AU656178B2 - Herbicides - Google Patents

Description

1

,L~T-

OPI DATE 21/10/92 AOJP DATE 26/11/92 APPLN. ID 14102 92 PCT NUMBER PCT/GB92/00376 'ION TREATY (PCT) INTE (51) International Patent Classification 5 (11) International Publication Number: WO 92/16511 C07D 239/52, 251/20, 239/26 Al C07D 239/34, 405/06 (43) International Publication Date: 1 October 1992 (01.10.92) (21) International Application Number: PCT/GB92/00376 (74) Agent: WELLS, Norman, David; Schering Agrochemicals Limited, Industrial Property Department, Chesterford (22) International Filing Date: 3 March 1992 (03.03.92) Park Research Station, Saffron Walden, Essex CBIO IXL (GB).

Priority data: 9105297.7 13 March 1991 (13.03.91) GB (81) Designated States: AT (European patent), AU, BE (European patent), BF (OAPI patent), BG, BJ (OAPI patent), (71) Applicant (for all designated States except US): SCHERING BR, CA, CF (OAPI patent), CG (OAPI patent), CH AGROCHEMICALS LIMITED [GB/GB]; Hauxton, (European patent), CI (OAPI patent), CM (OAPI pa- Cambridge CB2 5HU tent), CS, DE (European patent), DK (European patent), ES (European patent), FI, FR (European patent), GA (72) Inventors; and (OAPI patent), GB (European patent), GN (OAPI pa- Inventors/Applicants (for US only) HARDE, Christoph tent), GR (European patent), HU, IT (European patent), [DE/DE]; JOHANN, Gerhard [DE/DE]; KROGER, JP, KR, LU (European patent), MC (European patent), Gabriele [DE/DE]; REES, Richard [DE/DE]; TARA- ML (OAPI patent), MR (OAPI patent), NL (European RA, Gerhard [DE/DE]; Schering Aktiengesellschaft, patent), NO, PL, RO, RU, SD, SE (European patent), 170/178 Mfillerstrasse, D-1000 Berlin 65 GATES, SN (OAPI patent), TD (OAPI patent), TG (OAPI pa- Peter, Stuart [GB/GB]; Schering Agrochemicals Limited, tent), US.

Chesterford Park Research Station, Saffron Walden, Essex CBIO IXL Published With international sea:cl report.

(56: 78 (54)Title: HERBICIDES R- C X N N RI A R (57) Abstract Her .cidal haloacetic acid derivatives of formula and salts thereof, where: A is -N or -CH= X is halo; R I and R 2 which may be the same or different, each represent alkyl, alkoxy, haloalkyl, haloalkoxy, halo, alkylamino or dialkylamino;

R

3 is -CN, -COOR5, -CONRRT 7 -CSNH2, -CHO, -CH Z, -CH(OAkyl) 2 -CH2OH, -CH2OR 9 or a substituted or unsubstituted 5- or 6-membered heterocyclic group linked via a ring carbon atom which is between two rri.g heteroatoms; R 4 is H, or a substituted or unsubstituted alkyl, alkenyl, alkynyl, cycloalkyl, aryl or aralkyl group; R 5 is H, -N CRFaR6b, or a substituted or unsubstituted alkyl, alkenyl, alkynyl, cycloalkyl or aralkyl group; R 6 is H, or a substituted or unsubstituted alkyl, alkenyl, akynyl, cycloalkyl, aryl, aralkyl or heteroaryl group; R 7 is a group as defined for R 6 or is -SiR 8 -OH, -CN,

-OR

I0

-NH

2 or -NHRIO; or R 6 and R 7 together form a ring; R 8 is -NR6aR6b or a sunstituted or unsubstituted alkyl, alkenyl, alkynyl, cycloalkyl, aralkyl, aryl or heteroaryl group; R 9 is a substituted or unsubstituted alkyl, alkenyl, alkynyl, cycloalkyl, aralkyl or acyl group; R lo is a group as defined for R 9 or is a substituted or unsubstituted aryl or heteroaryl group; Z is

N-NR

6

R

12 or NOR 6 RI2 is a group as defined for R 6 or is a substituted or unsubstituted acyl group; and R6a and R6b, which may be the same or different, are each a group as defined for R 6 witl the proviso thai, when R 4 is ortho-substituted phenyl or naphthyl, any ortho-substituent thereon is halogen, -NO 2 -OH, -ORo 1 -SH, -SR 8

-SOR

s

-SO

2

R

8

-NH

2

-NR

6 aryl or heteroaryl, 1 WO 92/!6511 PCT/GB92/00376 Title: Herbicides Field of the invention This invention concerns new haloacetic acid derivatives having herbicidal activity, processes for their preparation and herbicidal compositions containing them.

Prior Art Certain pyrimidinyl and triazinyl acetic acid derivatives having herbicidal activity have previously been described, for example in our earlier European Patent specification no 410590.

