FR2735772A1 - CIS-2-AMINOCYCLOPENTANE-1-CARBOXYLIC ACID DERIVATIVES, PROCESS FOR THEIR PREPARATION, COMPOSITIONS CONTAINING THEM, AND THEIR USE - Google Patents

Abstract

The invention relates to a compound of formula (I): (CF DRAWING IN BOPI) wherein X represents a halogen or an alkyl group, with the proviso that X does not represent a p-methyl group. Fungicidal compositions comprising a compound of formula (I) and a process for preparing compounds of formula (I) are described. APPLICATION: Use of compounds or compositions for combating fungi, in particular fungal infections of plants.

Description

 The subject of the present invention is derivatives of cis-2-aminocyclopentane-1-carboxylic acid, a process for their preparation, compositions containing them and a method for their use in order to combat fungi, in particular fungal infections of plants.

 (1R, 2S) -cis-2-aminocyclopentane-1- carboxylic acid is known and described, for example in 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 microbicides intended for agriculture is described in documents JP 63083004 and JP 63287753, in which tests are described to demonstrate specifically their microbicidal activity against pathogens
Phytophthora infestans (downy mildew of tomatoes), Pyricularia oryzae (rice browning), Pseudoperonospora cubensis (downy mildew of cucurbits), Fusarium oxysporum f. sD.

cucumerium (Fusarium wilt of cucurbits) and Alternaria brassicicola (black spot disease of Chinese cabbage).

A method of combating the pathogen
Plasmopara viticola by application of cis-2-aminocyclopentane-1-carboxylic acid or one of its salts or esters to a plant or an environment in which a plant is found is described in document WO 94/03061.

 The present invention provides a compound of formula (I), in which X represents a halogen or an alkyl group, provided that X does not represent a p-methyl group.

 The term "halogen" refers to fluorine, chromium, bromine and iodine.

 The alkyl group advantageously contains 1 to 24, preferably 6 to 20, especially 10 to 15, carbon atoms and can be straight chain or branched chain. It is, for example, a group n-C12H23 or CH3 (C (CH3) 2) 3 (CH2) 2.

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

 In another aspect, the present invention provides a compound of formula (I), wherein X is in the para position relative to the sulfonic acid group.

In a further aspect, the present invention provides a compound of formula (Ia), in which
X represents a C2 to C24 alkyl group (especially C12 alkyl in straight chain or branched chain forms, such as an n-C12H23 or CH3 (C (CH3) 2) 3 (CH2) 2) group.

 In another aspect, the present invention provides a compound of formula (Ia) in which X represents a C8 to C24 alkyl group (in particular C10 to C15 alkyl) in a straight chain or branched chain form (but preferably in a straight chain shape).

In another aspect, the present invention provides a compound of formula (Ia) in which X represents a C8 to C24 alkyl group (preferably C10 to
C15) preferably in a straight chain form which is present in admixture with another compound of formula (Ia) in which X represents a C8 to C24 alkyl group (preferably C10 to C15 alkyl) and preferably in the form of 'a straight chain.

 The compounds of formula (Ia) can be prepared by reacting a compound of formula (II) with a compound of formula (III) preferably in a solvent (which may consist of a mixture of two different solvents) and in the range of temperatures from 0 to 500C (for example ambient temperature).

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

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

The compounds of formula (III) are known in the literature and can be prepared by methods known in the literature or by adaptation of methods appearing in the literature. Alternatively, a compound of formula (III) can be acquired in pure form or as a mixture with one or more other compounds of formula (III). For example the
NANSA 1393 (available from Albright and Wilson) consists of p-dodecylphenylsulfonic acid in which the straight chain dodecyl group predominates; or ARYLAN SBC (available from Akcros Chemicals Limited or Harcros
Chemicals UK Limited) consists of p- (essentially straight chain dodecyl) phenylsulfonic acid.

 A mixture of compounds of formula (III) can be purified by conventional methods of the literature such as a combination of distillation (for example by means of a rotating column), of chromatography (for example liquid chromatography under high pressure) and transformation into derivative (such as an esterification - the acid being regenerated once the purification is completed).

 The compounds of formula (I) exhibit fungicidal activity against a range of plant diseases.

