GB2293766A - Herbicidal compositions based on synergistic combination of glyphosate and 1,3,4,5-tetrasubstituted pyrazoles - Google Patents

Abstract

A herbicidal preparation comprises both a compound of general formula (I): <IMAGE> [wherein: R<1> is alkyl, alkenyl, alkynyl, benzyl, cycloalkyl or cycloalkenyl, all of which may be optionally substituted; R<2> is haloalkoxy; R<3> is halo; X is CN or halo; each Y is independently halo, CN, NO2, OH, alkyl, alkoxy, alkylthio, alkoxyalkyl, SO2alkyl, CONR<a>R<b> or heterocyclyl, or two Y groups together form a further ring; m is 0 - 4 R<a> and R<b> are independantly H or lower alkyl] and glyphosate (or a herbicidally acceptable salt or derivative thereof).

Description

HERBICIDAL PREPARATIONS The present invention relates to herbicidal treatments and preparations comprising two or more herbicidal components. More particularly, the invention relates to herbicidal mixtures containing the herbicide glyphosate or a salt or derivative thereof.

Glyphosate (N-phosphonomethylglycine) is a highly effective and commercially important herbicide which has a broad spectrum of activity and is of use in controlling weeds at various stages of growth, for example, it has been used in the control of emerging seedlings, maturing and established woody and herbaceous vegetation and aquatic plants. Typically, glyphosate will be applied in an aqueous solution as a post-emergent herbicide for the control of a wide variety of plant species.

Commercial formulations of glyphosate are usually aqueous solutions of a herbicidally acceptable salt such as an alkali metal, ammonium, alkyl sulphonium, or alkylphosphonium salt or the salt of an amine having a molecular weight of less than about 300. Well known and widely used salts of glyphosate include glyphosate-isopropylammonium, glyphosate-sesquisodium and glyphosate trimesium (also known as sulfosate).

It has now been found, however that glyphosate and its salts1 can be combined synergistically with other herbicidally active compounds to produce extremely active herbicidal preparations.

Therefore, in a first aspect of the present invention there is provided a herbicidal preparation comprising a compound of general formula (I) wherein: R1 is alkyl, alkenyl, alkynyl, benzyl, cycloalkyl or cycloalkenyl all of which may be optionally substituted; R is haloalkoxy; R3 is halo; X is CN or halo; each Y is independently halo, CN, NO2, OH, alkyl, alkoxy, alkylthio, alkoxyalkyl, SO2alkyl, CONRaRb, heterocyclyl or two Y groups together form a further ring; m is 0-4 Ra and Rb are independently H or lower alkyl; together with glyphosate or a herbicidally acceptable salt or derivative thereof.

The preparations of the present invention have a surprisingly high herbicidal activity which is greater than the sum of the activities of the individual herbicidal components. Thus the combination of a compound of general formula (I) and glyphosate or a glyphosate salt appears to display synergy. The preparations are capable of controlling the growth of a variety of plants including grass weeds, broad leaved weeds and sedges in a variety of situations such as agriculture and horticulture, forestry and amenity. A particular advantage of the preparations of the present invention is that they are able to provide post-emergence control of over-wintered weeds before planting a crop and, in the same application, to achieve control of weeds germinating subsequently.

The preparations of the present invention may be designed for the simultaneous, separate or seqential application of the two active ingredients but it is often simplest for the active ingredients to be applied simultaneously in a single composition.

In the context of the present invention, the term herbicidally acceptable salt includes alkali metal, ammonium, alkyl sulphonium, or alkylphosphonium salt or the salt of an amine having a molecular weight of less than about 300. In particular, the term includes glyphosate-isopropylammonium, glyphosate-sesquisodium and glyphosate trimesium (also known as sulfosate).

Glyphosate or any of its herbicidally acceptable salts may be employed in the preparations of the present invention although, tor some uses, glyphosate-trimesium is particularly suitable.

The preparations of the invention may contain a single compound of formula (I) or a mixture of such compounds.

As used herein, the term "alkyl" refers to straight or branched alkyl chains having up to 10 carbon atoms. The terms "lower" used in relation to "alkyl" means that the chains have from 1 to 4 carbon atoms.

The term "halogen" used herein includes fluorine, chlorine, bromine and iodine. Suitable optional substituents for alkyl, alkenyl, alkynyl, benzyl, cycloalkyl and cycloalkenyl, groups described herein include halogen such as chlorine, fluorine and bromine; haloalkyl such as trifluoromethyl; haloalkoxy such as trifluoromethoxy; aryl such as phenyl or naphthyl; cycloalkyl for example containing up to 7 ring atoms; or heterocyclyl containing for example up to 10 ring atoms up to three of which are selected from oxygen, nitrogen and sulphur, such as tetrahydrofuryl.

The group X is preferably attached to the phenyl ring at the 4-position and is preferably CN or chloro.

Preferred values for m are zero or 1. When m is other than zero, suitable examples of Y are fluorine and chlorine, preferably fluorine.

When m is 1, Y is preferably attached to the phenyl ring at the 2-position.

A preferred group R1 is C14 alkyl, especially methyl or ethyl.

Preferably R is a halomethoxy group in particular a dihalomethoxy group such as dichloromethoxy or difluoromethoxy, most preferably difluoromethoxy. Preferred examples of R3 include chlorine or fluorine, particularly chlorine.

The formula (I) given above is intended to include tautomeric forms of the structure drawn, as well as physically distinguishable modifications of the compounds which may arise, for example, from different ways in which the molecules are arranged in a crystal lattice, or from the inability of parts of the molecule to rotate freely in relation to other parts, or from geometrical isomerism, or from intra-molelcular or inter-molecular hydrogen bonding, or otherwise.

