EP0936864A1

EP0936864A1 - Fungicidal composition comprising an acylaminobenzamide (compound a) and process for preparing compound a

Info

Publication number: EP0936864A1
Application number: EP97909419A
Authority: EP
Inventors: Stephen Paul Heaney; Kevin Robert Lawson; Nicholas Russell Foster
Original assignee: Zeneca Ltd
Current assignee: Syngenta Ltd
Priority date: 1996-11-04
Filing date: 1997-10-14
Publication date: 1999-08-25
Also published as: GB9622926D0; ZA979294B; JP2001510454A; AR010039A1; AU4710897A; WO1998019539A1

Abstract

Fungicidal compositions comprising, as a first active ingredient, compound (A) and their use to combating fungal infections of plants. Also claimed is a process for preparing a compound of formula (I) wherein R is halogen or C1-4 alkyl.

Description

FUNGICIDAL COMPOSITION COMPRISING AN ACYLAMINOBENZAMIDE (COMPOUND A) AND PROCESS FOR PREPARING COMPOUND A

The present invention relates to a process for preparing acylaminobenzamides, to compositions comprising an acylaminobenzarnide and to a method of using said compositions to combat fungal infections of plants.

Fungicidal acylaminobenzamides are disclosed in EP-Al -0381330, EP-Al -0470711, EP-Al-0468683, EP-Al -0468682, WO93/14063 and WO94/00422. Compound No. 38 of Table I of EP-A1-0381330 has the structure:

and will be referred to hereinafter as Compound A.

The present invention provides a process for preparing a compound of formula (I):

wherein R is halogen or C,_.4 alkyl; the process comprising reacting a compound of formula (II)

with the compound of formula (III):

CH, F-C-CO₂CH₃ (III)

CH₃

Alkyl may be straight or branched chain and is, for example, methyl. Halogen is preferably fluorine or chlorine. It is preferred that R is chlorine. The process of the present invention is preferably carried out in a solvent. Preferred solvents include alcohols (especially methanol), polar solvents (such as acetonitrile, N,N- dimethylforrnamide or N-methylpyrrolidone), hydrocarbons (such as toluene or xylene) or ethers (such as tetrahydrofuran or 1 ,2-dimethoxy ethane). The process is preferably carried out at a temperature in the range 20-120°C (such as in the range 20-100°C, especially 20-80°C).

It is preferred that the process of the invention is carried out in the presence of a suitable base such as a methoxide, carbonate, hydride or hydroxide, of, an alkaline earth metal (such as calcium or magnesium) or, preferably, an alkali metal (such as sodium or potassium). Examples of suitable bases include sodium methoxide, potassium carbonate, sodium hydride and sodium hydroxide.

In one aspect the present invention provides a process for preparing a compound of formula (I) wherein the process is carried out in the presence of a surface active agent (such as an alkoxylate [for example SYPERONIC NP13] or a polyethylene glycol [for example PEG300]).

Typically the process of the present invention is carried out by adding a compound of formula (II) to a stirred slurry of a suitable base in a suitable solvent optionally in the presence of a surface active agent. The compound of formula (III) is then added and the mixture stirred at a temperature in the range of 20-120°C (especially 20-80°C) for a suitable length of time (such as between 1 and 5 hours). The compound of formula (I) can be purified using standard literature methods.

The present invention also provides a fungicidal composition comprising as a first active ingredient, Compound A; as a second active ingredient: kresoxim-methyl (also known as BAS490F), azoxystrobin (also known as ICIA5504), SSF126, N-methyl 2-[2-(2,5- dimethylphenoxymethyl)phenyl]-2-methoxyiminoacetamide, famoxadone, fluazinam, 5-(4- fluorophenyl)-2-methoxy-5-methyl-3-phenylamino-l,3-imidazolin-4-one, 5-methyl-5-[4-(2- methyl-4-thiazolylmethoxy)phenyl]-3-phenylamino- 1 ,3-oxazolidine-2,4-dione, 5-(4- fluorophenyl)-5-methyl-2-methylthio-3-phenylamino-l,3-imidazolin-4-one, 2-ethyl-5-(4- fluorophenyl)-5-methyl-3-phenylamino-l ,3-imidazolin-4-one or (55)-5-methyl-2-methylthio- 5-phenyl-3-phenylamino-l,3-imidazolin-4-one; and a suitable carrier or diluent. In one particular aspect the present invention provides a fungicidal composition comprising as a first active ingredient Compound A; as a second active ingredient, kresoxim- methyl, azoxystrobin or fluazinam; and a suitable carrier or diluent.

