WO1993014063A1

WO1993014063A1 - Fungicides

Info

Publication number: WO1993014063A1
Application number: PCT/GB1992/000068
Authority: WO
Inventors: Patrick Jelf Crowley; Alasdair Thomas Glen; Rosamund Alison Lansdown; Kevin Robert Lawson
Original assignee: Imperial Chemical Industries Plc
Priority date: 1992-01-13
Filing date: 1992-01-13
Publication date: 1993-07-22
Also published as: AU1160492A

Abstract

Fungicidal compounds having formula (I): in which A is F, Cl, Br or C1-2alkyl; B is H, F or Cl; R1 is C¿3-4? alkenyl, halo(C3-4)alkenyl, C3-4 alkynyl or halo(C3-4)alkynyl; R?2¿ is C¿1-4? alkyl, halo(C1-4)alkyl, C3-4cycloalkyl or halo(C3-4)cycloalkyl; R?3¿ is C¿1-2? alkyl, CH2F or CF3; and, when R?3¿ is C¿1-2? alkyl or CH2F, R?4¿ is C¿1-3? alkyl, allyl, propargyl or CHFR?5¿ wherein R5 is H or C¿1-2? alkyl, and, when R?3¿ is CF¿3, R?4 is the group C(R?6)(R7)R8¿ wherein R6 is H or C¿1-2? alkyl, R?7¿ is H, F, Br or C¿1-2? alkyl and R?8¿ is H or F.

Description

FUNGICIDES

This invention relates to novel fungicidal acylaminobenzamides, to processes for preparing them, to fungicidal compositions containing them and to methods of using them to combat fungi, especially fungal infections of plants.

Various acylaminobenzamides having fungicidal properties are described in EP-A-0127990 and EP-A-0381330.

According to the present invention there is provided a compound of the formula (I), in which A is F, Cl, Br or C_1-2 alkyl; B is H, F or Cl; R¹ is C_3-4 alkenyl, halo(C_3-4)alkenyl, C_3-4 alkynyl or halo(C_3-4)alkynyl; R² is C_1-4 alkyl, halo(C_1-4)alkyl, C_3-4cycloalkyl or halo(C_3-4)cycloalkyl; R³ is C_1-2 alkyl, CH₂F or CF₃; and, when R³ is C_1-2 alkyl or CH₂F, R⁴ is C_1-3 alkyl, allyl, propargyl or CHFR⁵ wherein R⁵ is H or C_1-2 alkyl, and, when R³ is CF₃, R⁴ is the group C(R⁶)(R⁷)R⁸ wherein R⁶ is H or C_1-2 alkyl, R⁷ is

H, F, Br or C_1-2 alkyl and R⁸ is H or F.

A preferred value of R³ and R⁴ is methyl.

Alkyl groups may be in the form of straight or branched chains. They include methyl, ethyl, (n-and iso-propyl). Alkenyl and alkynyl groups can also be in the form of straight or branched chains. They include allyl, crotyl, 1-methylprop-2-enyl and propargyl. Cycloalkyl includes, in particular, cyclopropyl.

Halo includes fluoro, chloro and bromo.

In one aspect the invention provides a compound of formula (I) in which R¹ is allyl, R² is methyl, and A, B, R³ and R⁴ are as defined above.

In another aspect the invention provides a compound of formula (I) in which R³ and R⁴ are both methyl, and A, B, R¹ and R² are as defined above.

In yet another aspect the invention provides a compound of formula (I) in which A is F or Cl, B is H or F, and R¹, R², R³ and R⁴ are as defined above. Of particular interest are compounds in which A and B are both F.

The invention is illustrated by the compounds listed in Table I which follows. The compounds have the general formula (I) in which the values A, B, R¹, R², R³ and R¹ are as listed.

TABLE II

Table II lists selected proton NMR data for certain compounds described in Table I. Chemical shifts are measured as ppm from tetra- methylsilane. Deuterochloroform was used as solvent. The operating frequency of the NMR spectrometer was 270 MHz. The following abbreviations are used: br = broad t = triplet

s = singlet q = quartet

d = doublet m = multiplet Compound NMR Data (δ)

No

1 (Pair of rotamers) 1.66(6H,d), 2.80 and 3.08(3H, each s),

3.70-3.77 and 4.0-4.4(2H,br d and v.br s), 5.11-5.33(2H,m), 5.61-5.95(1H,m), 7.42-7.48(1H,m), 7.79-7.84(1H,m),

8.3-8.4(1H,br d).

