HERBICIDAL COMPOUNDS
The present invention relates to novel pyridazinone derivatives, to processes
for their preparation, to herbicidal compositions which comprise the novel derivatives,
and to their use for controlling weeds, in particular in crops of useful plants, or for
inhibiting plant growth.
Thus, according to the present invention there is provided a compound of
Formula (I):
or an agronomically acceptable salt thereof,
wherein: -
selected from the group consisting of Al and A2
wherein
X1 is N or CR7;
X2 is N or CR8;
X3 is N or CR9;
X4 is N or CR6;
R is selected from the group consisting of hydrogen, halogen, cyano, Ci-
C6alkyl, C3-C6cycloalkyl, C2-C6alkenyl, C 4-C6cycloalkenyl, C2-C6alkynyl, C -
C6haloalkyl, Ci-C alkoxy, Ci-Cealkoxy-Ci-Cs-alkyl, Ci-C alkoxy-C2-
C6alkoxy-, C -C alkoxy-C2-C6alkoxy-C1-C3alkyl-, Cs-CecycloalkylCi-Csalkyl-,
amino, Ci-Cealkylamino, Ci-Cedialkylamino, Ci-C3
alkylcarbonylaminoC 1-C4alkyl-, Ci-C6alkyl-S(0)p-, Ci-C6alkyl-S(0)p- C1-C3-
alkyl, C1-C6haloalkyl-S(0)p- and C1-C6haloalkyl-S(0)p-C 1-C3-alkyl;
R is selected from the group consisting of hydrogen, hydroxyl, halo, nitro,
amino, cyano, C -C lk l, Ci-C3alkoxy, C3-C6cycloalkyl, C2-C6alkenyl, C -
C6alkynyl, Ci-Cehaloalkyl, Ci-Cealkoxy-Ci-Cs-alkyl, Cs-Cecycloalkyl-Ci-Csalkyl,
Ci-C6alkyl-S(0)p-, C1-C6alkyl-S(0) p- Ci-C3-alkyl, Ci-Cehaloalkyl-
S(0) p-, Ci-Qalkylamino, Ci-Qdialkylamino and C1-C6haloalkyl-S(0) p-C1-
C3-alkyl;
R4 is selected from the group selected from hydrogen, Ci-Cealkylcarbonyl,
arylcarbonyl, Ci-Cealkoxycarbonyl, C1-C6alkyl-S(0) p-, C C alkyl-
S(0) pcarbonyl- and aryl-S(0)p-, wherein said aryl groups may be optionally
substituted by one or more R1 1;
R5 is selected from the group consisting of hydroxyl, halogen, Ci-Cealkyl, Ci-
C6cycloalkyl, Ci-Cehaloalkyl, C2-C6alkenyl, C2-C6haloalkenyl, C2-C6alkynyl,
Ci-C6 alkoxy, C2-C6 alkenyloxy-, C3-C6cycloalkylCi-C 3-alkyl-, Ci-C6
alkoxyCi-C3alkyl, Ci-C alkoxy-C2-C6alkoxy, C -C alkoxy-C2-C6alkoxy-Ci-
C3alkyl,Ci-C6 haloalkoxy, Ci-Ce haloalkoxy-Ci-C 3alkyl, Ci-C6alkyl-S(0)p-,
Ci-C6haloalkyl-S(0)p-, aryl, aryl-S(0)p, heterocyclyl, heterocyclyl-S(0)p,
aryloxy, aryl-C2-C6alkyl-, aryl-CrCealkoxy-, heterocyclyloxy, heterocyclyl-
Ci-Csalkoxy-Ci-Csalkyl, hydroxycarbonyl, hydroxycarbonyl-Ci-C 3 alkoxy-,
Ci-C3 alkoxycarbonyl, Ci-C3 alkoxycarbonyl-Ci-C 3 alkoxy-, C -
C3alkylamino-, Ci-Csdialkylamino-, Ci-C3 alkylamino-S(0)p-, Ci-C3
alkylamino-S(0)p-C 1-C3alkyl-, Ci-C3 dialkylamino-S(0)p-, Ci-C3
dialkylamino-S(0)p-C 1-C3alkyl-, Ci-Csalkylaminocarbonyl-, Ci-
Csalkylaminocarbonyl-Ci-Csalkyl-, Ci-Csdialkylaminocarbonyl-, Ci-C3
dialkylaminocarbonyl-Ci-Csalkyl-, Ci-Csalkylcarbonylamino-, Ci-C3 alkyl-
S(0)p-amino-, C1-C3alkyl-S(0)p-C 1-C3alkylamino-, Ci-C3alkyl-S(0)paminoCi-
Csalkyl-, cyano and nitro, wherein said heterocyclyls are five or six
membered heterocyclyls containing from one to three heteroatoms each
independently selected from the group consisting of oxygen, nitrogen and
sulphur, and wherein the aryl or heterocyclyl components may be optionally
substituted by one or more substituents selected from the group consisting of
halo, Ci-C3alkyl, Ci-C3haloalkyl, Ci-C3 alkoxy, Ci-C3 haloalkoxy, phenyl,
cyano and nitro;
R6 and R9 are independently selected from the group consisting of hydrogen,
hydroxyl, halogen, Ci-Cealkyl, Ci-Cecycloalkyl, Ci-Cehaloalkyl, C2-C6alkenyl,
C2-C6haloalkenyl, C2-C6alkynyl, Ci-C6 alkoxy-, C2-C6 alkenyloxy-, C3-
CecycloalkylCi-Cs-alkyl-, Ci-C6 alkoxyCi-Csalkyl-, Ci-C6 alkoxy-C2-
C6alkoxy-, Ci-C6 alkoxy-C2-C6alkoxy-C1-C3alkyl-,C1-C6 haloalkoxy-, Ci-C6
haloalkoxy-Ci-Csalkyl-, C1-C6alkyl-S(0) p-, C1-C6haloalkyl-S(0) p-, aryl, aryl-
S(0) p-, heterocyclyl, heterocyclyl-S(0) p-, aryloxy-, aryl-C2-C6alkyl-, aryl-Cr
C6alkoxy-, heterocyclyloxy-, heterocyclyl-Ci-Qalkoxy-Ci-Qalkyl-,
hydroxycarbonyl, hydroxycarbonyl-Ci-Csalkoxy-, Ci-C3 alkoxycarbonyl-, Ci-
C3alkoxycarbonyl-Ci-C 3 alkoxy-, Ci-Csalkylamino-, Ci-Csdialkylamino-, Ci-
C3alkylamino-S(0) p-, Ci-C3 alkylamino-S(0) p-C1-C3alkyl-, Ci-C3
dialkylamino-S(0) p-, Ci-C3 dialkylamino-S(0) p-C1-C3alkyl-, C -
C3alkylaminocarbonyl-, Ci-Qalkylaminocarbonyl-Ci-Qalkyl-, Ci-
C3dialkylaminocarbonyl-, Ci-C3 dialkylaminocarbonyl-Ci-Csalkyl-, Ci-
C3alkylcarbonylamino-, Ci-C3 alkyl-S(0) p-amino-, C1-C3alkyl-S(0) p-C1-
C3alkylamino-, C1-C3alkyl-S(0)p- aminoCi-Qalkyl-, cyano and nitro, wherein
said heterocyclyls are five or six membered heterocyclyls containing from one
to three heteroatoms each independently selected from the group consisting of
oxygen, nitrogen and sulphur, and wherein the aryl or heterocyclyl
components may be optionally substituted by one or more substituents
selected from the group consisting of halo, Ci-Csalkyl, Ci-Cshaloalkyl, Ci-C 3
alkoxy, Ci-C 3 haloalkoxy, C1-C6alkyl-S(0) p-, phenyl, cyano and nitro;
R is selected from the group consisting of hydrogen, halogen, Ci-C 3 alkyl-,
Ci-C 3 alkoxy-, C2-C3alkenyl-, C2-C3alkynyl-, Ci-C 3 haloalkyl- and C \ -
Cshaloalkoxy-;
R is hydrogen; or
R5 and R9 can together form a saturated or unsaturated 5- or 6-membered
carbocyclic or heterocyclic ring, said heterocyclic ring comprising one or more
nitrogen and/or oxygen heteroatoms, the 5- or 6-membered ring being
12 optionally substituted by one or more R ; or
R6 and R9 can together form a saturated or unsaturated 5- or 6-membered
carbocyclic or heterocyclic ring, said heterocyclic ring comprising one or more
heteroatoms selected from the group consisting of nitrogen, oxygen and S(0) 2,
12 the 5- or 6-membered ring being optionally substituted by one or more R ; or
R6 and R8 can together form an unsaturated 5- or 6-membered carbocyclic or
heterocyclic ring, said heterocyclic ring comprising one or more nitrogen
heteroatoms, the 5- or 6-membered ring being optionally substituted by one or
13 more R ; and
R1 1 is selected from the group consisting of halo-, Ci-C 3alkyl, Ci-C 3 haloalkyl
and Ci-Cealkoxy;
12 R is selected from the group of hydrogen, cyano, halo-, oxy-, C -
C3alkylS(0)p-, Ci-C3 alkyl, C2-C3alkenyl, C2-C3alkynyl, Ci-C3 alkoxy and Ci-
C3 haloalkyl;
13 R is selected from the group of hydrogen, cyano, halo-, Ci-C3alkylS(0)p-,
Ci-C3 alkyl, C2-C3alkenyl, C2-C3alkynyl, morpholinyl- and Ci-C3 haloalkyl;
and
p = 0, 1 or 2.
Alkyl groups having a chain length of from 1 to 6 carbon atoms include, for
example, methyl (Me, CH ), ethyl (Et, C2H5), n-propyl, isopropyl (z-Pr), n-butyl (nbu),
iso-butyl (z ' -bu), sec-butyl and tert-butyl (t-butyl).
Alkenyl groups having a chain length of from 2 to 6 carbon atoms include, for
example, -CH=CH2 (vinyl) and -CH2-CH=CH2 (allyl).
Alkynyl groups having a chain length of from 2 to 6 carbon atoms include, for
example, -CºCH (ethynyl) and -CH2-CºCH (propargyl).
Cycloalkyl groups include c-propyl (c-Pr), c-butyl (c-Bu), c-pentyl and chexyl.
Halogen (or halo) encompasses fluorine, chlorine, bromine or iodine. The
same correspondingly applies to halogen in the context of other definitions, such as
haloalkyl or halophenyl.
Haloalkyl groups having a chain length of from 1 to 6 carbon atoms are, for
example, fluoromethyl, difluoromethyl, trifluoromethyl, chloromethyl,
dichloromethyl, trichloromethyl, 2,2,2-trifluoroethyl, 2-fluoroethyl, 2-chloroethyl,
pentafluoroethyl, l,l-difluoro-2,2,2-trichloroethyl, 2,2,3, 3-tetrafluoroethyl and 2,2,2-
trichloroethyl, heptafluoro-n-propyl and perfluoro-n-hexyl.
Suitable haloalkenyl radicals include alkenyl groups substituted one or more
times by halogen, halogen being fluorine, chlorine, bromine or iodine and especially
fluorine or chlorine, for example 2,2-difluoro-l-methylvinyl, 3-fluoropropenyl, 3-
chloropropenyl, 3-bromopropenyl, 2,3,3-trifluoropropenyl, 2,3,3-trichloropropenyl
and 4,4,4-trifluorobut-2-en-l-yl. Preferred C 2-C6alkenyl radicals substituted once,
twice or three times by halogen are those having a chain length of from 2 to 5 carbon
atoms. Suitable haloalkylalkynyl radicals include, for example, alkylalkynyl groups
substituted one or more times by halogen, halogen being bromine or iodine and,
especially, fluorine or chlorine, for example 3-fluoropropynyl, 5-chloropent-2-yn-l-yl,
5-bromopent-2-yn-l-yl, 3,3,3-trifluoropropynyl and 4,4,4-trifluoro-but-2-yn-l-yl.