Specific examples of compounds of the invention are listed in Table I.

TABLE I Comp R1 R2 R3 X Y m No 1 CH3 OCHF2 C1 4-C1 2-F 1 2 CH3 OCHF2 Cl 4-CN 2-F 1 Compound 1 is known in the art and its preparation is described in J0372460. Other compounds of formula (I) may be prepared by similar routes to those set out in J0372360.

In particular compounds of formula (I) may be prepared by halogenation of compounds of formula (II) in which R11 R2, X, Y and m are as defined in relation to formula (I). This may be done using conventional techniques as described in the prior art. In particular the reaction may be effected in a solvent such as a halogenated hydrocarbon (for example dichloromethane, chloroform and carbon tetrachloride); an aromatic hydrocarbon (such as benzene, toluene and xylene); an ester such as ethyl acetate; a nitrile such as acetonitrile or benzonitrile; a chain-like ether such as diethyl ether or methylcellosolve; a cyclic ether such as dioxane or tetrahydrofuran; dimethylsulphoxide or dimethylformamide. These solvents may be used individually, or they can be used in the form of mixtures. A particularly preferred solvent is acetonitrile.

Suitable halogenating agents include chlorinating agents such as chlorine, phosphorus trichloride, phosphorus pentachloride and sulphuryl chloride1 as well as other halogenating agents such as bromine and iodine.

The reaction temperature should be selected in the range from -3O0C to 1500C, preferably from 10 C to 250C which may be maintained by either the controlled addition of the chlorinating agent or cooling or both.

Compounds of formula (II) may be prepared from compounds of formula (III) in which R1, X, Y and m are as defined in relation to formula (I) by reaction with compounds of formula (RCZ), where Rc is a lower haloalkyl group and Z is a leaving group in the presence of a base as described in the art. Examples of suitable leaving groups include chlorine. A particularly preferred compound of formula (RCZ) is chlorodifluoromethane.

The reaction is suitably effected in the presence of a solvent or mixtures of solvents, in the presence or absence of a base and optionally in the presence of a catalyst at a temperature between -10 and 100"C.

The applicants have found that this reaction is preferably undertaken as a stirred biphasic phase transfer reaction in the presence of an organic solvent and aqueous base solution in the presence of a phase transfer catalyst, preferably at room temperature. Suitable organic solvents are not miscible with water and include chlorinated solvents, for example, dichloromethane and chloroform, aromatic solvents, for example, toluene, ethers, for example, diethylether and esters, for example, ethyl acetate.

Dichloromethane is a preferred solvent.

Suitable phase transfer catalysts include tetraalkylammonium or tetraalklylphosphonium salts, in particular tetrabutylphosphonium bromide.

Suitable bases are water soluble and include, but are not limited to, alkali and alkaline earth carbonates, bicarbonates and hydroxides, for example, sodium hydroxide.

In particular, the compound of formula (III) is dissolved in an organic solvent such as dichloromethane with the phase transfer catalyst and the solution is saturated with compound of formula (RCZ), usually by bubbling this compound in the form of a gas through the solution. The reaction is then initiated by the addition of an aqueous solution of base such as a 50% solution of aqueous sodium hydroxide and the mixture stirred vigorously at room temperature.

Compounds of formula (III) may be prepared from compounds of formula (IV) in which X, Y and m are as defined in relation to formula (I) and R4 is lower alkyl (preferably ethyl) by reaction with compounds of formula (X) where R1 is as defined in relation to formula (I). The reaction is carried out in the presence or absence of solvent, and optionally in the presence of a catalyst at temperatures of from -10 C to 1500C in particular the reflux temperature of any solvent present. Suitable solvents are those which dissolve both reactants and include alcohols, in particular the alcohol corresponding to the group R4 in the compound of formula (II). For 4 instance, when R4 is ethyl, a preferred solvent would be ethanol.

The applicants have found that the reaction may be carried out in the absence of any solvent. Thus the compound of formula (IV) is reacted directly with a appropriate alkylhydrazine, such as methylhydrazine, such as methylhydrazine at elevated temperature, for example at about 70"C.

Compounds of formula (IV), where X, Y and m are as defined in relation 4 to formula (I) and R4 is lower alkyl, may be prepared by reacting a compound of formula (V), wherein X, Y and m are defined in relation to formula (I) and R5 is a hydroxy or a leaving group, with a compound of formula (IX), where R6 is a group R4 as defined above, and R7 is an activating group, or R6 and R7 together form a cyclic activating group.

Suitable leaving groups R5 include halogen, in particular chlorine.

As used herein, the term 'activating' group means a group which increases the acidity of the hydrogen atoms on the adjacent carbon and is removable by acid catalysed hydrolysis, or by base catalysed hydrolysis, or by alcholysis.

Examples of activating groups R7 include carboxylic ester groups in particular alkyl ester groups, salts of carboxylate groups, nitriles and optionally N-substituted amides. In particular R7 is either a carboxylate 8 ester of formula C02R8 or a carboxylate salt of formula C02 R9 . Suitable groups R8 are optionally substituted alkyl groups such as ethyl, or R8 together with R6 may be joined to form a cyclic structure. Suitable cations for R9 are organic or inorganic cations. Preferably R9 is an inorganic cation such as an alkali metal cation, suitably potassium.

Particularly preferred compounds of formula (IX) are malonate half ester salts where R6 is lower alkyl in particular ethyl and R7 is a group CO,-R9+ where R9+ is an inorganic cation, in particular potassium.

