferably, each R6 is independently selected from hydrogen and methyl.
Each R7 is independently selected from the group consisting of Ci-C6alkyl, -S(0)2R15, -C(0)R15, - C(0)0R15 and -C(0)NR16R17. Preferably, each R7 is independently selected from the group consisting of Ci-C6alkyl, -C(0)R15 and -C(0)NR16R17. More preferably, each R7 is Ci-C6alkyl. Most preferably, each R7 is methyl.
Each R7a is independently selected from the group consisting of -S(0)2R15, -C(0)R15, -C(0)0R15 - C(0)NR16R17 and -C(0)NR6R15a. Preferably, each R7a is independently -C(0)R15 or -C(0)NR16R17.
R7b and R7c are independently selected from the group consisting of Ci-C6alkyl, -S(0)2R15, -C(0)R15, - C(0)0R15, -C(0)NR16R17 and phenyl, and wherein said phenyl is optionally substituted by 1 , 2 or 3 R9 substituents, which may be the same or different. Preferably, R7b and R7c are independently selected from the group consisting of Ci-C6alkyl, -C(0)R15 and -C(0)NR16R17. More preferably, R7b and R7c are Ci-C6alkyl. Most preferably, R7b and R7c are methyl.
Alternatively, R7b and R7c together with the nitrogen atom to which they are attached form a 4- to 6- membered heterocyclyl ring which optionally comprises one additional heteroatom individually selected from N, O and S. Preferably, R7b and R7c together with the nitrogen atom to which they are attached form a 5- to 6-membered heterocyclyl ring which optionally comprises one additional heteroatom individually selected from N and O. More preferably, R7b and R7c together with the nitrogen atom to which they are attached form an pyrrolidyl, oxazolidinyl, imidazolidinyl, piperidyl, piperazinyl or morpholinyl group.
Each R9 is independently selected from the group consisting of halogen, cyano, -OH, -N(R6)2, Ci-C4alkyl, Ci-C4alkoxy, Ci-C4haloalkyl and Ci-C4haloalkoxy. Preferably, each R9 is independently selected from the group consisting of halogen, cyano, -N(R6)2, Ci-C4alkyl, Ci-C4alkoxy, Ci-C4haloalkyl and Ci- C4haloalkoxy. More preferably, each R9 is independently selected from the group consisting of halogen, Ci-C4alkyl, Ci-C4alkoxy and Ci-C4haloalkyl. Even more preferably, each R9 is independently selected from the group consisting of halogen and Ci-C4alkyl.
Preferably E is -C(0)OR10, -C(0)NHS(0)2R12, -C(0)R24, -P(0)(R13)(OR10); or
C(0)NR6(CR6 2)qC(0)(0R1°).
X is selected from the group consisting of C3-C6cycloalkyl, phenyl, a 5- or 6- membered heteroaryl, which comprises 1 , 2, 3 or 4 heteroatoms individually selected from N, O and S, and a 4- to 6- membered heterocyclyl, which comprises 1 , 2 or 3 heteroatoms individually selected from N, O and S, and wherein said cycloalkyl, phenyl, heteroaryl or heterocyclyl moieties are optionally substituted by 1 or 2 substituents, which may be the same or different, selected from R9, and wherein the aforementioned CR1R2, Q and Z moieties may be attached at any position of said cycloalkyl, phenyl, heteroaryl or heterocyclyl moieties.
Preferably, X is selected from the group consisting of phenyl and a 4- to 6- membered heterocyclyl, which comprises 1 or 2 heteroatoms individually selected from N and O, and wherein said phenyl or heterocyclyl moieties are optionally substituted by 1 or 2 substituents, which may be the same or different, selected from R9, and wherein the aforementioned CR1R2, Q and Z moieties may be attached at any position of said phenyl or heterocyclyl moieties.
More preferably, X is a 4- to 6- membered heterocyclyl, which comprises 1 or 2 heteroatoms individually selected from N and O, and wherein said heterocyclyl moieties is optionally substituted by 1 or 2 substituents, which may be the same or different, selected from R9, and wherein the aforementioned CR1R2, Q and Z moieties may be attached at any position of said heterocyclyl moiety.
In one embodiment, X is a 5-membered heterocyclyl, which comprises 1 heteroatom, wherein said heteroatom is N, and wherein the aforementioned CR1R2, Q and Z moieties may be attached at any position of said heterocyclyl moiety. Preferably, X is a 5-membered heterocyclyl, which comprises 1 heteroatom, wherein said heteroatom is N, and wherein the aforementioned CR1R2 and Q moieties are attached adjacent to the N atom and the Z moiety is attached to the N atom
In another embodiment, X is phenyl optionally substituted by 1 or 2 substituents, which may be the same or different, selected from R9, and wherein the aforementioned CR1R2, Q and Z moieties may be attached at any position of said phenyl moiety. Preferably, X is phenyl and the aforementioned CR1R2 and Q moieties are attached in a postion para to the Z moiety.
n is 0 or 1 . Preferably, n is 0. Preferably, Z is selected from the group consisting of hydrogen, OH, Ci-C6alkyl, Ci-C6haloalkyl, Ci- Cehydroxyalkyl, -C(0)OR10, -C(0)NH0R11 , -0C(0)NH0R11 , -NR6C(0)NH0R11 , -C(0)NHS(0)2R12, - 0C(0)NHS(0)2R12, -NR6C(0)NHS(0)2R12, -S(0)20R10, -0S(0)20R10, -NR6S(0)20R10, -NR6S(0)OR10, -NHS(0)2R14, -S(0)OR10, -OS(0)OR10, -S(0)2NHC(0)R18, -S(0)2NHS(0)2R12, -0S(0)2NHS(0)2R12, - 0S(0)2NHC(0)R18, -NR6S(0)2NHC(0)R18, -N(0H)C(0)R15, -0NHC(0)R15, -NR6S(0)2NHS(0)2R12, - P(0)(R13)(OR10), -P(0)H(OR10), -0P(0)(R13)(0R1°) and -NR6P(0)(R13)(OR10).
More preferably, Z is selected from the group consisting of hydrogen, Ci-C6alkyl, Ci-C6haloalkyl, Ci- Cehydroxyalkyl, Ci-C6alkoxy, -C(0)OR10, -C(0)NH0R11 , -C(0)NHS(0)2R12, -S(0)2OR10, -OS(0)2OR10, -NR6S(0)20R10, -NHS(0)2R14, -S(0)OR10 and -P(0)(R13)(OR10).
Even more preferably Z is selected from the group consisting of hydrogen, Ci-C6alkyl, Ci-C6haloalkyl, Ci-Cehydroxyalkyl, Ci-C6alkoxy, -C(0)OR10, -C(0)NHS(0)2R12, -S(0)2OR10, and -P(0)(R13)(OR10).
Even more preferably still Z is selected from the group consisting of hydrogen, Ci-C6alkyl, Ci- C6haloalkyl, Ci-C6hydroxyalkyl and Ci-C6alkoxy,.
Most preferably Z is hydrogen, Ci-C6alkyl or Ci-C6hydroxyalkyl, especially hydrogen, methyl or CH2OH.
R10 is selected from the group consisting of hydrogen, Ci-C6alkyl, phenyl and benzyl, and wherein said phenyl or benzyl are optionally substituted by 1 , 2 or 3 R9 substituents, which may be the same or different. Preferably, R10 is selected from the group consisting of hydrogen, Ci-C6alkyl, phenyl and benzyl. More preferably, R10 is selected from the group consisting of hydrogen and Ci-C6alkyl. Most preferably, R10 is hydrogen.
R11 is selected from the group consisting of hydrogen, Ci-C6alkyl and phenyl, and wherein said phenyl is optionally substituted by 1 , 2 or 3 R9 substituents, which may be the same or different. Preferably, R11 is selected from the group consisting of hydrogen, Ci-C6alkyl and phenyl. More preferably, R11 is selected from the group consisting of hydrogen and Ci-C6alkyl. Even more preferably, R11 is Ci-C6alkyl. Most preferably, R11 is methyl.
R12 is selected from the group consisting of Ci-C6alkyl, Ci-C6haloalkyl, Ci-C6alkoxy, -OH, -N(R6)2 and phenyl, and wherein said phenyl is optionally substituted by 1 , 2 or 3 R9 substituents, which may be the same or different. Preferably, R12 is selected from the group consisting of Ci-C6alkyl, Ci-C6haloalkyl, Ci- C6alkoxy, -OH, -N(R6)2 and phenyl. More preferably, R12 is selected from the group consisting of Ci- Cealkyl, Ci-C6haloalkyl and -N(R6)2. Even more preferably, R12 is selected from the group consisting of methyl, -N(Me)2 and trifluoromethyl. Most preferably, R12 is methyl.
R13 is selected from the group consisting of -OH, Ci-C6alkyl, Ci-C6alkoxy, Ci-C6haloalkoxy, -O- propargyl, -O-allyl and phenyl. Preferably R13 is selected from the group consisting of Ci-C6alkyl, Ci- C6alkoxy, Ci-C6haloalkoxy, -O-propargyl or -O-allyl. More preferably, R13 is selected from the group consisting of -OH and Ci-C6alkoxy. Even more preferably, R13 is selected from the group consisting of methyl, ethyl, propyl, isopropyl, isobutyl, -O propargyl and -O-allyl.
R14 is Ci-C6haloalkyl. Preferably, R14 is trifluoromethyl.
R15 is selected from the group consisting of Ci-C6alkyl and phenyl, and wherein said phenyl is optionally substituted by 1 , 2 or 3 R9 substituents, which may be the same or different. Preferably, R15 is selected from the group consisting of Ci-C6alkyl and phenyl. More preferably, R15 is Ci-C6alkyl. Most preferably R15 is methyl.
R15a is phenyl, wherein said phenyl is optionally substituted by 1 , 2 or 3 R9 substituents, which may be the same or different. Preferably, R15a is phenyl optionally substituted by 1 R9 substituent. More preferably, R15a is phenyl.
R16 and R17 are independently selected from the group consisting of hydrogen and Ci-C6alkyl. Preferably, R16 and R17 are independently selected from the group consisting of hydrogen and methyl.
Alternatively, R16 and R17 together with the nitrogen atom to which they are attached form a 4- to 6- membered heterocyclyl ring which optionally comprises one additional heteroatom individually selected from N, O and S. Preferably, R16 and R17 together with the nitrogen atom to which they are attached form a 5- to 6-membered heterocyclyl ring which optionally comprises one additional heteroatom individually selected from N and O. More preferably, R16 and R17 together with the nitrogen atom to which they are attached form an pyrrolidyl, oxazolidinyl, imidazolidinyl, piperidyl, piperazinyl or morpholinyl group.
R18 is selected from the group consisting of hydrogen, Ci-C6alkyl, Ci-C6haloalkyl, Ci-C6alkoxy, -N(R6)2 and phenyl, and wherein said phenyl is optionally substituted by 1 , 2 or 3 R9 substituents, which may be the same or different. Preferably, R18 is selected from the group consisting of hydrogen, Ci-C6alkyl, Ci-C6haloalkyl, Ci-C6alkoxy, -N(R6)2 and phenyl. More preferably, R18 is selected from the group consisting of hydrogen, Ci-C6alkyl and Ci-C6haloalkyl. Further more preferably, R18 is selected from the group consisting of Ci-C6alkyl and Ci-C6haloalkyl. Most preferably, R18 is methyl or trifluoromethyl. r is 0, 1 or 2. Preferably, r is 0 or 2.
There is also provided a process for the preparation of compounds of formula (I):
Figure imgf000015_0001
Wherein Q, Z, X, n, R1 , R2, R3, R4, R5 and E are as defined herein;
It should be understood that compounds of formula (I) may exist/be manufactured in‘procidal form’, wherein they comprise a group‘G’. Such compounds are referred to herein as compounds of formula (l-IV).
G is a group which may be removed in a plant by any appropriate mechanism including, but not limited to, metabolism and chemical degradation to give a compound of formula (l-l), (l-V) or (l-VI) wherein E contains an acidic proton, for example see the scheme below: Whilst such G groups may be considered as‘procidal’, and thus yield active herbicidal compounds once removed, compounds comprising such groups may also exhibit herbicidal activity in their own right. In such cases in a compound of formula (l-IV), E-G may include but is not limited to, any one of (G1) to (G7) below and J indicates the point of attachment to the remaining part of a compound of formula (I):
Figure imgf000016_0001
In embodiments where E-G is (G1) to (G7), G, R19, R20, R21 , R22 and R23 are defined as follows:
G is Ci-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, -C(R21R22)0C(0)R19, phenyl or phenyl-Ci-C4alkyl-, wherein said phenyl moiety is optionally substituted by 1 to 5 substituents independently selected from halo, cyano, nitro, Ci-C6alkyl, Ci-C6haloalkyl or Ci-C6alkoxy.
R19 is Ci-C6alkyl or phenyl,
R20 is hydroxy, Ci-C6alkyl, Ci-C6alkoxy or phenyl,
R21 is hydrogen or methyl,
R22 is hydrogen or methyl,
R23 is hydrogen or Ci-C6alkyl. The compounds in Tables 1 to 9 below illustrate the compounds of the invention. The skilled person would understand that the compounds of formula (I) may exist as an agronomically acceptable salt, a zwitterion or an agronomically acceptable salt of a zwitterion as described hereinbefore. Table 1 :
This table discloses 3 specific compounds of the formula (T-1):
Figure imgf000017_0001
Wherein m, Q, R3, R4, R5 and Z are as defined in Table 1 , R1 and R2 are hydrogen and n is 0.