In another aspect the present invention provides a fungicidal composition comprising as a first active ingredient Compound A; as a second active ingredient, kresoxim-methyl or azoxystrobin; and a suitable carrier or diluent.

In another aspect the present invention provides a fungicidal composition as described above wherein the weight ratio of the first : second active ingredient is in the range 1 : 10 to 10:1 (especially in the range 1 :7 to 2:1, for example in the range 1 :4 to 2:1). The compositions of the invention are fungicidally active and can be used to control one or more of the following pathogens:

Erysiphe graminis (powdery mildew) on barley, wheat, rye and turf and other powdery mildews on various hosts such as Sphaerotheca macularis on hops, Sphaerotheca fuliginea on cucurbits (e.g. cucumber), Podosphaera leucotricha on apple and Uncinula necator on vines; Botrytis cinerea (grey mould) on tomatoes, strawberries, vegetables, vines and other hosts and other Botrytis spp. on other hosts; Plasmopara viticola on vines; other downy mildews such as Bremia lactucae on lettuce, Peronospora spp. on soybeans, tobacco, onions and other hosts, Pseudoperonospora humuli on hops and Pseudoperonospora cubensis on cucurbits; or Phytophthora infestans on potatoes and tomatoes and other Phytophthora spp. on vegetables, strawberries, avocado, pepper, ornamentals, tobacco, cocoa and other hosts.

In another aspect the present invention provides a method of combating fungi which comprises applying to a plant, to a seed of a plant or to the locus of the plant or seed a fungicidally effective amount of a composition as hereinbefore defined. The type of composition used in any instance will depend upon the particular purpose envisaged.

It is preferred that all compositions, both solid and liquid formulations, comprise 0.0001 to 95%, more preferably 1 to 85%, for example 1 to 25% or 25 to 60%, of a mixture of the active ingredients hereinbefore listed.

When applied to the foliage of plants, the compositions are applied at rates of 0.1 g to 10kg, preferably lg to 8kg, more preferably lOg to 4kg, of total weight of active ingredients per hectare. When used as seed dressings, the compositions are used at rates of 0.000 lg (for example 0.001 g or 0.05g) to lOg, preferably 0.005g to 8g, more preferably 0.005g to 4g, of total weight of active ingredients per kilogram of seed.

The compositions of the invention can be applied in a number of ways. For example, they can be applied directly to the foliage of a plant, to seeds or to the medium in which plants are growing or are to be planted, or they can be sprayed on, dusted on or applied as a cream or paste formulation, or they can be applied as a vapour or as slow release granules. Application can be to any part of the plant including the foliage, stems, branches or roots, or to soil surrounding the roots, or to the seed before it is planted, or to the soil generally, to paddy water or to hydroponic culture systems. The compositions may also be injected into plants or sprayed onto vegetation using electrodynamic spraying techniques or other low volume methods, or applied by land or aerial irrigation systems.

The term "plant" as used herein includes seedlings, bushes and trees. Furthermore, the fungicidal method of the invention includes preventative, protectant, prophylactic, systemic and eradicant treatments.

The compositions may be in the form of dustable powders or granules comprising a solid diluent or carrier, for example, a filler such as kaolin, bentonite, kieselguhr, dolomite, calcium carbonate, talc, powdered magnesia, fuller's earth, gypsum, diatomaceous earth or china clay. Such granules can be preformed granules suitable for application to the soil without further treatment. These granules can be made either by impregnating pellets of filler with the active ingredients or by pelleting a mixture of the active ingredients and powdered filler. Compositions for dressing seed may include an agent (for example, a mineral oil) for assisting the adhesion of the composition to the seed; alternatively the active ingredients can be formulated for seed dressing purposes using an organic solvent (for example, N-methylpyrrolidone, propylene glycol or N,N-dimethylformamide). The compositions may also be in the form of water dispersible powders or water dispersible granules comprising wetting or dispersing agents to facilitate the dispersion in liquids. The powders and granules may also contain fillers and suspending agents.

