CA2190001A1 - 4-benzoylisoxazole derivatives and their use as herbicides - Google Patents

4-benzoylisoxazole derivatives and their use as herbicides

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Publication number
CA2190001A1
CA2190001A1 CA 2190001 CA2190001A CA2190001A1 CA 2190001 A1 CA2190001 A1 CA 2190001A1 CA 2190001 CA2190001 CA 2190001 CA 2190001 A CA2190001 A CA 2190001A CA 2190001 A1 CA2190001 A1 CA 2190001A1
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Canada
Prior art keywords
optionally substituted
carbon atoms
group containing
branched
straight
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.)
Abandoned
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CA 2190001
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French (fr)
Inventor
John Morris
Christopher John Pearson
Derek Ian Wallis
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Bayer Agriculture Ltd
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Individual
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Publication date
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Publication of CA2190001A1 publication Critical patent/CA2190001A1/en
Abandoned legal-status Critical Current

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D261/00—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings
    • C07D261/02—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings
    • C07D261/06—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings having two or more double bonds between ring members or between ring members and non-ring members
    • C07D261/08—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings having two or more double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
    • 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
    • A01N43/72—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms
    • A01N43/80—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms five-membered rings with one nitrogen atom and either one oxygen atom or one sulfur atom in positions 1,2
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D261/00—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings
    • C07D261/02—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings
    • C07D261/06—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings having two or more double bonds between ring members or between ring members and non-ring members
    • C07D261/10—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings having two or more 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
    • C07D261/18—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Pest Control & Pesticides (AREA)
  • Plant Pathology (AREA)
  • Agronomy & Crop Science (AREA)
  • Engineering & Computer Science (AREA)
  • Dentistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Wood Science & Technology (AREA)
  • Zoology (AREA)
  • Environmental Sciences (AREA)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
  • Agricultural Chemicals And Associated Chemicals (AREA)

Abstract

The invention relates to 4-benzoylisoxazoles of formula (I), wherein R, R1, R2, R3, R4, X and n are as defined in the description, and to their use as herbicides.

Description

W09~1446 - 1- P~~ 13 FIELD OF THE INVENTION
This invention relates to novel 4-h~.l vyli~ui~ul~ derivatives, compositions containing them, processes for their ~ ,p~ ~Liull and their use as herbicides.
BACKGROUND ART
Herbicidal 4-~l~uyli~u~ul~ are known from the literature, for example in European Patent Publication Nos. 0418175, 0487195, 0524018, 0527036, 0527037, 0560482 and 0580439. However none of the above pllhlir~tinnc disclose or suggest the presence of an alku~..ubull~l~lillùalkylene or ~ul~llull~l~lillvalkylene ~ or Qllhctitllt~d aminoalkylidene ~ on the benzoyl ring.
DESCRIPTION OF THE INVENTION
The present invention provides 4-~.,~v~ u~vle derivatives of forrnula (1):

R =--(R2)n (I) wherein R represents hydrogen or -CO2R5;
Rl IC~JIC ' -a straight- or branched- chain alkyl group containing up to six carbon atomQ which is optionally ~ d by one or more halogen atoms; or a cycloalkyl group containing from three to six carbon atoms which is optionally ~,.I .~I;l.,t. d by one or more halogen atoms which may be the same or different;
R2 ICIJIU;~
a halogen atom;
.. . . _ _ a straight- or branched- chain alkyl, alkenyl or alkynyl group containing up to six carbon atoms which is optionally cl~hs1itlltPd by one or more halogen atoms;
a straight- or branched- chain alkyl group containing up to six carbon atoms which is cllhctihltt~d by a group -oR6;
a group selected from nitro, cyano, -CO2R6, -S(O)pR61, -O(CH2)mOR61,-COR61,-NR6R7~-CoNR8R9, oR6 -CH2S(O)pR61, -NR3R4 and phenyl optionally c-lhCtitl~t~d by from one to five groups R21 which may be the same or different;
R3 I~,IJlC~
hydrogen;
a straight- or branched- chain alkyl, alkenyl or alkynyl group containing up to ten carbon atoms which is optionally C~hCtitllt~d by one or more halogen atoms;
a cycloalkyl group containing from three to six carbon atoms which is optionally ' - ~ by one or more halogen atoms;
-(CH2)W (phenyl optionally ~. .1.,1 i l l . t- cl by from one to five groups R21 which may be the same or different);.
or -ORS;
R4 represents -S(O)qR10 or -C(Z)=Y;
or R3 and R4 together with the nitrogen atom to which they are attached may form a ring selected from the group consisting of:
~E~ ~E~ ~E) --N~ N~Y --N~l/NR5 Y Y Y
NR5 ~ E
N~NRS and --N~s(o wherein E represents an alkylene or alkylidene group containing up to three carbon atoms which is optionally c--h'-i-llt~d .. . : . . . .. .. _ . . . .. . ... .....
2 1 9 0 ~ O 1 PCTJEP9rt/0l8l3
-3 -by one or more groups R5 which may be the same or different;
X represents -(CR11R12)t n represent3 zero or an integer &om one or four;
R5 represents a straight- or branched- chain alkyl group containing up to six carbon atoms optionally cllhCtitllt~d by one or more halogen atoms;
R6 and R7, which may be the same or different, each hydrogen or a straight- or branched- chain alkyl, alkenyl or alkynyl group containing up to six carbon atoms optionally Cl-hctihltl d by one or more halogen atoms;
R61 represent~s a straight- or branched- chain alkyl, alkenyl or alkynyl group containing up to six carbon atoms optionally lS sllhctihlt~d by one or more halogen atoms;
R8 and R9, which may be the same or different, each 1~1~ _ hydrogen;
a straight- or branched- chain alkyl group containing up to six 20 carbon atoms optionally ~.,1,~1;~.. 1.~ by one or more halogen atoms;
or phenyl optionally ' ~ by &om one to five groups R21 which may be the same or different;
R10 I~ S~....a, a straight- or branched- chain alkyl, alkenyl or allynyl group containing up to six carbon atoms optionally ~ . . t~ by one or more halogen atoms;
a cycloalkyl group containing &rom three to six carbon atoms optionally ~ d by one or more halogen atoms;
or -(CH2)W (phenyl optionally 1.~ d by from one to five groups R21 which may be the same or different);
R11 and R12, which may be the same or different, each 3~11t~.-hydrogen;
a straight- or branched- chain alkyl group containing up to six carbon atoms optionally ~ by one or more halogen atoms;
a cycloalkyl group containing &om three to six carbon atoms WO 95131446 2 1 q O O (~ 1 PCT/EP9~i/01813
-4 -optionally s~lhctitlltpd by one or more halogen atoms;
or -(CH2)w-(phenyl optionally substituted by from one to five groups R21 which may be the same or different);
Y represents oxygen or sulphur;
Z is selected from the group consisting of R62, -NR63R64, -N(R63)NR64R65, -SR62 and oR62;
R62 ~
a straight- or branched- chain alkyl, alkenyl or alkynyl group containing up to six carbon atoms which is optionally ~ by one or more halogen atoms; or -(CH2)w-(phenyl optionally sllbctit~lt~d by from one to five groups R21 which may be the same or different);
R63, R64 and R65, which may be the same or different, each I ~,IJI, hydrogen;
a straight- or branched- chain alkyl, alkenyl or alkynyl group containing up to six carbon atoms which is optionally s~lbctihlt~d by one or more halogen atoms; or -lCH2)W (phenyl optionally CllhCtih~t~d by from one to five groups R21 which may be the same or different);
R21 represents a halogen atorn;
a straight- or branched- chain alkyl group containing up to three carbon atoms optionally Cl~hctihlt~d by one or more halogen atorns;
or a group selected from -oR5, nitro, cyano and -S(o)pR5;
m represents one, two or three;
p represents zero, one or two;
q represents zero, one or two, (preferably zero or hwo);
t represents one or two;
w represents zero or one;
and ~ri~llh-r~lly acceptable salts thereof, which possess valuable properties.
In certain cases the groups R1, R2, R3, R4, R5, R6, R61, R62 W095~31446 ' ` ;~ 1 9G~O 1 Pcr/Ep9sJol8l3 _ S _ R63, R64, R65, R7, R~, R9, R10, R 11, R12 and R21 may give rise to Stcl~O;~ a and geometric isomers. All such forrns are embraced by the present inYention.
These ~ ,u" I~ in certain aspeCb of their properties,for example their control post ~l.l.l~.,ll.~ of the weed species Ipomoea ~Lr~21~a and Am:lr~nthll~ retrAIfl~ possess un~YI7ert~rlly high levels of activity.
By the term "~griA~lltllr~lly acceptable salb" is meant salts the cations or anions of which are known and accepted in the art for the formation of salb for agricultural or horticultural use. Preferably the salb are water-soluble. Suitable salts with bases include alkali metal (eg. sodium and potassium), alkaline earth metal (eg. calcium and, ~ "),<~,",.-l,;." andamine(eg.,l;. IllAI~r~l_l~l;ll.,, , o-L,~l l il-C" ~ r and liv~
salts. Suitable acid addition salts, formed by ~ o~ of formula (I) containing an amino group, include salts with inorganic acids, for example ll~L. ' ' ' sulphates, L~ s and nitrates and salb with organic acids, for example acetic acid.
DETAILED DESCRIPI ION OF THE INVENTION
Cnmro--n-lc of formula (I) in which R4 represents -S(O)qR10 are preferred, as are ~Arll ~ 'l"J "' I~ of formula (I) in which X is (-CH2-)t and t is one.
Another preferred class of l . ' of formula (I) are those wherein:
Rl l~ b.-a straight- or branched- chain alkyl group containing up to three carbon atoms which is optionally ",l ,~l ;l ., l . d by one or more halogen atoms; or ~lululu,uyl or 1 ..,_~Lyl.r~lu,u.
R2 ~
a halogen atom;
a straight- or branched- chain alkyl, alkenyl or alkYnyl grûup containing up to four carbon atoms optionally ,l .l ,~ "t~ ~ by one or more halogen atoms;

a group selected from nitro, cyano, -S(O)pR61, -COR61, -NR6R7, -CONR8R9 and -oR6;
R3 ~ c~ La.-hydrogen;
a straight- or branched- chain alkyl, alkenyl or alkynyl group containing up to six carbon atoms which is optionally ~ i l " ~ d by one or more halogen atoms;
a cycloalkyl group containing from three to six carbon atoms which is optionally s~lhstih~t~pd by one or more halogen atoms;
-(CH2h, (phenyl optionally ~llhctitlltpd by from one to five groups R21 which may be the same or different);
or -oR5;
R4 represents -S(O)qR10 or -C(Z) =Y;
or R3 and R4 together with the nitrogen atom to which they are attached may form a ring selected from the group consisting of:
~E~ ~E~
N~ and --N`S(O)/
y wherein E represents an alkylene or alkylidene group containing up to three carbon atoms which is optionally sl~hCtitllt~d by one or more groups R5 which may be the same or different;
R6 r.,~ ,S~.Ita.-a straight- or branched- chain alkyl group containing up to six carbon atoms optionally sl-hctitl-tprl by one or rnore halogen atoms;
R7 r~ lc~,.. ;a.-hydrogen or a straight- or branched- chain alkyl group containing up to six carbon atorns optionally cl-hstih-ted by one or more halogen atoms;
R8 and R9, which may be the same or different, each represeMs a straight- or branched- chain alkyl group containing up to six carbon atoms optionally s~lhctitlltPd by one or more halogen atoms;
Rl I~

WO g5/31446 2 ~ 9 0 ~ 0 3 PCT/EP95/01813 a straight- or branched- chain alkyl group containing up to six carbon atoms optionally sl-hctitllt~d by one or more halogen atoms;
a cycloalkyl group containing from three to six carbon atoms optionally cllhCtihlt~d by one or more halogen atoms;
S or -(CH2)w-(phenyl optionally cllh'titl-t~d by from one to five groups R21 which may be the same or different);
R11 and R12, which may be the same or different, each hydrogen;
a shraight- or branched- chain alkyl group containing up to three carbon atoms optionally s~h~tih~t~d by one or more halogen atoms;
Y represents oxygen;
Z is selected from the group consisting of R62, -NR63R64, -SR62 and oR62;
R62 represents a straight- or branched- chain alkyl group containing up to four carbon atoms which is optionally ~ d by one or more halogen atoms;
R63, R64 and R65, which may be the same or different, each represents a straight- or branched- chain alkyl group containing up to six carbon atoms which is optionally ~ d by one or more halogen atoms;
m represents hwo; and t represents one.
A ~ preferred class of ~ .u~ of formula (I) are those wherein:
R1 represents .~.Iuulu,u;l, R2I~ t~.-a halogen atûm;
a straight- or branched- chain alkyl group containing up to three carbon atoms optionally ~ t- d by one or more halogen atoms;
or -S(O)pR61;
R3 represents a straight- or branched- chain alkyl group containing up to three carbon atoms which is optionally 'llh'titllt~d by one or more halogen atoms;

