WO2005056548A1

WO2005056548A1 - Enantiomerically pure epoxiconazole and its use as crop protection agent

Info

Publication number: WO2005056548A1
Application number: PCT/DK2004/000858
Authority: WO
Inventors: Niels Jacobsen; Anders Lohse; Harald Bernhard Teicher
Original assignee: Cheminova A/S
Priority date: 2003-12-11
Filing date: 2004-12-10
Publication date: 2005-06-23

Abstract

Compositions are provided comprising the compound (Ia) and the use of said compound in the control of harmful phytopathogenic fungi and a process for the reparation of the compound (Ia) which is (2S, 3R)-1[3-(22-chloro-phenyl)-2(4-fluoro-phenyl)-oxiranyl]mehyl-1H[1,2,4] triazole or the compound (Ib) which is (2R, 3S)-1[3-(2-chloro-phenyl)-2(4-fluoro-phenyl)-oxiranyl]methyl-1H-[1,2,4&die;triazole, in enantiomerically pure form. Also provided are compositions comprising the compound (Ib) and the use of said compound for influencing the growth of plants.

Description

Enantiomerically pure Epoxiconazole and its use as crop protection agent

The invention relates to compositions comprising the compound (la) and the use of said compound in the control of harmful phytopathogenic fungi. The inven- tion also relates to compositions comprising the compound (lb) and the use of said compositions for influencing the growth of plants.

The present invention further relates to a process for the preparation of the enantiomerically pure compound (la) which is (2S,3R)-l-[3-(2-chlorophenyl)-2-(4- fluorophenyl)oxiranyl]methyl-lH-[l,2,4]triazole or the compound (lb) which is (2R,3S)-l-[3-(2-chlorophenyl)-2-(4-fluorophenyl)oxiranyl]methyl-lH- [l,2,4]triazole

Background

The compound of formula (I), which is l-[3-(2-chlorophenyl)-2-(4- fluorophenyl)oxiranyl]methyl-lH-[l,2,4]triazole, is known as a fungicide from United States patent no. 4,906,652 and its use as a plant growth regulator known from European patent no. 315850- A2.

Due to the presence of two asymmetric carbon atoms in the oxirane ring (positions 2 and 3), the compound can exist as four difference isomers, i.e. a pair of diastereomers having either the E- or Z-form, also known as the trans or cis form respectively, each consisting of two enantiomers. According to United States patent no. 4,906,652 it is possible to produce exclusively the Z-form (2RS,3SR diastereomer, compound 8 in said patent) consisting of a 1:1 racemic mixture of the (2R,3S) and (2S,3R) forms. This racemic mixture is commer- cially known as Epoxiconazole (for instance sold under the trademark OPUS) and is used in the control of harmful phytopathogenic fungi. Epoxiconazole belongs to the class of pesticides termed "triazoles" generally known for their fungicidal and plant growth regulating effect. Many of these compounds possesses one or more asymmetric carbon atoms and hence exists in several structurally different isomeric forms. As illustrated by Spindler et al. in Chirality in Agrochemicals - Wiley 1998, p. 157-173, the fungicidal activity for a given compound can in some instances be restricted to a single enantiomer (e.g. Triadimenol, 4 enantiomers) and in some instances each enantiomer show varying relative activity towards different target organisms (e.g. Propiconazole, 4 enantiomers). The most active isomer out of 4 possible of the triazole fungicide Diclobutrazol has the 2R,3R configuration whereas in the structural closely related compound Triadimenol the most active isomer in contrast has the 2S,3R configuration as stated by Baldwin et al. in Pesticide Science, 1984, p. 157-166. Sugavanam in Pesticide Science, 1984, p. 296-302, describes the biological ac- tivity of the compound Paclobutrazol, a triazole compound, which also exists as 4 enantiomers of which 2 show only moderate fungicidal and plant growth regulating effect. The high activity observed can be assigned to the two others respectively, i.e. one possessing the fungicidal activity and the other the plant growth regulating effect. In view of the above there exists no clear picture as such in respect to a relationship between configuration and biological activity of triazole pesticides.

Hutta et al. in Journal of Chromatography 959 (2002), 143-152, claims an analytical HPLC method for the separation of the two Z-enantiomers in Epoxiconazole, but no proof of identity of the individual peaks is provided, nor are the en- antiomers characterised in any way and indeed no information of fungicidal activity of the enantiomers is described.

To the best of our knowledge the two individual isomers of the Z-form have not been isolated in pure or substantially pure form and characterised in respect of absolute configuration prior to the present invention.

While many compounds for the control of phytopatho genie fungi are provided, a need still exists for compounds with greater activity and improved effectiveness over current compounds. The present invention contributes vitally to plant dis- ease control and to cultivation of more resistive plant in the fields of agriculture and horticulture. For instance, application of a more active chemical substantially free from any inactive isomer forms is connected to adequate application of a smaller amount of the chemical, which leads to the improvement in economics of the processes of manufacture, transportation and field application and to the expectation of minimising the environmental pollution as well as the improvement in safety.

Summary of the invention

It has now been found that the optically pure (2S,3R)-enantiomer of Epoxicona- zole, which is (2S,3R)-l-[3-(2-chlorophenyl)-2-(4-fluorophenyl)- oxiranyl]methyl-lH-[l,2,4]triazole, (hereinafter referred to as compound la), is surprisingly more effective in the control of phytopathogenic fungi than the corresponding racemic Z-form or the enantiomerically pure (2R,3S)-enantiomer (compound lb).

Further, it has been found that the optically pure compound (lb) has a significantly higher influence on plant growth than the corresponding racemic Z-form or the enantiomerically pure (2S,3R)-enantiomer (compound la).

In one aspect, the present invention provides a composition suitable for controlling harmful fungi, comprising a solid or liquid carrier and the compound (la) substantially free from the compound (lb) or any of the other enantiomers having the general structure (I). The present invention also provides a method of controlling harmful fungi, which comprises treating the fungi or the materials, plants, soil or seed to be protected from fungal attack with an active amount of a compound formula (la) substantially free from the compound (lb) or any of the other enantiomers having the general structure (I).

In another aspect, the present invention provides a composition suitable for influencing the growth of plants, comprising a solid or liquid carrier and the compound (lb) substantially free from the compound (la) or any of the other enantiomers having the general structure (I). In yet another aspect, the present invention also provides a method for influencing the growth of plants, which comprises treating the plants, soil of seed with an active amount of a compound (lb) substantially free from the compound (la) or any other enantiomers having the general structure (I).

With respect to the term "substantially free from" as used herein, it shall be understood that the composition contains a greater proportion or percentage of the compound (la) or (lb), on a weight basis, in relation to the any other enantiomer of the formula (I), these percentages being based on the total amount of the compound (I) present. In a preferred embodiment, the term "substantially free from" as used herein means that the composition contains at least 70% by weight of the compound (la) or (lb), and 30% by weight or less of the other enantiomers having the general structure (I). In a more preferred embodiment, the term "substantially free from" means that the composition contains at least 80% by weight of the compound (la) or (lb) in relation to the any other enantiomer of the formula (I). In a still more preferred embodiment, the term "substantially free from" means that the composition contains at least 90% by weight of the compound (la) or (lb) in relation to the any other enantiomer of the formula (I). In an even more preferred embodiment, the term "substantially free from" means that the composition contains at least 99% by weight of the compound (la) or (lb) in relation to the any other enantiomer of the formula (I).

