Process for preparing 1-azolyl-4-hydroxy-butane derivatives and their physiologically tolerated salts with fungicidal and bactericidal effect

Start of patent period: 1980 02 15 Longest possible duration:

t Issued on: 1980 10 10

Inventor:

© dependence:

© Pamphlets considered to delineate the prior art:

Nr.358873

The invention relates to fungicidal and bactericidal agents containing as active ingredient component new 1-azolyl-4-hydroxy-butane derivatives.

It has already been disclosed that trityl-l, 2,4-triazoles, such as triphenyl (l, 2,4-triazol-1-yl) -methane, as well as substituted in the phenyl moiety 3,3-dimethyl-l- (imidazole) 1-yl) -l-phenoxy-butan-2-ones, such as 2,5-dichlorophenoxy-3,3-dimethyl-1- (imidazol-1-yl) -butan-2-one, have a good fungicidal activity ( see DE-OS 1795249 or 2325156). However, their effect is not always quite satisfactory, especially at low application rates and concentrations.

It has been found that the new 1-azolyl-4-hydroxybutane derivatives of the general formula

CH

- CH - C - C - CH₂ - 0 - R (I)

<img file="AT358873B_D0001.tif" />

CH₂X in which R is an acyl radical -CQ-R ', where R' is alkyl having 1 to 18 C atoms, X is hydrogen or the acetoxy group, Y is the CH group or a nitrogen atom, Z is halogen, the nitro group or phenyl, which is optionally halogen-substituted and n are integers from 0 to 2, and their physiologically acceptable salts and optical isomers surprisingly show a significantly higher fungicidal activity, in particular against cereal diseases, than the compounds known from the prior art Triphenyl- (1,2,4-triazol-1-yl) -methane and 2,5-dichlorophenoxy-3,3-dimethyl-1- (imidazol-1-yl) -butan-2-one which are chemically and operatively obvious substances are. Equally surprising is their additional bactericidal action.

The new 1-azolyl-4-hydroxybutane derivatives of the general formula (I) are obtained by reacting 1-bromo-4- (R-oxy) -butan-2-ones of the general formula

CH

Z,

O-CH-CO-C-CHj-OR

br

CH₂X (II) in which R, X, Z and n have the abovementioned meaning, with known azoles of the general formula

N ..

, Y /

NH (III) in which Y has the abovementioned meaning, if appropriate in the presence of a diluent and an acid binder, and optionally the azolyl ketones thereby obtained in a conventional manner selectively with complex borohydrides, optionally in the presence of a diluent reduced.

Furthermore, the l-azolyl-4-hydroxybutane derivatives which can be used according to the invention can be converted into the salts by reaction with acids.

In some cases, it proves to be advantageous, individual compounds, starting from the 4-acetoxy-l-azolyl-l-phenoxy-butan-2-ones, on the corresponding 1-azoly-1, 4-hydroxy-1-phenoxy-butane -2-one "to transcribe". For this purpose, the 4-acetoxy-l-azolyl-l-phenoxy-butan-2-ones are first

- 3 No. 358873 with conc. Hydrochloric acid in the presence of a diluent hydrolytically cleaved. The resulting l-azolyl-4-hydroxy-1-phenoxy-butan-2-ones are then optionally with

Acid chlorides, xyocyanates or sulfonyl chlorides reacted in a generally known manner (see.

also production instructions).

If 4-acetoxy-1-bromo-1- (4-chlorophenoxy) -3,3-dimethylbutan-2-one and 1,2,4-triazole are used as starting materials, the course of the reaction can be represented by the following formula scheme :

<img file="AT358873B_D0002.tif" />

The l-bromo-4- (R-oxy) -butan-2-ones to be used as starting materials are generally defined by the formula (II).

