NL8402002A - NEW AZOLE CONNECTIONS. - Google Patents

Description

"I." 4 X - 1 -

New azole compounds.

The invention relates to o (- </ - di-substituted 1-H-azole-1-ethanols.

The invention provides new t / -aryl- -Rj -1H- 1,2,4-triazole-1-ethanols, in which there is an olefinic group, which in the i-position of the (carbon atom) has at most 1 H- atom and has its double bond in the 2- or 3-position of the carbon atom and its ethers and esters (hereinafter compounds of the invention).

The invention also provides methods of preparing the compounds of the invention, the use of these compounds and compositions containing such compounds.

The (/ -aryl group of the compounds of the invention may well be an aromatic hydrocarbon (eg naphthyl, preferably phenyl) which is unsubstituted or substituted, or a heteroaromatic ring bonded through one of its ring carbon atoms (eg a 5- or 6-ring with 1 or 20 heteroatoms from the group 0, N and S, preferably furyl, thienyl or pyridyl) and is unsubstituted or substituted.

Examples of suitable tf-aryl groups are phenyl, unsubstituted or mono- or disubstituted with the substituents NO 2, halogen, alkyl, 2 - 5 - 5 alkyl, alkoxy, haloalkyl, haloalkenyl and haloalkoxy, phenyl or phenoxy, substituted or unsubstituted. Further examples of suitable O (-aryl groups) are the heteroaromatic 3-pyridyl group and 2-thienyl and 2-furyl, unsubstituted or substituted with halogen or lower alkyl (eg 5-Cl-2-thienyl and 5-t-butyl-2 furyl).

The O (-aryl group is preferably phenyl, substituted with K 2 and R 2, wherein and independently H, halogen, lower alkyl, lower alkenyl or lower alkoxy, unsubstituted or halogenated, phenyl or phenoxy, unsubstituted or substituted, or NÜ £.

8402002 # · »- 2 -

The term "lower" is used herein in its generally accepted sense, that is, the highest number of carbon atoms is limited, usually to 5, preferably to 4, carbon atoms.

An optional / suplituent in the compounds of the invention may well be F, Cl or Br.

A preferred subclass of compounds of the invention includes compounds of formula I, wherein and R 3 have the above meaning and esters and ethers of such ethanol compounds.

The olefinic group R ^ may be straight or branched, it may be aliphatic, carry cycloalkyl or phenyl groups, or contain additional multiple CC bonds and each branch may be saturated or may contain an olefinic and / or an alkaline (triple) bond .

Any phenyl group of R 1 can be substituted, especially mono- or disubstituted. Examples of suitable substituents of such phenyl groups are halogen, lower alkyl, lower alkoxy, lower haloalkyl (e.g. 20 CH 1 Cl, CF 1), lower haloalkoxy (e.g. OCF 1, OCI 2).

When the olefinic group (R 1) is branched, such branches may be contiguous to form a cycloaliphatic group (3- to 7-, especially 3- to 6-membered). The olefinic (double) bond may be included in the cycloaliphatic system (to form a cycloalkenyl group, which is at least 5-membered).

The carbon atoms of the olefinic (double) bond, as well as those of any additional aliphatic multiple CC bond, may be substituted with halogen (especially Cl, preferably Br) and in such case, preferably only one of the carbon atoms of the double bond mono-halogenated, and the halogen is preferably bonded to the carbon atom furthest from the C (carbon atom).

When the hydroxyl group of the compounds of the invention is etherified, such ethers are, in particular, without alkyl, C 1-4 alkenyl, alkinyl or aralkyl ethers (eg benzyl ether), preferably methyl, allyl or propargyl ethers (the latter of which may be halogenated at their double or triple bond) and when the hydroxy 1-5 group is esterified, such esters are in particular of aliphatic carboxylic acids, such as the acetate.

The compounds of the invention contain one or more chiral centers. Such compounds are generally obtained in the form of racemic, diasteromeric and / or cis / trans mixtures. However, such mixtures may be split, in whole or in part, into the individual compounds or desired isomeric mixtures, if desired, according to art-known methods.

Specifically, R ^ is a group of formula 7.15 where n is 0 or 1, R ^, Rg, and Rg are independently H, C 1-8 alkyi, C 8 -cycloalkyl, cycloalkyl-C 1-6 alkyl, unsubstituted or substituted phenyl or phenyl-G 2 -alkyl, which is unsubstituted or substituted on its phenyl moiety, are, R 1 -C 2 -g alkyl or C 8 -g alkenyl, R 2 H, halogen (especially chlorine or bromine), C 1 -g alkyl, C 8 -C 7 cycloalkyl, C 8 -25 cycloalkyl-C 1-6 alkyl, substituted or unsubstituted phenyl, or phenyl-C 1-6 alkyl, which is unsubstituted or substituted on its phenyl radical, and R 9 is H, C 1-6 alkyl C8 -g is alkinyl (especially 30 CsC-tC ^ Hg) or halogen (especially chlorine or bromine), where R 1 and R 1. can be together (GH2),

Rg and Rg together (22 ^ 2-4 can be z ^ 3n and R ^ and Rg together (Φ ^ 2-5 can be.