Compound R3 R4 R5 Z m Q
number
1.001 H H H -H 0 -
1.002 H H H -CH2OH 0
1.003 H H H -CH2OMe 0
Table 2:
This table discloses 3 specific compounds of the formula (T-2):
Figure imgf000017_0002
Wherein m, Q, R3, R4, R5 and Z are as defined in Table 2, R1 and R2 are hydrogen and n is 0.
Compound R3 R4 R5 Z m Q
number _
2.001 H H H -H 1 CH2
2.002 H H H -CH2OH 1 CH2
2.003 H H H -CH2OMe 1 CH2
Table 3:
This table discloses 3 specific compounds of the formula (T-3):
Figure imgf000017_0003
wherein m, Q, R3, R4, R5 and Z are as defined in Table 3, R1 and R2 are hydrogen and n is 0.
Compound R3 R4 R5 Z m Q
number _
3.001 H H H -H 2 CH2CH2
3.002 H H H -CH2OH 2 CH2CH2 Compound R3 R4 R5 Z m Q number
Figure imgf000018_0001
Table 4:
This table discloses 3 specific compounds of the formula (T-4):
Figure imgf000018_0002
wherein m, Q, R3, R4, R5 and Z are as defined above in Table 1 , R1 and R2 are hydrogen and n is 0.
Table 5:
This table discloses 3 specific compounds of the formula (T-5):
Figure imgf000018_0003
wherein m, Q, R3, R4, R5 and Z are as defined above in Table 2, R1 and R2 are hydrogen and n is 0.
Table 6:
This table discloses 3 specific compounds of the formula (T-6):
Figure imgf000018_0004
wherein m, Q, R3, R4, R5 and Z are as defined above in Table 3, R1 and R2 are hydrogen and n is 0.
Table 7:
This table discloses 3 specific compounds of the formula (T-7):
Figure imgf000018_0005
wherein m, Q, R3, R4, R5 and Z are as defined above in Table 1 , R1 and R2 are hydrogen and n is 0. Table 8:
This table discloses 3 specific compounds of the formula (T-8):
Figure imgf000019_0001
wherein m, Q, R3, R4, R5 and Z are as defined above in Table 2, R1 and R2 are hydrogen and n is 0.
Table 9:
This table discloses 3 specific compounds of the formula (T-9):
Figure imgf000019_0002
wherein m, Q, R3, R4, R5 and Z are as defined above in Table 3, R1 and R2 are hydrogen and n is 0.
The compounds of formula (I) may be prepared by the alkylation of compounds of formula (X), wherein R3, R4, R5 and E are as defined for compounds of formula (I), with a suitable alkylating agent of formula (W), wherein R1 , R2, Q, X, n and Z are as defined for compounds of formula (I) and LG is a suitable leaving group, for example, halide or pseudohalide such as triflate, mesylate or tosylate, in a suitable solvent at a suitable temperature, as described in reaction scheme 1 . Example conditions include stirring a compound of formula (X) with an alkylating agent of formula (W) in a solvent, or mixture of solvents, such as acetone, dichloromethane, dichloroethane, A/,A/-dimethylformamide, acetonitrile, 1 ,4-dioxane, water, acetic acid or trifluoroacetic acid at a temperature between -78°C and 150°C. Alkylating agents of formula (W) are commercially avaialable or are known in the literature and may include, but are not limited to, iodomethane, bromomethane, chloromethane, dimethylsulfate, iodoethane, bromoethane, chloroethane, diethylsulfate, 2-methoxyethyl trifluoromethanesulfonate, 2-bromoethyl methyl ether, 2- iodoethyl methyl ether, benzyl bromide, benzyl chloride, benzyl iodide, 2-bromoethanol, 2-iodoethanol, 2,2-difluoroethyl trifluoromethanesulfonate, 2-bromoethylamine hydrobromide, bromoacetic acid, methyl bromoacetate, 3-bromopropionoic acid, methyl 3-bromopropionate, 2-bromo-A/- methoxyacetamide, sodium 2-bromoethanesulphonate, 2,2-dimethylpropyl 2- (trifluoromethylsulfonyloxy)ethanesulfonate, 2-bromo-A/-methanesulfonylacetamide, 3-bromo-A/- methanesulfonylpropanamide, dimethoxyphosphorylmethyl trifluoromethanesulfonate, dimethyl 3- bromopropylphosphonate, 3-chloro-2, 2-dimethyl-propanoic acid and diethyl 2-bromoethylphosphonate. Such alkylating agents and related compounds are either known in the literature or may be prepared by known literature methods. Compounds of formula (I) which may be described as esters of /V-alkyl acids, which include, but are not limited to, esters of carboxylic acids, phosphonic acids, phosphinic acids, sulfonic acids and sulfinic acids, may optionally be subsequently partially or fully hydrolysed by treament with a suitable reagent, for example, aqueous hydrochloric acid or trimethylsilyl bromide, in a suitable solvent at a suitable temperature between 0°C and 100°C.
Reaction scheme 1
Figure imgf000020_0001
formula (X)
vy formula (I)
Additonally, compounds of formula (I) may be prepared by reacting compounds of formula (X), wherein R3, R4, R5 and E are as defined for compounds of formula (I), with a suitably activated electrophilic alkene of formula (B), wherein Z is -C(0)R15, -C(0)NR16R17, -C(0)OR10, -CHO, nitro, cyano, - S(0)20R10, -S(0)2NR16R17, -S(0)rR15, -P(0)(R13)(OR10) and R1 , R2, R1a, R10, R13, R15, R16 and R17 are as defined for compounds of formula (I), in a suitable solvent at a suitable temperature. Compounds of formula (B) are known in the literature, or may be prepared by known methods. Example reagents include, but are not limited to, acrylic acid, methacrylic acid, crotonic acid, 3,3-dimethylacrylic acid, methyl acrylate, ethene sulfonic acid, isopropyl ethylenesulfonate, 2,2-dimethylpropyl ethenesulfonate and dimethyl vinylphosphonate. The direct products of these reactions, which may be described as esters of N-alkyl acids, which include, but are not limited to, esters of carboxylic acids, phosphonic acids, phosphinic acids, sulfonic acids and sulfinic acids, may optionally be subsequently partially or fully hydrolysed by treament with a suitable reagent in a suitable solvent at a suitable temperature, as described in reaction scheme 2.
Reaction scheme 2
Figure imgf000020_0002
In a related reaction compounds of formula (I), wherein Q is C(R1aR2b), m is 1 , 2 or 3, n=0 and Z is - S(0)20H, -0S(0)20H or -NR6S(0)20H, may be prepared by the reaction of compounds of formula (X), wherein R3, R4, R5 and E are as defined for compounds of formula (I), with a cyclic alkylating agent of formula (E), (F) or (AF), wherein Ya is C(R1aR2b), O or NR6 and R1 , R2, R1a, R2b and R6 are as defined for compounds of formula (I), in a suitable solvent at a suitable temperature, as described in reaction scheme 3. Suitable solvents and suitable temperatures are as previously described. An alkylating agent of formula (E) or (F) may include, but is not limited to, 1 ,3-propanesultone, 1 ,4-butanesultone, ethylenesulfate, 1 ,3-propylene sulfate and 1 ,2,3-oxathiazolidine 2,2-dioxide. Such alkylating agents and related compounds are either known in the literature or may be prepared by known literature methods. Reaction scheme 3
Figure imgf000021_0001
formula (E), Where formula (F), Where m=2
m=1 and n=0 and n=0
O
Figure imgf000021_0002
or O— S=0
Figure imgf000021_0003
1 2b formula (I), wherein
R
Figure imgf000021_0005
is 1 , 2 or 3, n=0 and
2 1 a
R R = S03H, OSOJH or
NR6SO3H
formula (AF)
Where m=1 and
n=0
A compound of formula (I), wherein m is 0, n is 0 and Z is -S(0)20H, may be prepared from a compound of formula (I), wherein m is 0, n is 0 and Z is C(0)OR10, by treatment with trimethylsilylchlorosulfonate in a suitable solvent at a suitable temperature, as described in reaction scheme 4. Preferred conditions include heating the carboxylate precursor in neat trimethylsilylchlorosulfonate at a temperature between 25°C and 150°C. Reaction scheme 4
Figure imgf000021_0004
formula (I), wherein formula (I), wherein
m=0, n=0 m=0, n=0 and Z=C(0)0R10 and Z=S03H
Furthermore, compounds of formula (I) may be prepared by reacting compounds of formula (X), wherein R3, R4, R5 and E are as defined for compounds of formula (I), with a suitable alcohol of formula (WW), wherein R1 , R2, Q, X, n and Z are as defined for compounds of formula (I), under Mitsunobu-type conditions such as those reported by Petit et al, Tet. Lett. 2008, 49 (22), 3663. Suitable phosphines include triphenylphosphine, suitable azodicarboxylates include diisopropylazodicarboxylate and suitable acids include fluoroboric acid, triflic acid and bis(trifluoromethylsulfonyl)amine, as described in reaction scheme 5. Alcohols of formula (WW) are either known in the literature or may be prepared by known literature methods.
Reaction scheme 5
Figure imgf000022_0001
Acid, Ph3P
Compounds of formula (I) may also be prepared by reacting compounds of formula (C), wherein R3, R4, R5 and E are as defined for compounds of formula (I), with a hydrazine of formula (D), wherein R1 , R2, Q, X, n and Z are as defined for compounds of formula (I), in a suitable solvent or mixture of solvents, in the presence of a suitable acid at a suitable temperature, between -78°C and 150°C, as described in reaction scheme 6. Suitable solvents, or mixtures thereof, include, but are not limited to, alcohols, such as methanol, ethanol and isopropanol, water, aqueous hydrochloric acid, aqueous sulfuric acid, acetic acid and trifluoroacetic acid. Hydrazine compounds of formula (D), for example 2,2-dimethylpropyl 2- hydrazinoethanesulfonate, are either known in the literature or may be prepared by known literature procedures.
Reaction scheme 6
Figure imgf000022_0002
Compounds of formula (C) may be prepared by reacting compounds of formula (G), wherein R3, R4, R5 and E are as defined for compounds of formula (I), with an oxidising agent in a suitable solvent at a suitable temperature, between -78°C and 150°C, optionally in the presence of a suitable base, as described in reaction scheme 7. Suitable oxidising agents include, but are not limited to, bromine and suitable solvents include, but are not limited to alcohols such as methanol, ethanol and isopropanol. Suitable bases include, but are not limited to, sodium bicarbonate, sodium carbonate, potassium bicarbonate, potassium carbonate and potassium acetate. Similar reactions are known in the literature (for example Hufford, D. L; Tarbell, D. S.; Koszalka, T. R. J. Amer. Chem. Soc., 1952, 3014). Furans of formula (G) are known in the literature or may be prepared using literature methods.
Reaction scheme 7
Figure imgf000023_0002
Base
Figure imgf000023_0001
formula (C)
R' = H, C C4alkyl,
C1-C4alkyl carbonyl
Compounds of formula (X), wherein E is a carboxylic acid and R3, R4 and R5 are as defined previously, are well known in the literature, or may be prepared by known methods. See, for example, Atkinson, C. M., Rodway, R. E., J. Chem. Soc., 1 , 1959, Fischer et al, WO 2006000333, Guiles et al, WO 2009015208, O'Hara, F., Blackmond, D. G„ Baran, P. S„ J. Am. Chem. Soc., 135(32), 2013, 12122, Labelle et al, WO 2015153498, Johnston, A. J. S., Ling, K. B., Sale, D., Lebrasseur, N., Larrosa, I., Org. Lett., 18(23), 6094, 2016, Elbert, B. L., Farley, A. J. M., Gorman, T. W., Johnson, T. C., Genicot, C., Lallemand, B., Pasau, P., Flasz, J., Castro, J. L., MacCoss, M., Paton, R. S., Schofield, C. J., Smith, M. D., Willis, M. C., Dixon, D. J., Chem. Eur. J., 23(59), 14733, 2017, Beaumier et al, WO 2018096159 and Sparks et al, WO 2018125800.