Description In one aspect, this invention provides the compounds of the formula:

R

3

R

4 C X N N

(I)

R A R and salts thereof, where: A is or -CH=; X is halo; R' and R 2 which may be the same or different, each represent alkyl, alkoxy, haloalkyl, haloalkoxy, halo, alkylamino or dialkylamino;

R

3 is -CN, -COOR s

-CONRR

7

-CSNH

2 -CHO, -CH=Z, -CH(OAlkyl) 2

-CH

2 OH, -CH 2

OR

9 or a substituted or II WO 92/16511 PCT/GB92/00376 2 unsubstituted 5- or 6-membered heterocyclic group linked via a ring carbon atom which is between two ring heteroatoms;

R

4 is H, or a substituted or unsubstituted alkyl, alkenyl, alkynyl, cycloalkyl, aryl or aralkyl group;

R

5 is H, -N=CR"R 6b or a substituted or unsubstituted alkyl, alkenyl, alkynyl, cycloalkyl or aralkyl group;

R

0 is H, or a substituted or unsubstituted alkyl, alkenyl, alkynyl, cycloalkyl, aryl, aralkyl or heteroaryl group;

R

7 is a group as defined for R 6 or is -SO 2

R

8 -OH, -CN, -OR1 0

-NH

2 or -NHRI 0 or R 6 and R 7 together form a ring;

R

8 is -NR"R 6 b or a substituted or unsubstituted alkyl, alkenyl, alkynyl, cycloalkyl, aralkyl, aryl or heteroaryl group;

R

9 is a substituted or unsubstituted alkyl, alkenyl, alkynyl, cycloalkyl, aralkyl or acyl group;

RI

0 is a group as defined for R 9 or is a substituted or unsubstituted aryl or heteroaryl group; Z is =N-NR 6 R' or =NOR 6

R

1 2 is a group as defined for R 6 or is a substituted or unsubstituted acyl group; and

R

6 and R 6 b, which may be the same or different, are each a group as defined for R 6 with the proviso that, when R 4 is ortho-substituted phenyl or naphthyl, any ortho-substituent thereon is halogen, -NO 2 -OH, -OR 10 -SH, -SR, -SOR 8 -SO2R 8

-NH

2

NR

6

R'

0 aryl or heteroaryl.

Any alkyl group present in the molecule is preferably of 1 to 8 carbon atoms especially of 1 to 6 carbon atoms, and particularly of i to 4 carbon atoms. Specific preferred unsubstituted alkyl or alkyl-containing groups include methyl, ethyl, n-propyl, isopropyl, n-butyl, t-butyl, methoxy, ethoxy and n-propoxy.

When any alkyl group in the molecule is substituted, ^I WO 92/16511 PCT/GB92/00376 3 this may for example be by one or more halogen atoms (eg fluorine, chlorine or bromine), alkoxy groups of 1 to 4 carbon atoms (eg methoxy or ethoxy), hydroxy, nitro, mercapto, amino, substituted amino, cyano, acyl, aryl or heteroaryl groups, or groups of the formula -SR 8 or -SOR 8 Specific preferred substituted alkyl-containing groups include chloromethyl, bromomethyl, dichloromethyl, trifluoromethyl, difluoromethoxy, methoxyethyl and ethoxyethyl.

Any alkenyl or alkynyl group present in the molecule is preferably of 2 to 6 carbon atoms, for example allyl, vinyl or propargyl. Any such alkenyl or alkynyl group is preferably unsubstituted, though it may if desired be substituted for example by halogen.

Any cycloalkyl g oup present in the molecule is preferably of 3 to 7 carbon atoms, especially cyclopentyl or cyclohexyl. It is preferably unsubstituted.

Any halogen atom present in the molecule is preferably fluorine, chlorine or bromine.

The term 'aryl' is used herein to mean aromatic carbocycles, which may be mononuclear, eg phenyl, or polynuclear, eg naphthyl. Any aryl group present in the molecule is preferably a substituted or unsubstituted phenyl group. Accordingly, any aralkyl group present in the molecule is preferably a substituted or unsubstituted benzyl group.

Any aryl group present in the molecule, when substituted, is preferably substituted by one or more halogen atoms (eg fluorine, chlorine or bromine), alkyl or alkoxy groups of 1 to 4 carbon atoms (eg methyl, ethyl, methoxy or ethoxy), hydroxy, nitro, mercapto, amino, substituted amino (eg alkylamino, dialkylamino or acylamino groups, especially where.the alkyl moieties have from 1 to 4 carbon atoms), cyano, acyl, aryl or heteroaryl groups, or groups of the formula -SR or -SOR 1 1 WO 92/16511 PCT/GB92/00376 4 Thk term 'heteroaryl' is used herein to mean aromatic heterocyclic groups, which may be mononuclear or polynuclear. Mononuclear heterocyclic groups are preferably of 5 or 6 ring atoms and contain at least one atom of nitrogen, oxygen or sulfur, eg furyl, thienyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl, pyrazolyl, pyridinyl, pyrazinyl or thiadiazolyl. Polynuclear heterocyclic groups are preferably benzoheterocyclic groups, eg indolyl, benzofuranyl, benzimidazolyl or quinolinyl. Such mononuclear or polynuclear heterocyclic groups may, if desired, be substituted eg by one or more halogen atoms, eg chlorine, fluorine or bromine atoms, nitro groups, substituted or unsubstituted amino groups (eg alkylamino, dialkylamino or acylamino groups, especially where the alkyl moieties have from 1 to 4 carbon atoms), cyano groups, or alkyl or alkoxy groups of 1 to 4 carbon atoms, eg methyl, ethyl, methoxy or ethoxy.

The term 'acyl' is used herein to mean the residue of carboxylic, sulfonic or phosphorus-containing acids, for example alkanoyl, alkenoyl, alkynoyl, cycloalkanoyl, aralkanoyl, aroyl, carbamoyl, thiocarbamoyl, alkoxycarbonyl, sulfonyl, sulfamoyl and phosphonyl groups, in which any alkyl, alkenyl, alkynyl or aryl group may be substituted or unsubstituted.

The salts of the compounds of formula I are preferably those formed with alkali-metals (eg lithium, sodium or potassium), ammonium salts, or those formed with organic amines such as cyclohexylamine or piperidine.

A preferably represents -CH=.

X preferably represents chlorine, fuorine or bromine, especially fluorine.