The l-bromo-4- (R-oxy) -butan-2-ones of the general formula (II) to be used as starting materials are not yet known, but can be prepared by known processes, for example by known phenols of the general formula

<img file="AT358873B_D0003.tif" />

OH (IV) in which Z and n have the abovementioned meaning, with a bromoketone of the general formula

CH₃

I

Br - CH_a - CO - C - CHa - O - R, (V)

I

CHjX in which R and X have the abovementioned meaning, implements. The remaining active hydrogen atom is then exchanged in the usual way for bromine (see also the manufactur- ing instructions).

The bromoketones of formula (V) are well known compounds of organic chemistry. They are obtained by known ketones of the general formula

CH ₃

I

CH₃ - CO - C - CHjOH, (VI)

CH₂X

- 4 No. 358873 in which X^a is hydrogen or hydroxy, optionally reacted with acid chlorides, acid anhydrides, isocyanates' or sulfonyl chlorides in a generally known manner. The remaining active hydrogen atom is then exchanged in the usual way for bromine.

Suitable salts for the compounds of the formula (I) are salts with physiologically tolerated acids. These preferably include the hydrohalic acids, such as hydrochloric acid and hydrobromic acid, in particular hydrochloric acid, phosphoric acid, nitric acid, mono- and bifunctional carboxylic acids and Hy droxy car bonsäuren such as acetic acid, maleic acid, succinic acid, fumaric acid, tartaric acid, salicylic acid, citric acid, Sorbic acid, lactic acid or 1,5-naphthalenedisulfonic acid.

Suitable diluents for the reaction are preferably inert organic solvents. This includes preferably ketones, such as diethyl ketone, in particular acetone and methyl ethyl ketone; Nitriles, such as propionitrile, in particular acetonitrile; Alcohols, such as ethanol or isopropanol; Ethers, such as tetrahydrofuran or dioxane; Benzene; formamide; in particular dimethylformamide; and halogenated hydrocarbons, such as methylene chloride, carbon tetrachloride or chloroform.

The reaction is carried out in the presence of an acid binder. It is possible to add all customary inorganic or organic acid binders, such as alkali metal carbonates, for example sodium carbonate, potassium carbonate and sodium bicarbonate, or lower tertiary alkylamines, cycloalkylamines or aralkylamines, for example triethylamine, N, N-dimethylcyclohexylamine, dicyclohexylmethylamine, N, N-dimethylbenzylamine, furthermore pyridine and diazabicyclooctane.

In addition, one can use a corresponding excess of azole.

The reaction temperatures can be varied within a substantial range. In general, one works between about 20 to about 150 ° C, preferably at 60 to 120 ° C. In the presence of a solvent, it is expedient to work at the boiling point of the particular solvent.

When carrying out the process, it is expedient to use 1 to 2 mol of azole and 1 to 2 mol of acid binder per mole of the compounds of the formula (II). To isolate the compounds of formula (I), the solvent is distilled off, the residue taken up with an organic solvent and washed with water. The organic phase is dried over sodium sulfate and freed from the solvent in vacuo. The residue is purified by distillation or recrystallization.

For the selective reduction, suitable diluents for the reaction are preferably polar organic solvents. These include, preferably, alcohols, such as methanol, ethanol, butanol, isopropanol, and ethers, such as diethyl ether or tetrahydrofuran. The reaction is generally carried out at 0 to 30 ° C, preferably at 0 to 20 ° C performed. For this purpose, for 1 mole of the compound of formula (II) about 1 mole of a borohydride, such as sodium borohydride or lithium borohydride, a. To isolate the compounds of the formula (I), the residue is taken up, for example, in dilute hydrochloric acid, then made alkaline and extracted with an organic solvent, or mixed with water and shaken out with an organic solvent. The further work-up is carried out in the usual way.

The active compounds which can be used according to the invention have a strong fungitoxic and a bacteriotoxic action. They do not damage crops in concentrations necessary to combat fungi and bacteria. For these reasons, they are suitable for use as active ingredients in pesticides for controlling fungi and bacteria. Fungitoxic agents in crop protection are used to combat Plasmodiophoromycetes, Oomycetes, Chytridiomycetes, Zygomycetes, Ascomycetes, Basidiomycetes, Deuteromycetes.

