CA1314291C - Optically active tetrahydro-2-furanone derivative as microbicide - Google Patents

Abstract

5-16256/1+2/=/ZFO

Optically active tetrahydro-2-furanone derivative as microbicide Abstract of the Disclosure The (aS,1'R) enantiomer as well as the pair of (aR,1'S) and (aS,1'R) enantiomers and the (aR,1'R)(aS,1'R) diastereoisomers of the compound of formula

Description

- I - 1 3 ~ 4 2 9 1 5-1625611+2/=lZFO

Optically active tetrahydro-2-furanone derivative as microbicide The present invention relates to optically active (aS,l'R)-3-[N-(methoxyacetyl~-N-(3-chloro-2,6-dimethylphenyl)]aminotetrahydro-furan-2-one, to the preparation thereof, to microbicidal co~po-sitions which contain this compound as active component, and to theuse of such compositions as microbicides in plant protection.

3-[N-(Methoxyacetyl)-N-(3-chloro-2,6-dimethylphenyl)7aminotetra-hydrofuran-2-one is disclosed as a microbicidally active compound in German Offenlegungsschrift 2 804 299 or in the corresponding GB patent specification 1 577 702. According to this publication, the compound of formula I
/ \
Cl\ /CH3 1* O
' ~ ` ~ `a/ (I), CH3 ~CH2OCH3 has, as structural feature, a centre of asymmetry at the position marked by an asterisk. In the form of the racemate, thls compound can be resolved into the optical antipodes in conventional manner, the different configurations having microbicidal activity of different strength.

The publication r~ferred to above gives no indication as to how great this difference in activity may be, nor does it say which of the two antipodes actually has the greater micro~icidal activity.

Furthermore, the above publication makes no reference, within the broad chemical scope thereof, to further possibilities of isomerism beyond the furanone ring.

However, the compound of formula I conventionally obtainable as racemate exists not only in the form of a single pair of enantiomers by virtue of the asymmetric substitution at the lndicated *C-atom, but as a mixture of 4 isomers, i.e. of two diastereoisomeric pairs of enantiomers.

The reason is that the molecule, in addition to containing the aforementioned centre of asymmetry, has a rotation isomerism (atropisomerism) contingent on the chiral axis ( ~
and caused by the asymmetric chlorine-substitution of the 2,6-di-phenyl ring in which rotation is hindered. Racemic 3-[N-(methoxy-acetyl)-N-(3-chloro-2,6-dimethylphenyl)]aminotetrahydrofuran-2-one, named as compound 30 in German Offenlegungsschrift 2 804 299, is a 1:1 mixture consisting of two diastereoisomeric pairs of enantiomers which melt at 140~C and 115C respectively and which can be separ-ated from each other. A suitable method of separation is adsorption chromatography. Both pairs of enantiomers, as racemates, can be resolved into the optical antipodes in conventional manner. The (aS,l'S) and (aR,l'R) enantiomers of 3-[N-methoxacetyl~-N-(3-chloro-2,6-dimethylphenyl)]aminotetrahydrofuran-2-one can be isolated from the pair of (aS,l'S~(aR,1'R) enantiomers which melts at 140C and is obtained as by-product, and the (aR,l'S) and (aS,l'R)-3 enantiomers of 3-~N-(methoxyacetyl)-N-(3-chloro-2,6-di-methylphenyl)]aminotetrahydrofuran-2-one can be isolated from the desired pair of (aR,l'S)(aS,l'R) enantiomers which melts at 11~C, for example by chromatography on an optically active phase.

The approximate 1:1 composition of the diastereoisomeric pairs of enantiomers obtainable according to German Offenlegungsschrift 2 8Q4 299 varies from 45 to 55 %.

1 31~291 It has now been found that the (aS,l'R) enantiomer of 3-~N-(me-thoxyacetal)-N-(3-chloro-2,6-dimethylphenyl)]aminotetrahydro-furan-2-one has a surprisingly strongly enhanced microbicidal activity in conjunction with an unexpectedly long duration of action compared with the mixture of isomers of formula I.

Accordingly, the present invention relates also to a compound of formula I in which the proportion of (aS,l'R) enantiomer is greater than the 25 % by weight to be theoretically expected of a racemic mixture of two diastereoisomeric pairs of enantiomers. In 8 narrower sense, the present invention relates to a compound of formula I in which the proportion of (aS,l'R) enantiomer is at least 28 % by weight, preferably at least 40 % by weight and, most preferably, at least 50 % by weight. Most especially preferred for practical purposes as plant fungicide is a compound of formula I in which the proportion of (aS,l'R)enantiomer is at least 70 % by weight, in particular at least 90 % by weight. The invention further relates to the pure (aS,l'R) enantiomer of 3-1N-(methoxyacetylj-N~(3-chloro-2,6-dimethylphenyl)]aminotetrahydrofuran-2-one.

Racemic (aR,1'S)(aS,l'R)-3-[N-(methoxyacetyl)-N-(3-chloro-2,6-di-methylphenyl)]aminotetrahydrofuran-2-one also exhibits substantially increased microbicidal activity and duration of action compared with the mlxture of isomers of formula I, the extent of said increase in activity being smaller than that oF the (aS,1'R) enantiomer.

The pair of ~aR,l'S)(aS,l'R) enantiomers in an approximate ratio o~
1:1 of these two components (45:55 to 55:45), is particularly suitable for use as plant fungicide~

Hence the present invention also relates to the racemic mixture of (aR,l'S) and (aS,l'R) isomers.

~31~291 The preparation of the (aS,l'R) enantiomer of 3-[N-(methoxyacetyl)-N-(3-chloro-2,6-dimethylphenyl)]aminotetrahydrofuran-2-one can be effected by a two-step chromatographic separation of the mixture of isomers of formula I and of (aR,l'S)(aS,l'R)-3-EN-tmethoxyacetyl)-~-(3-chloro-2,6-dimethylphenyl)]aminotetrahydrofuran-2-one obtained therefrom which melts at 115C.

The first step of the separation of the racemic mixture of two diastereoisomeric pairs of enantiomers takes place on a stationary solid phase using a liquid phase (eluant) to giV2 the desired pair of (aR,l'S)(aS,l'R) enantiomers. For this separation step it is possible to use all adsorbing materials known to the skilled person, e.g. silica gel, Al203, or organic polymer resins ~polyamide, polyacrylamide and the like), as well as agarose, sepharose and, in particular, modified cellulose. Acetylated or benzoylated cellulose is especially suitable. The pair of (aR,l'S)(aS,l'R) enantiomers can then be used as obtained in formulated form as plant fungicide or can be further resolved.

The second separation step comprises separating the solution of the racemic mixture of (aR,l'S)- and (aS,l'R)-3-[N-(methoxyacetyl)-N-(3-chloro-2,6-dimethylphenyl)]aminotetrahydrofuran-2-one into the individual enantiomers on an optically active phase and isolating (aS,l'R)-3-lN-(methoxyacetyl)-N-(3-chloro-2,6-dimethylphenyl)]ami-notetrahydrofuran-2-one from the solution.

Acylated cellulose such as acetylated or benzoylated cellulose can be used for example as optically active phase. Examples are tri-acetyl cellulose and tris(3-methylbenzoyl)cellulose.