Preferred alkylalkynyl groups substituted one or more times by halogen are those
having a chain length of from 3 to 5 carbon atoms.
Alkoxy groups preferably have a chain length of from 1 to 6 carbon atoms.
Alkoxy is, for example, methoxy, ethoxy, propoxy, isopropoxy, n-butoxy, isobutoxy,
sec-butoxy or tert-butoxy or a pentyloxy or hexyloxy isomer, preferably methoxy and
ethoxy. Alkylcarbonyl is preferably acetyl or propionyl. Alkoxycarbonyl is, for
example, methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, isopropoxycarbonyl,
n-butoxycarbonyl, isobutoxycarbonyl, sec-butoxycarbonyl or tert-butoxycarbonyl,
preferably methoxycarbonyl, ethoxycarbonyl or tert -butoxycarbonyl. It should also
be appreciated that two alkoxy substituents present on the same carbon atom may be
joined to form a spiro group. Thus, the methyl groups present in two methoxy
substituents may be joined to form a spiro 1,3 dioxolane substituent, for example.
Such a possibility is within the scope of the present invention.
Haloalkoxy is, for example, fluoromethoxy, difluoromethoxy,
trifluoromethoxy, 2,2,2-trifluoroethoxy, 1,1,2,2-tetrafluoroethoxy, 2-fluoroethoxy, 2-
chloroethoxy, 2,2-difluoroethoxy or 2,2,2-trichloroethoxy, preferably
difluoromethoxy, 2-chloroethoxy or trifluoromethoxy.
Alkylthio (alky l - S-) groups preferably have a chain length of from 1 to 6
carbon atoms.
Alkylthio is, for example, methylthio, ethylthio, propylthio, isopropylthio, n-butylthio,
isobutylthio, sec-butylthio or tert-butylthio, preferably methylthio or ethylthio.
Alkylsulfmyl (alkyl-SO-) is, for example, methylsulfmyl, ethylsulfmyl,
propylsulfmyl, isopropylsulfmyl, n-butylsulfmyl, isobutylsulfinyl, sec-butylsulfinyl or
tert-butylsulfinyl, preferably methylsulfmyl or ethylsulfmyl.
Alkylsulfonyl (alkyl-S(0) 2-) is, for example, methylsulfonyl, ethylsulfonyl,
propylsulfonyl, isopropylsulfonyl, n-butylsulfonyl, isobutylsulfonyl, sec-butylsulfonyl
or tert-butylsulfonyl, preferably methylsulfonyl or ethylsulfonyl.
Alkylamino (alkyl-NH-) is, for example, methylamino, ethylamino, npropylamino,
isopropylamino or a butylamino isomer. Dialkylamino ((alkyl)2-N-) is,
for example, dimethylamino, methylethylamino, diethylamino, n-propylmethylamino,
dibutylamino or diisopropylamino. Preference is given to alkylamino groups having a
chain length of from 1 to 4 carbon atoms.
Cycloalkylamino or dicycloalkylamino is for example cyclohexylamino or
dicyclopropylamino.
Alkoxyalkyl groups preferably have from 1 to 6 carbon atoms. Alkoxyalkyl is,
for example, methoxymethyl, methoxyethyl, ethoxymethyl, ethoxyethyl, npropoxymethyl,
n-propoxyethyl, isopropoxymethyl or isopropoxyethyl.
Alkylthioalkyl groups preferably have from 1 to 6 carbon atoms.
Alkylthioalkyl is, for example, methylthiomethyl, methylthioethyl, ethylthiomethyl,
ethylthioethyl, n-propylthiomethyl, n-propylthioethyl, isopropylthiomethyl,
isopropylthioethyl, butylthiomethyl, butylthioethyl or butylthiobutyl.
Cycloalkyl groups preferably have from 3 to 6 ring carbon atoms and may be
substituted by one or more methyl groups; they are preferably unsubstituted, for
example cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl.
Aryl includes benzyl, phenyl, including phenyl as part of a substituent such as
phenoxy, benzyl, benzyloxy, benzoyl, phenylthio, phenylalkyl, phenoxyalkyl or tosyl,
may be in mono- or poly-substituted form, in which case the substituents may, as
desired, be in the ortho-, meta- and/or para-position(s). The term also includes, for
example, naphthalenyl.
Heterocyclyl, includes, for example, morpholinyl, tetrahydrofuryl and
heteroaryl.
Heteroaryl, including heteroaryl as part of a substituent such as heteroaryloxy,
means, for example, a five to ten (preferably five or six) member heteroaryl
containing one to three heteroatoms, each independently selected from the group
consisting of oxygen, nitrogen and sulphur. The term heteroaryl thus includes, for
example, benzofuranyl, benzimidazolyl, indolyl, isobenzofuranyl, furanyl, thiophenyl,
thiazolyl, oxazolyl, isoxazolyl, thiazolyl, pyrazolyl, isothiazolyl, pyridyl, pyridazinyl,
pyrazinyl, pyrimidinyl, pyridonyl, triazolyl, napthyridinyl and napthyridinonyl. The
heteroaryl component may be optionally mono or poly substituted as previously
defined.
Preferably, R1 is selected from the group consisting of Ala, Alb, Ale, Aid,
A2a, A2b and A2c:
wherein R5, R6, R7, R8, R9 and R13 are as defined in claim 1 and n is 0, 1, 2 or
3.
More preferably, R is selected from the group consisting of phenyl (e.g. Ala)
and 3-pyridyl (e.g. Alb). Even more preferably R1 is phenyl (e.g. Ala).
Preferably, R is selected from the group consisting of hydrogen, Ci-Cealkyl,
C2-C6alkenyl, C2-C6alkynyl, C 3-C6cycloalkyl, Ci-Cehaloalkyl Ci-Cealkoxy-Ci-
C3alkyl and C3-C6cycloalkyl-Ci-C 3alkyl. More preferably, R is selected from the
group consisting of hydrogen , amino, chloro, bromo, methyl, ethyl, isopropyl, vinyl,
propargyl, isopropenyl, methyl-S(0) p- , cyclopropyl, and cyano. Most preferably, R
is vinyl or methyl.
Preferably, R is selected from the group consisting of hydrogen, halo, cyano,
Ci-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, Ci-C6haloalkyl and C1-C6alkyl-S(0) p- . More
preferably, R is selected from the group consisting of hydrogen, halo and Ci-Cealkyl,
most preferably hydrogen.
Preferably, R4 is hydrogen.
Preferably, both R and R4 are hydrogen.
Preferably, R5 is selected from the group consisting of hydroxyl, halo, Ci-
Cealkyl, Ci-C6cycloalkyl, Ci-Cehaloalkyl, Ci-Cealkenyl, Ci-Cealkynyl, Ci-C6 alkoxy,
C -C alkoxyCi-C3alkyl, Ci-C6 alkoxy-C2-C6alkoxy, C -C alkoxy-C2-C6alkoxy-Ci-
C3alkyl, Ci-C6 haloalkoxy, Ci-C6 haloalkoxy-Ci-C 3alkyl, Ci-C6alkyl-S(0)p-, C
C6haloalkyl-S(0)p-, aryl, aryloxy, heterocyclyl, heterocyclyl-Ci-C 3alkoxy-Ci-C3alkyl,
Ci-C3alkylamino-, Ci-C3dialkylamino-, Ci-C3 alkylamino-S(0)p-, Ci-C3 alkylamino-
S(0)p-Ci-C 3alkyl-, Ci-C3 dialkylamino-S(0)p-, Ci-C3 dialkylamino-S(0)p-C 1-
C3alkyl-, Ci-C3alkylaminocarbonyl-, Ci-C3dialkylaminocarbonyl-, Ci-C3
dialkylaminocarbonyl-Ci-C 3alkyl-, Ci-C3alkylcarbonylamino-, Ci-C3 alkyl-S(0)pamino-,
cyano and nitro, wherein said heterocyclyls are five or six membered
heterocyclyls containing from one to three heteroatoms each independently selected
from the group consisting of oxygen, nitrogen and sulphur, and wherein the aryl or
heterocyclyl components may be optionally substituted by one or more substituents
selected from the group consisting of halo, Ci-C3alkyl, CrCshaloalkyl, Ci-C3 alkoxy,
Ci-C3 haloalkoxy, cyano and nitro.
The terms "aryl" and "heterocyclyl" are further defined above. However, in
the context of R5 phenyl, benzyl, isoxazolinyl, pyrimidinyl, morpholinyl, furyl and
thiophenyl are particularly preferred.
More preferably, R5 is selected from the group consisting of chloro, fluoro,
methyl, trifluoromethyl, 2-fluoroethyl-, methoxyethoxymethyl-,
trifluoromethoxymethyl-, methylS(0)p-, aryl, isoxazolinyl, morpholinyl, methyl-
S(0)p-dimethylamino-, cyano and nitro, wherein the aryl or heterocyclyl components
may be optionally substituted by one or more substituents selected from the group
consisting of chloro, methyl or trifluoromethyl. Even more preferably, R5 is selected
from the group consisting of chloro, methyl, trifluoromethyl, and methyl-S(0) p- .
Preferably, R6 is selected from the group consisting of hydrogen, halogen, Ci-
C6alkyl, Ci-Cehaloalkyl, C1-C6alkyl-S(0) p-, Ci-C 6cycloalkyl, C2-C6alkenyl, C2-
Cehaloalkenyl, C 2-C6alkynyl, C -C alkoxy-, Ci-Cehaloalkoxy, C2-C6alkenyloxy-, C3-
CecycloalkylCi-Cs-alkyl-, Ci-Ce alkoxyCi-C 3alkyl-, Ci-Ce alkoxy-C2-C6alkoxy-, nitro
and phenyl wherein the phenyl may be optionally substituted by one or more
substituents selected from the group consisting of halo, Ci-C3alkyl, Ci-Cshaloalkyl,
Ci-C3 alkoxy, Ci-C3 haloalkoxy, C1-C6alkyl-S(0) p-, phenyl, cyano and nitro. More
preferably, R6 is selected from the group consisting of hydrogen, halogen, Ci-Cealkyl,
Ci-Cehaloalkyl, Ci-C6alkyl-S(0) p-, C2-C6alkenyl and C2-C6alkynyl. Even more
preferably, R6 is selected from the group consisting of methyl, ethyl, chloro,
trifluoromethyl, and methyl-S(0) p- .
Preferably, R is selected from the group consisting of hydrogen, halogen and
Ci-C3 alkyl-. Most preferably R is hydrogen.
Preferably, R is selected from the group consisting of hydrogen, halogen and
Ci-C3 alkyl-. Most preferably R is hydrogen.
Preferably, R9 is selected from the group consisting of hydrogen, halogen,
Ci-Cealkyl, Ci-Cehaloalkyl, C1-C6alkyl-S(0) p-, Ci-C6cycloalkyl, C2-C6alkenyl, C2-
Cehaloalkenyl, C2-C6alkynyl, Ci-C6 alkoxy-, Ci-Cehaloalkoxy, C2-C6alkenyloxy-, C3-
CecycloalkylCi-Cs-alkyl-, C -C alkoxyCi-C3alkyl-, C -C alkoxy-C2-C6alkoxy-, nitro,
4,5-dihydroisoxazol-3-yl and phenyl wherein the phenyl may be optionally substituted
by one or more substituents selected from the group consisting of halo, Ci-C3alkyl,
Ci-C3haloalkyl, Ci-C3 alkoxy, Ci-C3 haloalkoxy, C1-C6alkyl-S(0) p-, phenyl, cyano
and nitro. More preferably, R9 is selected from the group consisting of hydrogen, 4,5-
dihydroisoxazol-3-yl, halogen, Ci-Cealkyl, Ci-Cehaloalkyl, Ci-C6alkyl-S(0) p-, C -
C6alkenyl and C2-C6alkynyl. Even more preferably R9 is hydrogen or 4,5-
dihydroisoxazol-3-yl.