35 In. the group of the formula 7 are preferably 8402002 * * - 4 - Ί ......... ... .. ----- - not more than two and preferably not more than one of the symbols R ^, Rg, Ry and Rg Cg_y cycloalkyl, Cg_y cycloalkyl-C ^ alkyl, phenyl (substituted or unsubstituted) or phenyl-C ^ ^ alkyl (substituted or unsubstituted on its phenyl radical) and as one or two of the 5 symbols R ^, Rg, Ry and Rg are such a cyclic group, it is preferably R ^ and / or Rg, most preferably R ^.

When R ^ and R ^ together are (CH2) 2_ ^, it is preferably (CH2> 2_ ^.

When R ^ Cg_g is alkenyl, it is convenient if the double bond is not in the 1 position.

Preferred groups of formula 7 have one or more of the following aspects:

Rg is H or C ^ g alkyl or, together with Rg <CV2-4> 15 Ry is H or C ^ g alkyl or, together with Rg <cV2-5>

Rg is H or C ^ _g alkyl or, together with Rg or Ry ^ CH2 ^ 2-4 ° f ^ CH2 ^ 2-"5>

Rg is H, Cl, Br, alkyl or C = C-t C ^ Hg, Rg is H, C ^ -g alkyl or, together with R8. (^ 2 ^ 2-6 n is 0, Ry, Rg and Rg are H or C ^ _g alkyl, n is 0, R ^ and Rg are each C ^ g alkyl or are together (C12) 2, Ry and Rg H or C ^ _g alkyl and Rg is H, C ^ g alkyl, Cl or Br, n is 0, or R ^ is H or C ^ _g alkyl and R ^ is C ^ _g alkyl, or R ^ and R together are (CH2) 2 _g, and Ry is H, n is 1, either R ^ is H or C ^ _g alkyl and R ^ is C ^ _g alkyl, or R ^ and R ^ are together (CH2) 2_g, and Rg, Ry,

Rg and Rg are H or C ^ _g alkyl, 30 n is 1, R ^ is H or C ^ g alkyl and R5 is C ^ _g alkyl, n is 1, R ^ is H or C ^ -g alkyl, R ^ is C ^ g alkyl, Rg together with Rg or Ry is (CH2) 2_ ^ or (CH2) 2_ ^, respectively, where the remaining substituent (Ry or Rg) is H 35, 8402002 • * - 5 - n is 1 , and at least two of the symbols Rg, R ^ and Rg are H,

Rg and Rg are H2 g ^ _g alkyl, R ^ is H and Rg is H, C ^ _g alkyl, Cl or Br, Rg and R ^, as well as one of the symbols Rg and Rg are, or R ^ H or C ^ g is alkyl, or Rg is C1-5 alkyl, or R ^ and Rg are together (CHgig ^

Unless otherwise stated, each C 1-8 alkyl group preferably contains 1 to 4, more preferably 1 or 2 carbon atoms and each cycloalkyl group in the compounds of the invention is preferably 3 to 6-membered.

The compounds of the invention are prepared by reacting a compound of the formula 2, wherein Μ H, is a metal or a trialkylsilyl group, with a 2-aryl-2-R 1 -5 oxirane compound, wherein R 1 is as defined above, or a reactive functional derivative thereof, optionally followed by the introduction of a chlorine or bromine substituent on one of the C atoms of the double bond of R 2 in the 2 or 3 position and / or by etherification or esterification of the hydroxyl group.

The compounds of the formula 1 are accordingly obtained by the following processes, wherein a) a compound of the formula 3, wherein R 1, R 8 and R 9 have the above meaning, or a reactive functional derivative thereof, is reacted with a compound of the formula 2, b) a compound of the formula la is obtained, in which Rg, Rg and Rg have the above meanings, either Rg * C ^ _g is alkyl, or Rg and Rg 'together are CCH2 ^ 2-6 is'

R 1 'is H or substituted or unsubstituted phenyl, and is chlorine or bromine, by cleavage from a compound of 8402002 * * - 6 - the formula 4, wherein X, R, R, R, R, R and R 'and n above have the meanings mentioned.