The compositions may also be in the form of soluble powders or granules, or in the form of solutions in polar solvents. Soluble powders may be prepared by mixing the active ingredients with a water-soluble salt such as sodium bicarbonate, sodium carbonate, magnesium sulphate or a polysaccharide, and a wetting or dispersing agent to improve water dispersibility/solubility. The mixture may then be ground to a fine powder. Similar compositions may also be granulated to form water-soluble granules. Solutions may be prepared by dissolving the active ingredients in polar solvents such as ketones, alcohols and glycol ethers. These solutions may contain surface active agents to improve water dilution and prevent crystallisation in a spray tank.

Emulsifiable concentrates or emulsions may be prepared by dissolving the active ingredients in an organic solvent optionally containing a wetting or emulsifying agent and then adding the mixture to water which may also contain a wetting or emulsifying agent. Suitable organic solvents are aromatic solvents such as alkylbenzenes and alkylnaphthalenes, ketones such as cyclohexanone and methylcyclohexanone, chlorinated hydrocarbons such as chlorobenzene and trichlorethane, and alcohols such as benzyl alcohol, furfuryl alcohol, butanol and glycol ethers.

Aqueous suspension concentrates of largely insoluble solids may be prepared by ball or bead milling with a dispersing agent with a suspending agent included to stop the solid settling.

Compositions to be used as sprays may be in the form of aerosols wherein the formulation is held in a container under pressure of a suitable propellant.

The active ingredients can be mixed in the dry state with a pyrotechnic mixture to form a composition suitable for generating in enclosed spaces a smoke containing the active ingredients.

Alternatively, the compositions may be used in micro-encapsulated form. They may also be formulated in biodegradable polymeric formulations to obtain a slow, controlled release of the active ingredients.

By including suitable additives, for example additives for improving the uptake, distribution, adhesive power and resistance to rain on treated surfaces, the compositions of the invention can be better adapted for various utilities. Other additives may be included to improve the biological efficacy of the various compositions. Such additives can be surface active materials to improve the wetting and retention on surfaces treated with the composition and also the uptake and mobility of the active ingredients, or additionally can include oil based spray additives, for example, certain mineral oil and natural plant oil (such as soya bean and rape seed oil) additives, or blends of them with other adjuvants.

The compositions can be used as mixtures with fertilisers (e.g. nitrogen-, potassium- or phosphorus-containing fertilisers). Compositions comprising only granules of fertiliser incorporating, for example coated with, the active ingredients are preferred. Such granules suitably contain up to 25% by weight of active ingredient.

Water dispersible powders, emulsifiable concentrates and suspension concentrates will normally contain surfactants, for example a wetting agent, dispersing agent, emulsifying agent or suspending agent. These agents can be cationic, anionic or non-ionic agents. Suitable cationic agents are quaternary ammonium compounds, for example, cetyltrimethylammonium bromide. Suitable anionic agents are soaps, salts of aliphatic monoesters of sulphuric acid (for example, sodium lauryl sulphate), and salts of sulphonated aromatic compounds (for example, sodium dodecylbenzenesulphonate, sodium, calcium or ammonium lignosulphonate, butylnaphthalene sulphonate, and a mixture of sodium diisopropyl- and triisopropylnaphthalene sulphonates).

Suitable non-ionic agents are the condensation products of ethylene oxide with fatty alcohols such as oleyl or cetyl alcohol, or with alkyl phenols such as octyl- or nonylphenol and octylcresol. Other non-ionic agents are the partial esters derived from long chain fatty acids and hexitol anhydrides, alkyl glucosides, polysaccharides and the lecithins and the condensation products of the said partial esters with ethylene oxide. Suitable suspending agents are hydrophilic colloids (for example, polyvinylpyrrolidone and sodium carboxymethylcellulose), and swelling clays such as bentonite or attapulgite.

Compositions for use as aqueous dispersions or emulsions are generally supplied in the form of a concentrate containing a high proportion of the active ingredients, the concentrate being diluted with water before use. These concentrates should preferably be able to withstand storage for prolonged periods and after such storage be capable of dilution with water in order to form aqueous preparations which remain homogeneous for a sufficient time to enable them to be applied by conventional spray equipment. The concentrates may conveniently contain up to 95%), suitably 1-85%, for example 1-25% or 25-60%, by weight of the active ingredient. After dilution to form aqueous preparations, such preparations may contain varying amounts of the active ingredients depending upon the intended purpose, but an aqueous preparation containing 0.0001 to 10%), for example 0.005 to 10%), by weight of active ingredients may be used.

The compositions of this invention may contain other compounds having biological activity, for example compounds having similar or complementary fungicidal activity or which possess plant growth regulating, herbicidal or insecticidal activity.