Examples of cyclic activating groups include compounds where R7 is a group of formula CO2R8 and R8 together with R6 forms a group > C(CH3)2. In this case, the compound of formula (IX) is Meldrum's acid.

The reaction may be carried out in the presence or absence of solvents or mixtures of solvents. Suitable solvents include chlorinated solvents such as dichloromethane, aromatic solvents such as toluene, ether solvents such as diethylether and tetrahydrofuran or nitriles such as acetonitrile.

A preferred solvent is acetonitrile.

Furthermore, the reaction is carried out optionally in the presence of a base, and in the presence or absence of a nucleophilic catalyst. An inert atmosphere such as nitrogen or argon may be employed. Temperatures of from '"0 to 2000C, preferably from -10 to 1000C, and most preferably from Oo to 100 C, are suitably employed. The reaction conditions which give optimal results will vary depending upon the specific nature of the compounds of formulae (V) and (IX). However the skilled chemist would be able to determine these readily.

Suitable bases for use in the reaction include inorganic bases such as alkali or alkaline earth metal hydroxides, bicarbonates, carbonates, hydrides or alcholates, in particular potassium carbonate, sodium hydroxide or sodium ethoxide. Alternatively organic bases such as tertiary amines, pyridine, optionally substituted pyridines, Hunigs base and diazobicycloundecane may be used.

Suitable nucleophilic catalysts include pyridine, optionally substituted pyridine, imidazole, tertiary amines such as trialkylamines, N-hydroxysuccinimide and optionally substituted imidazoles.

The reaction may also require the presence of a non basic inorganic salt. Suitable salts include but are not limited to magnesium salts, in particular magnesium halides such as magnesium chloride.

When R5 is hydroxy, (i.e. the compound of formula (V) is a compound of formula (VI), the compound of formula (IV) is preferably prepared using a base mediated reaction as described above but additionally in the presence of a dehydrating agent such as carbonyldiimidazole or a carbodiimide, for example N,N'dicyclohexylcarbodiimide. In this reaction, preferred temperatures are from 6OO to 150 0C, typically from 200 to 400C; a preferred solvent is dichloromethane and a preferred base is triethylamine.

Dimethylaminopyridine is a typical catalyst for this reaction.

When the compound of formula (IX) is Meldrum's acid, the reaction is suitably effected in the presence of a base and in particular Hunig's base.

Temperatures of from -600 to 1000C and in particular about OOC are preferred in these circumstances, and dichloromethane is a preferred solvent.

When the compound of formula (IX) is a malonate half ester salt, in particular potassium ethyl malonate, compound (V) is typically an acid chloride (i.e. R5 is chloride).

A typical process comprises the pre-formation of a slurry of the malonate half ester salt, a magnesium salt, preferably magnesium chloride, and a base, preferably triethylamine. The process is effected in an inert solvent, preferably acetonitrile, under an inert atmosphere of, for example, nitrogen, with vigorous stirring and cooling typically to about 10 C. The reaction is typically initiated by the careful addition of the compound of formula (V) to the cooled reaction mixture, usually at about OOC. The mixture is then stirred at a temperature between OOC to 1O00C, generally at room temperature, for an extended period, conveniently overnight.

Compounds of formula (V) may be readily prepared from the corresponding acid of formula (VI) by conventional techniques. For example, the acid of formula (VI) is reacted with thionylchloride in the presence or absence of a solvent or mixture of inert solvents, in the presence or absence of a base and in the presence or absence of an inert atmosphere such as nitrogen or argon. Suitably the reaction is effected at temperatures of between -6O0C and 1500C, typically at the reflux temperature of the solvent. Examples of solvents which can be employed include ethers such as diethylether, or aromatics such as toluene, or chlorinated solvents such as dichloromethane, or nitriles such as acetonitrile.

Compounds of formula (VI) may be prepared by the hydrolysis of esters of formula (VII), where m, X and Y are as defined in formula (I) and R10 is optionally substituted alkyl, for example methyl. The hydrolysis may be effected in the presence or absence of an organic solvent by either aqueous acid or aqueous base. Typical solvents include alcohols for example methanol, ethers, for example tetrahydrofuran, nitriles for example acetonitrile, amides, for example dimethylformamide, and dimethylsulphoxide. Typical acids include mineral acids, for example hydrochloric acid, and organic acids, for example toluenesulphonic acid and acetic acid. Typical bases include alkali and alkaline earth, hydroxides, hydrides, carbonates and bicarbonate for example sodium hydroxide and potassium carbonate.The reaction may be undertaken at temperatures between OOC to boiling point of the solvent, typically in the range OOC to 100"C.

Compounds of formula (VII) may be prepared from compounds of formula (VIII), where m and Y are as defined in formula (I), R10 is as defined in formula (VII) and Z is a leaving group by reacting with a cyanide salt in the presence or absence of a catalyst in an inert solvent under an optional inert atmosphere. Typical leaving groups include sulphonate esters, sulphones and halogen, for example chloro. Suitable catalysts are transition metals, for example nickel and palladium. Typical cyanide salts are either inorganic, typically alkali or alkaline earth cyanides for example potassium cyanides. Suitable solvents include ethers, for example diethylether, tetrahydrofuran; aromatics, for example toluene; chlorinated solvents for example dichloromethane; nitriles for example acetonitrile; amides for example dimethylformamide or dimethylsulphoxide.Suitable inert atmospheres include argon and nitrogen. Reaction temperatures may be in the range of 0 C to 25O0C. The reactions may be undertaken in an autoclave and at elevated temperatures. When undertaken without an autoclave a typical reaction temperature is reflux.