The method of the invention according to variant 5 a) can be carried out under analogous conditions as are known. for the preparation of azole-1-ethanols by reaction of an azole with an oxiran.

As. When formula 2 is H, the reaction with the oxiran compound can be carried out well in the presence of a base.

When in formula 2 M is a metal, it is preferably an alkali metal, for example Na.

If in the formula 2 M is trialkylsilyl, for example trimethylsilyl, the reaction can be carried out well in the presence of a base such as NaH.

The reaction process can be carried out well in a solvent which is inert under the reaction conditions, for example in dimethylformamide. A suitable reaction temperature is between room temperature and reflux temperature of the reaction mixture and when M in the formula 2 is trialkylsilyl it may well be above room temperature, for example between 70 and 90 ° C.

The term "reactive furonic derivative" used in connection with the above 2-aryl-2-R-oxiranes, such as the compounds of formula III, is intended to refer to any oxirane derivative which, by reaction with an azole of the formula 2 results in ethanol compounds of the invention. Several examples of such reactive derivatives are known in the art and a suitable example are the corresponding halogen hydrines (wherein the halogen is, for example, Cl or Br).

The conditions under which the compounds of the formula II can be reacted with the reactive functional derivatives of the above-defined 2-aryl-2-R-oxiranes are also known per se. The reaction of a compound with the formula 8402002 with the halohydrin derivative of a compound of the formula 3 can be carried out under the conditions described for the reaction with the oxiran compounds, but well in the presence of an additional equivalent of a base.

The separation of HX4 according to variant b) of the process of the invention can be carried out under basic conditions, for example, using NaH in an organic solvent which is inert under the reaction conditions, such as dimethylformamide. The reaction can be carried out well under heating, for example at 40 to 80 ° C.

Depending on the significance of the substituents in the dihalogen side chain of the compounds of the formula 4 - and as far as R ^ TH - some of the compounds of the formula 4 may also result in compounds of the formula 1 wherein the halogen is bonded to the other olefinic C atom, which is closer to the carbinol group (position isomers of compound of formula 1a).

The compounds of the invention can be recovered from the reaction mixture in a manner known per se and purified.

Ester and ether derivatives of the ethanol compounds of the invention may be obtained from the corresponding ethanol by known esterification or etherification methods.

The compounds of the invention can exist in free base form, in salt form, for example as an acid addition salt with an organic or inorganic acid, such as hydrochloride, or as an alcoholate, for example as Na-ethanolate and in metal complex form, for example with a metal from the growth Ib, Ila, Ilb, VIb, Vllb and III of the Periodic Table, such as copper and zinc and with anions such as chloride, sulfate and nitrate. The salt forms and metal complex forms can be obtained in known ways from the corresponding free forms and vice versa.

The starting materials can be obtained by known methods 8402002 m * - 8 - Examples of some such methods are given below * Depending on the meaning of the substituents, other methods may be more suitable.

The compounds of the formula III can obtain them a) from the corresponding halohydrins by treatment with a base, b) from the corresponding ketones of the formula III wherein R1, R2 and Rg are as defined above, by treatment with a compound of the formula 6 wherein m is 0 or 1, X is halogen or CH 2 SO 2 is R 2, 2 alkyl, in the presence of a base (alkali metal hydroxide or hydride) under conditions, or analogous conditions, as from the literature are known. When Rg is alkyl, especially straight Ggg, alkyl, eg n-dodecyl, the compound of formula 6 can also serve as a phase transfer catalyst.

Insofar as the preparation of the starting materials is not described, they are known or can be obtained by, or analogous to, methods described herein or known methods.

The compounds of the invention, in free form or in the form of pharmaceutically (or veterinary) acceptable salt or metal complex form, have interesting biological, in particular antimycotic, properties and are therefore indicated as a suitable medicament for the control of fungal diseases of humans or other animals.

The antimycotic activity can be determined by in vitro tests, for example, in the in vitro dilution series test on various families and species of mycetes, such as yeasts, fungal fungi and dermatophytes in concentrations of about 0.05 to about 50 µg / ml and also by in vivo tests, for example, by 8402002 * * - 9 - system, administering doses of about 3 to 100 mg / kg body weight to rats infected intravaginally with Candida albicans.

For the above use, the dose administered varies, of course, depending on the relative activity of the compounds used, the mode of administration and the desired treatment. Test results with, for example, 1-bromo-4- (4-chloro-phenyl) -3,53-dimethyl-5- (1,2,4-triazo-1-yl) pent-1-en-4-o1 on the model of the vaginal candidasis of the rat indicates that the doses to be administered are analogous to those generally recommended for ketoconazole. In general, satisfactory results are achieved when administered internally at a daily dose of 3 to 100 mg / kg body weight of the animal, which is administered manually in divided doses two to four times a day, or in a sustained release form. For larger mammals of about 70 kg body weight, the corresponding daily dose is, for example, 200 to 2000 mg, and dosage forms suitable for oral administration, for example, comprise 50 to 1000 mg of active substance.