9 (Pair of rotamers) 1.05 and 1.22(3H,each t), 1.66(6H,d), 3.23 and 3.56(2H,each q), 3.79 and 4.18(2H,each d), 5.10-5.30(2H,m), 5.62-5.96(1H,m), 7.18-7.35(2H,m), 7.61-7.70(1H,m), 8.3(1H,m).

15 (Pair of rotamers) 1.65. (6H,d), 2.88 and 3.08(3H,each s), 3.80 and 4.19(2H,each d), 5.14-5.30(2H,m), 7.24-7.32(2H,m), 7.61-7.92(1H,m), 5.0-8.4(1H,br m).

23 (Pair of rotamers) 1.65(6H,d), 2.31(1H,m), 2.94 and 3.18(3H,each s), 3.85-3.95 and 4.4(2H,br m and br s), 7.22-7.31(1H,m),

7.46-7.53(1H,m), 7.83(1H,d), 8.56(1H,br d).

The compounds of the invention can be made by, for example, the methods illustrated in Schemes 1, 2 and 3. Throughout these Schemes R¹, R², R³, R⁴, A and B, are as defined before.

In Scheme 1, compounds of formula (I) can be prepared by reacting compounds of formula (VI) with an acid chloride FC(R³)(R⁴)COCl in a suitable organic solvent such as methylene chloride or toluene in the presence of a base such as a tertiary amine (for example triethylamine) or an alkali metal carbonate or hydroxide (for example sodium bicarbonate or sodium hydroxide).

Alternatively, compounds of formula (I) can be prepared by reacting compounds of formula (VI) with an acid FC(R³)(R⁴)COOH in a suitable organic solvent such as dichloromethane or toluene in the presence of a suitable coupling agent (for example a carbodiimide salt such as dimethylaminopropyl ethyl carbodiimide hydrochloride).

Compounds of formula (VI) can be made by reduction of nitro compounds of formula (V) using standard methods known in the literature, such as iron powder in aqueous ethanol.

Compounds of formula (V) can be made by treatment of compounds of formula (IV) with a base (for example sodium hydride) and a compound of formula R²Z (where Z is a leaving group such as chloride, bromide, iodide or tosylate) in a suitable solvent (for example DMF or THF).

Amides of formula (IV) can be made from acid chlorides of formula (III) by reaction with an amine R¹R²NH in a suitable organic solvent (such as methylene chloride or toluene) or in water, in the presence of a base (such as triethylamine or sodium bicarbonate or excess amine R¹R²NH).

In Scheme 2, compounds of formula (I) can be prepared from compounds of formula (IX) by reaction with an amine R¹R²NH in a suitable organic solvent such as methylene chloride or tetrahydrofuran (THF) in the presence of a base such as triethylamine, sodium bicarbonate or excess R¹R²NH.

Acid chlorides of formula (IX) can be prepared from carboxylic acids of formula (VIII) by reaction with a standard reagent such as oxalyl chloride in a suitable dry solvent such as THF or methylene chloride and with a catalytic quantity of DMF being added if necessary.

Carboxylic acids of formula (VIII) can be prepared from the

appropriately substituted 4-aminobenzoic acid (VII) by reaction with an acid chloride FC(R³)(R⁴)COCl in water in the presence of at least two equivalents of a base such as an alkali metal carbonate or hydroxide (for example sodium bicarbonate). The substituted 4-aminobenzoic acids (VII) can generally be made by methods described in the literature.

In Scheme 3, compounds of formula (XV) may be prepared by reacting compounds of formula (XIV) with an acid FC(R³)(R⁴)COOH in a suitable organic solvent such as dichloromethane or toluene in the presence of a suitable coupling agent (for example a carbodiimide salt such as

dimethylaminopropyl ethyl carbodiimide hydrochloride).

Compounds of formula (XIV) may be prepared from compounds of formula

(XIII) by treatment with an acid (for example aqueous hydrogen chloride or trifluoroacetic acid) optionally in a solvent such as dichloromethane or tetrahydrofuran.

Compounds of formula (XIII) may be prepared from acids of formula (XII) by reaction with a secondary amine HNR¹R² in the presence of a coupling reagent (for example a carbodiimide salt such as

dimethylaminopropyl ethyl carbodiimide hydrochloride). A suitable organic solvent may be used such as dichloromethane or toluene.