R' is preferably chlo. o, methyl, methoxy, difluoromethoxy or ethoxy, especially methoxy.

R

2 is preferably methyl, methoxy or difluoromethoxy, especially methoxy.

i -L' WO 92/16511 PCT/GB92/00376

R

3 is preferably a group -COOR 5 where R 5 is optionallysubstituted alkyl of 1 to 4 carbon atoms, especially methyl, ethyl or tetrahydrofurylmethyl. Examples of other groups which R 3 may advantageously represent include CONR R 7 (where R 6 is hydrogen and R 7 is SO 2 CH3, SO 2

N(CH

3 2

NH

2 phenyl or 3-pyridyl, or where R 6 and R 7 together with the nitrogen atom to which they are attached form a ring, eg a morpholino group), -CH=Z (where Z is NNHCOCH 3 or

NOCH

2

COC

2

H

5

-CH(OCH

3 2 -CHO2R 9 (where R 9 is CHCO 2

C

2 H, or SO2CH 3 or a dioxolan, thiazolyl or oxadiazolinone ring.

R

4 is preferably an unsubstituted alkyl group, especially isopropyl, sec-butyl or an aryl group, especially phenyl.

Specific preferred compounds according to the invention are those of the Examples provided hereinafter.

The compounds of formula I where R 3 represents a group -COORs (in which R 5 is other than hydrogen), and R 4 represents hydrogen can be prepared by a process in which a compound of the formula:

Z

N N (II) R' A R2 where A, R' and R 2 are as defined hereinbefore, and Z is an anionic leaving group, for example halo or a group of formula -SO 2 Z' where Z' is alkyl of 1 to 4 carbon atoms or aryl, is reacted in the presence of a base with a compound of the formula XCH 2 COOR (where R is as defined hereinbefore but is other than hydrogen, and X is halogen) to give the desired compound.

The base employed is preferably lithium diisopropylamide, and the reaction is desirably effected 1 6 in a suitable solvent medium, eg tetrahydrofuran, and with cooling, eg to about -78 0

C.

The compounds of formula I where R 3 represents a group -CN, -COOR 5 or -CONR 6

R

7 may also be prepared by a process in which a compound of the formula:

R

3 R4- C H N-s N R A R

(III)

where A, R 2 and R 4 are as defined hereinbefore, and R 3 is -CN, -COOR 5 or -CONR 6 R (where R 5

R

6 and R 7 are as defined hereinbefore) is halogenated to give the desired compound.

The halogenation may be effected by conventional techniques depending on the nature of the halogen involved. For example, bromination may be effected by means of N-bromosuccinimide. Fluorination may be effected by first subjecting the compound of formula III to the action of a strong base, eg sodium hydride or lithium diisopropylamide, and reacting the formed anion with a fluorinating agent, eg N-fluoro-N-propyl-ptoluenesulfonamide or N-fluoro-N'-chloromethyltriethylenediamine salts.

Compounds of formula III and processes for their preparation are described in European Patent specification no 410590. Any compounds of formula III not described therein may be made by processes analogous to those described.

The compounds of formula I where R 3 represents a group -CN, -COOR 5 -CHO or -CH 2 OH, and RI and R 2 each represent alkyl, alkoxy, alkylamino or dialkylamino, may also be f: ,jV; TE SH-EET

J

i 7 prepared by a process in which a compound of the formula:

H

R

4 -C X N N (IV) RI A R 2 where R 2

R

4 X and A are as defined hereinbefore is subjected to the action of a suitable electrophile in the presence of a strong base, to give the desired compound.

The strong base employed may, for example, be butyllithium or lithium diisopropylamide, and the reaction is desirably effected at reduced temperature, eg at -78 0

C,

and in a suitable solvent medium, eg tetrahydrofuran.

Suitable electrophiles include cyanates (eg phenyl cyanate), chloroformates (eg alkyl chloroformates), aldehydes (eg formaldehyde) and formamides (eg formdimethylamide).

The compounds of formula IV where RI and R 2 are alkyl may be made by standard methods. The compounds of formula IV where R' and R 2 are alkoxy, alkylamino or dialkylamino may be prepared by reaction of a carboxylic acid derivative of the formula R 4 where R 4 and X are as defined hereinbefore and W is an acid, ester, acid chloride, amide or nitrile group, with a compound of the formula RI-C(=NH)-A-C(=NH)-R 2 where R 1

R

2 and A are as defined hereinbefore.

The compounds of formula I where R 4 is other than hydrogen can be prepared from the corresponding compounds in which R 4 is hydrogen by alkylation or arylation techniques known per se, or by analogous processes well Si.. SUBSTITUTE SHEET I POY11W r Iz, :J.

I -I NIFM WO 92/16511 PCT/GBP2/00376 8 known to those skilled in the art.

The compounds of formula I where R 3 is other than -CN,

-COOR

5 or -CONR 6

R

7 as defined hereinbefore, may be prepared from such compounds by conventional techniques well known to those skilled in the art.

In particular, the compounds of formula I where R 3 is carboxy can of course be prepared from the corresponding esters by hydrolysis, and many further conversions of the acid or ester function can be effected in known ways.

For example, the compounds of formula I where R 3 is a group -COOR 5 may be reduced, eg by means of diisobutylaluminium hydride, to the corresponding compounds where R 3 is a group -CHO (using one molar proportion of the hydride) or -CH 2 OH (using two molar proportions of the hydride). The reductions are conveniently effected in a suitable solvent medium, eg tetrahydrofuran, and with cooling, eg to 5 0

C.