In a preferred variant of the above described method of separation, all four enantiomers of the mixture of isomers obtainable according to German Offenlegungsschrift 2 ~04 299 can be separated in only one step instead of two steps. In this variant, the dilute solution of the mixture to be separated in a 1:1 mixture of hexane/isopropanol is adsorbed on to modified cellulose as optically active phase and eluted in succession with a suitable mobile phase (eluant). The solution is preferably adsorbed on to acylated cellulose (e.g.
acetylated or benzoylated cellulose), preferably tris(3-methyl-ben~oyl)cellulose, as stationary phase, and subsequently eluted with a 1:1 to 9:1 mixture of hexane/isopropanol. The solutions of the eluted isomers are collected in fractions and the isomers are isolated as residue after evaporation of the mixture of solvents.

In another preferred variant of the preparatory process, the pair of (aS,l'S)(aR,l'R) enantiomers which melts at 140C and is obtainable as by-product after separation of the mixture of isomers can be racemised once more to the starting mixture. Such racemisation or isomerisation can be effected for example by heating the pair of (aS,l'S)(aR,l'R) enantiomers to 140-180C in the melt, preferably in the presence of a tetraalkylammonium salt, e.g. tetrabutyl-ammonium bromide, until equilibrium is attained. The resultant product, which again consists of two pairs of diastereoisomeric enantiomers, can be recycled to the separation process. The present invention also relates to this additional reisomerisation process.

The racemisation of (aR,1'S)-3-[~-(methoxyacetyl~-N-(3-chloro-2,6-dimethylphenyl)]aminotetrahydrofuran-2-one by opening the lactone ring with alkali and by the subsequent cyclisation under suitable conditions is also possible. The racemate obtained by this pro-cedure can also be recycled to the separation process.

The absolute configuration of the enantiomers was determined by X-ray structural analysis and can be illustrated as follows:
/ \
~CH3 H.
(aS,l'S) enantiomer) ~
=~ C0-CH2-U-CH3 C~ \CH3 ! =o (aR,l'R) enantiomer) C~-CH2-O-CH 3 C~ /CH3 H.,i _ ! o (aR,l'S) enantiomer) ~
\CH 3 CO - CH 2 - O - CH 3 /CH3 H~-(aS,l'R) enantiomer) ~
=-\ CO-CH2-O-CH3 C~ CH3 The invention also relates to a process for obtaining (aR,l'R)-(aS,l'R)-3-[N-(methoxyacetyl~-N-(3-chloro-2,6-dimethylphenyl)]ami-notetrahydrofuran-2-one, which has also a substantially greater fungicidal activity than the racemate disclosed in German Offen-legungsschrift 2 804 2~. This pair of diastereoisomers in a ratio of 1:1 or approximately 1:1 (45:55 to 55:45) is an especially suitable plant fungicide, and it likewise constitutes a further object of this invention.

In the preparatory process of this invention, a combination of a) a method of separating two isomers of an intermediate and b) a subsequent chlorination process is used in accordance with the following scheme:

, 131~2~1 N~ separation / H3 H~ ~
~=~\ \ [e.g. chromatography] =~\ CO-CH2-O-CH3 (racemats) (l'R~ enantiomer ~ - ~ H~-Cl2 /
b) (l'R) enantiomer ~ (aR,l'R) enantiomer ~ - N\ - =0 C~CH2 I}CH3 Cl CH3 (aS,1'R) enantiomer The mixture of (aR,l'R) and (aS,l'R) enantiomers resulting from the chlorination can be used as obtained as fungicide or separated in turn by chromatography to obtain the (aS,l'R) enantiomer by the method of the initial separation step a).

Racemic 3-[N-methoxyacetyl)-N-(2,6-dimethylphenl)]aminotetrahydro-furan-2-one used as starting material is also disclosed in German Offenlegungsschrift 2 804 299 or GB patent specification 1 577 702.

For the above described chromatographic separation step a) it is possible to use all adsorbing materials known to the skilled person, e.g. silica gel, Al203, or organic polymer resins (polyamide, polyacrylamide and the like), and also agarose, sepharose and, in particular, modified cellulose. Acetylated or benzoylated cellulose is especially suitable.

131~2~1 The chlorination of (1'R)-3-N-(methoxyacetyl)-N-(2,6-dimethyl-phenyl)]aminotetrahydrofuran-2-one is conveniently carried out in an inert solvent. Suitable solvents are chlorinated aromatic and aliphatic hydrocarbons such as chlorobenzene, methylene chloride, chloroform, carbon tetrachloride and the like. It is preferred to use a lower alkanecarboxylic acld, e.g. formic acid, acetic acid or propionic acid. A preferred solvent is formic acid.

The chlorination is preferably carried out in the temperature range from 0 to 50C, e.g. at room temperature.

It is also useful to carry out the chlorination in the presence of a Lewis acid such as aluminium chloride, zinc chloride, iron(IlI) chloride or -tin(IV) chloride. A preferred Lewis acid is iron~III) chloride. The Lewis acid is used in an amount of 1-8 ~O~ based on the ~l'R) isomer to be chlorinated. The chlorination can also be carried out without a Lewis acid. The chlorination is carried out under normal pressure or slightly elevated pressure. Sulfuryl chloride is used for the chlorination; but chlorine is the preferred chlorina-ting agent.

Process a) for separating the ~l'R) enantiomer from racemic 3-[N-(methoxyacetyl)-N-(2,6-dimethylphenyl)]aminotetrahydrofuran-2-one on a solid phase (adsorption chromatography) and b~ the chlorination to give a mixture of (aR,l'R)(aS,1'R) isomers (atropisomers) results in a high yield of an active component that exhibits a fungicidal activity of the same order of magnitude as the highly active (aS,l'R)-3-[N-(methoxyacetyl)-N-(2,6-dimethylphenyl)laminotetra-hydrofuran-2-one.

It has been found that, in particular, (aS,l'R)-3-[N-methoxy-acetyl)-N-(2,6-dimethylphenyl)~aminotetrahydrofuran-2-one, and also racemic (aR,l'S)(aS,l'R)-3-lN-(methoxyacetyl)-N-(2,6-dimethyl-phenyl)~aminotetrahydrofuran-2-one and the mixture of (aR,l'R) and (aS,1'R) isomers of 3-[N-methoxyacetyl)-N-(2,6-dimethylphenl)~-aminotetrahydrofuran-2-one are greatly superior in microbicidal 131~2~

activity to the racemate existing in four isomeric forms disclosed in German Offenlegungsschrift 2 804 299. These two mi~tures of isomers and the (aS,l'R) enantiomer each have, for practical purposes, 8 very useful microbicidal spectrum for protecting cultivated plants without damage being caused to them by undesirable side-effects. Examples of cultivated plants within the scope of this invention are typically: cereals, maize, rice, vegetables, sugar beet, soya beans, ground nuts, fruits trees, ornamentals, and especially vines, hops, cucumber plants (cucumbers, marrows, melons), solanacea such as potatoes, tobacco and tomatoes, as well as banana, cocoa and natural rubber plants.

The (aS,l'R) enantio~er or the aforementioned mixtures of isomers thereof are able to inhibit or destroy fungi occurring on plants or parts of plants (fruit, b~ossoms, foliage, stems, tubers, roots) of these and related crops of useful plants, while at the same time the parts of plants that grow later are protected from attack by such fungi. The compounds are effective against the pathogenic fungi belonging to the following classes of fungi: Ascomycetes (e.g.
Erysiphaceae); Basidiomycetes such as especially rust fungi; Fungi imperfecti (e.g. Moniliales; and especially against the Oomycetes belonging to the class of Phycomycetes, e.g. Phytophthora, Perono-spora, Pseudoperonospora, Pythium or Plasmopara. The isomers also act systemically. They can further be used as seed dressing agents for treating seeds (fruit, tubers, grains) and plant cuttings to protect these from attack by fungal infections as well as from phytopathogenic fungi that occur in the soil.