Compounds of formula (XII) may be prepared by hydrolysis of compounds of formula (XI) by means of aqueous acid or base. Examples of suitable acids include sulphuric acid or hydrochloric acid. Suitable bases include sodium hydroxide or potassium hydroxide. Elevated temperatures may be optionally used (for example the mixture may be heated under reflux).

Compounds of formula (XI) may be prepared from compounds of formula (X) by treatment first with a strong base (for example a butyl lithium) followed by treatment with an alkoxycarbonyl chloride R'OCOCl where R' is, for example, a C_1-4alkyl group. A suitable solvent such as tetrahydrofuran may be used.

Compounds of formula (X) may be prepared from 3,5-difluorobenzoic acid by the Curtius reaction of the corresponding acid azide. 3,5-Difluoro- benzoic acid may be treated with an azide (for example diphenylphosphoryl azide) in the presence of an alcohol ROH which may be present in excess and thus act as solvent for the reaction. Elevated temperatures may

advantageously be used. 3,5-Difluorobenzoic acid is commercially

available.

The compounds of the invention may also be prepared using methods and techniques described in EP-A-0381330 and in EP Application No 91306443.2, the contents of which are incorporated herein by reference.

In another aspect, the invention provides processes as herein described for preparing the compounds of the invention.

The compounds of the invention show fungicidal activity across a range of plant diseases. They are, however, particularly active against the class of pathogens known as the phycomycetes (equivalent to the oomycetes). These include species of Phytophthora, Plasmopara, Peronospora and

Pseudoperonospora. Examples of pathogens which the invention compounds are particularly useful for controlling are: 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; Phytophthora infestans on potatoes and tomatoes and other Phytophthora spp. on vegetables,

strawberries, avocado, pepper, ornamentals, tobacco, cocoa and other hosts; and Pythium sp on rice, horticultural plants, vegetables and turf.

The invention therefore 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 compound as hereinbefore defined, or a composition containing the same.

The compounds may be used directly for agricultural purposes but are more conveniently formulated into compositions using a carrier or diluent. The invention thus provides fungicidal compositions comprising a compound as hereinbefore defined and an acceptable carrier or diluent therefor.

The compounds can be applied in a number of ways. For example, they can be applied, formulated or unformulated, directly to the foliage of a plant, to seeds or to other 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 invention compounds may also be injected into plants or sprayed onto vegetation using electrodynamic spraying techniques or other low volume methods.

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

The compounds are preferably used for agricultural and horticultural purposes in the form of a composition. The type of composition used in any instance will depend upon the particular purpose envisaged.

The compositions may be in the form of dustable powders or granules comprising the active ingredient (invention compound) and a solid diluent or carrier, for example, fillers such as kaolin, bentonite, kieselguhr, dolomite, calcium carbonate, talc, powdered magnesia, fuller's earth, gypsum, diatomaceous earth and 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 ingredient or by pelleting a mixture of the active ingredient 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 ingredient can be formulated for seed dressing purposes using an organic solvent (for example, N-methylpyrrol- idone, propylene glycol or N,N-dimethylformamide). The compositions may also be in the form of wettable 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 ingredient 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 ingredient 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 ingredient 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.

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 propellant, e.g. fluorotrichloromethane or dichlorodifluoromethane.

The invention compounds 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 compounds.

Alternatively, the compounds 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 substance.

By including suitable additives, for example additives for improving the distribution, adhesive power and resistance to rain on treated

surfaces, the different compositions can be better adapted for various utilities. Other additives may be included to improve the biological efficacy of the various formulations. Such additives can be surface active materials to improve the wetting and retention on surfaces treated with the formulation and also the uptake and mobility of the active material, 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 have been found to enhance several-fold foliar protectant activity against, for example, Plasmopara viticola.

The invention compounds 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 compound are preferred. Such granules suitably contain up to 25% by weight of the compound. The invention therefore also provides a fertiliser composition comprising a fertiliser and the compound of general formula (I) or a salt or metal complex thereof.

Wettable powders, emulsifiable concentrates and suspension

concentrates will normally contain surfactants, e.g. 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, the condensation products of the said partial esters with ethylene oxide, and the lecithins. 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 ingredient, 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 10-85%, for example 25-60%, by weight of the active ingredient. After dilution to form aqueous preparations, such preparations may contain varying amounts of the active ingredient depending upon the intended purpose, but an aqueous preparation containing 0.0005% or 0.01% to 10% by weight of active ingredient may be used.

