GB2290540A - Fungicidal salt of cis-2-amino-cyclopentane-1-carboxylic acid with a substituted benzenesulphonic acid - Google Patents

Abstract

A compound of formula (I): <IMAGE> wherein X is halogen or alkyl (provided that X is not p-methyl); fungicidal compositions comprising a compound of formula (I); methods of using said compounds of compositions to combat fungi, especially fungal infections of plants; and a process for preparing compounds of formula (I) are disclosed.

Description

CHEMICAL COMPOUNDS The present invention relates to cis-2-aminocyclopentane-1-carboxylic acid derivatives, to a process for preparing them, to compositions comprising them and to a method of using them to combat fungi, especially fungal infections of plants.

(1R,2)-Cis-2-aminocyclopentane-1-carboxyl ic acid is known and described in, for example, J. Antibiotics, Vol XLII, No 12, 1749 and 1756 (1989); J. Antibiotics Vol XLIII, No 1, 1(1990) and J. Antibiotics Vol XLIII, No 5, 513(1990). Its antifungal activity is also described.

The use of cis-2-aminocyclopentane-1-carboxylic acid and its salts and esters as agricultural microbiocides is disclosed in JP 63083004 and JP 63287753, where tests are described to show specifically their microbiocicidal activity against the pathogens: Phvtophthora infestans (tomato blight), Pvricularia orvzae (rice leaf blast), Pseudoperonospora cubensis (cucumber downy mildew), Fusarium oxysporum L ip. cucumerium (cucumber Fusarium wilt) and Alternaria brassicicola (Chinese cabbage sooty disease).

A process for combating the pathogen Plasmopara viticola by applying cis-2-aminocyclopentane-1-carboxylic acid or a salt or an ester thereof to a plant or locus thereof is disclosed in WO 94/03061.

The present invention provides a compound of formula (I), wherein X is halogen or alkyl, provided that X is not e-methyl.

Halogen includes fluorine, chlorine, bromine and iodine.

The alkyl group preferably contains from 1 to 24, more preferably 6 to 20, especially 10-15, carbon atoms and can be straight or branched chain.

It is, for example, n-C12H23, or CH3(C(CH3)2)3(CH2)2.

In one aspect the present invention provides a compound of formula (I), wherein X is alkyl.

In another aspect the present invention provides a compound of formula (I), wherein X is para disposed to the sulphonic acid group.

In a further aspect the present invention provides a compound of formula (Ia), wherein X is C2 24 alkyl (especially C12 alkyl in straight or branched chain forms, such as n-C12H23 or CH3(C(CH3)2)3(CH2)2).

In another aspect the present invention provides a compound of formula (Ia) wherein X is C8~24 alkyl (especially C10-15 alkyl) in straight or branched chain form (but preferably in straight chain form).

In another aspect the present invention provides a compound of formula (Ia) wherein X is C8-24 (preferably C10~15 alkyl) and preferably in straight chain form which is in admixture with another compound of formula (Ia) wherein X is C824 (preferably C10-15 alkyl) and preferably in straight chain.

Compounds of formula (I) may be prepared by reacting a compound of formula (II) with a compound of formula (III) preferably in a solvent (which may be a mixture of 2 different solvents) and in the temperature range 0-500C (such as room temperature).

Thus, in a further aspect the present invention provides a process for preparing a compound of formula (I).

The compound of formula (II) can be prepared by known literature methods.

Compounds of formula (III) are known in the literature and may be prepared by known literature methods or by adapting literature methods.

Alternatively a compound of formula (III) may be purchased either pure or in a mixture with one or more other compounds of formula (III). For example NANSA 1393 (available from Alright and Wilson) is g-dodecyl- phenylsulphonic acid in which straight chain dodecyl predominates; or ARYLAN SBC (available from Akcros Chemcials Limited or Harcros Chemicals UK Limited) is D-(straighter chain dodecyl)phenylsulphonic acid.

A mixture of compounds of formula (III) can be purified by standard literature methods such as a combination of distillation (for example using a spinning band), chromatography (for example high pressure liquid chromatography) or derivatisation (such as esterification - the acid being regenerated once purification has been completed).