WO 95131446 PCTII~P95101813 R4 represents -S(O)qR10;
R5 represents a straight- or branched- chain alkyl group containing up to three carbon atoms optionally cl~hstit~lted by one or more halogen atoms;
R61 represents methyl or ethyl;
R10 represents a straight- or branched- chain alkyl group containing up to three carbon atoms optionally Cllhctitllt~d by one or more halogen ator~s;
t represents one;
R11 and R12 each represent hydrogen; and n is zero, one or two Pcu Li~uldlly important ~;ulll~uullda of formula (I) include the following:
1. 4-[4-bromo-2-(N-methyl-N-I-I~,Ll,ylaull,hu.l,~l~u,,i,,o-methyl)benzoyl]-s-~y~lulJlu~qliauAclLùlel 2. 4-[4-chloro-3-(N-methyl-N-methylsul,ullu.. ~l~u.lI.lo-methyl)-2-lll~ hl~ ~uyl]-5-~lu~lu~J~l;auAc~ule;
3. 4-[4-chloro-3-(N-methyl-N-lll~Lh~:~ul~lu..~lcuuil.o-methyl)-2-1u~,.h~ llull,l~,~uyl]-S ~-~ JlUlJ,~lioUA~VlC:l 4. ethyl5-~luulu,uyl 1 [2-(N-methyl-N-,ll~LllJl~ul~hul.~l-I)benzoyl]isoxazole-3-c~l,uAyldle,
5. 5 ~lu,ulu~l q [2-(N-methyl-N-.elL~ l.o~' ' ',~ 4-L~iLh.ulu~ e.~uyl]isoxazole;
6. 4-[3,4-difluoro-2-(N-methyl-N-methylclllj' ,l- ., .~1)benzoyl]-5 ~y~,lu,ulu~liauAc~Ol~;
7. 4-[4-chloro-3-fluoro-2-(N-methyl-N-u.,lLy'~ '2~ yl)benzoyl]-5 ~lulJIu,uyliaùA~ul~,
8. 4-[4-chloro-2-(N-methyl-N-uu.,LIl~laul~uLully~ yl)benzoyl]-5 ~Iulu~u~;~uAc~vle;
9. 4-[2-(N-methyl-N-methylsull)llu..~l- ; ,u, Ih~l)benzoyl]-5 ~IUylU~qliauAc~ùle; and
10. 4-[4-fluoro-2-(N-methyl-N-methylsul~lul.~ ---,-, .I-yl)beyl]-5-~lù,ul`uluylisOAc~ûle~
The numbers 1 to 10 are assigned to these ~U~ J~" .l~ for reference and irl-~ntifi~-~ti-)n h~ ,;ucLrt-,-.
, . . _ _ _ _ WO 95/31446 2 1 ~ ~ 0 ~ 1 P~ 6l3 _ 9 _ Compounds of formula (I) may be prepared by the application or adaptation of known methods (i.e. methods heretofore used or described in the literature), for example as hereinafter described.
In the following ri~crrir~ir)n whe}e symbols appearing in formulae are not specifically defined, it is to be lln~i~rcrc c!d that they are "as h~ b~vl~ defined" in ac~uldd l~c with the first definition of each symbol in the crer ifi~rinn It is to be uud~ ood that in the dc~ ulio.~ of the following processes ~he sequences may be performed in different orders, and that suitable protecting groups may be required to achieve the ~ v . -l~ sought.
According to a feature of the present invention ~:U~ UUil~b of formula (I) in which R represents hydrogen may be prepared by the reaction of a compound of formula (II):
O O
R~ ~R4 (Il) wherein L is a leaving group and R 1, R2, R3, R4, n and X are as hcl ~;llb~. .; defined, with ~.J.L UA~' ~ or a salt of h~dluAyld~uc. II~ A~lalldulc h~d.. ' '- '- is generally preferred. Generally L is alkoxy, for example ethoxy, or N,N-20 dialkylamino, for example diu-.. ~ 1.. . uiuo. The reaction is generally carried out in an organic solvent such as ethanol or æ~ or a mixture of a water-miscible organic solvent and water, preferably in a ratio of orgarïic solvent: water of from 1:99 to 99:1, optionally in the presence of a base or acid acceptor such as tr;~,l.yl~.~ or sodium acetate at a Itlll~.ldLul~: from 0 to 100C.
According to a further feature of the present invention c.. l-u~ .. i~ of formula (I) in which R represents hydrogen may be prepared by the reaction of a compound of formula (III):
N~
(III) WO95/31446 ~1 9:~Q~ PCT/EP95101813 wherein Rl is as h.,~ b~ru~: defined and yl represents a carboxyl group or a reactive derivative thereof (such as a carboxylic acid chloride or carboxylic ester), or a cyano group, with an ~IplV~ C Ul~ it` reagent such as a Grignard reagent or an vl~;,.. ~vl,ll.;l"., reagent. The reaction is generally carried out in an inert solvent such as ether or tetrahydrofuran at a tGlll~J~ldlUlC
from 0C to the reflux ~C~ Ul~ of the mixture.
According to a further feature of the present invention v~ of formula (1) in which R is hydrogen may be prepared by reaction of a compound of formula (III), as hereinbefore defined, with an ~ Iu,vlid~e organotin reagent, such as a trialkyltin derivative, optionally using transition metal catalysis such as bis)~ yl~ k;~)palladium (II) dichloride, carried out in an inert solvent such as ~ d-urul~ul or dioxan at a hl~ u from 0 to the reflux ~ G of the mixture.
According to a further feature of the present invention of formula (1) in which R is hydrogen may also be prepared by the oxidation of a compound of formula (Illa):

U ~--(R2)n (ma) wherein Rl, R2, R3, R4, X and n are as ~ lb~,fu~ c defined.
The oxidation is performed using for example chromic acid (prepared from chromium trioxide and aqueous sulphuric acid) in acetone.
According to a further feature of the present invention ~r., ~ ". .l~ of formula (I) wherein R represents a group -CO2RS, q represents 0 or 2 and R2 represents a group Ræ which is as h~l~h~h~,fulG defined for R2 provided that p is 0 or 2, may be prepared by the reaction of a compound of formula (IV):

~ ~ 90~ 1
- 11 p c R \~/~1 (R22 (IV) wherein Rl, R22, R3, R4, X and n are as llc.~;lll,~fu~
defined, q is 0 or 2 and P is a leaving group such as N,N-dialkylamino, with R502CC(Z1) = NOH wherein R5 is as h~ b~fulc defined and z1 is a halogen atom. Generally zl is chlorine o} bromine. The reaction is generally performed in an inert solvent such as toluene or dichlolùu-~,~li~lc either in the presence of a base such as ~ L.~ lc or a catalyst such as a 4 Angstrom molecular sieve or fluoride ion.
According to a further feature of the present invention c~ ,uL~ll 7~ of formula I in which R represents a group -Co2R5, q represents 0 or 2 and R2 represents a group R22 as h.,l ~i-lb~fvl ~
defined, may be prepared by the reaction of a compound of formula (V):
. o l l XNR3R4 Rl ~ (R22)n (V) wherein Rl, Ræ, R3, R4, X and n are as h~,~h~h~fu~i defined and q represents 0 ûr 2, with a compound of formula R502CC(Zl)=NOH, wherein zl and R5 are as h~ b.,ful~
defined. The reaction is generally performed in an inert solvent such as toluene or i: ' ~Jll.~lh~ c optionally in the presence of a base such as ~ ku. il.c or a catalyst such as a 4 Angstrom molecular sieve or fluoride ion. The reaction can be carried out at a t~ between room t~ la~ul~ and the reflux of the mixture.
According to a further feature of the present invention Cul~ of formula (I) wherein R represents -Co2R5, q represents 0 or 2 and R2 represents a group RZ as h~ lb~rulc . , , . . . .. . _ . _ . . _ _ . . . . _ _ . . _ _ .

WO 95/31446 2 ~ 9 ~ PCTIEP95101813
-12-defined, may be prepared by the reaction of a salt of a compound of formula (Vl):
O. O
R~
b,~ (R22) (~) wherein Rl, Ræ, R3, R4, X and n are as h~,~cillb~,~v~c defined and q represents 0 or 2, with a compound of formula R502CC(Z1) = NOH, wherein R5 and z1 are as h~ cfvl ~
defined. Preferred salts include sodium or " ,. ~ ". 1 I l l salts. The reaction may be performed in an inert solvent such as I;~IIlVlUll~ dulc or ~c~t~-nitril~ at a ~ between room L~lu,u~.a~ul~ and the reflux ~IlIu~,ldLUI~ of the mixture.
According to a further feature of the present invendon compounds of formula I may be prepared by the reaction of a compound of formula (Vll):
n (Vll) wherein R, Rl, R2, X and n are as h.,.~,; L.,fvl~ defined and L1 is a leaving ~roup, with an amine of formula H-NR3R4, wherein R3 and R4 are as ll~ ,;lL~,fv~c defined. Ll is preferably selected from bromine, chlorine or methylsulphonyloxy (most preferably bromine). The reaction is typically carried out in the presence of a strong base such as potassium tert-butoxide in a polar solvent such as N,N- li-~ ylr-l "~"" :Ar at a l.,lllp~,la~ul~ between -20C and 10QC.
lu~ d;à~ in the ~ ,t,d aLiull of f~ l"J~ of formula (I) may be prepared by the -I.lJI;. ~1;.... or adaptation of known methods.
Compounds of formula (II) in which L represents alkoxy or N,N-dialkylamino may be prepared by the reaction of a compound of formula (Vl) with either a trialkyl ul~ rl~l Ill"lr such as triethyl .. . _ _ _ , . .. . . . _ ... .

WO9Ç/31446 f'J 1 9 0 ~ ~ j PCrrEP9Ç/01813
-13-ulll hf~ oraN,N-di~ ylrù ~ ll;flf dialkyl acetalsuchas N,N-~ lly!r~ l l l l ;flf dimethyl acetal.
The reaction with triethyl u- ~l~oru~ dlC can be carried out in the presence of acetic anhydride at the reflux tC.lllJ~.ld~UiC of the mixture and the reaction with di~ lylro~ .. lidf dialkyl acetal is carried out optionally in the presence of an inert solvent at a a~ulc from room ~ c to the reflux t~ d~UlC of the mixture.
Cnmro~nrlc of formula (Illa) may be prepared by the treatment of a compound of formula (m) above in which yl represents a carboxyl group such as an aldehyde, treatment witb an d,uplu~ c Ul~ ` reagent such as a Grignard reagent or or~n~lithi~-m reagent. The reaction is generally carried out in an inert solvent such as ether of tetral.~d.uru.dn at a t~ ulc rrom 0C to reflux t~ c of the mixture.
C-)mro~r~lc of formula (IV) may be prepared by the reaction of a compound of formula (Vlll) with a benzoyl chloride of formula (IX) Ri~c --XN(RR22R)4, (Vlll) (IX) wberein Rl, Ræ, R3, R4, X n and P are as h~,h~b~u~c defined provided that the group -XNR3R4 is not ortho to the carboxyl group, and q represents 0 or 2. The reaction is generally ca ried out in tbe presence of an organic base such as tri~lLyl~. u.~, in an inert solvent such as toluene or di~hLI-u~ f at a e between -20C and room ~ I c.
('omrollnAc of formula (V) may be prepared by the mf t lllqti~m of an acetylene of formula (X):
Rl~CH (X) - 30 wherein Rl is as ~ b.,fu~c defined, followed by reaction of the metal salt thus obtained with a benzoyl chloride of formula (IX).
The mf t~llqtinn is generally performed using n-butyl lithium in an , . . _ _ _ .. . . ... . .. . ..... .. ..