13 Preferably, R is hydrogen or methyl.
Compounds of Formula I may contain asymmetric centres and may be present
as a single enantiomer, pairs of enantiomers in any proportion or, where more than
one asymmetric centre are present, contain diastereoisomers in all possible ratios.
Typically one of the enantiomers has enhanced biological activity compared to the
other possibilities.
Similarly, where there are disubstituted alkenes, these may be present in E or
Z form or as mixtures of both in any proportion.
Furthermore, compounds of Formula I may be in equilibrium with alternative
hydroxyl tautomeric forms. It should be appreciated that all tautomeric forms (single
tautomer or mixtures thereof), racemic mixtures and single isomers are included
within the scope of the present invention.
The present invention also includes agronomically acceptable salts that the
compounds of Formula I may form with amines (for example ammonia,
dimethylamine and triethylamine), alkali metal and alkaline earth metal bases or
quaternary ammonium bases. Among the alkali metal and alkaline earth metal
hydroxides, oxides, alkoxides and hydrogen carbonates and carbonates used as salt
formers, emphasis is to be given to the hydroxides, alkoxides, oxides and carbonates
of lithium, sodium, potassium, magnesium and calcium, but especially those of
sodium, magnesium and calcium. The corresponding trimethylsulfonium salt may also
be used.
The compounds of Formula (I) according to the invention can be used as
herbicides by themselves, but they are generally formulated into herbicidal
compositions using formulation adjuvants, such as carriers, solvents and surfaceactive
agents (SFAs). Thus, the present invention further provides a herbicidal
composition comprising a herbicidal compound according to any one of the previous
claims and an agriculturally acceptable formulation adjuvant. The composition can be
in the form of concentrates which are diluted prior to use, although ready-to-use
compositions can also be made. The final dilution is usually made with water, but can
be made instead of, or in addition to, water, with, for example, liquid fertilisers,
micronutrients, biological organisms, oil or solvents.
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 compositions can be chosen from a number of formulation types, many of
which are known from the Manual on Development and Use of FAO Specifications
for Plant Protection Products, 5th Edition, 1999. These include dustable powders
(DP), soluble powders (SP), water soluble granules (SG), water dispersible granules
(WG), wettable powders (WP), granules (GR) (slow or fast release), soluble
concentrates (SL), oil miscible liquids (OL), ultra low volume liquids (UL),
emulsifiable concentrates (EC), dispersible concentrates (DC), emulsions (both oil in
water (EW) and water in oil (EO)), micro-emulsions (ME), suspension concentrates
(SC), aerosols, capsule suspensions (CS) and seed treatment formulations. The
formulation type chosen in any instance will depend upon the particular purpose
envisaged and the physical, chemical and biological properties of the compound of
Formula (I).
Dustable powders (DP) may be prepared by mixing a compound of Formula (I)
with one or more solid diluents (for example natural clays, kaolin, pyrophyllite,
bentonite, alumina, montmorillonite, kieselguhr, chalk, diatomaceous earths, calcium
phosphates, calcium and magnesium carbonates, sulphur, lime, flours, talc and other
organic and inorganic solid carriers) and mechanically grinding the mixture to a fine
powder.
Soluble powders (SP) may be prepared by mixing a compound of Formula (I)
with one or more water-soluble inorganic salts (such as sodium bicarbonate, sodium
carbonate or magnesium sulphate) or one or more water-soluble organic solids (such
as a polysaccharide) and, optionally, one or more wetting agents, one or more
dispersing agents or a mixture of said agents to improve water dispersibility/solubility.
The mixture is then ground to a fine powder. Similar compositions may also be
granulated to form water soluble granules (SG).
Wettable powders (WP) may be prepared by mixing a compound of Formula
(I) with one or more solid diluents or carriers, one or more wetting agents and,
preferably, one or more dispersing agents and, optionally, one or more suspending
agents to facilitate the dispersion in liquids. The mixture is then ground to a fine
powder. Similar compositions may also be granulated to form water dispersible
granules (WG).
Granules (GR) may be formed either by granulating a mixture of a compound
of Formula (I) and one or more powdered solid diluents or carriers, or from pr e
formed blank granules by absorbing a compound of Formula (I) (or a solution thereof,
in a suitable agent) in a porous granular material (such as pumice, attapulgite clays,
fuller's earth, kieselguhr, diatomaceous earths or ground corn cobs) or by adsorbing a
compound of Formula (I) (or a solution thereof, in a suitable agent) on to a hard core
material (such as sands, silicates, mineral carbonates, sulphates or phosphates) and
drying if necessary. Agents which are commonly used to aid absorption or adsorption
include solvents (such as aliphatic and aromatic petroleum solvents, alcohols, ethers,
ketones and esters) and sticking agents (such as polyvinyl acetates, polyvinyl alcohols,
dextrins, sugars and vegetable oils). One or more other additives may also be
included in granules (for example an emulsifying agent, wetting agent or dispersing
agent).
Dispersible Concentrates (DC) may be prepared by dissolving a compound of
Formula (I) in water or an organic solvent, such as a ketone, alcohol or glycol ether.
These solutions may contain a surface active agent (for example to improve water
dilution or prevent crystallisation in a spray tank).
Emulsifiable concentrates (EC) or oil-in-water emulsions (EW) may be
prepared by dissolving a compound of Formula (I) in an organic solvent (optionally
containing one or more wetting agents, one or more emulsifying agents or a mixture
of said agents). Suitable organic solvents for use in ECs include aromatic
hydrocarbons (such as alkylbenzenes or alkylnaphthalenes, exemplified by
SOLVESSO 100, SOLVESSO 150 and SOLVESSO 200; SOLVESSO is a Registered
Trade Mark), ketones (such as cyclohexanone or methylcyclohexanone) and alcohols
(such as benzyl alcohol, furfuryl alcohol or butanol), N-alkylpyrrolidones (such as Nmethylpyrrolidone
or N-octylpyrrolidone), dimethyl amides of fatty acids (such as C -
Cio fatty acid dimethylamide) and chlorinated hydrocarbons. An EC product may
spontaneously emulsify on addition to water, to produce an emulsion with sufficient
stability to allow spray application through appropriate equipment.
Preparation of an EW involves obtaining a compound of Formula (I) either as
a liquid (if it is not a liquid at room temperature, it may be melted at a reasonable
temperature, typically below 70°C) or in solution (by dissolving it in an appropriate
solvent) and then emulsifying the resultant liquid or solution into water containing
one or more SFAs, under high shear, to produce an emulsion. Suitable solvents for
use in EWs include vegetable oils, chlorinated hydrocarbons (such as chlorobenzenes),
aromatic solvents (such as alkylbenzenes or alkylnaphthalenes) and other appropriate
organic solvents which have a low solubility in water.
Microemulsions (ME) may be prepared by mixing water with a blend of one
or more solvents with one or more SFAs, t o produce spontaneously a
thermodynamically stable isotropic liquid formulation. A compound of Formula (I) is
present initially in either the water or the solvent/SFA blend. Suitable solvents for use
in MEs include those hereinbefore described for use in in ECs or in EWs. An ME
may be either an oil-in-water or a water-in-oil system (which system is present may
be determined by conductivity measurements) and may be suitable for mixing watersoluble
and oil-soluble pesticides in the same formulation. An ME is suitable for
dilution into water, either remaining as a microemulsion or forming a conventional
oil-in-water emulsion.
Suspension concentrates (SC) may comprise aqueous or non-aqueous
suspensions of finely divided insoluble solid particles of a compound of Formula (I).
SCs may be prepared by ball or bead milling the solid compound of Formula (I) in a
suitable medium, optionally with one or more dispersing agents, to produce a fine
particle suspension of the compound. One or more wetting agents may be included in
the composition and a suspending agent may be included to reduce the rate at which
the particles settle. Alternatively, a compound of Formula (I) may be dry milled and
added to water, containing agents hereinbefore described, to produce the desired end
product.
Aerosol formulations comprise a compound of Formula (I) and a suitable
propellant (for example n-butane). A compound of Formula (I) may also be dissolved
or dispersed in a suitable medium (for example water or a water miscible liquid, such
as n-propanol) to provide compositions for use in non-pressurised, hand-actuated
spray pumps.
Capsule suspensions (CS) may be prepared in a manner similar to the
preparation of EW formulations but with an additional polymerisation stage such that
an aqueous dispersion of oil droplets is obtained, in which each oil droplet is
encapsulated by a polymeric shell and contains a compound of Formula (I) and,
optionally, a carrier or diluent therefor. The polymeric shell may be produced by
either an interfacial polycondensation reaction or by a coacervation procedure. The
compositions may provide for controlled release of the compound of Formula (I) and
they may be used for seed treatment. A compound of Formula (I) may also be
formulated in a biodegradable polymeric matrix to provide a slow, controlled release
of the compound.
The composition may include one or more additives to improve the biological
performance of the composition, for example by improving wetting, retention or
distribution on surfaces; resistance to rain on treated surfaces; or uptake or mobility of
a compound of Formula (I). Such additives include surface active agents (SFAs),
spray additives based on oils, for example certain mineral oils or natural plant oils
(such as soy bean and rape seed oil), and blends of these with other bio-enhancing
adjuvants (ingredients which may aid or modify the action of a compound of Formula
(I))·
Wetting agents, dispersing agents and emulsifying agents may be SFAs of the
cationic, anionic, amphoteric or non-ionic type.
Suitable SFAs of the cationic type include quaternary ammonium compounds
(for example cetyltrimethyl ammonium bromide), imidazolines and amine salts.
Suitable anionic SFAs include alkali metals salts of fatty acids, salts of
aliphatic monoesters of sulphuric acid (for example sodium lauryl sulphate), salts of
sulphonated aromatic compounds (for example sodium dodecylbenzenesulphonate,
calcium dodecylbenzenesulphonate, butylnaphthalene sulphonate and mixtures of
sodium di-z propyl- and tri-zsopropyl-naphthalene sulphonates), ether sulphates,
alcohol ether sulphates (for example sodium laureth-3-sulphate), ether carboxylates
(for example sodium laureth-3-carboxylate), phosphate esters (products from the
reaction between one or more fatty alcohols and phosphoric acid (predominately
mono-esters) or phosphorus pentoxide (predominately di-esters), for example the
reaction between lauryl alcohol and tetraphosphoric acid; additionally these products
may be ethoxylated), sulphosuccinamates, paraffin or olefme sulphonates, taurates
and lignosulphonates.
Suitable SFAs of the amphoteric type include betaines, propionates and
glycinates.
Suitable SFAs of the non-ionic type include condensation products of alkylene
oxides, such as ethylene oxide, propylene oxide, butylene oxide or mixtures thereof,
with fatty alcohols (such as oleyl alcohol or cetyl alcohol) or with alkylphenols (such
as octylphenol, nonylphenol or octylcresol); partial esters derived from long chain
fatty acids or hexitol anhydrides; condensation products of said partial esters with
ethylene oxide; block polymers (comprising ethylene oxide and propylene oxide);
alkanolamides; simple esters (for example fatty acid polyethylene glycol esters);
amine oxides (for example lauryl dimethyl amine oxide); and lecithins.
Suitable suspending agents include hydrophilic colloids (such as
polysaccharides, polyvinylpyrrolidone or sodium carboxymethylcellulose) and
swelling clays (such as bentonite or attapulgite).