The compounds of formula (I) 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: Plasmonara viticola on vines; other downy mildews such as Bremia lactucae on lettuce; Peronosoora spp. on soybeans, tobacco, onions and other hosts; Pseudoperonospora humuli on hops and Pseudoneronospora cubensis on cucurbits; Phvtonhthora infestans on potatoes and tomatoes and other Phvtophthora spp. on vegetables, strawberries, avocado, pepper, ornamentals, tobacco, cocoa and other hosts; and Pvthium spp. on rice, horticultural plants, vegetables and turf.

The compounds may move acropetally/locally in plant tissue. Moreover, the compounds may be volatile enough to be active in the vapour phase against fungi on the plant.

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 hgereinbefore 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. 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 compound as hereinbefore defined.

When applied to the foliage of plants, the compounds of the invention are applied at rates of 0.19 to 10Kg, preferably 1g to 8Kg, more preferably 10g to 4Kg, of active ingredient (invention compound) per hectare.

When used as seed dressings, the compounds of the invention are used at rates of 0.00019 (for example 0.0019 or 0.059) to 109, preferably 0.005g to 89, more preferably 0.0059 to 4g, of active ingredient (invention compound) per kilogram of seed.

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, systemic 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.

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 dichlorodifluormethane.

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 uptake, 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, or blends of them with other adjuvants.

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, a compound of formula (I) 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 powders1 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 aromaqtic 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 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 ingredient depending upon the intended purpose, but an aqueous preparation containing 0.0001 to 10%, for example 0.005 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.

An additional fungicidal compound may be present in the composition of the invention. By including another fungicide, the resulting composition can have a broader spectrum of activity or a greater level of intrinsic 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 (fLS)-1-aminopropylphosphonic acid,(RS)-4-(4-chlorophenyl)-2-phenyl-2- -(lH-1,2,4-triazol-1-yl-methyl)butyronitrile,(Z)-N-but-2-enyloxymethyl-2- -chloro-2',6'-diethylacetanilide, 1-(2-cyano-2-methoxyiminoacetyl)-3-ethyl urea, 4-(2,2-difluoro-1,3-benzodioxol-4-yl)pyrrole-3-carbonitrile, 4-bromo-2-cyano-N,N-dimethyl-6-trifluoromethylbenzimidazole-1-sulphonamide, 5-ethyl-5,8-dihydro-8-oxo(1,3)-dioxol-(4,5-a)quinoline-7-carboxylic acid, a-[ff-(3-chloro-2,6-xylyl)-2-methoxyacetamidoj-g-butyrolactone, N-(2-methoxy-5-pyridyl)-cyclopropane carboxamide, alanycarb, aldimorph, ampropylfos, anilazine, azaconazole, BAS 490F, benalaxyl, benomyl, biloxazol, binapacryl, biteranol, blasticidin S, bromuconazole, bupirimate, butenachlor, buthiobate, captafol, captan, carbendazim, carbendazim chlorhydrate, carboxin, chinomethionate, chlorbenzthiazone, chloroneb, chlorothalonil, chlorozolinate, clozylacon, copper containing compounds such as copper oxychloride, copper oxyquinolate, copper sulphate1 copper tallate, and Bordeaux mixture, cycloheximide, cymoxanil, cyproconazole, cyprofuram, debacarb, di-2-pyridyl disulphide 1,1'-dioxide, dichlofluanid, dichlone, diclobutrazol, diclomezine, dicloran, didecyl dimethyl ammonium chloride, diethofencarb, difenoconazole, Q,Q-di-iso-propyl-S-benzyl thiophosphate, dimefluazole, dimetconazole, dimethomorph, dimethirimol, diniconazole, dinocap, dipyrithione, ditalimfos, dithianon, dodemorph, dodine, doguadine, edifenphos, epiconazole, etaconazole, ethirimol, ethoxyquin, ethyl (Z)-N-benzl-N-([methyl(methyl-thioethylideneamino-oxyCarbonyl)amino]thio)- -'3-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, furconazole-cis, guazatine, hexaconazole, hydroxyisoxazole, hymexazole, ICIA5504, imazalil, imibenconazole, ipconazole, iprobenfos, iprodione, isopropanyl butyl carbamate, isoprothiolane, kasugamycin, mancozeb, maneb, mepanipyrim, mepronil, metal axyl, metconazole, methfuroxam, metiram, metiram-zinc, metsulfovax, myclobutanil, NTN0301, neoasozin, nickel dimethyldithiocarbamate, nitrothal-isopropyl, nuarimol, ofurace, organomercury compounds, oxadixyl, oxoloinic acid, oxycarboxin, pefurazoate, penconazole, pencycyron, phenazin oxide, phosetyl-Al, phosphorus acids, phthalide, polyoxin D, polyram, probenazole, prochloraz, procymidone, propamocarb, propamocarb hydrochloride, propiconazole, propineb, propionic acid, prothiocarb, pyracarbolid, pyrazophos, pyrifenox, pyrimethanil, pyroquilon, pyroxyfur, pyrrolnitrin, quaternary ammonium compounds, quinconazole, quinomethionate, quintozene, rabenazole, sodium pentachlorophenate, streptomycin, sulphur, tebuconazole, techlorfthal am, tecnazene, tetraconazole, thiabendazole, thicyofen, thifluzamide, 2-(thiocyanomethylthio)benzothiazole, thiophanate-methyl, thiram, timibenconazole, tolclofos-methyl, tolylfluanid, triacetate salt of 1,1'-iminodi(octamethylene)diguanidine, triadimefon, triadimenol, triazbutyl, triazoxide, tricyclazole, tridemorph, triforine, triflumizole, triticonazole, validamycin A, vapam, vinclozolin, XRD-563, zineb and ziram. 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.

