GB2246352A - Fungicidal acylaminobenzene sulphonamides - Google Patents

Abstract

Fungicidal compounds of the formula (I): <IMAGE> in which D and E are independently H or F; X is O or S; and R<1> to R<4>, A and B have various specified values.

Description

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

According to the present invention there is provided a compound of the formula (I), A and B are independently H, fluoro, chloro, bromo, iodo, C1-4 alkyl, C1-4 alkoxy, halo(C1-4)alkyl, cyano, C1-4 alkoxycarbonyl, C1-4 alkoxymethyl, C1-4 alkylthiomethyl, C2-4 alkenyl, C2-4 alkynyl, C1-4 alkylcarbonyl, formyl, C1-4 alkylthio, carboxy, or nitro, provided that both A and B are not H;D and E are independently H or fluoro; R1 and R2 are independently C14 alkyl, C36 alkenyl (optionally substituted with halogen), C3-6 alkynyl (optionally substituted with halogen), C14 alkoxy, C1-4 haloalkyl, C3-6 cycloalkyl, C3-6 cycloalkyl(C1-4)alkyl, C1-4 alkoxy(Cl 4)alkyl, C1-4 alkylthio(C1-4)alkyl, or cyano; or R1 and R2 together with the nitrogen to which they are attached join to form a morpholine, piperidine, pyrrolidine or azetidine ring, which may be optionally substituted with C1-4 alkyl; R3 is H;R4 is trichloromethyl, C2-8 alkyl (optionally substituted with halogen, C1-8 alkoxy, azido, nitro, isocyano, -NR5R6 [where R5 and R6 are independently C1-4 alkyl, C14 alkylcarbonyl, or formyl], cyano, C1-4 alkylcarbonyl, formyl or R'S(O)n in which R' is C14 alkyl, C24 alkenyl or C2-4 alkynyl and n is 0, 1, or 2), cyclopropyl or cyclobutyl or cyclopentyl or cyclohexyl (all optionally substituted with C1-4 alkyl, halogen, C1-4 alkoxy, C1-4 alkylthio, C2-4 alkenyl, C2-4 alkynyl, cyano, C1-4 alkoxycarbonyl, azido, nitro, isocyano, or NR5R6[where R5 and R6 are independently H, C1-4 alkyl, C1-4 alkylcarbonyl, or formyl]), or R3 and R4 together with the group C(O)N to which they are attached join to form an azetidin-2-one ring which is optionally substituted with C14 alkyl; and X is O or S.

A preferred value of R4 is R(CH3)2C- in which R is halogen, C1-4 alkyl (especially methyl or ethyl) or C1-4 alkoxy (especially methoxy).

Alkyl groups and the alkyl moiety of other alkyl-containing groups can be in the form of straight or branched chains. Examples are methyl, ethyl, propyl (n-and iso-propyl), butyl (n-, sec, iso- and t-butyl), l,l-dimethylpropyl and l,l-dimethylbutyl. Alkenyl and alkynyl groups can also be in the form of straight or branched chains. Examples are 1,1-dimethylbut-3-enyl and 1,1-dimethylprop-2-ynyl.

Halogen includes fluorine, chlorine and bromine.

In one aspect the invention provides a compound of formula (I) in which A is halo or C1-4 alkyl; R1 and R are C1-4 alkyl; R4 is C2-8 alkyl optionally substituted with halogen or C1-4 alkoxy; B and R3 are H; and X is 0.

The invention is illustrated by the compounds listed in Table I which follows. The compounds have the formula (II) in which R1, R2, R4, A and B have the values given in the table.

TABLE I Compound R1 R2 R4 A B Mpt( C) No.