Compounds of formula (X), wherein E is -C(0)R24, -C(0)NH0R11 , -C(0)NHCN, -C(0)NR6(CR6 2)qZ, - C(0)NHS(0)2R12, and R3, R4, R5, R6, R11 , R12, R24, q and Z are as defined previously, may be prepared from a compound of formula (J), wherein T is a halogen or T is an ester or activated ester, for example -OCi-C6alkyl, pentafluorophenol, p-nitrophenol, 2,4,6-trichlorophenol, -0C(0)R“ or -0S(0)2R ", and R " is, for example, Ci-C6alkyl, Ci-C6haloalkyl or optionally substituted phenyl and R3, R4 and R5 are as defined previously, by reacting with an amine, for example but not limited to, of formula -R24, NH2OR11 , NH2CN, NHR6(CR6 2)qZ, NH2S(0)2R12, in a suitable solvent or mixture of solvents, optionally in the presence of a suitable base at a suitable temperature between -78°C and 200°C, as described in reaction scheme 8. Suitable bases include, but are not limited to, triethylamine, pyridine, N,N- diisopropylethylamine, an alkali metal carbonate, such as sodium carbonate, potassium carbonate or cesium carbonate, or an alkali metal alkoxide, such as sodium methoxide. Suitable solvents include, but are not limited to, dichloromethane, A/,A/-dimethylformamide, THF ortoluene. Compounds of formula (J) are either known in the literature or may be prepared by known literature methods or may be commercially available. formula (J) formula (X), wherein E is
-C(0)R24, -C(0)NH0R1 1 ,
-C(0)NHCN, -C(0)NR6(CR6 2)qZ,
-C(0)NHS(0)2R12
Compounds of formula (X), wherein E is -C(0)R24, -C(0)NH0R11, -C(0)NHCN, -C(0)NR6(CR6 2)qZ, - C(0)NHS(0)2R12, and R3, R4, R5, R6, R11 , R12, R24, q and Z are as defined previously, may be prepared from a carboxylic acid of formula (L) by classical amide bond forming reactions which are very well known in the literature, as described in reaction scheme 9. Such reactions include, but are not limited to, reacting a carboxylic acid of formula (L) with an amine, for example, of formula -R24, NH2OR11 , NH2CN, NHR6(CR62)qZ or NH2S(0)2R12, wherein R6, R11, R12, R24, q and Z are as defined for compounds of formula (I), in the presence of a suitable coupling agent in a suitable solvent or mixture of solvents, at a suitable temperature between -78°C and 200°C, and optionally in the presence of a suitable base. Suitable coupling reagents include, but are not limited to, a carbodiimide, for example dicyclohexylcarbodiimide or 1 -ethyl-3-[3-dimethylaminopropyl]carbodiimide hydrochloride, a phosphonic anhydride, for example 2,4,6-tripropyM ,3,5,2,4,6-trioxatriphosphorinane-2,4,6-trioxide, or a phosphonium salt, for example benzotriazol-1 -yloxy(tripyrrolidin-1 -yl)phosphonium hexafluorophosphate. Suitable solvents include, but are not limited to, dichloromethane, N,N- dimethylformamide, THF or toluene, and suitable bases include, but are not limited to, triethylamine, pyridine and A/,A/-diisopropylethylamine. Compounds of formula (L) are either known in the literature or may be prepared by known literature methods or may be commercially available.
Reaction scheme 9
Figure imgf000024_0001
formula (L) formula (X), wherein E is
-C(0)R24, -C(0)NH0R11 ,
-C(0)NHCN, -C(0)NR6(CR6 2)qZ,
-C(0)NHS(0)2R12 Compounds of formula (X), wherein E is -P(0)(R13)(OR10) or -P(0)H(OR10) and R3, R4 and R5 are as defined previously, may be prepared by reacting a compound of formula (P) with a reagent of formula P(R13)(OR10)2, P(O)(R13)(OR10)H and H3PO2 in an appropriate solvent, at an appropriate temperature, and optionally in the presence of an appropriate base and/or reagent such as tetrabutyl ammonium iodide, as described in reaction scheme 10. The direct product of this reaction may then be oxidised to a compound of formula (N) and, optionally, subsequently or partially hydrolysed to afford compounds of formula (X). Example oxidants include, but are not limited to, 2,3-dichloro-5,6-dicyano-1 ,4- benzoquinone, tetrachloro-p-benzoquinone, potassium permanganate, manganese dioxide, 2, 2,6,6- tetramethyl-1 -piperidinyloxy and bromine, and example hydrolysis conditions include treatment with aqueous hydrochloric acid or trimethylsilyl bromide, in a suitable solvent at a suitable temperature between 0°C and 100°C. Similar reactions are known in the literature, see for example Butkevicha, A. N., Sednevb, M. V., Shojaeia, H., Belova, V. N., Hella, S. W„ Org. Lett., 20, 1261 , 2018.
Reaction scheme 10
Figure imgf000025_0001
formula (X), wherein E is formula (N), wherein E is
-P(0)(R13)(0H) or -P(0)(R13)(0R10) or
-P(0)(0H)H -P(0)(0R1 °)H
The compounds according to the invention can be used as herbicidal agents in unmodified form, but they are generally formulated into compositions in various ways using formulation adjuvants, such as carriers, solvents and surface-active substances. 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 and WHO Specifications for Pesticides, United Nations, First Edition, Second Revision (2010). For water-soluble compounds, soluble liquids, water-soluble concentrates or water soluble granules are preferred. Such formulations can either be used directly or diluted prior to use. The dilutions can be made, for example, with water, liquid fertilisers, 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. 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 can 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. 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, A/,A/-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, 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, tetrahydrofurfuryl alcohol, hexanol, octanol, ethylene glycol, propylene glycol, glycerol, A/-methyl-2-pyrrolidone and the like.
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.
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 dodecylbenzenesulfonate; 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 alkylnaphthalenesulfonates, such as sodium dibutylnaphthalenesulfonate; dialkyl esters of sulfosu coin ate 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 be used in pesticidal formulations include crystallisation inhibitors, viscosity modifiers, suspending agents, dyes, anti-oxidants, foaming agents, light absorbers, mixing auxiliaries, antifoams, complexing agents, neutralising or pH-modifying substances and buffers, corrosion inhibitors, fragrances, wetting agents, take-up enhancers, micronutrients, plasticisers, glidants, lubricants, dispersants, thickeners, antifreezes, microbicides, and liquid and solid fertilisers.
The compositions according to the invention can 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 mixture to be applied. For example, the oil additive can be added to a spray tank in the desired concentration after a 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, 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. Preferred oil additives comprise alkyl esters of C8-C22 fatty acids, especially the methyl derivatives of C12-C18 fatty acids, for example the methyl esters of lauric acid, palmitic acid and oleic acid (methyl laurate, methyl palmitate and methyl oleate, respectively). Many oil derivatives are known from the Compendium of Herbicide Adjuvants, 10th Edition, Southern Illinois University, 2010.
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. The inventive compositions generally comprise from 0.1 to 99 % by weight, especially from 0.1 to 95 % by weight, of compounds of the present invention 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 may preferably be formulated as concentrates, the end user will normally employ dilute formulations.
The rates of application vary within wide limits and depend on the nature of the soil, the method of application, the crop plant, the pest to be controlled, the prevailing climatic conditions, and other factors governed by the method of application, the time of application and the target crop. As a general guideline compounds may be applied at a rate of from 1 to 2000 l/ha, especially from 10 to 1000 l/ha.
Preferred formulations can have the following compositions (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 composition of the present may further comprise at least one additional pesticide. For example, the compounds according to the invention can also be used in combination with other herbicides or plant growth regulators. In a preferred embodiment the additional pesticide is a herbicide and/or herbicide safener.
Thus, compounds of formula (I) can be used in combination with one or more other herbicides to provide various herbicidal mixtures. Specific examples of such mixtures include (wherein “I” represents a compound of formula (I)):- 1 + acetochlor; I + acifluorfen (including acifluorfen-sodium); I + aclonifen; I + alachlor; I + alloxydim; I + ametryn; I + amicarbazone; I + amidosulfuron; I + aminocyclopyrachlor ; I + aminopyralid; I + amitrole; I + asulam; I + atrazine; I + bensulfuron (including bensulfuron-methyl); I + bentazone; I + bicyclopyrone; I + bilanafos; I + bifenox; I + bispyribac-sodium; I + bixlozone; I + bromacil; I + bromoxynil; I + butachlor; I + butafenacil; I + cafenstrole; I + carfentrazone (including carfentrazone- ethyl); cloransulam (including cloransulam-methyl); I + chlorimuron (including chlorimuron-ethyl); I + chlorotoluron; I + cinosulfuron; I + chlorsulfuron; I + cinmethylin; I + clacyfos; I + clethodim; I + clodinafop (including clodinafop-propargyl); I + clomazone; I + clopyralid; I + cyclopyranil; I + cyclopyrimorate; I + cyclosulfamuron; I + cyhalofop (including cyhalofop-butyl); I + 2,4-D (including the choline salt and 2- ethylhexyl ester thereof); I + 2,4-DB; I + daimuron; I + desmedipham; I + dicamba (including the aluminum, aminopropyl, bis-aminopropylmethyl, choline, dichloroprop, diglycolamine, dimethylamine, dimethylammonium, potassium and sodium salts thereof); I + diclofop-methyl; I + diclosulam; I + diflufenican; I + difenzoquat; I + diflufenican; I + diflufenzopyr; I + dimethachlor; I + dimethenamid-P; I + diquat dibromide; I + diuron; I + esprocarb; I + ethalfluralin; I + ethofumesate; I + fenoxaprop (including fenoxaprop-P-ethyl); I + fenoxasulfone; I + fenquinotrione; I + fentrazamide; I + flazasulfuron; I + florasulam; I + florpyrauxifen; I + fluazifop (including fluazifop-P-butyl); I + flucarbazone (including flucarbazone-sodium);; I + flufenacet; I + flumetralin; I + flumetsulam; I + flumioxazin; I + flupyrsulfuron (including flupyrsulfuron-methyl-sodium);; I + fluroxypyr (including fluroxypyr-meptyl);; I + fluthiacet- methyl; I + fomesafen; I + foramsulfuron; I + glufosinate (including the ammonium salt thereof); I + glyphosate (including the diammonium, isopropylammonium and potassium salts thereof); I + halauxifen (including halauxifen-methyl); I + halosulfuron-methyl; I + haloxyfop (including haloxyfop-methyl); I + hexazinone; I + hydantocidin; I + imazamox; I + imazapic; I + imazapyr; I + imazaquin; I + imazethapyr; I + indaziflam; I + iodosulfuron (including iodosulfuron-methyl-sodium); I + iofensulfuron; I + iofensulfuron-sodium; I + ioxynil; I + ipfencarbazone; I + isoproturon; I + isoxaben; I + isoxaflutole; I + lactofen; I + lancotrione; I + linuron; I + MCPA; I + MCPB; I + mecoprop-P; I + mefenacet; I + mesosulfuron; I + mesosulfuron-methyl; I + mesotrione; I + metamitron; I + metazachlor; I + methiozolin; I + metobromuron; I + metolachlor; I + metosulam; I + metoxuron; I + metribuzin; I + metsulfuron; I + molinate; I + napropamide; I + nicosulfuron; I + norflurazon; I + orthosulfamuron; I + oxadiargyl; I + oxadiazon; I + oxasulfuron; I + oxyfluorfen; I + paraquat dichloride; I + pendimethalin; I + penoxsulam; I + phenmedipham; I + picloram; I + picolinafen; I + pinoxaden; I + pretilachlor; I + primisulfuron-methyl; I + prodiamine; I + prometryn; I + propachlor; I + propanil; I + propaquizafop; I + propham; I + propyrisulfuron, I + propyzamide; I + prosulfocarb; I + prosulfuron; I + pyraclonil; I + pyraflufen (including pyraflufen-ethyl): I + pyrasulfotole; I + pyrazolynate, I + pyrazosulfuron-ethyl; I + pyribenzoxim; I + pyridate; I + pyriftalid; I + pyrimisulfan, I + pyrithiobac-sodium; I + pyroxasulfone; I + pyroxsulam ; I + quinclorac; I + quinmerac; I + quizalofop (including quizalofop-P-ethyl and quizalofop-P-tefuryl),; I + rimsulfuron; I + saflufenacil; I + sethoxydim; I + simazine; I + S-metolachlor; I + sulcotrione; I + sulfentrazone; I + sulfosulfuron; I + tebuthiuron; I + tefuryltrione; I + tembotrione; I + terbuthylazine; I + terbutryn; I + thiencarbazone; I + thifensulfuron; I + tiafenacil; I + tolpyralate; I + topramezone; I + tralkoxydim; I + triafamone; I + triallate; I + triasulfuron; I + tribenuron (including tribenuron-methyl); I + triclopyr; I + trifloxysu Huron (including trifloxysulfuron-sodium); I + trifludimoxazin; I + trifluralin; I + triflusulfu ron; I + tritosulfuron; I + 4-hydroxy-1 -methoxy-5-methyl-3-[4-(trifluoromethyl)-2- pyridyl]imidazolidin-2-one; I + 4-hydroxy-1 ,5-dimethyl-3-[4-(trifluoromethyl)-2-pyridyl]imidazolidin-2-one; I + 5-ethoxy-4-hydroxy-1 -methyl-3-[4-(trifluoromethyl)-2-pyridyl]imidazolidin-2-one; I + 4-hydroxy-1 - methyl-3-[4-(trifluoromethyl)-2-pyridyl]imidazolidin-2-one; I + 4-hydroxy-1 ,5-dimethyl-3-[1 -methyl-5- (trifluoromethyl)pyrazol-3-yl]imidazolidin-2-one; I + (4R)1 -(5-tert-butylisoxazol-3-yl)-4-ethoxy-5-hydroxy-
3-methyl-imidazolidin-2-one; I + 3-[2-(3,4-dimethoxyphenyl)-6-methyl-3-oxo-pyridazine-4- carbonyl]bicyclo[3.2.1 ]octane-2,4-dione; I + 2-[2-(3,4-dimethoxyphenyl)-6-methyl-3-oxo-pyridazine-4- carbonyl]-5-methyl-cyclohexane-1 ,3-dione; I + 2-[2-(3,4-dimethoxyphenyl)-6-methyl-3-oxo-pyridazine-
4-carbonyl]cyclohexane-1 ,3-dione; I + 2-[2-(3,4-dimethoxyphenyl)-6-methyl-3-oxo-pyridazine-4- carbonyl]-5,5-dimethyl-cyclohexane-1 ,3-dione; I + 6-[2-(3,4-dimethoxyphenyl)-6-methyl-3-oxo- pyridazine-4-carbonyl]-2,2,4,4-tetramethyl-cyclohexane-1 ,3,5-trione; I + 2-[2-(3,4-dimethoxyphenyl)-6- methyl-3-oxo-pyridazine-4-carbonyl]-5-ethyl-cyclohexane-1 ,3-dione; I + 2-[2-(3,4-dimethoxyphenyl)-6- methyl-3-oxo-pyridazine-4-carbonyl]-4,4,6,6-tetramethyl-cyclohexane-1 ,3-dione; I + 2-[6-cyclopropyl-2- (3, 4-dimethoxyphenyl)-3-oxo-pyridazine-4-carbonyl]-5-methyl-cyclohexane-1 ,3-dione; I + 3-[6- cyclopropyl-2-(3,4-dimethoxyphenyl)-3-oxo-pyridazine-4-carbonyl]bicyclo[3.2.1 ]octane-2,4-dione; I + 2- [6-cyclopropyl-2-(3,4-dimethoxyphenyl)-3-oxo-pyridazine-4-carbonyl]-5,5-dimethyl-cyclohexane-1 ,3- dione; I + 6-[6-cyclopropyl-2-(3,4-dimethoxyphenyl)-3-oxo-pyridazine-4-carbonyl]-2,2,4,4-tetramethyl- cyclohexane-1 ,3,5-trione; I + 2-[6-cyclopropyl-2-(3,4-dimethoxyphenyl)-3-oxo-pyridazine-4- carbonyl]cyclohexane-1 ,3-dione; I + 4-[2-(3,4-dimethoxyphenyl)-6-methyl-3-oxo-pyridazine-4-carbonyl]- 2,2,6,6-tetramethyl-tetrahydropyran-3,5-dione and I + 4-[6-cyclopropyl-2-(3,4-dimethoxyphenyl)-3-oxo- pyridazine-4-carbonyl]-2,2,6,6-tetramethyl-tetrahydropyran-3,5-dione.