In another aspect, the present invention provides a method for the preparation of the compounds (la) and (lb) in substantially enantiomerically pure form. The invention further relates to said compounds prepared by the method described herein or isolated in substantially enantiomerically pure form from the racemic Z-mixture or from a racemic mixture of both the Z and E form. "Substantially enantiomerically pure" form of the active compound, as used herein, means that the desired isomer is synthesised or isolated at 95-100%, preferably 100%o, purity relative to any of the other enantiomers having the general struc- ture (I). The present invention also relates to novel intermediates, which are precursors to the compounds (la) and (lb). Said intermediates and the compounds (la) and (lb) may serve as starting materials for the preparation of other active compounds in enantiomerically pure form for either agrochemical or pharmaceu- tical use.

Description of the invention

The compound (la) is synthesised in substantially enantiomerically pure form in a process, which comprises the following steps:

a) contacting a compound of the formula (II),

which is Z-3-(2-Chlorophenyl)-2-(4-fluorophenyl)oxiranecarboxylic acid, with an optically active acid-salt forming resolving agent to form di- astereomeric salts and subjecting the so-formed diastereomeric salts to fractional crystallisation in a solvent to separate the (2R,3R) acid-salt from the (2S,3S) acid-salt salt and subsequently liberating the (2R,3R) acid from the salt;

b) treating the (2R,3R) enantiomer of the compound (II), i.e. compound (Ha), with an alkoxycarbonyl chloride to form an anhydride intermediate which is reduced with a reducing agent to produce a compound of formula (Ufa), which is (2S,3R)-3-(2-chlorophenyl)-2-(4-fluorophenyl)oxiranemethanol;

c) converting the compound (Ula) into a compound (IVa)

wherein L represents a leaving group other than OH; d) reacting the compound (IVa) in the presence of a base with lH-l,2,4-triazole or one of its salts.

The configuration of the asymmetric carbon atoms are classified as "R" or "S" in accordance with the Cahn-Ingold-Prelog rules, and although changes in the assignment of configuration are seen during the course of the above steps, the two phenyl groups on the oxiran ring maintain their orientation in space during the above procedure, and the change in assignment of configuration is merely a result of these rules.

The compound (lb) is synthesised in the same manner using the above step a) and onwards utilising the (2S,3S) isomer (compound lib) whereby intermediate compounds of the formula (Illb) and (INb) occur.

The acid-salt forming resolving agent employed in step a) is preferably an opti- cally active amine and in particular an optically active amine of the following formula (V)

where R¹ and R² are different and each represent Cι_-8 alkyl optionally substituted with one or more phenyl groups; phenyl or naphtyl which may be substituted with one or more C_1-4 alkyl groups. It is most preferred to use either one of the optical active isomers of 1-methylbenzyl amine. By example, the salt of (S)- 1-methylbenzyl amine and the (2R,3R) enantiomeric form of compound (II) is considerably less soluble than the diastereomer salt from (S)- 1-methylbenzyl amine and the (2S,3S) enantiomeric form of compound (II)). In contrast, the salt of (R)-l-phenylethylamine and the (2S,3S) enantiomeric form of compound (II) is considerably less soluble than the salt of the (2R,3R) enantiomeric form of compound (II) with (R)- 1 -phenyl ethylamine.

The salts that are diastereomers to each other show sufficiently large differences in solubility in numerous solvents. For example water belongs to this class of solvents. Preferably there are used as solvents primary or secondary alcohols having up to 6 carbon atoms or ethers and among these solvents especially those, which are miscible with water. For example, hexanol, butanol, methyl t-butyl ether and especially methanol, ethanol, propan-2-ol, dioxane and tetrahydrofuran can be used. Other solvents include propanol, butan-2-ol, 2-methyl-propanol. The solvents can also be used in mixtures with each other or in mixtures with water, but the mixtures are suitably so selected that the solvents form a single phase. The molar ratio of optically active acid-salt forming resolving agent to the compound of formula (II) is between 0.5 and 1. For separation of the diastereomer salts the procedure is by fractional crystallisation in the customary manner. The mixture is either brought to elevated temperatures and subsequently the solution cooled for the crystallisation or a mixture of (II) is held at a fixed temperature for the crystallisation and the acid-salt forming compound in the same or different solvent is added gradually. Once the salt of the (2R,3R)-acid has precipitated it is isolated by filtration and the (2R,3R) enantiomer, i.e. com- pound (Ha), separated from the salt by reaction with a mineral acid e.g. hydrochloric acid. One may if desired isolate the (2S,3S) isomer from the solvent.

In step b) the (2R,3R) enantiomer of the compound (II) is reacted with an alkoxycarbonyl chloride, preferably ethoxycarbonyl chloride to form the inter- mediate anhydride which is subjected to reduction by a reducing agent which may be selected among borohydrides, e.g. NaBH₄; aluminium hydrides e.g. those of formulae R R₄A1H, M[R₃R₄A1H₂] or MA1H₄, wherein R₃ and R₄ each independently of the other represents C_1- alkyl, and M is lithium or sodium. The use of NaBH is most preferred. The intermediate anhydride is prepared at tem- peratures between -20 and 40 °C in an organic solvent, e.g CH₂CI₂, in the presence of a base such as an alkali metal hydroxide or a tertiary amine e.g. trialkyl amine such as triethyl amine. A small molar excess of the alkoxy carbonyl chloride is preferably used. The intermediate anhydride may be isolated but is advantageously treated directly with the reducing agent at temperatures between -20 and 40 °C. The amount of reducing agent is in excess compared to the intermediate anhydride and usually in a molar excess between 2-6. The compound (Hla) can be isolated and purified if desired, but may also be used without further purification.

In step c) the conversion (or displacement) of the hydroxy group is done by standard means. In principle the leaving group L may be any suitable leaving group known within the art. It is within the skills of an ordinary practitioner to select a suitable leaving group. Typical leaving groups L includes halogen, preferably chlorine or bromine; Cι_-6-alkylsulfonyloxy such as methylsulfonyloxy; Cι_-6-haloalkylsulfonyloxy such as trifluoromethylsulfonyloxy; arylsulfonyloxy such as phenyl- or naphtylsulfonyloxy, where the aryl radical may, if appropriate, be substituted by one or more halogen or Cι_-6-alkyl groups, such as phenyl- sulfonyloxy, -toluenesulfonyloxy and ^-Cl-phenylsulfonyloxy. L is preferably chlorine, bromine, Cι_-6-alkyl- or phenyl-sulfonyloxy with methylsulfonyloxy be- ing most preferred.