1 CH3 CH3 (CH3)3C Cl H gum 2 CH3 CH3 CH3CH2(CH3)2C Cl H 3 CH3 CH3 CL(CH3)2C Cl H 4 CH3 CH3 Br(CH3)2C Cl H 5 CH3 CH3 F(CH3)2C Cl H 122-123.5 6 CH3 CH3 CH30(CH3)2C Cl H 7 CH3 CH3CH2 (CH3)3C Cl H gum 8 CH3 CH3CH2 CH3CH2(CH3)2C Cl H 9 CH3 CH3CH2 Cl(CH3)2C Cl H 10 CH3 CH3CH2 Br(CH3)2C Cl H 11 CH3 CH3CH2 F(CH3)2C Cl H 12 CH3 CH3CH2 CH30(CH3)2C Cl H 13 CH3 CH3 (CH3)3C CH3 H 142-143 14 CH3 CH3 CH3CH2(CH3)2C CH3 H 15 CH3 CH3 Cl(CH3)2C CH3 H 16 CH3 CH3 Br(CH3)2C CH3 H 17 CH3 CH3 F(CH3)2C CH3 H oil 18 CH3 CH3 CH30(CH3)2C CH3 H 19 CH3 CH3CH2 (CH3)3C CH3 H glass 20 CH3 CH3CH2 CH3CH2(CH3)2C CH3 H 21 CH3 CH3CH2 C1(CH3)2C CH3 H 22 CH3 CH3CH2 Br(CH3)2C CH3 H 23 CH3 CH3CH2 F(CH3)2C CH3 H 24 CH3 CH3CH2 CH30(CH3)2C CH3 H TABLE I (continued) Compound R1 R2 R4 A B Mpt( C) No.

25 CH3 CH3 (CH3)3C F H 26 CH3 CH3 CH3CH2(CH3)2C F H 27 CH3 CH3 C1(CH3)2C F H 28 CH3 CH3 Br(CH3)2C F H 29 CH3 CH3 F(CH3)2C F H 120-125 30 CH3 CH3 CH3O(CH3)2C F H 31 CH3 CH3CH2 (CH3)3C F H 32 CH3 CH3CH2 CH3CH2(CH3)2C F H 33 CH3 CH3CH2 C1(CH3)2C F H 34 CH3 CH3CH2 Br(CH3)2C F H 35 CH3 CH3CH2 F(CH3)2C F H oil 36 CH3 CH3CH2 CH30(CH3)2C F H 37 (CH3)2CH (CH3)2CH F(CH3)2C Cl H 120-121 38 (CH3)2CH H F(CH3)2C Cl H 176.5-177 The compounds of the invention can be made, for example by the methods illustrated in Schemes 1 to 3. Throughout these Schemes R1, R2, R4, A, B, D and E are as defined before.

In Scheme 1, compounds of formula (II) can be prepared from sulphonyl chlorides of formula (VI) by reaction with an amine RRNH in the presence of a base such as a tertiary amine (for example triethylamine), excess amine R1R2NH, or an alkali metal carbonate or hydroxide (for example potassium carbonate or sodium hydroxide), in a suitable solvent such as methylene chloride or toluene.

Sulphonyl chlorides of formula (VI) can be made from anilines of formula (V) by treatment with nitrous acid (generated for example from sodium nitrite and sulphuric acid), followed by sulphur dioxide gas in the presence of a copper salt (such as cuprous chloride), in a suitable solvent (such as acetic acid).

Anilines of formula (V) can be made by reduction of nitro compounds of formula (IV) using standard methods such as hydrogenation over a precious metal catalyst (such as palladium on charcoal) in a suitable solvent (such as ethyl acetate), or iron, or stannous chloride, in hydrochloric acid.

Nitro amides of formula (IV) can be made from known or commercially available anilines of formula (III), by treatment with an acid chloride of formula R4COC1, in a suitable solvent (such as methylene chloride), in the presence of a base such as a tertiary amine (for example triethylamine) or an alkali metal carbonate or hydroxide (for example potassium carbonate or sodium hydroxide).

Alternatively, sulphonyl chlorides of formula (VI) can be prepared from sulphonic acids of formula (XII), as shown in Scheme 2, by treatment with a standard reagent such as phosphorus pentachloride or thionyl chloride, in a suitable solvent such as methylene chloride or toluene.

Sulphonic acids of formula (XII) can be made from amino sulphonic acids of formula (XI), by reaction with an acid chloride of formula R4COC1, in a suitable solvent such as methylene chloride in the presence of a base such as a tertiary amine (for example triethylamine).