However, they are particularly active against the category of pathogens known as phycomycetes (equivalent to oomycetes). These agents include species of the genera Phytophthora, Plasmopara, Peronospora and
Pseudoperonospora. Examples of pathogens for which the compounds of the present invention are particularly useful for control purposes are Plasmopara viticola on the vine; other downy mildew such as Bremia lactucae on lettuce; PeronosDora spp. on soy, tobacco, onions and other hosts; Pseudoperonospora humuli on hops and Pseudoperonospora cubensis on cucurbits Phytohthora infestans on potatoes and tomatoes and other Phytophthora spp. on vegetables, strawberries, avocado, watercress, ornamental plants, tobacco, cocoa trees and other hosts; and
Pythium spp. on rice, horticultural plants, vegetables and lawn.

 The compounds can migrate acropetally / locally into the plant tissue. In addition, the compounds can be sufficiently volatile to be active in the vapor phase against fungi present on the plant.

 Accordingly, the present invention provides a method of combating fungi, which comprises applying to a plant, the seeds of a plant or the environment in which the plant or seeds is found in a quantity effective from the point of view fungicide of a compound corresponding to the above definition, or of a composition containing this compound.

 The compounds can be used directly in agriculture but are more conveniently formulated into compositions using a carrier or diluent. Thus, the present invention provides fungicidal compositions comprising a compound meeting the above definition and an acceptable carrier or diluent. It is preferred that all the compositions, consisting of solid formulations and liquid formulations, comprise 0.0001 to 95%, preferably 1 to 85%, for example 1 to 25 or 25 to 60%, of a compound corresponding to the definition cited above.

 When applied to plant foliage, the compounds of the present invention are applied at rates of 0.1 g to 10 kg, preferably 1 g to 8 kg, preferably 10 g to 4 kg, of ingredient active (compound of the present invention) per hectare.

 When used as seed disinfectants, the compounds of the present invention are used at rates from 0.0001 g (e.g. 0.001 g or 0.05 g) to 10 g, preferably from 0.005 g to 8 g , preferably from 0.005 g to 4 g, of active ingredient (compound of the present invention) per kilogram of seeds.

 The compounds can be applied in a number of ways. For example, they can be applied, in the formulated or unformulated state, directly to the foliage of a plant, to seeds or to another medium in which the plants grow or must be planted, or they can be sprayed, applied by dusting or applied in the form of a cream or paste, or they can be applied in the form of a vapor or in the form of slow-release granules.

 Application can be made to any part of the plant, including foliage, stems, branches or roots, or to the soil surrounding the roots, or to seeds before sowing, or to the soil generally , rice paddy water or hydroponics systems. The compounds of the present invention can also be injected into plants or sprayed onto vegetation using electrodynamic spraying techniques or other low volume methods.

 The term "plant" as used in the present invention includes seedlings, bushes and trees. Furthermore, the fungicidal method of the present invention includes preventive, protective, prophylactic, systemic and eradicating treatments.

 The compounds are preferably used in agriculture and horticulture in the form of a composition.

The type of composition used in any case depends on the particular application envisaged.

 The compositions may be in the form of powders for dusting or of granules comprising the active ingredient (compound of the present invention) and a diluent or solid support, for example fillers such as kaolin, bentonite, kieselguhr, dolomite, calcium carbonate, talc, pulverized magnesia, fuller's clay, gypsum, diatomaceous earth and porcelain earth. These granules can be preformed granules suitable for application to the soil without further treatment. These granules can be prepared by impregnating filler tablets with the active ingredient or by granulating a mixture of the active ingredient and a sprayed filler. The compositions for seed disinfection can comprise an agent (for example an oil mineral) intended to facilitate the adhesion of the composition to seeds; alternatively, the active ingredient can be formulated for seed disinfection using an organic solvent (e.g. N-methylpyrrolidone, propylene glycol or N, N-dimethylformamide). The compositions can also be in the form of wettable powders or water-dispersible granules comprising wetting or dispersing agents intended to facilitate dispersion in liquids. Powders and granules can also contain fillers and suspending agents.

 The compositions can also be in the form of soluble powders or granules, or in the form of solutions in polar solvents.

 Soluble powders can be prepared by mixing the active ingredient with a water-soluble salt such as sodium bicarbonate, sodium carbonate, magnesium sulfate or a polysaccharide, and with a wetting or dispersing agent to improve dispersibility / solubility in the water. The mixture can then be ground into a fine powder.

