DD268852A5 - SCHAEDLINGSBEKAEMPFUNGSMITTEL - Google Patents

Abstract

The present invention relates to pesticides containing as active ingredient an azole compound of the general formula I in addition to conventional extenders and / or formulation auxiliaries. In GB-PS 214 352 3 A 1-aryl-1-azolylmethyl-1,3-dihydroisobenzofurane be described as fungicides in crop protection. However, neither antifungal or anticonvulsant effects are described therein nor the compounds of the invention. The compounds used according to the invention and their stereoisomers and salts have advantageous fungicidal, antifungal and anticovulsive effects. Formula (I)

Description

(D

hergestallt,

A is CH or N

k is 1 or 2

η is 1,2 or 3

Ar is phenyl, biphenyl, phenoxyphenyl, phenoxythienyl, phenylthiophenyl, phenylsulfinylphenyl, phenylsulfonylpher.yl, Benzylphenyl, benzyloxyphenyl, benzylthiophenyl, fluorenyl, indanyl, 1,2,3,4-tetrahydronaphthyl, naphthyl or thienyl

wherein the benzene rings, the naphthalene system or the thiophene ring is unsubstituted or with one or two

Substituents which may be identical or different and each represent fluorine, chlorine, bromine, iodine, (C 1 -C ₈ ) -alkyl,

branched or unbranched, unsubstituted or substituted by 1-9 fluorine and / or chlorine atom, (C 3 -C ₈ ) -cycloalkyl, (C 1 -C ₄ ) -alkoxy, (C 1 -C ₄ ) -alkylthio, hydroxy, nitro or cyano,

W means the atoms necessary to complete a benzene, naphthalene or thiophene ring system, X is a radical <C (R ₃ I ₂ , as well as in the event that W necessary to complete a benzene or naphthalene ring system Atoms also means oxygen or sulfur, R ¹ and R ^{2 are the} same or different and each is hydrogen, fluorine, chlorine, bromine, iodine, (C ₁ -C ₈ J-AlKyI, unbranched or

branched, unsubstituted or substituted with 1-9 fluorine or chlorine atoms, _(C3-C8) cycloalkyl, (C | -C ₈₎ -alkoxy, (C, -C ₈₎ alkylthio,

Cyano or nitro, as well as for the case that at the same time W necessary for the completion of a benzene ring atoms

means

R ^{1 is} also phenyl, i'henoxy, phenylthio, Phehylsulfinyl, phenylsulfonyl, benzyl, benzyloxy rv lor hydroxy, wherein the Phenyl groups in these substituents may be unsubstituted and these substituents are the same or different and

in each case fluorine, chlorine, bromine, iodine, (C, -C ₄ ) -alkyl, branched or unbranched, unsubstituted or substituted by 1-9 fluorine or chlorine atoms, (C ₃ -C ₈ ) -cycloalkyl, (C | -C ₄ ) -Alkoxy, (CH ^ l-alkylthio, cyano or nitro, or R ¹ , R ² , if they are ortho-oriented, together represent a (C ₃ -C ₆ ) alkylene chain and R ³ as a substituent of KeMe- (CH ₂ I _n - or of X independently of one another is H or (Ci-Cn) -alkyl or two radicals R ³ , if they are bonded to the same C atom, a (C ₂ -C ₆ ) -

Alkylene chain and their stereoisomers and their salts. The (C) -C ₈ ) - or (C 1 -C ₄ ) -alkyl groups occurring as substituents or in conjunction with other substituents

may be unbranched or branched and, for example, the methyl, ethyl, propyl, 1-methyl-ethyl, butyl, 2-methylpropyl, 1,1-dimethyl-ethyl, pentyl, hexyl, heptyl or Octyl group; the fluorine- or chlorine-substituted alkyl groups may be, for example, the trifluoromethyl, trichloromethyl, JJ ^^ tetrafluoroethyl or nonafluorobutyl group; the (Cj-Cgl-cycloalkyl groups may be cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, or

Cyclooctyl group mean. The present invention relates to the compounds (I) in the form of the free base or an acid addition salt with

pharmaceutically or agriculturally acceptable acids.

Examples of such acids are inorganic acids such as hydrochloric acid, hydrobromic acid, hydriodic acid, sulfuric acid, Phosphoric acid, or nitric acid or organic acids such as malonic acid, oxalic acid, gluconic acid, camphorsulfonic acid, Benzenesulfonic acid, acetic acid, propionic acid or p-toluenesulfonic acid. The compounds (I) have at least one asymmetric C atom and can therefore be used as enantiomers and diastereomers

occur. The invention includes both the pure isomers and their mixtures. The mixtures of diastereomers can be prepared by conventional methods, for example by selective crystallization from suitable solvents or by

Chromatography on Kiessigel or alumina are separated into the components. Racemates can according to usual Methods are separated into the enantiomers, for example by salt formation with an optically active acid, Separation of the diastereomeric salts and release of the pure enantiomers by means of a base. Preference is given to compounds of the formula I, v. Orin W means the necessary to complete a benzene ring system atoms. X represents the methylene group, oxygen or sulfur, A is CH or N,

η is 1,2 or 3,

Ar is phenyl, 4-biphenylyl, 4-phenoxyphenyl, 4-phenylthiophenyl, fluorenyl, indanyl, 1,2,3,4-tetrahydronaphthyl or Thienyl means unsubstituted or attached to the benzene rings or the thiophene ring with one or two substituents

which may be identical or different and each represents fluorine, chlorine, bromine, (C 1 -C ₄ ) -alkyl, (Q) -C ₈ -cycloalkyl,

(C ¹ -C ₄ ) -alkoxy or trifluoromethyl, R ¹ and R ^{2 are} identical or different and each is hydrogen, fluorine, chlorine, bromine, trifluoromethyl, (C 1 -C ₈ ) -alkyl or (C 1 -C ₈ ) Alkoxy.

Of these compounds, of particular importance are those in which Ar is mono-halophenyl or 2,4-dihalophenyl wherein the halogen atoms are the same or different and

each represents fluorine or chlorine or Ar represents 4-biphenylyl, 4-phenoxyphenyl, 4-phenylthiophenyl or fluorenyl, unsubstituted or substituted on a benzene ring with one or two substituents and these substituents are the same or different and each is fluoro, chloro, trifluoromethyl, methyl or methoxy cover.

Of the latter, particular interests are those in which Ar is 4-chlorononyl, 4-fluorophenyl, 2,4-dichlorophenyl, 2,4- Difluorophenyl, 4-chloro-2-fluorophenyl, fluorenyl, 4-biphenylyl,

4-phenoxyphenyl or 4-phenylthiophenyl, where the latter groups are unsubstituted or in the

4 'position with fluorine, chlorine, methyl, methoxy or the Ti may be beforormormethyl group, R ¹ and R ^{2 are the} same or different and are hydrogen, fluorine, chlorine, trifluoromethyl, methyl or methoxy.

The urfindungsgemäße process for the preparation of compounds of formula (I) is characterized in that

a) a compound of the formula (II)

- N

in which A, W, X, k, n, R ¹ , R ⁷ and R ^{3 have} the meanings given in claim 1, with a compound of the formula (III) Ar-H (III)

wherein Ar has the meanings given in claim 1, in the presence of a Lewis acid or a strong protic acid with elimination of water to give a compound of formula (I).

It works in the temperature range from -20 ⁰ C to 100 ⁰ C, preferably from -10 to 50 ° C, optionally in the presence of an inert diluent. By a Lewis acid or a strong protic acid are the usual Friedel-Crafts catalysts to understand how they - as well as suitable diluents - z. 7-2a, pp. 17-21., Preferred diluents are dichloromethane, 1,2-dichloroethane, 1,1,2,2-tetrachloroethane or else chlorobenzene or dichlorobenzene, preferably aluminum trichloride is used as the catalyst 1.1 to 2.5, preferably 2.0 to 2.3, equivalents, based on the compound of the formula (II), of the catalyst are used, of the arylhydrocarbon of the formula (III) at least 1 equivalent, based on the compound of the formula (II) When the compound of the formula (III) is used in excess, it may simultaneously serve as a diluent.

The invention further relates to a process for the preparation of compounds of the formula (I), characterized in that b) a compound of the formula (IV "),

(IV) η '

< ^R 3> k

in which A, W, X, Ar, k, η, R ¹ , R ² and R ^{3 have} the meanings given in claim 1, in the presence of a Lewis acid or a strong proton acid with elimination of water to give a compound of the formula (I) implements. (R ³ is a substituent of the (CH ₂ ) _n chain).

By a Lewis acid or a strong protic acid are meant the usual Friedel-Crafts catalysts, as they

e.g. in "Houben-Weyl, Methoden der organischen Chemie", Vol. 7 / 2a, pp. 17-21

Aluminum trichloride, 85% sulfuric acid, polyphosphoric acid, 48% hydrobromic acid or hydrogen fluoride. In particular, one proceeds in such a way that when using aluminum chloride as Friedel-Crafts catalyst the Connection of the forms! (IV) in a suitable solvent, preferably dichloromethane, 1,2-dichloroethane or 1,1,2,2- Tetrachloroethane, in a temperature range of -20 ° C-80 ° C, preferably -10 ° C-50 ° C with 1.1 to 2.5, preferably 2.0 to

Brings 2.3 equivalents of aluminum chloride to the reaction.

When using sulfuric acid. Polyphosphoric, hydrobromic or hydrofluoric acid are the

used in large excess and serve simultaneously as Rea'.iionsmedium. In the case of sulfuric acid is carried out in the temperature range of -10 ° C-50 ° C, preferably from 0 ° C-30 ° C, using polyphosphoric or hydrobromic acid in the range of 60-15O ⁰ C, preferably from 80-120 ⁰ C, im the case of hydrogen fluoride in the range of -10 ⁰ C-IOO ⁰ CjVOrZUgSWeISeZWiSChBn 30 ° C-60 ° C, if necessary using an autoclave.

The invention further relates to a process for the preparation of compounds of the formula (I), characterized in that

c) one of the compounds of the formula (I) obtained according to a) or b), for which Ar is a phenyl or naphthyloxy compound substituted by an alkoxy group or for which R 'is an alkoxy group, subjected to ether cleavage and the product thus obtained

Compounds of the formula (I) for which R ^{1 represents} the hydroxyl group or for which Ar represents a hydroxy-substituted group Phenyl or naphthyl group, with a compound of the formula (V),

ER ⁴ (V)

wherein E is a reactive leaving group and R ^{4 is} a (C _: -C ₈ ) alkyl group or benzyl group according to claim 1 means. The ether cleavage is carried out in a conventional manner by heating the alkoxy compound with hydrobromic acid. The etherification with the compound (V) in which the reactive leaving group E is, for example, chlorine, bromine, iodine or a sulphonyloxy group such as 4-toluene, 4-chlorophenyl or methylsulfonyioxy, is carried out usually under the conditions of a Williamson ether synthesis (cf. Organikum, Organic-Chemical Basic Practical Course "Berlin'1969,

P. 223-226) or under the conditions of a phase transfer reaction by reacting the reactants in an aromatic hydrocarbon ₍ such as benzene, chlorobenzene, toluene or xylene with vigorous stirring in the presence of a

Phase transfer catalyst and either a powdered alkali hydroxide, such as. As sodium or potassium hydroxide or a concentrated aqueous solution thereof, preferably in a temperature range of 20 to 120 ° C, interact

Suitable phase starter catalysts are, for example, T-alkylbenzylammonium or tetraalkylammonium halides, hydroxides, hydrogensulfates having preferably 1 to 12 C atoms in the alkyl radical or crown ethers, such as, for example, 12-crown-4, 1-ti-crown-5, le-crown-öoder-dibenzo-ie-crown 6.

The invention further relates to a process for the preparation of compounds of the formula (I), characterized in that

1) a Verbin 'jr .., the formula (I) on a phenylthio group or phenylsulfonyl oxidized.