The following Examples illustrate the invention. Throughout the Examples the following abbreviation is used: m.pt. = melting point EXAMPLE 1 This Example illustrates the preparation of a 4-dodecylphenylsulphonate salt of cis-2-amino-cyclopentane-1-carboxylic acid.

To a solution of cis-2-aminocyclopentane-1-carboxylic acid (3.00g) in water (20ml) at 200C was added, with stirring, ARYLAN SBC Acid (available from Akcros Chemcials Limited) (7.58g) in 1,4-dioxan (20ml). The resulting clear solution was sitrred at 200C for 1.5 hours after which it was concentrated under reduced pressure to leave a thick, mobile oil which gradually gave a semi-solid on standing. Triturating with acetone gave the title compound as a while solid (8.221g, m.pt. 141-3"C).

EXAMPLE 2 This Example illustrates the preparation of a 4-dodecylphenylsulphonate salt of cis-2-aminocyclo-pentane-1-carboxylic acid.

To a solution of NANSA 1393 (available from Alright and Wilson)(3.79g) in dry dichloromethane (50ml) at 20"C was added, portionwise and with stirring, cis-2-aminocyclopentane-1-carboxylic acid (1.5g). A slight exotherm was noted. The reaction mixture was stirred at 20"C for 2 hours after which it was concentrated under reduced pressure to leave an oil. The oil was triturated with diethyl ether to provide the title compound as a white solid (3.869, m.pt. 130.5-133.5"C).

EXAMPLE 3 The products of EXAMPLES 1 and 2 were tested against the pathogen Plasmopara viticola by the following general method.

Vine plants were grown in soil less potting compost in 7cm diameter pots. The compounds were diluted in water to the required concentration immediately before use. The formulations (300 ppm of free base, ie 300 ppm of cis-2-aminocyclopentane-1-carboxylic acid) were sprayed on to the foliage of the young plants (5 to 6 leaves) in the compost. The sprays were applied to maximum retention.

The compounds were applied to the foliage (by spraying) seven days before the plant was inoculated with the disease. The foliar pathogen Plasmopara viticola was applied by spray as a zoosporangial suspension 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 was six days.

The disease level present (ie the leaf area covered by actively sporulating disease) on the third leaf (leaf one being the oldest leaf) of each of the treated plants was recorded.

Each assessment was then expressed as a percentage of the level of disease present on the untreated control plants.

Product of EXAMPLE % Disease Control 1 94 2 99 CHEMICAL COMPOUNDS (AS IN DESCRIPTION)

Claims (7)

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

   where X is halogen or alkyl, provided that X is not e-methyl.
2. 2. A compound as claimed in claim 1 wherein X is C224alkyl.
3. 3. A compound as claimed in claim 1 or 2 of formula (Ia):

   wherein X is C10-15 alkyl in straight or branched chain form.
4. 4. A process for preparing a compound according to claim 1 comprising reacting a compound of formula (II):

   with a compound of formula (III):

   at a temperature in the range 0-500C.
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 locus of the plants or seeds, a compound according to claim 1 or a composition according to claim 5.
7. 7. A compound of formula (I) substantially as hereinbefore described with reference to Example 1 or 2.