WO 95131446 2 ~ S~ O O O I PCT/EP95101813
-14-inert solvent such as ether or tetrahydrofuran at a L~ llJCldtulc from -78C to 0C. The ,~ ~l ,c~ reaction with the benzoyl chloride is carried out in the same solvent at a tclll~,cl~lul c bet veen -78C and room ~ ule.
Compounds o formula (Vl) may be prepa}ed by the reaction of an acid chloride of formula (IX) with the metal salt of a compound of formula (XI):
O O
R~ OtBu ~XI) wherein Rl is as h~.uu~ rulc defined, to give a compound of formula (XII):
O O
J \~2R4 CO2tBu (R )n (~) wherein Rl, R22~ R3, R4, X and n are as l~ rul~ defined and q is 0 or 2, which is ~ y dc~rl,ù~l~tcd to give a compound of formula (VI). The reaction to produce the metal salt of a compound of formula (Xl) is generally performed in a solvent such as a lower alcohol, preferably methanol. Preferably the metal is ~g ` The metal salt of the compound of formula (Xl) is ~ reacted with an acid chloride of formula (IX) in an inert solvent such as toluene or ~ ~ t .. ::, ;lr The dc~all,u~l~Liull is generally performed by refluxing the compound of formula (XII) in the presence of a catalyst, such as para-t~ nl c~llrhtmir acid, in an inert solvent e.g. toluene.
Alt~lllaliv~ly if the group -XNR3R4 is in the position ortho to the carboxyl group then the benzoyl chloride of formula (IX) may be replaced by a compound of formula (XIII):

woss/3~446 2~ ~05D~ r~ 3
- 15 -O O

R150 \~--(R22)n (xm) in which R22, R3, R4, X and n are as ~ ln,rul e defined and R15 is a lower alkyl group, preferably an ethyl group. The compound of formula (Xm) may be reacted with the metal salt of a compound of formula (X) in the manner described for the formation of i"t~ of formula (Xll).
mrolln~ic of formula (Vl) may also be prepared by the reaction of a benzoic acid ester of formula (XIV):

I~ XNR3R4 ~;--(R22)n (xr~ .
wherein R15, R21, R3, R4, X and n are as ~ ,h~.,ru/e defined, q is 0 or 2, with a compound of formula (XV):
Rl-C(O)-CH3 (XV) wherein Rl is as }~ b~fulc defined. The reaction is generally performed in a solvent such as diethyl ether, urul~l or N,N- lil.l.,lll~ ' Cl ' ~, in the presence of a base, preferably an aL~cali metal base such as sodium hydride or a lithiurn amide base such as lithium diiau~lu~ ide~ at a t~lu,u~ Lul~ from 0C to reflux t~,.lll)~,l_ ti.
mrolln-iC of formula (Vll) may be prepared from the ~,ulli auuuLu~, compound of formula (VII) in which Ll is replaced by hydrogen. Where Ll is bromine the reaction is preferably performed using N-l,., ~ in an inert solvent such as carbon t. 1.~ , optionally in the presence of UV light or a free radical initiator such as azo-bis-ia~ul~lu~ lile at a l,u~,~alul~ between room t~ lul~ and the reflux of the mixture.
Acid chlorides of formula (IX) in which the group -XNR3R4 wo ss/31446 2 ~ 1 F.~ ol~
- 16-is not ortho to the carboxyl group may be prepared by the reaction of a benzoic acid of formula (XVI):

(XVI) wherein R22, R3, R4, X and n are as ~.. ,.ci~ rulc defined and q is 0 or 2, and the group -XNR3R4 is not ortho to the carboxyl group, with a l ' ' 3 agent, for example thionyl chloride at the reflux lelll~laLulc of the mixture or with oxalyl chloride in an inert solvent such as di~ -u-l~ u-c or 1,2-d;~lllv-u~ u~ optionally in the presence of a catalyst such as N,N-dilll~ ' ~ at a from -20C to the reflux ~f " '1'- "1 ll ' C of the mixture.
A number of the benzoic acids of formula (XVI) are novel and as such constitute a further feature of the present invention.
T..~ ....P.l;-t~ C of formula (XIII) may be prepared by the reaction of the benzoic acids of formula (XVI) wi~h an alkyl ~ ' ' urullll.~t~, CIC02R15 such as ethyl ~llo~uru~ dt~. The reaction is carried out in the presence of a base such as an organic base (e.g. Ll;_~l,' ' - or pyridine) in an inert solvent such as Ji~lllvluu~,LL~.~, N,N~ or t~ .uru.~ll at a ~ . . . c between -40C and room ~ c. Compounds of formula (XVI) may be prepared from ~ .l-u~ in which the group XNR3R4 is replaced by a group XLI in which L1 is a leaving group (preferably chlorine or bromine) by reaction with the amino compound HNR3R4. The reaction is carried out in the presence of a strong base such as potassium tert-butoxide in a polar solvent such as N,N-di~ ,.L~"l ' at a t~ UlC between -20C and room ~ Lulc.
T-- - " of formulae (III), (vm), (X), (XIV) and (XV) are known or may be prepared by the ~ liu.. or s~ rtzltinn of known methods.
Those skilled in the art will appreciate that some ~OIIIIJUUII~
of formula (I) may be prepared by the illt~.~Ull._l~iUll of other W~9~i/31446 2~ qO~l ~UIIl~JUUlld:~ of formula (I) and such illt.,.~:ull.~ iul~ constitute yet more features of the present invention. Examples of such illL~.~ull~ iol~ are hereafter described.
According to a further feature of the present invention ~UIll~OUlld:~ in which p is one or two and/or q is one or two may be prepared by the oxidation of the sulphur atom of the ~;UII~ IJUlldillg .u~ in wbich p and/or q is zero or one. The oxidation of the sulphur atom is generally carried out using for example 3-~ lu~u~.uAyb~.lLuic acid in an inert solvent such as 10 dichlululll~.lld-lc at a t~,.. ~.. ~lllllt: from -40C to room 1` ~ .1~ ., 1 . ., ~, or hydrogen peroxide in acetic acid in the presence of acetic anhydride or Cull~ l dt~ sulphuric acid, or using potassium p~,-UAylllllllll~llll~h-~t~ as the oxidising agent.
The following EAamples illustrate the ~ dlatiOl~ of (~ ,.. l-., .. l~ of formula (I) and the Reference Examples illustrate the ,Ul~tJdldliùu of i--t- . ",. .I: .t. S in their synthesis. In the present m-p- means melting point. Where the letters NMR
appear, the ~ h~r~ rictirc of the proton nudear magnetic resonance spectrum follow. Unless otherwise specified the ~.,-~IIL~ are by weight.
F.~IVIPLF. 1 Crude 1-[4-bromo-2-(N-methyl-N-lll~ ulul~ullyl~llillo-methyl)phenyl]-3-~lu,ulu,u~. 2-(N,N-dilu.,~ L.~)propan-1,3-dione (0.86g) was dissolved in a mixture of ethanol and methanol and the mixture was cooled to -10C II~dluA~ldluil.., hydrochloride (0.21g) was added and the mixture was allowed to warm to room ~ and stirred for 1 hour. The resultant ~lcr~n~ n was poured onto cold water and extracted with ethyl acetate. The eAtracts were washed with brine, dried (arlhydrous Na2SO4) and filtered. The filtrate was uld~,d to dryness and the residue was purified twice by ~Illullld~utyd,ull~ to give 4-[4-bromo-2-(N-methyl-N-(Ill~ lsul~u~lu..~ yl)benzoyl]-5-c~lululu~
(0.36g) (compound 1) as a beige gum, NMR (CDC13) 1.2(m,2H), 135(m,2H), 2.6(m,1H), 2.8(s3H), 2.85(s,3H), 4.5(s,2H), 735(d,1H), .. . .. . .. . . . .. .

WO9~/31446 2;~ q~ PCT/EP95101813 7.55(d,1H), 7.85(s,1H), 8.2(s,1H).
The following ~u~ Juullda were similarly prepared:
4-[3,4-difluoro-2-(N-methyl-N-methylsul~ ull,~ l)benzoyl]-s-~ lu~ul u~ su~aLule (compound 6) as a yellow gum, NMR (CDC13) 1.2(m,2H), 1.35(m,2H), 2.59(m,1H), 2.8(s,6H), 2.53(s,2H), 7.25(m,2H), 8.2(s,1H);
4-[4-chloro-3-fluoro-2-(N-methyl-N-~ L.~lauliJllull,yl~l~ lyl)benzoyl]-5~ luiJluiJ~liau~a~lc (compound 7) as an orange gum, NMR (CDC13) 1.15(m,2H), 1.28(m,2H), 2.54(m,1H), 2.73(s,6H), 4.45(s,2H), 7.12(m,1H), 7.42(m,1H), 8.14(s,1H);
4-[4-chloro-2-(N-methyl-N-~ Ll~ ul~i~lu..~ )bellzoyl]-5-~luiJluv~yliau~aLvlc (compound 8), NMR (CDC13) 1.2(mt2H), 1.28(mt2H), 2.53(m, lH), 2.74(s,3H), 2.8(s,3H), 4.4(s,2H), 7.32(m,1H), 7.63(s,1H), 8.16(s,1H);
4-[2-(N-methyl-N :' ~la~liJl-u-.,' ' ~:)benzûyl]-5-~.,IU~lUiJ~IiaV.aLVlc (compound 9) as an orange gum, NMR
(CDC13) 1.15(m,2H), 1.29(~,2H), 255(m,1H), 2.72(s,3H), 2.8(s,3H), 4.45(s,2H), 7.38(m,1H), 7.5(m,2H), 7.65(m,1H), 8.18(s,1H);
4-[4-fluoro-2-(N-methyl-N-methy'isuliul-u--,~ h,~l)benzOyl]-5-~1uiJlu~l;
(compound 10) as a yeiiow gum, NMR (CDC13) 1.19(m,2H), 1.3(m,2H), 2.55(m,1H), 2.78(s,3H), 2.85(s,3H), 4.48(s,2H), 7.05(m,1H), 7.45(m,2H), 8.19(s,1H).
F~MPLF. 2 LuA.yla~ c ll.~dlu~lllo~idc (0.38g) was added to a stirred solution of 1-[4-chloro-3-(N-methyl-N~ a~ oll~lal-iil.û-methyl)-2-lll~L~ aul~ ~l]-3-cyclopropyl-2-cLLu~lil.,.ll~l~,.l~iJlu~aui-1,3-dione(2.0g)inethanol. Sodium acetate (0.43g) was then added. The resultant sl-~r~nr;o ~ was stirred at room lellliJ~-aLul~ for 2 hours and left to stand overnight.
It was evaporated to dryness and the residue was suspended in ether, washed with water, dried (anhydrous MgSO4) and filtered.

wo 95/3144C 2 1 9 0 0 0 1 PCTIEP95/01813 The filtrate was ~ u-d~,d to dryness and the residue was triturated with a mixture of ethyl acetate and hexane and filtered to give 4-[4-chloro-3-(N-méthyl-N-~ l-yl~ul~llu-~ yl)-2-methylsulul~ vyl]-5-~.lu~,.u~li~u,.a~ule (0.9g) (compound 2) as a cream solid, m.p. 128-13ûC
By IJI u~ ; in a similar manner 5-~lvl~l u,uyl~-[2-(N-methyl-N-IIl~ ul~llull,~ 1 q l~iLIuoluu~.llJll,~ vyl]isoxazole (compound 5) was prepared from the au~ulu,uliàlcl~ sl~hctitlltPd starting material, NMR (CDC13) 1.2(m,2H), 1.3(m,2H), 2.6(m,1H), 2.7(s,3H), 2.8(s,3H), 4.45(s,2H), 7.55(d,1H), 7.6(d,1H), 7.9(s,1H), 8.15(s,1H).
F~AMPL~ 3 3 ~'1 ' ùp~,.u.~yl .,-lLU;c acid (60%, 0.84g) was added to a 15 solution of 4-[4-chloro-3-(N-methyl-~ .. l_llyl~ull~'.vl~, ,1111;.1~1.1. ~JI)-2-II.~ V~I~V.YI]-5 (~IU!JIU~JYIi~U~UIC
(0.5g) in 1' ' ' ul~ he. The mixture was stirred at room l~llu~,~alul~; overnight then coûled to -25C and filtered. The filtrate was e a~ulat~d to dryness and the residue was purified by ~1ll ulllalu~ . ', on silica eluted with a mixture of ethyl acetate and ' ' ' ul.l~.Lau.~ to give 4-[4-chloro-3-(N-methyl-N-u~,lLJl..~l~}.v~l- .;...~ .Jl)-2-methylsul~,llvll~ ..Luyl]-5-~luylu~ ,. ùle (cûmpound 3, 0.14g) as a pale gum, NMR
(CDC13) 1.15(m,2H), 1.3(m,2H), 2.45(m,1H), 2.9(s,6H), 3.4(s,3H), 5.0(bs,2H), 7.25(d,1H), 7.7(d,1H), g.l(s,lH).
E-XAMPLF. 4 Potassium t-butoxide (1.79g) was added to a stirred, cooled solution of N-~_lll~ 'i ' ' ( 1.74g) in N,N-dimethyl form~m;~lP at -5C The mixture was stirred at 10C for 1.5 hours then re-cooled to -8C. A solution of crude ethyl 4-(2-blulllulllc~ lv~..Lu.~1)-5-~.lvlJlu~L;,v.~a~ulc-3-.a l,u~làLe (6.0g) in N,N- li~ rul Illalllid~ was added while, ~ the t~ .alul~ below 0C. The mixture was stirred at 0C for 1 hour and at room . . .I.. .- ~, . . ~; for 3 hours. The mixture was poured onto cold dilute hydrochloric acid and extracted with ethyl acetate. The WO 95/31446 ~ 2 1 9 0 (~ PCT/EP95/01813 organic phase was dried (anhydrous MgSO4) and filtered. The filtrate was evdlJo~ ; d to dryness and the residue was purified twice by ~Ill U~ U~ y on silica eluted with a mixture of ethyl acetate and ~luh~A~lc to give ethyl 5-cyclopropyl4-[2-(N-methyl-N-methylsul~,l-ullyl-, .;, -- " ll~yl)benzoyl]i5Oxazole-3 ~bu~l~le (Q88g) as a clear gum, NMR (CDC13) 1.05(t,3H), 1.15(m,2H), 13(m,2H), 23(m,1H), 2.8(s,3H), 2.85(s,3H), 4.0(q,2H), 4.6(s,2H), 7.25(t,1H), 7.35(d,1H), 7.55(t,1H), 7.75(d,1H).
R~FE;~F~CE EX~I~JIPI.F. 1 A mixture of crude 1-[4-bromo-2-(N-methyl-N-Ill~.lI,l~UlLJIIUll~l-",;~-J~.r~ l)phenyl]-3-~ "u.u~l~.u~.~..-1,3-dione (0.8g) and N,N-~ lr..~ dimethyl acetal in toluene was stirred at room t- . "I,r . ,.1.1l ~ for 0.5 hours and at 80C for 15 minutes. It was cooled to room ~ ; and ~ u~L~,d to dryness. Toluene was added and it was re c~a~ulah,d to gfve crude 1-[4-bromo-2-(N-methyl-N~ bulpl.ullJl-, ,. :l.yl)phenyl]-3-~lu~J-u~l-2-(N,N-dilll.,LIl~ )propan-13-dione (0.86g) as a red oil.
The following ~ u~ were similarly prepared:
3-~.lU~JlU~ [3,4-difluûro-2-(N-methyl-N-LIl~Lul,ull~ l)phenyl]-2-(N,N-dilll~,LII~' - 1 ...~.. :h~ )propan-l~3-diûne as an orange gum, NMR (CDC13) 0.66(m,2H), 0.9(m,2H), 1.17(m,1H), 2.09(m,1H), 2.76(s,6H), 2.8(s,3H), 3.1(s,brm), 4.5(s,2H), 7.2(m,3H);
1-[4-chloro-3-fluoro-2-(N-methyl-N-.,Lh~l~ul,uh~ l)phenyl]-3 ~ 1ulJlu~J~1-2-(N,N-liul~ )propan-1,3-dione, NMR 0.75(m,2H), 0.97(m,2H), 2.19(m,1H), 2.8(s,6H), 2.87(s,6H), 3.2(brm,1H), 4.55(s,2H), 7.25(m,2H);
1-[4-chloro-2-(N ~ ,Lllyl N
methylsul,ul.u.l~l~,..: .,... I~.~I)phenyl]-3 ~,1ul~lu~1-2-(N,N-dilll~Lll.~l - I I I; I I JI I . : l ,~ c)propan~1~3-dione as a yellow gum;
3-~.lol,lul,~ 1-[2-(N-methyl-N-35 methylsul~hu.lyl-,,.;.,.. , . ll ~I)phenyl]-2-(N,N-dill-~ ylene)propan-l~3-dione as an orange gum;