Target crops to be protected within the scope of the present invention comprise e.g. the following species of plants:
cereals (wheat, barley, rye, oats, rice, sorghum and related crops), beet (carrots, sugar beet and fodder beet), pomes, drupes and soft fruit (apples, pears, plums, peaches, almonds, cherries, straw-berries, raspberries and blackberries), leguminous plants (beans, lentils, peas, soybeans), oil plants (rape, mustard, poppy, olives, sunflowers, coconut, castor oil plants, cocoa beans, groundnuts), - lO - 1 31 ~ 2 ~

cucumber plants (cucumber, marrows, melons), fibre plants (cotton, flax, hemp, jute), citrus fruit (oranges, lsmons, grapefruit, mandarins), vegetables (spinach, lettuce, asparagus, cabbages, carrots, onions, tomatoes, potatoes, paprika), lauraceae (avocados, cinnamon, camphor), or maize, tobacco, nuts, coffee, sugar cane, tea, vines, chestnuts, hops, bananas, pineapples, grass (e.g. on golf-courses) and hay. This recitation constitutes no limitation.

The compounds of this invention are normally applied in the form of compositions and can be applied to the crop area, plant or sub-strate to be treated, simultaneously or in succession, with further compounds. These further compounds can be both fertilisers or micronutrient donors or other substances that influence plant growth. They can also be selective herbicides, insecticides, fungicides, bactericides, nematicides, mollusicides or mixtures of several of these substances if desired together with further carriers, surfactants or application promoting adjuvants custom-arily employed in the art of formulation.

Suitable carriers and adjuvants can be solid or liquid and corres-pond to the substances ordinarily employed in formulation tech-nology, e.g. natural or regenerated mineral substances, solvents, dispersants, wetting agents, tackifiers, thickeners, binders or fertilisers. Especially useful adjuvants are phospholipids.

A preferred method of applying a compound of this invention, or an agrochemical composition which contains at least one of said compounds, is foliar application. The number of applications and the rate of application depend on the risk of infestation by the corresponding pathogen (species of fungus). However, the compounds can also penetrate the plant through the roots via the soil (sys-temic action) by drenching the locus of the plant with a liquid formulation, or by applying the compounds in solid form to the soil, e.g. in granular form (soil application). The compounds may also be applied to seeds (coating) by impregnating the seeds either with a liquid formulation containing a compound of the invention, or 13142~1 coating them with a solid formulation. In special cases, further types of application are also possible, e.g. selective treatment of the plant stems or buds.

The compounds of the invention are used in unmodifled form or, preferably, together with the adjuvants conventionally employed in the art of formulation, and are therefore formulated in known manner to emulsifiable concentrates, coatable pastes, directly sprayable or dilutable solutions, dilute emulsions, wettable powders, soluble powders, dusts, granulates, and also encapsulations in e.g. polymer substances. As with the nature of the compositions, the methods of application, such as spraying, atomising, dusting, scattering, coating or pouring, are chosen in accordance with the intended objectives and the prevailing circumstances. Advantageous rates of application are normally from S0 g to 5 kg of active ingredient (a.i.) per hectare, preferably from 100 g to 2 kg a.i./ha, most preferably from 200 g to 600 g a.i./ha.

The formulations, i.e. the compositions, preparations or mixtures containing a compound (actlve ingredient3 of the invention and, where appropriate, a solid or liquid adjuvant, are prepared in known manner, e.g. by homogeneously mixing and/or grinding the active ingredient with extenders, e.g. solvents, solid carriers and, where appropriate, surface-active compouDds (surfactants).

Suitable solvents are: aromatic hydrocarbons, preferably the fractions containing 8 to 12 carbon atoms, e.g. xylene mixtures or substituted naphthalenes, phthalates such as dibutyl phthalate or dioctyl phthalate, aliphatic hydrocarbons such as cyclohexane or paraffins, alcohols and glycols and their ethers and esters, such as ethanol, ethylene glycol, ethylene glycol monomethyl or monoethyl ether, ketones such as cyclohexanone, strongly polar solvents such as N-methyl-2-pyrrolidone, dimethyl sulfoxide or dimethylformamide, as well as vegetable oils or epoxidised vegetable oils such as epoxidised coconut oil, sunflower oil or soybean oil; or water.

- 12 - 1 3 1 42 9 ~

The solid carriers used e.g. for dusts and dispersible powders, are normally natural mineral fillers such as calcite, talcum, kaolin, montmorillonite or attapulgite. In order to improve the physical properties it i5 also possible to add highly dispersed silicic acid or highly dispersed absorbent polymers. Suitable granulated adsorp-tive carriers are porous types, for example pumice, broken brick, sepiolite or bentonite; and suitable nonsorbent carriers are materials such as calcite or sand. In addition, a great number of pregranulated materials of inorganic or organic nature can be used, e.g. especially dolomite or pulverised plant residues, e.g. cork powder or sawdust.

Depending on the nature of active ingredient to be formulated, suitable surface-active compounds are non-ionic, cationic and/or anionic surfactsnts having good emulsifying, dispersing and wetting properties. The term "surfactants" will also be understood as comprising mixtures of surfactants.

Suitable anionic surfactants can be both water-soluble soaps and water-soluble synthetic surface-active compounds.

Suitable soaps are the alkali metal salts, alkaline earth metal salts or unsubstituted or substituted ammonium salts of higher fatty acids (C1o-C2z)~ e.g. the sodium or potassium salts of oleic or stearic acid, or of natural fatty acid mixtures which can be obtalned e.g. from coconut oil or tallow oil. Suitable aurfactants are also fatty acid methyltaurin salts as well as modified and unmodified phospholipids.

More frequently, however, so-called synthetic surfactants are used, especially fatty sulfonates, fatty sulfates, sulfonated benzimid-azole derivatives or alkylsulfonates~

Non-ionic surfactants are preferably polyglycol ether derivatives of aliphatic or cycloaliphatic alcohols, or saturated or unsaturated fatty acids and alkylphenols, said derivatives containing 3 to 30 131~291 glycol ether groups and 8 to 20 carbon atoms ln the (aliphatic) hydrocarbon moiety and 6 to 18 carbon atoms in the alkyl moiety of the alkylphenols.

~urther suitable non-ionic surfactants are the water-soluble adducts of polyethylene oxide with polypropylene glycol, ethylenediamino-propylene glycol and alkylpolypropylene glycol containing 1 to lO carbon atoms in the alkyl chain, which adducts contain 20 to 250 ethylene glycol ether groups and 10 to lO0 propylene glycol ether groups. These compounds usually contain l to 5 ethylene glycol units per propylene glycol unit.

Fatty acid esters of polyoxyethylene sorbitan, e.g. polyoxysthylene sorbitan trioleate, are also suitable non-ionic surfactants.

Cationic surfactants are preferably quaternary ammonium salts which contain, as N-substituent, at least one Cg-C22alkyl radical and, as further substituents, unsubstituted or halogenated alkyl, benzyl or hydroxy-lower alkyl radicals. The salts are preferably in the form of halides, methylsulfates or ethylsulfates, e.g. stearyltrimethyl-ammonium chloride or benzyldi(2-chloroethyl)ethylammonium bromide.