The compositions of the invention have a broad spectrum of activity and can be used against parasitic fungi and bacteria that infest parts of plants above ground or attack the plants from the ground, and against seed-borne pathogens.

They have a particularly good activity against parasitic fungi on aboveground plant parts, such as Erysiphe species, Podosphaera species and Venturia species, and against Pyricularia and Pellicularia species. Good effects are achieved against the causative agent of apple scab (Fusi- 5 Nr.358873 cladium dendriticum). They also show high activity against cereal diseases, such as against

Cornmeal and barley powdery mildew. It should be emphasized that the agents of the invention not only have a protective effect, but are also systemically effective. So it is possible to protect plants against fungal infestation, if the active ingredient on the soil and the root or on the seed feeds the aerial parts of the plant.

As plant protection agents, the compositions according to the invention can be used for soil treatment, for seed treatment and for the treatment of above-ground parts of plants.

The active compounds which can be used according to the invention are converted into the customary formulations, such as solutions, emulsions, suspensions, powders, pastes and granules. These are prepared in a known manner, for example by mixing the active compounds with extenders, ie liquid solvents, liquefied gases under pressure and / or solid carriers, optionally with the use of surface-active agents, ie emulsifiers and / or dispersants and / or foam-forming agents. In the case of using water as extender, for example, organic solvents can also be used as auxiliary solvents. Suitable liquid solvents are essentially: aromatics, such as xylene, toluene, benzene or alkylnaphthalenes, chlorinated aromatics or chlorinated aliphatic hydrocarbons, such as chlorobenzenes, Chloroethylenes or methylene chloride, aliphatic hydrocarbons, such as cyclohexane or paraffins, for example petroleum fractions, alcohols, such as butanol or glycol, and their ethers and esters, ketones, such as acetone, methyl ethyl ketone, methyl isobutyl ketone or cyclohexanone, strongly polar solvents, such as dimethylformamide and dimethyl sulfoxide, and water; by liquefied gaseous diluents or carriers are meant liquids which are gaseous at normal temperature and under normal pressure, for example aerosol propellants, such as dichlorodifluoromethane or trichlorofluoromethane; solid carriers: ground natural minerals, such as kaolins, clays, talc, chalk, quartz, attapulgite, montmorillonite or diatomaceous earth, and ground synthetic minerals, such as highly-dispersed silicic acid, alumina and silicates; as emulsifier; nonionic and anionic emulsifiers, such as polyoxyethylene fatty acid esters, polyoxyethylene fatty alcohol ethers, for example alkylarylpolyglycol ethers, alkylsulfonates, alkylsulfates, arylsulfonates and protein hydrolysates; as a dispersant: eg lignin, liquors and methylcellulose.

The active ingredients may be present in the formulations in admixture with other known active ingredients, such as fungicides, insecticides, acaricides, nematicides, herbicides, bird repellents, growth factors, plant nutrients and soil conditioners.

The formulations generally contain between 0.1 and 95% by weight of active compound, preferably between 0.5 and 90% by weight.

The active ingredients are used in the form of their formulations or the use forms prepared therefrom by further dilution, such as ready-to-use solutions, emulsions, suspensions, powders, pastes and granules. The application is done in a conventional manner, for example by pouring, spraying, spraying, dusting, spreading, dry pickling, wet pickling, wet pickling, slurry pickling or encrusting.

When used as foliar fungicides, the drug concentrations in the formulations can be varied over a wider range. They are generally between 0.1 and 0.00001 wt .-%, preferably between 0.05 and 0.0001%.

In the seed treatment, in general, amounts of active ingredient of 0.001 to 50 g / kg of seed, preferably 0.01 to 10 g are needed.

For soil treatment are amounts of active ingredient from 1 to 1000 g / cm^a Soil, in particular 10 to 200 g, required.

The versatile uses are shown in the examples below.