The compounds of the invention can be prepared and used in the free base form or in the form of pharmaceutically (or veterinary) acceptable salts (acid addition salts or alcoholates) or metal complexes. Generally, the salt forms exhibit the same order of action as the free base forms. Acids which can be used to prepare acid addition salt forms include, for example, hydrochloric, hydrobromic, sulfuric, nitric, fumaric and naphthalene-1,5-disulphonic acids.

The compounds of the invention can be mixed with conventional pharmaceutically (or veterinary) acceptable inert carriers and optionally other excipients. They can be used in analogy to a manner known for the use of standard compounds, such as ketoconazole. They may be administered in such dosage forms to be administered internally as tablets or capsules, or optionally topically, administered in conventional forms such as ointments or creams, or administered parenterally. The concentrations of the active agent naturally vary depending on the compound used, the desired treatment and the nature of the form of administration, and so on. In topical administration forms, satisfactory results are generally obtained at concentrations of 0.05 to 5, especially 0.1 to 1% by weight.

The compounds of the invention in free form or in agriculturally acceptable salt form (acid addition salt or alcoholate) or metal complex form are also suitable as fungicides to combat phytopathogenic fungi. Their beneficial fungicidal activity has been established by in vivo tests with test concentrations of about 0.00005 to 0.05% against Uromyces appendiculatus (bean rust) on French beans, against other rust fungi (such as Hemilei-15a, Puccinia) on coffee, wheat, geranium, snapdragon, against

Erysiphe cichoracearum on cucumber and against other powdered flour dew fungi (E. graminis f.sp. tritici, E. Graminis f.sp.hordei, Podosphaera leucotricha, Uncinula necator) on wheat, rye, apples and wine grapes. Further interesting actions have been observed in vitro against Ustilago maydis, among others, with test concentrations of about 10 to 160 ppm (calculated by volume of substrate). Since these tests also indicate good plant tolerance and good systemic activity, the compounds of the invention are indicated for the treatment of plants, seeds and soil to combat phytopathogenic fungi, for example Basidiomycetes, Ascomycetes and Deuteromycetes, in in particular, Basidiomycetes of the order Uredinales (rusting), such as Puccinia spp, Hemileia spp, Uromyces spp; Ascomycetes of the order Erysiphales (powdery mildew), such as Erysiphe spp, Podos-30 phaera spp, and Uncinula spp, and of the order Pleosporales, such as Venturia spp and also as Phoma, Khizoctonia, Helminthosporium, Pyricularia, Pellicularia (= Corticopsis), and Stereum spp.

The amount of compound to be used depends on different factors, such as the compound used, 8402002 - 11 -

• V

the subject of treatment (plant, soil, seed), the type of treatment (for example, watering, sprinkling, sprinkling, pollination, pouring), the purpose of the treatment (prophylactic or therapeutic), the fungi type to be treated and the time of application.

In general, satisfactory results are obtained when the compounds of the invention are used in an amount of about 0.005 to 2.0, preferably about 0.01 to 1 kg / ha, in case of treatment of plants or the soil, for example 0.04 to 0.125 kg of active ingredient (ab) per ha in harvests, such as grains, or concentrations of 1 to 5 g ab per hl in harvests, such as fruit, vineyards and vegetables (with an application volume of 300 to 1000 l / ha - depending on the size or leaf volume of the harvest - which is equivalent to an application rate of about 10-50 g / ha The treatment can be repeated at 8 to 30 day intervals if desired.

When the compounds of the invention are used for treating seeds, satisfactory results are generally obtained when the compounds are used in an amount of about 0.05 to 0.5, preferably about 0.1 to 0.3 g / kg seeds.

The term soil used herein is understood to refer to any conventional growing medium, be it natural or artificial.

The compounds of the invention can be applied to a wide variety of harvests, such as soybeans, coffee, ornamental plants (eg geranium, roses), vegetables (eg peas, cucumber, celery, tomatoes and bean plants), sugar beets, sugar cane, cotton, flax, corn, vineyards, apple-like fruit and stone fruits (eg apples, pears, plums) and are particularly suitable for use with cereals (eg wheat, oats, barley, rice) and apples.

In particular, the compounds of formula 35 with one or more of the following aspects have valuable biological properties: 6402002-12: R2 is 4-C1 R3 is H or 2-C1 R, H or CH ,, especially CEL 4 3 3 5 R ^ is CH ^

Rg, R ^ and Rg are H Rg is H, Cl or Br n is 0.