By including another fungicide, the resulting composition can have a broader spectrum of activity or a greater level of intrinsic activity than a composition containing only a first and second active ingredient. Further the other fungicide can have a synergistic effect on the fungicidal activity of the first or second active ingredient. Examples of fungicidal compounds which may be included in such compositions include (J?iS)-l-aminopropyl- phosphonic acid, (i?5)-4-(4-chlorophenyl)-2-phenyl-2-( 1 H- 1 ,2,4-triazol- 1 -ylmethyl)but- yronitrile, (2)-N-but-2-enyloxymethyl-2-chloro-2',6'-diethylacetanilide, 1 -(2-cyano-2- -methoxyiminoacetyl)-3 -ethyl urea, 4-(2,2-difluoro-l ,3-benzodioxol-4-yι)pyrrole-3- carbonitrile, 4-bromo-2-cyano-N,N-dimethyl-6-trifluoromethylbenzimidazole- 1 - sulphonamide, 5-ethyl-5,8-dihydro-8-oxo(l ,3)-dioxol-(4,5-g)quinoline-7-carboxylic acid, a-[N-(3-chloro-2,6-xylyl)-2-methoxyacetamido]-y-butyrolactone, 7v^r-(2-methoxy-5-pyridyl)- cyclopropane carboxamide, alanycarb, aldimorph, ampropylfos, anilazine, azaconazole, benalaxyl, benomyl, biloxazol, binapacryl, bitertanol, blasticidin S, bromuconazole, bupirimate, butenachlor, buthiobate, captafol, captan, carbendazim, carbendazim chlorhydrate, carboxin, CGA 245704, chinomethionate, chlorbenzthiazone, chloroneb, chlorothalonil, chlorozolinate, clozylacon, copper containing compounds such as copper oxychloride, copper oxyquinolate, copper sulphate, copper tallate, and Bordeaux mixture, cycloheximide, cymoxanil, cyproconazole, cyprodinyl, cyprofuram, debacarb, di-2-pyridyl disulphide l,l'-dioxide, dichlofluanid, dichlone, diclobutrazol, diclomezine, dicloran, didecyl dimethyl ammonium chloride, diethofencarb, difenoconazole, O,O-di-w -propyl-S-benzyl thiophosphate, dimefluazole, dimetconazole, dimethomorph, dimethirimol, diniconazole, dinocap, dipyrithione, ditalimfos, dithianon, dodemorph, dodine, doguadine, edifenphos, epoxiconazole, etaconazole, ethirimol, ethoxyquin, ethyl (Z)-N-benzyl-7V-([methyl(methyl- thioethylideneamino-oxycarbonyl)amino]thio)-β-alaninate, etridiazole, fenaminosulph, fenapanil, fenarimol, fenbuconazole, fenfuram, fenpiclonil, fenpropidin, fenpropimorph, fentin acetate, fentin hydroxide, ferbam, ferimzone, fluazinam, fludioxonil, fluoroimide, fluquinconazole, flusilazole, flutolanil, flutriafol, folpet, fuberidazole, furalaxyl, furametpyr, furconazole-cis, guazatine, hexaconazole, hydroxyisoxazole, hymexazole, imazalil, imibenconazole, ipconazole, iprobenfos, iprodione, isopropanyl butyl carbamate, isoprothiolane, kasugamycin, mancozeb, maneb, mepanipyrim, mepronil, metalaxyl, metconazole, methfuroxam, metiram, metiram-zinc, metsulfovax, myclobutanil, NTN0301, neoasozin, nickel dimethyldithiocarbamate, nitrothal-isopropyl, nuarimol, ofurace, organomercury compounds, oxadixyl, oxolinic acid, oxycarboxin, pefurazoate, penconazole, pencycuron, phenazin oxide, phosetyl-Al, phosphorus acids, phthalide, polyoxin D, polyram, probenazole, prochloraz, procymidone, propamocarb, propamocarb hydrochloride, prop- iconazole, propineb, propionic acid, prothiocarb, pyracarbolid, pyrazophos, pyrifenox, pyrimethanil, pyroquilon, pyroxyfur, pyrrolnitrin, quaternary ammonium compounds, quinconazole, quinomethionate, quintozene, rabenazole, sodium pentachlorophenate, streptomycin, sulphur, tebuconazole, techlofthalam, tecnazene, tetraconazole, thiabendazole, thicyofen, thifluzamide, 2-(thiocyanomethylthio)benzothiazole, thiophanatemethyl, thiram, timibenconazole, tolclofos-methyl, tolylfluanid, triacetate salt of 1 , l'-iminodi- (octamethylene)diguanidine, triadimefon, triadimenol, triazbutyl, triazoxide, tricyclazole, tridemorph, triforine, triflumizole, triticonazole, validamycin A, vapam, vinclozolin, XRD-563, zineb and ziram. The compositions of the invention can be mixed with soil, peat or other rooting media for the protection of plants against seed-borne, soil-borne or foliar fungal diseases. The following examples illustrate the invention