In Scheme 3, compounds of formula (II) can be made from anilinosulphonamides of formula (X) by reaction with acid chlorides of formula R4COCl, in a suitable solvent such as methylene chloride, in the presence of a base such as a tertiary amine (for example triethylamine) or an alkali metal carbonate or hydroxide (for example potassium carbonate or sodium hydroxide). Alternatively, compounds of formula (II) can be made from anilinosulphonamides of formula (X) by reaction with acids of formula R4COOH, in a suitable solvent such as dichloromethane, in the presence of a coupling agent such as a carbodiimide (for example dicyclohexylcarbodiimide). Amino sulphonamides of formula (X) can be made by reduction of nitro compounds of formula (IX) using standard methods such as hydrogenation over a precious metal catalyst (for example palladium on charcoal), or iron, or stannous chloride, in hydrochloric acid.

Nitro sulphonamides of formula (IX) can be made by reaction of the sulphonyl chlorides of formula (VIII) with amines of formula R1RNH, in a suitable solvent such as methylene chloride or toluene, in the presence of a base such as a tertiary amine (for example trhethylamine), or excess amine R1RNH, or an alkali metal carbonate or hydroxide (for example potassium carbonate or sodium hydroxide).

Nitro sulphonyl chlorides of formula (VIII) can be prepared from known or commercially available nitro anilines of formula (VII), by treatment with nitrous acid (generated by for example reaction with sodium nitrite and sulphuric acid), followed by sulphur dioxide gas in the presence of a copper salt (for example cuprous chloride) in a suitable solvent, such as acetic acid.

Alternatively, nitro sulphonyl chlorides of formula (VIII) can be made from nitro sulphides of formula (XIV) by reaction with a chlorinating agent, for example chlorine, in a suitable solvent (for example chloroform) in the presence of water. Nitro sulphides of formula (XIV) may be prepared from a suitable, known nitro halide (XIII) with benzyl mercaptan in suitable solvent (for example DMF) in the presence of a base (such as sodium hydride).

The compounds of the invention may also be prepared using methods and techniques described in EP-A-0381330 and in UK Application No. 9016577.0 and applications claiming priority therefrom, the contents of which are incorporated herein by reference.

In a further 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-methylpyrrolidone, 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.

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)-l-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-(lH-1,2,4-tri- azol-l-yl)quinazolin-4(3H)-one, 4-bromo-2-cyano-N,N-dimethyl-6-trifluoromethylbenzimidazole-l-sulphonamide, 5-ethyl-5,8-dihydro-8-oxo(1,3)-dioxol (4,5-g)quinoline-7-carboxylic acid, a-[N-(3-chloro-2,6-xylyl)-2-methoxy- acetamido]-r-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 l,l'-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)-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 l,l'-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.

Throughout the Examples the term 'ether' refers to diethyl ether, sodium sulphate was used to dry solutions and solutions were concentrated under reduced pressure. 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: HCl = hydrochloric acid TUF = tetrahydrofuran s = singlet DMF = N,N-dimethylformamide d = doublet NMR = nuclear magnetic resonance t = triplet IR = infrared q = quintuplet mpt = melting point m = multiplet EXAMPLE 1 This Example illustrates the preparation of 2-chloro-4-trimethylacetamido-N,N-dimethylbenzenesulphonamide (Compound No 1 of Table I).

Step 1 The preparation of 4-trimethylacetamido-2-chloronitrobenzene.

Trimethylacetyl chloride (0.9g) was slowly added to a stirred solution of 3-chloro-4-nitroaniline (1.5g) and triethylamine (2ml) in dichloromethane (50ml). After 4 hours, the solution was concentrated under reduced pressure and the residue dissolved in ethyl acetate. The organic extract was washed twice with water, dried, filtered, and concentrated to give a yellow solid (1.93g). Trituration with hexane gave 4-trimethylacetamido-2chloronitrobenzene (1.73g); 1H NMR (CDC13, 270 MHz) 6 1.32(9H,s), 7.62(1H,s), 7.92(1H,s), 7.95(1H,d) ppm; mpt. 129-1300c.

Step 2 The preparation of 4-trimethylacetamido-2-chloroaniline.