Thus, compounds Nos. 1, 35, 34 and 10 33 exhibit valuable biological activity under, and especially the latter compound.

The invention also provides fungicidal compositions containing, as fungicidal, a compound of the invention in free form or in agriculturally acceptable salt or metal complex form, optionally in combination with an agriculturally acceptable diluent (hereinafter diluent). They are obtained in the usual manner, for example, by mixing. a compound of the invention with a diluent and optional additional ingredients, such as surfactants.

The term diluents as used herein refers to liquid or solid, agriculturally acceptable material, which can be added to the active substance in order to bring it into a more convenient or more useful form, or to dilute the active ingredient into a conventional or desired effect strength. Examples of such diluents are talc, kaolin, diatomaceous earth, xylene and water.

Special preparations which are used in spray form, such as water-dispersible concentrates or wettable powders, may contain surfactants, such as wetting and dispersing agents, for example the condensation product of formaldehyde and naphthalene sulfonate, an alkyl laryl sulfonate, a lignin sulfonate fatty alkyl sulfate, an ethoxylated alkyl phenol and an ethoxylated fatty alcohol.

8402002 - 13 -

Generally, the compositions contain 0.01 to 90 wt% active agent, 0 to 20% fungicidally acceptable surfactant, and 10 to 99.99 wt% diluent (s). If desired, such preparations can be further diluted before use. Concentrated preparation forms, for example, emulsifiable concentrates, can generally contain from about 2 to 90% by weight, preferably from 5 to 70% by weight, of active agent. Usage forms of a formulation generally contain 0.00005 to 10 wt% compound of the invention as the active agent. Good examples of spray suspensions contain, for example, 0.0005 to 0.05, preferably 0.001 to 0.02, for example 0.001, 0.002 or 0.005% by weight of active substance.

In addition to the usual diluents and surfactants, the compositions of the invention may contain further special purpose additives, for example, stabilizers, deactivators (for solid compositions on active surface supports), plant adhesion improvers, corrosion inhibitors, anti-foaming agents and dyes. In addition, other fungicides with similar or complementary fungicidal activity may be present in the preparation, such as sulfur, chlorothalonil, dithiocarbamates, such as mancozeb, maneb, zineb, propineb, trichloromethanesulfenylphthalimides and analogues, such as captan, cap-tafol and folpet, benzimidazoles, such as benomyl, as well as other beneficial agents, such as insecticides.

Examples of fungicidal preparations for plants are the following (parts are parts by weight): a) wettable powder preparation.

10 parts of the compound of the invention are mixed and ground with 4 parts of synthetic fine silica, 3 parts of sodium lauryl sulfate, 7 parts of sodium lignin sulfonate, 66 parts of finely divided kaolin and 10 parts of diatomaceous earth, until the average particle size is about 5 micron. The resulting wettable powder is diluted with water before using it for a spray liquid, which can be used as a foliar spray, but also as a root drenching agent.

b. Granules

0.5 parts by weight of binder (nonionic surfactant) are sprayed onto 94.5 parts by weight of quartz sand in a tumbler mixer and the whole is thoroughly mixed. Then 5 parts by weight of the compound of the invention are added and thorough mixing is continued until a granular preparation having a particle size of 0.3 to 0.7 mm is obtained. The granules can be used by incorporating them in the soil near the plants to be treated.

c. Emulsion concentrate.

10 parts by weight of the compound of the invention are mixed with 10 parts by weight of emulsifier and. 80 parts by weight of 15 isopropanol. The concentrate is diluted with water to the desired concentration.

d. Seed sauce.

45 parts of the compound of the invention are mixed with 1.5 parts of diamylphenol decaglycol etherethylene oxide addition product, 2 parts of spinning oil, 51 parts of fine talc and 0.5 parts of the coloring agent Khodamine B. The mixture is ground in a contraplex mill at 10,000 rpm, until an average particle size of less than 20 microns is obtained. The resulting dry powder shows good adhesion and can be applied to seeds, for example, by mixing in a slowly rotating vessel for 2 to 5 minutes.

The following examples further illustrate the present invention. All temperatures are in ° C. RF values are on silica gel.

30 8402002 - 15 -

End connections.