The compounds of formula I where R 3 is -CH20H can be acylated or etherified to give the corresponding compounds where R3 is a group -CH 2 0R 9 The compounds of formula I where R 3 is -CHO can be converted by known techniques to the corresponding hydrazones (eg by reaction with a compound of formula

H

2

N-NR

6

R

1 2 in a suitable solvent medium, eg an alcohol), oximes (eg by reaction with a compound of formula H 2

NOR

6 in a suitable solvent medium, eg an alcohol), ketals, 1,3dioxolanes, 1,3-dithiolanes, 1,3-dioxanes, 1,3-dithianes or imidazolidines (eg by heating in the presence of an acid catalyst with a compound of formula RQH or

HQ-(CH

2 2 3 -QH where Q is 0, S or NH).

In addition, the compounds of formula I where R 3 is carboxy may be converted to the corresponding compounds in which R 3 is a group -CONHSO 2

R

8 by a two-stage process in which the acid is first reacted with thionyl chloride to give the corresponding acyl chloride, and this is then

I

i WO3 92/16511 PCT/GB92/00376 9 reacted with a compound of the formula NaNHS0 2

R

8 to give the desired compound.

The salts of the compounds of formula I may be prepared by reaction of the corresponding unsalified compound of formula I with an appropriate salt-forming base by methods known per se.

The compounds of formula I where R 3 is -CN can be converted by known techniques into the corresponding thioamides where R 3 is -CSNH 2 (eg by reaction with hydrogen sulfide in a suitable base such as pyridine).

The compounds of formula I where R 3 is a heterocycle may be prepared by ring closure procedures well known per se carried out on the corresponding compounds of fornula I where R 3 is -CN, -CSNH 2 or -CONR 67 For example, the compounds of formula I where R 3 is -CN may be converted by the action of ammonia into the corresponding compounds where R 3 represents -C(=NH)NH 2 which may be further reacted with a-haloketones, a-haloacid chlorides or /-diketones to give, respectively, the corresponding imidazoles, imidazolones and pyrimidines. Similarly, ring closure reactions may be performed on the compounds of formula I where R 3 represents -CSNH 2 for example by reaction thereof with dibromoethane, or on the compounds of formula I where

R

3 is -CONR 6

R

7 for example by reaction thereof with an acid chloride or anhydride.

The compounds of formula I and the salts thereof are herbicidally-active against a wide range of broadleaf and grass weeds, but are comparatively safe to certain crop species. They may thus be of use as herbicides, and especially as selective herbicides, particularly in cereals, eg maize, wheat or rice, in best crops, eg sugar beet, in soybeans or in cotton.

In another aspect, therefore, this invention provides a herbicidal composition which comprises one or more compounds of formula I or salts thereof in association WO 92/16511 PCT/GB92/00376 with a suitable carrier and/or surface active agent.

The compositions of the invention usually contain from 0.01 to 99% by weight of the present compounds, and are normally produced initially as concentrates containing from 0.5 to 99%, preferably from 0.5 to 85%, and especially from 10 to 50% by weight thereof. Such concentrates are diluted if necessary before application to the locus to be treated such that the active ingredient comprises from 0.01 to 5% by weight of the formulation applied.

The carrier may be water, in which case an organic solvent may also be present, though this is not usually employed. A flowable uspension concentrate may be formed by grinding the compound with water, a wetting agent and a suspending agent,e.g. xanthan gum.

The carrier may alternatively be a water immiscible organic solvent, e.g. a hydrocarbon which boils within the range 130-270 0 C, e.g. xylene, in which the compound is dissolved or suspended. An emulsifiable concentrate containing a water immiscible solvent may be formed with a surface active agent so that the concentrate acts as a self-emulsifiable oil on admixture with water.

The carrier may alternatively be a water-miscible organic solvent e.g. 2-methoxyethanol, methanol, propylene glycol, diethylene glycol, diethylene glycol monoethyl ether, methylformamide or dimethylformamide.

The carrier mavy alternatively be a solid, which may be finely divided or granular. Examples of suitable solids are limestone, clays, sand, mica, chalk, attapulgite, diatomite, perlite, sepiolite, silicas, silicates, lignosulfonates and solid fertilizers. The carrier can be natural or synthetic or can be modified natural material.

Wettable powders soluble or dispersible in water may be formed by admixing the compound in particulate form with a particulate carrier or spraying molten compound on WO 92/16511 PCT/GB92/00376 11 to the particulate carrier, admixing a wetting agent and a dispersing agent and finely grinding the whole powder mixture.

An aerosol composition may be formed by admixing the compound with a propellant, e.g. a polyhalogenated alkane such as dichlorofluoromethane, and suitably also with a solvent.

The term 'surface active agent' is used in the broad sense to include materials variously called emulsifying agents, dispersing agents and wetting agents. Such agents are well known in the art.

The surface active agents used may comprise anionic surface active agents, for example mono- or di-esters of phosphoric acid with a fatty alcohol ethoxylate, or salts of such esters, fatty alcohol sulfates such as sodium dodecyl sulfate, ethoxylated fatty alcohol sulfates, ethoxylated alkylphenol sulfates, lignin sulfates, petroleum sulfonates, alkylaryl sulfonates such as alkyl-benzene sulfonates or lower alkylnaphthalene sulfonates, salts of sulfonated naphthaleneformaldehyde condensates, salts of sulfonated phenolformaldehyde condensates, or more complex sulfonates such as the amide sulfonates, e.g. the sulfonated condensation product of oleic acid and N-methyl taurine or the dinlkyl sulfosuccinates e.g. the sodium sulfonate of dioctyl succinate.