The surfactants customarily employed in formulation technology are descrlbed, inter alia, in the following publications:

McCutcheon's Detergents and Emulsifiers Annual, MC Publishing Corp., Ridgewood, New Jersey, 1979;
Dr. ~elmut Stache "Tensid Handbuch" (Handbook of Surfactants), Carl Hanser Verlag MunichlVienna 1981.

In the storage sector, preferred additives are those that are safe for human and animal nutrition.

The fungicidal compositions of this invention normally contain 0.1 to 95 ~0 by weight of the (aS,l'R) enantiomer in a higher proportion of the four isomers of the compound of formula I than - 14 - 1 31 ~2~1 that corresponding to the theoretical amount of 25 % by weight, together with 99.9 % to 5 % by weight of a solid andlor liquid carrier.

Preferred compositions are those in which the active component comprises 28 % by weight or more of the (aS,l'R) enantiomer or those containing in addition an equally large or lesser amount of the (aR,l'S) enantiomer.

Further preferred compositions are those in which the active component comprises 40 % by weight or more of the (aS,l'R) enantio-mer and those containing in addition an equally large or a lesser amount of the (aR,l'R) enantiomer or an equally large or lesser amount of the (aR,l'S) enantiomer.

Particularly preferred compositions are those in which the active component comprises 50 % by weight or more of the (aS,1'R) enantio-mer and those in which the active component additionally comprises an amount of the (aR,1'R) enantiomer or of the (aR,1'S) enantiomer to make up lOO % by weight or also a lesser amount.

Further preferred compositions are those in which the active component comprises 70 % by weight or more of the (aS,l'R) enantio-mer, in particular those in which the active component comprises preponderantly (90 % by weight or more) the (aS,l'R) enantiomer.

The particulars given above thus refer to amounts of the four isomers of 3-~N-(methoxyacetyl)-N-(2,6-dimethylphenyl)]aminotetra-hydrofuran-2-one, the (aS,l'R) enanatiomer of which is preferably the ma~or constituent, followed proportionately by either tke (aR,l'R) or the (aR,l'S) enantiomer, while each of the remaining enantiomers may be present in smaller amounts.

The indicated amounts refer exclusively to the compound of formula I
and include small amounts of other compounds which may possibly be present in the compositions of the invention.

.,,,, ~ , Whereas commercial products will preferably be formulated as concen-trates, the end user will normally employ dilute formulations.

The compositions may also contain further auxiliaries such as stabilisers, antifoams, viscosity regulators, binders, tackifiers as well as fertilisers or other active ingredients for obtaining special effects.

Such agrochemical compositions constitute an object of the present invention.

The following Examples illustrate the invention, without implying any limitation to what is disclosed therein. Parts and percentages are by weight.

Preparatory Examples 1.1 Preparation of the pair of (aR,l'S)(aS,l'R) enantiomers of 3-~N-(methoxyacetyl)-N-(3-chloro-2,6-dimethylphenyl)]aminotetra-hydrofuran-2-one, and of the pair of (aS,l'S)~aR,l'R) enantiomers of 3-[N-(methoxyacetyl)-N-(3-chloro-2,6-dimethylphenyl)]aminotetra-hydrofuran-2-one 70 g of the mixture of isomers of 3-[N-(methoxyacetyl)-N-(3-chloro-2,6-dimethylphenyl)]aminotetrahydrofuran-2-one obtained according to German Offenlegungsschrift 2 ao4 299, are separated into the individual isomers in a flas~ chromatography column (silica gel with a 1:1 mixture of ethyl acetateldiethyl ether as eluant).
Result:
33.8 g of (aS,l'S)(aR,1'R)-3-[N-(methoxyacetyl)-N-(3-chloro-2,6-di-methylphenyl)]aminotetrahydrofuran-2-one, m.p. 140C, 32.5 g of (aR,l'S)(aS,l'R)-3-[N-(methoxyacetyl)-N-~3-chloro-2,6-di-methylphenyl)]aminotetrahydrofuran-2-one, m.p. 115C.

- 16 - 1 31 4 29 ~

1.2 Preparation of (aS,l'S)-3-[N-(methoxyacetyl)-N-(3-chloro-2,6-dimethylphenyl)]aminotetrahydrofuran-2-one and (aR,l'R)-3-EN-(meth-oxyacetyl)-N-(3-chloro-2,6-dimethylphenyl)]aminotetrahydrofuran-2-one enantiomers 1 g of (aS,l'S)(aR,l'R)-3-~N-(methoxyacetyl)-N-(3-chloro-2,6-di-methylphenyl)3aminotetrahydrofuran-2-one ls separated into the individual enantiomers in a medium pressure chromatography column packed with triacetyl cellulose under a pressure of 2 bar with an eluant consisting of a mixture of ethanol (95 % vol. %) and water (5 vol. ~O).
Result:
0.215 g of (aR,l'R)-3-1N-(methoxyacetyl)-N-(3-chloro-2,6-dimethyl-phenyl)]aminotetrahydrofuran-2-one, m.p. 117-120C [~]2D4 in CHCl3): -64 + 1 (ee >98 %), 0.232 g of (aS,l'S)-3-[N-(methoxyacetyl)-N-(3-chloro-2,6-dimethyl-phenyl)]aminotetrahydrofuran-2-one, m.p. llS-117C, E~]2DO (in CHCl3): -64 + 1 (ee >99 %).

1.3 Preparation of (aR,l'S)-3-[X-(methoxyacetyl)-N-(3-chloro-2,6-dimethylphenyl)]aminotetrahydrofuran-2-one and (aS,1'R)-3-[~-(methoxyacetyl)-N-(3-chloro-2,6-dimethylphenyl)]aminotetrahydro-furan-2-one enantiomers 0.5 g of (aR,l'S)(aS,l'R)-3-[N-(methoxyacetyl)-N-(3-chloro-2,6-di-methylphenyl)~aminotetrahydrofuran-2-one is separated into the lndividual enantiomers in a medium pressure chromatography column packed with triacetyl cellulose under a pressure of 2 bar with an eluant consisting of a mixture of ethanol (95 % vol. %) and water (5 vol. %).
Result:
0.154 g of (aR,l'S)-3-~N-(methoxyacetyl)-N-(3-chloro-2,6-di-methylphenyl)]aminotetrahydrofuran-2-one, m.p. 98-100C, [~]D
(in CHCl3): -91.2 + 1 (ee >95 %), - 17 - 1 31 ~ 29 ~

0.152 g of highly active (aS,l'R)-3-[N-(methoxyacetyl)-N-(3-chloro-2~6-dimethylphenyl)]aminotetrahydrofuran~2-one~ m.p. 94~96C, [~32D (in CHCl3): +96 ~ 1 (ee >99 %).

1.4 Prepsration of the individual (aS,l'S), (aR,l'R), (aR,l'S) and (aS,l'R) isomers of 3-[N-(methoxyacetyl)-N-(3-chloro-2,6-dimethyl-phenyl)]aminotetrahydrofuran-2-one in one separation step from the mixture thereof 20 ~l of a l % solution of the mixture of isomers in a 1:1 mixture of hexane/2-propanol are applied to a HPLC column (0.46 x 25 cm) packed with tris(3-methylbenzoyl)cellulose. The chromatography is carried out at a rate of flow of l ml/min. with an eluant consisting of 60:49 mixture of hexane/2-propanol. The four isomers are separ-ated under these conditions. The retention times of the individual isomers are as follows:

isomeTs retention time (min.) (aR,l'S) 21.7 (aS,l'S) 31.0 (aS,l'R) 42.5 (aR,l'R) 67.7 The isomers are isolated in pure form after evaporation of the mixture of solvents and after drying the residue. (The physical data correspond to the values given in the preceding Examples). The tris(3-methylbenzoyl)cellulose used in the stationary phase is prepared as follows:

50 ml of heptanol are added to 10 g of tris(3-methylbenzyl)cellulose in 300 ml of methylene chloride. The resultant solution is then added dropwise to a solution of 0.7 ~O sodium lauryl sulfate (Z40 ml), which is stirred at 400 rpm. Methylene chloride is then removed by evaporation at the same rate of stirring at 40-42C

131~2~

(bath temperature). The residue is isolated by filtration and washed with water and ethanol. The powdery product is dried at 80C for 20 hours in a vacuum drler. Yield: 9.6 g (96 % of theory). The spherical particles having a diameter of 10-20 ~m can, if required, be fractionated by sieving or sedimentation. Further physical properties of the product:

specific surface area: 57.8 m2/g (according to BET) heat of fusion ~H : 12.7 Jlg.