wo 95~31446 2 ~ 9 0 D O 1 PCTIEP95/01813 3-~.lolulu~1-1-[4-fluûro-2-(N-methyl-N-IlI~.~II,yl~UI~IIUll,y~ y~)phenyl]-2-(NlN
~UU~.Il~l-.. " :l~ylene)propan-1,3-dione.
~F,Fli',RF,~CE EXAMPI F 2 A miAture of 1-[4-chloro-3-(N-methyl-N-ll.~Lllyl~ull.hul.~l-~"~ Ih~'l)_2_1l~ UI~ ..JI]-3 (y~ lu~yl,ulu,udll-1,3-dione (l.Bg) and ~ llylul ~ .r. ,. . I-A~ ( 1.38g) in acetic anhydride was stirred and heated at refluA for 4 hûurs. It was cooled and evaporated to dryness. The residue was dissolved in toluene and re-~a~Jol~t~.d to 6ive 1-[4-chloro-3-(N-methyl-N-methylsullul.u..,~l~-.-' ,...- :l~l)-2-ll~ llyl~ul~ 'yl~ l]-3~
~lv,u~u,uyl-2 ell-uAyl.-~lllyl~ -uy~ul-l~3-dione (2.0g) as a brown oil.
lS By u-u~c~.6 in a similar manner 3-~luylu,u~: 2-~ uA,~u~ -1-[2-(N-methyl-N-l-l~ 's~ ul-J~
4-~lill~.v.u...~ J'i ' jl]propan-1,3-dione was prepared from the a~lulu,uliat~ d starting material.
12F,FFUF.~CE EX~MPLF` 3 AmiAtnreofethyl 5-~,lùl~ul~yl ~ (2-~ ,.h~ cl. vyl)-isoAaA,ole-3~1.uAylale (6.71g) and N-l,.l ' ' ''- (4.15g) in carbon l ~ . l was stirred and irradiated using a UV
r~ .r AI reactor for 1 hour. The mixture was cooled to 0C
for 2 hours and filtered. The filtrate was c~a~ulat~,d to dryness to give crude eth~yl 4-(2-blu~v~ lb.,l~vyl)-5-~loulu,uyli~uAa~ule-3 ~lluAylht~, (6.0g).
RF.l;'F~F.1~1~F F,~AMP!,F, 4 A solution of methyl 4-bromo-2-(N-methyl-N-methylsul,uLu ,' ' :' ,:)benzoate (6.25g) and ~lu~-u,uyl methyl ketone (3.13g) in tetrah~l-urul~ul was added to a stirred of sodium hydride (80% oil tli~r~rC;~m; 134g) in ~.lal~ urul UI containing a little methanol while heating at reflux.
The resultant mixture was cooled and methanol was added followed by cold aqueous sodium b;~alLullale solution. It was extracted with WO95/31446 . ,`~ 2l9aoal PCT/EP95101813 ethyl acetate, washed with brine, dried (anhydrous Na2S04) and filtered. The filtrate was evaporated to dryness. Attempted purification of the residue by ~ ulllalu~l~LAully on silica gave crude 1-[4-bromo-2-(N-methyl-N-methylsulul~ul.ylA..,;".-",~ il,yl)phenyl]-3-S ~lvlu~ul~lulup~l-1,3-dione (0.8g) as a white solid which could not be further purified.
Ul; ~RFI~CE EXAMPLE 5 A solution of 4-chlorû-3-(N-methyl-N-l~ yl~ul~hullyl-:i, ,;".. ". IllJl)-2-lll.,.llJl~ullJ}l~ lb~l-Lu~l chloride (2.4g) in toluene was added to a solution of t-butyl 3~ lulu~u~1-3-u~uulu~;ul~dle enolate (1.9g) in toluene and the mixture was stirred at room t~.~l,u.,.~lul~i overnight. Il~J,. ' ' - acid (2M) was added and the mixture was stirred for 1 hour. The layers were separated and the organic layer was washed with I~JdIU~IIIUIiC acid (2M) and water, dried (anhydrous MgS04) and filtered. 4-Toluene sulphonic acid (Q076g) was added to the resultant solution and the mixture was stirred and heated at reflux for 6 hours. After cooling the solution was washed with brine, dried (anhydrous MgS04) and filtered. The filtrate was e~a~ul~LI,d to dryness and the residue was purified by .,11l~ on silica eluted with a mixture of ethyl acetate and hexane to give 1-[4-chloro-3-(N-methyl-N-methylsul,ul,uu~ 1)-2 ..,~ J s~ lJ~ Ull~l]-3-~lu,ul uy~ ulu< u-1,3-dione (1.Og) as a yellow oil, NMR (CDC13) l.O5(rn,2H), 1.25(m,2H), 1.75(m,1H), 2.4(s,3H), 2.7(s,3H), 3.0(s,3H), 4.9(s,2H), 6.1(s,1H), 7.4(d,1H), 7.45(d,1H), 15.9-16.1(bs,1H).
By ~ diu,~ in a similar manner 3 ~,luu~ullyl-l-(2-1"~,Ll,~l,ul,~,l":)propan-1,3-dione was prepared, NMR(CDC13) 1.0(m,2H), 1.25(m,2H), 1.7(m,1H), 2.55(s,3H), 6.0(s,1H), 7.2-7.4(m,3H), 7.5(d,1H), 15.9-16.4(bs,1H).
l2F.F~I~Fl~CE EX~MP! F. 6 T~ lyl~ul ill~ (1.34ml) was added to a stirred cooled solution of 2-(N-methyl-N-methylsul~uhu,~ ".;.,.. ". illJI)-4-trifluu, UUI~.ll~ll,.,llLUiC acid (3.0g) in N,N-dil~ ylrul l~ullidc while ... . . ... .. .. . ~ _ _ _ _ , WO 9~1446 2 ~ 9 ~ G O 1 PCT/EP95/~1813 -a -" ~ i"; . ,~ the i~ ,u ~ below 0C The mixture was stirred at -10C for 0.5 hours then ethyl chlu-urullllalc (0.92ml) was added.
The miAture was again stirred at -10C for 0.75 hours then a solution of t-butyl 3-~lu~lulJyl-3-u~uylu~J;ulld~c ~
enolate (1.95g) in N,N-dil.l~.ill~lr.,""~ was added while A;l~ the~ ult;below-5C. Themixturewasstirred at 0C for Q5 hours and at room L~ l,u~,la~u~ overnight. It was treated with l.,J.~ acid (2M) and stirred for 0.5 hours then extracted with ethyl acetate, dried (anhydrous MgSO4) and filtered.
The filtrate was ~v~ul~ to dryness and the residue was dissolved in toluene and treated with 4-to~ ,l,./";r acid (O.lg). The mixture was heated at reflux for 2 hours, cooled and diluted with ethyl acetate. The mixture was washed with brine, dried (anhydrûus MgSO4) and filtered. The filtrate was cv~.l,u.~t~,~ to dryness and 15 the residue was purified by "I.,.. ~t~ on silica eluted with a mixture of ethyl acetate and ~.loll~,A~.Le to give 3 ~1u~J~u~yl-1-[2-(N-methyl-N-l..~ l.u..~ 4-uu~u~ h_l.yl]propan-1,3-dione (0.53g) as a clear ûil.
The following ~- '-''l'~J'''''I` were similarly prepared:
3-~lulJ~u,ujl-1-[3,4-difluoro-2-(N-methyl-N-...~,ih,~ h,l)phenyl]propan-1,3-dione as a beige solid, m p. 9~91C;
1 -[4-chloro-3-fluoro-2-(N-methyl-N-methylsul,ul.v..~' hyl)phenyl]-3-~.lu~..u~lp.u~.all-1,3-dione, m p. 8~82C;
1-[4-chlûro-2-(N-methyl-N-I-u--~l--~ '------ lll~ )phenyl]-3-~lu~Jlu~ u~ rll3 dione, as a beige gum NMR (CDC13) 0.95(m,2H), 1.15(m,2H), 1.69(m,1H), 2.74(s,3H), 2.83(s,3H), 4.51(s,2H), 5.9(s,1H), 7.25(m,1H), 7.38(m,1H), 7.59(m,1H);
3-~.luu. u~l-1-[2-(N-methyl-N-ul~l~ull~ l)phenyl]propan-1,3-dione as an orange gum, NMR (CDC13) 1.02(m,2H), 1.24(m,2H), 1.78(m,1H), 2.78(s,3H), 2.9(s,3H), 4.6(s,2H), 5.99(s,1H), 7.36(m,1H), 7.5(m,2H), 7.68(m, lH);
3-.~.lu~-u~yl-1-[4-fluoro-2-(N-methyl-N-WO 95/31446 ~ 1 q O ~ 0 7 PCT/l~P95101813 -24.
methylsul~ o~ . il.yl)phenyl]propan-1,3-dione as a beige gum, NMR (CDCl3) 0.95(m,2H), I.l5(m,2H), 1.69(m,1H), 2.75(s,3H), 2.85(s,3H), i.55(s,2H), 5~9(s,1H), 6.95(m,1H), 7.35(m,1H), 7.,45(m,1H).
RFI FUF.NCE EX~MPr.F 7 A mixture of ~ L''' - ""' (3.7g) in methanol containing carbon L~ o (0.5ml) was warmed gently to initiate the reaction. It was heated at 50C for 1 hour then cooled t-butyl 3-~ U~lU~1-3-~v~lulJ;ollalc (27.6g) was added and the mixture was stirred and heated at reflux for 2 hours. It was cooled and ~va,uul~Lcd to dryness. Toluene was added and it was re c.a~ulaL~,d to give the ; "., enolate of t-butyl 3-c~lu~lu~yl-3-o~.v~lu~;~llà~e (38.6g) as a white solid.
RFFEI'FNCE F.X~Mp! F. 8 Oxalyl chloride (l.Oml) was added to a solution of 4-chloro-3-(N-methyl-N-~ Lll~ yhu~~ l)-2- ' ,~bull ll~"lyl-benzoic acid (2.3g) in~' ' ' uLll~,.hal~c containing dul.~,Lll~ul '- (1 drop). The mixture was stirred and heated at reflux for Q75 hours then cooled and e.a,uulat~,~ to dryness to give 4-chloro-3-(N-methyl-N-LIl.,.h~ 1,yl)-2-lU",h~ LLV~I chloride (2.4g) as a brown oil.
R l ~ r.l .CE EXAMpl F. 9 Amixture of 1-(2-Lu~.~ Jh~ 1)-3 ~1u~lluL~ Jlu,uàll-1,3-dione (10.23g) and ~ (1.21g) in methanol was heated with carbon l~ .l, l .l. .. ;~ f (Q3ml). The mixture was stirred until .,llce ceased and the mixture was c~a~ulat~,~ to dryness.
Toluene was added and it was e.alJUlat~ to dryness. The residue was dissohed in ~t .--`~ and heated at 70C. A solution of ethyl chloro-~ t~t.' (7.67g) in ~ ~: ...., l . il~ was added and the mixture was stirred and heated at 70C for 1 hour. The mixture was cûoled and h~llu.,~l.,lic acid (2M) was added. It was stirred for 0.25 hours then extracted with ethyl acetate, washed with brine, dried (anhydrous MgSO4) and filtered. The filtrate was eva~Jul~l~,d wo 95/31446 2 1 9 0 ~ O ~ PCTÆP9510]8~3 to dryness and the residue was purified by ~ ulllaLu~la~lly on silica eluted with cyclohexane. The main product was dissolved in di~ lull~Lllallc and washed with aqueous sodium hydroxide (2M), brine, dried (anhydrous MgSO4) and filtered to give ethyl 5-S y~lu~i~l q (2-1.. ~"l.yll,~ )isoxazole-3-~all.uAyla~e (8.41g) as a brown gum, NMR (CDCl3) 1.15(t,3H), 1.2(m,2H), 1.3(m,2H), 2.35(r41H), 2.55(s,3H), 4.05(q,2H), 7.2-7.4(r44H).
Rli.F~RFl~'F F~Mpl,F 10 Potassium t-butoAide (5.89g) was added to a solution of N-methyl~ ly~ (6.0g) in N,N-dil--~l-y1 r. " .,.~.,. rl~
The mixture was stirred for 0.75 hours and methyl 4-bromo-2-blu~ul~lc~lylbenzoate (15.4g) was added. It was stirred for 0.25 hours then poured ontû a mixture of ice and brine. It was treated with aqueous r ' chloride solution and eAtracted with ethyl acetate, washed with water, dried (anhydrous MgSO4) and filtered.
The filtrate was cva~ula~,d and the residue was re-crystallised from a mixture of ethyl acetate and n-hexane tû give methyl 4-bromo-2-(N-methyl-N-methylsul~uLvu~' ~I)benzoate (15.33g) as a white solid, m p. 105.6-107.2UC
By 1~ u~.,cliu~l!, in a similar manner the fûllowing ~ v~
were prepared from the al/~lu~ t~ d starting materials.
methyl 4-chloro-2-fluoro-3-(N-methyl-N-.u~,L~ h~,..,' ', :)benzoate, NMR (CDC13) 2.75(s,3H), 2.95(s,3H), 3.95(s,3H), 4.55(s,2H), 7.85(d,1H), 7.9(t,1H);
methyl 2-(N-methyl-N-l..~,Lh~' Il.l.~...,' ~ .,1)-4 Lli[luulu,..~LJ ~ ~va~e~ mp. 92.2-9A6C;
methyl 3,4-difluoro-2-(N-methyl-N-methylsul~ u.. yl ~ .... Ih,:)berlzoate, as a brown gum, NMR(D6-DMSO) 2.62(s,3H), 2.95(s,3H), 3.86(s,3H), 4.62(s,2H), 7.6(m,2H);
methyl 4-chloro-3-rduoro-2-(N-methyl-N-methylsuL~Jllo.l.~l-".;.... ll~yl)benzoate, m.p. 80-81.8C;
methyl 4-chloro-2-(N-methyl-N-ul~ h.. ll~JllvllJ~. l;l,.. :I,~I)benzoate m.p. 92-95C;
methyl 2-(N-methyl-N-uu~ Jl ,;" "". ll,yl)benzoate as an orange oil, NMR (CDC13) 2.82(s,3H), 2.92(s,3H), 3.88(s,3H), WO95131446 ` 2t sooal PCrlEP95/01813 7.35(m,1H), 7.55(m,1H), 7.68(m,1H), 7~95(m,1H);
methyl 4-fluoro-2-(N-methyl-N-methylsul~ u-lyl~l":~ lyl)benzoate, NMR (CDC13) 2~81(s,3H), 2~,88(s,3H), 3~85(s,3H), 4~71(s,2H), 6~96(m,1H), 7~38(m,1H), 5 7.95(m,1H)-12F.FFUl;.NCE FX~VIPI F. 11 Sodium ll~`u~ 2g) was addcd to a stirred solution of methyl 4-chloro-2-fluoro-3-(N-methyl-N-u~,Lllyl~ul~llu.l~ I)benzoate (5~0g) in tetrahydrofuran and the mixture was stirred at room t~ Lulc overnight~ It was washed with water, dried (anhydrous MgSO4) and filtered~ The filtrate was evaporated to dryness to give methyl 4-chloro-3-(N-methyl-N-ul~,.l.,~.~u.,ul.u.. ,~l-,,.;.. ~ ::.JI)-2-methylsulphenyl-benzoate (4.0g) as a yellow gum, NMR (CDC13) 2~4(s,3H), 2.7(s,3H), 3.0(s,3H), 3.95(s,3H), 4.9(s,2H), 7.45(s,2H).
RFFE~FNCE FX~MPI.F 17.
A mixture of methyl 4-chloro-2-fluoro-3-ul~,.i.~lL..,..~u~.Lc (63g) and N-l,.. ~ (63g) in carbon tetrachloride was stirred and heated at reflux for 4 hours. The cooled solution was washed with water, dried (arlhydrous MgSO4) arld filtered. The filtrate was Lv~uldt~ to dryûess to give methyl 3-LIu~u~ -4-chloro-2-[luul~L (87g) as a red oil NMR (CDC13) 3.95 (s,3H), 4.65(s,2H), 7.25(d,1H), 7.9(t,1H).
By plù e~ iri a similar marmer methyl 2-blulllulll~uyl-4-~liLL.~lulll~,.h~lL..,.~Luale, NMR (CDC13) 3~92(s,3H), 4~9(s,2H), 7~65(d,1H), 7~75(s,1H), 9.1(d,1H) was prepared from the a,u~lU~l;dt~ h~tit--t~d starting material. In this case the reaction was il I ~.di~t~d with UV light irlstead of heating to reflux~
Similarly prepared were the following c~.. ~l..~..,..l~
methyl 2 ~1UIl.~ ,LIIJ' 3,4--lia~JIubc~uaLe as an orange oil, NMR (CDC13) 3.95(s,3H), 5.03(s,2H), 7.2(m,1H), 7.73(m,1H);
methyl 2-bluluul..~,Ll.yl 1 chloro-3-llL~..ùl; ~.~u~L~, m~p~ 91-93C;
methyl 2-L I ulllulll~ 4-~l~lul u~ Lu~Le as a brown oil, NMR
-WO~S/31446 2 I q (~ F~.l/r.l~ . 16l3 (CDC13) 3.95(s,3H), 4.9(s,2H), 7.35(m,1H), 7.6(m,1H), 7.95(m,1H);
methyl 2-b~u~l~u~ yl4-Auvlul/~,l~udlc as a pale brown oil, NMR (CDC13) 3.9(s,311), 4.9(s,2H), 7.02(m,2H), 7.95(m,1H).
S RF.FF.RF.I~ . F.XAMPr.F. 1'~
A mixture of methyl 2-(N-methyl-N-..~ ulyllu~
lyl)-4-~linU~lUlll~ lh~llLUdl~ (4.27g) and aqueous sûdium hydroxide (2M) in methanol was stirred and heated at reflux for 20 minutes. The cooled solution was poured into ice and acidified with Lrd-u~ lolic acid. The solid was filtered off to give 2-(N-methyl-N-methylsul,ul.u.,~'~,.,;.. ,. Ihrl)-4 I~iAuu~ulu~ u;c acid (4.03g) as a beige solid, m.p. 178.6-The following ~ were similarly prepared:
3,4-difluoro-2-(N-methyl-N-'i Jl -~ JI)benzoic acid as a brown solid, NMR(D6-DMSO)2.67(s,3H), 2.95(s,3H), 4.19(s,2H), 7.5(m,1H), 7.65(m,1H);
4-chloro-3-fluoro-2-(N-methyl-N-methylsul,uhc,..... ~' ' JI)berlzoic acid as a white solid, m.p.
150-160.5C;
4-chloro-2-(N-methyl-N :' ,' 'j ' ~I-~,;,,I~,;I)benzoic acid as a cream solid, m p. 205-205.5C;
2-(N-methyl-N ~ I ",;,Ihyl)benzoic acid, m p. 158-159C;
4-fluoro-2-(N-methyl-N-methylsullul.u..~'-..;...~.., :I.yl)benzoic acid, m.p. 186-1925C (dec.).
RF.li'F~F.l~('F. FX~MP~ F. 14 ~`- .. ,. _ . I . .. I ~ d sulphuric acid (8 ml) was added to a solution of3,4-difluoro-2-u.~ll.ylb~l.,uic acid (43 g) in methanol, and stirred for 16 hours under refluL The cooled mixture was . ~ ,. ,- - ,1. ,. l . d to half volume in vacuo, water added, and the remaining methanol e~d~uu.dt~d. The mixture was extracted (ethyl acetate) and the extract washed (sodium carbonate solution then with brine), dried c ' ~ sulphate) and c ~ a~ul dt~,d to give methyl 3,4-difluoro-2-wo 95/31446 ~ 1 9 o ~ o ~ PCT/EP95/01813 ylb~l~udlc (34 g) as an ûrange solid, m.p. 44~6C.
The following C,UIII~JUUlld:~ were similarly prepared:
methyl 4-chloro-2-~ .,,u~le, NMR (CDC13) 2.5(s,3H), 3.8(s,3H), 7.1~(m,2H), 7.88(d,1H);
methyl 4-fluoro-2--1l.,.l.~ll,.,.lLu~lc, NMR (CDC13) 2.6(s,3H), 3.88(s,3H), 6.9(m,2H), 7.92(m,1H).
E2F~l'FNCE F.XAMP~ F. l.C
A stirred solution of 3,4-d;Lluûlul/~.~uic acid (Slg) in dry tetrall, ~1 urul~ was treated at -75C under an inert ~lllos~ c with a solution of n-buL~" ' in hexanes (139 ml of 2.5M
solution) during 1 hour. After 1 hour, an additional 139 ml of the n-butyl lithium solution was added. After 20 hour, methyl iodide (50 ml) was added during 30 minutes and the mixture allowed to slowly warm to room ~ c overnight, then poured onto ice and saturated sodium bi~.l,u..~t~, solution and stirred for 30 minutes.
The mixture was washed with ether, saturated with sodium chloride and acidified with }.~JI. "( ~ acid. This was extracted (ethyl acetate) and the extract washed ~brine), dried ( ~, sulphate) and c~.,u, ' to give 3,4-difluoro-2--ll~.. ;.. ~lb~.~ uic acid (25.1g), m.p. 152.5-153.5C
By ,UI U~ ,dillg in a similar manner 4-chloro-3-fluoro-2-Ill~,lll~lb~.~u;c acid, m.p. 198-199C was prepared.
~F.~ F.N('F F.XAMPI.F. lC
Potassium carbonate (82.9g) was added to a stirred solution of 4-chloro-3-fluoro-2-u.~,Lll.~ ~u;c acid (112g) in dry acetone. After 1 hour methyl iodide (92.1g) was added and the mixture stirred overnight under reflux. The cooled mixture was filtered, washed with acetone and the solvent ~. ~,u, ' The residual oil was dissolved in ether, washed (water), dried ( ~ ~ sulphate) and ulaLc~ to give methyl 4-chloro-3-fluoro-2-lll.,Lh.~L~.,Lu (116.8g) as a pale yellow oil, NMR (CDC13) 2.53(d,3H), 3.90(s,3H), 7.25(m,1H), 7.63(m,1H).