Example I: 2- (4-chlorophenyl) -3,3-dimethyl-1— (1,2,3-triazol-1-yl) -hex-5-en-5 2-ol

Stage 1

Men. adds 5.6 g of 1- (4-chlorophenyl) -2,2-dimethyl-ΙΟ-pent-4-en-1-one to 68 ml of toluene. 12.9 g of dodecyldimethylsulfonium methylsulfate are added thereto and the mixture is stirred for 5 minutes. 2.8 g of finely powdered KOH is added to the suspension thus obtained. This mixture is stirred at 35 ° for 22 hours, poured on ice and extracted with ether. The organic extract is washed three times with water and then with saturated aqueous sodium chloride solution (brine), dried over MgSO 2 and concentrated by rotoevaporation. The residue thus obtained is a colorless oil containing 50.5% 2- (4-chlorophenyl) -2- (1,1-dimethyl-3-butenyl) -oxiran (by gas chromatography) in addition to dead 20 cylethyl sulfide.

Stage 2

To 5.8 g of 1,2,4-triazole in 31 ml of dimethyl-25 formamide (DMF), 5.8 g of CO 2 CO 2 are added and the mixture is heated to an internal temperature of 90 °. To this is added 9.6 g of crude (50.5% oxiran reaction product from step 1 over 10 minutes) and this mixture is stirred at 90 [deg.] For 18 hours. Then the reaction mixture is cooled to room temperature, taken up in CH2-1 and washed. three times with water The organic phase is dried over MgSO 4, evaporated (by rotoevaporation) and stripped off from the remaining DMF under high vacuum The residue is recrystallized from CH 2 Cl 2 / hexane to give the pure the title compound in the form of white crystals, mp 87-89 °.

35 8402002 - 16 -

J V

According to the procedure of Example I, using the appropriate starting materials of the formula III, the following compounds of the formula 1 are obtained: 5 Compound _Rj_ R2 R3 Rf / mp 1 C (CH3) 2-CH2-CH = CH2 4-Cl H 87-89 ° 2 C (CH3) 2-CH2-C (CH3) = CH2 4-C1 H 83-84 ° (1) 3 C (CH3) 2-CH2-CH = CH-CH3 4-C1 H 61 -63 ° (2) 4 CH (CH3) -CII = CH2 2-C1 4-C1 102-104 ° 10 (A) / 135-137 ° (B) (3) 5 C (CH3) 2-CH2-CH = CH-CsC-t, C4H9 4-G1 H HClS115e (dec.)

6 - CH -CH = CH9 4-Cl H

15 L — J

7 C (CH3) 2-CH2-C (CH3) = CH2 4-F H

8 C (CH3) 2-CH2-CH = C (CH3) 2 4-Cl H

9 c (CH 3) 2 -Q 4-Cl H

20

10 C (CH 3) 2 -CH 2 -Q 4-Cl H

11 C (CH3) 2-CH2-CH = CH - ^ - - Cl 4-Cl H

12 C (CH3) 2-CH2-CC1 = CH2 4-Cl H

13 C (CH3) 2-CH2-CBr = CH2 4-Cl H.

14 C-CH 4 -CI 3 = CHO 4-Cl H

CH (CH3) -CH2-CH = C122-Cl H 25 °

CH 16 (CH2-CH = C12) 2 4-Cl H

^ ch9-ch = ch9

17 CH. 4-Cl H

^ C6H5 18 CH / "CH2-C (CH3) -CH2_72 4-Cl H 74-76 °

CH (4F-C6H5) CH2-CH = CH2 4-Cl H

8402002 - 17 -

-CII -CII = CII-4-C1 H

20 CCC6%; 2 2

6 3 4-C1 H

21 5 ^, - (4-c ^ o-c6h4)

2 J 4-Cl E

22 <2_β3ζ - <:( 0Η3) -0Η2 „c (C%> 2-CH-CH2 4-C1 2-C1

-C (CH 3 = CH 4 -Cl H

10 24 CC <% '2 3 2

25 0 (003) 2 - ^ - ¾ 4'01 B

26 0 (0) 3 ^ 2 - ^ - ° ° ¾ ^ 4 "C1 H

27 00 (^ - ^ ¾ 4'01 H

28 00 (02 ^ -¾ 4'C1 E

15 c (CH) = Cl 4 ~ cl 2 29 << ^ ch2-c (ch3) -ch 2 30 CS (C6S5) -CH-CH 2 4-C1 1 31 chCch2c6h5) -g- (ch3). 20 32 H 4 "C1 92'95 ° 33 c ^ cB; 3) 2-CII-C 4-Cl 4 104-106 ° 34 c (ch 3) 2-CII = C 1 -C 4 114-116 ° 35 ci (CH3) -CIl = CiBr 4-Cl 2-Cl 155-161 ° 25 (1) Purification by chromatography on silica gel with hexane / ethyl acetate (9: 1) and pure ethyl acetate.

Recrystallization from C12C12 / hexane (colorless crystals).

(2) As under (1), but recrystallization from hexane.