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, Fourteenth Edition, British Crop Protection Council, 2006.
The compound of formula (I) can also be used in mixtures with other agrochemicals such as fungicides, nematicides or insecticides, examples of which are given in The Pesticide Manual.
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).
Compounds of formula (I) of the present invention may also be combined with herbicide safeners. Preferred combinations (wherein T represents a compound of formula (I)) include:- I + benoxacor, I + cloquintocet (including cloquintocet-mexyl); I + cyprosulfamide; I + dichlormid; I + fenchlorazole (including fenchlorazole-ethyl); I + fenclorim; I + fluxofenim; l+ furilazole I + isoxadifen (including isoxadifen-ethyl); I + mefenpyr (including mefenpyr-diethyl); I + metcamifen; I + N-(2-methoxybenzoyl)- 4-[(methylaminocarbonyl)amino] benzenesulfonamide and I + oxabetrinil. Particularly preferred are mixtures of a compound of formula (I) with cyprosulfamide, isoxadifen (including isoxadifen-ethyl), cloquintocet (including cloquintocet-mexyl) and/or N-(2-methoxybenzoyl)-4- [(methyl-aminocarbonyl)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 a lithium, sodium, potassium, calcium, magnesium, aluminium, iron, ammonium, quaternary ammonium, sulfonium or phosphonium salt thereof as disclosed in WO 02/34048, 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) with the safener).
The compounds of formula (I) of this invention are useful as herbicides. The present invention therefore further comprises a method for controlling unwanted plants comprising applying to the said plants or a locus comprising them, an effective amount of a compound of the invention or a herbicidal composition containing said compound. ‘Controlling’ means killing, reducing or retarding growth or preventing or reducing germination. Generally the plants to be controlled are unwanted plants (weeds).‘Locus’ means the area in which the plants are growing or will grow.
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-emergence; post-emergence; application to the seed furrow; no tillage application etc.), the crop plant, the weed(s) 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.
The application is generally made by spraying the composition, typically by tractor mounted sprayer for large areas, but other methods such as dusting (for powders), drip or drench can also be used.
Useful plants in which the composition according to the invention can be used include crops such as cereals, for example barley and wheat, cotton, oilseed rape, sunflower, maize, rice, soybeans, sugar beet, sugar cane and turf.
Crop plants can also include trees, such as fruit trees, palm trees, coconut trees or other nuts. Also included are vines such as grapes, fruit bushes, fruit plants and vegetables.
Crops are to be understood as also including those crops which have been rendered tolerant to herbicides or classes of herbicides (e.g. ALS-, GS-, EPSPS-, PPO-, ACCase- 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®. 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 synthesise 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 to include 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 flavour).
Other useful plants include turf grass for example in golf-courses, lawns, parks and roadsides, or grown commercially for sod, and ornamental plants such as flowers or bushes.
Compounds of formula (I) and compositions of the invention can typically be used to control a wide variety of monocotyledonous and dicotyledonous weed species. Examples of monocotyledonous species that can typically be controlled include Alopecurus myosuroides, Avena fatua, Brachiaria plantaginea, Bromus tectorum, Cyperus esculentus, Digitaria sanguinalis, Echinochloa crus-galli, Lolium perenne, Lolium multiflorum, Panicum miliaceum, Poa annua, Setaria viridis, Setaria faberi and Sorghum bicolor. Examples of dicotyledonous species that can be controlled include Abutilon theophrasti, Amaranthus retroflexus, Bidens pilosa, Chenopodium album, Euphorbia heterophylla, Galium aparine, Ipomoea hederacea, Kochia scoparia, Polygonum convolvulus, Sida spinosa, Sinapis arvensis, Solanum nigrum, Stellaria media, Veronica persica and Xanthium strumarium.
The compounds of formula (I) are also useful for pre-harvest desiccation in crops, for example, but not limited to, potatoes, soybean, sunflowers and cotton. Pre-harvest desiccation is used to desiccate crop foliage without significant damage to the crop itself to aid harvesting.
Compounds/compositions of the invention are particularly useful in non-selective burn-down applications, and as such may also be used to control volunteer or escape crop plants.
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
The Examples which follow serve to illustrate, but do not limit, the invention.
Formulation Examples Wettable powders a) b) c) active ingredients 25 % 50 % 75 %
sodium lignosulfonate 5 % 5 %
sodium lauryl sulfate 3 % 5 %
sodium diisobutylnaphthalenesulfonate 6 % 10 %
phenol polyethylene glycol ether 2 %
(7-8 mol of ethylene oxide)
highly dispersed silicic acid 5 % 10 % 10 %
Kaolin 62 % 27 %
The combination is thoroughly mixed with the adjuvants and the mixture is thoroughly ground in a suitable mill, affording wettable powders that can be diluted with waterto give suspensions of the desired concentration.
Emulsifiable concentrate
active ingredients 10 %
octylphenol polyethylene glycol ether 3 %
(4-5 mol of ethylene oxide)
calcium dodecylbenzenesulfonate 3 %
castor oil polyglycol ether (35 mol of ethylene oxide) 4 %
Cyclohexanone 30 %
xylene mixture 50 %
Emulsions of any required dilution, which can be used in plant protection, can be obtained from this concentrate by dilution with water.
Dusts a) b) c)
Active ingredients 5 % 6 % 4 %
Talcum 95 %
Kaolin 94 %
mineral filler 96 %
Ready-for-use dusts are obtained by mixing the combination with the carrier and grinding the mixture in a suitable mill.
Extruded granules
Active ingredients 15 % sodium lignosulfonate 2 %
carboxymethylcellulose 1 %
Kaolin 82 %
The combination 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.
Coated granules
Active ingredients 8 %
polyethylene glycol (mol. wt. 200) 3 %
Kaolin 89 %
The finely ground combination is uniformly applied, in a mixer, to the kaolin moistened with polyethylene glycol. Non-dusty coated granules are obtained in this manner.
Suspension concentrate
active ingredients 40 %
propylene glycol 10 %
nonylphenol polyethylene glycol ether (15 mol of ethylene oxide) 6 %
Sodium lignosulfonate 10 %
carboxymethylcellulose 1 %
silicone oil (in the form of a 75 % emulsion in water) 1 %
Water 32 %
The finely ground combination is intimately mixed with the adjuvants, giving a suspension concentrate from which suspensions of any desired dilution can be obtained by dilution with water.
Slow Release Capsule Suspension
28 parts of the combination are mixed with 2 parts of an aromatic solvent and 7 parts of toluene diisocyanate/polymethylene-polyphenylisocyanate-mixture (8:1). This mixture is emulsified in a mixture of 1 .2 parts of polyvinylalcohol, 0.05 parts of a defoamer and 51 .6 parts of water until the desired particle size is achieved. To this emulsion a mixture of 2.8 parts 1 ,6-diaminohexane in 5.3 parts of water is added. The mixture is agitated until the polymerization reaction is completed.
The obtained capsule suspension is stabilized by adding 0.25 parts of a thickener and 3 parts of a dispersing agent. The capsule suspension formulation contains 28% of the active ingredients. The medium capsule diameter is 8-15 microns.
The resulting formulation is applied to seeds as an aqueous suspension in an apparatus suitable for that purpose.
List of Abbreviations: Boc = fe/ -butyloxycarbonyl
br = broad
CDC = chloroform-d
CD3OD = methanol-d
°C = degrees Celsius
D2O = water-d
DCM = dichloromethane
d = doublet
dd = double doublet
dt = double triplet
DMSO = dimethylsulfoxide
EtOAc = ethyl acetate
h = hour(s)
HCI = hydrochloric acid
HPLC = high-performance liquid chromatography (description of the apparatus and the methods used for HPLC are given below)
m = multiplet
M = molar
min = minutes
MHz = mega hertz
mL = millilitre
mp = melting point
ppm = parts per million
q = quartet
quin = quintet
rt = room temperature
s = singlet
t = triplet
THF = tetrahydrofuran
LC/MS = Liquid Chromatography Mass Spectrometry
Preparative Reverse Phase HPLC Method: Compounds purified by mass directed preparative HPLC using ES+/ES- on a Waters FractionLynx Autopurification system comprising a 2767 injector/collector with a 2545 gradient pump, two 515 isocratic pumps, SFO, 2998 photodiode array (Wavelength range (nm): 210 to 400), 2424 ELSD and QDa mass spectrometer. A Waters Atlantis T3 5micron 19x10mm guard column was used with a Waters Atlantis T3 OBD, 5micron 30x100mm prep column.
Ionisation method: Electrospray positive and negative: Cone (V) 20.00, Source Temperature (°C) 120, Cone Gas Flow (L/Hr.) 50
Mass range (Da): positive 100 to 800, negative 115 to 800.
The preparative HPLC was conducted using an 11.4 minute run time (not using at column dilution, bypassed with the column selector), according to the following gradient table:
Figure imgf000036_0002
515 pump Oml/min Acetonitrile (ACD)
515 pump 1 ml/min 90% Methanol/10% Water (make up pump)
Solvent A: Water with 0.05% Trifluoroacetic Acid
Solvent B: Acetonitrile with 0.05% Trifluoroacetic Acid
PREPARATION EXAMPLES
Example 1 : Preparation of (1-methylpyridazin-1-ium-4-yl)phosphonic acid bromide A2
S methylpyridazin-1-ium iodide
Figure imgf000036_0001
Methyl iodide (2.33 mL) was added drop wise over 30 minutes to pyridazine (2 g) and stirred at room temperature for 1 hour. The resulting solid was filtered off and washed with iso-hexane to give 1- methylpyridazin-1-ium iodide as a hygroscopic orange solid.
Ή NMR (400MHz, CD3OD) 9.87 (d, 1 H), 9.54 (d, 1 H), 8.72-8.64 (m, 1 H), 8.61-8.53 (m, 1 H), 4.70 (s, 3H)
Step 2: Preparation of (1 -methylpyridazin-1 -ium-4-yl)phosphonic acid bromide A2
To a solution of 1 -methylpyridazin-1 -ium iodide (0.5 g) in acetonitrile (1 1 mL) at 0°C was added trimethyl phosphite (0.29 mL) followed by sodium iodide (0.37 g). This mixture was heated at 40°C for 1 hour. After cooling to room temperature the reaction mixture was quenched with water and extracted twice with dichloromethane. The combined organic extracts were dried over magnesium sulfate and concentrated. The residue was dissolved in chloroform (4.5 mL), cooled to 0°C and bromine (0.128 mL) was added drop wise. The reaction mixture was slowly warmed to room temperature, concentrated and purified by preparative reverse phase HPLC to afford a 5:1 mixture of (1 - methylpyridazin-1 -ium-4-yl)phosphonic acid and methoxy-(1 -methylpyridazin-1 -ium-4-yl)phosphinate which was used directly in the next step. The 5:1 mixture of (1 -methylpyridazin-1 -ium-4-yl)phosphonic acid and methoxy-(1 -methylpyridazin-1 -ium-4-yl)phosphinate (0.2 g) was dissolved in dichloromethane (2 mL) and bromotrimethylsilane (0.43 mL) was added drop wise at room temperature. The reaction mixture was stirred for a further 3 hours at this temperature then concentrated to afford (1 - methylpyridazin-1 -ium-4-yl)phosphonic acid bromide as an orange gum.