Similar compositions can also be granulated to form water-soluble granules. Solutions can be prepared by dissolving the active ingredient in polar solvents such as ketones, alcohols and glycol ethers. These solutions may contain surfactants to improve dilution in water and to prevent crystallization in a spray tank.

 Emulsifiable concentrates or emulsions can be prepared by dissolving the active ingredient in an organic solvent optionally containing a wetting or emulsifying agent, 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 trichloroethane, and alcohols such as benzyl alcohol, furfuryl alcohol , butanol and glycol ethers.

 Essentially insoluble solid suspension concentrates can be prepared by grinding in a ball mill or a ball mill with a dispersing agent, a suspending agent being incorporated to interrupt the sedimentation of the solids.

 The compositions intended to be used in the form of spray liquids can be in the form of aerosols in which the formulation is kept in a container under the pressure of a propellant gas, for example fluorotrichloromethane or dichlorodifluoromethane.

 The compounds of the present invention can be mixed in the dry state with a pyrotechnic mixture to form a composition making it possible to generate in enclosed spaces a smoke containing the compounds.

 Alternatively, the compounds can be used in micro-encapsulated form. They can also be prepared in biodegradable polymeric formulations to achieve slow controlled release of the active substance.

 By incorporating suitable additives, for example additives intended to improve absorption, distribution, adhesive power and resistance to rain on the treated surfaces, the different compositions can be better adapted to various uses. Other additives can be incorporated to improve the biological efficacy of the various formulations. These additives may be surface-active materials intended to improve wetting and retention on the surfaces treated with the formulation and also the absorption and mobility of the active substance, or may also comprise spraying additives based on oil, for example certain mineral oils and natural vegetable oils (such as soybean oil and rapeseed oil) or mixtures of these additives with other adjuvants.

 The compounds of the present invention can be used in the form of mixtures with fertilizers (for example fertilizers containing nitrogen, potassium or phosphorus). Compositions comprising only fertilizer granules containing, for example by coating, a compound of formula (I) are preferred. These granules suitably contain up to 25% by weight of the compound. Consequently, the present invention also provides a fertilizer composition comprising a fertilizer and the compound of general formula (I) or one of its salts or metal complexes.

 Wettable powders, emulsifiable concentrates and suspension concentrates usually contain surfactants, for example a wetting agent, a dispersing agent, an emulsifying agent or a suspending agent. These agents can be cationic, anionic or nonionic agents.

 Suitable cationic agents are quaternary ammonium compounds, for example cetyltrimethylammonium bromide. Suitable anionic agents are soaps, salts of aliphatic monoesters of sulfuric acid (e.g. sodium lauryl sulfate), and salts of sulfonated aromatic compounds (e.g. sodium dodecylbenzenesulfonate, sodium lignosulfonate, calcium or ammonium, butylnaphthalenesulfonate, and a mixture of diisopropyl- and triisopropylnaphthalenesulfonates).

 Suitable nonionic agents are the condensation products of ethylene oxide with fatty alcohols such as oleyl alcohol or cetyl alcohol, or with alkylphenols such as octyl- or nonylphenol and octylcresol . Other nonionic 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 (eg polyvinylpyrrolidone and sodium carboxymethylcellulose), and swellable clays such as bentonite or attapulgite.

 The compositions intended to be used in the form of 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 long periods of time and, after such storage, be able to be diluted with water in order to form aqueous preparations which remain homogeneous for a sufficient time to allow their application by means of a conventional spraying device. Concentrates can conveniently contain up to 95%, suitably 1 to 85%, for example 1 to 25 W or 25 to 60, by weight of the active ingredient. After dilution to form aqueous preparations, these preparations may contain amounts variables of the active ingredient depending on the intended purpose, but an aqueous preparation containing 0.0001 to 10%, for example 0.005 to 10%, by weight of active ingredient can be used.

 The compositions of the present invention can contain other compounds endowed with biological activity, for example compounds having a similar or complementary fungicidal activity or which possess a activity of regulation of plant growth, herbicide, or insecticide.