WO 95/31446 2 1 ~ O O O ~ PCT/EP95/01813 UTILIlY
According to a feature of the present invention, there is provided a method for controlling the growth of weeds (i.e.
undesired vegetation) at a locus which comprises applying to the locus a herbicidally effective amount of at least one isoxazole derivative of formula (I) or an agrir lltllr~lly acceptable salt thereof.
For this purpose, the isoxazole derivatives are normally used in the form of herbicidal ~ e~ in A~o~ l with ~
diluents or carriers and/or surface active agents suitable for use in herbicidal .. ,.~ ), for example as h~ drt~r described.
The ~ of formula (I) show herbicidal activity against dicotyledonous (i.e. broad-leafed) and I-ul.~cul~.cdul.uu~ (i.e.
grass) weeds by pre- and/or post ~ ...u~,C Al~L~ ilJ~
By the term "pre~ .~n~,c ~ Alillll" is meant application to the soil in which the weed seeds or seedlings are present before e.~ ..., e of the weeds above the surface of the soil. By the term "post ~ is meant -;-,u' ~ lll to the aerial or exposed portions of the weeds which have emerged above the surface of the soil.
For example, the ~ u .l~u -1~ of formula (1) may be used to control the growth of:
broad-leafed weeds, for example, ~h-ltil~n ll.f .
~mor~nth-lc retrofl~lnlc Ri~1~nc pilnco (~ lyl~ hllm (~olillm ~orin~ rynmfl~A s~ e.g. [pon~ ~ pll~Fllrea~i~
~a~a sinq~ic ~rV~ncic ~rllAmlm n~nlm and~a~hil~m ~lIUI~ and grass weeds, for example Aln~ mlc ~v ~ rif c Avena ~a. D~~tArio ~A l ~ A I ;~ Echin~l hlrlA crl lc--e..Ili ~ ~m bicolor, Fl~llcin~ in-lica and r~tAriq c~ e g r~tArio fo~l-rii or ~i~tArio viri~lic and sedges, for example, CS per~-c f crlll~nt~lc The amounts of ~. . .I.u~ of formula (I) applied vary with the nature of the weeds, the ~ used, the time of Allllli. Al ;~11 the climatic and edaphic conditiorls and (when used to control the growth of weeds in crop-growing areas) the nature of the crops. When applied to a crop-growing area, the rate of arplir:lti~n WO 95/31446 2 1 9 ~ PCT/EP95/01813 should be sufficient to control the growth of weeds without causing sllh~t~nti~l p~,.lll~lllCl.l damage to the crop. In general. taking these factors into account, application rates between O.Olkg and Skg of active material per hectare give good results. However, it is to be S ~lntl~rctnod that higher or lower "~ rates may be used, depending upon the particular problem of weed control U ulllel cd.
The colllluuulul~ of formula (I) may be used to control select*ely the growth of weeds, for example to control the growth of those species h~ b~ful~ m~nti--nP~ by pre- or post e.-le~ ce ~ iUll in a directional or non-directional fashion, e.g. by directional or non-directional spraying, to a locus of weed infestation which is an area used, or to be used, for growing crops, for example cereals, e.g. wheat, barley, oats, maize and rice, soya beans, field and dwarf beans, peas, lucerne, cotton, peanuts, flax, onions, carrots, cabbage, oilseed rape, sunflower, sugar beet, and p. . . "~ . ,. .l or sown grassland before or after sowing of the crop or before or after e..l~ ,..cc of the crop. For the selective control of weeds at a locus of weed infestation which is an area used, or to be used, for growing of crops, e.g. tbe crops L ~-hlb~fol~i m~ntinn~
~rplir--~ n rates between O.Olkg and 4.0kg, and preferably between O.Olkg and 2.0kg, of active material per hectare are particularly suitable.
The ~ u ~ of formula (I) may also be used to control the growtb of weeds, especially tbose indicated above, by pre- or post-C.ll~,.L~ rrlir~t in ~ h- d orchards and other tree-growing areas, for example forests, woods and parks, and , e.g. sugar cane, oil palrn and rubber ~ , For this purpose tbey may be applied in a directional or non- directional fashion (e.g. by directional or non-directional spraying) to the weeds or to the soil in which they are expected to appear, before or after planting of the trees or p~-"~ at ~ uli~ ~;.." rates between 0.25kg and 5.0kg, and preferably between 0.5kg and 4.0kg of active material per hectare.
The .~ .u~ of formula (I) may also be used to control the growth of weeds, especially those indicated above, at loci which are .. , .... . _ _ . . . . ... . ... .. ..... . _ . _ . _ WO 95/31446 ;;~ ~ ~ o ~ ~ ~ PCTIEP95~01813 not crop-growing areas but in which the control of weeds is nevertheless desirable.
Examples of such non-crop-growing areas include airfields, industrial sites, railways, roadside verges, the verges of rivers, irrigation and other waterways, scrublands and fallow or uncultivated land, in particular where it is desired to control the growth of weeds in order to reduce fire risks. When used for such purposes in which a total herbicidal effect is frequently desired, the active ~ u.~ are normally applied at dosage rates higher than those used in crop-growing areas as hcic;~ fulc described. The precise dosage will depend upon the nature of the vegetation treated and the effect sought.
Pre- or post ~ ,e ~ and preferably pre-. '- ~,~ - - dlJ~ iUll~ in a directional or non-directional fashion (e.g. by directional or non-directional spraying) at ~ ." rates between l.Okg and 20.0kg, and preferably between 5.0 and lO.Okg, of active material per hectare are particularly suitable for this purpose.
When used to control the growth of weeds by prc-e.ll~ c~
~ the ~ of formula (l) may be ill~ull~u.~ into the soil in which the weeds are expected to emerge. It will be c-~J,ulc~;dted that when the ~ . ' of formula (I) are used to control the growth of weeds by post ell.~ lKc ~l~u~ l i.e. by 1 ;.... to the aerial or exposed portions of emerged weeds, the ~ .,,.1.~, ,,,,l~ of formula (I) will also normally come into contact with the soil and may also then exercise a pre e..l.,. ~ CC control on later ~. .,,;,.~1;,.~ weeds in the soil.
Where especially prolonged weed control is required, the application of the ~..,.I.u.,..,l~ of formula (I) may be repeated if required.
According to a further feature of the present invention~ there are provided ~ r~ C suitable for herbicidal use ~
one or more of the isoxazole derivatives of formula (1), in ~CCOriotion with, and preferably ~ b~ l,y dispersed in, one or more ~ c a~ri~ltl-r~ly- acceptable diluents or carriers and/or surface active agents [i.e. diluents or carriers and/or surface -32- ~
active agents of the type generally accepted in the art as being suitable for use in herbicidal ~U~ OaiLiu-ls and which are ~lmpqtihko with ~ of formula (I)]. The term "1"~",~ y dispersed~ is used to include ~ o~ in which the culll,uuullda of formula (I) are dissolved in other ~;ulll,u~ La.
The term "herbicidal ~ J~;l ;""`" is used in a broad sense to include not only ~ ~ which are ready for use as herbicides but also .. ,..... , l .. l . ~ which muât be diluted before use. Preferably, the ~ulll,uOSiLiulla contain from 0.05 to 90% by weight of one or more ~..... l,.J.. l~ of formula (I).
The herbicidal ~-.,.l.r~;l ;....~ may contain both a diluent or carrier and surface-active (e.g. wetting, dispersing, or emulsifying) agent. Surface-active agents which may be present in herbicidal ~:ulll~u~iLiuua of the present invention may be of the ionic or non-ionic types, for example ~ l- t- ~, yuat-,.ll~l~ ""~l-~'l-;"' derivatives, products based on .~ s of ethylene oxide with alkyl and polyaryl phenols, e.g. nonyl- or octyl-phenols, or carboxylic acid esters of ~Jlluaulbi~ which have been rendered soluble by . ;r~ of the free hydroxy groups by .. ",~ ;.... with ethylene oxide, alkali and alkaline earth metal salts of sulphuric acid esters and sulphonic acids such as dinonyl- and dioctyl-sodium 51111-1.... ...... ~t.r ~ and alkali and alkaline earth metal salts of high molecular weight sulphonic acid derivatives such as sodium and calcium li~nclllrh~qt~c and sodium and calcium alk~ll,.,. ~..c clllrhnnq-tPs~
Suitably, the herbicidal ~ according to the present invention may comprise up to 10% by weight, e.g. from 0.05% to 10% by weight, of su.L~e q~tive agent but, if desired, herbicidal according to the present invention may comprise higher u- upo. Liulla of aulL~c q~tive agent, for example up to 1~%
by weight in liquid rn~-~lcifiql ~o Cllcren~ . ,-t~ ~ and up to 25% by weight in liquid water soluble ~ t~, Examples of suitable solid diluents ûr carriers are qlllminillm silicate, talc, calcined magnesia, kieselguhr, tricalcium phosphate, powdered cork, absorbent carbon black and clays such as kaolin and bentonite. The solid ~ n~ I i-J ~ (which may take the form of -WO 95/31446 2 ~ ~ O ~ O 1 PCTIEP9~/01813 dusts, granules or wettable powders) are preferably prepared by grinding the ~ of formula (I) with solid diluents or by iullyl U~ the solid diiuents or carriers with solutions of the . ~.."l/.,,l~ of formula (I) in volatile solvents, ~aluOl~ the S solvents and, if necessary, grinding the products so as to obtain powders. Granular f~rrn~ tilmc may be prepared by absorbing the lu ~ of formula (I) (dissolved in suitable solventsl which may if desired, be volatile) onto the solid diluents or carriers in granular form and, if desired, ~v~ul~ the solvents, or by ~ ulula~ill~, .ulll~u~iliùlLc in powder form obtained as described above. Solid herbicidal ~ UI~llly wettable powders and granules, may contain wetting or dispersing agents (for example of the types described above), which may also, when solid, serve as diluents or carriers.
Liquid ~ according to the invention may take the form of aqueous, organic ûr aqueous-organic solutions, ~ nc and emulsions which may h.~ul~ulrle a ~uuL~,e - ~, agent.
Suitable liquid diluents for i~.ul~uul~iull in the liquid ~ ;h include water, glycols, hL-~h, L urU. rU.yl alcohol, ~' ~l r' ~
~l ' '- ~l isu~ullulullc~ toluene, xylenel mineral, animal and vegetable oils and light aromatic and, ~I.h l....'r fractions of petroleum (and mixtures of these diluents). Surface-active agents, which may be present in the liquid ~ ul"~ may be ionic or non-ionic (for example of the types described above) and may, when liquid, also serve as diluents or carriers.
Powders, dispersible granules and liquid ~ in the form of ~ may be diluted with water or other suitable diluents, for example mineral or Yegetable oils, rua~ ul~u ly in the case of liquid l l lll~ . ll . ,,t~; in which the diluent or carrier is an oil, to give ~ ready for use.
When desired, liquid ~ of the compound of formula (I) may be used in the form of self elU~;ryi lg ~ . . I I l ..t~ .~
containing the active substances dissolved in the ~luulsiryill~ agents or in solvents containing ~I..ul~iryi~ agents ~ r with the active cllhst~r~c, the simple addition of water to such conC~ u., producing ~ ready for use.
.. . . . . . . .