Example 1: Sprout Treatment Test / Powdery Mildew / Protective (Leaf destroying Mycosis)

To prepare a suitable preparation of active compound, 0.25 part by weight of active compound in 25 parts by weight of dimethylformamide and 0.06 part by weight of alkylaryl polyglycol ether are added and 975 parts by weight of water are added. The concentrate is diluted with water to the desired final concentration of the spray mixture.

To test for protective effectiveness spray the einblättrigen barley young plants

Nr.358873

- 6 of the variety blackbird dews with the preparation of active compound. After drying, the barley plants are dusted with spores of Erysiphe graminis var.hordei.

After 6 days Venveilzeit the plants at a temperature of 21 to 22 ° C and a humidity of 80 to 90% evaluates the stocking of plants with mildew pustules. The degree of precipitation is expressed as a percentage of the infestation of the untreated control plants. 0% means no infestation and 100% the same degree of infestation as in the untreated control.

The lower the powdery mildew case, the more effective the active ingredient.

Active ingredients, active ingredient concentrations in the spray mixture and infestation levels are shown in Table I below.

Table I

Shoot treatment test / powdery mildew / protective

<td>drugs</td><td>Infestation in% of untreated Control one Drug concentration in the Spray mixture of 0.025% by weight</td>

<td>untreated N</td><td>100.0</td>

<td>V "</td><td></td>

<td>&lt;Ο&gt; - * - &lt;ο&gt; O (known) CH s,</td><td>100.0</td>

<td>CI- / O- / -O-CH-CO-C-CH_8th-O-CO-CH₃\ - / I 1 jg CHa N</td><td></td>

<td>so₃H</td><td>0.0</td>

<td>CD x 1/2 | Q SO₃H</td><td></td>

- 7 No. 358873

Table I (continued)

<td colspan="2">drugs</td><td>Infestation in% of untreated Control at one Drug concentration in the spray mixture of 0.025% by weight</td>

<td>0₂N _</td><td>CHa _ / O) -O-CH-CO-C-CHj-O-CO-CHa \ 2 ± / 1 | 'CH. / ^ N II ll</td><td>50.0</td>

<td>(5)</td><td>ll N</td><td></td>

<td>&lt;Ö</td><td>CHa \ O-CH-CO-CHa-C-O-CO-CHa ./ v = i / ι ι N CHa ιί ^ II</td><td>50.0</td>

<td>(6)</td><td>N-</td><td></td>

<td>CI_</td><td>/ O '- / \ O-CH-CO-C-CHj-O-CO-CHa \ Si / \ S ± / ι ι N CHa / \ n</td><td>32.5</td>

<td>(7)</td><td>N--</td><td></td>

<td>CI (8)</td><td>CI / CH₃'C' \ O-CH-CO-C-CHa-O-CO-CHa \ _ / | | 1 CHa / \ N ll_J N-</td><td>0.0</td>

<td></td><td>CHa I</td><td></td>

<td>&lt;0</td><td>\ ¹\ - O-CH-CO-C-CHa-O-CO-CHa / 1 1 , N CHa \ n II</td><td>0.0</td>

<td>(10)</td><td>II II N</td><td></td>

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Table I (continued)

<td colspan="3">drugs</td><td>Infestation in% of untreated Control at one Drug concentration in the Spray mixture of 0.025% by weight</td>

<td></td><td></td><td>CHa-O-CO-CHa I</td><td></td>

<td rowspan="2">CI (11)</td><td>&lt;Q&gt; -</td><td>1 - o-ch-co-c-ch₃1 ch₃-o-co-ch₃ΓΊι</td><td>16.3</td>

<td></td><td>N</td><td></td>

<td></td><td></td><td>ch₃</td><td></td>

<td>0_aN -</td><td>&lt;E&gt;</td><td>1 - O-CH-CO-C-CHi-O-CO-CHa | 1</td><td>0.0</td>