 An additional fungicidal compound may be present in the composition of the present invention. By incorporating another fungicide, the resulting composition may have a broader spectrum of activity or a higher degree of intrinsic activity than the compound of general formula (I) alone. In addition, the other fungicide can have a synergistic effect on the fungicidal activity of the compound of general formula (I). Examples of fungicidal compounds which can be incorporated into the composition of the present invention are acid (RS) - l-aminopropylphosphonique, le (RS) -4- (4-chlorophényl) -2-phenyl-2- (1H-1,2,4-triazole-1-yl-methyl) butyronitrile, le (Z) -N-but -2-enyloxymethyl-2-chloro-2 ', 6'-diethylacetanilide, 1- (2-cyano-2-methoxyiminoacetyl) -3-ethylurea, 4- (2,2-difluoro-1,3- benzo dioxole-4-yl) pyrrole- 3-carbonitrile, 1e4-bromo-2-cyano-N, N- dimethyl-6-trifluoromethylbenzimidazole-1-sulfamide, 5-ethyl-5,8-dihydro- 8- acid oxo (1,3) -dioxol- (4,5-g) quinoline7-carboxylic, v- [N- (3-chloro-2,6-xylyl) -2-methoxyacéta- mido] -g-butyrolactone, N- (2-methoxy-5-pyridyl) -cyclopropanecarboxamide, alanycarb, aldimorph, ampropylfos, anilazine, azaconazole, BAS 490F, benalaxyl, benomyl, biloxazole, binapacryl , bitertanol, blasticidin S, bromuconazole, bupirimate, butenachlor, buthiobate, captafol, captan, carbendazim, carbendazim hydrochloride, carboxin, quinomethionate, chlorbenzthiazone, chloroneb, chlorothalonil, chlorozolinacon , copper-containing compounds such as copper oxychloride, copper oxyquinolate, copper sulfate, copper tallate and Bordeaux mixture, cycloheximide, cymoxanil, cyproconazole, cyprofuram, debacarb, 1, di-2-pyridyl disulfide dioxide, dichlofluanide, dichlone, diclobutrazole, diclomezin, dicloran, didecyldimethylammonium chloride, diethofencarb, difenoconazole, 0,0-di-iso- propyl-5-benzyl-thiophosphate, ledimefluazole, dimetconazole, dimethomorph, dimethirimol, diniconazole, dinocap, dipyrithione, ditalimfos, dithianon, dodemorph, dodine, doguadine, edifenphos zole, etaconazole, ethirimol, ethoxyquin, (Z) -N-benzyl -N- ([methyl (methyl - thioethyl ideneaminooxycarbonyl) amino] thio) -B-alaninate, etridiazole, fenaminosulph, fenapanil, fenarimol, fenbuconazole, fenfuram, fenpiclonil, fenpropidine, fenpropimorph, fentine acetate, fentine hydroxide, ferbam, ferimzone, fluazinam, fludiox fluoroimide, fluquinconazole, flusilazole, flutolanil, flutriafol, folpet, fuberidazole, furalaxyl, furconazole-cis, guazatine, hexaconazole, hydroxyisoxazole, hymexazole, ICIA5504, imazil , imibenconazole, ipconazole, iprobenfos, iprodione, isopropanylbutylcarbamate, isoprothiolane, kasugamycin, mancozeb, maneb, mepanipyrim, mepronil, metalaxyl, metconazole, methfox , metiram, metiram-zinc, metsulfovax, myclobutanil, NTN0301, neoasozine, dimethyldi nickel thiocarbamate, nitrothal-isopropyl, nuarimol, ofurace, organic mercury compounds, oxadixyl, oxolinic acid, oxycarboxin, pefurazoate, penconazole, pencycuron, phenazine-oxide, phosetyl-Al, phosphorus-derived acids, phthalide, polyoxin D, polyram, probenazole, prochloraz, procymidone, propamocarb, propamocarb hydrochloride, propiconazole, propineb, propionic acid, prothiocarb , pyracarbolid, pyrazophos, pyrifenox, pyrimethanil, pyroquilon, pyroxyfur, pyrrolnitrine, quaternary ammonium compounds, quinconazole, quinomethionate, quintozene, rabenazole, sodium pentachlorophenate, streptom sulfur, tebuconazole, techlofthalam, tecnazene, tetaconazole, thiabendazole, thicyofene, thifluzamide, 2- (thiocyanomethylthio) benzothiazole, thiophanate-methyl, thiram, timibenconazole, tol clofos-methyl, tolylfluanide, 1,1'-iminodi (octamethylene) diguanidine triacetate, triadimefon, triadimenol, triazbutyl, triazoxide, tricyclazole, tridemorph, triforine, triflumizole, triticonazole A, vapam, vinclozoline, XRD-563, zineb and ziram. The compounds of general formula (I) can be mixed with soil, peat or other rooting media to protect plants from seed, soil or leaf fungal diseases.