In principle the displacement agent may be any suitable displacement agent known within the art. It is within the skills of an ordinary practitioner to select a suitable displacement agent for a particular reaction. Typical displacement agents include sulfonyl chlorides such as methansulfonyl chloride and p- toluensulfonyl chloride; thionyl chloride or bromide, phosphorus chlorides or bromides such as PC1₃ or PC1₅; phosphoryl chloride or bromide e.g. POCI₃ or POBr₃.

It is within the skills of the average practitioner to select suitable conditions for a particular conversion reaction based on the particular selected leaving group and displacement agent.

The final step d) is carried out in the presence of a solvent, but may be performed without, at temperatures from 0 to 120 °C. Preferred solvents include ke- tones e.g. acetone, methyl ethyl ketone and cyclohexanone; nitriles e.g. acetoni- trile; esters e.g. ethyl acetate; ethers, e.g. diethyl ether, tetrahydrofuran and diox- ane; sulfoxides, e.g. dimethylsulfoxide (DMSO); amides, eg. dimethylforma- mide (DMF), dimethylacetamide and N-methylpyrrolidone, and sulfolane, as well as mixtures of these. The base may be chosen by example among alkali metal carbonates, e.g. sodium carbonate, potassium carbonate, sodium bicarbon- ate and potassium bicarbonate; alkali metal hydroxides e.g. lithium hydroxide, sodium hydroxide and potassium hydroxide.

The starting compound (II), mainly in its Z-form, is prepared by known methods. The main area in which the compound of formula (la) is used is in the control of harmful phytopathogenic fungi. Thus, the compound of formula (la) has, for practical field application purposes, a very advantageous curative, preventive and systemic action for protecting cultivated plants without having undesired side-effects on such plants. In the context of the present invention, cultivated plants are, for example, cereals (wheat, barley, rye, oats, rice); beet (sugar beet and fodder beet); pomes, drupes and soft fruit (apples, pears, plums, peaches, almonds, cherries, strawberries, raspberries and blackberries); leguminous plants (beans, lentils, peas, soybeans); oil plants (rape, mustard, poppy, olives, sun- flowers, coconut, castor oil plants, cocoa beans, groundnuts); cucumber plants (cucumber, marrows, melons); fibre plants (cotton, flax, hemp, jute); citrus fruit (oranges, lemons, grapefruit, mandarins); vegetables (spinach, lettuce, asparagus, cabbages, carrots, onions, tomatoes, potatoes, paprika) or plants such as maize, tobacco, nuts, coffee, sugar cane, tea, vines, hops, bananas, avocados and natural rubber plants, as well as ornamentals.

The compound of formula (la) is effective especially against the phytopathogenic fungi belonging to the following classes: Ascomycetes e.g. Erysiphe, Ven- turia, Pyrenophora, Calonectria graminicola; Basidiomycetes, e.g. rusts (Puc- cinia) and smuts (Tilletia and Ustilago); Deuteromycotina, e.g. Helminthospo- rium, Fusarium, Septoria, Cercospora.

The pathogens that are controlled are especially those attacking cereals at any stage of development, whether it be on emergence, on bushing, on ripening or on sowing. Cereal types, which may be mentioned are, for example, wheat, rye, barley, oats, rice, maize and sorghum. The following important pathogens inter alia are controlled by the compound (la):

Tilletia caries (barley, wheat, rye) Drechslera teres (barley, wheat) Fusarium nivale (rye) Fusarium culmorum (wheat) Erysiphe graminis (cereals)

Erysiphe cichoracearum and Sphaerotheca fuliginea (Cucurbitaceae)

Podosphaera leucotricha (apples)

Uncinula necator (vines) Puccinia graminis (wheat, barley, rye, oats)

Rhizoctonia solani (cotton, lawns)

Ustilago tritici (wheat)

Ustilago maydis (maize)

Helminthosporium gramineum (barley, wheat) Helminthosporium oryzae (rice)

Venturia inaequalis (scab - apples)

Septoria nodorum (wheat)

Septoria triticii (wheat)

Puccinia recondita (wheat) Puccinia hordei (barley)

Botrytis cinerea (gray mold - strawberries and vines)

Cercospora arachidicola (groundnuts)

Pseudocercosporella herpotrichoides (wheat, barley, rye)

Pyrenophora teres (barley) Pyricularia oryzae (rice)

Hemileia vastatrix (coffee) Alternaria solani (potatoes, tomotoes) Sclerotium rolfsii (groundnuts and lawns) Phakops or a pachyrhizi soyabean)

The compound of formula (la) is particular useful for the control of diseases caused by Ascomycetes (e.g. Mildew); Basidiomycetes (e.g. Rusts), and Deu- teromycetes (Septoria) on cereals and in particularly on wheat and barley. Further, the compound of formula (la) may be used in the dressing of seeds to protect against such diseases as Fusarium, Septoria, Tilletia, Ustilago and Helminthosporium on cereals, Rhizoctonia solani on cotton and Pyricularia oryzae on rice

The compound of formula (la) or (lb) can be converted into the customary for- mulations, such as solutions, emulsions, suspensions, dusts, powders, pastes or granules. The use forms here depend on the particular intended use. The formulations are prepared in a known manner, eg. by extending the active compound with solvents and/or carriers, if desired using emulsifiers and dispers- ants, where if water is used as a diluent other organic solvents can also be used as auxiliary solvents.

Suitable auxiliaries for this purpose are mainly: solvents such as aromatics (eg. xylene), chlorinated aromatics (eg. chloroben- zenes), paraffins (eg. petroleum fractions), alcohols (eg. methanol, butanol), ke- tones (eg. cyclohexanone), amines (eg. ethanolamine, dimethylformamide) and water; carriers such as ground natural minerals (eg. kaolins, aluminas, talc, chalk) and ground synthetic minerals (eg. highly disperse silica, silicates); emulsifiers such as nonionic and anionic emulsifiers (eg. polyoxyethylene fatty alcohol ethers, alkylsulfonates and arylsulfonates) and dispersants such as lignin-sulfite waste liquors and methylcellulose.

Suitable surface-active substances are the alkali metal, alkaline earth metal and ammonium salts of aromatic sulfonic acids, eg. lignosulfonic, phenolsulfonic, naphthalenesulfonic and dibutylnaphthalenesulfonic acid, and also of fatty acids, alkyl- and alkylarylsulfonates, alkyl-, lauryl ether and fatty alcohol sulfates, as well as salts of sulfated hexa-, hepta- and octadecanols, and also of fatty alcohol glycol ethers, condensation products of sulfonated naphthalene and its derivatives with formaldehyde, condensation products of naphthalene or of the naphthalenesulfonic acids with phenol and formaldehyde, polyoxyethylene octylphe- nol ether, ethoxylated isooctyl-, octyl- or nonylphenol, alkylphenol or tributyl- phenylpolyglycol ethers, alkylaryl polyether alcohols, isotridecyl alcohol, fatty alcohol ethylene oxide condensates, ethoxylated castor oil, polyoxyethylene or polyoxypropylenealkyl ethers, lauryl alcohol polyglycol ether acetate, sorbitol esters, lignin-sulfite waste liquors or methylcellulose.