The selective preparation of a mixture of (aR,l'R) and (aS,l'R) isomers of 3-[N-(methoxyacetyl)-N-(3-chloro-2,6-dimethylphenyl)]-aminotetrahydrofuran-2-one by chlorination of (l'R)-3-[N-(methoxy-acetyl)-N-(3-chloro-2,6-dimethylphenyl)]aminotetrahydrofuran-2-one can be effected readily and in high yield (Example 2.1). When formulated, this mixture can be used as a highly effective plant microbicide. If desired, however, the (aS,l'R) enantiomer can also be separated therefrom (Example 2.2).

The (l'R)-3-[N-(methoxyacetyl)-N-(3-chloro-2,6-dimethylphenyl)]-aminotetrahydrofuran-2-one to be used as starting material for the chlorination can be separated from the corresponding racemate in accordance with the procedure of Example 2Ø

Preparatory Examples 2.0 Separation of the enantiomer intermediates (l'S)-3-[N-(meth-oxyacetyl)-N-(3-chloro-2,6-dimethylphenyl)]aminotetrahydrofuran-2-one and (l'R)-3-[N-(methoxyacetyl)-N-(3-chloro-2,6-dimethyl-phenyl)]aminotetrahydrofuran-2-one . . _ _ . . . _ _ .

2 g of 3-[N-(methoxyacetyl)-N-(3-chloro-2,6-dimethylphenyl)]amino-tetrahydrofuran-2-one are separated into the two enantiomers in a medium pressure chromatography column packed with triacetyl cellu-lose under a pressure of 2 bar with an eluant consisting of ethanol (95 vol. %) and water (5 vol. ~O).
Result:
0.808 g of (l'R)-3-[N-(methoxyacetyl)-N-(3-chloro-2,6-dimethyl-phenyl)]aminotetrahydrofuran-2-one, m.p. 63-65C, [~]D (in CHCl3): +84.5 ~ 1 (ee >99 %), 0.978 g of (l'S)-3-[N-(methoxyacetyl)-~-(3-chloro-2,6-dimethyl-phenyl)]aminotetrahydrofuran-2-one, m.p. 62-64~C, [~]2D0 (in CHCl3): -80.3 ~ 1 (ee >95 %) 2.1 Preparation of an approximately 1:1 mixture of ~aR,1'R)- and ~aS,1'R)-3-[N-(methoxyacetyl)-N-(3-chloro-2,6-dimethylphenyl)]-aminotetrahydrofuran-2-one 0.222 g of (1'R)-3-[N-(methoxyacetyl)-N-(3-chloro-2,6-dimethyl-phenyl)]aminotetrahydrofuran-2-one of formula I is dissolved in 30 ml of formic acid. Then 0.06 g of chlorine are bubbled into the solution at room temperature in the presence of a trace of iron(III) chloride. The solution is stirred for about 1 hour and the solvent is removed by evaporation under reduced pressure. The residue is dissolved in ethyl acetate and the solution is extracted with water.
The extract is dried over sodium sulfate, filtered, and the filtrate - 20 - 1 31 ~ 29 ~

is concentrated by evaporation. The dried mixture melts at 79-82C
and consists of about 50 ~/O of each of the two isomers, i.e. the ratio of the isomers varies from 45:55 to 55:45.

2.2 Preparation of pure (aS,l'R)-3-[N-(methoxyacetyl)-N-(3-chloro-2,6-dimethylphenyl)]aminotetrahydrofuran-2-ona .. .. . . .. _ The residue obtained from the chlorination in Example 2 is dissolved in ethyl acetate. The solution is extracted with water and the aqueous extract is dried over sodium sulfate, filtered, and the filtrate is concentrated by evaporation. The crude mixture is separated in a flash column packed with silica gel and eluted with a 1:3 mixture of ethyl acetate/hexane.
Result:
0.070 g of (aR,1'R)-3-EN-(methoxyacetyl)-N-~3-chloro-2,6-dime~hyl-phenyl)3aminotetrahydrofuran-2-one, [~]D (in CHCl3): +63.8 + 2, 0.075 g of (aS,l'R)-3-~N-~methoxyacetyl)-N-~3-chloro-2,6-dimethyl-phenyl)~aminotetrahydrofuran-2-one, E~D (in CHCl3): +88 + 3.

Formulation Examples for compounds of formula I, including isomers and mixtures thereof which can be prepared in accordance with Examples 1.1 to 1.4 and 2.1 and 2.2.
.. . .. _ . .

EPercentages of ~aS,1'R) isomer in the compound of formula I
indicated in brackets]

1. Emulsifiable concentrates a) b) c) a compound of formula I 25 % 40 % 50 %
[70 % of (aS,l'R)~
calclum dodecylbenzenesulfonate 5 % 8 % 6 %
castor oil polyethylene glycol ether (36 moles of ethylene oxide~ 5 %
tributylphenol polyethylene glycol ether (30 moles of ethylene oxide) - 12 % 4 %

cyclohexanone - 15 % 20 %
xylene mixture 65 % 25 % 20 %

Emulsions of any required concentration can be produced from such concentrates by dilution with water.

2. Solutions a) b) c) d) a compound of formula I 80 % lO % 5 % 95 %
[40 % of (aS,l'R)]
ethylene glycol monomethyl ether 20 % - - -polyethylene glycol (mol.wt. 400) - 70 % - -N-methyl-2-pyrrolidone - 20 %
epoxidised coconut oil - - 1 % 5 %
petroleum distillate (boiling range 160-190C) - - 94 %

These solutions are suitable for application in the form oE micro-drops.

3. Granulates a) b) a compound of formula I 5 % 10 %
180 % of (aS,l'R)]
kaolin 94 %
highly dispersed siliclc acid1 %
attapulgite - 90 %

The active ingredient is dissolved in methylene chloride, the solution is sprayed onto the carrier, and the solvent is subsequent-ly evaporated off in vacuo.

4. Dusts a) b) a compound of formula I 2 % 5 %
[50 % of (aS,l'R)]
highly dispersed silicic acidl % 5 %
talcum 97 %
kaolin - 90 %

131~291 Ready-for-use dusts are obtained by intimately mixing the carriers with the active lngredient.

5. Wettable powders a) b) c) a compound of formula I 25 % 50 % 75 %
[g2 % of (aS,l'R)]
sodium lignosulfonate 5 % 5 %
sodium lauryl sulfate 3 % - 5 %
sodium diisobutylnaphthalenesulfonate - 6 % 10 %
octylphenol polyethylene glycol ether (7-8 moles of ethylene oxide) - 2 %
highly dispersed silicic acid 5 % 10 % 10 %
kaolin 62 % 27 ~0 The active ingredient is thoroughly mixed with the adjuvants and the mixture is thoroughly ground in a suitable mill, affording wettable powders which can be diluted with water to give suspensions of the desired concentration.