4-trimethylacetamido-2-chloronitrobenzene (3.0g) was dissolved in methanol and hydrogenated at atmospheric pressure using platinum on carbon (5X) as catalyst. After 9 hours, the catalyst was removed by filtration and the residue evaporated. The pink residue was recrystallised from ethanol/water to give pink leaves of 4-trimethyl-acetamido-2-chloroaniline (2.13g); 1H NMR (CDC13, 270 MHz) 6 1.28(9H,s), 4.11(1H,s), 6.72(1H,d), 7.19(1H,d), 7.58(1H,s), 7.80(1H,s) ppm; mpt. 171-1720c.

Step 3 The preparation of 4-trimethylacetamido-2-chlorobenzenesulphonyl chloride.

4-Trimethylacetamido-2-chloroaniline (2.2g) was dissolved in a mixture of concentrated aqueous HCl (5ml) and glacial acetic acid (2ml). The solution was cooled to OOC and sodium nitrite (0.67g) in water (lml) was slowly added. After 10 minutes, the reaction mixture was added to a saturated solution of sulfur dioxide in glacial acetic acid (20ml), containing copper(I) chloride (0.5g) as a suspension. The mixture was stirred for 30 minutes, partitioned between ether and water, and the separated organic extract washed twice with dilute aqueous HC1. The ether layer was dried, filtered, and concentrated to give 4-trimethylacetamido-2chlorobenzenesulphonyl chloride as an oil (1.83g) which was used without further purification in the succeeding step and in Example 2.

Step 4 The preparation of 2-chloro-4-trimethylacetamido-N,N-dimethylbenzenesulphonamide.

Crude 4-trimethylacetamido-2-chlorobenzenesulphonyl chloride (0.41g) was dissolved in aqueous dimethylamine (40%; excess). After 3 hours, the residue was partitioned between ethyl acetate and water and the organic layer was dried, filtered, and concentrated to give a brown oil (0.372g).

Chromatography on silica eluting with ethyl acetate/hexane (1:1) gave 2-chloro-4-trimethylacetamido-N,N-dimethylbenzenesulphonamide (0.183g); 1H NMR (CDC13, 270 MHz) 6 1.32(9H,s), 2.84(6H,s), 7.48(1H,d), 7.75(1H,s), 7.91(1H,s), 7.93(1H,d) ppm.

EXAMPLE 2 This Example illustrates the preparation of 2-chloro-4-trimethylacetamido-N-ethyl-N-methylbenzenesulphonamide (Compound No 7 of Table I).

Crude 4-trimethylacetamido-2-chlorobenzenesulphonyl chloride (prepared in Example 1, step 3) (1.5g) was slowly added to a vigorously stirred solution of methylethylamine (3ml) in pyridine (5ml) at 100C. The pyridine was removed under reduced pressure and the residue dissolved in ethyl acetate, washed with dilute aqueous HCl, dried, filtered, and concentrated to give a brown oil (1.03g). Chromatography on silica eluting with ethyl acetate/hexane (1::1) gave 2-chloro-4-trimethylacetamido-N-ethyl-N-methylbenzenesulphonamide (0.53g). 1H NMR (CDCl3, 270 MHz) b 1.14(3H,t), 1.33(9H,s), 2.87(3H,s), 3.25(2H,q), 7.46(1H,d), 7.59(1H,s), 7.91(1H,s), 7.96(1H,d) ppm.

EXAMPLE 3 This Example illustrates the preparation of 2-methyl-4-(dimethyl fluoroacetamido)-N ,N-dimethylbenzenesulphonamide (Compound No 17 of Table I).

Step 1 The preparation of 2-methyl-4-ni tro-N,N-dimethylbenzenesulphonamide.

2-Methyl-4-nitroaniline (5.0g) was dissolved in a mixture of concentrated aqueous HC1 (20ml) and glacial acetic acid (10ml), the solution stirred, cooled to OOC, and a solution of sodium nitrite (2.3g) in water (4ml) slowly added. After 10 minutes, the mixture was slowly added to a suspension of copper) chloride (1.0g) in glacial acetic acid (40ml) saturated with sulfur dioxide. Sulfur dioxide was bubbled through continuously throughout the addition. The ether layer was washed with dilute aqueous HC1 (x2), dried, filtered, and concentrated. The residue was carefully added to a stirred solution of dimethylamine (40t aqueous; excess). After 10 minutes, the mixture was treated with dilute aqueous HCl and extracted with ethyl acetate.The organic layer was washed with water, dried, filtered and concentrated to give a yellow oil (1.83g); 1H NMR (270 MHz; CDC13) 6 2.73(3H,s), 2.96(6H,s), 8.05(1H,d), 8.13(1H,s), 8.15(1H,d) ppm.