Suitable oxidizing agents for the oxidation to the sulfoxide are e.g. Hydrogen peroxide or peracids such as peracetic acid or m-chloroperbenemic acid or sodium or potassium metaperiodate; for the oxidation to the sulfone, the same oxidizing agents are suitable with the exception of Metaperjodate. Suitable solvents for the oxidation with peracids are, for. B.

Methylene chloride or chloroform, for the oxidation with periodate alcohol / water mixtures. The preferred temperature range is between -2O ⁰ C and 5O ⁰ C.

The invention furthermore relates to compounds of the formula (II), and also to their salts and their stereoisomers.

HO CH ₂ - N

(CH ^) _n

wherein A, W, X, n, K, R ^1, R ² and ^R: have the meanings given in claim 1, with the proviso that (II) is not compounds 1 -H / droxy-1 (azol-1 - ylmethyD-1,2,3,4-th.-Hydrohydro-naphthalene, wherein "azole" 1 H-imidazole or 1,2,4-triazole is to be understood.

The compounds of the formula (II) exhibit antimicrobial, in particular antifungal properties. It therefore binds suitable for controlling fungi in humans and animals. By anticonvulsive action, the compounds of formula (II) are further suitable for the treatment and prevention of epileptic disorders. By fungicidal and wa.öhstumsregulierende properties, they are also suitable as pesticides.

The present invention relates to the compounds (II) in the form of the free base or an acid addition salt or a physiologically hydrolyzable and acceptable derivative.

Examples of pharmaceutically acceptable solvating acids are inorganic acids such as hydrochloric, hydrobromic, hydroiodic, sulfuric, phosphoric or nitric acid or organic acids such as malonic, oxalic, gluconic, camphorsulfonic, benzenesulfonic, acetic, propionic or p-toluenesulfonic acid.

Suitable physiologically hydrolyzable and acceptable derivatives are, for example, derivatives derivatized at the hydroxy group which are hydrolyzable under physiological conditions to the free acids, which in turn are physiologically acceptable, i. H. at the necessary; Doses are non-toxic.

The compounds (II) have at least one asymmetric carbon atom and can therefore occur as enantiomers and diastereomers. The invention includes both the pure isomers and their mixtures. The mixtures of diastereomers can be separated into the components by conventional methods, for example by selective crystallization from suitable solvents or by chromatography on silica gel or alumina. Racemates can be separated by customary methods in the enantiomers, for example by salt formation with an optically active acid, separation of the diastereomeric salts and release of the pure enantiomers by means of a base.

The invention further provides a process for the preparation of compounds of the formula (II), which comprises reacting a compound of the formula (VI)

(Vl) _f

in which W, X, k, n, R ¹ , R ² and R ^{3 have} the meanings given in claim 1, with a sulfur ylide of the formula (VII),

, (CH ₂ ), S CH ₉ (VII) ₁

wherein ζ is 0 or 1,

to a compound only formula (VIII) umseut

0 ~ 7

(VIII)

and then the 7? roindung of formula (VIII) with a compound of formula (IX)

wherein A has the meanings given in claim 1 and M represents hydrogen, the trimethylsilyl or a metal equivalent meaning, to a compound of formula (II).

For this wii d in a first reaction step for the preparation of the compounds of formula (VIII) a ketone of formula (Vl), in the R ¹ , R ² , R ³ , W, X, k and η have the meanings given above, with a Schwefelelyhd of formula (VII) in an inert Solvent, preferably dimethyl sulfoxide, or in mixtures of Dimetliylsulfoxid with other inert solvents,

z. B. tetrahydrofuran reacted. In this case, when using a sulfurylidene of the formula (VII), for which ζ = O, a

Temperature range between -10 ° C and 50 ⁰ C, preferably between ^{0 0} C and 3O ⁰ C appropriate; when using a Schwefelelylids of formula (VII), for which ζ = 1, a temperature range between ^{0 0} C and 8O ⁰ C, preferably between 20 ⁰ C and The preparation of the ketones of the formula (VI) or the sulfur ylides (VII) is carried out according to methods described in the literature. So

For example, compounds (VI) are synthesized as described in Org. Gynth. Coll. Vol. IV p. 898 or loc. cit. Vol. Il S. 569 produced.

The conversion of the intermediates of the formula (VIII) into the end products of the formula (II) takes place in a second Reaction step by reaction with a compound of formula (IX), in which A and M are as defined above

hab'in, in an inert solvent, e.g. N, N-dimethylformin, Ν, Ν-dimethylacetamide, dimethyl sulfoxide, acetonitrile,

Benzonitrile, sulfolane, N-methylpyrrolidone, dioxane or tetrahydrofuran, in a temperature range between 20 ⁰ C and 15O ⁰ C. The compound (IX) may in the form of an alkali or alkaline earth metal salt, preferably as the sodium salt, or in the form of

free base in the presence of a strong base. Suitable bases are, for. As alkali or alkaline earth metal hydrides, amides or a.Koholate.

The second reaction step can also be carried out by reacting the compound of formula (VIII) with imidazole or Triazole in equivalent amounts, or with imidazole or triazole in excess, without solvent in one Temperature range of 90-160 ⁰ C brings to reaction. The process described above can be conveniently carried out as a one-pot process by a A compound of the formula (VI) having a sulfur ylide of the formula (VII) as described above to give a compound of the formula (VIII)

and then this without workup of the reaction mixture and without isolation of the compound

Formula (VIII) by adding a compound of formula (IX) to the reaction mixture to give a compound of formula (II)

and in the form of the free base or an acid addition salt or a physiologically hydrolyzable and acceptable

Isolated derivative. The invention furthermore relates to compounds of the formula (IV)

OH ^

- C - CH ₂ --N Ar ^{Na =}

wherein A, Ar, W, k, R ¹ , R ² and R ^{3 have} the meanings given in claim 1 and m is 3 or 4. R ₃ is in this

Formula of the substituent of the chain - (CH ₂ ) ^. These compounds which are required as intermediates for the preparation of the compounds of the formula (I) likewise show

antimicrobial, in particular antifungal properties and are therefore suitable for controlling fungi in humans and animals. Furthermore, the compounds have fungicidal and growth-regulating properties and are therefore also known as

Pesticides suitable. The invention further provides a process for the preparation of compounds of the formula (IV), characterized

characterized in that a compound of the formula (X)

wherein W, Ar, k, R ¹ , R ² and R ^{3 have} the meanings given in claim 1 and m is 3 or 4, with a Schwefelelylid of formula (VII) according to claim 7 to a compound of formula (Xl)

(XI) - Ar

and then reacting the compound of the formula (XI) with a compound of the formula (IX) according to claim 7 to give a compound of the formula (IV).

The procedure is such that, as described above, a solution of the sulfuryl of formula (VII) in one of the solvents described above and this, as above in the reaction of a compound of formula (VII) with a compound of formula (Vl ), with a ketone of the formula (X) to give an epoxide of the formula (XI) and this di'nn, as described above in the reaction of the compound of formula (VIII) to a compound of formula (II), with ai Compounds the compound of formula (IX) to give a compound of formula (IV). The conversion of a compound of the formula (X) into a compound of the formula (IV) may usefully (analogously to the conversion of the compound of the formula [VI] into a compound of the formula [II] without isolation of the intermediate of the formula (XI) The invention further relates to a process for the preparation of compounds of the formula (X)

Il

χ:

R ₀ ^(R 3> k

where W, Ar, k, R ¹ and R ^! have the meanings given in claim 1 and m = 3, characterized in that a compound of the formula (XII)

hydrogenated in the presence of a metal catalyst to obtain a compound of formula (X).

The procedure is as follows, that a compound of formula (XII) in an inert solvent with the addition of a Hydrogenation catalyst in a pressure range of 1-10 bar, but preferably at 1 bar, in a temperature range between 0 and

100 ⁰ C, preferably 20-50 ° C, reacted with hydrogen and thereby ring opening of the cyclopropane ring a compound of

Formula (X). Suitable solvents are all hydrogenation-resistant and non-deactivating catalyst Solvents in question, for. As methanol, ethanol, tetrahydrofuran, hexane, toluene or mixtures of these solvents. When Metal catalysts are the usual Hvdrierkatalysatoren in question, as e.g. in "Houben-Weyl, Methods of Organic Chemistry ", Vol. 4/1 c, p 18/19 are described, but preferably palladium on activated carbon. The starting materials for the processes described above are known or can analogously described methods

getting produced.

For compounds of formula (X), unless they are prepared according to claim 10, some are given below Suggested synthetic possibilities in the event that W, the atoms required to complete a benzene ring system

means:

CO- (CH ₂ ) _n -COOH (XIII)

Wolff

1) Kishner reduction

2) SOCl ₂

3) NH ₃ →

4) SOCl ₂

1.) ArMgBr -CN

Et ₂ O

< ^CH 2> n ₊ 1

(XIV) 2.) H ⁺ / H ₂ O

(CH ₂ J _{n + 1} -C-Ar (X)

• (XVI a) X = Cl (XVI b) X = Br

1) Mg / Et ₂ O (XVI b) 2) ArCN ^

3)

Ό H ₂ / Pd

2) HOR / H +

3) LiAlH ₄

4) SOCl ₂ or PBr ₅

(XIV) as under a) _m n = 2

₃ - C-Ar (X)

Except as described in claim 9 for the preparation of the compounds of formula (IV), the latter can still be provided by the following methods (Examples in the case where W represents the atoms required to complete a benzene ring system):

a) Ar-C-CH ₂ X "+

(XVII) X = Cl, Br ^{R <} , 1 OH

(XVIII)

CH ₂ X

Ar or

(XVIII), (XIX)

(IX)

(IV)

b) Ar-G-C (XX)

(CH ₂ ) _n MgBr

(IV)

The compounds of formula I and their acid addition salts are valuable drugs. They have an antimicrobial effect in particular

and are useful for the prevention and treatment of PiU infections in humans and in various mammalian species.

The new compounds are very effective in vitro against dermal fungi, such as. B. Trichophyton mentagrophytes, Microsporum

canis, Epidermophyton floccosum; against molds, such. B. Aspergillus niger or yeasts, such as. Candida albicans, C. tropicalis, Toi ulopsis glabrata and Trichosporon cutaneum or against protozoa such as Trichomonas vaginalis or T.

fetus, or against gram-positive and gram-negative bacteria.

Also in vivo, z. In experimental mouse kidney canidosis, the compounds are oral or parenteral Application a very good systemic effect, eg. Against Candida albicans. Likewise, there is a very good effect against

various causative agents of dermal mycoses (e.g., Tnchophyton mentagrophytes) on guinea pigs after oral, parenteral or especially local application.

Examples of indications in human medicine include: Dermatomyko Jen and systemic mycoses by Trichophyton mentagrophytes and other trichophytonae, species of microsporin, Epidermophyton floccosum, fungi and biphasic fungi as well as molds. Examples of indications in veterinary medicine include: All dermatomycoses and systemic mycoses, in particular those caused by the above-mentioned pathogens. The compounds of the formula (I) and (II) in addition to their antimicrobial properties and CNS Wirkuny, in particular

anticonvulsant effect. They are well-effective in the antiepileptic drug-specific assays. So they show strong

Action against pentetrazole or electroshock-induced convulsions in mice. The present invention includes pharmaceutical preparations, in addition to non-toxic, inert pharmaceutical

suitable carriers contain one or more active substances according to the invention or which consist of one or more active substances according to the invention and processes for the preparation of these preparations.

Non-toxic inert pharmaceutically acceptable carriers are solid, semi-solid or liquid diluents, To understand fillers and formulation aids of any kind. As dosage forms are, for example, tablets, dragees, capsules, pills, aqueous solutions, suspensions and Emulsions, optionally sterile injectable solutions, non-aqueous emulsions, suspensions and solutions, ointments, Creams, pastes, lotions, sprays, etc. into consideration. The therapeutically active compounds should preferably be described in the abovementioned pharmaceutical preparations in

a concentration of about 0.01 to 99.0, preferably from about 0.05 to 50 wt .-% of the total mixture.

The above-listed pharmaceutical preparations may, in addition to the active compounds according to the invention also further

contain active pharmaceutical ingredients.