The surface active agents may also comprise non-ionic agents, for example condensation products or fatty acid esters, fatty alcohols, fatty acid amides or alkyl-substituted phenols with ethylene oxide, fatty esters of polyhydric alcohol ethers e.g. sorbitan fatty acid esters, condensation products of such esters with ethylene oxide e.g. polyoxyethylene sorbitan fatty acid esters, block copolymers of ethylene oxide ad propylene oxide, acetylenic glycols such as 2,4,7,9-tetramethyl-5h4 WO 92/16511 PCT/GB92/00376 12 decyn-4,7-diol, or ethoxylated acetylenic glycols.

The surface active agents may also comprise cationic agents, for example alkyl- and/or aryl-substituted quaternary ammonium compounds such as cetyl trimethylammonium bromide, or ethoxylated tertiary fatty amines.

Preferred surface active agents include ethoxylated fatty alcohol sulfates, lignin sulfonates, alkyl-aryl sulfonates,salts of sulfonated naphthaleneformaldehyde condensates, salts of sulfonated phenolformaldehyde condensates, sodium oleoyl N-methyltauride, dialkyl sulfosuccinates, alkyl phenol ethoxylates, and fatty alkyl ethoxylates.

The present active compounds may be admixed with another pesticide, eg a herbicide, fungicide or insecticide, or a plant growth regulator, particularly' another herbicide. Suitable further herbicides include trietazine, linuron, MCPA, dichlorprop, isoxaben, diflufenican, metolachlot, fluometuron, oxyfluorfen, fomesafen, bentazone, prometryne, norflurazon, chlomazone, EPTC, imazaquin, and especially isoproturon, methabenzthiazuron, trifluralin, ioxynil, bromoxynil, benazolin, mecoprop, fluroxypyr, alachlor, acifluorfen, lactofen, metribuzin, pendimethalin, ethofumesate, benfuresate, phenmedipham, benzophenap, butachlor, chlomethoxyfen, dimepiperate, mefenacet, molinate, naproanilide, oxadiazon, piperophos, prometryne, pyrazoxyfen, pyrazosulfuron-ethyl, bensulfuron, simetryne, pyrazolate, pretilachlor, thiobencarb and pyributicarb.

The present compounds may be applied to plants, the soil, land or aquatic areas, and particularly to a locus at which a crop is growing. The compounds are active both pre- and post-emergence, and may be employed at rates of from 1g to 2kg/ha.

S- 'I .Li C- 3I3 I. .LAIJU W.LI C suitable carrier and/or surface active agent.

WO 92/16511 PCT/GB92/00376 13 Examples The invention is illustrated by the following Examples, in which Me methyl, Et ethyl, Pr propyl, Bu butyl, s-Bu l-methylpropyl, Oct octyl, cyhex cyclohexyl, THF tetrahydrofuryl and Ph phenyl.

Example 1 Ethyl 2-fluoro-2-(4,6-dimethoxvpyrimidin-2-vl)acetate Butyllithium (21ml of a 1.6M solution in hexane) was added to di-isopropylamine (4.94ml) in dry tetrahydrofuran (100ml) under nitrogen at a temperature of -78 0 C, and the mixture was stirred for 30 minutes. A solution of ethyl fluoroacetate (2.51g) in dry tetrahydrofuran (20ml) was then added at a temperature of -60aC, and the mixture w.s stirred for 1 hour. Hexamethylphosphoric triamide (5.12ml) was added, and the mixture was stirred for a further 10 minutes. Then 4,6-dimethoxy-2methylsulfonylpyrimidine (5.0g) was added portionwise, and the temperature of the reaction mixture rose within hours to room temperature. The reaction mixture was washed with saturated ammonium chloride and sodium chloride solution, the aqueous phase was extracted with ethyl acetate, and the combined organic layers were dried over magnesium sulfate and evaporated. The product obtained was chromatographed on silica gel using hexane/ethyl acetate (0-20% ethyl acetate), to give the desired compound as a yellow oil (0.56g), refractive index at 20 0 C 1.4829.

Example 2 Ethyl 2-(4 6-dimethoxyprimidin-2-yl -2-fluoro-3methylbutanoate Butyllithium (12.8ml of a 1.6M solution in hexane) was added to di-isopropylamine (3.05ml) in dry tetrahydrofuran (120ml) under nitrogen at a temperature of -780C, and the mixture was stirred for 30 minutes. The product of Example 1 (3.4g) in dry tetrahydrofuran WO 92/16511 PCT/GB92/00376 14 was then added at a temperature of -65 0 C, and the mixture was stirred for 1 hour, during which the temperature rose to -30 0 C. After cooling to -60 0 C, 3.18g of hexamethylphosphoric triamide were added, and the mixture was stirred for 15 minutes. Then 2-iodopropane (3.4g) was added, and the mixture was stirred at room temperature for 72 hours, after which it was diluted with 100ml diethyl ether, and washed with a saturated ammonium chloride and sodium chloride solution. The aqueous phase was extracted with diethyl ether, and the organic layer was dried over magnesium sulfate and evaporated. The yellow oil obtained was finally chromatographed on silica gel using hexane/ethyl acetate ethyl acetate) to give 1.46g of the desired product, refractive index at 20 0 C 1.4756.

Example 3 Methyl 2-(4,6-dimethoxvpyrimidin-2-yl)-2-fluoro-2phenylacetate Method A Methyl 2-(4,6-dimethoxypyrimidin-2-yl)-2phenylacetate (1.2g) was dissolved in tetrahydrofuran the solution was cooled to 5°C, and n-butyllithium in hexane; 1.7ml) was added dropwise. The solution was stirred for 20 minutes and was then diluted with toluene (14ml). N-fluoro-N-propyltoluenesulfonamide (1.5g) was added, and the solution was stirred for hours under nitrogen at room temperature, then poured into saturated ammonium chloride solution (300ml). It was extracted with ether, and the organic layer was washed and dried, then evaporated to dryness. The residue was purified by column chromatography on silica eluting with ether in petrol 60-80, giving the desired product, 0.95g, as a yellow oil.