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

A fungicidal compound which may be present in the composition of the invention may be one which is capable of combating ear diseases of cereals (e.g. wheat) such as Septoria, Gibberella and Helminthosporium spp., seed and soil-borne diseases and downy and powdery mildews on grapes and powdery mildew and scab on apple, etc. By including another fungicide, the composition can have a broader spectrum of activity than the compound of general formula (I) alone. Further the other fungicide can have a synergistic effect on the fungicidal activity of the compound of general formula (I). Examples of fungicidal compounds which may be included in the composition of the invention are (RS)-1-aminopropylphosphonic acid, (RS)-4- -(4-chlorophenyl)-2-phenyl-2-(1H-1,2,4-triazol-1-ylmethyl)butyronitrile, (Z)-N-but-2-enyloxymethyl-2-chloro-2',6'-diethylacetanilide, 1-(2-cyano-2- -methoxyiminoacetyl)-3-ethyl urea, 3-(2,4-dichlorophenyl)-2-(1H-1,2,4-tri- azol-1-yl)quinazolin-4(3H)-one, 4-bromo-2-cyano-N,N-dimethyl-6-trifluoro- methylbenzimidazole-1-sulphonamide, 5-ethyl-5,8-dihydro-8-oxo(1,3)-dioxol- (4,5-g)quinoline-7-carboxylic acid, α-[N-(3-chloro-2,6-xylyl)-2-methoxy- acetamido]-γ-butyrolactone, aldimorph, anilazine, benalaxyl, benomyl, biloxazol, binapacryl, bitertanol, blasticidin S, bromuconazole,

bupirimate, buthiobate, captafol, captan, carbendazim, carboxin, chlorbenzthiazone, chloroneb, chlorothalonil, chlorozolinate, copper containing compounds such as copper oxychloride, copper sulphate and Bordeaux mixture, cycloheximide, cymoxanil, cyproconazole, cyprofuram, di-2-pyridyl

disulphide 1,1'-dioxide, dichlofluanid, dichlone, diclobutrazol,

diclomezine, dicloran, difenoconazole, dimethamorph, dimethirimol, diniconazole, dinocap, ditalimfos, dithianon, dodemorph, dodine,

edifenphos, etaconazole, ethirimol, ethyl (Z)-N-benzyl-N-([methyl(methyl- thioethylideneamino-oxycarbonyl)amino]thio)-β-alaninate, etridiazole, fenapanil, fenarimol, fenfuram, fenpiclonil, fenpropidin, fenpropimorph, fentin acetate, fentin hydroxide, flutolanil, flutriafol, flusilazole, folpet, fosetyl-aluminium, fuberidazole, furalaxyl, furconazole-cis, guazatine, hexaconazole, hydroxyisoxazole, imazalil, imibenconazole, iprobenfos, iprodione, isoprothiolane, kasugamycin, mancozeb, maneb, mepanipyrim, mepronil, metalaxyl, methfuroxam, metsulfovax, myclobutanil, neoasozin, nickel dimethyldithiocarbamate, nitrothal-isopropyl, nuarimol, ofurace, organomercury compounds, oxadixyl, oxycarboxin, pefurazoate, penconazole, pencycuron, phenazin oxide, phthalide, polyoxin D, polyram, probenazole, prochloraz, procymidone, propamocarb, propiconazole, propineb, prothiocarb, pyrazophos, pyrifenox, pyroquilon, pyroxyfur, pyrrolnitrin, quinomethionate, quintozene, SSF-109, streptomycin, sulphur, tebuconazole, techlofthalam, tecnazene, tetraconazole, thiabendazole, thicyofen, thiophanate-methyl, thiram, tolclofos-methyl, triacetate salt of

1,1'-iminodi (octamethylene)diguanidine, triadimefon, triadimenol,

triazbutyl, tricyclazole, tridemorph, triforine, validamycin A,

vinclozolin, zarilamid and zineb. The compounds of general formula (I) can be mixed with soil, peat or other rooting media for the protection of plants against seed-borne, soil-borne or foliar fungal diseases.