(3) Diastereomeric Forms A and B from the corresponding starting diastereomeric material.

35 1402002 - 18 -

Example II: 1-Bromo-4- (2,4-dichlorophenyl) -3-methyl-5- (1,2,4-triazol-1-yl) -pent-1-en-4-ol 5 At 1 g 4- (2,4-dichlorophenyl) -3-methyl-5- (1,2,4-triazol-1-yl) pent-1-en-4-ol in 20 ml CHCl 4 is added with cooling (with ice water ) and stirring a solution of 0.5 g Br 2 in 3 ml CHCl 2. The mixture is allowed to warm to room temperature, after which it is evaporated under vacuum and the residue is taken up in 10 ml of dry DMF. After adding 77 mg of NaH, the mixture is stirred at 60 ° for 20 hours and poured into water. This mixture is extracted with ethyl acetate, the organic phase is evaporated to dryness, the resulting residue is purified by chromatography on silica gel with ethyl acetate and recrystallized from CHCl 3 / diisopropyl ether (mp 155-161 °).

According to the procedure of Example II, using the appropriate starting material, compound No. 33 (mp 104-106 °) can be obtained. Compound No. 33, however, is preferably prepared by the method of Example I.

20

Intermediates A. 5-chloro-4- (2,4-dichlorophenyl) -3-methyl-pent-1-en-4-ol: 25

0, 2,4-trichloroacetophenone is reacted with krotyl bromide to give a diastereomer mixture, which is split by chromatography on silica gel with toluene / hexane (1: 1).

Diastereomer A: Rf = 0.34 B: Rf = 0.45.

B. 1- (4-chlorophenyl) -2,2-dimethyl-pent-4-en-1-one.

To a reaction mixture of 28 g of powdered Η0Η 8402002 - 19 - ia 500 ml of toluene, 45 g of 4-chlorophenyl isopropyl ketone are added over 30 minutes at room temperature, with stirring, followed by 8.1 g of tetrabutyl ammonium bromide, the inner temperature being 30 ° rises. After stirring for 2 hours, 28.7 allyl chloride in 100 ml of toluene are added. The mixture is then stirred at room temperature overnight, poured into ice water, extracted with ether and the organic phase is washed with water and brine, dried over MgSO4 and evaporated. Fractional distillation of the crude residue gives the title compound as a colorless oil, boiling point 95 ° / 0.4 mm Hg.

G. 1- (4-chlorophenyl) -2,2,4-trimethyl-pent-4-en-1-one.

A solution of 36 g of 4-chlorophenyl-15 isopropyl ketone in 40 ml of DMF is added dropwise, under a blanket of NO, to a suspension of 12 g of 80% NaH in 30 ml of DMF and the mixture is stirred at 40 ° for an additional 2 hours. A solution of 36.2 g of 3-chloro-2-methyl-1-propene in 40 ml of DMF is then added dropwise, within 15 minutes and at room temperature, and the mixture is stirred for another hour. After addition of water, the reaction mixture is taken up in ether, washed with water and brine, dried over MgSO4 and evaporated. Fractional distillation of the crude residue gives the title compound as a colorless oil, bp 104-110 ° / 0.4 mm Hg.

D. (1- (4-chlorophenyl) -2,2,8,8-tetramethylnon-4- and -6-yn-1-one.

This compound is obtained in analogy to B. using 4-chlorophenyl isopropyl ketone and 1-bromo-6,6-dimethylhept-2-en-4-yn as starting materials.

E. (E) -1- (4-chlorophenyl) -2,2-dimethyl-hex-4-en-1-one.

This compound is obtained in analogy to 35 DEG C. using (E) -1-bromo-2-butene instead of 8402002 -20-N * V-3-chloro-2-methyl-1-propene.

F. 1 - - - chlorophenyD 2 Z-dimethylbut-S-en-1-one.

This compound is obtained by alkylation of 1 - (4-chlorophenyl) -2-methylbut-3-en-1-one with iodomethane according to the procedure of C.

G. 4-Bromo-1- (4-chlorophenyl) -2,2-dimethylbut-3-en-1-one.

This compound is obtained by adding Br2 to 1- (4-chlorophenyl) -2,2-dimethylbut-3-en-1-one, followed by cleavage of HBr from the Br addition product.

15 Fungicidal effect.

1. Laboratory test.

The interesting fungicidal activity of the compounds of the invention is illustrated by the following test results with compound No. 1.

Fungus Plant EC 90 *

Mildew 25 Erysiphe cucumber 7

Erysiphe wheat 6

Podosphaera apple 15 grains 8incinula

Rust 30 Uromyces honey 2

Puccinia triti wheat 25 * Concentration of the spray liquid in ppm, which allows 90% control of the fungal disease (after sprinkling until dripping).