Alternatively compound of formula (I) may be prepared from a compound of formula (XX) where R1, R21 R3, Y and m are as defined in relation to formula (I) by reaction with a cyanide salt by a method chosen from standard literature procedures known to those skilled in the art. Typical procedures use the Sandmeyer reaction and may be undertaken on an aqueous solution of compounds of formula (XX) or a suspension of an isolated salt of compounds of formula (XX).

A copper or nickel cyanide, typically a copper cyanide, for example cuprous cyanide, is added to a cooled reaction mixture at typically less than 10 C. An inorganic cyanide, typically on alkali cyanide for example sodium cyanide, may also be added with stirring as a solid or in aqueous solution. The mixture is then warmed to a temperature between 30"C to 100 C, typically 50"C-70"C, until the reaction goes to completion.

Compounds of formula (XX) may be formed from compounds of formula (XXI) by diazotisation of the amino group attached to the phenyl ring by standard literature procedures involving treatment with either an inorganic nitrite in acid or an organic nitrite. For example, the amine may be suspended in water acidified by the addition of an inorganic acids, typically aqueous hydrochloric acid, and the suspension cooled to O-10 C, typically 0 C. An aqueous solution of an inorganic nitrite, typically an alkali nitrite, for example sodium nitrite, is added dropwise to the stirred cold suspension.

On completion of the addition of the nitrite solution the reaction mixture is cooled and stirred for a further period, typically 20-30 minutes. The aqueous solution may be used directly. Alternatively, after the addition of an aqueous solution of hydrotetrafluoroboric acid, the reaction mixture is allowed to warm to room temperature with occasional stirring. A precipitate of compound of formula (XX) as its tetrahydrofluorborate salt may be collected by filtration.

Compounds of formula (XXI) may be produced from compounds of formula (XXI I) by reduction of the nitro group attached to the phenyl ring by a method chosen from standard literature procedures by those skilled in the art.

Typical procedures include, but are not limited to, catalytic hydrogenation, or hydride donor reagents, or metal in acid or a metal salt in acid redox active transition metal compounds.

For example compounds of formula (XXI I) maybe reduced by titanium trichloride, in an inert organic solvent, for example acetone, at a reduced temperature from 200C to -780C, typically less than 100C.

Referring to Scheme A compounds of formula (XXI I) may be prepared from compounds of formula (VIIA) or formula (VIA) where Y and m are as described in formula (I) and R10 is as described in formula (VII) by a procedure similar to that described above for the preparation of compounds of formula (I) from compounds of formula (VII) or formula (VI).

Alternatively the compounds of formulae (VIIA), (VIA), (VA), (IVA), (IIIA) and (IIA) may be converted to their corresponding cyano derivatives, compounds of formula (VII), (VI), (V), (IV), (III) and (II) respectively by the previously described procedures for the conversion of compounds of formula (XXII) to compounds of formula (I). Not all of the conditions outlined above will be suitable and effect the conversion of all of the nitro compounds to the corresponding cyano compounds. Suitable conditions will be apparent to those skilled in the art.

The cyano compounds of formula (VII), (VI), (V), (IV), (III) and (II) could be converted to a compound of formula (I) as previously described.

Variations of the above procedures will be apparent to the skilled person in the art, as well as alternative processes for preparing the compounds of the invention.

In the preparations of the invention, the ratio of glyphosate or glyphosate salt to the compound of formula (I) may vary considerably but will suitably be within the range of 2000:1 to 1:10, particularly 50:1 to 1:1 and most suitably 10:1 to 1:1 by weight.

The rate of application of the preparations of the invention will depend on a number of factors including, for example, the particular compound of general formula (I) which is used, the identity of the plants whose growth is to be inhibited, the formulations selected for use, whether the preparation is to be applied for foliage or root uptake and whether the different active ingredients of the preparation are applied simultaneously, separately or sequentially.

When the preparation comprises a single preparation containing both active ingredients will be generally be applied for foliar uptake because glyphosate is not suitable for root uptake. However, with the development of glyphosate-resistant crops, it is anticipated that application for root uptake will become more common.

As a general guide an application rate of from 0.001 to 20 kilograms per hectare of the compound of general formula (I) is suitable while from 0.025 to 1 kilograms per hectare may be preferred. The amount of glyphosate can be calculated from the ratios of glyphosate to compound fo formula (I) given above.

The preparation may be formed of the active compounds alone but will more usually contain a solid or liquid diluent. Such preparations may be either dilute preparations, which are ready for immediate use, or concentrated preparations, which must be diluted before use, usually with water.

Preferably the preparations contain from 0.01% to 90% by weight of the active ingredients. Dilute preparations ready for use preferably contain from 0.01 to 2% of active ingredients, while concentrated preparations may contain from 20 to 90% of active ingredients, although from 20 to 70% is usually preferred. The following discussion refers to compositions but it should be bourne in mind that a preparation of the present invention may comprise a single composition containing both active ingredients or, alternatively, separate compositions.

Solid compositions may be in the form of granules, or dusting powders wherein the active ingredients are mixed with a finely divided solid diluent, e.g. kaolin, bentonite, kieselguhr, dolomite, calcium carbonate, talc, powdered magnesia, Fuller's earth and gypsum. They may also be in the form of dispersible powders or grains, comprising a wetting agent to facilitate the dispersion of the powder or grains in liquid. Solid compositions in the form of a powder may be applied as foliar dusts.