Suitable insecticides which may be incorporated in the composition of the invention include buprofezin, carbaryl, carbofuran, carbosulfan, chlorpyrifos, cycloprothrin, demeton-s-methyl, diazinon, dimethoate, ethofenprox, fenitrothion, fenobucarb, fenthion, formothion, isoprocarb, isoxathion, monocrotophos, phenthoate, pirimicarb, propaphos and XMC.

Plant growth regulating compounds are compounds which control weeds or seedhead, formation, or selectively control the growth of less desirable plants (e.g. grasses).

Examples of suitable plant growth regulating compounds for use with the invention compounds are 3,6-dichloropicolinic acid,

1-(4-chlorophenyl)-4,6-di-methyl-2-oxo-1,2-dihydropyridine-3-carboxylic acid, methyl-3,6-dichloroanisate, abscisic acid, asulam, benzoylprop-ethyl, carbetamide, daminozide, difenzoquat, dikegulac, ethephon, fenpentezol, fluoridamid, glyphosate, glyphosine, hydroxybenzonitriles (e.g.

bromoxynil), inabenfide, isopyrimol, long chain fatty alcohols and acids, maleic hydrazide, mefluidide, morphactins (e.g. chlorfluoroecol),

paclobutrazol, phenoxyacetic acids (e.g. 2,4-D or MCPA), substituted benzoic acid (e.g. triiodobenzoic acid), substituted quaternary ammonium and phosphonium compounds (e.g. chloromequat, chlorphonium or

mepiquatchloride), tecnazene, the auxins (e.g. indoleacetic acid, indolebutyric acid, naphthylacetic acid or naphthoxyacetic acid), the cytokinins (e.g. benzimidazole, benzyladenine, benzylaminopurine, diphenylurea or kinetin), the gibberellins (e.g. GA₃, GA₄ or GA₇) and triapenthenol.

The following Examples illustrate the invention.

Where shown, infrared and NMR data are selective; no attempt is made to list every absorption in all cases. The following abbreviations are used throughout:

THF = tetrahydrofuran d = doublet

BOC = t-Butoxycarbonyl m = multiplet

NMR = nuclear magnetic resonance s = singlet

br = broad

EXAMPLE 1

This Example illustrates the preparation of 2,6-difluoro-4-(2-fluoro- -2-methylpropanamido)-N-methyl-N-prop-2-enylbenzamide (Compound No. 15 of Table I).

Step 1

Preparation of 1,3-difluoro-5-(1,1-dimethylethoxycarbamoyl)benzene 3,5-Difluorobenzoic acid (24.0g, 152mmol) was added to a stirred solution of diphenylphosphoryl azide (46.01g, 167mmol) in t.-butanol (300ml). After 15 minutes, triethylamine (18.46g, 182mmol) was added dropwise over 10 minutes. The mixture was heated at reflux for 2 hours before cooling, concentration to ca 100ml on a rotary evaporator and pouring into water (500ml). The mixture was repeatedly extracted with ethyl acetate and the organic extracts were dried (MgSO₄) and concentrated under reduced pressure to give a sticky brown solid (41.6g). Recrystallisation from hexane gave the product as pale orange crystals (23.5g).

Step 2

Preparation of methyl 2,6-difluoro-4-(1,1-dimethylethoxy- carbamoyl)benzoate.

A solution of n-butyl lithium in hexane (89ml; 2.5M, 222mmol) was added dropwise to a stirred solution of 1,3-difluoro-5-(1,1-dimethylethoxy- carbamoyl)benzene (20.1g, 87.8mmol) and tetramethylethylenediamine (25.7g, 222mmol) in THF (600ml) kept below -60°C under nitrogen. Methyl

chloroformate (16.9, 176mmol) in THF (100ml) was added dropwise over 30 minutes and the resulting solution allowed to warm to room temperature and then stand for 20 hours before adding water (200ml). The organic layer was separated and the aqueous residue repeatedly extracted with diethyl ether. The combined organic phases were washed (brine), dried (MgSO₄) and evaporated to give an orange oil (28.9g) which was crystallised from methanol to give the product as a solid (4.2g). Evaporation of the mother liquors and recrystallisation of the residue from methanol (twice) gave a further 1.5g of product.

Step 3

Preparation of 2,6-difluoro-4-(1,1-dimethylethoxycarbamoyl)benzoic acid.