WO 9S/31446 ~ PCTIEP95101813 Liquid concentrates in which the diluent or carrier is an oil may be used without further dilution using the cl~ ù~ tic spray technique.
Herbicidal .U.~ o~iLiol~ according to the present invention S may also contain, if desired, cull.. ,.. iùllàl adjuvants such as adhesives, protective colloids, thickeners, ~cll~.la~ agents, stabilisers, sP?~P~Prin~ agents, anti-caking agents, colouring agents and corrosion inhibitors. These adjuvants may also serve as carriers or diluents.
Unless other~vise specified, the following l,~ lLa~s are by weight. Preferred herbicidal comrnCiti()nc according to the present invention are:
aqueous SllcrPncir~ , which comprise from 10 to 70% af one or more ~..,.,I.u.,,..l~ of formula (I), from 2 to 10% of surface-active agent, from 0.1 to 5% of thickener and from 15 to 87.9% of water;
wettable powders which comprise from 10 to 90% of one or more ~ ù . .l.., ,- 1~ of formula (I), from 2 to 10% of surface-active agent and from 8 to 88% of solid di.uent or carrier;
water soluble or water dispersible powders which comprise from 10 to 90% of one or more .u ~l~u~ of formu.a (I), from 2 to 40% of sodium carbonate and from 0 to 88% of solid diluent;
liquid water soluble .u ''`f 1~ C which comprise from S to 50%, e.g. 10 to 30%, of one or more, ,,u~..d~ of formula (1), from 5 to 25% of bUlra~ ive agent and from 25 to 90%, e.g. 45 to 85%,ofwatermisciblesolvent,e.g. ~ h~yl~ P ora mixture of water-miscible solvent and water;
~.iquid ~ r ' cù~...,.4~lat~,j which comprise from 10 to 70% of one or more l~,,,,,l, ,,-l~ of formul.a (I), from 5 to 15% of ~u.r~ agent, from 0.1 to 5% of thickener ar.d from 10 to 84.9% of organic solvent;
granules which comprise from 1 to 90%, e.g. 2 to 10% of one or more c~ of formula (I), from 0.5 to 7%, e.g. 0.5 to 2%, of surface-active agent and from 3 to 98.5%, e.g. 88 to 97.5%, of granular carrier and Pnnlllcifiol~lP cùl~C~ lat~ which comprise 0.05 to 90%, and .