<td></td><td></td><td>_ZN CHa ii Ύ</td><td></td>

<td>(12)</td><td></td><td>N ..........</td><td></td>

<td></td><td></td><td>CI</td><td></td>

<td>CI_</td><td>&lt;Ö&gt;</td><td>ch₃1 - O-CH-CO-C-CHa-O-CO-CHa | |</td><td>50.0</td>

<td></td><td></td><td>N CH₃II 1</td><td></td>

<td>(13)</td><td></td><td>N</td><td></td>

<td></td><td></td><td>CHa I</td><td></td>

<td>CI</td><td>-\O/-</td><td>1 - O-CH-CO-C-CHa-O-CO-CHa</td><td></td>

<td></td><td>\ Y_ /</td><td>ι ι ch₃ι Ί</td><td>13.8</td>

<td>(14)</td><td></td><td>'N</td><td></td>

<td></td><td></td><td>CHa</td><td></td>

<td></td><td colspan="2">\ -O-CH-CO-C-CH_a-O-CO-CH_8th</td><td></td>

<td></td><td>_ / |</td><td>1</td><td>0.0</td>

<td></td><td>N</td><td>CHa</td><td></td>

<td></td><td colspan="2">1 1</td><td></td>

<td>(15)</td><td></td><td>N</td><td></td>

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Example 2: Barley powdery mildew test (Erysiphe graminis var. Hordei) / systemic (fungal cereal disease)

The application of the active ingredients is carried out as a powdered seed treatment agent. They are prepared by stripping the respective active ingredient with a mixture of the same Gewichts5 share talc and diatomaceous earth to a finely powdered mixture with the desired drug concentration.

For seed treatment shake barley seeds with the ironed. Active ingredient in a sealed glass bottle. The seed is sown with 3 χ 12 seeds in flower pots 2 cm deep in a mixture of one part by volume of Fruhstorfer unit earth and one part by volume of quartz sand. The germination and the casserole are carried out under favorable conditions in the greenhouse. 7 days after sowing, when the barley plants have unfolded their first leaf, they are pollinated with fresh spores of Erysiphe graminis var. Hordei and at 21 to 22 ° C and 80 to 90% rel. Humidity and Lststündiger exposure further cultivated. Within 6 days the typical mildew pustules develop on the leaves.

The degree of infestation is expressed as a percentage of the infestation of the untreated control plants. Thus, 0% means no infestation and 100% the same degree of infestation as in the untreated control. The active ingredient is the more effective the lower the mildew case is.

Active ingredients, active substance concentrations in the seed treatment agent as well as its application rate and the percentage of powdery mildew fall from the following Table II.

Table II

Barley powdery mildew test (Erysiphe graminis var. Hordei) / systemic

<td>&gt; Active substances</td><td>active compound concentration in the mordant in parts by weight</td><td>Pickling agent quantity in g / kg seed</td><td>Infestation in% of untreated control</td>

<td>unstained^N- II 1 \ / N N</td><td></td><td></td><td>100.0</td>

<td>&lt;5) -ς &lt;ο) (known) 1 / J Cl /</td><td>25</td><td>10</td><td>88, B</td>

<td>-O-CH-CO-C (CHj) 1 ^N^C1 INI (known)</td><td>25</td><td>10</td><td>100.0</td>

Nr.358873

Table II (continued)

<img file="AT358873B_D0004.tif" />

- 11 No. 358873

Table II (continued)

<td colspan="2">drugs</td><td>Concentration of active ingredient in the preparation in Gen.-S!</td><td>Pickling agent in uandmenge in g / kg seed</td><td>Infestation in% of untreated control</td>

<td></td><td>CH.</td><td></td><td></td><td></td>

<td>(Ο) ·</td><td>1 O-CH-CO-C-CH, -O-CO-CH,</td><td></td><td></td><td></td>

<td>\ _ /</td><td>z \ II II</td><td>25</td><td>10</td><td>27.5</td>

<td>(12)</td><td>II II N</td><td></td><td></td><td></td>

<td>z</td><td>z^clCH. |</td><td></td><td></td><td></td>

<td>^ci-(O)-</td><td>1 -0-CH-C0-C-CH_t-0-CO-CH_S</td><td></td><td></td><td></td>

<td>\ _ /</td><td>z \ ^CHIII II</td><td>25</td><td>10</td><td>3.8</td>

<td>(13)</td><td>II II N</td><td></td><td></td><td></td>

<td></td><td>CH, I</td><td></td><td></td><td></td>

<td>^a-(O)-</td><td>1 O-CH-CO-C-CH, -O-CO-CH, | 1</td><td>25</td><td>10</td><td>0.0</td>