The preparation of the abovementioned pharmaceutical preparations is carried out in the customary manner by known methods,

z. B. by mixing the active substance or substances with the carrier or excipients.

The present invention also includes the use of the active compounds according to the invention and of pharmaceuticals Preparations containing one or more active substances according to the invention in human and veterinary medicine for Prevention, amelioration and / or cure of the diseases listed above. The active substances or the pharmaceutical preparations can be administered locally, orally, parenterally, intraperitoneally and / or rectally

become.

In general, it has proven to be advantageous in both human and veterinary medicine, the or d; o

active compounds according to the invention in total amounts of at least about 0.05, preferably 0.1, in particular 0.5 mg and at most 200, preferably 100, in particular 30 mg / kg body weight per 24 hours, based on an adult of the

Weight of 75kg, optionally in the form of several to give the desired results. The total amount is administered in 1 to 8, preferably in 1 to 3 single doses. However, it may be necessary to deviate from the doses mentioned, depending on the type and Body weight of the object to be treated, the nature and severity of the disease, the nature of the preparation and the Application of the drug and the period or interval within which administration takes place. So it can be in

In some cases, it may be sufficient to get along with less than the amount of active ingredient mentioned above while in others

If the above-mentioned amount of active ingredient must be exceeded. The definition of the required optimal Dosage and mode of administration of the active ingredients can easily be carried out by any person skilled in the art on the basis of his specialist knowledge. The compounds of the formula (I) according to the invention are further distinguished by an outstanding fungicidal action

phytopathogenic fungi. Even fungal pathogens already infiltrated into the plant tissue can be successfully controlled successfully. This is particularly important and advantageous in those fungal diseases that can no longer be effectively controlled after infection with the usual fungicides. The spectrum of action of the new

Compounds detects a variety of different phy.opathogenic fungi, such as. B. Piricularia oryzae, Pellicularia sasakii,

various types of rust, but especially Venturia inaequalis, Cercospora species and powdery mildew fungi in fruit, vegetable,

Cereal and ornamental Bnu. The new compounds of general formula (I) are also suitable for use in technical fields, for example

as a wood preservative, as a preservative in paints, in Kühlschmiermittein door metalworking or as

Preservatives in drilling and cutting oils. The new compounds can be used as wettable powders, emulsifiable concentrates, sprayable solutions, dusting agents, mordants, Dispersions, granules or microgranules are used in the usual preparations. Injection powders are understood in water to be uniformly dispersible preparations, in addition to the active ingredient except

optionally a diluent or inert or wetting agent, for. As polyoxethylated alkylphenols, polyoxethylated

Fatty alcohols, alkyl or alkylphenylsulfonates and dispersants e.g. Sodium lignosulfonate, 2,2'-dinaphthylmethane

6,6'-di-sulfonic acid sodium, dibutylnaphthalene-sulfonic acid Natri τι or oleoylmethyltaurin also contain sodium.

Their preparation is carried out in the usual manner, for. B. by grinding and mixing of the components. Emulsifiable concentrates may, for. B. by dissolving ('as active ingredient in an inert organic solvent, eg., Butanol, Cyclohexanone, dimethylformamide, xylene or honey-boiling aromatics or hydrocarbons with the addition of

one or more emulsifiers are produced. In the case of liquid active substances, the proportion of solvent can also be omitted completely or partially. As emulsifiers can be used, for example: Alkylarylsuifonsaure calcium salts, such as

Calcium dodecylbenzenesulfonate, or nonionic emulsifiers such as fatty acid polyglycol esters, alkylaryl polyglycol ethers, Fatty alcohol polyglycol ethoxyl, propylene oxide-ethylene oxide condensation products, Fe'.talcohol-propylene oxide-ethylene oxide Condensation products, AiKylpolyglykolether, sorbitan fatty acid esters, Polyoxethylensorbitanfettsäureester od? R Polyoxethylensorbitester. Dusts are obtained by grinding the active substance with finely divided, solid substances, eg. Talc, of course, like toning Kaolin, bentonite, pyrophillite or diatomaceous earth obtained. Granules can be prepared either by spraying the active ingredient onto adsorptive, granulated inert material

or by applying active ingredient concentrates by means of binders, for. As polyvinyl alcohol, polyacrylic acid sodium or other mineral oils on the surface of carriers such as sand, kaolinite or granulated inert material. It is also possible to use suitable active ingredients in the manner customary for the production of fertilizer granules, if desired in

Mixture with fertilizers, be granulated. In wettable powders, the active ingredient concentration is e.g. about 10-90% by weight, the remainder to 100% by weight consists of conventional Formulation components. In the case of emulsifiable concentrates, the active ingredient concentration may be about 10-80% by weight of active ingredient,

for sprayable solutions about Ί -20Gew .-% amount. In the case of granules, the active ingredient content depends, in part, on whether the active compound is liquid or solid and which granulating aids, fillers, etc. are used.

In addition, the active substance formulations mentioned optionally contain the customary adhesive, wetting, dispersing, Emulsifying, penetration, solvents, fillers or carriers. For use, the concentrates present in commercially available form are optionally diluted in the usual manner, for. B.

for wettable powders, emulsifiable concentrates, dispersions and sometimes also for micro-granules by means of water.

Dusty and granulated preparations and sprayable solutions are usually not before use

more diluted with other inert substances.

Depending on the indication, the required application rates can vary within wide limits and also vary within Dependence on external factors such as bed conditions, climatic conditions. In general, the dose levels are

between 0.01 and 10 kg of active ingredient per ha, in particular between 0.15 and 1.0 g per ha.

Also mixtures or mixed formulations with other active ingredients, such as. As insecticides, acaricides, herbicides, Fertilizers, growth regulators or other fungicides may be possible, with u. U. also synergistic Increases in impact can be achieved. In the following, some formulation examples are given: A dusting agent is obtained by mixing 10 parts by weight of active compound and 90 parts by weight of talc as inert material and mixing in

crushed a hammer mill.

A wettable powder readily dispersible in water is obtained by adding 25 parts by weight of active compound, 65 parts by weight

quaternary quartz as an inert material, 10 parts by weight of lignosulfonic acid potassium and 1 part by weight of oleoylmethyltaurine acid

Mix sodium as wetting and dispersing agent and grind in a pin mill. A dispersion concentrate readily dispersible in water is prepared by adding 20 parts by weight of active compound

6 parts by weight of alkylphenol polyglycol ether (Triton X 207), 3 parts by weight of isotridecanol polyglycol ether (8AeO) and 71 parts by weight of paraffinic mineral oil (boiling range, for example, about 255 to over 377 ° C) and ground to a fineness below 5 microns in a ball mill.

An emulsifiable concentrate can be prepared from 15 parts by weight of active compound, 75 parts by weight of cyclohexanone as Solvent and 10 parts by weight of ethoxylated nonylphenol (10AeO) as emulsifier.

11-268 852 Ausfühungsbelsplel

The following examples serve to illustrate the invention, ohi.a restricting the same. Experimental part

Example 1 6,7-Dichloro-4- (4-chlorophenyl) -4- (1H-imidazol-1-ylmethyl) -2,3-dihydro-benzopyran

CH ₂ - Nj

A solution of 4.6 g (0.011 mol) of 2- (4-chlorophenyl) -4- (3,4-dichlorophenoxy) -1- (1H-imidazol-1-yl) -butan-2-ol (Example 17) in 150 ml of 1 , 2-dichloroethane was stirred at - 10 ⁰ C are added under stirring with 3.1 g (0.023 mol) of anhydrous aluminum chloride. It was allowed to come to room temperature and stirred for 6 h. It was then poured onto ice, basified with 2N sodium hydroxide solution, the organic phase was washed with water, dried and concentrated. The crude product was chromatographed on silica gel with ethyl acetate / methanol 9: 1. A colorless oil was obtained which crystallized on trituration with diethyl ether. Yield: 2.8 g (60.8% of theory) M.p .: 94 ⁰ C dec. (Product crystallized with '/ 3 diethyl ether)

Example 7-Chloro-4 - (- chlorophenyl-4- (1,2,4-triazol-1-ylmethyl) -2,3-dihydro-pyran

Analogously to Example 1, 4.0 g (0.011 mol) of 2- (4-chlorophenyl) -4- (3-chlorophenoxy) -1- (1,2,4-triazol-1-yl) -butan-2-ol (Example 18) with 3.0 g (0.22 mol) of aluminum chloride in 150 ml of 1,2-dichloroethane. For purification was chromatographed on silica gel with methylene chloride / ethyl acetate 2: 1. 2.5 g of glassy product were obtained (66.1% of theory).

Example 3

7-chloro-4- (4-chlorophenyl) -4- (1H-imidazol-1-ylmethyl) -2,3-dihydro-thiopyran

Cl

Analogously to Example 1, 3.9 g (0.010 mol) of 2- (4-chlorophenyl) -1- (1H-imidazol-1-yl) -4- (3-chlorophenylthio) -butan-2-ol (Example 21) r, reacted with 2.7 g (0.020 mol) of aluminum chloride in 100 ml of 1,2-dichloroethane. Chromatography on silica gel with ethyl acetate / methanol 19: 1 gave a colorless resin (2.3 g, 61.3% of theory) which crystallized on trituration with diethyl ether. Mp .: 143-144 ⁰ C.

Example 4

1 - {1 H -imidazole-1-ylmethyl-1 - (4-trifluoromethyl-phenyl) -allylic

At room temperature, 7.0 g (0.019 mol) of 1- (1H-imidazol-1-yl) -5-phenyl-2- (4-trifluoromethylphenyl) -pentan-2-ol (Example 22) in 30 ml of 85% sulfuric acid entered. The mixture was stirred for 2 h at room temperature, poured onto ice, basified with 10% sodium hydroxide solution and shaken with methylene chloride. The organic phase was dried, concentrated and the residue chromatographed on silica gel (ethyl acetate / methanol 9: 1). This gave 4.7 g (70.5% of theory) of a colorless resin.

Example 5

1- (4-bromophenyl) -1- (1,2,4-triazol-1-yl-methyl-tetralin

To a suspension of 11.6 g (0.03 mol) of 2- (4-bromophenyl) -5-phenyl-1- (1,2,4-triazol-1-yl) -pentan-2-ol (Example 24). in 200 ml of 1,2-dichloroethane was added at room temperature 8.4 g (0.063 mol) of aluminum chloride. After the exothermic reaction had subsided for 4 h at room temperature, poured onto ice, basified with sodium hydroxide solution, the organic phase separated, dried and concentrated. The crude product was chromatographed on silica gel with ethyl acetate. This gave 7.2 g (65.2%) of colorless oil, which crystallized on trituration with diethyl ether

Mp .: 121 ^° C

Example β 1- [4- (4-chlorobenzyloxy) -phenyl] -1- (1H-imidazol-1-ylmethyl) -tetralin

A mixture of 1.5 g (4.9 mmol) of 1- (4-hydroxy-o-phenyl) -1- (1 H -imidazol-1-ylmethyl) (Example 7), 0.3 g

Tetrabutylamnonium bromide, 0.8 g (4.9 mmol) 4-chlorobenzyl chloride, 5 ml of 50% sodium hydroxide solution and 30 ml of toluene was refluxed for 5 hours with vigorous stirring, worked up with water, the organic phase was separated, the aqueous phase was extracted by shaking again with methylene chloride and the combined After chromatography on silica gel (ethyl acetate / methanol 9: 1) an oil was obtained which crystallized on trituration with ethyl acetate.

Yield: 1.4 g (66% of theory) M.p .: 132-133 ⁰ C.