6. Emulsifiable concentrate a compound of formula I E28 % of (aS,l'R)3 10 %
octylphenol polyethlene glycol ether (4-5 moles of ethylene oxide) 3 %
calcium dodecylbenzenesulfonate 3 %
castor oil polyglycol ether (35 moles of ethylene oxide) 4 %
cyclohexanone 30 %
xylene mixture 50 %

Emulsions of any required concentration can be obtained from this concentrate by dilution wlth water.

?. Dusts a) b~
a compound of formula I [97 % of (aS,l'R)] 5 % 8 %
talcum 95 %
kaolin - 92 %

131~2~

Ready-for-use dusts are obtained by mixing the active ingredient with the carrier, and grinding the mixture in a suitable mill.

8. Extruder granulate a compound of fo}mula I [85 % of (aS,l'R)] 10 ~o sodium lignosulfonate 2 %
carboxymethylcellulose 1 %
kaolin 87 %

The active ingredient is mixed and ground with the adjuvants, and the mixture is subsequently moistened with water. The mixture is extruded and then dried in a stream of air.

9. Coated granulate a compound of formula I [90 % of (aS,1'R)] 3 %
polyethylene glycol (mol.wt. 200)3 %
kaolin 94 %

The finely ground active ingredient is uniformly applied, in a mixer, to the kaolin moistened with polyethlene glycol. ~on-dusty coated granulates are obtained in this manner.

10. Suspension concentrate a compound of formula I [55 % of (aS,1'R)] 40 %
ethylene glycol 10 %
nonylphenol polyethylene glycol (15 moles of ethylene oxide) ~ %
sodium lignosulfonate 10 %
carboxymethylcellulose 1 %
37 Y0 aqueous formaldehyde solution0.2 %
silicone oil in the form of a 75 %
aqueous emulsion 0.8 %
water 32 %

- 24 - 1 31 ~ 2~

The finely ground active ingredient is intimately mixed with the adjuvants, giving a suspension concentrate from which suspensions of any desired concentration can be obtained by dilution with water.

3. Biological ~xamples 3.1 Pythium ultimum on Beta vulgaris (sugar beet, cv. Kleinwanzleben Monogerm~ and Pythium ultimum on Zea mays (maize, cv. Sweet Corn) Test subject: soil fungus: protective local soil application.

Test method: Mycellum of Pythium ultimum is mixed with soil (500 ml of mycelium suspension per 10 litares of soil) and 250 ml plastic dishes are filled with the fungus/soil mixture. After incubation for 4 days at 10C, 10 seeds of the test plant (maize or sugar beet) are sown in each dish. On the next day, 50 ml of a spray solution of each test compound-prepared from a 25 % wettable powder and water are poured in concentrations of 20, 6, 2, 0.6, 0.2, 0.6 and 0.02 ppm on to the dishes. After an incubation phase of 7 days at 22C, the activity of the test compounds is assessed by counting the number of emerged plants in accordance with the following rating:

microbicidal activity in % rating > 95 0-50 ~ (= no activity) The results are reported in Table 1.

2s- 131~291 Table 1 Isomer of the Rating ** at a concentration of compound of active ingredient (ppm) formula I
(active ingredient) 20 o 20.6 0.2 0.06 1. mixture of maize1 1 2 6 9 9 isomers * beet1 1 1 2 8 8 2. racemate maize1 3 8 9 9 9 (aS,l'S)(aR,l'R) beet 2 2 8 9 3. racemate maize 1 2 3 5 8 9 (aR,l'S)(aS,l'R) beet 1 1 1 1 5 8 * According to German Offenlegungsschrift 2 0804 299 consisting of 4S % of the pair of (aR,l'S)(aS,l'R) diastereoisomers and 55 % of the pair of (aS,l'S)~aR,l'R) diastareolsomers of the compound of formula I.

** Rating as average of 3 parallel tests.

The racemate 3) of this invention exhibits fungicidal activity in the concentration range down to 0.6-0.2 ppm.

3.2 Action against ~hytophthora infestans on tomato plants a) Residual-protective action After a cultivation period of 3 weeks, tomato plants are sprayed with a spray mixture (0.02 % a.i.) prepared from a wettable powder formulation of the test compound. After 24 hours the tomato plants are infected with a sporangia suspension of the fungus. Evaluation of fungus attack is made after the plants have been incubated for 5 days at 90-100 % relative humidity and 20C.

- 26 - 1 31 ~291 b) Systemic activity After a cultivation period of 3 weeks, tomato plants are sprayed with a spray mixture (0.002 % a.i., based on the volume of the soil) prepared from a wettable powder formulation of the test compound.
Care is taken that the spray mixture does not come into contact with the parts of the plants above the soil. After 48 ho~rs the treated plants are infected with a sporangia suspension of the fungus.
Evaluation of fungus attack is made after the infected plants have been incubated for 5 days at 90-100 % relative humidity and 20C.

The results were evaluated in accordance with the rating described in Example 3.1 and the concentration necessary to achieve the rating 1-2 is based in each case on the concentration of the most active (aS,l'R) enantiomer. The concentration factors (f) obtained in this manner are listed in Table 2.

3.3 Plasmopara viticola on vines (vine seedlings, cv. Gutedel (Chasselas), in 3 pots, each with 1 plant per test compound a) Residual protective foliar application Five-week-old vine seedlings are sprayed with a spray mixture prepared from a formulation of the test compound and infected 1 day later with a sporangia suspension (200,000 sporangiaslml) of P. viticola. The infected seedlings are incubated at 20C in a greenhouse. A 14 hour incubation phase at 100 % relative humidity is followed by incubation for 4 days at 75-85 % and, finally, to induce sporulation, by incubation for one further night at 100 % humidity.
Evaluation of fungus attack i8 made after this 6 day incubation period (rating as in Example 3.1).

b) Systemic activity Five-week-old vine seedlings are sprayed with a spray mixture prepared from a formulation of the test compound. Three days later the plants are infected with a sporangia suspension (200,000 sporangias/ml) of P. viticola. The test is carried out as described in a).

The concentration factors calculated in accordance with Example 3.2 are listed in Table 3.

3.4 Systemic action against Pythium debaryanum on Beta vulgaris The fungus is cultivated on carrot chip nutrient solution and added to a mixture of soil and sand. The infected soil is filled into flower pots in which sugar beet seeds are then sown. Immediately after sowing, an aqueous suspension of the test compound formulated as wettable powder is poured on to the soil (20 ppm a.i., based on the volume of the soil). The pots are then stood for 3 weeks in a greenhouse at c. 20~C. The soil is kept uniformly moist during this time by gentle spraying.

The test is evaluated by counting the number of emerged sugar beet plants as well as the number of healthy and sick plants.

The concentration factors calculated in accordance with Example 3.2 are indicated in Table 2.

3.5 Systemic action against Pythium debaryanum on Zea mais The fungus is cultivated on carrot chip nutrient solution and added to a mixture of soil and sand. The infected soil is filled into flower pots in which maize seeds are then sown. Immediately after sowing, an aqueous suspension of the test compound formulated as wettable powder is poured on to the soil (20 ppm a.i., based on the - 28 - 131~291 volume of the soil). The pots are then stood for 3 weeks in a greenhouse at c. 20C. The soil is kept uniformly moist during this time by gentle spraying.