Method B 4,6-Dimethoxy-2- (-fluorobenzyl)pyrimidine Dimethyl malonimidate dihydrochloride (11.0g) was -i L ;ij WO 92/16511 PCT/GB92/00376 suspended in dichloromethane (100ml) at -40 0 C. Ethyl diisopropylamine (38.9ml) was added dropwise over minutes at -40 0 C, followed by 2-fluoro-2-phenylacetyl chloride (11.0g) in dichloromethane (15ml) over 10 minutes at -40 0 C. The reaction mixture was allowed to warm to room temperature and stand overnight. It was then diluted further with dichloromethane, washed with ammonium chloride solution, then with water, and was dried over magnesium sulfate. The dichloromethane solution was evaporated to dryness to give 13.9g of the desired product.

Methyl 2-(4,6-dimethoxvpvrimidin-2-vl)-2-fluoro-2phenylacetate n-Butyllithium (2.5M in hexane, 1.7ml) was added to diisopropylamine (0.59ml) under nitrogen in dry tetrahydrofuran (15ml) at -78 0 C. This solution was stirred for 30 minutes, then a solution of the product of stage above (l.0g) in tetrahydrofuran (10ml) was added over 20 minutes. Methyl chloroformate (0.4g) in dry tetrahydrofuran (10ml) was added over 15 minutes at -78 0

C,

and the reaction mixture was allowed to warm slowly to room temperature, after which it was added to aqueous ammonium chloride solution. The mixture was extracted with ether, the extracts being washed with water, dried over magnesium sulfate, and evaporated to dryness to give 1.08g of the desired product, identical to that of Method A above.

Example 4 Methyl 2-chloro-2-(4,6-dimethoxypvrim:din-2-vl)-2phenylacetate Methyl 2-(4,6-dimethoxypyrimidin-2-yl)-2phenylacetate (2.0g) and N-chlorosuccimimide (2.0g) were stirred at reflux in carbon tetrachloride (25ml) under a bright light for 18 hours. The reaction mixture was filtered and evaporated to dryness, and the residue was

J'

t-butyl, methoxy, ethoxy and n-propoxy.

When any alkyl group in the molecule is substituted, WO 92/16511 PCT/GB92/00376 16 purified by column chromatography on silica eluting with ether:hexane yielding the desired product (2.16g) as a pale yellow oil.

Example 2-Fluoro-3-methyl-2-(4,6-dimethoxy-l,3,5-triazin-2vl)butan-l-ol Ethyl 2-fluoro-3-methyl-2-(4,6-dimethoxy-1,3,5triazin-2-yl)butanoate (1.5g) (see Example 11 below) was dissolved in tetrahydrofuran (40ml), and the solution was cooled to 5 0 C under nitrogen. Di-isobutyl aluminium hydride (llml of 1.0M in hexane) was added, and the mixture was stirred for 24 hours at room temperature, after which it was treated dropwise with water (5ml). The solution was stirred for a further 30 minutes, and silica (10g) was added. The suspension was filtered, and the solution was dried and evaporated. The residue was purified by chromatography, yielding the desired compound (0.22g) as a white solid, mp 72-750C.

Example 6 2-Fluoro-3-methvl-2-(4,6-dimethoxy-1,3,5-triazin-2vl)butvl acetate The product of Example 5 (0.60g) was dissolved in dry ether (40ml) with triethylamine (0.35ml) at 5 0 C, and acetyl chloride (0.18ml) in dry ether (10ml) was added dropwise. The solution was left to stand at room temperature for 2 days, after which it was filtered, and residue was purified by chromatography, giving 0.35g of the desired product as a clear oil.

Example 7 2-Fluoro-3-methyl-2-(4,6-dimethoxvpyrimidin-2-v1)butanoic acid Methyl 2-fluoro-3-methyl-2-(4,6-dimethoxypyrimidin-2yl)butanoate (l.0g) (see Example 9 below) was dissolved in methanol (7m1), and was treated with 5N sodium hydroxide WO 92/16511 PCT/GB92/00376 17 solution (1.5ml) at 5-10 0 C. The methanol was evaporated off, and the residue was treated with water, then made acid with 5N hydrochloric acid, saturated with sodium chloride, and extracted with ether. The ethereal solution was washed with saturated sodium chloride solution and dried over magnesium sulfate. The product obtained by evaporation of the ether was triturated with pentane, yielding the desired product (0.87g).

Examples 8-48 The following compounds of formula I in which R' and

R

2 are both methoxy may be prepared by methods analogous to those of the above Examples: Analogous to method of Example 1 No A R 3 R

X

8 N COOEt H F yellow oil Analogous to method of Example 2 No A R 3 R X 9 CH COOMe i-Pr F rd 1.4762 CH COOEt s-Bu F colourless oil 11 N COOEt i-Pr F mp 48-49 0

C

12 N COOEt s-Bu F yellow oil 13 N COOEt CH(Et) 2 F bpl60°C/0. mm Hg 14 N COOEt CH 2 COt-Bu F pale yellow gum N COOEt n-Pr F pale yellow gum 16 N COOEt CH(Me)Ph F pale yellow gum 17 N COOEt CH(Me)COOEt F pale yellow gum 18 N COOEt CH(Me)CN F pale yellow gum 19 N COOEt CH(Me)COMe F pale orange oil Analogous to method of Example 3 (Method B) 20 CH COOn-pentyl Ph F yellow oil Analogous to method of Example 4 No A R 3 R