Step 2 The preparation of 2-methyl-4-amino-N,N-dimethylbenzenesulphonamide.

2-Methyl-4-nitro-N-N-dimethylbenzenesulphonamide (1.0g) was dissolved in absolute ethanol (50ml) and the solution stirred vigorously whilst iron powder (0.5g) and dilute aqueous HCl (5.0ml) were added. The resulting suspension was stirred for 1.25 hours, then filtered through hyflo, concentrated and the residue partitioned between ethyl acetate and aqueous HCl (0.5M). The organic layer was dried, filtered, and concentrated to give 2-methyl-4-amino-N,N-dimethylbenzenesulphonamide as a brown solid (1.15g).

Step 3 The preparation of 2-methyl-4-dimethylfluoroacetamido-N,N-dimethylbenzenesulphonamide.

Oxalyl chloride (0.70g) in dichloromethane (10ml) was slowly added to a stirred solution of dimethylfluoroacetic acid (0.61g) in dichloromethane (10ml) containing 1 drop of DMF. After 45 minutes, 2-methyl-4-amino-N,Ndimethyl-benzenesulphonamide (1.0g) in dichloromethane was added, followed by triethylamine (lml). After 1 hour, the solution was filtered, washed with dilute aqueous HC1, filtered through phase-separating paper, and concentrated to give a brown oil.Chromatography on silica, eluting with ethyl acetate/hexane (1:3) gave 2-methyl-4-dimethylfluoroacetamido-N,Ndimethylbenzenesulphonamide as an oil (0.224g); 1U NMR (270 MHz; CDC13) 6 1.78(6H,d), 2.71(3H,s), 2.78(6H,s), 7.55(1H,m), 7.60(1H,m), 7.89(1H,d), 8.26(1H,s) ppm.

EXAMPLE 4 This example illustrates the preparation of 2-methyl-4-trimethylacetamido-N,N-dimethylbenzene-sulphonamide (Compound No 13 of Table I).

Step 1 The preparation of 2-methyl-4-trimethylacetamidobenzenesulphonic acid.

To a stirred solution of 2-methyl-4-aminobenzenesulphonic acid (6.6g) in pyridine (30ml) was added trimethylacetyl chloride (4.23). The mixture was heated to 600C for 4.5 hours and the solution was then concentrated.

The residue was recrystallised from chloroform/hexane to give 2-methyl-4trimethyl-acetamidobenzenesulphonic acid (7.38g).

Step 2 The preparation of 2-methyl-4-trimethylacetamidobenzenesulphonyl chloride.

2-Methyl-4-trimethylacetamidobenzenesulphonic acid (5.0g) was fused with phosphorous pentachloride (5.0g) at 1100C with stirring for 3 hours.

The resulting oil/solid was cooled to 500C and poured into crushed ice.

The mixture was extracted with ether, the ether layer washed with water, dried, filtered and concentrated to give 2-methyl-4-trimethylacetamidobenzenesulphonyl chloride as a yellow oil (5.3g), which was used without further purification in the succeeding step and in Example 5.

Step 3 The preparation of 2-methyl-4-trimethylacetamido-N,N-dimethylbenzenesulphonamide.

Crude 2-methyl-4-trimethylacetamidobenzenesulphonyl chloride (2.0g) was slowly added to a vigorously stirred 40% aqueous solution of dimethylamine (10ml) at 100C. The resulting mixture was warmed to room temperature. After 45 minutes, the suspension was extracted with ethyl acetate and the organic layer was washed twice with water, dried, filtered, and concentrated to give a yellow oil (1.13g). Chromatography on silica, eluting with ethyl acetate/hexane (1:1) gave 2-methyl-4-trimethylacetamido N,N-dimethylbenzenesulphonamide (0.26g); 1H NMR (270 MHz; CDC13) 6 1.33(9U,s), 2.59(3H,s), 2.77(6H,s), 7.43(1H,s), 7.47(1H,d), 7.57(1H,s), 7.86(1H,d) ppm; mpt 142-1430C.