The ester prepared in Step 2 (2.87g, 10mmol) was heated under reflux in a mixture of sodium hydroxide (1.6g, 40mmol), methanol (50ml) and water (15ml). After 4 hours, the solution was allowed to cool to room

temperature and stand for 20 hours. The mixture was evaporated, water (50ml) was added and the resulting solution washed with ethyl acetate. The aqueous layer was acidified to pH 2-3 (cHCl) and extracted with ethyl acetate. The combined organic phases were dried (MgSO,) and evaporated to give a cream coloured solid (2.32g), shown by NMR to consist of the desired product admixed with approximately 15% of 2,6-difluoro-4-aminobenzoic acid. This material was used without further purification in Step 4.

Step 4

Preparation of N-methyl-N-prop-2-enyl-2,6-difluoro-4-(1,1-dimethyl- ethoxycarbamoyl)benzamide.

Dimethylaminopropyl ethyl carbodiimide hydrochloride (0.79g, 4mmol) was added in portions to a stirred solution of the acid prepared in Step 3 (1.0g, 3.66mmol), 4-dimethylaminopyridine (catalytic) and methyl allyl amine (725μl, 7.4mmol). After 2 hours, the mixture was washed with water, dried (MgSO₄) and evaporated to give the crude product as a pale yellow oil (620mg). Chromatography on silica eluting with hexane/ethyl acetate gave the pure product as a colourless oil (260mg).

Step 5

Preparation of N-methyl-N-prop-2-enyl-2,6-difluoro-4-aminobenzamide.

The crude BOC protected aniline prepared in Step 4 (260mg, 0.8mmol) was stirred in trifluoroacetic acid (1.5ml) and dichloromethane (1.5ml) for 1.5 hours. The solvents were removed and the residue partitioned between dichloromethane and saturated aqueous sodium bicarbonate. The organic layer was separated, dried (MgSO₄) and evaporated to give the product as a pale yellow crystalline solid (180mg). Step 6

Preparation of 2,6-difluoro-4-(2-fluoro-2-methylpropanamido)-N- methyl-N-prop-2-enylbenzamide.

Dimethylaminopropyl ethyl carbodiimide hydrochloride (170mg) was added in portions over 15 minutes to the aniline prepared in Step 5 (180mg, 0.8mmol), 4-dimethylaminopyridine (catalytic) and fluoroisobutyric acid (110mg) in dichloromethane (2ml). After 2. hours, the solution was evaporated and the product was isolated as a colourless gum (200mg) by chromatography on silica, eluting with hexane/ethyl acetate (2:1). H NMR (270MHz;CDCl₃) (pair of rotamers) δ 1.65(6H d), 2.88 and 3.08(3H,each s), 3.80 and 4.19(2H,each d), 5.14-5.30(2H,m), 7.24-7.32(2H,m),

7.61-7.92(1H,m), 5.0-8.4(1H,br m) )

The following are examples of compositions suitable for agricultural and horticultural purposes which can be formulated from the compounds of the invention. Such compositions form another aspect of the invention. Percentages are by weight.

EXAMPLE 2

An emulsifiable concentrate is made up by mixing and stirring the ingredients until all are dissolved.

Compound No. 15 of Table I 10%

Benzyl alcohol 30%

Calcium dodecylbenzenesulphonate 5%

Nonylphenolethoxylate (13 mole ethylene oxide) 10%

Alkyl benzenes 45%

EXAMPLE 3

The active ingredient is dissolved in methylene dichloride and the resultant liquid sprayed on to the granules of attapulgite clay. The solvent is then allowed to evaporate to produce a granular composition. Compound No. 15 of Table I 5%

Attapulgite granules 95%

EXAMPLE 4

A composition suitable for use as a seed dressing is prepared by grinding and mixing the three ingredients.

Compound No. 15 of Table I 50%

Mineral oil 2%

China clay 48% EXAMPLE 5

A dustable powder is prepared by grinding and mixing the active ingredient with talc.

Compound No. 15 of Table I 5%

Talc 95%

EXAMPLE 6

A suspension concentrate is prepared by ball milling the ingredients to form an aqueous suspension of the ground mixture with water.

Compound No. 15 of Table I 40%

Sodium lignosulphonate 10%

Bentonite clay 1%

Water 49%

This formulation can be used as a spray by diluting into water or applied directly to seed.

EXAMPLE 7

A wettable powder formulation is made by mixing together and grinding the ingredients until all are thoroughly mixed.