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. Examples
of such mixtures are (in which T represents a compound of Formula I). I + acetochlor,
I + acifluorfen, I + acifluorfen-sodium, I + aclonifen, I + acrolein, I + alachlor, I +
alloxydim, I + ametryn, I + amicarbazone, I + amidosulfuron, I + aminopyralid, I +
amitrole, I + anilofos, I + asulam, I + atrazine, I + azafenidin, I + azimsulfuron, I +
BCPC, I + beflubutamid, I + benazolin, I + bencarbazone, I + benfluralin, I +
benfuresate, I + bensulfuron, I + bensulfuron-methyl, I + bensulide, I + bentazone, I +
benzfendizone, I + benzobicyclon, I + benzofenap, I + bicyclopyrone, I + bifenox, I +
bilanafos, I + bispyribac, I + bispyribac-sodium, I + borax, I + bromacil, I +
bromobutide, I + bromoxynil, I + butachlor, I + butamifos, I + butralin, I +
butroxydim, I + butylate, I + cacodylic acid, I + calcium chlorate, I + cafenstrole, I +
carbetamide, I + carfentrazone, I + carfentrazone-ethyl, I + chlorflurenol, I +
chlorflurenol-methyl, I + chloridazon, I + chlorimuron, I + chlorimuron-ethyl, I +
chloroacetic acid, I + chlorotoluron, I + chlorpropham, I + chlorsulfuron, I + chlorthal,
I + chlorthal-dimethyl, I + cinidon-ethyl, I + cinmethylin, I + cinosulfuron, I +
cisanilide, I + clethodim, I + clodinafop, I + clodinafop-propargyl, I + clomazone, I +
clomeprop, I + clopyralid, I + cloransulam, I + cloransulam-methyl, I + cyanazine, I +
cycloate, I + cyclosulfamuron, I + cycloxydim, I + cyhalofop, I + cyhalofop-butyl,, I
+ 2,4-D, I + daimuron, I + dalapon, I + dazomet, I + 2,4-DB, I + I + desmedipham, I +
dicamba, I + dichlobenil, I + dichlorprop, I + dichlorprop-P, I + diclofop, I + diclofopmethyl,
I + diclosulam, I + difenzoquat, I + difenzoquat metilsulfate, I + diflufenican,
I + diflufenzopyr, I + dimefuron, I + dimepiperate, I + dimethachlor, I +
dimethametryn, I + dimethenamid, I + dimethenamid-P, I + dimethipin, I +
dimethylarsinic acid, I + dinitramine, I + dinoterb, I + diphenamid, I + dipropetryn, I
+ diquat, I + diquat dibromide, I + dithiopyr, I + diuron, I + endothal, I + EPTC, I +
esprocarb, I + ethalfluralin, I + ethametsulfuron, I + ethametsulfuron-methyl, I +
ethephon, I + ethofumesate, I + ethoxyfen, I + ethoxysulfuron, I + etobenzanid, I +
fenoxaprop-P, I + fenoxaprop-P-ethyl, I + fentrazamide, I + ferrous sulfate, I +
flamprop-M, I + flazasulfuron, I + florasulam, I + fluazifop, I + fluazifop-butyl, I +
fluazifop-P, I + fluazifop-P-butyl, I + fluazolate, I + flucarbazone, I + flucarbazonesodium,
I + flucetosulfuron, I + fluchloralin, I + flufenacet, I + flufenpyr, I +
flufenpyr-ethyl, I + flumetralin, I + flumetsulam, I + flumiclorac, I + flumicloracpentyl,
I + flumioxazin, I + flumipropin, I + fluometuron, I + fluoroglycofen, I +
fluoroglycofen-ethyl, I + fluoxaprop, I + flupoxam, I + flupropacil, I + flupropanate, I
+ flupyrsulfuron, I + flupyrsulfuron-methyl-sodium, I + flurenol, I + fluridone, I +
flurochloridone, I + fluroxypyr, I + fiurtamone, I + fluthiacet, I + fluthiacet-methyl, I
+ fomesafen, I + foramsulfuron, I + fosamine, I + glufosinate, I + glufosinateammonium,
I + glyphosate, I + halosulfuron, I + halosulfuron-methyl, I + haloxyfop, I
+ haloxyfop-P, I + hexazinone, I + imazamethabenz, I + imazamethabenz-methyl, I +
imazamox, I + imazapic, I + imazapyr, I + imazaquin, I + imazethapyr, I +
imazosulfuron, I + indanofan, I + indaziflam, I + iodomethane, I + iodosulfuron, I +
iodosulfuron-methyl-sodium, I + ioxynil, I + isoproturon, I + isouron, I + isoxaben, I
+ isoxachlortole, I + isoxaflutole, I + isoxapyrifop, I + karbutilate, I + lactofen, I +
lenacil, I + linuron, I + mecoprop, I + mecoprop-P, I + mefenacet, I + mefluidide, I +
mesosulfuron, I + mesosulfuron-methyl, I + mesotrione, I + metam, I + metamifop, I
+ metamitron, I + metazachlor, I + methabenzthiazuron, I + methazole, I +
methylarsonic acid, I + methyldymron, I + methyl isothiocyanate, I + metolachlor, I +
S-metolachlor, I + metosulam, I + metoxuron, I + metribuzin, I + metsulfuron, I +
metsulfuron-methyl, I + molinate, I + monolinuron, I + naproanilide, I + napropamide,
I + naptalam, I + neburon, I + nicosulfuron, I + n-methyl glyphosate, I + nonanoic
acid, I + norflurazon, I + oleic acid (fatty acids), I + orbencarb, I + orthosulfamuron, I
+ oryzalin, I + oxadiargyl, I + oxadiazon, I + oxasulfuron, I + oxaziclomefone, I +
oxyfluorfen, I + paraquat, I + paraquat dichloride, I + pebulate, I + pendimethalin, I +
penoxsulam, I + pentachlorophenol, I + pentanochlor, I + pentoxazone, I +
pethoxamid, I + phenmedipham, I + picloram, I + picolinafen, I + pinoxaden, I +
piperophos, I + pretilachlor, I + primisulfuron, I + primisulfuron-methyl, I +
prodiamine, I + profoxydim, I + prohexadione-calcium, I + prometon, I + prometryn,
I + propachlor, I + propanil, I + propaquizafop, I + propazine, I + propham, I +
propisochlor, I + propoxycarbazone, I + propoxycarbazone-sodium, I + propyzamide,
I + prosulfocarb, I + prosulfuron, I + pyraclonil, I + pyraflufen, I + pyraflufen-ethyl, I
+ pyrasulfotole, I + pyrazolynate, I + pyrazosulfuron, I + pyrazosulfuron-ethyl, I +
pyrazoxyfen, I + pyribenzoxim, I + pyributicarb, I + pyridafol, I + pyridate, I +
pyriftalid, I + pyriminobac, I + pyriminobac-methyl, I + pyrimisulfan, I + pyrithiobac,
I + pyrithiobac-sodium, I + pyroxasulfone, I + pyroxsulam, I + quinclorac, I +
quinmerac, I + quinoclamine, I + quizalofop, I + quizalofop-P, I + rimsulfuron, I +
saflufenacil, I + sethoxydim, I + siduron, I + simazine, I + simetryn, I + sodium
chlorate, I + sulcotrione, I + sulfentrazone, I + sulfometuron, I + sulfometuron-methyl,
I + sulfosate, I + sulfosulfuron, I + sulfuric acid, I + tebuthiuron, I + tefuryltrione, I +
tembotrione, I + tepraloxydim, I + terbacil, I + terbumeton, I + terbuthylazine, I +
terbutryn, I + thenylchlor, I + thiazopyr, I + thifensulfuron, I + thiencarbazone, I +
thifensulfuron-methyl, I + thiobencarb, I + topramezone, I + tralkoxydim, I + tri-allate,
I + triasulfuron, I + triaziflam, I + tribenuron, I + tribenuron-methyl, I + triclopyr, I +
trietazine, I + trifloxysulfuron, I + trifloxysulfuron-sodium, I + trifluralin, I +
triflusulfuron, I + triflusulfuron-methyl, I + trihydroxytriazine, I + trinexapac-ethyl, I
+ tritosulfuron, I + [3-[2-chloro-4-fluoro-5-(l-methyl-6-trifluoromethyl-2,4-dioxol,
2,3,4-tetrahydropyrimidin-3-yl)phenoxy]-2-pyridyloxy]acetic acid ethyl ester (CAS
RN 353292-31-6). The compounds of the present invention may also be combined
with herbicidal compounds disclosed in WO06/024820 and/or WO07/096576.
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 b e used in the above-mentioned
formulations (in which case "active ingredient" relates to the respective mixture of
compound of Formula I with the mixing partner).
The compounds of Formula I according to the invention can also be used in
combination with one or more safeners. Likewise, mixtures of a compound of
Formula I according to the invention with one or more further herbicides can also be
used in combination with one or more safeners. The safeners can be AD 67 (MON
4660), benoxacor, cloquintocet-mexyl, cyprosulfamide (CAS RN 22 1667-31-8),
dichlormid, fenchlorazole-ethyl, fenclorim, fluxofenim, furilazole and the
corresponding R isomer, isoxadifen-ethyl, mefenpyr-diethyl, oxabetrinil, N-isopropyl4-(
2-methoxy-benzoylsulfamoyl)-benz amide (CAS RN 2 2 16 6 8-34-4). Other
possibilities include safener compounds disclosed in, for example, EP0365484 e.g N-
(2-methoxybenzoyl)-4-[(methylaminocarbonyl)amino]benzenesulfonamide.
Particularly preferred are mixtures of a compound of Formula I with cyprosulfamide,
isoxadifen-ethyl, cloquintocet-mexyl and/or N-(2-methoxybenzoyl)-4-[(methylaminocarbonyl)
amino]benzenesulfonamide.
The safeners of the compound of Formula I may also be in the form of esters
or salts, as mentioned e.g. in The Pesticide Manual, 14th Edition (BCPC), 2006. The
reference to cloquintocet-mexyl also applies to 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 present invention still further provides a method of selectively controlling
weeds at a locus comprising crop plants and weeds, wherein the method comprises
application to the locus of a weed controlling amount of a composition according to
the present invention. '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- or postemergence;
seed dressing; 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. Maize is particularly
preferred.
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 glufosinateresistant
maize varieties commercially available under the trade names
RoundupReady® and LibertyLink®.
In a preferred embodiment the crop plant is rendered tolerant to HPPDinhibitors
via genetic engineering. Methods of rending crop plants tolerant to HPPDinhibitors
are known, for example from WO0246387. Thus in an even more preferred
embodiment the crop plant is transgenic in respect of a polynucleotide comprising a
DNA sequence which encodes an HPPD-inhibitor resistant HPPD enzyme derived
from a bacterium, more particularly from Pseudomonas fluorescens or Shewanella
colwelliana, or from a plant, more particularly, derived from a monocot plant or, yet
more particularly, from a barley, maize, wheat, rice, Brachiaria, Chenchrus, Lolium,
Festuca, Setaria, Eleusine, Sorghum or Avena species.
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.
The compositions can be used to control unwanted plants (collectively,
'weeds'). The weeds to be controlled may be both monocotyledonous species, for
example Agrostis, Alopecurus, Avena, Brachiaria, Bromus, Cenchrus, Cyperus,
Digitaria, Echinochloa, Eleusine, Lolium, Monochoria, Rottboellia, Sagittaria, Scirpus,
Setaria and Sorghum, and dicotyledonous species, for example Abutilon, Amaranthus,
Ambrosia, Chenopodium, Chrysanthemum, Conyza, Galium, Ipomoea, Nasturtium,
Sida, Sinapis, Solanum, Stellaria, Veronica, Viola and Xanthium. Weeds can also
include plants which may be considered crop plants but which are growing outside a
crop area ('escapes'), or which grow from seed left over from a previous planting of a
different crop ('volunteers'). Such volunteers or escapes may be tolerant to certain
other herbicides.
The compounds of the present invention can be prepared using the following methods.