Example 7

1 - (4-Hydroxyphenyl) -1 - (1 H -imidazol-1-ylmethyl-tetralin

OV OH

5.0 g (0.015 mol) of 1- (1H-imidazol-1-yl) -5-phenyl-2- (4-methoxyphenyl) -pentan-2-ol (Compound No. 20, Table 2) was mixed with 50 ml 48% Hydrobromic acid for 6 hours under reflux. For workup, the acid was removed in vacuo, the solid residue was heated with aqueous ammonia solution and filtered with suction. This gave 4.2 g (93.1% of theory) of colorless solid. Mp: 272-275 ⁰ C

Example 8

5- (4-chlorobenzyloxy) -1- (2,4-dichlorophenyl) -1 - (1 H -imidazol-1-ylmethyl-tetralin

CH

Analogously to Example 6, 1.40 g (3.9 mmol) of 1- (2,4-dichlorophenyl) -5-hydroxy-1- (1H-imidazol-1-ylmethyl) tetralin (Example 9), containing 0.63 g (3 , 9mMol) chlorobenzyl chloride with the addition of 0.30 g of tetrabutylammonium bromide in a mixture of 50ml of toluene and 5ml 50% sodium hydroxide solution. Chromatography on silica gel gave 0.8 g of colorless crystals (41.2% of theory). FP: 184-185 ⁰ C

Example 9

1 - (2,4-dichlorophenyl) -5-hydroxy-1 - (1 H -imidazol-1-yl-methyl-tetralin

1.7 g (4.4 mmol) of 1- (2,4-dichlorophenyl) -1- (1H-imidazol-1-ylmethyl) -5-methoxy-te'raline (Compound No. 42, Table 1, prepared analogously to Example 5 ) from 2- (2,4-dichlorophenyl) -1- (1H-imidazol-1-yl) -5- (2-methoxyphenyl) -pentan-2-ol, Compound No. 26, Table 2) were dissolved in 30 ml Glacial acetic acid / 48% hydrobromic acid (1: 1) heated under reflux for 6 h. After cooling, the acid mixture was removed in vacuo, solid residue is briefly heated with aqueous ammonia solution and filtered with suction. This gave 1.4 g (89.2% of theory) of a colorless solid

 FP: 245 ° CZers.

Example 10

1- (4-chlorophenyl) -1- (1H-imidazol-1-ylmethyl) indan

CH ₂ -N,

In a 10 ml V4A autoclave, 2.5 g (7.6 mmol) of 2- (4-chlorophenyl) -1- (1H-imidazol-1-yl) -4-phenvl-butan-2-ol (Example 26) in FIG. 2, 5 ml of anhydrous hydrofluoric acid under argon atmosphere at 50 ° C for 24 h. At ⁰ ° C., it was poured onto 100 g of ice, adjusted to pH 10 with 40% strength potassium hydroxide solution and extracted four times with 50 ml of methylene chloride each time. The combined organic phases were dried and concentrated. Chromatography on silica gel with ethyl acetate / methanol 9: 1 gave 0.1 g of a colorless resin (42.6% of theory).

Example 11

1 - (3,4-dimethylphenyl) -1 - (1 H -imidazol-1-ylylmethyl-tetralin

- CH ₅ -N

5.7 g of finely powdered 1-hydroxy-1- (iH-imicazol-1-ylmethyl) -tetralin (0.025 mol) (Example 33) in a mixture of 100 ml of o-xylene / methylene chloride 1: 1 was washed at room temperature with 7 , 0g (0.53 mol) of aluminum chloride. After the exothermic reaction had subsided, stirring was continued for one hour at room temperature. For workup, the mixture was poured onto ice, basified with sodium hydroxide solution, the organic phase was dried and concentrated in vacuo. Chromatography on silica gel (ethyl acetate / methanol 9: 1) left a colorless oil which crystallized on trituration with cyclohexane. Yield: 3.6 g (45.5%) m.p .: 102-103 ⁰ C.

Example 12

1- (3,4-dimethylphenyl) -1- (1H-imidazol-1-ylmethyl) -2,3,4,5-tetrahydro-benzocycloheptatrien

9.7 (0.04 mol) of 1-hydroxy-1- (1H-imidazol-1-yl-methyl) -SA-tetrahydro-benzocycloheptatriene (Compound No. 3, Table 3) were dissolved in a mixture of 150 ml analogously to Example 11 o-xylene / 1,2-dichloroethane was reacted 1: 1 by adding 11.1 g (0.083 mol) of aluminum chloride, following Example 11. Chromatography on silica gel with ethyl acetate gave a colorless oil which was triturated with diethyl ether Yield: 1.9 g (14.4% of theory) mp: 158-16O ⁰ C

Example 13 1- (4-Biphenyl) -1- (1H-imidazol-1-ylmethyl) indan

To a cooled to ⁰ ° C suspension of 10.0 (0.047 mole) of 1-hydroxy-1- (1H-imidazoM-ylmethyl) indan (Compound No. 1. Table 3) in a mixture of 60 g of biphenyl and 60 ml of 1,2-dichloroethane was added 13.1 g (0.98 mol) of aluminum chloride. To Cooling of the exothermic reaction was stirred for one hour. The procedure was analogous to Example 11. To Chromatography on silica gel with ethyl acetate / methanol 9: 1 gave a colorless oil which was triturated with diethyl ether

crystallized.

Yield: 10.7 g / 65.4% of theory)

Mp .: 123-125 ⁰ C

Example 14

1 - (1 H -imidazole-1-ylmethyl) -1- (4-phenylthiophenyl) tetralin

To a cooled to O ⁰ C suspension of 6.5 g (0.029 mol) of finely powdered 1-hydroxy-1- (1H-imidazol-1-ylmethyli-tetralin (Example 33) in a mixture of 25ml diphenyl sulfide and 50ml 1,2- After the exothermic reaction had subsided, stirring was continued for 3 hours at room temperature, the mixture was poured onto ice and made alkaline with sodium hydroxide solution, shaken with methylene chloride, dried and the organic phase was concentrated Chromatography on silica gel (ethyl acetate / methanol 9: 1) gave a colorless oil which crystallized on trituration with diethyl ether

Yield: 8.5 g (72.2% of theory) M.p .: 124 ⁰ C.

Example 15

1- (1H-imidazol-1-ylmethyl) -1- (4-phenylsulfinylphenyl) tetralin

To a solution of 3.0 g (7,6mMol) 1- (1H-imidazol-1-ylmethyl) -1- (4-phenylthioph3nyl) tetralin (Example 14) in 80ml of methylene chloride were added dropwise at -10 ⁰ C a solution of 1.7 g (7.6 mmol) of 70% 3-chloroperbenzoic acid in 80 ml of methylene chloride. After standing overnight, the mixture was stirred with sodium bicarbonate solution, the organic phase was dried and concentrated. Chromatography on silica gel (ethyl acetate / methanol 9: 1) gave 2.6 g of colorless resin (82.9% of theory).

Example 16 1- (iH -imidazol-1-ylmethyl) -1- (4-phenylsulfonyiphenyl) tetralin

To a solution of 3.5 g (8.8 mmol) of 1- (1H-imidazol-1-ylmethyl) -1- (4-phenylthiophenyl) tetralin (Example 14) in 100 ml of methylene chloride was added dropwise at 0 ° C a solution of 3 , 4g (17.6 mmol) of 70% m-chloroperbenzoic acid in 80 ml of methylene chloride. After standing overnight, the mixture was stirred with sodium bicarbonate solution, the organic phase was dried and concentrated. Chromatography on silica gel (ethyl acetate / methanol 9: 1) gave a colorless gum which crystallized on trituration with diethyl ether

Yield: 3.0 g (79.5% of theory) M.p .: 143-144 ⁰ C.

Example 16a

1- (2-chloro-thien-5-yl) -1- (1H-imidazol-1-ylmethyl) -3,3-dimethyl-indan

To a cooled to -10 ⁰ C suspension of 6.5 g (27 mmol) of 1- (1H-imidazol-1-ylmethyl) -3,3-dimethyl-indan-1-ol (Example 36) in a Gomisch from 50ml 1 , 2-dichloroethane and 20 ml of 2-chlorothiophene were added 8.0 g (60 mmol) of aluminum trichloride. After the exothermic reaction had subsided for 6 h at room temperature, poured onto ice, made alkaline with 30% sodium hydroxide solution, the organic phase separated, washed with water, dried and concentrated. Chromatography on silica gel gave 5.7 g of a yellow, glassy mass.

Table 1 contains the end products described above and further compounds of the formula (I) which can be synthesized analogously to the examples given

a) Compounds of formula (I), for which W is the atom required to complete a benzene ring. The position indications for H ¹ and R ² in Table 1 relate to the formula shown below; they do not conform to the usual rules of nomenclature

(I)

Table 1

Verb.-Nr. A 1 CH 2 N 3 CH 4 CH 5 N 6 CH 7 CH 8th CH 9 CH 10 CH 11 CH 12 CH 13 CH 14 CH 15 CH 16 CH

2 2

-Q-Br

2 2

2 2

> OH

O S

CH ₂

CH ₂

CH ₂ CH ₂

CH ₂ CH ₂ CH ₂

CH ₂ CH ₂ CH ₂ CH ₂

CH ₂ .

CH ₂ *) crystallized with 1/3 mol of diethyl ether

kr

-φ-ci

R ¹ R ² 3-Cl 4-Cl 3-Cl H 3-Cl H H H H H H H H H

i ^w

-Q-Cl 2-OCH ₂ -QC J

-Q-Cl CHo

-0-I0

2-OH H H H H H H H H H H H H H H H

* ^c

94 * Zers. *

Resin 143-144

resin

121

132-133 272-275

184-135 245 Zers. resin

102-103 158-160 123-125 124

Resin 143-146

Table 1 (continued)

Conn No, A 17 CH 18 CH 18a N 19 CH 19a N 20 CH 20a N 21 N 22 CH 23 N 24 CH 25 CH 26 N 27 CH 27a N 28 CH 29 CH 30 CH 31 CH 31a N 32 CH 32a N 33 CH 33a N 34 N 35 CH 35a N 36 CH 37 N 38 CH

X η O 2 CH ₂ 1 CH ₂ 1 CH ₂ 2 CH ₂ 2 CH ₂ 2 CH ₂ 1 Ql ₂ 2 CH ₂ 2 Ql ₂ 2 CH ₂ 2 CH ₂ 2 CH ₂ 2 CH ₂ 1 CH ₂ 1 CM, 1 CH ₂ 2 CH ₂ 2 CH ₂ 1 CH ₂ 1 CH ₂ 2 CH ₂ 2 CH ₂ 2 CH ₂ 1 CH ₂ 2 CH ₂ 1 CH ₂ 1 CH ₂ 2 CH ₂ 2 CH ₂ 2

Il

Il

η it ti it

Il

Il Il Il

! I

Cl '"

Il It

R ¹ R ² 3-Cl H H H H H H H H H H H H H H H 3-Cl H 3-Cl H 4-Cl H 3-a 4-Cl 3-Cl 4-Cl H H H H 3-F H H H 3-F H H H H H H H H H H H H F H H H H H H H H H 2-Cl H

Fp 'C resin

147-149 99-100

127-128 147-148 141-142 119-121 145-146 168-169

104-105 122-124

66-68 111-112 132-133 102-104 resin

125-127 156-158 resin

-19- 268 352

Table 1 (continued)

Verb.-Nr. A X η 39 CH CH ₂ 2 39a N CH ₂ 2 40 CH CH ₂ 2 41 N CH ₂ CVI 42 CH CH ₂ 2 42a N CH ₂ 2 43 CH CH ₂ 2 44 CH CH ₂ 1 45 CH CH ₂ CVJ 46 CH CH ₂ CVJ <7 CH CH ₂ 2 47a N CH ₂ 2 48 N CH ₂ 2 49 CH CH ₂ 2 50 CH CH ₂ 2 51 CH CH ₂ CVJ 51a N CH ₂ 2 52 N CH ₂ 2 53 CH CH ₂ 1 54 CH CH ₂ 2 55 CH CH ₂ 2 56 CH CH ₂ 3

Ar

Il

η η

ti

Il

: Ö> -ci

> Br

> CH,

> CF,

2-F 2-F

2-CH ₅ 2-OCH

H H H H H H

2-0- (O) -Cl 2-0- ^ Vci

4-C1 3-F

Il

H H H

H H H

H H H H

H H H H

H H H H Fp "C

141-143 155-157 154-155

199-200

197-198 159-160

127-128 56-57 Zers. *

133 110-112 91-93 81-83 129-131 Resin 139-141

*) crystallized with 1/2 mol of diethyl ether

Table 1 (Port setting)