Ή NMR (400MHz, CD3OD) 9.90 (d, 1 H), 9.64 (d, 1 H), 8.81 (dd, 1 H), 4.71 (s, 3H) (2 x P(OH) protons missing)
Example 2: Preparation of 1 -methylpyridazin-1 -ium-4-carboxylate A3
methyl 1 -methylpyridazin-1 -ium-4-carboxylate iodide A1
Figure imgf000037_0001
To a solution of methyl pyridazine-4-carboxylate (1 g) in dichloromethane (10 mL) was added iodomethane (2.26 mL) and the reaction mixture was stirred at room temperature for 2 days. The resulting solid was filtered off and recrystallised from dichloromethane and acetone (2:1 ratio) to afford methyl 1 -methylpyridazin-1 -ium-4-carboxylate iodide which was used directly in the next step. Ή NMR (400 MHz, D2O) 9.82 (d, 1 H), 9.75 (d, 1 H), 8.90 (dd, 1 H), 4.63 (s, 3H), 3.99 (s, 3H)
Step 2: Preparation of 1 -methylpyridazin-1 -ium-4-carboxylate A3
A solution of methyl 1 -methylpyridazin-1 -ium-4-carboxylate iodide (0.2 g) in concentrated hydrochloric acid (4 mL) was heated at 80°C for 3 hours. After cooling to room temperature the reaction mixture was concentrated and the crude product was triturated with acetone to afford 1 -methylpyridazin-1 -ium- 4-carboxylate as a tan solid.
Ή NMR (400MHz, CD3OD) 9.98 (d, 1 H), 9.85 (d, 1 H), 8.99 (dd, 1 H), 4.74 (s, 3H)
Example 3: Preparation of methyl-(1-methylpyridazin-1-ium-4-yl)phosphinate A10
Figure imgf000038_0002
To a solution of 1 -methylpyridazin-1 -ium iodide (0.5 g) in acetonitrile (1 1 ml_) was added
diethoxy(methyl)phosphane (0.304 ml_) followed by sodium iodide (0.371 g). The reaction mixture was heated at 40°C for 60 minutes. After cooling to room temperature the reaction mixture was quenched with water and extracted twice with dichloromethane. The combined organic extracts were dried over sodium sulfate, filtered and the filtrate concentrated to afford crude 4-[ethoxy(methyl)phosphoryl]-1 - methyl-4H-pyridazine which was used in the next step without further purification.
Step 2: Preparation of 4-[ethoxy(methyl)phosphoryl]-1 -methyl-pyridazin-1 -ium bromide A63
Figure imgf000038_0001
To a solution of 4-[ethoxy(methyl)phosphoryl]-1 -methyl-4H-pyridazine (0.2 g) in chloroform (5 ml_) was added bromine (0.133 ml_) drop wise at 0°C. The reaction mixture was warmed to room temperature, stirred for a further hour, then concentrated to afford crude 4-[ethoxy(methyl)phosphoryl]-1 -methyl- pyridazin-1 -ium bromide which was used in the next step without further purification.
Ή NMR (400 MHz, CD3OD) 10.03 (d, 1 H), 9.83-9.78 (m, 1 H), 9.04-8.97 (m, 1 H), 4.79-4.77 (m, 3H), 4.17-4.01 (m, 2H), 2.05-1 .98 (m, 3H), 1 .41 -1 .36 (m, 3H)
Step 3: Preparation of methyl-(1 -methylpyridazin-1 -ium-4-yl)phosphinate A10
A solution of 4-[ethoxy(methyl)phosphoryl]-1 -methyl-pyridazin-1 -ium bromide (0.1 g) in concentrated aqueous hydrochloric acid (2 ml_) was heated at reflux for 5 hours. After cooling to room temperature the rection mixture was concentrated to afford methyl-(1 -methylpyridazin-1 -ium-4-yl)phosphinate as a brown gum.
Ή NMR (400 MHz, D20) 9.61 (d, 1 H), 9.47 (d, 1 H), 8.52 - 8.64 (m, 1 H), 4.57 (s, 3H), 1 .53 (d, 3H) Example 4: Preparation of 2-[(1-methylpyridazin-1-ium-4-carbonyl)amino]propanoate A19
Figure imgf000039_0002
To a mixture of pyridazine-4-carboxylic acid (0.25 g), 0-(Benzotriazol-1 -yl)-A/,A/,A/',A/'- tetramethyluronium tetrafluoroborate (0.726 g) and fe/ -butyl 2-aminopropanoate hydrochloride (0.403 g) in acetonitrile (10 ml_) was added trimethylamine (0.709 ml_). After stirring at room temperature for 2 hours the reaction mixture was concentrated, dilluted with 2M aqueous hydrochloric acid and extracted twice with dichloromethane. The combined organic phases were dried over sodium sulfate and concentrated. The crude product was purified by silica gel chromatography eluting with 0-100% ethyl acetate in hexanes to afford crude te/ -butyl 2-(pyridazine-4-carbonylamino)propanoate which was used directly in the next step. Step 2: Preparation of fe/ -butyl 2-[(1 -methylpyridazin-1 -ium-4-carbonyl)amino]propanoate A65
Figure imgf000039_0001
To a solution of fe/ -butyl 2-(pyridazine-4-carbonylamino)propanoate (0.37 g) in dichloromethane (0.5 ml_) was added iodomethane (0.302 ml_) drop wise. The reaction mixture was stirred at room temperature for 5 days. The crude product was purified by preparative reverse phase HPLC to afford fe/ -butyl 2-[(1 -methylpyridazin-1 -ium-4-carbonyl)amino]propanoate iodide which was used directly in the next step.
Ή NMR (400 MHz, CD3OD) 9.97 (d, 1 H), 9.82 - 9.77 (m, 1 H), 8.96 - 8.90 (m, 1 H), 4.73 (s, 3H), 4.53 (d, 1 H), 1 .59 - 1 .50 (m, 3H), 1 .49 (s, 9H) (NH proton missing) Step 3: Preparation of 2-[(1 -methylpyridazin-1 -ium-4-carbonyl)amino]propanoate A19 A solution of fe/ -butyl 2-[(1 -methylpyridazin-1 -ium-4-carbonyl)amino]propanoate (0.104 g) in formic acid (5 mL) was stirred at room temperature for 48 hours. The reaction mixture was concentrated to afford 2-[(1 -methylpyridazin-1 -ium-4-carbonyl)amino]propanoate.
Ή NMR (400 MHz, CD3OD) 9.96 (d, 1 H), 9.80 (d, 1 H), 8.94 (dd, 1 H), 4.73 (s, 3H), 4.57 (q, 1 H), 1 .54 (d, 3H) (NH proton missing)
Example 5: Preparation of 1-methyl-N-methylsulfonyl-pyridazin-1-ium-4-carboxamide iodide A28
ethylsulfonylpyridazine-4-carboxamide
Figure imgf000040_0001
A mixture of pyridazine-4-carboxylic acid (0.5 g), 4-dimethylaminopyridine (0.646 g),
methanesulfonamide (0.508 g) and L/,L/'-dicyclohexylmethanediimine (1 .025 g) in dichloromethane (28 mL) was stirred at room temperature for 6 days. The reaction mixture was filtered, concentrated and purified by silica gel chromatography eluting with 0-10% methanol in dichloromethane to afford crude A/-methylsulfonylpyridazine-4-carboxamide which was used without further purification in the next step.
Step 2: Preparation of 1 -methyl-/V-methylsulfonyl-pyridazin-1 -ium-4-carboxamide iodide A28
To a solution of A/-methylsulfonylpyridazine-4-carboxamide (0.3 g) in acetone (2 mL) was added iodomethane (0.26 mL). After stirring at 40°C for 6 hours the reaction mixture was cooled to room temperature and concentrated. The crude product was triturated with methanol to afford 1 -methyl-A/- methylsulfonyl-pyridazin-1 -ium-4-carboxamide iodide as an off white solid.
Ή NMR (400 MHz, CD3OD) 8.27 (s, 1 H), 8.26 (d, 1 H), 7.35 (dd, 1 H), 3.20 (s, 3H), 1 .71 (s, 3H) (NH proton missing) Example 6: Preparation of 1-butylpyridazin-1-ium-4-carboxylic acid chloride A33
Figure imgf000041_0001
Step 1 : Preparation of methyl 1 -butylpyridazin-1 -ium-4-carboxylate iodide A64
Figure imgf000041_0002
To a solution of methyl pyridazine-4-carboxylate (0.7 g) in acetone (20 mL) was added 1 -iodobutane (1 .86 g) at room temperature. The mixture was stirred for 72 hours then concentrated and partititoned between dichloromethane (20 mL) and water (20 mL). The aqueous phase was concentrated and purified by preparative reverse phase HPLC to afford methyl 1 -butylpyridazin-1 -ium-4-carboxylate iodide.
Ή NMR (400 MHz, D20) 9.89 (d, 1 H), 9.82 (s, 1 H), 8.95 (m, 1 H), 4.89 (t, 2H), 4.04 (s, 3H), 2.09-2.00 (m, 2H), 1 .37-1 .32 (m, 2H), 0.90 (t, 3H)
Step 2: Preparation of 1 -butylpyridazin-1 -ium-4-carboxylic acid chloride A33
A suspension of methyl 1 -butylpyridazin-1 -ium-4-carboxylate iodide (0.4 g) in concentrated aqueous hydrochloric acid (60 mL) was heated at 60°C for 24 hours. After cooling to room temperature the reaction mixture was concentrated and purified by preparative reverse phase HPLC to afford 1 - butylpyridazin-1 -ium-4-carboxylic acid chloride as brown liquid.
Ή NMR (400 MHz, D20) 9.71 (d, 1 H), 9.61 (s, 1 H), 8.64 (dd, 1 H), 4.76 (t, 2H), 2.07-2.00 (m, 2H), 1 .36-1 .31 (m, 2H), 0.91 (t, 3H) (C02H proton missing)
Example 7: Preparation of 1-[(4-cyanophenyl)methyl]pyridazin-1-ium-4-carboxylic acid bromide A38
Figure imgf000041_0003
Step 1 : Preparation of methyl 1 -[(4-cyanophenyl)methyl]pyridazin-1 -ium-4-carboxylate bromide To a solution of methyl pyridazine-4-carboxylate (0.7 g) in acetone (15 mL) was added 4- bromomethylbenzonitrile (1 .95 g) at room temperature and the reaction mixture was heated at reflux for 24 hours. The reaction mixture was concentrated and partitioned between water (20 mL) and dichloromethane (20 mL). The aqueous phase was concentrated and purified by preparative reverse phase HPLC to afford methyl 1 -[(4-cyanophenyl)methyl]pyridazin-1 -ium-4-carboxylate bromide as a white solid.
Ή NMR (400 MHz, D20) 10.01 (d, 1 H), 9.75 (d, 1 H), 9.94 (dd, 1 H), 7.76 (d, 2H), 7.63 (d, 2H), 6.1 1 (s, 2H), 3.97 (s, 3H)
Step 2: Preparation of 1 -[(4-cyanophenyl)methyl]pyridazin-1 -ium-4-carboxylic acid bromide A38 To a suspension of 1 -[(4-cyanophenyl)methyl]pyridazin-1 -ium-4-carboxylate bromide (0.3 g) in acetonitrile (3 mL) was added bromotrimethylsilane (0.41 g) drop wise at room temperature. The reaction mixture was stirred for 4 days at this temperature and concentrated. The crude product was purified by preparative reverse phase HPLC to afford 1 -[(4-cyanophenyl)methyl]pyridazin-1 -ium-4- carboxylic acid bromide as brown solid.
Ή NMR (400 MHz, D20) 9.84 (d, 1 H), 9.58 (s, 1 H), 8.68 (dd, 1 H), 7.76 (d, 2H), 7.61 (d, 2H), 6.06 (s, 2H) (C02H proton missing)
Example 8: Preparation of 1-methyl-3-pyrimidin-2-yl-pyridazin-1-ium-4-carboxylate A43
Figure imgf000042_0001
Step 1 : Preparation of methyl 3-bromopyridazine-4-carboxylate
Figure imgf000042_0002
To a solution of methyl 3-hydroxypyridazine-4-carboxylate (0.5 g) in acetonitrile (20 mL) was added phosphoryl bromide (1 .02 g) potionwise at 0°C, followed by heating at 100°C for 1 hour. After cooling to room temperature the reaction mixture was quenched with crushed ice and basified with saturated aqueous sodium bicarbonate. The aqueous phase was extracted with dichloromethane (3 x 50 mL), dried over sodium sulfate and concentrated to afford crude methyl 3-bromopyridazine-4-carboxylate which was used in the next step without further purification.
Step 2: Preparation of methyl 3-pyrimidin-2-ylpyridazine-4-carboxylate
Figure imgf000043_0001
To a solution of methyl 3-bromopyridazine-4-carboxylate (0.4 g) in 1 ,4-dioxane was added 2- (tributylstannyl)pyrimidine (0.748 g), copper(l) iodide (0.052 g) and cesium fluoride (0.56 g). The reaction mixture was purged with argon for 10 minutes and tetrakis(triphenylphosphine)palladium(0) (0.212 g) was added. After purging with argon for a further 10 minutes the reaction mixture was heated at 90°C for 16 hours. After cooling to room temperature the reaction mixture was filtered through diatomaceous earth and washed through with 10% methanol in dichloromethane (2 x 50 ml_). The filtrate was concentrated and purified by silica gel chromatography eluting with 3% methanol in dichloromethane to afford methyl 3-pyrimidin-2-ylpyridazine-4-carboxylate which was used in the next step without further purification.