EXAMPLE 1 This Example illustrates the preparation of Compound A. To stirred mixture of 2-chloro-4-nitro-N,N-dimethylbenzamide (lOg) in water

(200ml) at 80°C was added sodium dithionite (22.4g). The resultant mixture was then stirred under reflux for 3 hours, allowed to cool to 50°C and concentrated hydrochloric acid (40ml) added. After heating at 80°C for 15 minutes the mixture was cooled, ice (200ml) was added followed by sodium carbonate (35.7g approximately, to pH 10) at 5°C. After stirring at ambient temparature for 15 minutes the precipitate that had formed was filtered off and washed with water (200ml) to give 2-chloro-4-amino-N,N-dimethylbenzamide (5.1g). Sodium methoxide (3.3g, 0.06mol) and xylene (20ml) were added to a stirred mixture of xylene (50ml) and polyethylene glycol 300 (PEG300; 0.5ml). After 5 minutes dried 2- chloro-4-amino-N,N-dimethylbenzamide (9.93g) and xylene (10ml) were added with stirring. The mixture was stirred for 10 minutes and methyl 2-fluoroisobutyrate (6.66g) was added over 25 minutes. After a further amount of xylene (10ml) had been added, the reaction mixture was stirred for 2.75 hours at room temparature and then warmed to 48-50°C for 0.25 hour. The reaction mixture was stirred for 6 hours at room temparature and then allowed to stand overnight. The reaction mixture was then filtered to leave a filtrate containing Compound A. EXAMPLE 2

This Example illustrates the preparation of Compound A.

2-Chloro-4-amino-N,N-dimethylbenzamide (2.0g) and methyl 2-fluoroisobutyrate (1.33g) were mixed with 1 ,2-dimethoxyethane (70ml) at 20°C in dry apparatus under nitrogen. Sodium methoxide (0.544g) was added quickly and the mixture was refluxed for 1.5 hours. The mixture was cooled and poured into cold aqueous hydrochloric acid (2M). The aqueous was extracted with ethyl acetate (twice), the organic extracts were combined, washed with brine, dried (over anhydrous magnesium sulphate), filtered and the filtrate evaporated in vacuo to leave an oil. The oil was taken up in a little diethyl ether, the solution cooled, triturated to initiate solid formation, and pentane added. The solid formed was filtered off to leave Compound A as a cream solid (1.992g, 69%) yield; melting point 133- 134°C).

EXAMPLE 3 This Example illustrates the preparation of Compound A.

A stirred mixture of 2-chloro-4-amino-N,N-dimethylbenzamide (l.Og), potassium carbonate (700mg) and toluene (20ml) was refluxed until approximately half of the toluene had been distilled off. Methyl 2-fluoroisobutyrate (605mg) was added and the resulting mixture refluxed for 2 hours after which time a catalytic quantity of 18-crown-6 was added. After a further 4.5 hours reflux 4A sieves were added. After a further 16 hours reflux, analysis showed that Compound A had been produced in 60% yield. EXAMPLE 4

This Example illustrates the preparation of Compound A.

To a stirred dispersion of sodium hydride (4.4g of a 60% dispersion in oil pre- washed with xylene (10ml)) in xylene (40ml) under nitrogen was added tert-amyl alcohol (10.5g) over 1.5 hours and whilst keeping the temperature in the range 20-23°C. A further amount of xylene (10ml) was added and the mixture was heated to 60°C. 2-Chloro-4-amino-N,N- dimethylbenzamide (19.85g) was added over 7 minutes followed by a further amount of xylene (10ml). The reaction mixture was heated to 70°C and methyl 2-fluoroisobutyrate (13.33g) added over 20 minutes and the reaction mixture was kept at 70°C for 1.75 hours by which time the reaction mass was difficult to stir.