EXAMPLE 5 This Example illustrates the preparation of 2-methyl-4-trimethylacetamido-N-ethyl-N-methylbenzene-sulphonamide (Compound No 19 of Table I).

To a stirred solution of crude 2-methyl-4-trimethylacetamidobenzenesulphonyl chloride (prepared in Example 4, step 3) at OOC in dichloromethane was slowly added ethylmethylamine (1.6g). After 30 minutes, the solvent was removed under reduced pressure and the residue partitioned between ethyl acetate and water. The organic phase was dried, filtered, and concentrated to give a yellow oil, (0.83g). Chromatography on silica, eluting with ethyl acetate/hexane (1:1) gave 2-methyl-4-trimethylacetamido-N-ethyl-N-methylbenzenesulphonamide (0.155g) as a glass; 1H NMR (270 MHz; CDC13) 6 1.15(3H,t), 1.33(9H,s), 2.56(3H,s), 2.77(3H,s), 3.20(2H,q), 7.46(1H,d), 7.54(1H,s), 7.57(1H,s), 7.84(1H,d) ppm.

EXAMPLE 6 This example illustrates the preparation of 2-chloro-4-(dimethylfluoroacetamido)-N,N-dimethylbenzenesulphonamide (compound No.5 of Table I).

Step 1 Preparation of 4-benzylthio-3-chloronitrobenzene.

Sodium hydride (60% in oil; 1.04g) was suspended in dry DMF (25ml) under nitrogen and the stirred mixture was cooled in an ice bath. Benzyl mercaptan (3.lml) was added in portions, then cooling was removed and stirring continued until a clear solution resulted. The solution was added portionwise to a stirred solution of 3,4-dichloronitrobenzene (5g) in dry DMF (25ml). After 1 hour, the mixture was poured into water and the solid product was recovered by filtration. Washing repeatedly with water and drying under vacuum gave the title compound (6.9g), mpt 105-1070C, which was used without further purification in step 2.

Step 2 Preparation of 2-chloro-4-nitrobenzenesulphonylchloride 4-Benzylthio-3-chloronitrobenzene (5g) ws dissolved in chloroform (50ml) and water (50ml) was added. The mixture was cooled to 100C and chlorine bubbled through while stirring vigorously. After 90 minutes, the organic layer was separated, washed with aqueous sodium metabisulphite, dried (MgS04) and concentrated under reduced pressure to give an orange oil (3.4g). Heating under high vacuum at 1000C gave the product as a brown oil (2.4g) which was used without further purifiction in step 3.

Step 3 Preparation of 2-chloro-4-nitro-N,N-dimethylbenzenesulphonamide To a stirred solution of 2-chloro-4-nitrobenzensulphonylchloride (2.4g) in dichloromethane (25ml) was added dimethylamine (40% in water; lOml). After 5 minutes, the organic layer was separated, washed with 5% aqueous HCl and with saturated aqueous sodium bicarbonate, dried (MgS04) and concentrated under reduced pressure to give a brown solid (1.95g). The product was isolated as sand coloured crystals (1.6g), mpt 111.5-112.50C, by recrystallisation from chloroform/hexane and used without further purification in step 4.

Step 4 Preparation of 4-amino-2-chloro-N,N-dimethylbenzenesulphonamide 2-Chloro-4-nitro-N,N-dimethylbenzenesulphonamide (1.25g) was added portionwise to a stirred mixture of Tin-II-chloride (2.7g) in concentrated aqueous HC1 (5ml), cooled in an ice bath. After 30 minutes, cooling was removed, and the mixture allowed to warm to room temperature, diluted with water and extracted with ether. The aqueous layer was basified with aqueous sodium hydroxide and extracted twice with dichloromethane. The combined organic extracts were washed with brine, dried (MgS04) and concentrated under reduced pressure to give the product as a white powder (770mg), mpt 130-1310C.Similarly prepared, but using 3,4-difluoronitrobenzene as starting material for step 1, was 4-amino-2-fluoro-N,Ndimethylbenzenesulphonamide. 1H NMR (270MHz; CDC13) 6 2.77 (3H,s), 2.78(3H,s), 4.25 (2H,bs), 6.37-6.48(2H,m), 7.58(1H,t) ppm.