Liquid compositions may comprise a solution or dispersion of the active ingredients in water optionally containing a surface-active agent, or may comprise a solution or dispersion of the active ingredients in a water-immiscible organic solvent which is dispersed as droplets in water.

Surface-active agents may be of the cationic, anionic, or non-ionic type or mixtures thereof. Examples of cationic agents include quaternary ammonium compounds (e.g. cetyltrimethylammonium bromide). Suitable anionic agents are soaps; salts of aliphatic mono ester of sulphuric acid, for example sodium lauryl sulphate; and salts of sulphonated aromatic compounds, for example sodium dodecylbenzenesulphonate, sodium,calcium, and ammonium lignosulphonate, butylnaphthalene sulphonate, and a mixture of the sodium salts of diisopropyl and triisopropylnaphthalenesulphonic acid.

Suitable non-ionic agents are the condensation products of ethylene oxide with fatty alcohols such as oleyl alcohol and cetyl alcohol, or with alkylphenols such as octyl- or nonyl- phenol (e.g. Agral 90) or octyl-cresol. Other non-ionic agents are the partial esters derived from long chain fatty acids and hexitol anhydrides, for example sorbitan monolaurate; the condensation products of the partial ester with ethylene oxide; the lecithins; and silicone surface active agents (water soluble surface active agents having a skeleton which comprises a siloxane chain e.g. Silwet L77). A suitable mixture in mineral oil is Atplus 411F.

Aqueous solutions or dispersions may be prepared by dissolving the active ingredients in water or an organic solvent optionally containing wetting or dispersing agent(s) and then, when organic solvents are used, adding the mixture so obtained to water optionally containing wetting or dispersing agent(s). Suitable organic solvents include, for example, ethylene dichloride, isopropyl alcohol, propylene glycol, diacetone alcohol, toluene, kerosene, methylnaphthalene, the xylenes and trichloroethylene.

Compositions for use in the form of aqueous solutions or dispersions are generally supplied in the form of a concentrate containing a high proportion of the active ingredients, and the concentrate is then diluted with water before use. The concentrates are usually required to withstand storage for prolonged periods and after such storage, to be capable of dilution with water to form aqueous compositions which remain homogeneous for a sufficient time to enable them to be applied by conventional spray equipment. Concentrates conveniently contain 20-90%, preferably 20-70%, by weight of the active ingredients. Dilute compositions ready for use may contain varying amounts of the active ingredients depending upon the intended purpose; amounts of 0.01% to 10.0% and preferably 0.1% to 2%, by weight of active ingredients are normally used.

A preferred form of concentrated composition comprises finely divided active ingredients which have been dispersed in water in the presence of a surface-active agent and a suspending agent. Suitable suspending agents are hydrophilic colloids and include, for example, polyvinylpyrrolidone and sodium carboxymethylcellulose, and the vegetable gums, for example gum acacia and gum tragacanth. Preferred suspending agents are those which impart thixotropic properties to, and increase the viscosity of the concentrate. Examples of preferred suspending agents include hydrated colloidal mineral silicates, such as montmorillonite, beidellite, nontronite, hectorite, saponite, and saucorite. Bentonite is especially preferred. Other suspending agents include cellulose derivatives and polyvinyl alcohol.

The preparations of the invention may comprise, in addition to one or more compounds of formula (I) and glyphosate or a salt or derivative thereof, one or more additional compounds which possess biological activity. This compound will generally be a herbicide having a complementary action in the particular application Examples of useful complementary herbicides include: A. benzo-2,1,3-thiadiazin-4-one-212-dioxides such as bentazone; B. hormone herbicides, particularly the phenoxy alkanoic acids such as MCPA, MCPA-thioethyl, dichlorprop, 2,4,5-T, MCPA, 2,4-D, 2,4-DB, mecoprop, trichlopyr, clopyralid, and their derivatives (e.g.. salts, esters and amides); C. 1,3 dimethylpyrazole derivatives such as pyrazoxyfen, pyrazolate and benzofenap; D.Dinitrophenols and their derivatives (e.g.. acetates) such as dinoterb, dinoseb and its ester1 dinoseb acetate; E. dinitroaniline herbicides such as dinitramine, trifluralin, ethalflurolin, pendimethalin, oryzalin; F. arylurea herbicides such as diuron, flumeturon, metoxuron, neburon, isoproturon, chlorotoluron, chloroxuron, linuron, monol inuron, chlorobromuron, daimuron, methabenzthiazuron; G. phenylcarbamoyloxyphenylcarbamates such as phenmedipham and desmedipham; H. 2-phenylpyridazin-3-ones such as chloridazon and norflurazon; I. uracil herbicides such as lenacil, bromacil and terbacil; J. triazine herbicides such as atrazine, simazine, aziprotryne, cyanazine, prometryn, dimethametryn, simetryne, and terbutryn; K. phosphorothioate herbicides such as piperophos, bensulide, and butamifos; ; L. thiolcarbamate herbicides such as cycloate, vernolate, molinate, thiobencarb, butylate , EPTC , tri-allate, di-allate, esprocarb, tiocarbazil, pyridate, and dimepiperate; M. 1,2,4-triazin-5-one herbicides such as metamitron and metribuzin; N. benzoic acid herbicides such as 2,3,6-TBA, dicamba and chloramben; 0. anilide herbicides such as pretilachlor, butachlor, alachlor, propachlor, propanil, metazachlor, metolachlor, acetochlor, and dimethachlor; P. dihalobenzonitrile herbicides such as dichlobenil, bromoxynil and ioxynil; Q. haloalkanoic herbicides such as dalapon, TCA and salts thereof; R. diphenylether herbicides such as lactofen, fluroglycofen or salts or ester thereof, nitrofen, bifenox, aciflurofen and salts and esters thereof, oxyfluorfen, fomesafen, chlornitrofen and chlomethoxyfen; S. phenoxyphenoxypropionate herbicides such as diclofop and esters thereof such as the methyl ester, fluazifop and esters thereof, haloxyfop and esters thereof, quizalofop and esters thereof and fenoxaprop and esters thereof such as the ethyl ester; T. cyclohexanedione herbicides such as alloxydim and salts thereof, sethoxydim, cycloxydim, tralkoxydim, and clethodim;; U. sulfonyl urea herbicides such as chlorosulfuron, sulfometuron, metsulfuron and esters thereof; benzsulfuron and esters thereof such as DPX-M6313, chlorimuron and esters such as the ethyl ester thereof pirimisulfuron and esters such as the methyl ester thereof, 2-[3-(4-methoxy-6-methyl-1,3,5 triazin-zyl)-3-methylureidosulphonyl) benzoic acid esters such as the methyl ester thereof (DPX-LS300) and pyrazosulfuron; V. imidazolidinone herbicides such as imazaquin, imazamethabenz, imazapyr and isopropylammonium salts thereof, imazethapyr; W. arylanilide herbicides such as flamprop and esters thereof, benzoylprop-ethyl, diflufenican; X. organoarsenical herbicides such as monosodium methanearsonate (MSMA); Y. herbicidal amide derivative such as napropamide, propyzamide, carbetamide, tebutam, bromobutide, isoxaben, naproanilide and naptal am;; Z. miscellaneous herbicides including ethofumesate, cinmethylin, difenzoquat and salts thereof such as the methyl sulphate salt, clomazone, oxadiazon, bromofenoxim, barban, tridiphane, flurochloridone, quinchlorac, mefanacet, and triketone herbicides such as sulcotrione; AA. Examples of useful contact herbicides include: bipyridylium herbicides such as those in which the active entity is paraquat and those in which the active entity is diquat; * These compounds are preferably employed in combination with a safener such as dichlormid.