Step 3: Preparation of methyl 1 -methyl-3-pyrimidin-2-yl-pyridazin-1 -ium-4-carboxylate iodide A48
Figure imgf000043_0002
To a solution of 3-pyrimidin-2-yl-pyridazine-4-carboxylic acid methyl ester (0.28 g) in acetone (20 ml_) was added iodomethane (1 ml_) drop wise at room temperature. The reaction mixture was stirred at room temperature for 72 hours and the resulting precipitate was filtered off and washed with acetone (20 ml_) to afford methyl 1 -methyl-3-pyrimidin-2-yl-pyridazin-1 -ium-4-carboxylate iodide as a brown solid.
Ή NMR (400 MHz, D20) 9.96-9.94 (d, 1 H), 8.98-8.96 (d, 2H), 8.91 -8.89 (d, 1 H), 7.73-7.70 (t, 1 H),
4.74 (s, 3H), 3.86 (s, 3H)
Step 4: Preparation of 1 -methyl-3-pyrimidin-2-yl-pyridazin-1 -ium-4-carboxylate A43
A mixture of methyl 1 -methyl-3-pyrimidin-2-yl-pyridazin-1 -ium-4-carboxylate iodide (0.1 g), concentrated aqueous hydrochloric acid (2.5 ml_) and water (2.5 ml_) was heated at 50°C for 16 hours. The reaction mixture was concentrated and triturated with methyl fe/ -butyl ether (20 ml_) to afford 1 - methyl-3-pyrimidin-2-yl-pyridazin-1 -ium-4-carboxylate as a grey solid. Ή NMR (400 MHz, D20) 9.70 (d, 1 H), 8.92 (t, 2H), 8.51 (d, 1 H), 7.65 (m, 1 H), 4.64 (s, 3H)
Example 9: Preparation of 1-methyl-5-phenyl-pyridazin-1-ium-4-carboxylic acid 2,2,2- trifluoroacetate A44
Figure imgf000044_0001
Step 1 : Preparation of A/,A/-dimethylpyridazine-4-carboxamide
Figure imgf000044_0002
A solution of methyl pyridazine-4-carboxylate (1 .5 g) in dimethyl amine (10 mL, 33% in ethanol) was stirred at 100°C for 3 hours in a sealed vessel. The reaction mixture was cooled, concentrated and purified by silica gel chromatography eluting with 80% ethyl acetate in hexane to afford N,N- dimethylpyridazine-4-carboxamide as a off white solid.
Ή NMR (400MHz, CDCb) 9.32 (dd, 1 H), 9.24 (dd, 1 H), 7.51 (dd, 1 H), 3.16 (s, 3H) 3.01 (s, 3H)
Step 2: Preparation of A/,A/-dimethyl-5-phenyl-pyridazine-4-carboxamide
Figure imgf000044_0003
To a solution of A/,A/-dimethylpyridazine-4-carboxamide (1 g) in tetrahydrofuran (20 mL) was added phenylmagnesium bromide (7.9 mL, 1 M in tetrahydrofuran) drop wise. The reaction mixture was stirred at room temperature for 18 hours. After cooling to 0°C, the reaction mixture was quenched with saturated aqueous ammonium chloride (10 mL), diluted with water (150 mL) and extracted with ethyl acetate (3 x 150 mL). The combined organic phases were washed with brine, dried over anhydrous sodium sulfate and concentrated. To a solution of this crude poduct in tetrahydrofuran (20 mL) was added 2,3,5,6-tetrachloro-1 ,4-benzoquinone (1 .07 g) and the reaction mixture was heated at 70°C for 18 hours. The reaction mixture was cooled to room temperature, concentrated and purified by silica gel chromatography eluting with 70% ethyl acetate in hexane to afford A/,A/-dimethyl-5-phenyl- pyridazine-4-carboxamide as off white solid. Ή NMR (400 MHz, CDCb) 9.37 (s, 1 H) 9.22 (s, 1 H) 7.50-7.56 (m, 5H) 2.97 (s, 3H) 2.45 (s, 3H)
Step 3: Preparation of 5-phenylpyridazine-4-carboxylic acid
Figure imgf000045_0001
To A/,A/-dimethyl-5-phenyl-pyridazine-4-carboxamide (0.35 g) was added a solution of sodium hydroxide (0.25 g) in water (7 mL) and the reaction mixture was heated at 100°C for 72 hours. The reaction mixture was cooled to room temperature, concentrated and extracted with acetone (2 x 20 mL). The combined organic phases were concentrated to afford 5-phenylpyridazine-4-carboxylic acid as a white solid.
Ή NMR (400MHz, de-DMSO) 9.09 (s, 1 H), 8.89 (s, 1 H), 7.71 (dd, 2 H), 7.39-7.48 (m, 3H) (CO2H proton missing)
Step 4: Preparation of methyl 1 -methyl-5-phenyl-pyridazin-1 -ium-4-carboxylate iodide
Figure imgf000045_0002
To a solution of 5-phenylpyridazine-4-carboxylic acid (0.3 g) in acetone (3 mL) at 0°C was added iodomethane (0.47 mL) drop wise. After warming to room temperature the reaction mixture was stirred for 40 hours. The reaction mixture was concentrated and washed methyl te/ -butyl ether (2 x 10 mL). The crude product was dried under vacuum to afford methyl 1 -methyl-5-phenyl-pyridazin-1 -ium-4- carboxylate iodide which was used in the next step without further purification.
Step 5: Preparation of 1 -methyl-5-phenyl-pyridazin-1 -ium-4-carboxylic acid 2,2,2-trifluoroacetate A44 A solution of methyl 1 -methyl-5-phenyl-pyridazin-1 -ium-4-carboxylate iodide (0.34 g) in 2M aqueous hydrochloric acid (6.8 mL) was heated at 80°C for 40 hours. The reaction mixture was concentrated and purified by preparative reverse phase HPLC (trifluoroacetic acid is present in the eluent) to afford 1 -methyl-5-phenyl-pyridazin-1 -ium-4-carboxylic acid 2,2,2-trifluoroacetate.
Ή NMR (400MHz, D20) 9.63 (s, 1 H), 9.48 (s, 1 H), 7.75-7.52 (m, 5H), 4.60 (s, 3H) (CO2H proton missing) Example 10: Preparation of 2-[(1-methylpyridazin-1-ium-4-carbonyl)amino]acetic acid 2,2,2- trifluoroacetate A46
Figure imgf000046_0001
Step 1 : Preparation of methyl 2-(pyridazine-4-carbonylamino)acetate
Figure imgf000046_0002
To a mixture of pyridazine-4-carboxylic acid (200 mg), methyl 2-aminoacetate hydrochloride (0.243 g), 3-(ethyliminomethyleneamino)-A/,A/-dimethyl-propan-1 -amine hydrochloride (0.37 g), 1 - hydroxybenzotriazole (0.022 g) in dichloromethane (4.03 ml_) was added Hunig's Base (0.87 ml_). The reaction mixture was stirred at room temperature overnight. The reaction mixture was diluted with chloroform and washed with water (3 x 20 ml_). The organic layer was dried over sodium sulfate, concentrated and purified by silica gel chromatography eluting with 90 to 100% ethyl acetate in isohexane to give methyl 2-(pyridazine-4-carbonylamino)acetate.
Ή NMR (400MHz, d-DMSO) 9.52-9.59 (m, 2H) 9.47 (dd, 1 H) 8.02 (dd, 1 H) 4.10 (d, 2H) 3.68 (s, 3H)
Step 2: Preparation of methyl 2-[(1 -methylpyridazin-1 -ium-4-carbonyl)amino]acetate 2,2,2- trifluoroacetate A45
Figure imgf000046_0003
A solution of methyl 2-(pyridazine-4-carbonylamino)acetate (0.5 g) in acetone (5 ml_) was cooled to 0°C and iodomethane (0.8 ml_) was added drop wise. The solution was warmed to room temperature and stirred for 40 hours. The reaction mass was concentrated, washed with methyl te/ -butyl ether and purified by preparative reverse phase HPLC (trifluoroacetic acid is present in the eluent) to afford methyl 2-[(1 -methylpyridazin-1 -ium-4-carbonyl)amino]acetate 2,2,2-trifluoroacetate.
Ή NMR (400 MHz, D20) 9.87 (d, 1 H), 9.74 (d, 1 H), 8.87 (dd, 1 H), 4.71 (s, 3H), 4.30 (s, 2H), 3.79 (s, 3H) (NH proton missing)
Step 3: Preparation of 2-[(1 -methylpyridazin-1 -ium-4-carbonyl)amino]acetic acid 2,2,2-trifluoroacetate A46
A solution of methyl 2-[(1 -methylpyridazin-1 -ium-4-carbonyl)amino]acetate 2,2,2-trifluoroacetate (0.40 g) in 2M aqueous hydrochloric acid (8 ml_) was stirred at room temperature for 24 hours. The reaction mixture was concentrated and purified by preparative reverse phase HPLC (trifluoroacetic acid is present in the eluent) to afford 2 2-[(1 -methylpyridazin-1 -ium-4-carbonyl)amino]acetic acid 2,2,2- trifluoroacetate.
Ή NMR (400MHz, D20) 9.85 (d, 1 H), 9.73 (d, 1 H), 8.86 (dd, 1 H), 4.70 (s, 3H), 4.25 (s, 2H) (NH and C02H protons missing)
Example 11 : Preparation of 1-(2-methoxyethyl)pyridazin-1-ium-4-carboxylate
trifluoromethanesulfonate A5
Figure imgf000047_0001
Step 1 : Preparation of 2-methoxyethyl trifluoromethanesulfonate
Figure imgf000047_0002
A mixture of 2-methoxyethanol (0.518 mL), pyridine (0.635 mL) and dry dichloromethane (15 mL) was cooled to ~0°C and trifluoromethylsulfonyl trifluoromethanesulfonate (1 .22 mL) was added dropwise. The reaction was stirred for 20 minutes. The mixture was partitioned between ethyl acetate and water. The organic phase was washed with brine, dried over magnesium sulfate and concentrated with care to give 2-methoxyethyl trifluoromethanesulfonate, which was used without further purification.
Ή NMR (500 MHz, CDCh) 4.64-4.60 (m, 2H), 3.73-3.69 (m, 2H), 3.42 (s, 3H) (ethyl acetate also present)
Step 2: Preparation of methyl 1 -(2-methoxyethyl)pyridazin-1 -ium-4-carboxylate
trifluoromethanesulfonate A6 To a solution of methyl pyridazine-4-carboxylate (0.16 g) in dichloromethane (2 ml_) was added 2- methoxyethyl trifluoromethanesulfonate (1 .218 g) and the reaction was stirred at room temperature for 18 hours. The reaction mixture was partitioned between ethyl acetate and water. The aqueous phase was washed with further ethyl acetate, concentrated and purified by preparative reverse phase HPLC to give methyl 1 -(2-methoxyethyl)pyridazin-1 -ium-4-carboxylate trifluoromethanesulfonate.
Ή NMR (400 MHz, CD3OD) 9.97 (d, 1 H), 9.93-9.88 (m, 1 H), 9.01 (dd, 1 H), 5.16-5.09 (m, 2H), 4.10 (s, 3H), 4.04-3.95 (m, 2H), 3.35-3.33 (m, 3H)
Step 3: Preparation of 1 -(2-methoxyethyl)pyridazin-1 -ium-4-carboxylate trifluoromethanesulfonate A5 A mixture of methyl 1 -(2-methoxyethyl)pyridazin-1 -ium-4-carboxylate trifluoromethanesulfonate (0.04 g) and concentrated hydrochloric acid (2 ml_) was heated at 80°C for 4 hours. The mixture was concentrated to give 1 -(2-methoxyethyl)pyridazin-1 -ium-4-carboxylate trifluoromethanesulfonate.
Ή NMR (400 MHz, CD3OD) 9.97 (d, 1 H), 9.89 (d, 1 H), 8.99 (dd, 1 H), 5.13 (s, 2H), 3.98-4.03 (m, 2H), 3.35 (s, 3H) (CO2H proton missing)
Example 12: Preparation of 1-(2-hydroxyethyl)pyridazin-1-ium-4-carboxylate A9
Figure imgf000048_0001
Step 1 Preparation of methyl 1 -(2-hydroxyethyl)pyridazin-1 -ium-4-carboxylate iodide
Figure imgf000048_0002
A mixture of methyl pyridazine-4-carboxylate (1 g) and 2-iodoethanol (1 .413 ml_) was heated at 70°C for 5 hours. The reaction mixture was partitioned between ethyl acetate and water. The aqueous phase was concentrated to give crude methyl 1 -(2-hydroxyethyl)pyridazin-1 -ium-4-carboxylate iodide, which was used without further purification. The major impurity is methyl 2-(2-hydroxyethyl)pyridazin- 2-ium-4-carboxylate iodide.
Step 2: Preparation of 1 -(2-hydroxyethyl)pyridazin-1 -ium-4-carboxylate A9
Crude methyl 1 -(2-hydroxyethyl)pyridazin-1 -ium-4-carboxylate iodide (0.8 g) was heated at 80°C in 2M aqueous hydrochloric acid (8 mL) for 3 hours. The reaction was concentrated and purified by preparative reverse phase HPLC to give 1 -(2-hydroxyethyl)pyridazin-1 -ium-4-carboxylate as a brown solid.
Ή NMR (400 MHz, CD3OD) 9.73 (s, 2H), 8.69-8.75 (m, 1 H), 4.90-4.96 (m, 2H), 4.06-4.13 (m, 2H) (OH proton missing)
Example 13: Preparation of 3-chloro-1 ,6-dimethyl-pyridazin-1-ium-4-carboxylate A8
Figure imgf000049_0001
To a mixture of 3-chloro-6-methyl-pyridazine-4-carboxylic acid (0.1 g) and toluene (3 mL) was added dimethyl sulfate (0.548 mL) and the mixture was stirred at reflux for 6 hours. The reaction was concentrated and partitioned between water and dichloromethane. The aqueous layer was concentrated and purified by preparative reverse phase HPLC to give 3-chloro-1 ,6-dimethyl-pyridazin- 1 -ium-4-carboxylate as a tan solid.