X

21 CH COOMe H Br mp 74-76 0

C

22 CH COOMe Ph Br pale yellow oil -1 especially methoxy.

WO 92/16511 PCr/GB92/00376 various appropriate methods No A R 3 23 CH COOn-Oct 24 CH COON=C (Me) 2 25 CH CONHSO 2 Me 26 CH COON=C(Me) 2 27 CH 2-COOCH 2

THF

28 CH CHO 29 CH l,3-dioxolan-2-yl 30 CH 4,5-dihydro-5-oxo- 1,2, 4-oxadiazol-3-yl 31 CH 4,5-dihydrothiazol -2-yl s -Bu Ph Ph 2 -MePh 3 -MePh Ph Ph i-Pr 1 -naphthy 1 32 CH CH 2 0H Ph F 33 CH CH 2

OCH

2 COOEt i-Pr F 34 CH CH 2 0SO 2 Me s-Bu F N COOn-Bu i-Pr F 36 N CN Ph F 37 N CH=N'NHCOMe Ph F 38 N CONHNH 2 Ph F 39 N COOn-Bu Ph Cl CH CH=NOCH 2 COOEt n-Pr F 41 N CONHPh cyhex F 42 CU COOn-Bu i-Pr F The following compounds of f ormula I where~ RI and R 2 1 are both methyl inay be prepared by methods analogous to those described above: 43 CU CONHSO 2 Me i-Pr F 44 CU CONHS0 2 N(Me) 2 Ph F The following compound of formula I where RI is chioro and R 2 is methoxy may be prepared by methods analogous to those'described above: CU COOEt CH=2CCH 2

F

The following compounds of f ormula I where RI and R 2 are difluoromethoxy may prepared by methods analogous WO 92/16511 PCT/GB92/00376 19 to those described above: 46 CH COOEt 2-ClPh F 47 CH COOCH 2 Ph 3-ClPh F 48 CH CONH-3-pyridyl Ph F HERBICIDAL EXAMPLE A (Pre-Emergence) Seeds of the test species listed below were each sown in 8.5cm square pots filled to within 2cm of the top with sterile loam, and were covered with a 2-5mm layer of loam.

The pots were watered, and then treated by application to the soil surface in a spray cabinet with the compounds of the Examples listed below formulated as a solution/suspension in 3:1 by volume of acetone and the wetting agent polyoxyethylene (20 mols) monolaurate solution (10 g per litre). The concentration of each test compound and volume of application were calculated to give the desired rate of application of the compound in 200 litres per hectare.

After 3 to 4 weeks growth in a glasshouse (minimum temperature 16 0 C for temperate species, 21 0 C for nontemperate species, 16 hours per day photoperiod) the plants were visually assessed for any herbicidal response.

Al. differences from an untreated control were scored accordingly to an index where 0 no effect, 1 1-24% effect, 2 25-69% effect, 3 70-89% effect and 4 90-100% effect. In the table below, the following letters are used to denote the plant species: a Triticum aestivum (wheat) b Hordeum vulgare (barley) c Beta vulgaris (sugar beet) d Bressica napus (rape) e Alopecurus myosuroides (blackgrass) f Avena fatua (wild oat) g Elymus repens (couch) h Bromus sterili (barren brome) i Viola arvensis (field pansy) I WO 92/16511 PCT/GB92/00376 j Stellaria media (chickweed) k Galium aparine (cleavers) 1 Matricaria inodora (scentless mayweed) m Polyvonum lapathifolium (Pale persicaria) n Veronica persica (Buxbaum's speedwell).

The results obtained were as follows: Ex K/ha a b c d e f g hi 1j m n 2 0.125 4 4 4 4 4 4 4 4 4 4 4 4 4 4 3 0.125 4 3 4 4 4 4 4 4 4 3 4 4 4 10 0.125 3 4 4 4 4 3 4 4 4 4 4 4 4 4 11 0.125 4 4 2 4 4 3 4 4 2 4 4 1 4 4 12 0.125 4 3 3 4 4 3 4 4 3 4 3 1 4 4 13 0.125 2 2 3 4 4 1 4 3 3 4 3 3 4 4 0.125 3 4 2 3 4 2 4 4 1 3 3 0 4 4 16 0.125 2 2 1 1 2 2 4 2 1 0 3 1 3 3 HERBICIDAL EXAMPLE B (Post-Emergence) The plant species listed below were grown in square pots containing sterile loam in a glasshouse (minimum temperature 16 0 C for temperate species, 21°C for non-temperate species, 16 hours per day photoperiod), and were treated in a spray cabinet at the 2-3 leaf stage with the compounds of the Examples listed below formulated as a solution/suspension in 3:1 by volume of acetone and the wetting agent polyoxyethylene (20 mols) monolaurate solution (10 g per litre). The concentration of each test compound and volume of application were cal'ulated to give the desired rate of application of the compound in 200 litres per hectare.

After 3-4 weeks, the plants were visually assessed for any herbicidal response. All differences from an untreated control were scored according to an index where 0 no effect, 1 1-24% effect, 2 25-69% effect, 3 70-89% effect and 4 90-100% effect.