Aqueous use forms can be prepared from emulsion concentrates, dispersions, pastes, wettable powders or water-dispersible granules by addition of water. To prepare emulsions, pastes or oil dispersions, the substrates can be homogenized in water as such or dissolved in an oil or solvent, by means of wetting agents, adhesives, dispersants or emulsifiers. However, concentrates consisting of active substance, wetting agent, adhesive, dispersant or emulsifier and possibly solvent or oil can also be prepared which are suitable for dilution with water.

Powder, scattering and dusting compositions may be prepared by mixing or joint grinding of the active substances with a solid carrier.

Granules, eg. coated, impregnated and homogeneous granules, can be prepared by binding the active compounds to solid carriers. Solid carriers are mineral earths such as silica gel, silicic acids, silicates, talc, kaolin, limestone, lime, chalk, bole, loess, clay, dolomite, diatomaceous earth, calcium sulfate and magnesium sulfate, magnesium oxide, ground synthetic materials, fertilizers, such as ammonium sulfate, ammonium phosphate, ammonium nitrate, ureas and vegetable products, such as cereal flour, tree bark meal, wood meal and nutshell meal, cellulose powder or other solid carriers. The active compound concentrations in the ready-to-use preparations can be varied within relatively wide ranges.

Very generally, the compositions contain from 0.0001 to 95% by weight of active compound. Formulations containing more than 95% by weight of active compound can be applied highly successfully in the ultra-low volume process

(ULV), it even being possible to use the active compound without additives. While concentrated compositions are more preferred as commercially available goods, the end consumer uses, as a rule, dilute compositions. Such pesticidal compositions are part of the present invention. The compositions are applied in amounts sufficient as to provide a fungicidal active amount of the compound (la). Such amount are usually from 0.02 to 1 kg or more of active ingredient per hectar.

When used to influence the growth of plants the compositions are applied in amounts sufficient as to provide a plant growth influencing active amount of the compound (lb). Such amounts are usually from 0.01 to 5 kg or more of active ingredient per hectare.

The active compound of formula (la) according to the invention, as such or in its formulations can also be used as a mixture with known fungicides, bactericides, acaricides, nematicides or insecticides, for example to widen the spectrum of action or to prevent the build-up of resistance. In many cases, synergistic effects are obtained, i.e. the activity of the mixture is greater than the activity of the individual components. Examples of particularly advantageous mixtures are the following compounds.

Fungicides:

2-aminobutane; 8-hydroxyquinoline sulphate; 2-phenylphenol (OPP), aldi- morph, ampropylfos, anilazine, azaconazole, azoxystrobin, benalaxyl, benodanil, benomyl, binapacryl, biphenyl, bitertanol, blasticidin-S, bromuconazole, bupirimate, buthiobate, calcium polysulphide, captafol, captan, carbendazim, carboxin, carpropamid, quinomethionate, chloroneb, chloropicrin, chlorothalonil, chlozolinate, cufraneb, cyazofamid, cymoxanil, cyproconazole, cyprodinil, cyprofuram, dichlorophen, diclobutrazol, diclocymet, diclofluanid, diclomezin, dicloran, di- ethofencarb, difenoconazole, diflumetorim, dimethirimol, dimethomorph, dini- conazole, dinocap, diphenylamine, dipyrithion, ditalimfos, dithianon, dodine, drazoxolon, edifenphos, enestroburin, epoxiconazole(racemic), ethaboxam, ethirimol, etridi- azole, famoxadone, fenamidone, fenarimol. fenbuconazole, fenfuram, fenhexamid, fenitropan, fenpiclonil, fenpropidin, fenpropimorph, fentin acetate, fentin hydroxide, ferbam, ferimzone, fluazinam, fludioxonil, flumoφh, fluoromide, fluoxastrobin, fluquinconazole, flusilazole, flusulfamide, flutolanil, flutriafol, folpet, fosetyl-aluminium, fthalide, fuberidazole, furalaxyl, furmecyclox, guazatine, hexachlorobenzene, hexaconazole, hymexazol, imazalil, imibenconazole, iminoctadine, iprobenfos (IBP), iprodione, iprovali- carb, isoprothiolane, kasugamycin, copper preparations such as: copper hydroxide, copper naphthenate, copper oxychloride, copper sulphate, copper oxide, ox- ine-copper and Bordeaux mixture, mancopper, mancozeb, maneb, mepanipyrim, metconazole, kresoxim-mefhyl, mepronil, metalaxyl, metconazole, methasulfocarb, methfuroxam, metiram, me- tominostrobin, metrafenone, metsulfovax, myclobutanil, nickel dimethyldithiocarbamate, nitrothal-isopropyl, nuarimol, ofurace, oxadixyl, oxamocarb, oxycarboxin, pefurazoate, penconazole, pencyuron, phosdiphen, picoxystrobin, pimaricin, piperalin, polyoxin, probenazole, prochloraz, procymidone, propamocarb, propi- conazole, propineb, prothioconazole, pyraclostrobin, pyrazophos, pyrifenox, pyrimethanil, pyroquilon, quinoxyfen, quintozene (PCNB), silthiofam, simeconazole, spiroxamine, sulphur and sulphur preparations, tebuconazole, tecloftalam, tecnazene, tetraconazole, thiabendazole, thicyofen, thifluzamide, thiophanate-methyl, thiram, tolclophos-methyl, tolylfluanid, tri- adimefon, triadimenol, triazoxide, trichlamide, tricyclazole, tridemoφh, triflox- ystrobin, trifiumizole, triforine, triticonazole, validamycin, vinclozolin, zineb, ziram, zoxamide. Bactericides: bronopol, dichlorophen, nitrapyrin, nickel dimethyldithiocarbamate, kasugamy- cin, octhilinone, furanecarboxylic acid, oxytetracyclin, probenazole, streptomycin, tecloftalam, copper sulphate and other copper preparations.

Insecticides/ Acaricides/Nematicides: abamectin, acephate, acetamiprid, acrinathrin, alanycarb, aldicarb, alphamethrin, amitraz, avermectin, azadirachtin, azinphos, azocyclotin,

Bacillus thuringiensis, bendiocarb, benfuracarb, bensultap, betacyfluthrin, bifenazate, bifenthrin, bistrifluron, BPMC, brofenprox, bromophos, bufencarb, buprofezin, butocarboxin, butylpyridaben, cadusafos, carbaryl, carbofuran, carbophenothion, carbosulfan, cartap, chloetho- carb, chloroethoxyfos, chlorfenapyr, chlorofenvinphos, chlorofluazuron, chloromephos, chloropyrifos, chromafenozide, cis-resmethrin, clothianidin, clo- cythrin, clofentezine, cyanophos, cycloprothrin, cyfluthrin, cyhalothrin, cy- hexatin, cypermethrin, cyromazine, deltamethrin, demeton, difenthiuron, diazinon, dichlofenthion, dichlorvos, di- cliphos, dicrotophos, diethion, diflubenzuron, dimethoate, dimethylvinphos, dinotefuran, dioxathion, disulfoton, edifenphos, emamectin (-benzoate salt), esfenvalerate, ethiofencarb, ethion, ethofenprox, ethoprophos, etoxazole, etrimphos, fenamiphos, fenzaquin, fenbutatin oxide, fenitrothion, fenobucarb, fenothiocarb, fenoxycarb, fenpropathrin, fenpyrad, fenpyroximate, fenthion, fenvalerate, fipronil, flonicamid, fluazinam, fluazuron, flucycloxuron, flucythrinate, flufenoxuron, flufenprox, fluvalinate, fonophos, formothion, fosthiazate, fubfen- prox, furathiocarb, gamma-cyhalothrin,