Compounds of formula (la) may be prepared from compounds of formula (I) as
shown in reaction scheme 1.
Reaction scheme 1
Compounds of formula (la), in which R4 is hydrogen, may be prepared from
compounds of formula 1 in which R4 is lower alkyl, for example methyl, by heating
with morpholine (Nagashima, Hiromu et al. Heterocycles, 26(1), 1-4; 1987); or by
reaction with boron tribromide in a suitable solvent such as dichloromethane.
Compounds of formula (1) may be prepared from compounds of formula (2) as shown
in reaction scheme 2.
Reaction scheme 2
Compounds of formula (1) in which R4 is lower alkyl, for example methyl, may be
prepared from compounds of formula (2), in which X is a suitable leaving group such
as chlorine or bromine, by reaction with a suitable metal alkoxide, for example
sodium methoxide, in a suitable solvent such as dioxane;
Compounds of formula (2) may be prepared from compounds of formula (3) as shown
in reaction scheme 3.
Reaction scheme 3
(3) (2)
Compounds of formula (2) in which X is a suitable leaving group such as chlorine or
bromine may be prepared from compounds of formula (3) by reaction with a suitable
hydrazine in the presence of a suitable acidic solvent such as aqueous hydrochloric
acid either with heating or microwave catalysis.
Compounds (3) in which R2 and X are both chlorine or bromine, and R3 is hydrogen
are commercially available.
Compounds (3) in which R2 and R3 are as defined above may be prepared according
to known procedures for example as disclosed in Bioorganic and Med. Chem., 2010,
18(14), 5224, Bioorganic and Med. Chem., 2008, 14(19), 9056 and WO03/093220.
Compounds of formula (2) may also be prepared from compounds of formula (2a) as
show in reaction scheme 4
Reaction scheme 4
(2a) (2)
Compounds of formula (2) may be prepared from compounds of formula (2a) in
which X and Z are halogens such as bromine, chlorine or iodine, by reaction with a
suitable metal or metalloid derivative Y-M (e.g. a boronic acid or ester, a trialkyltin
derivative, a zinc derivative or a Grignard reagent) in the presence of a suitable base
(e.g. an inorganic base, such as potassium phosphate or caesium fluoride), a metal
source (e.g. a palladium source, such as Pd (OAc)2) and optionally a ligand for the
metal (e.g. a phosphine ligand) in a suitable solvent (e.g. a single solvent, such as
dimethylformamide, or a mixed solvent system such as a mixture of dimethoxyethane
and water or toluene and water). The metal catalyst and ligands may also be added as
a single, pre-formed complex (e.g. a palladium/phosphine complex, such as
bis(triphenylphosphine)palladium dichloride or [I , -
bis(diphenylphosphino)ferrocene] palladium dichloride dichloromethane adduct).
Compounds of formula (2a) may be prepared from compounds of formula (3a) as
shown in reaction scheme 5.
Reaction scheme 5
(3a) (2a)
Compounds of formula (2a) in which X and Z are suitable leaving groups such as
chlorine or bromine, may be prepared from compounds of formula (3a) by reaction
with a suitable hydrazine in the presence of a suitable acidic solvent such as aqueous
hydrochloric acid either with heating or microwave catalysis.
Examples
Example 1
2-[3-f4,5-dihvdroisoxazol-3-yl)-2-methyl-4-methylsulfonyl-phenyll-4-hydroxy-5-
methylsulfanyl-pyridazin-3-one
Step 1
4,5-dibromo-2-[3-f4,5-dihvdroisoxazol-3-yl)-2-methyl-4-methylsulfonylphenyll
pyridazin-3-one
To a suspension of [3-(4,5-dihydroisoxazol-3-yl)-2-methyl-4-methylsulfonylphenyl]
hydrazine (1.8 g, 6.7 mmol) in 4M hydrobromic acid (25 ml) was added 3,4-
dibromo-2-hydroxy-2H-furan-5-one (2. If, 8.0 mmol) at 25 °C. The solution was
refluxed for 3 hours. The reaction mixture was extracted with ethyl acetate, washed
with water, dried over anhydrous magnesium sulphate and concentrated under
reduced pressure. The residue was purified by flash column chromatography on silica
gel eluting with ethyl acetate in iso-hexane (0-100 %), to give the 4,5-dibromo-2-[3-
(4,5-dihydroisoxazol-3-yl)-2-methyl-4-methylsulfonyl-phenyl]pyridazin-3-one as a
yellow solid (1.68g).
1H NMR (CDC13) :
8.1 (lH,d), 8.0(lH,s), 7.55(lH,d), 4.6 (2H,t), 3.35 (2H,br), 3.2(3H,s), 2.1(3H,s)
Aryl hydrazines such as [3-(4,5-dihydroisoxazol-3-yl)-2-methyl-4-methylsulfonylphenyljhydrazine
may be prepared from the corresponding bromide according to
literature procedures e.g. as described in Tetrahedral Letters 40 (1999) 3543-3546, or
from the aniline as described in Org. Synth. 1941, Coll. Vol. 1, 442. 3-(3-bromo-2-
chloro-6-methylsulfonyl-phenyl)-4,5-dihydroisoxazole can be prepared as reported for
example in DE 19820722. 3,4-dibromo-2-hydroxy-2H-furan-5-one is commercially
available.
Step 2
5-bromo-2-[3-f4,5-dihvdroisoxazol-3-yl)-2-methyl-4-methylsulfonyl-phenyll-4-
methoxy-pyridazin-3-one
A solution of sodium methoxide in methanol (5.4 mol/1, 0.68ml, 3.7mmol) was added
drop wise over 4 hours to a stirred solution of4,5-dibromo-2-[3-(4,5-dihydroisoxazol-
3-yl)-2-methyl-4-methylsulfonyl-phenyl]pyridazin-3-one (1.676 g, 3.412 mmol) in
dioxane (20 ml) at room temperature under an atmosphere of nitrogen. The resulting
mixture was stirred at room temperature for a further hour, and then poured into a
mixture of water (50 ml) and dichloromethane (50 ml). The organic layer was
separated and the aqueous layer extracted with dichloromethane (2 x 50 ml). The
combined organic extracts were washed with water, then brine, dried over magnesium
sulphate and concentrated under reduced pressure. The residue was purified by flash
column chromatography on silica gel using ethyl acetate in iso-hexane (0-100 %) as
eluent, to give 5-bromo-2-[3-(4,5-dihydroisoxazol-3-yl)-2-methyl-4-methylsulfonylphenyl]
-4-methoxy-pyridazin-3 -one (600 mg as a white solid.
1H NMR (CDC13) :
8.1 (lH,d), 8.0(lH,s), 7.55(lH,d), 4.6 (2H,t), 4.3 (3H,s), 3.35(2H,br), 3.2(3H,s),
2.1(3H,s)
Step 3
2-[3-f4,5-dihvdroisoxazol-3-yl)-2-methyl-4-methylsulfonyl-phenyll-4-methoxy-5-
methylsulfanyl-pyridazin-3-one
The 5-bromo-2-[3-(4,5-dihydroisoxazol-3-yl)-2-methyl-4-methylsulfonyl-phenyl]-4-
methoxy-pyridazin-3-one (200 mg, 0.45mmol) was dissolved inN,Ndimethylformamide
(5 ml, 64 mmol). Sodium thiomethoxide (40 mg, 0.54 mmol)
was added and the reaction mixture quickly darkened in colour from yellow to red.
LCMS after 2 hours showed good conversion to the desired product but there was still
starting material present. More sodium thiomethoxide was added to drive the reaction
to completion. Water and diethyl ether were added. The organic extracts were washed,
dried over anhydrous magnesium sulphate and evaporated to yield a 1:1 mixture of 2-
[3-(4,5-dihydroisoxazol-3-yl)-2-methyl-4-methylsulfonyl-phenyl]-4-methoxy-5-
methylsulfanyl-pyridazin-3-one (60 mg, 0.15 mmol) and 2-[3-(4,5-dihydroisoxazol-
3-yl)-2-methyl-4-methylsulfonyl-phenyl]-4,5-bis(methylsulfanyl)pyridazin-3-one (60
mg, 0.14mmol) as a yellow solid.
This mixture was used directly without further purification in the following reaction.
Step 4
2-[3-f4,5-dihvdroisoxazol-3-yl)-2-methyl-4-methylsulfonyl-phenyll-4-hydroxy-5-
methylsulfanyl-pyridazin-3-one
2-[3-(4,5-dihydroisoxazol-3-yl)-2-methyl-4-methylsulfonyl-phenyl]-4-methoxy-5-
methylsulfanyl-pyridazin-3-one (55 mg, 0.13 mmol) and 2-[3-(4,5-dihydroisoxazol-3-
yl)-2-methyl-4-methylsulfonyl-phenyl]-4,5-bis(methylsulfanyl)pyridazin-3-one (55
mg, 0.13 mmol) were dissolved in acetonitrile (9 ml) in a 20ml microwave tube and
sodium iodide (100 mg, 0.67 mmol) was added. Chloro(trimethyl)silane (0.15 ml, 1.2
mmol) was added and the yellow reaction mixture immediately went red-orange. The
reaction mixture was stirred in a microwave vial at 100°C for 35 minutes and then
was poured into water, basified with 2M aqueous sodium hydroxide and extracted into
ether. The organic extracts were dried over anhydrous magnesium sulphate and
evaporated to yield recovered 2-[3-(4,5-dihydroisoxazol-3-yl)-2-methyl-4-
methylsulfonyl-phenyl]-4,5-bis(methylsulfanyl)pyridazin-3-one as a pale yellow solid
(47mg). The basic aqueous layer was acidified with 2M hydrochloric acid and
extracted with dichloromethane. The organic extracts were washed with an aqueous
solution of sodium metabisulphite and passed through a second phase separation
cartridge, then evaporated to yield 2-[3-(4,5-dihydroisoxazol-3-yl)-2-methyl-4-
methylsulfonyl-phenyl]-4-hydroxy-5-methylsulfanyl-pyridazin-3-one as a pale yellow
solid (50mg).
Example 2
2-[3-f4,5-dihvdroisoxazol-3-yl)-2-methyl-4-methylsulfonyl-phenyll-4-hvdroxy-5-
methylsulfonyl-pyridazin-3-one
Step 1
2-[3-f4,5-dihvdroisoxazol-3-yl)-2-methyl-4-methylsulfonyl-phenyll-4-hydroxy-5-
methylsulfonyl-pyridazin-3-one
2-[3-(4,5-dihydroisoxazol-3-yl)-2-methyl-4-methylsulfonyl-phenyl]-4-hydroxy-5-
methylsulfanyl-pyridazin-3-one (70 mg, 0.18mmol) was dissolved in acetic acid (5
ml); hydrogen peroxide (0.4 ml, lmmol) was added, and the pale pink reaction
mixture was heated at 50°C for 2 hours. The reaction mixture was cooled and
partitioned between water and dichloromethane. The organic extracts were separated
and washed with saturated sodium hydrogen carbonate. The aqueous layer was very
carefully acidified and re-extracted with dichloromethane. The combined organic
extracts were passed through a phase-separation cartridge and evaporated to yield 2-
[3-(4,5-dihydroisoxazol-3-yl)-2-methyl-4-methylsulfonyl-phenyl]-4-hydroxy-5-
methylsulfonyl-pyridazin-3-one as a pinky-white solid (35 mg).
2-[3-(4,5-dihydroisoxazol-3-yl)-2-methyl-4-methylsulfonyl-phenyl]-4-hydroxy-5-
methylsulfanyl-pyridazin-3-one was prepared as described in Example 1.