Verb.-Nr. A X η 1 1 57 OT CH ₂ CVJ 1 57a N CH ₂ 2 CVJ 58 OT OT ₂ 2 1 58a N CH ₂ 2 1 59 OT OT ₂ CVI 1 59a N CH ₂ 2 2 60 CH OT ₂ CVJ 2 60a N CH ₂ 2 1 61 OT OT ₂ CVJ 1 62 OT CH ₂ 1 63 OT OT ₂ 1 64 OT CH ₂ 1 65 CH C ¹ H ₂ 2 66 OT OT ₂ 1 67 OT CH ₂ 1 67a N CH ₂ 68 OT CH ₂ 69 OT CH ₂ 70 OT CH ₂ 71 OT CH ₂ 71a N CH ₂ 72 OT CH ₂ 73 OT CH ₂ 73a N CH ₂ 74 OT OT ₂ 74a N CH ₂

Ar

-OOT,

MKO) -F

* crystallized with 1/2 mol of diethyl ether »crystallized with 1 mol of methanol

R ¹ R ² H H H H H H H (H H H H H H H H H 3-F H 2-Cl H 3-Cl H 4-F H H H H H H H H 2-F H H 2-CH, H H H H H H H 2-Cl H H H H H H H H H

Fp ⁰ C 120-121 122-124 76-77 Zers. * 103-104 Zers. **

121-122 resin resin resin

120-122 136-137

138-139

Table 1 (Port setting)

Varb.-Nr. A X η 75 CH CH ₂ 2 75a N CH ₂ 2 76 CH CH ₂ 1 76a N CH ₂ 1 77 CH CH ₂ 2 77a N CH ₂ 2 78 CH CH ₂ CVJ 78a N CH ₉ 2 Z 79 CH CH ₂ 2 79a N CH ₂ 2 80 CH CH ₂ 2 80a N CH_ 2

Ar

R ¹ R ² H H H H H H H H H H H H II H H H H H H H H H

Pp * C

87 88 89 90 91 92 93

CH CH, CH CH, CH CH,

CH CH,

CH CH,

CH CH,

CH CH CH

CH ₂ CH ₂

CH CH,

CH CH

CH, CH,

CHΟΙ, CH CH,

CH CH,

CH CH,

-O-

Cl

-ti

Cl

Cl

1 - (O) -C (CH ₃ )

118-119 127-129

91-92 136-138

159-160 165-167

Resin 121-122 resin

121-122 resin 187-189 *

118-120 93-96 resin

120-122 resin

136-138 147-148

78-80

*) Hydrochloride

 Table 1 (Port setting)

Verb.-Nr. A X η 97 CH CH ₂ 2 98 CH CH ₂ 2 99 N CH ₂ 2 100 CH CH ₂ 2 101 N CH ₂ 2 102 CH CTU 2

Ar

R ¹

Pp * C

111 112 113 114 115 116 11 "118 119 120

CH

CH

CH N

CH

CH

CH

CH

CH

CH

CH,

CH

CH,

CH,

CH ₂ CTU

CH ₂

CH

CH ₂

CH ₂

CH ₂

CH ₂

CH

Cl

Cl 2

2 2

F 2

2 2

2 2 2 2 2 2 2 2 2 2

 ©>

H H H H H H H H H H H H H H H H H H H H H H H H H H

H H rf H H H H H H H H H H H H H H H 2-F 5-F

Table 1 (continued)

Verb.-Nr. AXn

ArR ¹

Fp 'C

121 122 123

124 125 126 127

128 129

130 131 132 133 134 135 136

137

138 139 140 141 142 143 144 145

146 147 148 149 150 151

CH

CH

CH CH CH CH

N CH

CH

CH

CH

CH

CH

CH

CH

CH

CH

CH

CH,

CH,

CH,

CH,

CH,

CH,

CH,

O O O O S S

CH

O O O O S S O

O O O O S

3 3 3 3 3 3 3

3 - (

3 3 3 3 3 3 3 3

3 3 3 3 3 3

H H H H H H 103-105 > -Cl 2 Cl 4-Cl 3-Cl 4-Cl 2-F 5-F H H H H 3-Cl H 3-Cl H 4-Cl H 4-Cl H 4-F H 4-F H 4-Cl H 4-Cl H -F3-Cl H 3-Cl H 4-Cl II 4-Cl H 4-F H 4-F 4-Cl H 4-Cl H Cl 3 Cl H 3-Cl II 4-Cl H 4-Cl H 4-F H 4-F H 4-Cl H

Table 1 (Continuation) ύ X η Ar R ¹ H Fp 'C Verb.-Nr. A O 3 3-C1 H 152 CH O 3 Il 3-C1 H 153 N O 3 Il 4-C1 H 154 CH O 3 Il 4-C1 H 155 N O 3 Il 4-F H 156 CH O 3 Il 4-F H 157 N S 3 Il 4-Cl H 158 CH S 3 Il 4-Cl H 159 N (CH ₃ ), 2 - <ö) - <ö) H resin 160 CH

Compounds of the formula I where R, <I H ' Table 1a

Verb.Nr.

Ar

R ¹ R ²

Fp ⁰ C

CH CH ₂

CH CH ₂

CH

CH

CH

CH S

4-biphenylyl 2-thienyl-5-Cl H

H H CH ₃ CH ₃ resin H H CH ₃ CH ₃ resin H 3-Cl CH ₃ CH ₃ H 3-Cl CH ₃ CH ₃ H 3-Cl - (CH ₂ ) 5 '

H H

CH.

CH,

Compounds of the formula (I) in which W denotes the atoms necessary to complete a naphthalene ring system: Cl

Verb.-Nr. A Pp L-Cj 167 168 CH V 214 177

Preparation of the starting materials

a) Preparation of the compounds of the formula (IV)

Example 17

2- (4-chlorophenyl) -4- (3,4-dichlorophenoxy) -1- (1H-imidazol-1-yl) -butan-2-ol (starting material for Example 1)

OH

0 - CH ₂ --CH ₂ --C - CH ₂ -

/ -N

¹ U

To a mixture of 6.1 g (0.023 mol) of 2- (4-chlorophenyl) -1- (1H-imidazol-1-yl) -butane-2,4-diol (preparation: EP-OS 150036), 3 8g

(0.023 mol) of 3,4-dichlorophenol and 6.5 g (0.025 mol) of triphenylphosphine in 100 ml of dry tetrahydrofuran was added dropwise

Cooling at 20 ⁰ C, a solution of 4.5 g (0.025 Md!) Azodicarbonsäurediethylester in 10ml dry tetrahydrofuran. To Stirring was concentrated overnight and the mixture was mixed with kieselge! chromatographed with ethyl acetate / methanol 9: 1. The Product was eluted from the column as the last component. A colorless oil was obtained which was triturated with diethyl ether

crystallized.

Yield: 7.0 g (73.9%), mp. 139-14O ⁰ C Example 18

2- (4-chlorophenyl) -4- (3-chlorophenoxy! -1 - (1,2,4-triazol-1-yl) -butan-2-ol

(Starting product for example 2)

0 - CH ₀ - CH "-

- N

Analogously to Example 17, 6.9 g (0.026 mol) of 2- (4-chlorophenyl) -1- (1,2,4-triazol-1-yl) -butan-2,4-diol (Example 19) 3.5 g ( 0.027 mol) of 3-chlorophenol, 7.0 g (0.027 mol) of triphenylphosphine and 5.0 (0.029 mol) of diethyl azodicarboxylate. After chromatography on silica gel product is eluted as penultimate fraction) 4.0 g (40.1% of theory) of resinous product were isolated.

Example 19

2- (4-chlorophenyl) -1- (1,2,4-triazol-1-yl) -butane-2,4-diol

CI_ "

C-CH ₂ - CH ₂ OH

To a solution of 1.5 g of lithium aluminum hydride in 50 ml of dry tetrahydrofuran was added dropwise with stirring and cooling a solution of 8.9 g (0.029 mol) of 3- (4-chlorophenyl) -3-hydroxy-4- (1, '!, 4- Triazol-1-yl) -butyric acid ethyl ester (Example 20). After stirring at room temperature for 6 hours, it was carefully decomposed with water while cooling, filtered off with suction from the inorganic material, dried and concentrated. A colorless oil was obtained which crystallized on trituration with diethyl ether. Yield: 7.0 g (89.8% of theory) M.p .: 108-109 ⁰ C.

Example 20 Ethyl 3- (4-chlorophenyl) -3-hydroxy-4- (1,2,4-triazol-1-yl) butyrate

Was placed 100 ml of a 1 M solution of lithium bis (trimethylsilyl) amide in tetrahydrofuran before and added dropwise at -78 ⁰ C 9,7ml dry ethyl acetate. After stirring for 15 minutes at the same temperature, it was diluted slowly with 100 ml of dry tetrahydrofuran and then at -78 ° C was added portionwise 22.1 g (0.1 mol) of finely powdered 4-chlorophenyl- (1,2,4-triazole-1). yl) -methyl-ketone. The mixture was stirred for 2 hours at -78 ⁰ C, poured into water, extracted with methylene chloride, dried the organic phase and concentrated. The crude product was chromatographed on silica gel with ethyl acetate. This gave 12.1 g of colorless crystals (39.5% of theory), mp.: 93-94 ⁰ C.

Example 21

2- (4-chlorophenyl) -1- (1H-imidazol-1-yl) -4- (3-chlorophenylthio) -butan-2-ol (starting material for Example 3)

S-CHOCH,

CHo - N

/ = N

12.0 g (0.045 mol) of 2- (4-chlorophenyl) -1- (1H-imidazol-1-yl) -butan-2,4-diol (EP-OS 1,50036) 7,0g (0.048 mol Chromatography on silica gel (the product was eluted from the column as the last fraction) afforded 6.5 g of colorless resin (36.8% of theory) on a silica gel gel (0.051 mol) of diethyldodecarboxylate (0.051 mol). Th.).

Example 22

1 - (1 H -imidazole-i-yl) -5-phenyl-2- (4-tf-isluoromethyl-phenyl) -pentan-2-ol

(Starting product for example 4)

OH - C - CH

 0

To a suspension of 1.8 g of sodium hydride (80% in oil) (0.06 mol) in 100 ml of dry dimethyl sulfoxide was added while cooling at a temperature of 1 & -20 ° C in portions 13.2g (0.065 mol) Trimethylsulfoxoniumjodid and stirred until End of gas evolution. A solution of 14.6 g (0.05 mol) of 1-phenyl-3- (4-trifluoromethylbenzene / propane (Example 23) in 100 ml of dry dimethyl sulfoxide was added, and the reaction was allowed to proceed to 50 ° C. after cooling the weakly exothermic reaction heated. After one hour, gave 4.5 g (0.05 mol) of imidazole sodium salt to the mixture, stirred for an additional hour at 5O ⁰ C and 3 hours at 80 ° C. for workup was poured onto ice, added with methylene chloride, The organic phase was dried and concentrated, purified by chromatography on silica gel (ethyl acetate / methanol 9: 1) to give a colorless oil which crystallized on trituration with diethyl ether

Yield: 12.6g (67.3% of theory..) M.p .: 147-148 ⁰ C.

Example 23

1-phenyl-3- (trifluoromethyl-benzoyl) propane

A solution of 29.0 g (0.20 mol) was added dropwise to a Grignard solution prepared from 5.4 g (0.22 mol) of magnesium turnings and 50.0 g (0.22 mol) of 4-bromobenzotrifluoride in 100 ml of dry diethyl ether. Phenylbutyronitrile in 50ml of dry diethyl ether. The reaction mixture boiled and was stirred at reflux for a further 3 hours. The mixture was allowed to cool, poured onto ice, rendered strongly acidic with 10% strength sulfuric acid and the mixture was stirred for 30 minutes. Subsequently, the organic phase was separated, the water phase was extracted by shaking again with ether and the combined organic phases were dried and concentrated. The oily residue was stirred with methanol. Upon cooling and grinding, 30.8 g (52.7% of theory) of colorless product crystallized out

Mp .: 56-58 ⁰ C.