HCH, heptenophos, hexaflumuron, hexythiazox, imidacloprid, indoxacarb, iprobenfos, isazophos, isofenphos, isoprocarb, isoxathion, ivermectin, lambda-cyhalothrin, lufenuron, malathion, mecarbam, mevinphos, mesulfenphos, metaldehyde, methacrifos, methamidophos, methidathion, methiocarb, methomyl, methoxyfenozide, metol- carb, milbemectin, monocrotophos, moxidectin, naled, nitenpyram, omethoate, oxamyl, oxydemethon M, oxydeprofos, parathion A, parathion M, permethrin, phenthoate, phorate, phosalone, phosmet, phosphamidon, phoxim, pirimicarb, pirimiphos, profenofos, promecarb, propaphos, propoxur, prothiofos, prothoate, pymetrozin, pyrachlophos, pyri- daphenthion, pyresmethrin, pyrethrum, pyridaben, pyrimidifen, pyriproxifen, quinalphos, salithion, sebufos, silafluofen, spinosad, spirodiclofen, sulfotep, sulprofos, tebufenozid, tebufenpyrad, tebupirimiphos, teflubenzuron, tefluthrin, temephos, terbam, terbufos, tetrachlorvinphos, thiafenox, thiamethoxam thiodicarb, thio- fanox, thiomethon, thionazin, thuringiensin, tralomethrin, triarathen, triazophos, triazuron, trichlorfon, triflumuron, trimethacarb, vamidothion, XMC, xylylcarb, zetamethrin.

Especially preferred (synergistic) mixture partners are benzimidazole fungicides

(e.g. benomyl, carbendazim, fuberidazole, thiabendazole), imidazole/triazole fungicides (e.g. azaconazole, bitertanol, bromuconazole, cyproconazole, difenoconazole, fenbuconazole, fluquinconazole, flusilazole, flutriafol, hexaconazole, imazalil, ipconazole, metconazole, myclobutanil, paclobutrazol, penconazole, propiconazole, prochloraz, prothioconazole, tebuconazole, tetraconazole, tridi- mefon, triadimenol, triticonazole, uniconazole), carboxamide fungicides (e.g. boscalid, flutolanil, thifiuzamide), moφholine fungicides (e.g. dimethomoφh, dodemoφh, fenpropimoφh, fenpropidin, flumoφh, spiroxamine, tridemoφh), neonicotinoid insecticides, (e.g. acetamiprid, clothianidin, dinotefuran, imida- cloprid, nitenpyram, thiacloprid, thiamethoxam), phenylamide fungicides (e.g. benalaxyl, furalaxyl, metalaxyl, metalaxyl-M, ofurace, oxadixyl), organophos- phate insecticides (e.g. chloφyrifos, chloφyrifos-methyl, dimethoate, malathion, phosalone), pyrethroid type insecticides (e.g. acrinathrin, bifenthrin, bioallethrin, bioresmethrin, cyfluthrin, cyhalothrin, cypermethrin, deltamethrin, esfenvalerate, fenvalerate, gamma cyhalothrin, lambda cyhalothrin, permethrin, resmethrin, tau fluvalinate, tefluthrin, tralomethrin), strobilurin type fungicides (e.g. azox- ystrobin, dimoxystrobin, famoxadone, fenamidone, fluoxastrobin, kresoxim- methyl, metominostrobin, picoxystrobin, pyraclostrobin, trifloxystrobin), abamectin, caφropamide, captan, chlorothalonil, cyprodinil, fenhexamid, fipronil, fluazinam, folpet, fosethyl-al, iprodione, iprovahcarb, mancozeb, maneb, metiram, metrafenone, pyrimefhanil, quinoxyfen, sulfur, thiophanate- methyl, thiram, tolylfluanid, vinclozolin, zineb, and zoxamide.

A mixture with other known active compounds, such as herbicides or with fertil- izers or growth regulators (e.g. mepiquat and salts there of) is also possible.

The active compound of formula (lb) according to the invention, as such or in its formulations can also be used as a mixture with known plant growth regulators, fungicides, bactericides, acaricides, nematicides or insecticides. In many cases, synergistic effects are obtained, i.e. the activity of the mixture is greater than the activity of the individual components.

Examples of particularly advantageous mixtures are the following plant growth regulating compounds:

antiauxins: clofibric acid, 2,3,5-tri-iodobenzoic acid, auxins: 4-CPA, 2,4-D, 2,4-DB, 2,4-DEP, dichloφrop, fenoprop, IAA, IBA, naphthaleneacetamide, α-naphthaleneacetic acid, 1-naphthol, naphthoxyacetic acid, potassium naphthenate, sodium naphthenate, 2,4,5-T cytokinins: 2iP, benzyladenine, kinetin, zeatin defoliants: calcium cyanamide, dimethipin, endothal, ethephon, meφhos, me- toxuron, pentachlorophenol, thidiazuron, tribufos ethylene inhibitors: aviglycine, 1-methylcyclopropene ethylene releasers: ACC, etacelasil, ethephon, glyoxime, growth inhibitors: abscisic acid, ancymidol, butralin, carbaryl, chloφhonium, chloφropham, dikegulac, flumetralin, fluoridamid, fosamine, glyphosine, isopyrimol, jasmonic acid, maleic hydrazide, mepiquat, piproctanyl, prohy- drojasmon, propham, 2,3,5-tri-iodobenzoic acid moφhactins: chlorfluren, chlorflurenol, dichlorflurenol, flurenol growth retardants: chlormequat, daminozide, fiuφrimidol, mefluidide, pa- clobutrazol, tetcyclacis, uniconazole growth stimulators: brassinolide, forchlorfenuron, hymexazol unclassified plant growth regulators: benzofluor, buminafos, carvone, ciobutide, clofencet, cloxyfonac, cyclanilide, cycloheximide, epocholeone, ethychlozate, ethylene, fenridazon, heptopargil, holosulf, inabenfide, karetazan, lead arsenate, methasulfocarb, prohexadione, pydanon, sintofen, triapenthenol, trinexapac.