Step 5 Preparation of 2-chloro-4-(dimethylfluoroacetamido)-N,N-dimethylbenzenesulphonamide.

A solution of dimethylfluoroacetyl chloride was prepared by adding oxalyl chloride (250us) to a stirred solution of dimethylfluoroacetic acid (300mg) and DMF (1 drop) in dichloromethane (2ml) under nitrogen. The solution of the acid chloride was added portionwise to a stirred mixture of 4-amino-2-chloro-N,N-dimethylbenzenesulphonamide (600mg), triethylamine (710us) and dimethylaminopyridine (catalytic) under nitrogen. After 1 hour, the mixture was diluted with dichloromethane and washed with 5% aqueous HC1 and saturated aqueous sodium bicarbonate, dried (MgS04) and concentrated under reduced pressure to give a brown oil. The pure product was isolated by chromatography on silica, eluting with hexane/ethyl acetate (3:1) to give a colourless solid (410mg), mpt 122-123.50C. Similarly prepared were: 2-chloro-4-(dimethylfluoroacetamido)-N-isopropylbenzenesulphonamide, mpt 176.5-1770C (compound No.38 of Table I), 2-chloro-4-(dimethylfluoroacetamido)-N,N-diisopropylbenzenesulphon- amide, mpt 120-121 C (compound No.37 of Table I), and 2-fluoro-4-(dimethylfluoracetamido)-N-methyl-N-ethybenzenesulphonamide, H NMR (270MHz; CDC13) 6 1.15 (3H,t), 1.67(6H,d), 2.85(3H,s), 3.22(2H,q), 7.21-7.28(1H,m), 7.76-7.88(2H,m), 8.32(1H,bd) (compound No.35 of Table 1).

EXAMPLE 7 This Example illustrates the preparation of 2-fluoro-4-(dimethylfluoroacetamido)-N,N-dimethylbenzenesulphonamide (compound No.29 of Table I).

To a stirred solution of 4-amino-2-fluoro-N,N-dimethylbenzenesulphon- amide (660mg) and fluorodimethylacetic acid (480mg) in dry dichloromethane (lOml) under nitrogen was added dicyclohexylcarbodiimide (940mg). After 48 hours, the precipitate was removed by filtration and the filtrate concentrated under reduced pressure and redissolved in dichloromethane.

The solution was washed twice with dilute aqueous HCl, dried (MgS04) and concentrated under reduced pressure. The residue was purified by chromatography on silica, twice, eluting first time with ethyl acetate/hexane (1:1) and second time with ethyl acetate hexane (1:4). The product was isolated as a solid, mpt 120-1250C.

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

Compound No. 13 of Table I 10% Benzyl alcohol 30% Calcium dodecylbenzenesulphonate 5% Nonylphenolethoxylate (13 mole ethylene oxide) 10% Alkyl benzenes 45% EXAMPLE 9 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. 13 of Table I 5% Attapulgite granules 95% EXAMPLE 10 A composition suitable for use as a seed dressing is prepared by grinding and mixing the three ingredients.

Compound No. 13 of Table I 50% Mineral oil 2% China clay 48% EXAMPLE 11 A dustable powder is prepared by grinding and mixing the active ingredient with talc.

Compound No. 13 of Table I 5% Talc 95% EXAMPLE 12 A suspension concentrate is prepared by ball milling the ingredients to form an aqueous suspension of the ground mixture with water.

Compound No. 13 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 13 A wettable powder formulation is made by mixing together and grinding the ingredients until all are thoroughly mixed.

Compound No. 13 of Table I 25% Sodium lauryl sulphate 2% Sodium lignosulphonate 5% Silica 25% China clay 43D EXAMPLE 14 The compounds were tested against a variety of foliar fungal diseases of plants. 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. For the foliage diseases, the formulations (100 ppm active ingredient) were sprayed onto the foliage and 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. Tween 20, to give a final concentration of 0.05%, was added when the sprays were applied to cereals.

For most of the tests the compound was applied to the soil (roots) and to the foliage (by spraying) one or two days before the plant was inoculated with the disease. An exception was the test on Erysiphe graminis in which the plants were inoculated 24 hours before treatment.