Example 24

2- (4-Bromophenyl) -5-phenyl-1- (1,2,4-triazol-1-yl) -pentan-2-ol (starting material for Example 5)

Oh ^ _n

- C - CH ₉ - N JL ² ^ J

br

To a suspension of 3.3 g (0.11 mol) of sodium hydride (80% in oil) in 150 ml of dry dimethyl sulfoxide was added under cooling at 15-2O ⁰ C in portions 24.2 g (0.11 mol) Trimethylsulfoxoniumjodid and stirred until to the end of gas evolution. A solution of 26.6 g (0.09 mol) of 1- (4-bromobenzoyl) -3-phenylpropane (Example 25) in 100 ml of dimethyl sulfoxide / tetrahydrofuran 1: 1 was then added. The mixture was stirred for one hour at room temperature and an additional hour at 5O ⁰ C. Then was added 1,2,4-triazole sodium salt 9.0 g (0.10 mol) and stirring was continued for 3 hours at 50 ⁰ C. For work-up was poured onto water, carried out with methylene chloride, the organic phase dried and concentrated. Chromatography on silica gel with ethyl acetate gave a colorless oil which crystallized on trituration with diethyl ether. Yield: 16.8 g (48.3% of theory) M.p .: 9O ⁰ C

Example 25 1- (4-bromobenzoyl) -3-phenyl-propane

- Br

To a Grignard solution prepared from 8.8 g (0.36 mol) of magnesium turnings and 69.8 g (0.35 mol) of i-bromo-3-phenylpropane in 250 mL of dry diethyl ether was added dropwise a solution of 60.0 g (0.33 g) Mol) 4-bromo-benzonitrile in 250 ml of dry diethyl ether. After the exothermic reaction had subsided, the mixture was stirred at reflux for 6 h. After cooling, it was poured onto ice, acidified with 10% strength sulfuric acid and the mixture was stirred for one hour. The mixture was stirred several times with methylene chloride, the combined organic phases were dried and concentrated. The residue was recrystallized from methanol.

Yield: 53,2g colorless crystals (53.2%) mp .: 60-61 ⁰ C.

Example 26

2- (4-chlorophenyl) -1- (1H-imidazol-1-yl) -4-phenylbutan-2-ol (starting material for Example 10)

-Q

To a solution of Dimethylsulfoxoniummethylid prepared analogously to Example 22 from 7.2g (0.24 mol) of sodium hydride (80% in oil) and 57.2g (0.26 mol) of trimethylsulfoxonium iodide in 250ml of dry dimethyl sulfoxide was added a solution of 49.0g (0.20 mol) of 1- (4-chlorobenzoyl) -2-phenyl-ethane (Example 27) in 150 ml of dry dimethylsulfoxide. The mixture was stirred 3h at room temperature and 1 h at 5O ⁰ C. After addition of 18.9 g (0.21 mol) of imidazole sodium salt further 5h at 8O ⁰ C was stirred. After cooling, it was poured onto ice and stirred with 400 ml of methylene chloride. A part of the desired product remained undissolved and was sucked off. The methylene chloride phase was dried and concentrated. The remaining oil was stirred with diethyl ether with further product crystallizing out

Total yield: 44,7g (68.4% of theory..) M.p .: 186-188 ⁰ C.

Example 27 1- (4-Chlorobenzoyl) -2-phenyl-ethane

- CH,

75.0 g (0.31 mol) of 3- (4-chlorophenyl) -1-phenyl-1-propen-3-one (prepared by aldol condensation from 4-chloroacetophenone and benzaldehyde) were dissolved in 200 ml of tetrahydrofuran and hydrogenated after addition of 5 g Palladium / carbon catalyst (5% Pd) under normal conditions. After the end of the hydrogen absorption, the catalyst was filtered off and concentrated. The residue was recrystallized from ethanol

 Yield: 57.0 g (75.4% of theory) mp: 76-78-C

Example 28

5- [2- (4-Chlorophenoxy) phenyl] -2- (2,4-dichlorophenyl) -1- (1 H -imidazol-1-yl) ₍ ) -decan-2-ol (starting material for Compound No.45, Table 1)

OH CH ₂ --CH ₂ - CH ₂ --C - CH ₂

-0

To a solution of dimethylsulfoxoniummethylid prepared analogously to Example 22 from 3.6 g (0.12 mol) of sodium hydride (80% in oil) and 28.6 g (0.13 mol) of trimethylsulfoxonium iodide in 150 ml of dry dimethyl sulfoxide was added a solution 41.0 ( 0.10 mol) of 1- [2- (4-chlorophenoxy) phenyl] -3- (2,4-dichlorobenzoyl) -propane (Example 29) in 150 ml of dry dimethyl sulfoxide.

Tetrahydrofuran (1: 1). The mixture was stirred for 3 h at room temperature and one hour at 50 ⁰ C. At this temperature was added imidazole sodium salt to 10.0 g (0.11 mol), stirred for 4 h at 50 ⁰ C and 1 h at 80 ⁰ C. Workup analogous to Example 22. Chromatography on silica gel gave 17.0 g (34.7% of theory) of colorless crystals mp: 159-160 ° C.

Example 29 1- [2- (4-Chlorophenoxy) phenyl] -3- (2,4-dichlorobenzoyl) -propane

CH ₂ - CH ₂ -

-Cl

A solution of 42.5 g (0.10 mol) of E-1- [2- (4-chlorophenoxy) phenyl] -2- (2,4-dichlorobenzoyl) -cyclopropane (Example 30) in 250 mL of tetrahydrofuran was added after addition of 5 0g palladium / carbon catalyst (5% Pd) hydrogenated under normal conditions. Filtration of the catalyst and concentration gave 41.0 g (96.0% of theory) of a resinous product which was reacted without further purification.

Example 30

E-1- [2- (4-chlorophenoxy) phenyl) -2- (2,4-dichlorobenzoyl) -cyclopropane

-Cl

To a solution prepared analogously to Example 22 from 5.3 g (0.18 mol) of sodium hydride (fO% in oil) and 42.5 g (0.19 mol) of trimethylsulfoxonium iodide in 250 ml of dry dimethyl sulfoxide solution of D'methylsulfoxoniummethylid under cooling a solution of 60.0 g (0.15 mol) of 1- (2- (4-chlorophenoxy) phenyl! -3- (2,4-dichlorophenyl) -1-propen-3-one, Example 31). The mixture was stirred at room temperature for 3 h, poured onto 1.5 l of water and the precipitated solid was filtered off with suction. For cleaning was boiled with 200ml of ethanol.

Yield: 42.5 g of colorless crystals (67.8% of theory)

Mp .: 74-75 ⁰ C

Example 31

1- [2- (4-chlorophenoxy) phenyl] -3- (2,4-dichlorophenyl) -1-propen-3-one

= CH -

To a solution of 56.7 g (0.3 mol) of 2,4-dichloroacetophenone and 68.0 g (0.3 mol) of 2- (4-chlorophenoxy) benzaldehyde (Example 32) in 400 ml of methanol was added 6 ml of 15 with stirring % potassium hydroxide solution. The mixture was stirred at room temperature for 8 h, neutralized with glacial acetic acid and poured onto water. The mixture was stirred with methylene chloride, the organic phase was dried and concentrated. For purification, it was chromatographed on silica gel (hexane / methylene chloride 1: 1). 102.0 g (84.2% of theory) of yellow oil were obtained.

Example 32 2- (4-chlorophenoxy) benzaldehyde

In a solution of 154.3 (1.2 mol) of 4-chlorophonol in 11 dry dimethylformamide was added in portions with cooling 33.0g (1.1 mol) of sodium hydride (80% in oil). After the evolution of gas was added 124,1g (1.0 mol) of 2-fluorobenzaldehyde was added and stirred for 6 hours at 80 ⁰ C. After cooling, it was poured onto ice and filtered off with suction the precipitated product.

Dissolve again in methylene chloride, shake with water, dry and concentrate. Recrystallization from cyclohexane gave 149.3 g of colorless crystals (64.2% of theory).

Table 2 lists the compounds described above and further compounds of the formula IV which can be synthesized analogously to the above examples

a) Compounds of the formula (IV), for which W is the atom required to complete a benzene ring system.

OH

X - (CH ₂ ) _n -C-Ar CH ₂

Table 2

Verb.-Nr. A X η 1 CH 0 2 CVI N 0 CVJ 3 CH 0 CVJ 4 CH S CVI 5 CH CH ₂ CVI 6 N CH ₂ CVJ 7 CH CH ₂ CVJ 8th N CH ₂ CVJ 9 CH CH ₂ CVJ 10 CH CH ₂ CVI 11 N CH ₂ CVI 12 CH CH ₂ 1 13 N CH ₂ 1 14 CH CH ₂ 3 15 CH CH ₂ CVJ 16 N CH ₂ CVJ 17 CH CH ₂ .-, C 18 N CH ₂ CVJ 19 CH CH ₂ CVI 20 CH CH ₂ 2 21 CH 2 22 CH CH ₂ CVJ

Ar

 © -

> Br

Cl

R ¹ R ² 3-Cl H 3-C H 3-Cl 4-Cl 3-C H H H H H 3-Cl H 3-Cl H 4-Cl K 3-Cl 4-Cl 3-Cl 4-Cl II H H H H H H H H H H U ix H H H K H H 5-Ρ H H H

Pp ^e C

77-79 resin 139-140 "resin 164-165

148-149 Resin 185-187 182-183 111-112

186-188

127-128 121-125

144-145 90

93-94

164-166

160-161

177-178

168-169

Table 2 (continued) Part no. A X

CH

CH

CH

CH

CH

CH

CH

CH

CH

CH

CH CH CH

CH ₂ CH ₂ CH ₂ CH ₂ CH ₂ CH ₀

CH ₂ CH ₂ CH ₂ CH ₂ CH ₂ CH ₂ CH ₂ CHo

CH CH

2 2 2 2 2

2 1

2 2 2

Ar

Cl

Il Il Il Il Il

Cl

- (2) 1hienyl

4-Cl

2-C1

2-OCH

2-CH ₅ '

2-CH

H H H H H H

H H H

H H H H H H H

! Fp -C

126

153-155

154-157

140-141

164-165

120-122

resin

159-160

177-179

93-95

144-146

109-111

134-136

156-157

147-149 176-178 150-152

B) compounds of the formula (IV) for which VV is the atom required to complete a naphthalene ring system

OH

(CH ₉ ), - C - CH ₉ - N

(IV)

Preparation of the starting materials of the formula (II)

Example 33

1-Hydroxy-1 - (1 H -imidazol-1-ylmethyl) tetraun

/ -N

verb .No. A 36 CH 37 N

Ppl'Cj 102-103 97-98

To a similar to Example 22 from 19.6 g (0.65 mol) of sodium hydride (80% in oil) and 157.0 g (0.71 mol) of trimethylsulfonium iodide in 75uml dry dimethyl sulfoxide prepared solution of dimethylsulfoxonium gave a solution of 79.6g (0.55 mol) of 1-tetraion in 150 ml of dry dimethyl sulfoxide / tetrahydrofuran 1: 1 and stirred for 5 h at room temperature. In the meantime, by adding 16.4 g (0.55 mol) of sodium hydride (80% in oil) to a solution of 74.1 g (1.1 mol) of imidazole in 300 ml of dry dimethyl sulfoxide, an equimolar solution of j Imidazole / imidazole sodium salt and then poured these to the epoxide solution. After standing overnight, the mixture was stirred for 2 h at 80 ° C and poured after cooling on ice. The mixture was stirred with 11 methylene chloride and the methylene chloride phase was stirred twice with 500 ml of 2 η hydrochloric acid. The combined acid phases were made alkaline with 50% sodium hydroxide solution and extracted twice with 500 ml of methylene chloride each time. The combined organic phases were dried and concentrated. The remaining oil was triturated with ethyl acetate / diethyl ether. Fs crystallized 75.2 g (60.4% of theory) of colorless crystals. Mp: 152-154 ° C