The invention is illustrated by the following examples:

Example 1 - preparation of the starting material (II) To a stirred solution of 60.0 g (0.22 mol) 3-(2-chlorophenyl)-2-(4- fluorophenyl)oxiranecarbaldehyde (94 % (Z)-isomer) in 200 ml acetonitrile was added 1.6 g NaH₂PO₄ dissolved in 20 mL water. The mixture was cooled with ice and 20 ml 35% H₂O₂ was added in one portion. A solution of 32 g 80% pure NaClO₂ in 280 mL water was then added with stirring at 8 - 10 °C during 2 hours. After additional stirring, 10 g of NaHSO₃ was added, followed by 600 mL t-butyl methylether. The organic phase was washed with 400 mL water, dried with anhydrous sodium sulfate and the solvent evaporated to leave crude (Z)-3- (2-chlorophenyl)-2-(4-fluorophenyl)oxiranecarboxylic acid (11). Yield 58.4 g. Example 2 - preparation of the compound (Ila)

100.0 g (0.34 mol) of the racemic compound (II) from example 1 is dissolved in 400 mL methanol and the solution cooled in an ice bath to 0-3°C. Over a period of 5 hours, 20.6 g (0.17 mol) (S)-l-methylbenzylamine dissolved in 680 mL methanol is added with stirring. Stirring is then continued at 0-3° C for 4 hours. The white precipitate formed during the reaction is filtered off and washed with 100 mL ice cooled ethanol. This precipitate is then stirred at room temperature with 200 mL 1M HC1 and 300 mL t-butylmethylether until all solids are dissolved. The phases are separated and the organic phase is washed with 200 mL water, dried with anhydrous Na₂SO₄ and concentrated on a rotary evaporator at 60° C/12 mm to give white crystals of (2R,3R)-3-(2-chlorophenyl)-2-(4- fluorophenyl)oxiranecarboxylic acid (Ila). Yield 32g (64% of theory). Enantiomeric purity 99.6%) by chiral HPLC. Optical rotation: [ ]²⁰D=-14° (CHC1₃) 62.9 MHz ¹³C NMR (CDCI₃, ppm): 168.0, 162.9 (doublet, =257 Hz), 133.4, 132.0, 131.1, 130.1, 129.2, 128.9, 127.9, 126.5, 115.3 (doublet J=l 2 Hz), 65.9 and 63.3.

Example 3 - preparation of compound (lib) Using the same procedure as in example 2, employing (R)-l-methylbenzylamine instead of the (S)-enantiomer, (2S,3S)-3-(2-chlorophenyl)-2-(4-fluorophenyl)- oxiranecarboxylic acid (lib) is prepared. Yield 31g (62%> of theory). Enantiomeric purity 99.7% by chiral HPLC. Optical rotation: [ ]²⁰D= 14° (CHCI3) ¹³C NMR: identical to that of compound (Ha).

Example 4 - preparation of the compound (Ilia)

10.5 g (0.036 mol) of the compound (Eta) is dissolved in 200 mL CH₂C1₂ comprising 4 g N(CH₂CH₃)₃ and the mixture cooled to 0 °C. Over a 1 hour period 4.1 g (0.038 mol) of ethoxycarbonyl chloride dissolved in 10 mL CH2CI2 was added to the reaction mixture and stirred for an additional 2 hour period. The reaction mixture was then slowly added under stirring to a solution of 5.4 g NaBH₄ in 100 mL absolute ethanol while maintaing the temperature at 0 °C. Af- ter one hour, the mixture was left to stand for 12 hours with continuos stirring at room temperature. The reaction mixture was washed with 200 ml of water, extracting the water phase with CH₂CI2 and the combined organic phases washed with 100 ml of 1M hydrochloric acid followed by washing with 100 ml water and drying the organic phase over Na₂SO₄. The solvent was removed by evapo- ration at reduced pressure to give a clear oil from which the (2S,3R)-3-(2- chlorophenyl)-2-(4-fluorophenyl)oxiranemethanol crystallises out. Yield 9.6g (96% of theory). Enantiomeric purity 96.4% by chiral HPLC. Optical rotation: [α]²⁰D=-47° (CHCI3) 62.9 MHz ^,3C NMR (DMSO-d_6> ppm): 162.0(doublet, =243 Hz), 135.3, 133.6, 132.4, 129.9, 129.3, 128.9, 128,2, 127.4, 115.4 (doublet, J=21 Hz), 66.0, 63.9 and 61.3.

Example 5 - preparation of compound (IHb)

Using the same procedure as in example 4, employing the (2S,3S) enantiomer (Hb) instead of the (2R,3R) enantiomer (Ila), (2R,3S)-3-(2-chlorophenyl)-2-(4- fluorophenyl)oxiranemethanol (IHb) is prepared. Yield 9.1g (91%> of theory).

Enantiomeric purity higher than 99.8%> by chiral HPLC.

Optical rotation: [α]²⁰D= 48° (CHCI3)

¹³C NMR: identical to that of compound (Ilia).

Example 6 - preparation of compound (IVa, L = OSO^CHV)

To a mixture of 8.0g (0.029 mol) of compound (fl a) and 3.8g (0.038 mol) Et₃N in 45 mL toluene at room temperature is added 3.9 g (0.037 mol) CH₃SO2Cl dis- solved in 4 mL toluene under stirring. Stirring is continued for one hour, and then 100 mL of water is added. Extraction with 100 mL of t-butylmethylether, washing of the ethereal phase with 50 mL water, drying with anhydrous sodium sulfate and evaporation of the solvent yields 9.6 g of crude product. Recrystalli- 5 sation from 150 ml of 2-propanol with cooling to 0°C produces white crystals of (2S,3R)-3-(2-chlorophenyl)-2-(4-fluorophenyl)oxiranylmethyl methanesulfonate (IVa, L = OSO₂CH₃). Yield 8.9 g (87 % of theory). Enantiomeric and di- astereomeric purity higher than 99.8 % by chiral HPLC. Optical rotation: [α]²⁰D=-50° (CHC1₃) 10 62.9 MHz ¹³CNMR (CDC1₃, ppm): 162.9 (doublet, J=248 Hz), 132.9, 132.2, 132.1, 129.9, 129.3, 128.1, 127.9, 127.3, 115.8 (doublet, J=22 Hz), 69.9, 64.3, 63.2 and 37.5.

Example 7 - preparation of compound (IVb, L = OSO2CH3 15 Using the same procedure as in example 6, employing the (2R,3S) enantiomer (Hlb) instead of the (2S,3R) enantiomer (Ilia), (2R,3S)-3-(2-chlorophenyl)-2-(4- fluorophenyl)oxiranylmethyl methanesulfonate (IVb, L = OSO₂CH₃) is prepared. Yield 9.2 g (90 % of theory). Enantiomeric and diastereomeric purity higher than 99.8 % by chiral HPLC. 20 Optical rotation: [α]²⁰D=50° (CHC1₃) ¹³C NMR: identical to that of compound (Hla).

Example 8 - preparation of compound (la) from compound (IVa, L = OSO^CHV) A mixture of 7.9 g (0.022 mol) of compound (IVa, L = OSO₂CH₃), 1.82 g (0.026

25 mol) 1,2,4-triazole and 4.39 g (0.032 mol) finely ground K₂CO₃ in 60 mL dimethyl sulfoxide, is stirred at room temperature for 18 hours. Then 200 ml of water is added with stirring, and stirring continued for 30 min. The precipitate is then filtered, washed with water and recrystalized from 75 mL of 2-propanol with cooling in ice, producing white crystals of (2S,3R)-l-[3-(2-chlorophenyl)-

30 2-(4-fluorophenyl)oxiranyl]methyl-lH-[l,2,4]triazole (la). Yield 5.9 g (81% of theory). Enantiomerical and diastereomerical purity higher than 99.8 % by Chiral HPLC.