35 8402002 <* - 21 -

Particularly favorable action is observed in these tests after treatment with compound No. 33.

2 * Field tests 5 2.1. Mildew control in wheat.

Wheat infested with Erysiphe graminis is treated with a spray liquid containing compound No. 1 as active ingredient (a.b.) at a concentration of 300 mg. A.b./l spray liquid. A spraying volume of 500 l / ha is used. The treatment allows significant control of the mildew infestation.

15

Wheat infested with Puccinia stri-iformis (yellow rust) is treated with a spray liquid containing compound No. 1 at a concentration of 100 mg a.b./l spray liquid. A spray volume of 1000 l / ha is used.

The treatment allows a considerable control of the rust pest.

25 8402002

Claims (10)

1. New o-aryl-o--Rj-1H-1,2,4-triazole-1-ethanols, in which there is an olefinic group, which in the 1-position of the tf-carbon atom has at most 1 H-atom and has its double bond at the 2- or 3-position of the CX'-carbon atom and its ethers and esters, in free form or in acid addition salt, alcoholate or metal complex form. 2. A compound according to claim 1, characterized in that it has the formula 1, wherein R 1 is as defined in claim 1 and 10 is Rg and Rg, independently H, C 1-4 alkyl, C 0-5 alkenyl or C 1-6 alkoxy , unsubstituted or halogenated, phenyl or phenoxy, unsubstituted or substituted, NO 2, or halogen and ethers and esters thereof, in free form or in acid addition salt, alcoholate or metal complex form. A compound according to claim 2, characterized in that R 1 is a group of the formula 7, wherein n is 0 or 1, R 1, R 9 and R 9 independently H, C 1 -g alkyl, C 8 -cycloalkyl, C 8 -cycloalkyl- C 1-4 alkyl, substituted or unsubstituted phenyl, or phenyl-C 1-6 alkyl, which is unsubstituted or substituted on its phenyl radical, Ry H, halogen, C 1 -g alkyl, C 8 -cy cycloalkyl, C 8 -cy cyeloalkyl-C 1 -alkyl, unsubstituted or substituted phenyl, or phenyl-C 7 g alkyl, which is unsubstituted or substituted on its phenyl radical, and Rg H, C ^ _g is alkyl, Cg ^ g alkinyl or halogen, where R ^ and Rg may be together (CHg), 8402002 φ - 23 - Rg and Rg are together (®2 ^ 2-4 and R ^ and Rg together may be CCH2-5-5. 1H- * t, 2,4-triazole-1-ethanol according to claim 3, characterized in that 5 n is 0, R2 is 4-C1, Rg is H or 2 -C1 is R, H or CH0, 4 is 3 Rg CHg, R and Rg are H and Rg is H, Cl or Br. Compound according to claim 4, characterized in that it is a) 1-bromo-4- (4-chlorophenyl) -3,3-dimethyl-5-15 (1,2,4-triazol-1-yl) - pent-1-en-4-or, or b) 1-chloro-4- (4-chlorophenyl) -3,3-dimethyl-5- (1,2,4-triazol-1-yl) -pent-1 -en-4-ol, or c) 1-bromo-4- (2,4-dichlorophenyl) -3-methyl-5- (1,2,4-triazol-1-yl) -pent-1-en- 4-o1. 6. A process for the preparation of a compound as defined in any one of claims 1 to 5, characterized in that a compound of formula 2, wherein Μ H, is a metal or a trialkylsilyl group, is reacted with a 2 -aryl-2-R 2 -oxiran compound, wherein R 2 is as defined in claim 1, or a reactive functional derivative thereof, optionally followed by the introduction of a chlorine or bromine substituent on one of the C atoms of the double bond of R. | on the 2- or 3-position and / or by etherification or esterification of the hydroxyl group and the compound 30 thus obtained in free form or in the form of an acid addition salt, an alcoholate or a metal complex. The method of claim 6, substantially described as in the examples. 8. Product, obtained a method according to claim 6 or 7. 8402002 - 24 - V- 9. Agricultural or horticultural preparation with a fungicidal effect, characterized in that it contains a compound according to any one of claims 1 to 5 or 8 in free form or in the form of an agriculturally acceptable acid addition salt, alcoholate or metal complex, optionally in combination with an agriculturally acceptable diluent. 10. Pharmaceutical or veterinary preparation, characterized in that it contains a compound according to any one of claims 1-5 or 8 in free form or in the form of a pharmaceutically or veterinarily acceptable acid addition salt, alcoholate or metal complex, optionally in combination with a pharmaceutically or veterinarily acceptable diluent or carrier. 15 8402002