WO 95/31446 ~ PCT/EP95101813 -preferably from 1 to 60% of one or more ~:UIIIIJUUI-d~ of formula (I), from 0.01 to 10%, and preferably from 1 to 10%, of surface-active agent and from 9.99 to 99.94%, and prefeMbly from 39 to 98.99%, of organic solvent.
Herbicidal ~ according to the present invention may also comprise the ~;CIIII~UUII~ of formula (I) in ~ccr~ri:ltit)n with, and preferably h-...,..~ dispersed in, one or more other pesticidally active c~ u ~ and, if desired, one or more ~nmr~tihl~ pesticidally acceptable diluents or carriers, surface-active agents and ~ull._llLiu~al adjuvants as h~ L.. ,EuiG described.
Examples of other pesticidally active ~(.. "l.u.. l~ which may be included in, or used in ~.. j .. ; ;.-ll with, the herbicidal .. ,l.~
of the present invention include herbicides, for example to increase the range of weed species controlled for example alachlor [2-chloro-2,6'-diethyl-N-(methoxy-methyl) ~ l l ], atrazine [2-chloro-4-~ih~lalliulo-6-isu~lul)~' -1,3,5-triazine], IJIUIIIU~IIII [3,5-dibromo 1 ~ -u~L '-], ~' ' i ' u~.[N'-(3-chloro-4-ujl)-N~N-diul.,;l~l~u~ ]~ cyanazine [2-chloro-4-(1-cyano-1- .ll.,~I~,lh,' -) 6 1,l1l~1a... ll~-1,3,5-triazine], 2,4-D [2,4-2û A~ rtir acid], dicamba [3,6-dichloro-2-u~ - acid], .l;f .~ [1,2- dimethyl-3,5-diphenyl-Lu~ salts], flall.~Jlu~ l [methyl N-2-(N- benzoyl-3-chloro-4-lluùlùa~ r ' ' ], r.~ ulull [N'-(3-trifluoro--I.,llljll~ll~,l.~l)-N~N-~ Lh~ d]~ isu~ulu~ull [N'-(4-25 isu,u.u~l~ )-N,N-di~.,;Ljlu.. ~.], ;.. l;- A- ~, e.g. synthetic uld~, e.g. F ~ and ~,~ .. ,l,. i.., and fungicides, e.g.
~all,~Ul.àt~,S, e.g. methyl N-(1-butyl-carbamoyl- L ' ' 2-yl)~alballlalG~ and triazoles e.g. 1-(4-chloro-phenoxy)-3,3- dimethyl-1-(1,2,4-triazol-1-yl)-butan-2-one.
Pesticidally active ~ u~ and other biologically active materials which may be included in, or used in . , with, the herbicidal ~ r ~ of the present invention, for example those h.,l ~,h-L ~f~.- G m~nti- nP~I and which are acids, may, if desired, be utilized in the form of ~;ull~l.;iol~al derivatives, for example alkali metal and amine salts and esters.
According to a further feature of the present invention there is ... . . . ... . . ... . . .... . . ..

WO 95/31446 ~ I q (3 ~ ~ ~ PCT/EP95/01813 _ provided an article of m ~nllf~rtllre comprising at least one of the isoxazole derivatives of formula (I) or, as is preferred, a herbicidal ~ o~ as h~, ~;lL~ulc described, and preferably a herbicidal COllCc~lLlaLc which must be diluted before use, ~,UIII~Jli~lill~ at least one of the isoxazole derivatives of formula (I) within a container for the aforesaid derivative or derivatives of forrnula (I), or a said herbicidal ÇUIII~U~iLiUII, and instructions physically associated with the aforesaid container setting out the maMer in which the aforesaid derivative or derivatives of formula (I) or herbicidal ~u~ o~iL;u~ contained therein is to be used to control the growth of weeds. The containers will normally be of the types conventionally used for the storage of chemical substances which are solid at normal ambient ;~ r ~ ,,, and herbicidal çullllJu~ilio~
particularly in the form of ço,~ , for example cans and drums of metal, which may be internally lacquered, and plastics materials, bûttles ûr glass and plastics materials and, when the contents of the container is a solid, for example granular, herbicidal ÇUlll~U~ilio,~, boxes, for example ûf cardboard, plastics materials and metal, or sacks. The corltainers will norrnally be of sufficient capacity to contain amounts of the isoxazole derivative or herbicidal ~ mr~iti-~n~ sufficient to treat at least one acre of ground to control the growth of weeds therein but will not exceed a size which is ,UII~ .. for .,OI~ tiullal methods of handling. The instructions will be physically associated with the container, for example by being printed directly thereon or on a label or tag affixed thereto. The directions will normally indicau that the contents of the container, after dilution if necessary, are to be applied to control the growth of weeds at rates Of l ,lul i~
between O.Olkg and 20kg of active material per hectare in the 30 manner and for the purposes L~,.. ,;llb~,'ulé described.
The following Examples illustrate herbicidal ~ ;o~
according to the present invention:
E~MPLF. Cl 35 A soluble ~on~ llldLe is formed from:
Active ingredient (compound 1) 20% w/v , .... _ ...... _ .. ... ......... .... . . . _ . .

WO 9S131446 2 ~ 9 () L~ O 1 PCTIEP9~101813 Potassium hydroxide solution 33% w/v 10% v/v Tetral.r.llu~u.~u.~l alcohol (THFA) 10% v/v Water to 100 vûlumes~
by stirring THFA, active ingredient (compound 1) and 90%
volume of water and slowly adding the potassium hydroxide solution until a steady pH 7-8 is obtained t~hen making up to volume with water.
Similar soluble c-,, . l .. l~c may be prepared as described above by replacing the isoxazole (compourld 1) with other . ~ l,.J .l~ of formula (I).
~XAMPLI~
A wettable powder is formed from:
Active ingredient (compound 1) 50% w/w Sodiumdodc~ll,.,.lL~.-c~ ll.l.. ---t~ 3% w/w 15Sodium l;v~ 5% w/w Sodiumr ''-~icall~l ~ l r~ 2% w/w Microfine silicon dioxide 3% w/w and China clay 37~o w/w by blending the above ingredients together and grinding the 20mixture in an air jet mill.
Similar wettable powders may be prepared as descTibed above by replacing the isoxazole (compound 1) with other ~.. l u .l~ of formula (I).
F.~AMPI F C3 25A water soluble powder is formed from:
Active ingredient (compound 1) 50% w/w Sodium dodc~lh. ~ . lrhrr^~^ 1% w/w Microfine silicon dioxide 2% w/w Sodium' ' 47% w/w by mixing the above ingredients and grinding the above mixture in a hammer mill.
Similar water soluble powders may be prepared as described above by replacing the isoxazole (compound 1) with other l.u~ of formula (I).
The ~ ., 1 ~, .1~ of the invention have been used in herbicidal ~plir^~ti~m~ according to the following ~ cd..-~.

21 so~al wo 95/31446 PCT/EP95/01813 MFTHOD OF USE OF HERBICIDAL COMPOUNDS:
a) General Appropriate quantities of the CUIII~JUUllt~:~ used to treat the plants were dissolved in acetone to give solutions equivalent to ~rrlir:ltinrl rates of up to 4000g test compound per hectare (g/ha).
These solutions were applied from a standard laboratory herbicide sprayer delivering the equivalent of 290 litres of spray fluid per hectare.
b) Weed rnntrol: Prc~ . .,. P
10 The seed3 were sown in 70 mm square, 75 mm deep plastic pots in non-sterile soil . The quantities of seed per pot were as follows:-Weed ~crPriP~ Avvrox n~lmhPr of seeds/vot 1) Broad-lP~fP~wpp~lc Abutilon ~- ''l'k'''`l; 10 Am~r nth-lc retroflexus 20 Galium aparine 10 Ipomoea purpurea 10 .
Sinapis arvensis . 15 Xanthium~LI~..... l~.liulll 2 2) Gr~cc w~P~ic Alopecurus Ill~J~ulo;d~;, 15 Avena fatua 10 Frhir- ' '~~ crus-galli 15 Setaria viridis 20 3)~ç5!y~,c Cyperus esculentus 3 1) Broad-lP:~fP~l Cotton 3 Soya 3 2) ~a~c Maize 2 Rice 6 Wheat 6 WO95/31446 ~ ~aO(:1l PC'rJEP95~0~813 The ~ v~ of the invention were applied to the soil surface, containing the seeds, as described in (a). A single pot of each crop and each weed was allocated to each treatment, with unsprayed controls and controls sprayed with acetone alone.
After treatment the pots were placed on capillary matting kept hn a glass house, and watered overhead . Visual ~c.~ccnn~ nt of crop damage was made 20-24 days after spraying. The results were expressed as the p~ reduction in growth or damage to the crop or weeds, in ~ with the plants hn the control pots.
c) Weed control: Post ~ e The weeds and crops were Sown directly into John Innes potting compost in 75 mm deep, 70 mm square pots except for Amaranthus which was pricked out at the seedhing stage and f.,..~ to the pots one week before spraying. The plants were then grown in the ~ ' until ready for spraying with the u .-l~ used to treat the plants. The number of plants per pot were as follows :-1) Broad l~f~rl w~ c Weed 5rr~ c Nllmh~ r of ~t~ntC per ~ot Growth C~
20Abuthon~ l.. ;.. t; 3 1-21eaves Am~nthllc retroflexus 4 1-2 leaves Galium aparine 3 15t whorl Ipomoea ptlrpurea 3 1-2 leaves Shnapis arvensis 4 2 leaves Xanthium :~llUlLlaliULU 1 2-3 leaves 2) Gr~cc w~ ~-ic Weed svecies N~lmh~r of pl~nt~ per ~ot Growth ,ct:~,r~
Alopecurus ~h~J~u-~lidcs 8-12 1-2 leaves Avena fatua 12-18 1-2 leaves Frhinrl~hlr~a crus-galli 4 2-3 leaves Setaria viridis 15-25 1-2 leaves.
3) Sed~es Weed ~c~ c NllmhPr nf ~nl~ntc ~ner pot Growth ct:~e Cyperus esculentus 3 3 leaves.

WO 95/31446 2 1 9 ~ ~ PCT/l~P95~01813 1) Broad l~f~
Crops Nllmh~r of vl~ntc per vot Growth Cotton 2 1 leaf Soya 2 2 leaves.
2) Grass Crovs Nllmh~r of ~Iqnt~ per vot Growth Ct:tSt' Maize 2 2-3 leaves Rice 4 2-3 leaves Wheat S 2-3 leaves.
The .. l,u ~ used to treat the plants were applied to the plants as described in (a). A single pot of each crop and weed species was allocated to each treatment, with unsprayed controls and controls sprayed with acetone alone.
After treatment the pots were placed on capillary matting in a glass house, and watered overhead once after 24 hours and then by controlled sub-irrigation. Visual: ~ of crop damage and weed control was made 20-24 days after spraying. The results were expressed as the y~ reduction in growth or damage to the crop or weeds, in ~ . with the plants in the control pots.
The ~"..~ of the invention, used at 1 kg/ha or less, have shown an excellent level of herbicidal activity together with crop tolerance on the weeds used in the foregoing ~
When applied pre- or post ~ at lOOOg/ha or less ~l .. ,l.. ,.. - l~ 1 to 10 gave at least 905~ reduction in growth of one or more of the weed species.
When applied post ~ at 250g/ha or less ~ulllyuuud~ 1 to 10 gave at least 80% reduction in the growth of Ipomoea ~rQa and Am~r~qnthl~c retr-lfl~ ~n.c

Claims (10)

-41-
1. A 4-benzoylisoxazoles derivative of formula (I):
(I) wherein:
R represents hydrogen or -CO2R5;
R1 represents:-a straight- or branched- chain alkyl group containing up to six carbon atoms which is optionally substituted by one or more halogen atoms; or a cycloalkyl group containing from three to six carbon atoms which is optionally substituted by one or more halogen atoms which may be the same or different;
R2 represents:-a halogen atom;
a straight- or branched- chain alkyl, alkenyl or alkynyl group containing up to six carbon atoms which is optionally substituted by one or more halogen atoms;
a straight- or branched- chain alkyl group containing up to six carbon atoms which is substituted by a group -OR6;
a group selected from nitro, cyano, -CO2R6, -S(O)pR61, -O(CH2)mOR61, -COR61, -NR6R7, -CONR8R9, -OR6, -CH2S(O)pR61, -NR3R4 and phenyl optionally substituted by from one to five groups R21 which may be the same or different;
R3 represents:-hydrogen;
a straight- or branched- chain alkyl, alkenyl or alkynyl group containing up to ten carbon atoms which is optionally substituted by one or more halogen atoms;
a cycloalkyl group containing from three to six carbon atoms which is optionally substituted by one or more halogen atoms;
-(CH2)w-(phenyl optionally substituted by from one to five groups R21 which may be the same or different);
or -OR5;