The test is evaluated by counting the number of emerged sugar beet plants as well as the number of healthy and sick plants.

The concentration factors calculated in accordance with Example 3.2 are indicated in Table 2.

Table 2 . . ~
Isomer of the Concentration factors (f) of compound of the tests formula I 3.2 3.3 3.4 3.5 (actlve ingredient) a b a b aS,l'R enantiomer 1 <1 <1 1 1 l mixture of isomers* 3.3 l <1 3.3 3.3 lO
aS,1'S enantiomer 3.3 3.3 ~3 lU lO 3.3 aR,l'R enantiomer 33 3.3 >3 lOO lO 33 aR,l'S enantiomer 33 3.3 >3 3.3 33 10 It is evident from Table 2 that the (aS,l'R) enantiomer of this invention has on average a 3-30 times better activity than the other three enantiomers and the racemate (mixture of isomers according to German Offenlegungsschrift 2 804 299).

3.6 Inhibition of fungus growth in vitro (agar incorporation test) 0.1 ml of a 0.75 % solution of each test compound in acetone is diluted with 15 ml of water under sterile conditions. 1 ml of each stock solution or of the sterile dilution series prepared therefrom by addltion of water is incorporated at 50C in 19 ml of nutrient medium in petri dishes of 9 cm diameter. The concentrations of each test compound are 50, 5, 0.5, 0.05 and 0.005 ppm per dish. Two hours 131~291 later these dishes and the control dishes without test compound are inoculated with Phytophthora capsici in the form of agar discs (0.6 mm 0, the side overgrown with fungus face down). The inocul-ated cultures are kept at 60-70 % relative humidity and at 18C in the dark until evaluation is made. After 4-6 days, when the control petri dish is two-thirds overgrown with fungus, the test series is evaluated by plotting the concentration of test compound loga-rithmically against the radial growth (of the control test in %) on graph paper. To compare the individual test compounds, that con-centration of each test compound is determined at which growth is 50 % of the control test (ELso value). The ELso values are reported in Table 3:

Table 3 Isomer of compound of ELso formula I at ppm (active ingredlent) a.i./dish . .. _ . _ aS,1'R enantiomer 0.011 (aR,1'R) and ~aS,1'R) 0.011 diastereoisomers mixture of isomers* 0.064 aR,l'S enantiomer 0.26 aS,1'S enantiomer 0.62 aR,l'R enantiomer 2.7 Test 3.6 shows that an equally pronounced activity ls achieved with an approximately 1:1 mixture of the highly active (aS,1'R) enantio-mer with the (aR,1'R) enantiomer.

3.7 Example for determining the long-term activity as soil fungicide Each of the test compounds formulated as wettable powder is stirred in 100 ml of water and mixed with 20 litres of soil. The concen-tration of the test compounds is based on dry soil.

~31'~2~1 Tobacco plants (Hocks variety) grown in sterile soil are planted in the 5- to 6-leaf stage in soil which contains fungicide (in 5 litre pots). Two days later the furrows on both sides of the plant are artificially infected by inoculation of altogether 2 x 20 ml of a spore suspension (containing 10,000 sporangias/ml) of Phytophthoraa nicotianae.

Evaluation is made at regular intervals with ratings (R) on a scale from 1-100 on the basis of withering of the leaves, damage to the stalk and extent of damage. ~here protection is complete, R = 0.

The plant is regarded as being protected until the first typical signs of disease appear. The test lasts 100 days during which time the tobacco plant ripens.

The long-term activity of the individual test compounds is compared with the aid of factors. This is done by determining the duration of action in days in respect of the indi~idual test compounds employed in different concentrations (ppm), at which action the protect-ion (R) corresponds to that of the mixture of isomers* (defined in Table 1) at a concentration of 0.25 ppm after 50 days. The com-parison factor (f) is calculated in accordance with the formula:
0.25 duration (days) f = _ , conc. (ppm) 50 The factors so calculated for the individual test compounds are summarised in Table 4, which shows the pronounced long-term action of the (aS,l'R) enantiomer and the (aR,l'S) and (aS,l'R) pair of enantiomers compared with the other three enantiomers and with two mixtures.

- 31 - ~ 91 Table 4 Isomer of the compound of Factor of formula I the long-(active ingredient) lasting ---~ action aR,1'R 0.025 (aS,1'S)(aR,l'R) 0.17 aR,l'S 0.17 aS,l'S 0.25 mixture of isomers*
(aR,l'S)(aS,l'R) ~of the 2 invention]
aS,l'R [of the invention] 4 3.8 Action against Phytophthora infestans on tomatoes a) Residual-protective action b) Systemic action The test method corresponds to that described in Example 3.2.

3.9 Action against Plasmopara viticola on vines a) Residual-protective action b) Systemic action The test method corresponds to that described in Example 3.3.

The pair of (aR,l'S)(aS,l'R) enantiomers and the ~aR,l'R)(aS,l'R) diastereoisomers were tested side by side in both indications and their activity was compared with the most active (aS,1'R) enantio-mers, which was tested in parallel. Table 5 shows, on the lines of Table 2, at a how much higher rate of concentration each of the ~ 32 - ~ 13~429~

diastereoisomers had to be used (concentration factor f) to achieve the same complete activity (95 %; rating 1) as the (aS,1'R) enant-iomer.

Table 5 . . .~
Isomers of the compound of Concentration factor f) formula I (active ingredient) Ex. 3.8 Ex. 3.9 a) b) a) b) . ..
aS,l'R enantiomer 1 1 pair oE (aR,l'S)(aS,l'R) 3.3 3.3 1 3.3 enantiomers .. ___ . __ (aR,l'R)(aS,l'R) 1 10 ~.3 diastereoisomers . _ In contrast to the results of Table 2, which show the (aS,l'R) enantiomer to be an outstanding active component compared with the other enantiomers and with the racemic compound (mixture of isomers*) of the prior art, Table 5 shows a surprisingly similar degree of activity of the pair of enantiomers, although the active (aS,l'R) enantlomer is only one of the two constituents of each pair. This result indicates an evident interaction of the enantio-mers which is able to enhance the biological activlty.

Claims (48)

1. A fungicidal composition which contains as active ingredient 0.1 to 95% by weight of the 4 possible isomers of 3-[N-(methoxyacetyl)-N(3-chloro-2,6-dimethylphenyl]aminotetra-hydrofuran-2-one in unequal distribution, wherein the proportion of active (aS,1'R) enantiomer is greater than 25%, together with a suitable carrier therefor.

2. A composition according to claim 1, wherein the proportion of (aS,1'R) enantiomer is 28% by weight or more.

3. A composition according to claim 1, wherein the proportion of (aS,1'R) enantiomer is 40% by weight or more.

4. A composition according to claim 1, wherein the proportion of (aS,1'R) enantiomer is 50% by weight or more.

5. A composition according to claim 1, wherein the proportion of (aS,1'R) enantiomer is 70% by weight or more.

6. A composition according to claim 1, wherein the proportion of (aS,1'R) enantiomer is 90% by weight or more.

7. A composition according to claim 1, wherein the active (aS,1'R) enantiomer constitutes the highest proportion, followed -33a- 21489-7348 by an equally high or lower proportion of either the (aR,1'R) or (aR,1'S) enantiomer.

8. A composition according to claim 7, wherein the active ingredient comprises a mixture of more than 50% of the (aS,1'R) enantiomer and the (aR,1'R) enantiomer.