The following examples illustrate the present invention. In all examples, the following abbreviation is used
PF = melting point.

EXAMPLE 1
This example illustrates the preparation of a cis-2-amino-cyclopentane-lcarboxylic acid 4-dodecylphenylsulfonate.

 ARYLAN SBC Acid (available from Akcros Chemicals Limited) is added to a solution of cis-2-aminocyclopentane-1-carboxylic acid (3.00 g) in water (20 ml) at 200 ° C., with stirring. (7.58 g) in 1,4-dioxane (20 ml). The resulting clear solution was stirred at 200C for 1.5 hours, after which time it was concentrated under reduced pressure, leaving a thick mobile oil which gradually gave a semi-solid substance at rest. Trituration with acetone gave the title compound as a white solid (8.221 g, m.p. 141-30C).

EXAMPLE 2
This example illustrates the preparation of a 4-dodé cylphenylsulfonate of cis-2-aminocyclo-pentane-lcarboxylic acid.

 To a solution of NANSA 1393 (available from Albright and Wilson) (3.79 g) in anhydrous dichloromethane (50 ml) at 200C was added, in portions and with stirring, cis-2-aminocyclopentane acid. l-carboxylic (1.5 g). A slight release of heat was noted. The reaction mixture was stirred at 200C for 2 hours, after which time it was concentrated under reduced pressure, leaving an oil. The oil was triturated with diethyl ether to give the title compound as a white solid (3.86 g, m.p. 130.5-133.50C).

EXAMPLE 3
The products of Examples 1 and 2 were tested against the pathogenic agent Plasmopara viticola by the following general method.

 Vine plants were grown in soilless potting compost in 7 cm diameter pots. The compounds were diluted in water to the required concentration immediately before use. The formulations (300 millionths of free base, i.e. 300 millionths of cis-2-aminocyclopentane-1-carboxylic acid) were sprayed on the foliage of young plants (5 or 6 leaves) in the compost. Spray liquids were applied for maximum retention.

 The compounds were applied to the foliage (by spraying) 7 days before seeding the plant with the pathogen. The leaf pathogen Plasmopara viticola was applied by spraying a suspension of zoosporangia on the leaves of the test plants. After seeding, the plants were placed in an appropriate environment to allow the infection to take place and were incubated until the disease was ready for evaluation. The period between seeding and evaluation was 6 days.

 The extent of the disease (i.e. the leaf area covered by the actively sporulating pathogen) on the third leaf (which leaf is the oldest) of each of the treated plants was noted.

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

Example product% of disease on control
1 94
2 99
CHEMICAL COMPOUNDS (APPEARING IN THE DESCRIPTION)

 It goes without saying that the present invention has only been described for explanatory purposes, but in no way limiting, and that numerous modifications can be made thereto without departing from its scope.

Claims (7)

 1. Compound characterized in that it corresponds to formula (I)

 wherein X represents a halogen or an alkyl group, provided that X does not represent a p-methyl group.  2. Compound according to claim 1, characterized in that X represents a C2 to C24 alkyl group.  3. Compound according to claim 1 or 2, characterized in that it corresponds to the formula (Ia)

 wherein X represents a straight chain or branched chain C10 to C15 alkyl group.  4. Method for preparing a compound according to claim 1, characterized in that it comprises the reaction of a compound of formula (II)

  with a compound of formula (III)

 at a temperature in the range of 0 to 500C.  5. A fungicidal composition characterized in that it comprises a fungicidal effective amount of a compound according to claim 1 and a fungicidal acceptable carrier or diluent.  6. Method for combating fungi, characterized in that it comprises the application to plants, to plant seeds or to the medium in which the plants or seeds are found, of a compound according to claim 1 or a composition according to claim 5.  7. Compound characterized in that it corresponds to formula (I) essentially as described above with reference to Example 1 or 2.