Example 3
2-[3-f4,5-dihvdroisoxazol-3-yl)-2-methyl-4-methylsulfonyl-phenyll-4-hvdroxy-5-
methyl-pyridazin-3-one
Step 1
2-[3-f4,5-dihvdroisoxazol-3-yl)-2-methyl-4-methylsulfonyl-phenyll-4-methoxy-5-
methyl-pyridazin-3-one
A mixture o f 5-bromo-2-[3-(4,5-dihydroisoxazol-3-yl)-2-methyl-4-methylsulfonylphenyl]-
4-methoxy-pyridazin-3-one (200mg, 0.45mmol), -[3-(4,5-dihydroisoxazol-3-
yl)-2-methyl-4-methylsulfonyl-phenyl] -4-methoxy-pyridazin-3 -One, [1,
bis(diphenylphosphino)ferrocene]palladium (II) dichloride dichloromethane adduct
(80mg, 0.09 mmol) in tetrahydrofuran (2ml) was heated to reflux followed by the
addition of methylzinc chloride (2.0mol/l, 0.23ml,0.45mmol). The reaction mixture
was heated at reflux for 2 hours then allowed to cool to room temperature. Upon
cooling, the reaction mixture was diluted with saturated ammonium chloride solution
and extracted with ethyl acetate. The organics were filtered through Celite, dried over
anhydrous magnesium sulphate and concentrated under reduced pressure. The residue
was purified using column flash column chromatography eluting with ethyl acetate in
iso-hexane, t o give 2-[3-(4,5-dihydroisoxazol-3-yl)-2-methyl-4-methylsulfonylphenyl]-
4-methoxy-5-methyl-pyridazin-3-one (0.123 g) as a yellow solid.
8.1 (lH,d), 7.7(lH,s), 7.6(lH,d), 4.6 (2H,t), 4.2 (3H,s), 3.4(2H,br), 3.2 (3H,s)
2.2(3H,s), 2.1(3H,s)
5-bromo-2-[3-(4,5-dihydroisoxazol-3-yl)-2 -methyl-4-methylsulfonyl-phenyl]-4-
methoxy-pyridazin-3-one prepared as described above in example 1.
Step 2
2-[3-f4,5-dihvdroisoxazol-3-yl)-2-methyl-4-methylsulfonyl-phenyll-4-hydroxy-5-
methyl-pyridazin-3-one
A mixture of 2-[3-(4,5-dihydroisoxazol-3-yl)-2-methyl-4-methylsulfonyl-phenyl]-4-
methoxy-5-methyl-pyridazin-3-one.
2-[3-(4,5-dihydroisoxazol-3-yl)-2-methyl-4-methylsulfonyl-phenyl]-4-methoxy-5-
methyl-pyridazin-3-one (0.12 g, 0.33 mmol) and sodium hydroxide monohydrate (3
mol/1, 2 ml, 6 mmol,) and refluxed for 3 hours under an atmosphere of nitrogen. The
reaction was then allowed to cool to room temperature. The resulting residue was
washed with diethyl ether (15 ml) and water. The aqueous layer was slowly acidified
using concentrated hydrochloric acid until the product precipitated and the solution
was acidic (pH 5). The product was dried in a vacuum oven overnight to leave 2-[3-
(4,5-dihydroisoxazol-3 -yl)-2-methyl-4-methylsulfonyl -phenyl]-4-hydroxy-5 -methylpyridazin-
3-one( 0.09g) as a pale yellow solid.
Example 4
5-chloro-2-[2-chloro-4-ftrifluoromethyl)phenyll-4-hvdroxy-pyridazin-3-one
Step 1:
4,5-dichloro-2-[2-chloro-4-ftrifluoromethyl)phenyllpyridazin-3-one
To a suspension of [2-chloro-4-(trifluoromethyl)phenyl]hydrazine (0.5g, 2.37mmol)
in 4M hydrochloric acid (6ml) was added 3,4-dichloro-2-hydroxy-2H-furan-5-one
(0.4g, 2.37mmol) at 25°C. The mixture was heated under microwave irradiation at
140°C for 2 hours, and then allowed to cool to room temperature. The reaction
mixture was diluted with ethyl acetate and washed with water. The organic extracts
were dried over magnesium sulphate and evaporated, then purified by reverse phase
HPLC to give 4,5-dichloro-2-[2-chloro-4-(trifluoromethyl)phenyl]pyridazin-3-one as
a yellow solid (135mg).
7.95(1H, s), 7.8(lH,s), 7.7(1H, d), 7.5(1H, d)
3,4-dichloro-2-hydroxy-2H-furan-5-one (mucochloric acid) is commercially available.
Aryl hydrazines such as [2-chloro-4-(trifluoromethyl)phenyl]hydrazine may be
prepared according to literature procedures e.g. from the commercially available
bromides as described in Tetrahedral Letters 40 (1999) 3543-3546 or from the aniline
as described in Org. Synth. 1941, Coll. Vol. 1, 442.
Step 2 :
5-chloro-2-[2-chloro-4-ftrifluoromethyl)phenyll-4-methoxy-pyridazin-3-one
A solution of sodium methoxide solution (30% in methanol, 5.4M, 0.07ml, 0.42 mmol)
was added drop wise over 5 minutes to a stirred solution of 4,5-dichloro-2-[2-chloro-
4-(trifluoromethyl)phenyl]pyridazin-3-one (135mg, 0.39 mmol) in dioxane (1.9ml)
at room temperature under an atmosphere of nitrogen. The resulting mixture was
stirred at room temperature for a further hour, and then poured into a mixture of water
(25 ml) and dichloromethane (25 ml). The organic layer was separated and the
aqueous layer extracted with dichloromethane (2 x 25 ml). The combined organic
extracts were washed with water, then brine, dried over magnesium sulphate and
concentrated under reduced pressure, to give 5-chloro-2-[2-chloro-4-
(trifluoromethyl)phenyl]-4-methoxy-pyridazin-3-one as the major product together
with some of the isomeric 4-chloro-2-[2-chloro-4-(trifluoromethyl)phenyl]-5-
methoxy-pyridazin-3-one as an orange solid (107mg). This was used directly without
further purification.
7.9(1H, s), 7.8(lH,s), 7.7(1H, d), 7.5(1H, d), 4.2 (3H,s)
Step 3 :
5-chloro-2-[2-chloro-4-ftrifluoromethyl)phenyll-4-hvdroxy-pyridazin-3-one
A mixture of 5-chloro-2- [2-chloro-4-(trifluoromethyl)phenyl] -4-methoxy-pyridazin-3 -
one and 4-chloro-2- [2-chloro-4-(trifluoromethyl)phenyl] -5-methoxy-pyridazin-3 -one
(107mg, 0.277mmol) and morpholine (2,5ml) was heated at 100°C for 3 hours under
an atmosphere of nitrogen. The reaction mixture was allowed to cool to room
temperature and then evaporated under reduced pressure. The resulting residue was
dissolved in ethyl acetate (15ml) and washed with 2M hydrochloric acid (3 x 15ml)
and brine (15ml). The organic extract was dried over magnesium sulphate and
purified by reverse phase HPLC to give 5-chloro-2-[2-chloro-4-
(trifluoromethyl)phenyl]-4-hydroxy-pyridazin-3-one as a white solid (35mg) along
with its isomer 4-chloro-2-[2-chloro-4-(trifluoromethyl)phenyl]-5-hydroxy-pyridazin-
3-one as a white solid (lOmg).
5-chloro-2-[2-chloro-4-(trifluoromethyl)phenyl]-4-hydroxy-pyridazin-3-one: 7.9(1H,
s), 7.8(lH,s), 7.7(1H, d), 7.6(1H, d)
4-chloro-2-[2-chloro-4-(trifluoromethyl)phenyl]-5-hydroxy-pyridazin-3-one: 7.9(1H,
s), 7.8(lH,s), 7.7(1H, d), 7.6(1H, d)
Example 5
4-Isopropenyl-l-[2-methylsulfonyl-4-ftrifluoromethyl)phenyll-4H-pyridazine-
5.,6-dione
Step 1
Tert-butyl N-[2-methylsulfonyl-4-ftrifluoromethyl)anilinol carbamate
To a stirred mixture of l-bromo-2-methylsulfonyl-4-(trifluoromethyl)benzene (13.2
mmol, 4.00 g) , tert-butyl carbazate (26.4 mmol, 3.56 g) , Cs2C0 3 (13.2 mmol, 4.34 g)
and Pd(dppf)Cl 2. Dichloromethane adduct (2.64 mmol, 2.20 g) under a nitrogen
atmosphere was added degassed toluene (27ml). Nitrogen was bubbled through the
reaction mixture for 15min before stirring at 105°C under an atmosphere of nitrogen.
The reaction mixture was heated for 2hr, then cooled, diluted with dichloromethane
(50ml), and the residue in the reaction flask was scratched out with more
dichloromethane. The combined organic layers were filtered, washed through with
fresh dichloromethane till washings clear and concentrated under reduced pressure to
give a red brown oil. Using a volume of 200ml silica slurried in a glass column with
1:l/Et 20:isohexane as solvent, the crude material was taken up in a minimum of
dichloromethane, added to the silica and eluted with the same solvent. Fractions
containing the desired product were collected, giving 2.95g of a sticky pale yellow
solid which was tritrated with isohexane, filtered and air dried to give
tert-butyl N-[2-methylsulfonyl-4-(trifluoromethyl)anilino]carbamate as a pale brown
solid (2.63g).
1H NMR(CDC13) : 58.07(lH,s), 7.95(lH,brs), 7.72(lH,d), 7.22(lH,d), 6.45(lH,brs),
3.20(3H,brs), 1.50(9H,s)
Step 2 :
2,3-dibromo-4- [2-methylsulfonyl-4-(trifluoromethvDphenyll hydrazonolbut-2-
enoic acid
To tert-butyl N-[2-methylsulfonyl-4-(trifluoromethyl)anilino]carbamate (5.28 mmol,
1.87 g) was added 4M aqueous hydrochloric acid (20ml). The reaction was stirred at
110°C for 30min, cooled to 70°C and mucobromic acid (5.28 mmol, 1.39 g) was
added in one portion. An immediate yellow precipitate formed; the reaction mixture
was stirred at this temperature for 2hr then hot filtered, washing out the flask with
25ml hot water. The resulting yellow solid was taken up in ethyl acetate, dried over
magnesium sulphate, filtered and concentrated under reduced pressure giving (Z,4Z)-
2,3-dibromo-4-[[2-methylsulfonyl-4-(trifluoromethyl)phenyl]hydrazono]but-2-enoic
acid as a yellow solid (2.44 g).
lH NMR(CDCl 3+drop d6DMSO): 510.30(lH,s), 8.59(lH,s), 8.05(lH,s), 7.93(lH,d),
7.79(lH,d), 3.12(3H,s)
Step 3
4,5-dibromo-2-[2-methylsulfonyl-4-ftrifluoromethyl)phenyllpyridazin-3-one
To a stirred solution of (Z,4Z)-2,3-dibromo-4-[[2-methylsulfonyl-4-
(trifluoromethyl)phenyl]hydrazono]but-2-enoic acid (1.65 g, 1.00 equiv) in
tetrahydrofuran (30ml) at room temperature, was added 1, 1'-carbonyldiimidazole
(0.614g) in one portion. The reaction mixture was then stirred at 50°C for 1 hour
then cooled, and concentrated under reduced pressure to give a purple oil. This oil
was taken up in the minimum of dichloromethane and added to a lOg isolute
cartridge, eluting with dichloromethane. The fractions containing the desired product
were combined and concentrated under reduced pressure to give 4,5-dibromo-2-[2-
methylsulfonyl-4-(trifluoromethyl)phenyl]pyridazin-3-one as an off white solid
(l-12g).