Example 34 4-Methyl-1- (1H -imidazol-1-ylmethyl) indan-1-ol

CH ₂ -N

/ = N

To a solution of dimethylsulfoxonium methylide prepared analogously to Example 22 from 6.4 g (0.21 mol) of sodium hydride (80% in oil) and 50.9 (0.23 mol) of trimethylsulfoxonium iodide in 250 ml of dry dimethyl sulfoxide was added a solution of 26, 0g (0.18 mol) of 4-methyl-indan-1-one (Example 35) in 170 ml of dry tetrahydrofuran. The mixture was stirred at room temperature for 1 h and at 50 ° C. for 1 h. At this temperature, 16.2 g (0.18 mol) of imidazole sodium salt and 12.2 g (0.18 mol) of imidazole were added. The mixture was stirred for a further hour at 50 ° C and 3h at 80 ° C. The procedure was analogous to Example 33. 17.8 g of colorless crystals (43.8% of theory) were obtained. Mp: 155-157 ⁰ C

Example 35 4-Methylindan-1-one

CH-

a) 2-methylcinnamic acid was hydrogenated on palladium / carbon and the resulting 3- (2-methylphenyl) propionic acid (mp 97-98 ^e C) was converted with thionyl chloride into the acid chloride (bp: 125 ° C./20 mm).

b) To a suspension of 40.0 g (0.3 mol) Aiuminiumtrichlorid in a mixture of 200ml carbon disulfide and 100ml of 1,2-dichloroethane was added dropwise with vigorous stirring at a temperature of 20 ⁰ C 50.6g (0.28 mol) 3- (2-MethylphenyD-propionic acid chloride was stirred at room temperature for 6 h, poured onto ice and rendered strongly acidic with concentrated hydrochloric acid, the organic phase was dried and concentrated, and the crude product was recrystallised from ethanol. 66.2% of theory) of yellow crystals

Mp .: 103-104 ⁰ C

Example 36

1 - ( "IH-imidazol-1-ylmathyl) -3,3-dimethyl-indan-1-ol

CH ₃ ^CH 3

To a solution of dimethylsulfoxonium methylide prepared from 6.5 g of sodium hydride (80% in oil) and 50.0 g (0.23 mol) of trimethylsulfoxonium iodide in 300 ml of dry dimethylsulfoxide was added a solution of 32.0 g (0.20 mol) 3.3 -Dimethylindan-1-one prepared from 3-methyl-3-phenylbutyric acid (J.Amer.Chem.Soc.76, 1911 [1954]) by conversion to the acid chloride and cyclization with aluminum chloride, in 100 ml of dry dimethyl sulfoxide. The mixture was stirred 2 h at room temperature and 2 h at 5O ⁰ C. After addition of 14.0 g (0.2 mol) of imidazole and 18.0 g (0.2 mol) of imidazole sodium salt was further 2 h at 5O ⁰ C and 2 h at 50 ° C and 2 h at 7O ⁰ C stirred. After cooling, it was poured onto ice, neutralized with dry ice and the precipitated product was filtered off with suction. For purification, the crude product was heated with ethyl acetate. This gave 20.0 g of colorless crystals '41% d. Th.) Mp. 166-168 ° C

Table 3 lists further compounds of the formula (II) (for which W represents the atoms necessary to complete a benzene ring system), which can be synthesized analogously to the above examples. The position data for R ¹ and R ² refer to the formula shown below, they do not correspond to the usual nomenclature rules.

(II)

Table 3

Verb.-Nr. A 1 CH 2 CH 3 CH 4 N VJL CH 6 CH 7 CH 8th CH 9 CH 10 CH 11 CH 12 CH vj CH 14 CH

15 16 17 18 19 20 21 22 23 24 25 26 27 28

CH CH CH CH CH CH CH CH CH CH CH CH CH N

X η CH ₂ 1 S 2 CH ₂ 3 CH ₂ 3 CH ₂ .1 CH ₂ 1 CH ₂ 1 CH ₂ 1 CH ₂ 1 CH ₂ 1 CH ₂ 1 CH ₂ 1 CH ₂ 1 CH ₂ 1

CH, CH, CH.

CH "

CH ₂ CH,

CH,

CH,

CH ,.

O O

2 2 2 2 1 2 2 2 2 2 2 2 3 3

R ¹ R ² H H H H H H H H 3-Cl 4-C1 3-F H 2-F H 4-F H 3-CH ₃ H 4-CH ₃ H 3-0-cg) H ⁴ ^ vQ) H 2-CH ₃ H 5-CH ₃ H

Fp * C

2-CH ₃ 2-Cl 3-Cl 2-F

2-0-C ₆ H ₅ 4-0-C ₆ H ₅

3-0-C ₆ H ₅

4-SC ₆ H ₅

3-F

3-OCH ₃

4-OCH3

1-OCH ₃

4-CH,

4-Cl

4-Cl

5-F

I29-I3O 162-163 164-165 108-109 164-165 148-149 144-146 175-176 149-151 152-154

136-138

172 (hydrochloride)

155-157 149-150

190-191 163-165 159-160

Resin 119-121 138-139 131-133 162-165 158-159 161-162 143-145

Continuation of Table 3

Verb.-Nr. A X η R ¹ R ² Fp * C H 29 CH O 3 4-Cl H 30 N O 3 4-Cl H 31 CH O 3 3-C1 H 32 N O 3 3-Cl H 33 CH O 3 4-F H 34 N O 3 4-F H 35 CH S 3 H H 36 N S 3 H H 37 CH S 3 4-Cl H 38 N S 3 4-Cl

Compounds of the formula II in which W denotes the C atoms required to complete a naphthalene, tetrahydronaphthalene or thiophene ring system.

No.

CH ₀ -N

177-178 ⁰ C

Mp 184-186 ° C

CH ₂ -N

Mp 153-155 ⁰ C

No.

HO CH ₂ -N

Mp 205-210 ⁰ C

HIGH"-

Mp 142-144 ° C

45

HOCH ₉ -N

Mp 14O-142 ° CFp. 163-165 ° C

HO CHo-N

UJ

CH-

Biological examples A) Medicines The in vitro tests for antifungal activity were performed in the serial dilution test on major fungi (Trichophyton

mentagrophytes, Trichophyton rubrum, Microsporum canis), yeasts (Candida albicans) and molds (Aspergillus niger) (Material and methodology: Microtitration technique published in Mykosen 27, 14 (1984).) As can be seen in Table 4, in these in vitro assays Compounds of the invention good antifungal

Properties superior to those of reference clotrimazole.

Table 4 Trichophyton Minimum inhibitory concentration Mg / ml Microsporum Candida Aspergillus mentagrophytes Trichophyton canis albicans Niger preparation (100/25) rubrum (150/120) (200/175) (500/284) Connection no. 0.97 (101/58) 0.97 1.95 0.97 Table 1 0.12 0.97 0.12 1.95 0.97 20 0.24 0.12 0,007 0.48 1.95 36 0.48 0.06 0.06 0.97 1.95 60 0.48 0.06 0.06 0.97 0.97 13 0.97 0.12 0.06 1.95 1.95 70 0.97 0.97 0.97 3.9 1.95 67 0.97 Material and Methods: Microtitration published in Mykosen 27,14 Heft 1 (1984) clotrimazole

As an example of the high in vivo local activity of the compounds according to the invention become treatment results

Experimentally with Trichophyton mentagrophytes infected laboratory animals.

To determine the local efficacy in each case two 450-50Og guinea pigs (strain Pirbrigh't white)

with 1.5 x 10 * conidia / animal in the epidermis, spread to 6 infection points, infected.

The treatment of the animals took place dermal from the 3rd day after the infection on 5 consecutive days Apply a 0.1% preparation solution to 3 sites of infection on the back. The other back was with vehicle

treated without a preparation in the same way.

In addition to the animals treated with the substances according to the invention, two animals were incubated with the reference substance Clotrimazole treated, two animals left untreated after inactivation. As can be seen in Tabel's 5, the compounds of the invention showed a much greater reduction of Mycosis scleremia as the standard preparation clotrimazole, i. the antifungal effect of the invention Compound was superior to clotrimazole up to 80%. Table 5

concentration

Preparation Compound No. Table 1

Mycoses (Diameter in mm) Vehicle Controls Xi (s) n "

Preparation + vehicle

X ₁ (S)

difference

Xi -x ₂ (%)

dermal 20 14 (1.7) 6 4.3 (1.8) 6 9.7 (138.5) 5 χ 0.1% 36 14.6 (3) 6 3.3 (1.5) 6 11.3 (161.4) 60 15.5 (2,3) 6 4.5 (0.8) 6 11 (157.1) 13 14.5 (2.5) 6 3.7 (0.9) 6 10, P (154.2) 70 15.8 (3.2) 6 3 (0.8) 6 12.8 (182.8) 67 10.7 (1,2) 6 3.2 (0.8) 6 7.5 (107.1) clotrimazole 14.6 (1.7) 6 7.6 (0.4) fi 7 (100) controls - 14 (2,2) 12 - - infected animals untreated

η = number of measured values

The anticonvulsant activity of compounds I and II is evidenced by the data of Table 10, which is determined as follows

were:

Antagonism to Pentetrazole-Induced Spasms (Mouse)

(PTZ)

Method:

Groups of 10 male mice (strain: NMRI, SPF-71, KF) weighing 18-22 g are used in this experiment. The substances to be tested are suspended in water in a 1% suspension of tylose (methyl hydroxyethyl cellulose) and orally administered by gavage in a volume of 10 mg / kg body weight. The control group receives a corresponding volume of Tylose suspension without test substance.

Pentetrazole (Cardiazol [R]) is injected subcutaneously rüfsubstanzen in aqueous solution in a dose of 125 mg / kg body weight 1 hour after administration of ^D. This dose produces tonic extensor cramps of the hind limbs in 90-100% of the control animals within the observation period of 60 minutes after the injection. The protective effect of the test substance is assessed when the number of convulsive animals is reduced compared to the control group.

If there is a protective effect of the test substance, a mean effective dose (ED-50) is determined graphically (Litchfield and Wilcoxon) or computationally (probit analysis).

Literature: E.A. SWINYARD, J. Pharmacol. Exp. Ther. 106, (1952), 319-330

Antagonism against electroshock-induced convulsions (mouse)

(ECS)

Method:

Groups of 6 male mice (strain: NMRI, SPF-71, KF) weighing 18-22g are used in this experiment. The substances to be tested are suspended in water in a 1% suspension of tylose (methyl hydroxyethyl cellulose) and orally administered by gavage in a volume of 10 ml / kg body weight. The control group receives a corresponding volume of Tylose suspension without test substance.

One hour after administration of the test substance, the animals are given an electric shock via corneal electrodes (current 12-22 mA, duration 0.2 sec., 50 Hz), after the current intensity had been determined in a second control group and tonic in 100% of the animals Extensor cramp of the hind limbs causes.

The number of animals protected by the test substance from an extensor cramp serves as a measure of anticonvulsive

Effect in this test.

protective effect of the test substance is a mean effective dose (ED-50) graphically (Litchfield and Wilcoxon)

orisch (probit analysis) determined

 r: E.A. SWINYARD, in: Experimental Models of Epilepsy, Raven Press, New York, 1972, p.433-458.

Tabei. 10 ED ₆₀ O.) LD- _M (mg / kg p. ECS (mg / kg per os) Ptz 34 No. 46 17.3 Verb. 59, tabl. 1 16 35.1 > 300 Verb. 13, Tab. 1 30 24.6 > 300 Verb 53, Tab. 1 55 55.1 Verb. 33, Tab. 1 15.4 60 Verb. 65, Tab. 1 17.2 18.2 Verb. 32, Tab. 1 70 300 Verb 1, Tab.3 9.3 Verb 11, tab. 3

Biological Examples B) Plant Protection

Trial I

Wheat plants are strongly inoculated in the 3-leaf stage with conidia of wheat powdery mildew (Erysiphe graminis) and placed in a greenhouse at 20 ° C and a relative humidity of 90-95%. 3 days after inoculation, the plants are evenly wetted with the compounds listed in Table 6 in the indicated drug concentrations. After an incubation period of 10 days, the plants are examined for infestation with wheat powdery mildew. The level of infestation is expressed in% of infected leaf area, based on untreated, infected control plants (= 100% infestation). The result is summarized in Table 6.