Compound No. 15 of Table I 25%

Sodium lauryl sulphate 2%

Sodium lignosulphonate 5%

Silica 25%

China clay 43%

EXAMPLE 8

A soluble powder is made by mixing and grinding the ingredients to form an homogeneous powder.

Compound No. 15 of Table I 10%

Sodium dioctylsulphosuccinate 2%

Sodium lignosulphonate 5%

Sodium benzoate 20%

Sodium bicarbonate 63%

EXAMPLE 9

A soluble granule is made by adding 10-20% water to the soluble powder composition prepared as described in Example 8 to form damp granules, which are then dried.

EXAMPLE 10

A water soluble concentrate is made by mixing together and dissolving the active ingredient in the other ingredients.

Compound No. 15 10% C_13/15 alcohol/7 mole ethylene oxide 5%

Propylene glycol monomethyl ether 85%

EXAMPLE 11

The compounds were tested against the diseases Plasmopora viticola on vine and Phytophthora infestans lycopersici on tomato. The technique employed was as follows.

The plants were grown in John Innes Potting Compost (No. 1 or 2) in 4cm diameter minipots. The test compounds were formulated either by bead milling with aqueous Dispersol T or as a solution in acetone or

acetone/ethanol which was diluted to the required concentration immediately before use. The formulations (100 ppm active ingredient) were sprayed onto the foliage or applied to the roots of the plants in the soil. The sprays were applied to maximum retention and the root drenches to a final concentration equivalent to approximately 40 ppm a.i. in dry soil.

For most of the tests the compounds were applied to the soil (roots) or to the foliage (by spraying) one or two days before the plant was inoculated with the disease. The pathogens were applied by spray as spore suspensions onto the leaves of test plants. After inoculation, the plants were put into an appropriate environment to allow infection to proceed and then incubated until the disease was ready for assessment. The period between inoculation and assessment varied from four to seven days according to the disease and environment.

The disease control was recorded by the following grading:

4 = no disease

3 = trace-5% of disease on untreated plants

2 = 6-25% of disease on untreated plants

1 = 26-59% of disease on untreated plants

0 = 60-100% of disease untreated plants

The results are shown in Table III. TABLE III

Pv = Plasmopara viticola

Pil = Phytophthora infestans lycopersici syst = root drench

prot = foliar spray

CHEMICAL FORMULAE

(in description)

Scheme 1

O

Claims

CLAIMS 1. A compound of the formula (I):

(I)

in which A is F, Cl, Br or C_1-2 alkyl; B is H, F or Cl; R¹ is C_3-4 alkenyl, halo(C_3-4)alkenyl, C_3-4 alkynyl or halo(C_3-4)alkynyl; R² is C_1-4 alkyl, halo(C_1-4)alkyl, C_3-4cycloalkyl or halo(C_3-4)cycloalkyl; R³ is C_1-2 alkyl, CH₂F or CF₃; and, when R³ is C_1-2 alkyl or CH₂F, R⁴ is C_1-3 alkyl, allyl, propargyl or CHFR⁵ wherein R⁵ is H or C_1-2 alkyl, and, when R ³ is CF₃, R⁴ is the group C(R⁶)(R⁷)R⁸ wherein R⁶ is

H or C_1-2 alkyl, R ⁷ is H, F, Br or C_1-2 alkyl and R⁸ is H or F.

2. A compound according to claim 1 in which R ¹ is allyl and R² is methyl.

3. A compound according to claim 1 or 2 in which R ³ and R⁴ are both

methyl.

4. A compound according to any one of the preceding claims in which A is F or Cl and B is H or F.

5. A compound according to any one of claims 1 to 3 in which A and B are both F.

6. A process for preparing a compound according to claim 1 which

comprises reacting in a suitable organic solvent in the presence of a base either

(a) a compound of formula (VI):

with an acid chloride FC(R³)(R⁴)COCl; or

(b) a compound of formula (IX):

with an amine R¹R²NH;

or reacting in a suitable organic solvent in the presence of a suitable coupling agent a compound of formula (XIV) :

with an acid FC(R³)(R⁴)COOH; wherein A, B, R¹, R², R³ and R⁴ have the meanings given in claim 1.

7. A fungicidal composition comprising a fungicidally effective amount of a compound according to claim 1 and a fungicidally acceptable carrier or diluent therefor.

8. A method of combating fungi which comprises applying to plants, to the seeds of plants or to the locus of the plants or seeds, a compound according to claim 1 or a composition according to claim 7.