Foliar 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 fourteen 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 II.

TABLE II Compound Puccinia Erysiphe Pyricularia Venturia Plasmopara Phytophthora No. recondita graminis oryzae inaequalis viticola infestans (Table I) (Wheat) (Wheat) (rice) (Apples) (Vines) (Tomatoes) 1 4 4 0 - 2 0 5 0 0 0 2 4 0 7 4 0 3 - 3 0 13 4 0 0 1 4 0 19 2 0 0 4 3 0 23 - 0 0 0 4 3 29 2 0 0 1 4 3 CHEMICAL FORMULAE (in description)

Scheme 1

Scheme 2 E A E A U2N 4 011 3U S03U < SO D B (XI) D B (XII) H E A E A 0 R1 0 R4- C -Nl S02N\ R4- C- N > 02C1 4 ii SO,-N D/B( U R2 U (11) VI) Scheme 3

Claims (6)

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

   A and B are independently H, fluoro, chloro, bromo, iodo, C1-4 alkyl, C1-4 alkoxy, halo(C1-4)alkyl, cyano, C1-4 alkoxycarbonyl, C1-4 alkoxymethyl, C1-4 alkylthiomethyl, C2-4 alkenyl, C24 alkynyl, C14 alkylcarbonyl, formyl, C1-4 alkylthio, carboxy, or nitro, provided that both A and b are not H; D and E are independently H or fluoro;R1 and R are independetly C1-4 alkyl, C3-6 alkenyl (optionally substituted with halogen), C3-6 alkynyl (optionally substituted with halogen), C1-4 alkoxy, C1-4 haloalkyl, C3-6 cycloalkyl, C3-6 cycloalkyl(C1-4)-alkyl, C1-4 alkoxy(C1-4)alkyl, C1-4 alkylthio(C1-4) alkyl, or cyano; or R1 and R together with the nitrogen to which they are attached join to form a morpholine, piperidine, pyrrolidine or azetidine ring, which may be optionally substituted with C1-4 alkyl; R3 is H;R4 is trichloromethyl, C2-8 alkyl (optionally substituted with halogen, C1-8 alkoxy, azido, nitro, isocyano, -NR5R6 [where R5 and R6 are independently C1-4 alkyl, C1-4 alkylcarbonyl or formyl], cyano, C1-4 alkylcarbonyl, formyl or R'S(O)n in which R' is C1-4 alkyl, C2-4 alkenyl or C2-4 alkynyl and n is 0, 1, or 2), cyclopropyl or cyclobutyl or cyclopentyl or cyclohexyl (all optionally substituted with C1-4 alkyl, halogen, C1-4 alkoxy, C1-4 alkylthio, C2-4 alkenyl, C2-4 alkynyl, cyano, C1-4 alkoxycarbonyl, azido, nitro, isocyano, or NR56[where R5 and R6 are independently H, C1-4 alkyl, C1-4 alkylcarbonyl, or formyl]), or R3 and R4 together with the group C(O)N to which they are attached join to form an azetidin-2-one ring which is optionally substituted with C1-4 alkyl; and X is O or S.
2. 2. A compound according to claim 1 in which R4 is R(CH3)2C- wherein R is halogen, C1-4 alkyl or C1-4 alkoxy.
3. 3. A compound according to claim 1 in which A is halo or C14 alkyl; R1 and R2 are C14 alkyl; R4 is C28 alkyl optionally substituted with 3 halogen or C14 alkoxy; B and R3 are U and X is 0.
4. 4. A process for preparing a compound according to claim 1, in which X is O and R3 is H, which comprises reacting in a suitable solvent in the presence of a base (a) a compound of formula (VI):

   with an amine RRNH; or (b) an anilinosulphonamide of formula (X):

   with an acid chloride R4COC1; or which comprises reacting in a suitable solvent in the presence of an activating agent the compound of formula (X) with an acid of formula R4COOH.

   wherein R1, R2, R4, A, B, D and E have the meanings given in claim 1.
5. 5. A fungicidal composition comprising a fungicidally effective amount of a compound according to claim 1 and a fungicidally acceptable carrier or diluent therefor.
6. 6. A method of combating fungi which comprises applying to plants, to the seeds of plants or 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 5.