<td></td><td>N CH, z \ II II</td><td></td><td></td><td></td>

<td>(14)</td><td>II II -N</td><td></td><td></td><td></td>

<td></td><td>CH,</td><td></td><td></td><td></td>

<td colspan="2">/ -O-CH-CO-C-CH, -O-CO-CH, \ - / 1 1 N CHj z \</td><td>25</td><td>10</td><td>55.0</td>

<td>II (15)</td><td>'N</td><td></td><td></td><td></td>

Example 3: Bacterial test / Xanthomonas oryzae

Solvent dispersant: water other additives:

11.75 parts by weight of acetone 0.75 parts by weight of alkylaryl polyglycol ether

987.50 parts by weight parts by weight

The amount of active ingredient required for the desired active substance concentration in the spraying liquid is mixed with the specified amount of solvent and dispersing agent and the concentrate is diluted with the stated amount of water.

With the spray liquid splashed about 30 days old rice plants to dripping wet.

The plants remain until dry in a greenhouse at temperatures of 22 to 24 ° C and a relative humidity of about 70%. Thereafter, needles are dipped in an aqueous bacterial suspension of Xanthomonas oryzae and the plants are inoculated by piercing the leaves. The plants are after inoculation 24 h at 100% relative humidity and

No.358873 then in a room at 26 to 28 ° C and 80% relative humidity. 10 days after the inoculation, the infestation in all injured by sting, inoculated leaves of previously treated with preparation plants in value numbers from 1 to 9 is evaluated. 1 means 100% action, = good effect, 5 = moderate effect and 9 = no effect.

Active ingredients, drug concentrations and results are shown in Table III below:

Table III

<img file="AT358873B_D0005.tif" />

- 13 No. 358873

Requirements for the preparation of active substance compounds Regulation 1:

CH₃

CI_ / () '_o-ch-co-c-ch₂-o-co-ch

II

N CH₃ / \ n

Ν '

SO₃H /

so₃H

To a suspension of 21 g (0.3 mol) of triazole and 30 g (0.2 mol) of potassium carbonate in 200 ml of 5 acetone is added dropwise at boiling a solution of 36.3 g (0.2 mol) of crude 4-acetoxy -l-bromo-1- (4-chlorophenoxy) -3,3-dimethyl-butan-2-one in 50 ml of acetone. After one hour of heating under reflux, it is filtered and the filtrate is concentrated by distilling off the solvent in vacuo. The residue is taken up in 200 ml of methylene chloride, washed three times with 50 ml of water, dried over sodium sulfate and concentrated. The remaining residue is dissolved in 100 ml of acetone 10 and treated with 36 g (0.1 mol) of 1,5-naphthalenedisulfonic acid actahydrate in 100 ml of acetone. The resulting crystalline precipitate is filtered off with suction and dried. 45 g (45% of theory) of 4-acetoxy-1- (4-chlorophenoxy) -3,3-dimethyl-1- (1,2) are obtained.

Preparation of the starting product

CH ₃

CI.

al ·⁷/ -O-ch-co-c-ch₂-o-co-ch₃

Br CH₃

170 g (0.72 mol) of 4-acetoxy-1-bromo-3,3-dimethyl-butan-2-one in 200 ml of acetone are added over 100 minutes to a suspension of 92.1 g (0.72 mol) of 4 -Chlorophenol and 108 g (0.72 mol) of potassium carbonate in 1000 ml of acetone. After lSstündigem heating with stirring and reflux is filtered off and the filtrate was concentrated by distilling off the solvent in vacuo. The Rück20 stand is taken up in 200 ml of methylene chloride, washed three times with 50 ml of water, dried over sodium sulfate and concentrated. The oily residue is distilled. This gives 153 g (72% of theory) of 4-acetoxy-l- (4-chlorophenoxy) -3,3-dimethyl-butan-2-one of melting point 140 to

145 ° C / 0.26 mbar.