Optical rotation: [α]²⁰D=-121° (CHC1₃)

62.9 MHz ¹³C NMR (DMSO-d₆, ppm): 116.8 (doublet, J=245 Hz), 151.3, 144.6, 132.9, 132.3, 132.1, 130.0, 129.2, 128.3, 127.9, 127.5, 115.2 (doublet, J=22 Hz), 64.3, 63.6 and 50.0.

Example 9 - preparation of compound (lb) from compound (IVb, L =

Using the same procedure as in example 8, employing the (2R,3S) enantiomer (IVb, L = OSO2CH₃) instead of the (2S.3R) enantiomer (IVa, L = OSO₂CH₃), (2R,3S)-l-[3-(2-chlorophenyl)-2-(4-fluorophenyl)oxiranyl]methyl-lH- [1,2,4] triazole (lb) is prepared. Yield 5.6 g (78% of theory). Enantiomerical and diastereomerical purity higher than 99.8 % by Chiral ΗPLC. Optical rotation: [α]²⁰D=120° (CΗCI3)

¹³C NMR: identical to that of compound (la).

Example 10 - preparation of compound (TV a, L = CD

To a mixture of 3.1 g (0.011 mol) of (ma), 1.1 g (0.014 mol) of pyridine and 10 ml of toluene, 1.5 g (0.013 mol) of thionyl chloride is added with stirring, keeping the temperature below 40° C. After 30 min. at room temperature, the reaction mixture is stirred at 100° C for 120 min., and is then poured into a mixture of 25 ml of water and 40 ml of toluene in a separatory funnel. After separation af the aqueous phase, the toluene phase is washed with 25 ml of a saturated aque- ous solution of sodium bicarbonate and then with 25 ml of water. The toluene solution is then dried with sodium sulphate and the solvent evaporated to give a semisolid residue. Recrystallization from 10 ml of

2-propanol gives (2R,3R)-2-(chloromethyl)-3-(2-chlorophenyl)-2-(4- fluorophenyl)oxirane (IVa, L = CI). Yield 2.0 g (61 % of theory). Optical rotation: [α]²⁰ D= -92° (CHC1 )

62.9 MHz ¹³C NMR (CDCI₃, ppm): 162.7 (doublet, J=247 Hz), 133.2, 133.1, 132.6, 129.7, 129.2, 128.5, 128.0, 127.1, 115.5 (doublet, J=22 Hz), 65.7, 65.0 and 45.5.

Example 11 - preparation of compound (IVa, L = Br)

To a stirred mixture of 4.0 g (0.014 mol) of (HJa), 5.6 g (0.022 mol) of triphenylphosphine and 70 ml of methylene chloride held at 0° C is added 6.2 g (0.018 mol) of tetrabromomethane during 30 min. After stirring the mixture for further 3 hrs at 0° C, the mixture is washed with with 25 ml of a saturated aqueous solution of sodium bicarbonate and then with 25 ml of water. The organic phase is then dried with sodium sulphate and the solvent evaporated to give a solid residue. This residue is dissolved in 100 ml of methylene chloride: hexane, and filtered through 150 g of silica gel by means of a further 150 ml volume of the same solvent. Evaporation of the solvent and recrystallization of the residue from 20 ml of 2-propanol gives (2R,3R)-2-(bromomethyl)-3-(2 chlorophenyl)-2- (4-fluorophenyl)oxirane (IVa, L = Br). Yield 4.2 g (88 % of theory). Optical rotation: [α]²⁰ D= -118° (CHC1₃) 62.9 MHz ¹³C NMR (CDC1₃, ppm): 162.7 (doublet, J= 247 Hz), 133.5, 133.1, 132.5, 126.6, 129.2, 128.4, 128.2, 127.9, 127.1, 115.5 (doublet, J=22 Hz), 66.9, 64.8 and 33.6.

Example 12 - preparation of compound (la) from compound (IVa, L = CD

A mixture of 2.3 g (0.0078 mol) of compound (IVa, L = CI), 0.64 g (0.0092 mol) 1,2,4-triazole and 1.6 g (0.011 mol) finely ground K₂CO₃ in 20 mL dimethyl sulfoxide, is stirred at 50°C for 13 hrs. Then 75 ml of water is added with stirring, and stirring continued for 30 min. The precipitate is then filtered, washed with water and recrystalized from 20 mL of 2-propanol with cooling in ice, producing white crystals of (2S,3R)-l-[3-(2-chlorophenyl)-2-(4- fluorophenyl)oxiranyl]methyl-lH-[l,2,4]triazole (la). Yield 1.8 g (71 % of the- ory). Enantiomeric and diastereomeric purity higher than 99.8 % by Chiral HPLC. Optical rotation and 62.9 MHz ¹³C NMR identical to that of example 8. Example 13 - preparation of compound (la) from compound (IVa, L = Br) A mixture of 1.7 g (0.0050 mol) of compound (IVa, L = Br), 0.52 g (0.0075 mol) 1,2,4-triazole and 1.04 g (0.0075 mol) finely ground K₂CO₃ in 20 mL dimethyl sulfoxide, is stirred at 50°C for 18 hrs. Then 50 ml of water is added with stirring, and stirring continued for 30 min. The precipitate is then filtered, washed with water and recrystahzed from 12 mL of 2-propanol with cooling in ice, producing white crystals of (2S,3R)-l-[3-(2-chlorophenyl)-2-(4- fluorophenyl)oxiranyl]methyl-lH-[l,2,4]triazole (la). Yield 1.1 g (64 % of theory). Enantiomeric and diastereomeric purity higher than 99.8 %> by Chiral ΗPLC. Optical rotation and 62.9 MHz ¹³C NMR identical to that of example 8.

Example A - Control effect on Septoria nodorum and Septoria triticii (Deu- teromycetes) on agar medium. Standard formulations were prepared by mixing under stirring the following ingredients (all amounts in grams):

^a Blend of aromatic hydrocarbons. Available from Exxon ^b) Alcohol emulsifier blends. Available from AkzoNobel Standard KDA agar plates were inoculated with a fungal suspension of Septoria triticii, or Septoria nodorum, respectively. Solutions containing 0.3; 1 and 3g/L ai were applied as single 5μL drops directly on the surfaces of the inoculated plates, which where incubated for 24hrs at 23°C. The fungus growth inhibitory activity was determined as the diameter of the fungus free "halo" around the site of application.

Table 1 : Control effect on Septoria nodorum and Septoria triticii (Deuteromy- cetes) on agar medium. Values are average diameters in cm of fungal-free zone around site of application.