The preparations of the invention are capable of controlling a range of both annual and perennial weeds although its effects are particularly marked for perennial weeds such as Elvmus repens, Cvnodon dactvlon, ImDerata cviindrica, Ottochloa nodosa, Paspalum coniugatum, Sorghum halepense, Cirsium arvense, Convolvulus arvensis and Cvoerus rotundus, which are commercially important species. The preparations appear to have an especially significant effect on grass species, in particular Elvmus reopens, Imperata cvlindrica and Sorghum halepense.

The preparations of the present invention may be used on a range of crops depending upon the selectivity of the compound of general formula (I) which is employed. For example, preparations containing Compound 1 of Table I are especially useful for the control of weeds in soya and similar crops because they are extremely soya selective and, as just mentioned are particularly effective in controlling Sorahum halepense which is a commercially important weed in soya.

The combination of a compound of general formula (I) and glyphosate or one of its salts or derivatives is, of course, useful in a method of weed control and therefore, in a second aspect of the invention, there is provided a method of limiting the growth of, severely damaging or killing weeds, the process comprising applying to the weeds, separately, simultaneously or sequentially a compound of general formula (I) and glyphosate or a salt or derivative thereof.

It is often simplest to apply the active ingredients as a single composition comprising a compound of general formula (I) as defined above together with glyphosate or an agriculturally acceptable salt or derivative thereof.

In particular, the method is of use in controlling grasses, especially Elvmus reDens, Imperata cvlindrica and Sorahum halepense, in crops such as soya.

The invention is illustrated by the following Examples. The abbreviations used in the Examples have the following meanings: MR spectrum: nuclear magnetic resonance spectrum which were recorded at 270 or 400 MHz. (This refers to the proton magnetic resonance spectrum unless otherwise stated). The following abbreviations are used to indicate the multiplicity of the peaks in the NMR spectrum: s (singlet); d (doublet); t (triplet); q (quartet) quin (quintet) m (multiplet; br (broad).

IR spectrum: infra-red absorption spectrum.

MS: mass spectrum GC: gas chromatography TLC: thin layer chromatography m.p.: melting point b.p: boiling point EXAMPLE 1 This example illustrates the preparation of Compound 2 in Table I.

Step A Preparation of methyl 4-chloro-2-fluorobenzoate 4-Chloro-2-fluorobenzoic acid (40g) was dissolved in methanol (350cm3). Concentrated sulphuric acid (3cm3) was added and the mixture heated at reflux for 6 hours. After cooling the mixture was concentrated in vacuo and the residue dissolved in chloroform. Insoluble material was removed by filtration and the filtrate was washed with water, dried over anhydrous magnesium sulphate, and filtered. The filtrate was concentrated in vacuo to give a pale orange liquid which slowly solidified on standing (27.49, 63%). This material was used directly without further purification.

& (CDCl3): 3.95(3H,s); 7.2(1H+1H,,m); 7.90(1H,m).

Step B Preparation of Bistriphenylphosphine nickel (II) bromide complex.

Bistriphenylphosphine nickel (II) bromide was prepared as described by Yamamoto in Chem. Abs. 50:3996i. Triphenylphosphine (249) and anhydrous nickel (II) bromide (209) were stirred together in n-butanol (200cm3) and the mixture heated at reflux for 2 hours. On cooling a green crystalline solid was formed. The solid was collected by filtration, washed with n-butanol, dried and used without further purification (43.49).

Step C Preparation of methyl 4-cyano-2-fluorobenzoate.

A procedure based on those of Sakahibara et al., Bull. Chem: Soc.