In the table below, the letters used denote the same plant species as in Herbicidal Eample A: WO 92/16511 W092/6511PCT/GB92/00376 Ex 2 3 9 11 12 13 15 16 19 The results Kgf/ha a b 0.125 4 4 0.25 4 4 0.125 4 4 0.125 1 1 0.125 4 4 0.125 2 4 0.25 2 2 0.25 4 4 0.25 2 2 0.125 2 2 obtained were as follows: c d R f _h -i k lmn 4 44 44 44 44 24 2 4 43 44 34 44 24 4 4 44 44 44 44 44 4 2 22 02 23 42 02 0 2 34 4 442 44 04 2 2 3 444 32 44 13 2 2 34 34 41 14 03 3 3 4 4 4 3 4 3 4 4 1 4 3 2 3 433 32 13 03 2 2 22 22 31 23 0 34 21a Throughout this specification and the claims which follow, unless the context requires otherwise, the word "comprise", or variations such as "comprises" or "comprising", will be understood to imply the inclusion of a stated integer or group of integers but not the exclusion of any other integer or group of integers.

I. 1 1; 940922,p:oper\dab, t 412,spc,21 I

Claims (8)

1. 2. The compounds according to claim 1 in which R' is chloro, methyl, methoxy, difluoromethoxy or ethoxy.
2. 3. The compounds according to claim 1 or claim 2 in which R 2 is methyl, methoxy or difluorolthoxy.
3. 4. The compounds according to any/of claims 1 to 3 in which X is chlorine, bromine or fluorine. The compounds according to any, of claims 1 to 4 in which R 3 is a group -COOR3 where R 5 is alkyl of 1 to 4 carbon atoms.
4. 6. The compounds according to any/of claims 1 to 5 in which R 4 is hydrogen, alkyl of 1 to 4 carbon atoms, or phenyl
5. 7. Methyl 2-(4,6-dimethoxypyrimidin-2-yl)-2-fluoro-2- phenylacetate.
6. 8. A herbicidal composition which comprises from 0.01 to 99% by weight of one or more compounds according one to anyof claims 1 to 7, in association with a suitable carrier and/or surface active agent.
7. 9. A method of combating weeds at a locus infested or liable to be infested therewith which comprises r: ^I P pi miii- -I p -_I Y~. -24- applying to said locus an effective amount of one or more compounds according to any one of claims 1 to 7. A method according to claim 9 in' which the amount applied is from 0.001 to 2 kg/ha.
8. 11. Haloacetic acid derivatives of the formula herbicidal compositions containing them or methods of combating weeds involving them, substantially as hereinbefore described with reference to the Examples. DATED this 23rd day of September, 1994 Schering Agrochemicals Limited By Its Patent Attorneys DAVIES COLLISON CAVE I. 444 t S r t o' 1 P~ *P S ~r 1PJ 940922,p:\opez\db, 41412.sp,24 INTERNATIONAL SEARCH REPORT Intwnstluaia1 Application No PCT/GB 92/00376 L.CASSIFICATION OF SUILEC MATMI If seia classification symnbols apply, indkcateall) 0 According to Interntiocal Patent assflation (0PC) or to bath Natioazi ass flnatlnn and tic Int.Cl. 5 C07D239152; C070251/20; C07D239/26; C070239/34 C07D405/06 U. FUUM.S SEARCHED Minimum Documentation Soxcbd ClassIfication System Cassiflcatlon Symnbols Int.Cl. 5 C07D Documentation Searched other than Minimum Documentation to the Extent that such Documents are Included In the Fields Searched Ml. DOCUMEN-TS CONSIDERED TO HE RELEVANTS category o] Cittion of Document, IL with indication, where appropriate, of the relevant passages L2 Relevant to Claim No.13 A EP,A,0 410 590 (SCHERING) 30 January 1991 1,8,9 cited in the application see claims A EP,A,O 353 640 (HOECHST) 7 February 1990 1,8,9 see claims 0 Special categories of cited documents 10 'T later d~oment published after the lntenaulonal filing date 'A ocmntdfi~gthe genra state of the ant which Is am or priority date and not In conflict with the application but A doumen defningcited to undetvsnd the principle or theory underiying the considered to be of pamticular relevance Invention earlier document but published on or after the interi.ational Xr document of particular relevance; the claimed invention fi'ling date cannot he. considere navel or cannot be considered to W' document which may throw doubts on priority calm(s) or Involve an Inventive stop which is cited to establish the publication date of anohe -r document of particular relevance; the claimed Invention citaion or other special reason (as specified) cannot be considered to Involve an inventive step when the 0' document referrig to an oral disclosure =se, exhibition or document Is comblned with one or more other such docu- other meam Monts such combknatn being obvioc.- to a person skilled I" document published prior to the international fling date bu in thet. later than the priority date clalmed document memons of the same patent family IV. CERTIFICATION Date of the Actua Completion of the Internniluial Search Date of Malling of this International Search Report 22 APRIL 1992 28, 04. 92 Intaeana l Searching Authority Signatur of Authorized Officer h EUROPEAN PATENT OFFCE FRANCOIS J. C. fers PCTJISA/Z10 In.rmi aed) (J7er 1USn ANNEX TO THE INTERNATIONAL SEARCH REPORT ON INTERNATIONAL PATENT APPLICATION No. GB 9200376 SA 57294 M&i annex lists the petent famiy members relating to the patent documents cited in the above-mentioned international mnarch report. The members we as contained in the European Patent Office EDP file on The European Patent Ofic is in no way liable for these particulars which are merely given for the purpose of information. 22/04/92 Pa ment Publication Patent family Publication cited in marF report -T date meinberks) date IEP-A-0410590 30-01-91 JP-A- 3058976 14-03-91 EP-A-0353640 07-02-90 DE-A- 3826230 08-02-90 IAAU-A- 3914489 08-02-90 JP-A- 2282371 19-11-90 US-A- 5053072 01-10-91 Q o o eal bu i mi efK ora fteEroenPtn fie o 28