Ή NMR (400 MHz, CD3OD) 8.32 (s, 1 H), 4.47 (s, 3H), 2.92 (s, 3H)
Example 14: Preparation of 1-(2-carboxyethyl)pyridazin-1-ium-4-carboxylic acid chloride A21
Figure imgf000049_0002
Step 1 : Preparation of methyl 3-(trifluoromethylsulfonyloxy)propanoate
Figure imgf000049_0003
A solution of methyl 3-hydroxypropanoate (0.518 mL), pyridine (0.635 mL) in dry dichloromethane (15 mL) was cooled to ~0°C and trifluoromethylsulfonyl trifluoromethanesulfonate (1 .22 mL) was added dropwise. After stirring for 20 minutes the reaction mixture was diluted with dichloromethane and washed with water. The organic phase was dried over sodium sulfate and concentrated with care to give methyl 3-(trifluoromethylsulfonyloxy)propanoate, which was used without further purification. Ή NMR (400 MHz, CDCb) 4.79 (t, 2H), 3.78 - 3.72 (m, 3H), 2.86 (t, 2H)
Step 2: Preparation of methyl 1 -(3-methoxy-3-oxo-propyl)pyridazin-1 -ium-4-carboxylate 2,2,2- trifluoroacetate A23 To a solution of methyl pyridazine-4-carboxylate (0.43 g) in dichloromethane (1 mL) was added methyl
3-(trifluoromethylsulfonyloxy)propanoate (3.4 g) and the reaction was stirred at room temperature for 18 hours. The reaction mixture was concentrated and purified by preparative reverse phase HPLC (trifluoroacetic acid is present in the eluent) to give methyl 1 -(3-methoxy-3-oxo-propyl)pyridazin-1 -ium-
4-carboxylate 2,2,2-trifluoroacetate as a brown oil.
Ή NMR (400 MHz, CD3OD) 10.12 (d, 1 H), 9.89 (d, 1 H), 9.02 (dd, 1 H), 5.21 (t, 2H), 4.10 (s, 3H), 3.67 (s, 3H), 3.28 (t, 2H) Step 3: Preparation of 1 -(2-carboxyethyl)pyridazin-1 -ium-4-carboxylic acid chloride A21
Methyl 1 -(3-methoxy-3-oxo-propyl)pyridazin-1 -ium-4-carboxylate 2,2,2-trifluoroacetate (0.06 g) was heated at 80°C in 2M aqueous hydrochloric acid (2 mL) for 4 hours. The reaction was concentrated to give 1 -(2-carboxyethyl)pyridazin-1 -ium-4-carboxylic acid chloride.
Ή NMR (400 MHz, CD3OD) 10.1 1 (d, 1 H), 9.87 (d, 1 H), 8.99 (dd, 1 H), 5.19 (t, 2H), 3.26 (t, 2H) (CO2H protons missing)
Example 15: Preparation of 2-[[1-(2-carboxyethyl)pyridazin-1-ium-4-carbonyl]amino]propanoic acid chloride A50
Figure imgf000050_0001
Step 1 : Preparation of methyl 2-(pyridazine-4-carbonylamino)propanoate
Figure imgf000050_0002
To a mixture of pyridazine-4-carboxylic acid (2 g) in acetonitrile (64.5 mL) was added triethylamine (6.81 mL), 2, 4, 6-tripropyl-1 ,3, 5,2,4, 6-trioxatriphosphorinane-2, 4, 6-trioxide (50% solution in ethyl acetate, 19.19 mL) followed by methyl 2-aminopropanoate hydrochloride (2.525 g) and the mixture was stirred at room temperature for 16 hours. The reaction was concentrated and partitioned between ice cold water and ethyl acetate. The organic layer was washed with saturated aqueous sodium bicarbonate, dried over sodium sulfate, concentrated and purified by silica gel chromatography eluting with a mixture of ethyl acetate and cyclohexane to give methyl 2-(pyridazine-4- carbonylamino)propanoate.
Ή NMR (400 MHz, CDCb) 9.58 (s, 1 H), 9.37 (d, 1 H), 7.88 (dd, 1 H), 4.75-4.85 (m, 1 H), 3.80(s, 3H), 1 .54(d, 3H) (NH proton missing)
Step 2: Preparation of 3-[4-[(2-methoxy-1 -methyl-2-oxo-ethyl)carbamoyl]pyridazin-1 -ium-1 - yljpropanoic acid 2,2,2-trifluoroacetate A51
Figure imgf000051_0001
To a mixture of methyl 2-(pyridazine-4-carbonylamino)propanoate (0.7 g) and acetonitrile (10.5 mL) was added 3-bromopropanoic acid (0.54 g) and the mixture was heated at 60°C for 16 hours. The reaction was concentrated and purified by preparative reverse phase HPLC (trifluoroacetic acid is present in the eluent) to give 3-[4-[(2-methoxy-1 -methyl-2-oxo-ethyl)carbamoyl]pyridazin-1 -ium-1 - yljpropanoic acid 2,2,2-trifluoroacetate.
Ή NMR (400 MHz, D20) 9.93-10.05 (m, 1 H), 9.71 -9.82 (m, 1 H), 8.80-8.94 (m, 1 H), 5.10-5.25 (m, 2H), 4.64-4.74 (m, 1 H), 3.76-3.83(m, 3H), 3.26-3.35 (m, 2H), 1 .43-1 .60 (m, 3H) (NH and C02H protons missing)
Step 3: Preparation of 2-[[1 -(2-carboxyethyl)pyridazin-1 -ium-4-carbonyl]amino]propanoic acid chloride A50
A mixture of 3-[4-[(2-methoxy-1 -methyl-2-oxo-ethyl)carbamoyl]pyridazin-1 -ium-1 -yl]propanoic acid (0.1 g) and 2M aqueous hydrochloric acid (2 mL) was stirred at room temperature for 24 hours. The reaction was concentrated and the resulting residue was washed with cyclohexane followed by methyl fe/ -butyl ether and dried to give 2-[[1 -(2-carboxyethyl)pyridazin-1 -ium-4-carbonyl]amino]propanoic acid chloride.
Ή NMR (400 MHz, D20) 9.89 (d, 1 H), 9.66 (d, 1 H), 8.79 (dd, 1 H), 5.09 (t, 2H), 4.53 (q, 1 H), 3.19 (t, 2H), 1 .44 (d, 3H) (NH and C02H protons missing) Example 16: Preparation of 1-[3-(methylamino)-3-oxo-propyl]pyridazin-1-ium-4-carboxylic acid 2,2,2-trifluoroacetate A56
Figure imgf000052_0001
Step 1 : Preparation of 3-bromo-N-methyl-propanamide
Figure imgf000052_0002
A solution of 3-bromopropanoyl chloride (2 g) in dichloromethane (35 ml_) was cooled to ~5°C and methanamine (2M in tetrahydrofuran, 1 1 .7 ml_) was added dropwise. The mixture was allowed to warm to room temperature and was stirred for 18 hours. The reaction mixture was concentrated and partitioned between dichloromethane and saturated aqueous sodium bicarbonate. The organic layer was washed with further saturated aqueous sodium bicarbonate, dried over sodium sulfate and concentrated to give 3-bromo-N-methyl-propanamide as a white solid, which was used without further purification.
Ή NMR (400 MHz, CDCb) 5.61 (brs, 1 H), 3.64 (t, 2H), 2.85 (d, 3H), 2.75 (t, 2H)
Step 2: Preparation of 1 -[3-(methylamino)-3-oxo-propyl]pyridazin-1 -ium-4-carboxylic acid 2,2,2- trifluoroacetate A56
To a mixture of pyridazine-4-carboxylic acid (0.25 g) and acetonitrile (5 ml_) was added 3-bromo-N- methyl-propanamide (0.502 g) and the mixture was heated at 80°C for 16 hours. Water (2.5 ml_) was added and heating was continued at 80°C for 16 hours. The reaction was concentrated, triturated with methyl te/ -butyl ether and purified by preparative reverse phase HPLC (trifluoroacetic acid is present in the eluent) to give 1 -[3-(methylamino)-3-oxo-propyl]pyridazin-1 -ium-4-carboxylic acid 2,2,2- trifluoroacetate.
Ή NMR (400 MHz, D20) 9.78 (d, 1 H), 9.64 (d, 1 H), 8.72 (dd, 1 H), 5.1 1 - 5.04 (m, 2H), 3.08 - 3.01 (m, 2H), 2.59 - 2.54 (m, 3H) (NH and C02H protons missing)
Example 17: Preparation of 1-[2-(methylsulfamoyl)ethyl]pyridazin-1-ium-4-carboxylic acid 2,2,2- trifluoroacetate A55 Step 1 : Preparation of N-methylethenesulfonamide
Figure imgf000053_0001
A solution of 2-chloroethanesulfonyl chloride (1 .28 ml_) in dichloromethane (35.3 ml_) was cooled to ~5°C and methanamine (2M in tetrahydrofuran, 1 1 .7 ml_) was added dropwise. The mixture was allowed to warm to room temperature and was stirred for 18 hours. The reaction mixture was concentrated and partitioned between dichloromethane and saturated aqueous sodium bicarbonate. The organic layer was washed with further saturated aqueous sodium bicarbonate, dried over sodium sulfate and concentrated to give N-methylethenesulfonamide, which was used without further purification.
Step 2: Preparation of 1 -[2-(methylsulfamoyl)ethyl]pyridazin-1 -ium-4-carboxylic acid 2,2,2- trifluoroacetate A55
A mixture of pyridazine-4-carboxylic acid (0.2 g), 2,2,2-trifluoroacetic acid (1 ml_), water (1 ml_) and N- methylethenesulfonamide (0.234 g) was heated at 100°C for 16 hours. The reaction was
concentrated, triturated with methyl te/ -butyl ether and purified by preparative reverse phase HPLC (trifluoroacetic acid is present in the eluent) to give 1 -[2-(methylsulfamoyl)ethyl]pyridazin-1 -ium-4- carboxylic acid 2,2,2-trifluoroacetate.
Ή NMR (400 MHz, D20) 9.89 (d, 1 H), 9.75 - 9.71 (m, 1 H), 8.81 (dd, 1 H), 5.27 (t, 2H), 4.00 - 3.94 (m, 2H), 2.62 - 2.59 (m, 3H) (NH and C02H protons missing)
Example 18: Preparation of methyl 1-[2-(methanesulfonamido)-2-oxo-ethyl]pyridazin-1-ium-4- carboxylate 2,2,2-trifluoroacetate A25
Figure imgf000053_0002
Step 1 : Preparation of 2-bromo-N-methylsulfonyl-acetamide To a solution of methanesulfonamide (1 g) in toluene (63 ml_) was added 2-bromoacetyl bromide (3.7 ml_) drop wise at room temperature. The reaction mixture was then heated at 1 10°C for 5 hours.
The reaction was cooled to room temperature and then placed in an ice bath. The resulting precipitate was filtered off, washed with cold toluene and dried under vacuum to give 2-bromo-N-methylsulfonyl- acetamide as a pale yellow solid.
Ή NMR (400 MHz, CDCb) 8.81 (br s, 1 H), 3.95 (s, 2H), 3.35 (s, 3H)
Step 2: Preparation of methyl 1 -[2-(methanesulfonamido)-2-oxo-ethyl]pyridazin-1 -ium-4-carboxylate 2,2,2-trifluoroacetate A25
A mixture of methyl pyridazine-4-carboxylate (0.5 g), 2-bromo-N-methylsulfonyl-acetamide (0.939 g) and acetone (3 ml_) was stirred at room temperature for 120 hours. The reaction was concentrated and purified by preparative reverse phase HPLC (trifluoroacetic acid is present in the eluent) to give methyl 1 -[2-(methanesulfonamido)-2-oxo-ethyl]pyridazin-1 -ium-4-carboxylate 2,2,2-trifluoroacetate. Ή NMR (400 MHz, D20) 9.87 (d, 1 H), 9.81 (d, 1 H), 9.01 (dd, 1 H), 5.64 (s, 1 H), 4.01 (s, 3H), 3.03 (s, 3H)(NH and one CH2 protons missing)
Additional compounds in Table A were prepared by analogous procedures, from appropriate starting materials.
Table A
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
BIOLOGICAL EXAMPLES
Post-emergence efficacy
Seeds of a variety of test species were sown in standard soil in pots. After cultivation for 14 days (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 dissolution of the technical active ingredient formula (I) in a small amount of acetone and a special solvent and emulsifier mixture referred to as IF50 (1 1 .12% Emulsogen EL360 TM + 44.44% N-methylpyrrolidone + 44.44% Dowanol DPM glycol ether), to create a 50g/l solution which was then diluted to required concentration using 0.25% or 1 % Empicol ESC70 (Sodium lauryl ether sulphate) + 1 % ammonium sulphate as diluent. The test plants were then grown in a glasshouse under controlled conditions (at 24/16°C, day/night; 14 hours light; 65 % humidity) and watered twice daily. After 13 days the test was evaluated (100 = total damage to plant; 0 = no damage to plant). Test plants:
Ipomoea hederacea (IPOHE), Euphorbia heterophylla (EPHHL), Chenopodium album (CHEAL), Amaranthus palmeri (AMAPA), Lolium perenne (LOLPE), Digitaria sanguinalis (DIGSA), Eleusine indica (ELEIN), Echinochloa crus-galli (ECHCG), Setaria faberi (SETFA) The results are shown in Table B (below). A value of n/a indicates that this combination of weed and test compound was not tested/assessed.