Japan, 61 1985-1990 (1988), was used.

A mixture of methyl 4-chloro-2-fluorobenzoate (11.329), prepared as described in Step A, bistriphenylphosphine, nickel (II) bromide (1.489) prepared as described in Step B, zinc powder (400mg), and triphenylphosphine (1.049) in acetonitrile was stirred at 580C under an inert atmosphere of nitrogen for 1 hour. Potassium cyanide (4.309) was added and a slight exotherm observed. The mixture was stirred for a further 4 hours at 580C. Further equivalents of bistriphenylphosphine nickel (II) bromide (1.489), zinc powder (400mg) and triphenylphosphine (1.049) were added and the mixture was stirred and heated for a further 5 hours.

After cooling the reaction was filtered through hy-flo and the residue washed with acetonitrile. The filtrate and washings were combined and absorbed on sorbasil silica gel. The desired product was isolated by elution with hexane:ethyl acetate. Removal of the solvent from the relevant fractions under vacuo gave a white crystalline solid, (11.929, 55%) which was used in the next step without further purification 8 H (CDCl3): 3.95(3H,s); 7.5(1H+1H, m); 8.05(1H,m).

Step D Preparation of 4-cyano-2-fluorobenzoic acid Sodium hydroxide pellets (4.879) were added to a solution cooled by an ice bath of methyl 4-cyano-2-fluorobenzoate (19.89), prepared as described 3 in Step C, dissolved in ethanol (180cm3). The reaction solution became milky. The mixture was stirred at room temperature overnight, then diluted with water and extracted with diethyl ether. The aqueous solution was cooled with an ice bath and acidified with concentrated hydrochloric acid, and extracted with diethyl ether (3x150cm3). The ether extracts were combined, dried over anhydrous magnesium sulphate and filtered. The filtrate was concentrated under vacuo to give a white solid (15.89, 86.5%).

bH (CDCl3): 8 7.75(1H,dd); 7.95(1H+1H,m).

Step E Preparation of ethyl 3-(4-cyano-2-fluorophenyl)-3-oxopropionate 3 Thionyl chloride (150cm ) was added to 4-cyano-2-fluorobenzoic acid (15.89), prepared as described in Step D, and the mixture heated at reflux for 3 hours. After cooling excess thionyl chloride and other volatiles were removed under vacuo to give a pale yellow liquid, crude 4-cyano-2-fluorobenzoylchloride, which was used directly without further purification.

Potassium ethyl malonate (32.41g) was added to dry acetonitrile (120cm3) and the mixture cooled to 100C under an inert atmosphere of nitrogen. Triethylamine (17.979) and magnesium chloride (19.96g) were added with vigorous stirring and the mixture was allowed to warm to room temperature and then stirred for 2F hours. The resulting slurry was cooled to OOC, the crude 4-cyano-2-fluorobenzoyl chloride was added dropwise over approximately 15 minutes, and then further triethylamine (1.797g) was added. The reaction mixture was allowed to warm to room temperature and stirred overnight.

acetonitrile was removed under vacuo. The residue was mixed with toluene. The mixture was concentrated under vacuo and ethyl acetate added.

The mixture was cooled to 10 C, 2N hydrochloric acid (160cm3) was added with vigorous stirring and the mixture temperature maintained at less than 25"C. The two resulting phases were separated and the aqueous phase extracted with further ethyl acetate. The combined ethyl acetate extracts were washed with 2N hydrochloric acid then water, dried over anhydrous magnesium sulphate, and filtered. The filtrate was concentrated under vacuo to give a semi solid residue. The desired product was isolated by column chromatography on sorbasil silica gel eluting with hexane:ethyl acetate 3:1. Concentration of the relevant fractions under vacuo gave a pale orange solid, the desired product as a mixture of keto/enol tautomers (10.65g, 52%).

Step F Preparation of 1-methyl -3-(4-cyano-2-fluorophenyl ) -3-hydroxy- pyrazole Ethyl 3- (4-cyano-2-fl uoprophenyl ) -3-oxopropi onate (5.2g) was suspended in ethanol (5cm3). Methylhydrazine (1.129) was added to the stirred mixture over 10 minutes. The mixture was then stirred overnight at room temperature. Hexane and ethanol were then added to mixture which was stirred for approximately 30 minutes.

The crude desired product was filtered off, washed with hexane, dried, and used without further purification (3.849, 80%). SH (CDCl3): 3.55(3H,s); 5.8(1H,d); 7.6(1H,dd); 7.8(1H,dd); 8.0(1H,t).

Step G Preparation of 1-methyl-3.(4-cyano-2-fluorophenyl)-5-difluoro- methoxypyrazol e.

Crude 1-methyl -3- (4-cyano-2-fl uorophenyl ) -5-hydroxy-pyrazole (3.669), prepared as described in Step F, was suspended in methylene chloride, to which was added tetrabutylphosphonium bromide (1.919).

Chlorodifluoromethane gas was bubbled through the suspension until the mixture was saturated. 50% Aqueous sodium hydroxide (35cm3) was added dropwise to the vigorously stirred suspension. When the addition was complete the mixture was stirred at room temperature for a further 1 hour.

The reaction mixture was then diluted with water and the two phases separated. The aqueous phase was extracted with methylene chloride and the extracts were combined with the organic phase. The combined organic phases were dried over anhydrous magnesium sulphate, filtered and concentrated under vacuo. The residue was absorbed onto sorbasil silica gel and purified by column chromatography eluting with hexane:diethyl ether 3:1.