A sample of the reaction mass was filtered (overnight), the residue slurried in water and the pH adjusted to 1 using dilute sulphuric acid. The aqueous was extracted with diethyl ether and gas chromatographic analysis of the ethereal solution showed Compound A to be present.

EXAMPLE 5

This Example illustrates the preparation of a soluble powder formulation comprising Compound A and azoxystrobin.

Dry powdered Compound A, azoxystrobin, POLYFON H, AEROSOL OT-B, sodium benzoate and sodium bicarbonate were mixed together in a ribbon blender until a homogenous blend was obtained. The powder blend was then dry milled by passing it through a Glenn-Creston UCM with a 0.25mm screen. The milled powder was re-blended in the ribbon blender for thirty minutes, after which it is discharged.

POLYFON H and AEROSOL OT-B are trade marks or trade names. 11

EXAMPLE 6

This Example illustrates the preparation of a tank mix comprising Compound A and azoxystrobin.

A soluble powder containing Compound A can be made using the methodology of Example 5 and the following components:

A suspension concentrate formulation of azoxystrobin can be made by blending the components listed in either of the following lists:

Depending on the spray volume to be applied, the required quantity of soluble powder containing Compound A is dispersed in water (half the total volume that will be used to spray) in a spray tank. The required quantity of suspension concentrate containing azoxystrobin is then added to the mixture in the spray tank. Finally water is added to makeup the spray solution to the correct volume. The content of the spray tank is agitated throughout the mixing process.

POLYFON H, AEROSOL OT-B, BENTOPHARM B20, MORWET D425, KELZAN and PROXEL GXL are trade marks or trade names. EXAMPLE 7

Testing of a composition of the invention against Phytophthora infestans (downy mildew) on potatoes in a test area (4.5m²)

An aqueous solution comprising Compound A (200g/ha) and azoxystrobin (125g/ha) was applied to the test area at a rate of 3001/ha. Seven applications were made, spaced 7-10 days apart, depending upon disease pressure. Disease control was assessed 11 days after the seventh application.

It was found that the treated plot had, on average, 9.4% foliar tissue covered by downy mildew whereas the untreated plot had 88.3% foliar tissue covered by downy mildew.

Claims

1. A fungicidal composition comprising as a first active ingredient Compound A:

as a second active ingredient: kresoxim-methyl, azoxystrobin, SSF126, N-methyl 2-

[2-(2,5-dimethylphenoxymethyl)phenyl]-2-methoxyiminoacetamide, famoxadone, fluazinam, 5-(4-fluorophenyl)-2-methoxy-5-methyl-3-phenylamino-l,3-imidazolin-4- one, 5 -methyl-5 - [4-(2-methy l-4-thiazolylmethoxy)phenyl]-3 -phenylamino- 1,3- oxazolidine-2,4-dione, 5-(4-fluorophenyl)-5-methyl-2-methylthio-3-phenylamino- 1 ,3-imidazolin-4-one, 2-ethyl-5-(4-fluorophenyl)-5-methyl-3 -phenylamino- 1 ,3- imidazolin-4-one or (5.S)-5-methyl-2-methylthio-5-phenyl-3-phenylamino-l ,3- imidazolin-4-one; and a suitable carrier or diluent.

2. A fungicidal composition as claimed in claim 1, comprising as a second active ingredient: kresoxim-methyl, azoxystrobin or fluazinam.

3. A fungicidal composition as claimed in claim 1 or 2 wherein the weight ratio of the first : second active ingredient is in the range 1 :10 to 10:1.

4. A method of combating fungi which comprises applying to a plant, to a seed of a plant or to the locus of the plant or seed a fungicidally effective amount of a composition as claimed in claim 1.

5. A process for preparing a compound of formula (I):

wherein R is halogen or C,.₄ alkyl, the process comprising reacting a compound of formula (II):

with the compound of formula (III)

CH, I ³ F-C-CO₂CH₃ (III)

CH₃

6. A process as claimed in claim 5 wherein the process is carried out in the presence of a solvent and a surface active agent.

7. A process as claimed in claim 6 wherein the surface active agent is an alkoxylate or a polyethylene glycol.

8. A process as claimed in claim 5, 6 or 7 wherein the process is carried out in the presence of a base which is a methoxide, carbonate, hydride or hydroxide, of an alkaline earth metal or an alkali metal.

9. A process as claimed in claim 8 wherein the base is sodium methoxide, potassium carbonate, sodium hydride or sodium hydroxide.