56.9 g (0.2 mol) of 4-acetoxy-1- (4-chlorophenoxy) -3,3-dimethyl-butan-2-one are dissolved in 350 ml of tetra-25-chlorocarbon. At room temperature, 10.3 g (0.2 mol) of bromine are added dropwise so that steady consumption occurs. Then allowed to stir for 30 min at room temperature. After distilling off the solvent in vacuo 4-acetoxy-l-bromo-l- (4-chlorophenoxy) -3,3-dimethyl-butan-2-one is obtained quantitatively, which can be further reacted directly.

- 14 No. 358873

Regulation 2:

CH₃

<img file="AT358873B_D0006.tif" />

-N g (0.05 mol) of 4-acetoxy-1-bromo-1- [4- (4'-chlorophenyl) -phenoxy] -3,3-dimethyl-butan-2-one are dissolved in 20 ml of acetone and in the boiling heat to 5.5 g (0.08 mol) of imidazole and 7.5 g of 5 (0.05 mol) of potassium carbonate in 80 ml of acetone was added dropwise. After lSstündigem heating under reflux is filtered and the filtrate is concentrated by distilling off the solvent in vacuo. The remaining oil is washed with 50 ml of water and extracted or recrystallized in ether. This gives 9 g (42.2% of theory) of 4-acetoxy-1- [4- (4'-chlorophenyl) -phenoxy] -3,3-dimethyl-1- (imidazol-1-yl) -butane-2 -one of melting point 110 to 112 ° C.

Regulation 3

<img file="AT358873B_D0007.tif" />

To 42.8 g (0.1 mol) of 4-acetoxy-1- [4- (4¹-Chlorophenyl) -phenoxy] -3,3-dimethyl-1- (imidazol-1-yl) -butan-2-one (Example 2) in 200 ml of methanol is added 12 ml of concentrated hydrochloric acid and heated at reflux for 8 hours. The solvent is then distilled off in vacuo and the residue is mixed with 50 ml of saturated sodium bicarbonate solution and 50 ml of pentane. After 2 h, the crystalline product is filtered off with suction. 38.9 g (100% of theory) of 1- [4- (4'-chlorophenyl) -phenoxy] -3,3-dimethyl-4-hydroxy-1- (imidazol-1-yl) -butane-2 are obtained -on of melting point 133 to

135 ° C.

Regulation 4

<img file="AT358873B_D0008.tif" />

CH₃

I

- C - CH₂ - 0 - CO - C (CH₃)₃

I ch₃

7.72 g (0.02 mol) of 1- [4- (4'-chlorophenyl) -phenoxy] -3,3-dimethyl-4-hydroxy-1- (imidazol-1-yl) -butan-2-one (Example 3) are dissolved in 50 ml of methylene chloride, treated with 5 ml of pivaloyl chloride and heated for 5 h under reflux. The solvent is then distilled off in vacuo, the residue taken up in methylene chloride, washed twice with 50 ml of saturated sodium bicarbonate solution and concentrated. The residue is taken up in 50 ml of pentane, whereby it crystallizes. This gives 5.3 g (60% of theory) of 1- [4- (4'-chlorophenyl) -phenoxy] -3,3-dimethyl-1- (imidazol-1-yl) -4-pivaloyloxy-butane-2 -on of melting point 98 to 103 ° C.

Analogous to the above hinanhten rules, the following examples of the general formula

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CH₃

<img file="AT358873B_D0009.tif" />

<img file="AT358873B_D0010.tif" />

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<img file="AT358873B_D0011.tif" />