The desired product was obtained as a white solid by concentrating under vacuo the relevant fractions (1.56g, 32%). SH (CDCl3): 3.8(3H,s); 6.6(1H,t); 6.4(1H,d); 7.45(1H+1H,m); 8.15(1H,t).

Step H Preparation of 1-methyl-3-(4-cyano-4-fluorophenyl) -4-chloro- -5-difluoromethoxypyrazole, compound (1) of Table I.

1-Methyl-3-(4-cyano-2-fluorophenyl)-5-difluoromethoxypyrazole (540mg), prepared as described in Step G, was suspended in acetonitrile (5cm3).

Sulphuryl chloride (273mg) was added dropwise to the stirred suspension and the internal temperature maintained at less than 25"C. When the addition was complete the reaction mixture was stirred at room temperature for approximately 1 hour while the reaction was monitored for completion by GC.

The reaction mixture was poured into a saturated aqueous solution of sodium bicarbonate and extracted with diethyl ether (3x20cm3). The combined diethyl ether extracts were washed with a saturated aqueous solution of sodium bicarbonate and then water, dried over anhydrous magnesium sulphate and filtered. The filtrate was concentrated under vacuo to give the desired product as a pale yellow gum which solidified on standing (515mg).

M.pt 90-910C. 8H (CDCl3): 3.85(3H,s); 6.7(1H,t); 7.5(1H+1H,m); 7.7(1H,m).

EXAMPLE 2 In this example, Compound 1 of Table I was used and was prepared according to the method set out in J03072460. Three formulations were used as follows.

(1) Glyphosate-trimesium at a calculated application rate of 1000 g/ha; (2) Compound 1 of Table I at a calculated rate of 63g/ha together with 0.5% of the alkylpolyglucoside surfactant sold under the code AL2042 (ICI plc, UK); (3) glyphosate-trimesium and Compound 1 of Table I at calculated rates of 1000 g/ha and 63 g/ha respectively togther with 0.5% of the surfactant AL2042.

Required aliquots of each formulation were added to a 25 ml volumetric flask and made up to volume with deionised water. This was sprayed in three replicates onto well-established perennial plants in pots giving a volume rate equivalent to 200 1/aha. Plants of each test species were then returned to warm or temperate glasshouse environments as appropriate for optimal growth.

The plant species treated were: AGRRE Elvmus repens CYNDA Cvnodon dactvlon IMPCY Imperata cvlindrica OTT NO Ottochloa nodosa PASCO Paspalum coniugatum SORHA Sorghum halepense CIRAR Cirsium arvense CONAR Convolvulus arvensis CYPRO Cvperus rotundus Damage to plants was assessed at intervals after spraying by comparison with untreated plants, on a 0-100% scale where 0% is no damage and 100% is complete kill and the results are set out in Table II below.

The results for each of the tests are shown together with the expected value for test 3 if there is no synergy between the two compounds.

TABLE II DAMAGE (%) FORM AGRRE CYNDA IMPCY OTTNO PASCO SORHA CIRAR CONAR CYPRO (1) 20 17 8 33 13 23 9 18 10 (2) 10 13 5 22 10 11 20 68 17 (3) 43 22 32 37 17 53 22 69 18 E 28 28 13 48 22 31 27 74 25 (E = Expected result if no synergy) In Table II, the expected result is calculated using the Colby formula as follows: E = X + Y - XY 100 Where E is the expected result and X and Y are the results for the two individual components. This formula is a standard one used by those skilled in the art.

The results show that the preparation containing the Compound 1 and glyphosate trimesium is considerably more effective in controlling AGRRE, IMPCY and SORHA than either Compound 1 or glyphosate trimesium alone. More surprisingly, for these weeds, the preparation is more effective than would have been expected from a calculation of the sum of the effects of the two individual components.

Scheme A

Claims (10)

1. CLAIMS 1. A herbicidal preparation comprising a compound of general formula (I):

   wherein: R1 is alkyl, alkenyl, alkynyl, benzyl, cycloalkyl or cycloalkenyl all of which may be optionally substituted; R2 is haloalkoxy; R3 is halo; X is CN or halo; each Y is independently halo, CN, N02, OH, alkyl, alkoxy, alkylthio, alkoxyalkyl, SO2alkyl, CONRaRb, heterocyclyl or two Y groups together form a further ring; m is 0-4 Ra and Rb are independently H or lower alkyl; together with glyphosate or a herbicidally acceptable salt or derivative thereof.
2. 2. A herbicidal preparation as claimed in claim 1, wherein the glyphosate salt is glyphosate-trimesium.
3. 3. A herbidical preparation as claimed in claim 1 or claim 2 wherein, in general formula (I), the group X is attached to the phenyl ring at the 4-position and is CN or chloro.
4. 4. A preparation as claimed in any one of claims 1 to 3, wherein m is zero or 1.
5. 5. A preparation as claimed in claim 4, wherein m is 1 and Y is fluorine or chlorine.
6. 6. A preparation as claimed in claim 5, wherein Y is attached to the phenyl ring at the 2-position.
7. 7. A preparation as claimed in any one of the preceding claims, wherein the compound of general formula (I) is Compound 1 or Compound 2 of Table I.
8. 8. A preparation as claimed in any one of claims 1 to 7, for use on a soya crop.
9. 9. A preparation as claimed in any one of claims 1 to 7 for use in limiting the growth of, severely damaging or killing grasses such as Elvmus repents, Iioerata cvlindrica and Sorghum halepense.
10. 10. A method of limiting the growth of, severely damaging or killing weeds, the process comprising applying to the weeds a preparation as claimed in any one of claims 1 to 7.