Table β Compound No.

 Table 1

with wheat powdery mildew affected leaf area in%

mg active ingredient / liter spray mixture

500 250 125 60

21 0 0 0 0 23 0 0 0 0 2 0 0 0 0 52 0 0 0 0 34 0 0 0 0 33 0 0 0 0 29 0 0 0-3 3 123 0 0 0-3 3 51 0 0 0 0-3 20 0 0 0-3 3 31 0 0 0 0 64 0 0 3 3-5 34 (Table 1) U 0 0-3 3 52 (Table 1) 0 0 0 0 2 (Table 1) 0 0 0-3 0-3 23 (Table 1) 0 0 0 0-3 21 (TaD. 1) 0 0 0 0 Example No. 36 0 0 0-3 0-3 42 (Table 3) 0 0 0-3 3 10 (Table 3) 0 0 0 0-3 untreated. infected 100 plants

Try Il

Cucumber plants (variety Delikateß) are strongly inoculated in the 2-leaf stage with a conidia suspension of cucumber powdery mildew (Erysiphe cichoracearum). After a drying time of the spore suspension of 30 minutes, the plants are placed in a greenhouse at 22 ⁰ C and 90% relative humidity.

3 days after infection, the plants with the compounds listed in Table 7 and drug concentrations are wetted evenly to drip wet. After 10 days, the rating is done. The level of infestation is expressed in% of infected leaf area, based on untreated, infected control plants (= 100% infestation). The result is summarized in Table 7.

Table 7

Connection no.

with cucumber powdery mildew affected leaf area in%

mg active ingredient / liter spray mixture

500 250 125 60

21 (Tab. 1) 0 0 0 0 23 (Table 1) 0 0 0 0 52 (Table 1) 0 0 0 0 31 0 0 0 0 10 (Table 3) 0 0 0 0 untreated, infected 1C0 plants

Trial III

Apple pads (BM IX) were uniformly wetted in the 4-leaf stage with the claimed compounds in the application concentrations mentioned in Table 8. After drying of the drug coating, the plants were heavily infected with conidia of apple scab (Venturia inaequalis) and placed in a drip-wet climate chamber whose temperature was 22 ⁰ C and their relative humidity was 100%. After an infection time of 48 hours, the plants were placed in a greenhouse with 18 ⁰ C and a relative humidity of 95-100%.

After an incubation period of 14 days, the plants were examined for infestation with apple scab (Venturia inaequalis). The assessment of the infestation was done as usual by inspection. The degree of infestation of the apple scab plants was expressed in% of infected leaf area relative to untreated, infected plants and is shown in Table 8.

Table 8

Compound no.% Scab attack at mg active substance / l spray mixture 500 250 125 60

21 (Tab. 1) 0 0 0 0-3 2 (Table 1) 0 0 0 0 52 (Table 1) 0 0 0 0-3 59 (Table 1) 0 0 0 0-3 34 (Table 1) 0 0 0 0-3 33 (Table 1) 0 0 0 0-3 42 (Table 3) 0 0 0 0-3 untreated, infected 100 plants

Trial IV

Sugar beet plants were evenly wetted in the 6-leaf stage with the claimed compounds in the application rates listed in Table 9. After the active substance coating had dried on, the plants were strongly inoculated with conidia of the beetle pathogen of the turnip (Cercospora beticola) and placed in a drip-wet climate chamber with about 100% relative humidity and 25 ° C. 48 hours later the plants came back to a greenhouse. 14 days later they were examined for infestation with leaf spot disease. The level of infestation was expressed in% of infected leaf area, relative to untreated, infected control plants (= 100%). The results are summarized in table.

Table 9

Compound No. Cercospora beticola infested leaf area

Table 1 in% at mg of active ingredient per liter of spray mixture

500 250 125 60

23 0 0 0 0-3 2 0 0 0 0 59 0 0 0 0-5 34 0 0 0 0-3 33 0 0 0 0 unbehdndelte, infected 100 plants

Try V

Biomalzagar was added to the claimed compounds in the concentrations indicated in Table 10. After solidification of the agar, inoculation was carried out with Pseudocercosporella cultures. Each 20μΙ ί iner spore suspension were applied to the center of the agar plate. The experiments were evaluated 6 days after inoculation. The efficiency of the active ingredients is expressed in% compared to the control (agar medium without active substance).

Table 10

Connection efficiency over pseudo-

cercosporella herpotrichoides

in% at ppm active ingredient no. 500 250 125

75 (Table 1) 100 100 100

64 (Table 1) 100 100 100

66 (Table 1) 100 100 100

73 (Table 1) 100 100 100

71 (Table 1) 100 100 100

80 (Table 1) 100 100 100

64 (Table 1) 100 100 100

33 (Table 1) 100 100 100

5S (Tab.1) 100 100 100

25 (Table 1) 100 100 100

32 (Table 1) 100 100 100

50 (Table 1) 100 100 100

79 (Table 1) 100 100 100

40 (Table 1) 100 100 100

60 (Table 1) 100 100 100

Continuation of Table 10

Connection efficiency over pseudo-

cercosporella herpotrichoides in% at ppm active ingredient

No. 500 250 125

53 (Table 1) 100 100 100 36 (Tab. 1) 100 100 100 30 (Table 1) 100 100 100 24 (Tab. 1) 100 100 100 13 (Table 1) 100 100 100 86 (Table 1) 100 100 100 10 (Table 3) 100 100 100 11 (Table 3) 100 100 100 control 100

Claims (4)

1. pest control agent, characterized in that it comprises as active ingredient an azole compound of the general formula I. wherein A is CH or N, k is 1 or 2 means η is 1,2 or 3 Ar is phenyl, biphenyl, phenoxyphenyl, phenoxythienyl, phenylthiophenyl, phenylsulfinylphenyl, phenylsulfonylphenyl, benzylphenyl, benzyloxyphenyl, benzylthicphenyl, fluoranyl, indonyl, 1,2,3,4-tetrahydronaphthyl, or thienyl, the benzene rings, the naphthalene system or the thiophene ring unsubitituting or may be substituted with one or two substituents which are the same or different and each is fluoro. Chlorine, bromine, iodine, (C ₁ -C ₈ -alkyl), branched or unbranched, unsubstituted or substituted by 1-9 fluorine and / or chlorine atom, (C ₃ -C ₈ ) -cycloalkyl, (C ₁ -C ₄ -J -Alkoxy, (C ₁ -C ₄ -alkylthio, hydroxy, nitro or cyano, W denotes the atoms necessary to complete a benzene ·, naphthalene or thiophene ring system, X is a radical C (R ₃ J ₂₎ and, in the case where W is the atom needed to complete a benzene or naphthalene ring system, also oxygen or sulfur, R ¹ and R ^{2 are the} same or different and each is hydrogen, fluorine , chloro, bromo, iodo, (C ₁ -C ₈₎ -alkyl unbranched, or branched, unsubstituted or substituted with 1-9 fluoro or Chloratomon, (C; jC ₈₎ cycloalkyl, (C ₁ -C ₈ J- AIkOXy, (CH ^ J-alkylthio, cyano or nitro mean, as well as in the event that W at the same time the necessary to complete a benzene ring atoms, R ¹ is phenyl, phenoxy, phenylthio, phenylsulfinyl, phenylsulfonyl, benzyl, benzyloxy or hydroxy in which the phenyl groups in these substituents can be unsubstituted or substituted by one or two substituents and these substituents are identical or different and in each case fluorine, chlorine, bromine, iodine, (C ₁ -C ₄ ) -alkyl, branched or unbranched, unsubstituted or by 1-9 fluoro o the chlorine atoms substituted, (C ₃ -C ₈ J-CyClOaIkyI, (C ₁ -C ₄ ) alkoxy, (CT-CJ-alkylthio, cyano or nitro mean, or R ¹ , R ² , if they are ortho-oriented, together is a (C ₃ -C ₅ ) alkylene chain and R ³ as a substituent of the chain (CH ₂ ) or of X independently of one another is H or (C ₁ -C ₈ ) -alkyl or two radicals R ³ , if they are attached to the same C- Atom bonded are a (C ^ CeJ-alkylene chain and their stereoisomers and their salts in addition to conventional extenders and / or formulation auxiliaries. 2. Pest control agent according to claim 1, characterized in that in the compounds of the forms! I at least one of the substituents or indices has the following meaning: W is the atom necessary to complete a benzene ring system, X is the methylene group, oxygen or sulfur, A is CH or H, η is 1.2 or 3, Ar is phenyl, biphenylyl-phenoxyphenyl, phenylthiophenyl, fluoronyl-indanyl, 1,2,3,4-tetrahydronaphthyl or thienyl, unsubstituted or substituted on the benzene rings or on the thiophene ring with one or two substituents which may be the same or different and each is fluoro , Chlorine, bromine (C ₁ -C ₄ -alkyl), (C ₁ -C ₄ (C ₁ -C ₄ ) -alkoxy or trifluoromethyl, R ¹ and R ^{2 are} identical or different and each represents hydrogen, fluorine, chlorine, bromine, trifluoromethyl, (C ₁ -C ₈ -alkyl or (C ₁ -C 6) -alkoxy. 3. Pesticidal composition according to claim 1, characterized in that in the compounds of the formula I Ar is mono-halophenyl or 2,3-Dihaloger.phenyl, where the halogen atoms are the same or different and each represents fluorine or chlorine or Ar 4-biphenylyl, 4-phenoxyphenyl, 4-phenylthiophenyl or fluoronyl unsubstituted or substituted on a benzene ring with one or two substituents and these substituents are the same or different and each represents fluorine, chlorine, trifluoromethyl, methyl or methoxy. 4. Pesticidal composition according to claim 1, characterized in that in the compounds of formula I at least one of the substituents and indices has the following meaning: Ar4-chlorophenyl, 4-fluorophenyl, 2,4-dichlorophenyl, 2,4-difluorophenyl, 4-chloro-2-fluorophenyl, fluoranyl, 4-biphenylyl, 4-phenoxyphenyl or 4-phenylthiophenyl, where the latter three groups are unsubstituted or in the 4'-position with fluorine, chlorine, methyl, methoxy or trifluoromethyl may be substituted, R ¹ and R ^{2 are the} same or different and are hydrogen, fluorine, chlorine, trifluoromethyl, methyl or methoxy. 5. A method for controlling or preventing an infestation of crops by phytopathogenic fungi, characterized in that a compound of formula (I) according to claim 1 is allowed to act on the plant or threatened by fungal attack surfaces, plants or seeds. Field of application of the invention The invention relates to a process for the preparation of 1-aryl-; -azolylmethyl-benzocycloalkene derivatives and their use as crop protection agents, in particular as fungicides or as growth regulators or as pharmaceuticals, in particular as antimycotics and anticonvulsants. Characteristic of the known state of the art GB-PS 2143523 A describes 1-aryl-1-azolylmethyl-1,3-dihydroisobenzofurans as fungicides in crop protection. However, neither antifungal or anti-onvulsive effects are described therein nor the compounds of the invention. Object of the invention The aim of the invention is to provide novel compounds having a broad spectrum of activity, in particular with antimycotic activity, which can be used in agriculture and in the technical field and for the treatment of fungal infections in the human and veterinary field. Explanation of the essence of the invention The invention is based on the object. Find compounds with the desired properties and process for their preparation. It has now been found that the compounds according to the invention, which differ substantially from the abovementioned compounds by the nature of the ring system, have very good antimicrobial, in particular fungicidal, antifungal properties. They are therefore suitable for controlling fungi in humans, animals or plants. By anticonvulsive action, the compounds of the invention are further suitable for the treatment and prevention of epileptic diseases. They also have growth-regulating properties for plants. According to the invention, azole derivatives of the formula (I)