1H NMR(CDC13) : 58.12(lH,s), 7.93(lH,s), 7.75(lH,d), 7.40(lH,d), 3.20(3H,s)
Step 4
5-bromo-4-methoxy-2-[2-methylsulfonyl-4-ftrifluoromethyl)phenyllpyridazin-3-
one
To 1,4-dioxane (15ml) was added under nitrogen 4,5-dibromo-2-[2-methylsulfonyl-4-
(trifluoromethyl)phenyl]pyridazin-3-one (1.35 g). The mixture was stirred at room
temperature as a solution of sodium methoxide (3.06 mmol, 0.169 g, 1.08 equiv)
(0.55mls of 30% sodium methoxide in methanol in 4.8ml methanol and 7.2 ml 1,4-
dioxane) was added via syringe pump over 3.25 hr and then stirred for a further lhr at
room temperature. The reaction mixture was poured into water (25ml) and extracted
with ethyl acetate (2x 20ml); the organic extracts were combined and washed with
water and saturated brine before drying over magnesium sulphate, then filtered and
concentrated under reduced pressure to give the crude product as a thick orange oil
( 1.33g). This oil was purified by column chromatography on silica, and eluting with a
gradient of hexane/ethyl acetate to give 5-bromo-4-methoxy-2-[2-methylsulfonyl-4-
(trifluoromethyl)phenyl]pyridazin-3-one (0.780 g) and also the isomeric 4-bromo-5-
methoxy-2-[2-methylsulfonyl-4-(trifluoromethyl)phenyl]pyridazin-3-one (0.307 g) as
cream solids.
1H NMR(CDC13) :
5-bromo-4-methoxy-2- [2-methylsulfonyl-4-(trifluoromethyl)phenyl]pyridazin-3 -one :
58.42(lH,brs), 8.07(lH,dd), 7.96(lH,s), 7.64(lH,d), 4.30(3H,s), 3.24(3H,s)
4-bromo-5-methoxy-2- [2-methylsulfonyl-4-(trifluoromethyl)phenyl]pyridazin-3 -one :
58.40(lH,brs), 8.05(lH,dd), 7.90(lH,s), 7.60(lH,d), 4.17(3H,s), 3.25(3H,s)
Step
5-isopropenyl-4-methoxy-2-[2-methylsulfonyl-4-ftrifluoromethyl)phenyll
pyridazin-3-one
Nitrogen was bubbled through 1,2-dimethoxyethane (8ml) for 15 minutes before
adding to a mixture of 5-bromo-4-methoxy-2-[2-methylsulfonyl-4-
(trifluoromethyl)phenyl]pyridazin-3-one (0.65 g) , caesium fluoride (0.46 g),
isopropenylboronic acid pinacol ester (0.27 g) and[l,l'-
bis(diphenylphosphino)ferrocene]palladium(II)dichloride dichloromethane adduct
(0.13 g) in a 20ml microwave vial. The mixture was gently stirred as nitrogen was
bubbled through for a further 5 minutes, before capping the vial. The mixture was
microwaved for 30min at 150°C then allowed to cool and filtered and washed through
with ethyl acetate. The filtrate was concentrated under reduced pressure giving a thick
red-brown oil which was purified by column chromatography on silica, loading in a
minimum of dichloromethane and eluting with a gradient of isohexane/ethyl acetate.
Fractions containing the desired product were concentrated under reduced pressure to
give 5-isopropenyl-4-methoxy-2-[2-methylsulfonyl-4-
(trifluoromethyl)phenyl]pyridazin-3-one as a thick brown oil (0.290 g).
1H NMR (CDCI3) : 58.40(lH,s), 8.04(lH,d), 7.80(lH,s), 7.66(lH,d), 5.40(lH,m),
5.34(lH,m), 4.17(3H,s), 3.28(3H,s), 2.17(3H,s)
Step 6
4-isopropenyl-l-[2-methylsulfonyl-4-ftrifluoromethyl)phenyll-4H-pyridazine-5.,
6-dione
5-isopropenyl-4-methoxy-2-[2-methylsulfonyl-4-(trifluoromethyl)phenyl]pyridazin-3-
one (0.232 g) in morpholine (0.520 g) was stirred at 100°C for 45min. The reaction
mixture was cooled, and excess morpholine removed under high vacuum. The
resulting residue was taken up in dichloromethane, washed quickly with 1M aqueous
hydrochloric acid and passed through a phase separator. The filtrate was concentrated
under reduced pressure to give the crude product as a pale brown solid (170mg). This
crude material was taken up in a minimum of dichloromethane and purified by
column chromatography on silica eluting with ethyl acetate. Fractions containing the
desired product were combined and concentrated under reduced pressure to give 4-
isopropenyl- 1-[2-methylsulfonyl-4-(trifluoromethyl)phenyl] -4H-pyridazine-5 ,6-dione
as a pink solid (0.085g).
1H NMR (CDC13): 58.45(lH,brs), 8.05(lH,d), 7.91(lH,s), 7.66(lH,d), 5.63(lH,brs),
5.49(lH,brs), 3.25(3H,s). Melting point: 144°C-147°C.
TABLE CI - Examples of herbicidal compounds of the present invention.

CMP R2 X3 R5 R6 R9 NMR
8.01 ( 1 H, s), 7.80 ( 1
1.023 -Br N -CH3 -CF3 - H, d), 7.70 ( 1 H, d),
2.48 (3 H, s)
8.03 ( 1 H, d) 7.99 ( 1 H,
s) 7.84 ( 1 H, d) 5.55 ( 1
H, s) 5.44 ( 1 H, t) 2.45
1.024 -CH(CH 3)=CH N -CH3 -CF3 - (3 H, s) 2.20 - 2.24 (3
H, m)652
7.86 ( 1 H, s), 7.81 ( 1
H, d), 7.68 ( 1 H,
1.025 -S-CH 3 N -CH3 -CF3 - d),
2.63 (3 H, s), 2.49 (3
H, s)
1.026 -CN CR9 -CH3 - S(0) 2Me
7.91(2H,d),
7.82(lH,d), 7.70
1.027 H N -CH3 -CF3 - (lH,d), 6.78 (lH,d),
2.48(3H,s)
(TFA Salt)
1.028 H N -CH3 -CF3 -
8.31 ( 1 H, s), 7.84 ( 1
H,d), 7.70 ( 1 H, d),
1.029 -S(0) 2Me N -CH3 -CF3 - 3.35 (3 H, s), 2.50 (3
H, s)
8.25 ( 1 H, s), 7.87 ( 1
H, d), 7.73 ( 1 H, d),
1.030 -S(0)Me N -CH3 -CF3 -S(0) 2M e 3.01 (3 H, s), 2.49 (3
H, s)
CMP R 2 X3 R 5 R 6 R 9 NMR
0.96 - 1.03 (2 H, m)
1.09 - 1.17 (2 H, m)
1.97 - 2.08 ( 1 H, m)
1.031 -cPr CR9 -S(0) 2Me -CF 3 H 3.25 (3 H, s) 7.48 ( 1 H,
s) 7.62 - 7.66 ( 1 H, m)
8.02 - 8.06 ( 1 H, m)
8.41 - 8.44 ( 1 H, m)
8.44 ( 1 H, d), 8.03 -
8.12 ( 1 H, m), 7.98 ( 1 1.032 -Br CR9 -S(0) 2Me -CF 3 H H, s), 7.65 ( 1 H, d),
3.24 (3 H, s)
8.44 ( 1 H, d), 8.06 ( 1
H, dd), 7.86 ( 1 H, d), 1.033 H CR9 -S(0) 2Me -CF 3 H 7.67 ( 1 H, d), 6.74 ( 1
H, d), 3.24 (3 H, s)
8.43 ( 1 H, d), 8.05 ( 1
H, dd), 7.83 ( 1 H, s), 1.034 -S-CH 3 CR9 -S(0) 2Me -CF 3 H 7.65 ( 1 H, d), 3.26 (3
H, s), 2.61 (3 H, s)
3.84 (3 H, s) 6.73 ( 1 H,
d, J=4.8 Hz) 7.89 ( 1 H,
1.035 H N -S(0) 2Me -CF 3 - d, J=4.8 Hz) 8.34 ( 1 H,
d, J=8.6 Hz) 8.41 -
8.45 ( 1 H, m)
1.28 (3 H, t, J=7.8 Hz)
2.63 (2 H, q, J=7.5 Hz)
3.35 (3 H, s) 7.23 ( 1 H, 1.036 -ethyl N -S(0) 2Me -CF 3 - br. s.) 7.83 ( 1 H, s)
8.07 ( 1 H, d, J=8.1 Hz)
8.16 ( 1 H, d, J=7.5 Hz)
8.16(lH,s),
7.75(2H,m),
1.037 -ethyl CR9 -S(0) Me -CI H 7.45(lH,d),
3.21(3H,s),2.63(2H,q),
1.30(3H,t)
8.16(lH,s),7.75(2H,m),
1.038 -ethyl CR9 -S(0) Me -ethyl H 7.45(lH,d), 3.21(3H,s),
2.63(2H,q), 1.30(3H,t)

TABLE C2 - Examples of herbicidal compounds of the present invention.
Compound R2 R5 R13a R13b
2.001 Ethyl -CF3 H H
2.002 Methyl -CF3 Methyl Methyl
TABLE C3 - Examples of herbicidal compounds of the present invention.
Compound R2 R8 R7
3.001 Methyl Methyl -phenyl
3.002 Methyl Methyl
3.003 Methyl Methyl n-butyl
TABLE C4 - Examples of herbicidal compounds of the present invention.
Compound R2 R5 R6
4.001 Methyl -CF3
TABLE C5 - Examples of herbicidal compounds of the present invention.
Compound R2 R6 R9
5.007 -CH3 H CH C(=CH )-CH -
5.008 -CH3 H Benzyl-
5.009 -CH3 H CH OCH CH -
5.010 -CH3 -CF Me
5.01 1 -CH -CF CH =CHCH -
5.012 -CH H
5.013 -CH H
5.014 -CH H
Compound R2 R6 R9
5.015 -CH3 H 3C1, 4-F-phenyl-
5.016 -CH3 H 4-MeO-phenyl-
5.017 -CH3 H 4-Me-phenyl
5.01 8 -CH3 H Phenyl-
5.019 -CH H 3-F,4-Me-phenyl-
5.020 -CH H 2-Cl,4-Me-phenyl-
5.021 -CH H 3-CN-phenyl-
5.022 -CH H

TABLE C6 - Examples of herbicidal compounds of the present invention.
Compound R6 R7
6.001 H -CH CH=CH
6.002 3-Cl-phenyl- Pr
6.003 3-F-phenyl- chexyl-
2-Me,5-Cl
6.004 3-F-phenylphenyl
-
6.005 c-propyl n-butyl
Biological Examples
Seeds of a variety of test species are sown in standard soil in pots (Alopecurus
myosuroides (ALOMY), Setaria faberi (SETFA), Echinochloa crus-galli (ECHCG),
Solarium nigrum (SOLNI), Amaranthus retoflexus (AMARE), Ipomoea hederacea
(IPOHE)). After cultivation for one day (pre-emergence) or after 8 days cultivation
(post-emergence) under controlled conditions in a glasshouse (at 24/1 6°C, day/night;
14 hours light; 65 % humidity), the plants are sprayed with an aqueous spray solution
derived from the formulation of the technical active ingredient in acetone / water
(50:50) solution containing 0.5% Tween 20 (polyoxyethelyene sorbitan monolaurate,
CAS R 9005-64-5). Compounds ae applied at 1000 g/h.The test plants are then
grown in a glasshouse under controlled conditions in a glasshouse (at 24/1 6°C,
day/night; 14 hours light; 65 % humidity) and watered twice daily. After 13 days for
pre and post-emergence, the test is evaluated for the percentage damage caused to the
plant. The biological activities are shown in the following table on a five point scale
(5 = 80-100%; 4 = 60-79%; 5=40-59%; 2=20-39%; 7=0-19%).