Example B - Control effect on Puccinia recondita (Basidiomycetes) on wheat. Wheat (Triticum aestivum L.). was cultivated in pots under greenhouse condi- tions. At 7 days after germination four leaves (second leaf) from four separate seedlings were divided into 4 regions using a non-toxic marker. Region 1 was toward the leaf base, while region 4 was the leaf tip area. The seedlings were inoculated with a fungal suspension of Puccinia recondita. The inoculated seedlings were incubated for a period of 24h at 18°C. Solutions, using the standard formulations in example A, containing 0.0067 and 0.00067g/L ai were applied as three 5μL drops directly on the surfaces of region 2 of the inoculated leaves. The fungus growth inhibitory activity was determined as the absence or presence of the fungus in region 2 (contact activity) and regions 1, 3 and 4 (systemic activity). Table 2: Control effect on Puccinia recondita (Basidiomycetes) on wheat. Values represent fungal occurrence in respective leaf regions (arbitrary values).

Example C - Control effect on Puccinia recondita on wheat (climate chamber). Wheat (Triticum aestivum L.) was cultivated in pots under controlled conditions in a climate chamber. 2 days before spraying (curative) or 1 day after spraying (preventative) the seedlings were inoculated with a fungal suspension of Puccinia recondita. The inoculated seedlings were incubated for a period of 24h at 18°C. Plants were sprayed with the racemic and chiral solutions at rates of 0.3, 1, 3, 10, 30, 100 or 300g/Ha, respectively. Fungicidal effect was determined visually as the absence or presence of the fungus on the leaves. By fitting the effect data to a sigmoidal dose-response curve the ED50 value was determined. Table 3: Control effect on Puccinia recondita on wheat (climate chamber).

Example D - Control effect on Puccinia recondita on wheat (semi-field trials). Wheat (Triticum aestivum L.) was cultivated in pots under controlled conditions in a climate chamber. Plants were sprayed with the racemic and chiral solutions at rates of 0.3, 1, 3, 10, 30, 100 or 300g/Ha, respectively. One day after spraying the seedlings were inoculated with a fungal suspension of Puccinia recondita. The inoculated seedlings were incubated for a period of 24h at 18°C. Following inoculation and spraying, plants where transferred to a semi-field plot, consisting of a greenhouse table erected in the immediate vicinity of a wheat field. Fungi- cidal effect was determined visually as the absence or presence of the fungus on the leaves. By fitting the effect data to a sigmoidal dose-response curve the ED50 value was determined.

Table 4: Control effect on Puccinia recondita on wheat (semi-field trials).

Example E - Effect of seed treatment on germination and seedling emergence (greenhouse).

Wheat (Triticum aestivum L.) and barley (Hordeum vulgare L.) seeds where seed-treated by adding 50μl of lOg/L racemic and chiral solutions, respectively, to lOg of seed. The treated seeds where mechanically agitated to evenly coat all seeds, and allowed to dry. For each treatment, 5 pots where sown with 10 seeds in each pot, and the effect of seed treatment on germination and seedling emergence was monitored.

Table 5: Average plant height, seven days after sowing.

Claims

P A T E N T C L A I M S 1. A process for the preparation of a compound of the formula (la)

which is (2S,3R)-l-[3-(2-chloroρhenyl)-2-(4-fluorophenyl)oxiranyl]-methyl-lH- [l,2,4]triazole said process comprising the steps of a) contacting a compound of the formula (II),

which is Z-3-(2-Chloro-phenyl)-2-(4-fluoro-phenyl)oxiranecarboxylic acid, with an optically active acid-salt forming resolving agent to form diastereomeric salts and subjecting the so-formed diastereomeric salts to fractional crystallisation in a solvent to separate the (2R,3R) acid-salt from the (2S,3S) acid-salt and subse- quently liberating the (2R,3R) acid from the salt; b) treating the (2R,3R) enantiomer of the compound (II) with an alkoxycarbonyl chloride to form an anhydride intermediate which is reduced with a reducing agent to produce a compound of formula (πia),

c) converting the compound (IHa) into a compound (IVa)

2. A process according to claim 1, wherein the acid-salt forming resolving agent is an optically active amine.

3. A process according to claim 2, wherein then optically active amine is a compound of the formula (V)

wherein R and R are different and each represent C_1-8 alkyl optionally substituted with one or more phenyl groups; phenyl or naphtyl which may be substituted with one or more Cι_-4 alkyl groups.

4. A compound (la) which is (2S,3R)-l-[3-(2-chlorophenyl)-2-(4- fluorophenyl)oxiranyl]methyl-lH-[l,2,4]triazole.

5. A compound (lb) which is (2R,3S)-l-[3-(2-chlorophenyl)-2-(4- fluorophenyl)oxirany]lmethyl-lH-[l,2,4]triazole.

6. A compound of formula (III) in its (2S,3R) or (2R,3S) configuration

7. A compound according to claim 6, which is (2S,3R)-3-(2- chlorophenyl)-2-(4-fluorophenyl)-oxiranemethanol.

8. A compound of the formula (IVa) or (IVb)

(IVa) (IVb) where in L represents a leaving group other than OH.

9. A compound according to claim 8 of the formula (IVa).

10. A compound according to claim 8 wherein L represents halogen, Cι_-6-alkyl sulfonyloxy or arylsulfonyloxy wherein the aryl group optionally is substituted with one or more halogen or Cι_-6-alkyl groups.

11. A compound according to claim 10 wherein L represents CI, Br or

12. A composition for controlling harmful fungi comprising at least 70%) by weight of the compound (la) relative to the compound (lb) or any of the other enantiomers having the general structure (I)

13. A composition according to claim 12, further comprising a solid or liquid carrier.

14. A composition according to claim 12 or 13 wherein the weight of the compound (la) relative to the compound (lb) or any other of the enantiomers having the general structure (I) is at least 80%.

15. A composition according to claim 14 wherein the weight of the compound (la) relative to the compound (lb) or any other of the enantiomers having the general structure (I) is at least 90%₀.

16. A composition according to claim 15 wherein the weight of the compound (la) relative to the compound (lb) or any other of the enantiomers having the general structure (I) is at least 99%.

17. A method of controlling harmful fungi, which comprises treating the fungi or the materials, plants, soil or seed to be protected from fungal attack with an active amount of a composition according to claim 12.

18. A composition for influencing the growth of plants comprising at least 70%) by weight of the compound (lb) relative to the compound (la) or any of the other enantiomers having the general structure (I)

19. A composition according to claim 18, further comprising a solid or liquid carrier.

20. A composition according to claim 18 or 19 wherein the weight of the compound (lb) relative to the compound (la) or any other of the enantiomers having the general structure (I) is at least 80%>.

21. A composition according to claim 20 wherein the weight of the compound (lb) relative to the compound (la) or any other of the enantiomers having the general structure (I) is at least 90%>.

22. A composition according to claim 21 wherein the weight of the compound (lb) relative to the compound (la) or any other of the enantiomers having the general structure (I) is at least 99%).

23. A method of influencing the growth of plants, which comprises treating the plants, soil or seed with an active amount of a composition accord- ing to claim 18.