9. A composition according to claim 7, wherein the active ingredient comprises a mixture of more than 50% of the (aS,1'R) enantiomer and the (aR,1'S) enantiomer.

10. 3-[N-(methoxyacetyl)-N-(3-chloro-2,6 dimethyl-phenyl)]aminotetrahydrofuran-2-one, wherein the proportion of (aS,1'R) enantiomer is greater than 25%.

11. 3-[N-tmethoxyacetyl)-N-(3-chloro-2,6 dimethyl-phenyl)]aminotetrahydrofuran-2-one, wherein the proportion of (aS,1'R) enantiomer is at least 28% by weight.

12. 3-[N-(methoxyacetyl)-N-(3-chloro-2,6 dimethyl phenyl)]aminotetrahydrofuran-2-one, wherein the proportion of (aS,1'R) enantiomer is at least 40% by weight.

13. 3-[N-(methoxyacetyl)-N-(3-chloro-2,6 dimethyl-phenyl)]aminotetrahydrofuran-2-one, wherein the proportion of (aS,1'R) enantiomer is at least 50% by weight.

14. 3-[N-(methoxyacetyl)-N-(3-chloro-2,6 dimethyl-phenyl)]aminotetrahydrofuran-2-one, wherein the proportion of (aS,1'R) enantiomer is at least 70% by weight.

15. 3-[N-(methoxyacetyl)-N-(3-chloro-2,6 dimethyl-phenyl)]aminotetrahydrofuran-2-one, wherein the proportion of (aS,1'R) enantiomer is at least 90% by weight.

- 34a - 21489-7348

16. The (aS,1'R) enantiomer of 3-[N-(methoxyacetyl)-N-(3-chloro-2,6-dimethylphenyl)]aminotetrahydrofuran-2-one.

17. The racemate of (aR,1'S)- and (aS,1'R)-3-[N(methoxy-acetyl)-N-(3-chloro-2,6 dimethylphenyl)]aminotetrahydrofuran-2-one.

18. The mixture of (aS,1'R) and (aR,1'R) diastereoisomers of 3-[N-(methoxyacetyl)-N-(3-chloro-2,6 dimethylphenyl)]amino-tetrahydrofuran-2-one.

19. A process for the preparation of the pair of (aR,1'S) and (aS,1'R) enantiomers of 3-[N-(methoxyacetyl)-N-(3-chloro-2,6-dimethylphenyl)]aminotetrahydrofuran-2-one, which comprises sep-arating the corresponding racemate consisting of two pairs of diastereoisomeric enantiomers from the pair of (aS,1'S)(aR,1'R) enantiomers by adsorption on a stationary solid phase and elution with a liquid phase.

20. A process according to claim 19, wherein the solid phase is an adsorbing material based on agarose, sepharose, cellulose, polyamide or polyacrylamide.

21. A process according to claim 20, wherein the adsorbing material is benzoylated or acetylated cellulose.

22. A process according to claim 21, wherein the adsorbing material is triacetyl cellulose.

23. A process according to claim 19, wherein the solid phase is an adsorbing material based on silica gel or aluminium oxide.

24. A process for the preparation of the (aS,1'R) enantiomer of 3-[N-(methoxyacetyl)-N-(3-chloro-2,6-dimethylphenyl)]aminotetra-hydrofuran-2-one, which comprises separating a solution of the racemate consisting of (aR,1'S)- and (aS,1'R)-3-[N-(methoxyacetyl)-N-(3-chloro-2,6-dimethylphenyl)]aminotetrahydrofuran-2-one into the individual enantiomers by chromatography on an optically active solid phase and isolating the (aS,1'R) enantiomer from said sol-ution.

25. A process according to claim 24, wherein triacetyl cellulose is used as optically active solid phase.

26. A process according to claim 24, wherein tris(3-methylbenzoyl)-cellulose is used as optically active solid phase.

27. A process for the preparation of (aR,1'R)(aS,1'R)-3-[N-(meth-oxyacetyl)-N-(3-chloro-2,6-dimethylphenyl)]aminotetrahydrofuran-2-one, which comprises chlorinating (1'R)-3-[N-(methoxyacetyl)-N-(3-chloro-2,6-dimethylphenyl)]aminotetrahydrofuran-2--one in a suitable solvent at 0°-50°C in the presence or absence of a Lewis acid.

28. A process for the preparation of (aR,1'R)(aS,1'R)-3-[N-(meth-oxyacetyl)-N-(3-chloro-2,6-dimethylphenyl)]aminoteetrahydrofuran-2-one, which comprises separating the (1'R) enantiomer from racemic 3-[N-(methoxyacetyl)-N-(3-chloro-2,6-dimethylphenyl)]aminotetra-hydrofuran-2-one a) by adsorption on a solid phase and b) chlorin-ating the resultant (1'R) enantiomer in a suitable solvent at 0°-50°C in the presence or absence of a Lewis acid.

29. A process according to claim 28, wherein silica gel or Al2O3 is used as solid phase.

30. A process according to claim 28, wherein a solid phase based on cellulose is used.

31. A process according to claim 30, wherein acylated cellulose is used as solid phase.

32. A process according to claim 31, wherein acetylated cellulose is used as solid phase.

33. A process according to claim 32, wherein triacetyl cellulose is used as solid phase.

34. A process according to claim 31, wherein benzoylated cellulose is used as solid phase.

35. A process according to claim 31, wherein tris(3-methylbenzyl)-cellulose is used as solid phase.

36. A process according to either of claims 27 or 28, wherein the solvent for the chlorination step is a halogenated hydrocarbon.

37. A process according to either of claims 27 or 28, wherein the solvent for the chlorination step is an alkanoic acid.

38. A process according to claim 37, wherein the alkanoic acid is formic acid.

39. A process according to claim 37, wherein the alkanoic acid is acetic acid.

40. A process according to either of claims 27 or 28, wherein the chlorination is carried out at room temperature.

41. A process according to either of claims 27 or 28, wherein chlorine is used as chlorinating agent

42. A process according to either of claims 27 or 28, wherein sulfuryl chloride (SO2Cl2) is used as chlorinating agent.

43. A process according to either of claims 27 or 28, wherein the chlorination is carried out in the absence of a Lewis acid.

44, A Process according to either of claims 27 or 28, wherein the Lewis acid is aluminium chloride, zinc chloride or tin(IV) chloride.

45. A process according to either of claims 27 or 28, wherein the Lewis acid is iron(III) chloride.

46. A process for the preparation of the optically active (aS,1'R) isomer of 3-[N-(methoxyacetyl)-N-(3-chloro-2,6-dimethylphenyl)]-aminotetrahydrofuran-2-one, which comprises chlorinating a solution of (1'R)-3-[N-(methoxyacetyl)-N-(3-chloro-2,6-dimethylphenyl)]-aminotetrahydrofuran-2-one and isolating said (aS, 1'R) isomer of 3-[N-(methoxyacetyl)-N-(3-chloro-2,6 dimethylphenyl)]aminotetra-hydrofuran-2-one from the reaction mixture by adsorption chromato-graphy of the (aR,1'R) enantiomer also obtained.

47. A method of controlling plant destructive microorganisms, which comprises applying to the plant or to the locus thereof a microbicidally effective amount of a composition according to claim 1.

48. A method of controlling plant destructive microorganisms, which comprises applying to the plant or to the locus thereof a microbicidally effective amount of the (aR,1'R) and (aS,1'R) isomers of 3-N-(methoxacetyl)-N-(3-chloro-2,6-dimethylphenyl)]aminotetrahydrofuran-2-one.