Table B - Control of weed species by compounds of formula (I) after post-emergence application
Figure imgf000067_0001
Figure imgf000068_0001

Claims

1 . Use as a herbicide, of a compound of formula (I) or an agronomically acceptable salt or zwitterionic species thereof:
Figure imgf000069_0001
wherein
R1 is selected from the group consisting of hydrogen, halogen, Ci-C6alkyl, C2-C6alkenyl, C2- Cealkynyl, Cs-Cecycloalkyl, Ci-C6haloalkyl, -OR7, -OR15a, -N(R6)S(0)2R15, -N(R6)C(0)R15, - N(R6)C(0)0R15, -N(R6)C(0)NR16R17, -N(R6)CHO, -N(R7a)2 and -S(0)rR15;
R2 is selected from the group consisting of hydrogen, halogen, Ci-C6alkyl and Ci-C6haloalkyl; and wherein when R1 is selected from the group consisting of -OR7, -OR15a, -N(R6)S(0)2R15, - N(R6)C(0)R15, -N(R6)C(0)0R15, -N(R6)C(0)NR16R17, -N(R6)CHO, -N(R7a)2 and -S(0)rR15, R2 is selected from the group consisting of hydrogen and Ci-C6alkyl; or
R1 and R2 together with the carbon atom to which they are attached form a C3-C6cycloalkyl ring or a 3- to 6- membered heterocyclyl, which comprises 1 or 2 heteroatoms individually selected from N and O;
Q is (CR1aR2b)m;
m is 0, 1 , 2 or 3;
each R1a and R2b are independently selected from the group consisting of hydrogen, halogen, Ci-Cealkyl, Ci-C6haloalkyl, -OH, -OR7, -OR15a, -NH2, -NHR7, -NHR15a, -N(R6)CHO, -NR7bR7c and -S(0)rR15; or
each R1a and R2b together with the carbon atom to which they are attached form a C3- C6cycloalkyl ring or a 3- to 6- membered heterocyclyl, which comprises 1 or 2 heteroatoms individually selected from N and O;
R3, R4 and R5 are independently selected from the group consisting of hydrogen, halogen, nitro, cyano, -NH2, -NR6R7, -OH, -OR7, -S(0)rR12, -NR6S(0)rR12, Ci-C6alkyl, Ci-C6haloalkyl, C3- C6cycloalkyl, C3-C6halocycloalkyl, C3-C6cycloalkoxy, C2-C6alkenyl, C2-C6haloalkenyl, C2- C6alkynyl, Ci-C3alkoxyCi-C3alkyl-, hydroxyCi-Cealkyl-, Ci-C6haloalkoxy, Ci-C3haloalkoxyCi- C3alkyl-, Ci-C6alkoxycarbonyl, C3-C6alkenyloxy, C3-C6alkynyloxy, Ci-C6alkylcarbonyl, Ci- C6alkylaminocarbonyl, di-Ci-C6alkylaminocarbonyl, -C(R8)=NOR8, phenyl and heteroaryl, wherein the heteroaryl moiety is a 5- or 6-membered monocyclic aromatic ring which comprises 1 , 2, 3 or 4 heteroatoms individually selected from N, O and S, and wherein any of said phenyl or heteroaryl moieties are optionally substituted by 1 , 2 or 3 substituents R9, which may be the same or different;
each R6 is independently selected from hydrogen and Ci-C6alkyl;
each R7 is independently selected from the group consisting of Ci-C6alkyl, -S(0)2R15, -C(0)R15, -C(0)0R15 and -C(0)NR16R17;
each R7a is independently selected from the group consisting of -S(0)2R15, -C(0)R15, -C(0)0R15 -C(0)NR16R17 and -C(0)NR6R15a;
R7b and R7c are independently selected from the group consisting of Ci-C6alkyl, -S(0)2R15, - C(0)R15, -C(0)0R15, -C(0)NR16R17 and phenyl, and wherein said phenyl is optionally substituted by 1 , 2 or 3 R9 substituents, which may be the same or different; or
R7b and R7c together with the nitrogen atom to which they are attached form a 4- to 6-membered heterocyclyl ring which optionally comprises one additional heteroatom individually selected from N, O and S; and
each R9 is independently selected from the group consisting of halogen, cyano, -OH, -N(R6)2, Ci-C4alkyl, Ci-C4alkoxy, Ci-C4haloalkyl and Ci-C4haloalkoxy;
E is selected from the group consisting of of -C(0)OR10, -CHO, -C(0)R24, -C(0)NH0R11 , - C(0)NHCN, -C(0)NHR25, -S(0)2NHR25, -C(0)NR6(CR6 2)qC(0)(0R1°),
C(0)NR6(CR6 2)qS(0)2(0R10) and -C(0)NR6(CR6 2)qP(0)(R13)(0R1°), -(CR6 2)qC(0)OR10, - (CR6 2)qS(0)2(0R10), -(CR6 2)qP(0)(R13)(OR10), -0C(0)NH0R11 , -0(CR6 2)qC(0)0R1°, -
0C(0)NHCN, -0(CR6 2)qS(0)2(0R10), -0(CR6 2)qP(0)(R13)(0R10), -NR6C(0)NH0R11 , -
NR6C(0)NHCN, -C(0)NHS(0)2R12, -0C(0)NHS(0)2R12, -NR6C(0)NHS(0)2R12, -S(0)20R10, - 0S(0)20R10, -NR6S(0)20R10, -NR6S(0)OR10, -NHS(0)2R14, -S(0)OR10, -S(CR6 2)qC(0)OR10, - S(CR6 2)qS(0)2(0R10), -S(CR6 2)qP(0)(R13)(OR10), -OS(0)OR10, -S(0)2NHCN, -S(0)2NHC(0)R18, -S(0)2NHS(0)2R12, -0S(0)2NHCN, -0S(0)2NHS(0)2R12, -0S(0)2NHC(0)R18,
NR6S(0)2NHCN, -NR6S(0)2NHC(0)R18, -N(0H)C(0)R15, -0NHC(0)R15,
NR6S(0)2NHS(0)2R12, -P(0)(R13)(OR10), -P(0)H(OR10), -OP(0)(R13)(OR10),
NR6P(0)(R13)(OR10) and tetrazole;
q is 1 -3
X is selected from the group consisting of C3-C6cycloalkyl, phenyl, a 5- or 6- membered heteroaryl, which comprises 1 , 2, 3 or 4 heteroatoms individually selected from N, O and S, and a 4- to 6- membered heterocyclyl, which comprises 1 , 2 or 3 heteroatoms individually selected from N, O and S, and wherein said cycloalkyl, phenyl, heteroaryl or heterocyclyl moieties are optionally substituted by 1 or 2 substituents, which may be the same or different, selected from R9, and wherein the aforementioned CR1R2, Q and Z moieties may be attached at any position of said cycloalkyl, phenyl, heteroaryl or heterocyclyl moieties;
n is 0 or 1 ; Z is selected from the group consisting of hydrogen, Ci-C6alkyl, Ci-C6haloalkyl, Ci- C6hydroxyalkyl, Ci-C6alkoxyCi-C6alkyl, nitro, halo, haloalkoxy, cyano, -NH2, -OH, -OR7, - C(0)R15, -C(0)NR16R17, -C(0)OR10, -CHO, -C(0)NH0R11 , -C(0)NHCN, -0C(0)NH0R11, - 0C(0)NHCN, -NR6C(0)NH0R11 , -NR6C(0)NHCN, -C(0)NHS(0)2R12, -0C(0)NHS(0)2R12, - NHR7, -N(R7)2, -NR6C(0)NHS(0)2R12, -NR6S(0)2R15, -S(0)20R10, -0S(0)20R10, -
NR6S(0)2OR10, -NR6S(0)OR10, -NHS(0)2R14, -S(0)rR15, -S(0)OR10, -S(0)2NR16R17 - OS(0)OR10, -S(0)2NHCN, -S(0)2NHC(0)R18, -S(0)2NHS(0)2R12, -0S(0)2NHCN, -
0S(0)2NHS(0)2R12, -0S(0)2NHC(0)R18, -NR6S(0)2NHCN, -NR6S(0)2NHC(0)R18, -
N(0H)C(0)R15, -0NHC(0)R15, -NR6S(0)2NHS(0)2R12, -P(0)(R13)(OR10), -P(0)H(OR10), - 0P(0)(R13)(0R1°), -NR6P(0)(R13)(OR10), tetrazole;
R10 is selected from the group consisting of hydrogen, Ci-C6alkyl, phenyl and benzyl, and wherein said phenyl or benzyl are optionally substituted by 1 , 2 or 3 R9 substituents, which may be the same or different;
R11 is selected from the group consisting of hydrogen, Ci-C6alkyl and phenyl, and wherein said phenyl is optionally substituted by 1 , 2 or 3 R9 substituents, which may be the same or different;
R12 is selected from the group consisting of Ci-C6alkyl, Ci-C6haloalkyl, Ci-C6alkoxy, -OH, - N(R6)2 and phenyl, and wherein said phenyl is optionally substituted by 1 , 2 or 3 R9 substituents, which may be the same or different;
R13 is selected from the group consisting of -OH, Ci-C6alkyl, Ci-C6alkoxy, Ci-C6haloalkoxy, -O- propargyl, -O-allyl and phenyl;
R14 is Ci-Cehaloalkyl;
R15 is selected from the group consisting of Ci-C6alkyl and phenyl, and wherein said phenyl is optionally substituted by 1 , 2 or 3 R9 substituents, which may be the same or different;
R15a is phenyl, wherein said phenyl is optionally substituted by 1 , 2 or 3 R9 substituents, which may be the same or different;
R16 and R17 are independently selected from the group consisting of hydrogen and Ci-C6alkyl; or
R16 and R17 together with the nitrogen atom to which they are attached form a 4- to 6-membered heterocyclyl ring which optionally comprises one additional heteroatom individually selected from N, O and S;
R18 is selected from the group consisting of hydrogen, Ci-C6alkyl, Ci-C6haloalkyl, Ci-C6alkoxy, -N(R6)2 and phenyl, and wherein said phenyl is optionally substituted by 1 , 2 or 3 R9 substituents, which may be the same or different;
R24 is a peptide moiety comprising one, two or three amino acid moieties independently selected from the group consisting of Ala, Cys, Asp, Glu, Phe, Gly, His, lie, Lys, Leu, Met, Asn, Pro, Gin, Arg, Ser, Thr, Val, Trp and Tyr, wherein said peptide moiety is bonded to the rest of the molecule via a nitrogen atom in the amino acid moiety; R25 is selected from the group consisting of 5- or 6- membered heteroaromatic moieties, optionally substituted with one or more groups independently selected from R2 or;
R25 is selected from the group consisting of 5- or 6- membered heteroaromatic moieties, containing at least two N atoms, optionally substituted with one or more groups independently selected from R9;
and
r is 0, 1 or 2;
with the proviso that the use of pyridazocidin as herbicide is excluded.
2. A compound of formula (I) as defined in claim 1 , wherein R3, R4 and R5 are each independently hydrogen, Ci-C6alkyl, or Ci-C6alkoxy, with the proviso that said compound is not pyridazocidin.
3. The compound of claim 2, wherein R1 and R2 are independently selected from the group consisting of hydrogen and Ci-C6alkyl.
4. The compound according to claim 2 or claim 3, wherein each R1a and R2b are independently selected from the group consisting of hydrogen, Ci-C6alkyl, -OH and -NH2
5. The compound according to any one of claims 2 to 4, wherein m is 0.
6. The compound according to any one of claims 2 to 5, wherein R3 and R4 are independently selected from the group consisting of hydrogen, Ci-C6alkyl, and Ci-C6alkoxy.
7. The compound according to any one of claims 2 to 6, wherein R3 , R4 and R5 are independently hydrogen or methyl.
8. The compound according to any one of claims 2 to 7, wherein E is -C(0)OR10, - C(0)NHS(0)2R12, -C(0)R24, -P(0)(R13)(OR10); or C(0)NR6(CR6 2)qC(0)(0R1°).
9. A compound according to any one of claims 2 to 8, wherein Z is selected from the group consisting of hydrogen, Ci-C6alkyl, Ci-C6haloalkyl, Ci-C6hydroxyalkyl, Ci-C6alkoxy, -C(0)OR10, -C(0)NHS(0)2R12, -S(0)20R10, and -P(0)(R13)(OR10).
10. The compound according to claim 9, wherein Z is hydrogen, Ci-C6alkyl or Ci-C6hydroxyalkyl.
11. The compound according to any one of claims 2 to 10, wherein n is 0.
12. Use of a compound as defined in any one of claims 2 to 11 as a herbicide.
13. An agrochemical composition comprising a herbicidally effective amount of a compound of formula (I) as defined in any one of claims 1 to 11 and an agrochemically-acceptable diluent or carrier.
14. A method of controlling or preventing undesirable plant growth, wherein a herbicidally effective amount of a compound of formula (I) as defined in any one of claims 1 to 11 , or a herbicidal composition according to claim 13, is applied to the plants, to parts thereof or to the locus thereof.
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