R4 represents -S(O)qR10 or -C(Z)=Y;
or R3 and R4 together with the nitrogen atom to which they are attached may form a ring selected from the group consisting of:
and wherein E represents an alkylene or alkylidene group containing up to three carbon atoms which is optionally substituted by one or more groups R5 which may be the same or different;
X represents -(CR11R12)t-n represents zero or an integer from one or four;
R5 represents a straight- or branched- chain alkyl group containing up to six carbon atoms optionally substituted by one or more halogen atoms;
R6 and R7, which may be the same or different, each represents:-hydrogen or a straight- or branched- chain alkyl, alkenyl or alkynyl group containing up to six carbon atoms optionally substituted by one or more halogen atoms;
R61 represents a straight- or branched- chain alkyl, alkenyl or alkynyl group containing up to six carbon atoms optionally substituted by one or more halogen atoms;
R8 and R9, which may be the same or different, each represents:-hydrogen;
a straight- or branched- chain alkyl group containing up to six carbon atoms optionally substituted by one or more halogen atoms;
or phenyl optionally substituted by from one to five groups R21 which may be the same or different;

R10 represents:-a straight- or branched- chain alkyl, alkenyl or alkynyl group containing up to six carbon atoms optionally substituted by one or more halogen atoms;
a cycloalkyl group containing from three to six carbon atoms optionally substituted by one or more halogen atoms;
or -(CH2)w-(phenyl optionally substituted by from one to five groups R21 which may be the same or different);
R11 and R12, which may be the same or different, each represents:-hydrogen;
a straight- or branched- chain alkyl group containing up to six carbon atoms optionally substituted by one or more halogen atoms;
a cycloalkyl group containing from three to six carbon atoms optionally substituted by one or more halogen atoms;
or -(CH2)w-(phenyl optionally substituted by from one to five groups R21 which may be the same or different);
Y represents oxygen or sulphur;
Z is selected from the group consisting of R62, -NR63R64, -N(R63)NR64R65, -SR62 and -OR62;
R62 represents:-a straight- or branched- chain alkyl, alkenyl or alkynyl group containing up to six carbon atoms which is optionally substituted by one or more halogen atoms; or -(CH2)w-(phenyl optionally substituted by from one to five groups R21 which may be the same or different);
R63, R64 and R65, which may be the same or different, each represents:-hydrogen;
a straight- or branched- chain alkyl, alkenyl or alkynyl group containing up to six carbon atoms which is optionally substituted by one or more halogen atoms; or -(CH2)w-(phenyl optionally substituted by from one to five groups R21 which may be the same or different);
R21 represents a halogen atom;
a straight- or branched- chain alkyl group containing up to three carbon atoms optionally substituted by one or more halogen atoms;
or a group selected from -OR5, nitro, cyano and -S(O)pR5;
m represents one, two or three;
p represents zero, one or two;
q represents zero, one or two;
t represents one or two;
w represents zero or one;
or an agriculturally acceptable salt thereof.
2. A compound according to claim 1 in which R4 represents -S(O)qR10.
3. A compound according to claim 1 or 2 in which X
represents (-CH2-)t, wherein t represents 1.
4. A compound according to claim 1 in which:
R1 represents:-a straight- or branched- chain alkyl group containing up to three carbon atoms which is optionally substituted by one or more halogen atoms; or cyclopropyl or 1-methylcyclopropyl;
R2 represents:-a halogen atom;
a straight- or branched- chain alkyl, alkenyl or alkynyl group containing up to four carbon atoms optionally substituted by one or more halogen atoms;
a group selected from nitro, cyano, -S(O)pR61, -COR61, -NR6R7, -CONR8R9 and -OR6;
R3 represents:-hydrogen;
a straight- or branched- chain alkyl, alkenyl or alkynyl group containing up to six carbon atoms which is optionally substituted by one or more halogen atoms;
a cycloalkyl group containing from three to six carbon atoms which is optionally substituted by one or more halogen atoms;
-(CH2)w-(phenyl optionally substituted by from one to five groups R21 which may be the same or different);
or -OR5;
R4 represents -S(O)qR10 or -C(Z)=Y;
or R3 and R4 together with the nitrogen atom to which they are attached may form a ring selected from the group consisting of:

and wherein E represents an alkylene or alkylidene group containing up to three carbon atoms which is optionally substituted by one or more groups R5 which may be the same or different;
R6 represents:-a straight- or branched- chain alkyl group containing up to six carbon atoms optionally substituted by one or more halogen atoms;
R7 represents:-hydrogen or a straight- or branched- chain alkyl group containing up to six carbon atoms optionally substituted by one or more halogen atoms;
R8 and R9, which may be the same or different, each represents a straight- or branched- chain alkyl group containing up to six carbon atoms optionally substituted by one or more halogen atoms;
R10 represents:-a straight- or branched- chain alkyl group containing up to six carbon atoms optionally substituted by one or more halogen atoms;
a cycloalkyl group containing from three to six carbon atoms optionally substituted by one or more halogen atoms;
or -(CH2)w-(phenyl optionally substituted by from one to five groups R21 which may be the same or different);
R11 and R12, which may be the same or different, each represents:-hydrogen;
a straight- or branched- chain alkyl group containing up to three carbon atoms optionally substituted by one or more halogen atoms;
Y represents oxygen;
Z is selected from the group consisting of R62, -NR63R64, -SR62 and OR62;
R62 represents a straight- or branched- chain alkyl group containing up to four carbon atoms which is optionally substituted by one or more halogen atoms;

R63, R64 and R65, which may be the same or different, each represents a straight- or branched- chain alkyl group containing up to six carbon atoms which is optionally substituted by one or more halogen atoms;
m represents two; and t represents one.
5. A compound according to any one of the preceding claims in which:
R1 represents cyclopropyl;
R2 represents:-a halogen atom;
a straight- or branched- chain alkyl group containing up to three carbon atoms optionally substituted by one or more halogen atoms;
or -S(O)pR61;
R3 represents a straight- or branched- chain alkyl group containing up to three carbon atoms which is optionally substituted by one or more halogen atoms;
R4 represents -S(O)qR10;
R5 represents a straight- or branched- chain alkyl group containing up to three carbon atoms optionally substituted by one or more halogen atoms;
R61 represents methyl or ethyl;
R10 represents a straight- or branched- chain alkyl group containing up to three carbon atoms optionally substituted by one or more halogen atoms;
t represents one;
R11 and R12 each represent hydrogen; and n is zero, one or two.
6. A compound according to claim 1 which is:
4-[4-bromo-2-(N-methyl-N-methylsulphonylamino-methyl)benzoyl]-5-cyclopropylisoxazole;
4-[4-chloro-3-(N-methyl-N-methylsulphonylaminomethyl)-2-methylsulphenylbenzoyl]-5-cyclopropylisoxazole;
4-[4-chloro-3-(N-methyl-N-methylsulphonylaminomethyl)-2-methylsulphenylbenzoyl]-5-cyclopropylisoxazole;
ethyl 5-cyclopropyl-4-[2-(N-methyl-N-methylsulphonyl-aminomethyl)benzoyl]isoxazole-3-carboxylate;

5-cyclopropyl-4-[2-(N-methyl-N-methylsulphonylaminomethyl)-4-trifluoromethylbenzoyl]isoxazole;
4-[3,4-difluoro-2-(N-methyl-N-methylsulphonylaminomethyl)benzoyl]-5-cyclopropylisoxazole;
4-[4-chloro-3-fluoro-2-(N-methyl-N-methylsulphonylaminomethyl)benzoyl]-5-cyclopropylisoxazole;
4-[4-chloro-2-(N-methyl-N-methylsulphonylaminomethyl)benzoyl]-5-cyclopropylisoxazole;
4-[2-(N-methyl-N-methylsulphonylaminomethyl)benzoyl]-5-cyclopropylisoxazole; or 4-[4-fluoro-2-(N-methyl-N-methylsulphonylaminomethyl)-benzoyl]-5-cyclopropylisox azole.
7. A herbicidal composition comprising an effective amount of a 4-benzoylisoxazole derivative according to any one of claims 1 to 6 or an agriculturally acceptable salt thereof, in association with an agriculturally acceptable diluent or carrier and/or surface active agent.
8. A method for the control of weeds at a locus which comprises applying to said locus an effective amount of a 4-benzoylisoxazole derivative according to any one of claims 1 to 6 or an agriculturally acceptable salt thereof.
9. A method according to claim 8 wherein the locus is an area used, or to be used for the growing of crops and the 4-benzoylisoxazole derivative is applied at an application rate of from 0.01 to 1.0 kg/ha.
10. A process for the preparation of 4-benzoylisoxazole derivative of formula (I) as defined in claim 1 which comprises:
(a) where R represents hydrogen, the reaction of a compound of formula (II):
(II) wherein L is a leaving group and R1, R2, R3, R4, n and X are as defined in claim 1, with hydroxylamine or a salt of hydroxylamine;
(b) where R represents hydrogen, the reaction of a compound of formula (III):
(III) wherein R1 is as defined in claim 1 and Y1 represents a carboxyl group or a reactive derivative or a cyano group, with an appropriate organometallic reagent;
(c) where R is hydrogen, the oxidation of a compound of formula (IIIa):
(IIIa) wherein R1, R2, R3, R4, X and n are as defined in claim 1;
(d) where R represents a group -CO2R5, q represents 0 or 2 and R2 represents a group R22 which is as hereinbefore defined for R2 provided that p is 0 or 2, the reaction of a compound of formula (IV):
(IV) wherein R1, R3, R4, X and n are as defined above, q is 0 or 2, R22 is as defined above and P is a leaving group, with R5O2CC(Z1)=NOH wherein R5 is as defined in claim 1 and Z1 is a halogen atom (e) where R represents a group -CO2R5, q represents 0 or 2 and R2 represents a group R22 as defined above, the reaction of a compound of formula (V):
(V) wherein R1, R3, R4, X and n are as defined in claim 1, R22 is as defined above and q represents 0 or 2, with a compound of formula R5O2CC(Z1)=NOH, wherein R5 is as defined n claim 1 and Z1 is as defined above;
(f) wherein R represents -CO2R5, q represents 0 or 2 and R2 represents a group R22 as defined above, the reaction of a salt of a compound of formula (VI):
(VI) wherein R1, R3, R4, X and n are as hereinbefore defined, R22 is as defined above and q represents 0 or 2, with a compound of formula R5O2CC(Z1)=NOH, wherein R5 is as defined in claim 1 and Z1 is as defined above;
(g) the reaction of a compound of formula (VII):
(VII) wherein R, R1, R2, X and n are as defined in claim 1 and L1 is a leaving group, with an amine of formula H-NR3R4, wherein R3 and R4 are as defined in claim 1;
(h) where p is one or two and/or q is one or two, the oxidation of the corresponding compound of formula (I) in which p is zero or one and/or q is zero or one;
optionally followed by the conversion of the compound of formula (I) thus obtained into an agriculturally accpetable salt thereof.
CA 2190001 1994-05-17 1995-05-12 4-benzoylisoxazole derivatives and their use as herbicides Abandoned CA2190001A1 (en)

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US7153813B2 (en) 2002-02-19 2006-12-26 Bayer Aktiengesellschaft Substituted aryl ketones

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US6297198B1 (en) 1996-05-14 2001-10-02 Syngenta Participations Ag Isoxazole derivatives and their use as herbicides
GB9714302D0 (en) 1997-07-07 1997-09-10 Rhone Poulenc Agrochimie Process
DE19920791A1 (en) 1999-05-06 2000-11-09 Bayer Ag Substituted benzoyl isoxazoles
DE10209645A1 (en) * 2002-03-05 2003-09-18 Bayer Cropscience Ag Substituted aryl ketones
WO2011012248A2 (en) 2009-07-29 2011-02-03 Bayer Cropscience Ag 2-(3-aminobenzoyl)-3-cyclopropyl-3-oxopropane nitriles and use thereof as herbicides
US20190152992A1 (en) 2016-06-29 2019-05-23 Orion Corporation Benzodioxane derivatives and their pharmaceutical use
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GB9215551D0 (en) * 1992-07-22 1992-09-02 Rhone Poulenc Agriculture New compositions of matter

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US7456133B2 (en) 2001-05-09 2008-11-25 Bayer Cropscience Ag Substituted arylketones
US7153813B2 (en) 2002-02-19 2006-12-26 Bayer Aktiengesellschaft Substituted aryl ketones

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