Claims
1. A compound of Formula (I) :
or an agronomically acceptable salt thereof,
wherein: -
R is selected from the group consisting of Al and A2
wherein
X1 is N or CR7;
X2 is N or CR8;
X is N or CR9;
X4 is N or CR6;
R is selected from the group consisting of hydrogen, halogen, cyano, Ci-
C6alkyl, C3-C6cycloalkyl, C2-C6alkenyl, C 4-C6cycloalkenyl, C2-C6alkynyl, Ci-
C6haloalkyl, Ci-C alkoxy, Ci-Cealkoxy-Ci-Cs-alkyl, Ci-C alkoxy-C2-
C6alkoxy-, Ci-C6 alkoxy-C2-C6alkoxy-C1-C3alkyl-, Cs-CecycloalkylCi-Qalkyl-,
amino, Ci-Cealkylamino, Ci-Cedialkylamino, Ci-C3
alkylcarbonylaminoC 1-C4alkyl-, Ci-C6alkyl-S(0)p-, Ci-C6alkyl-S(0)p- C1-C3-
alkyl, C1-C6haloalkyl-S(0)p- and C1-C6haloalkyl-S(0)p-C 1-C3-alkyl;
R is selected from the group consisting of hydrogen, hydroxyl, halo, nitro,
amino, cyano, Ci-Cealkyl, Ci-C3alkoxy, C3-C6cycloalkyl, C2-C6alkenyl, C -
C6alkynyl, Ci-Cehaloalkyl, Ci-Cealkoxy-Ci-Cs-alkyl, Cs-Cecycloalkyl-Ci-Csalkyl,
Ci-C6alkyl-S(0)p-, Ci-C6alkyl-S(0) p- Ci-C3-alkyl, Ci-C6haloalkyl-
S(0) p-, Ci-Qalkylamino, Ci-Qdialkylamino and C1-C6haloalkyl-S(0) p-C1-
C3-alkyl;
R4 is selected from the group selected from hydrogen, , Ci-Cealkylcarbonyl,
arylcarbonyl, Ci-Cealkoxycarbonyl, C1-C6alkyl-S(0) p-, Ci-Cealkyl-
S(0) pcarbonyl- and aryl-S(0)p-, wherein said aryl groups may be optionally
substituted by one or more R1 1
R5 is selected from the group consisting of hydroxyl, halogen, Ci-Cealkyl, -
Cecycloalkyl, Ci-Cehaloalkyl, C2-Cealkenyl, C2-Cehaloalkenyl, C2-C6alkynyl,
Ci-C6 alkoxy, C2-C6 alkenyloxy-, C3-C6cycloalkylCi-C 3-alkyl-, Ci-C6
alkoxyCi-C3alkyl, Ci-C6 alkoxy-C2-C6alkoxy, Ci-C6 alkoxy-C2-C6alkoxy-Ci-
C3alkyl,Ci-C 6 haloalkoxy, Ci-C6 haloalkoxy-Ci-C 3alkyl, Ci-C6alkyl-S(0)p-,
Ci-C6haloalkyl-S(0)p-, aryl, aryl-S(0)p, heterocyclyl, heterocyclyl-S(0)p,
aryloxy, aryl-C2-C6alkyl-, aryl-Ci-Cealkoxy-, heterocyclyloxy, heterocyclyl-
Ci-C3alkoxy-Ci-C 3alkyl, hydroxycarbonyl, hydroxycarbonyl-Ci-C 3 alkoxy-,
Ci-C3 alkoxycarbonyl, Ci-C3 alkoxycarbonyl-Ci-C 3 alkoxy-, Ci-
C3alkylamino-, Ci-C3dialkylamino-, Ci-C3 alkylamino-S(0)p-, Ci-C3
alkylamino-S(0)p-Ci-C 3alkyl-, Ci-C3 dialkylamino-S(0)p-, Ci-C3
dialkylamino-S(0)p-Ci-C 3alkyl-, Ci-C3alkylaminocarbonyl-, Ci-
Csalkylaminocarbonyl-Ci-Qalkyl-, Ci-C3dialkylaminocarbonyl-, Ci-C3
dialkylaminocarbonyl-Ci-Csalkyl-, Ci-Csalkylcarbonylamino-, Ci-C3 alkyl-
S(0)p-amino-, C1-C3alkyl-S(0)p-C 1-C3alkylamino-, Ci-C3alkyl-S(0)paminoCi-
Csalkyl-, cyano and nitro, wherein said heterocyclyls are five or six
membered heterocyclyls containing from one to three heteroatoms each
independently selected from the group consisting of oxygen, nitrogen and
sulphur, and wherein the aryl or heterocyclyl components may be optionally
substituted by one or more substituents selected from the group consisting of
halo, Ci-C3alkyl, Ci-C3haloalkyl, Ci-C3 alkoxy, Ci-C3 haloalkoxy, phenyl,
cyano and nitro;
R6 and R9 are independently selected from the group consisting of hydrogen,
hydroxyl, halogen, -C lkyl, Ci-Cecycloalkyl, Ci-Cehaloalkyl, C2-C6alkenyl,
C2-C6haloalkenyl, C2-C6alkynyl, C -C alkoxy-, C2-C6 alkenyloxy-, C3-
CecycloalkylCi-Cs-alkyl-, Ci-C alkoxyCi-Csalkyl-, Ci-C alkoxy-C2-
C6alkoxy-, C -C alkoxy-C2-C6alkoxy-C1-C3alkyl-,C 1-C6 haloalkoxy-, C -C
haloalkoxy-CrQalkyl-, C1-C6alkyl-S(0) p-, C1-C6haloalkyl-S(0) p-, aryl, aryl-
S(0) p-, heterocyclyl, heterocyclyl-S(0) p-, aryloxy-, aryl-C2-C6alkyl-, aryl-Cr
C6alkoxy-, heterocyclyloxy-, heterocyclyl-Ci-Csalkoxy-Ci-Csalkyl-,
hydroxycarbonyl, hydroxycarbonyl-Ci-C 3alkoxy-, Ci-C3 alkoxycarbonyl-, Ci-
Csalkoxycarbonyl-Ci-Cs alkoxy-, Ci-Csalkylamino-, Ci-Qdialkylamino-, Ci-
C3alkylamino-S(0) p-, C C3 alkylamino-S(0) p-C1-C3alkyl-, C C3
dialkylamino-S(0) p-, Ci-C3 dialkylamino-S(0) p-C1-C3alkyl-, Ci-
C3alkylaminocarbonyl-, Ci-Csalkylaminocarbonyl-Ci-Csalkyl-, Ci-
C3dialkylaminocarbonyl-, Ci-C3 dialkylaminocarbonyl-Ci-Csalkyl-, C -
C3alkylcarbonylamino-, Ci-C3 alkyl-S(0) p-amino-, C1-C3alkyl-S(0) p-C1-
C3alkylamino-, C1-C3alkyl-S(0)p- aminoCi-Csalkyl-, cyano and nitro, wherein
said heterocyclyls are five or six membered heterocyclyls containing from one
to three heteroatoms each independently selected from the group consisting of
oxygen, nitrogen and sulphur, and wherein the aryl or heterocyclyl
components may be optionally substituted by one or more substituents
selected from the group consisting of halo, Ci-C3alkyl, Ci-C3haloalkyl, Ci-C3
alkoxy, Ci-C3 haloalkoxy, Ci-C 6alkyl-S(0) p-, phenyl, cyano and nitro;
R is selected from the group consisting of hydrogen, halogen, Ci-C3 alkyl-,
Ci-C3 alkoxy-, C2-C3alkenyl-, C2-C3alkynyl-, Ci-C3 haloalkyl- and Ci-
Cshaloalkoxy-;
R is hydrogen; or
R5 and R9 can together form a saturated or unsaturated 5- or 6-membered
carbocyclic or heterocyclic ring, said heterocyclic ring comprising one or more
nitrogen and/or oxygen heteroatoms, the 5- or 6-membered ring being
12 optionally substituted by one or more R ; or
R6 and R9 can together form a saturated or unsaturated 5- or 6-membered
carbocyclic or heterocyclic ring, said heterocyclic ring comprising one or more
heteroatoms selected from the group consisting of nitrogen, oxygen and S(0) 2,
12 the 5- or 6-membered ring being optionally substituted by one or more R ; or
R6 and R8 can together form an unsaturated 5- or 6-membered carbocyclic or
heterocyclic ring, said heterocyclic ring comprising one or more nitrogen
heteroatoms, the 5- or 6-membered ring being optionally substituted by one or
13 more R ; and
R1 1 is selected from the group consisting of halo-, Ci-C3alkyl, Ci-C3 haloalkyl
and Ci-C6alkoxy;
12 R is selected from the group of hydrogen, cyano, halo-, oxy-, C -
C3alkylS(0)p-, Ci-C3 alkyl, C2-C3alkenyl, C2-C3alkynyl, Ci-C3 alkoxy and Ci-
C3 haloalkyl;
13 R is selected from the group of hydrogen, cyano, halo-, Ci-C3alkylS(0)p-,
Ci-C3 alkyl, C2-C3alkenyl, C2-C3alkynyl, morpholinyl- and Ci-C3 haloalkyl;
and
p = 0, 1 or 2.
A compound according to claim 1, wherein R3 and/or R4 is hydrogen.
A compound according to claim 1 or claim 2, wherein R1 is selected from the
group consisting of Ala, Alb, Ale, Aid, A2a, A2b and A2c:
wherein R5, R6, R7, R8, R9 and R13 are as defined in claim 1 and n is 0, 1, 2 or
3.
4. A compound according to claim 3, wherein R1is Ala or Alb.
5. A compound according to any one of the previous claims, wherein R is
selected from the group consisting of hydrogen, amino, chloro, bromo, methyl,
ethyl, isopropyl, vinyl, isopropenyl, methyl-S(0) p-, cyclopropyl and cyano.
6. A compound according to any one of the previous claims, wherein R5 is
selected from the group consisting of hydroxyl, halogen, Ci-Cealkyl, Ci-
Cecycloalkyl, Ci-Cehaloalkyl, Ci-C6 alkoxy, Ci-C6 alkoxyCi-Csalkyl, Ci-C6
alkoxy-C2-C6alkoxy-C 1-C3alkyl, Ci-C6 haloalkoxyCi-Csalkyl, Ci-Cealkyl-
S(0) p-, aryl, aryloxy, heterocyclyl-Ci-Csalkoxy-CrCsalkyl, Ci-
Csdialkylamino-, C1-C3alkyl-S(0) p-amino-C1-C3dialkyl, cyano and nitro.
7. A compound according to claim 6, wherein R5 is selected from the group
consisting of chloro, methyl, trifluoromethyl, and methylS(0) p- .
8. A compound according to any one of the previous claims, wherein R6 is
selected from the group consisting of hydrogen, halogen, -C lkyl, C -
Cehaloalkyl, Ci-C6alkyl-S(0) p-, C2-C6alkenyl and C2-C6alkynyl.
9. A compound according to any one of the previous claims, wherein R is
selected from the group consisting of hydrogen, halogen and Ci-C3 alkyl-.
10. wherein R9 is
selected from the group consisting of hydrogen, 4,5-dihydroisoxazol-3-yl
halogen, C C alkyl, Ci-Cehaloalkyl, C1-C6alkyl-S(0) p-, C2-C6alkenyl and C -
Cealkynyl.
11. A herbicidal composition comprising a herbicidal compound according to any
one of the previous claims and an agriculturally acceptable formulation
adjuvant.
12. A herbicidal composition according to claim 11, further comprising at least
one additional pesticide.
13. A herbicidal composition according to claim 12, wherein the additional
pesticide is a herbicide or herbicide safener.
14. A method of controlling weeds at a locus comprising application to the locus
of a weed controlling amount of a composition according to any one of claims
11 to 13.
15. Use of a compound of Formula (I) as defined in claim 1 as a herbicide.