4-phenoxy-4-imidazolo(1,2,4-triazolo)butanol esters,their preparation and fungicidal and bactericidal compositions containing them

The present invention relates to certain new 1azolyl-^-hydroxy-outune derivatives, to a process for their preparation ano to their use as fungicides and bactericides.

It has already beer, disclose(: that certain trityl-].0 2,4-triazoles, such as tripher.yl-(l,2,4-triazol-l-yl )zetixine, and certain 5t3-0imethyl-l-(in1idazol-l-yl)-jphenoxy-butan-2-ones substituted in the phenyl part, such as 2,5-c ichloropher.oxy-3,3-d inethyl-1-( iinidazol-l-yj )-buran -2-one, possess a good fungiciaal activity (see G-ersan Offenlegungsschrift (German published specification) 1,795,249 and 2,325,156. However, their action is not always entirely satisfactory, especially if low amounts and low concentrations are used.

The compounds of formula I below fall within the scope of the general formula disclosed in German Patent Specification No. 2,325,156. However, none of the new compounds according to the invention are specifically disclosed or named in the German specification and tests have shown (see comparison compound B herein) that the new compounds according to the invention show markedly better activity than a compound known from said German patent specification.

Trie present invention now provides, as new compound the l-azolyl-4-hydroxy-butane derivatives of the general for.:: uia

<img file="IL52662A_D0001.tif" />

in which

R represents hydrogen or an acyl radical -CO-R¹ in which r1 represents alkyl optionally substituted by halogen or phenyl; or represents cycloalkyl;

a ־־ r

A represents a keto group or a CH(OB) grouping,

X represents hydrogen or an -OR grouping, wherein

R has the abovementioned meaning, 1

X represents alkyl,

Y represents the CH group or a nitrogen atom,

Z represents halogen, nitro or halophenylj and n represents 0, 1 or 2, and their salts.

The compound of this invention exhibit powerful fungicidal and bactericidal properties.

Preferably, R represents hydrogen or an acyl radical -CO-r\ in which • . I ' ' ' . ί . ' . 1

R represents straight-chain or branched alkyl with 1 to 18 carbon atoms (which is optionally substituted by halogen or phenyl) or represents cycloalkyl with to 7 carbon atoms; and — 3 — represents alkyl with 1 or 2 carbon atoms;

z represents halogen, nitro or halophenyl;

n represents 0, 1 or 2;

and X represents hydrogen or an OR grouping in which R has the meaning given in the foregoing.

Those compounds of the formula (I) in which A represents the CH(OH) group, possess two asymmetrical carbon atoms and can therefore exist as the two geometrical isomers (erythro-form and threo-form), which may be formed in varying ratios.

In both cases, they exist as optical e

isomers. All isomers are intended to be covered by the formula (I).

The invention also provides a process for the preparation of a l-azolyl-4-hydroxy-butane derivative of the formula (1). in which a l-bromo-4-(R-oxy)butan-2-_One of the general formula

DI

-o - CH - CO - C - CH₂ - R (Π) ^Zn ^Br CHgX in which

X» X , Z and n have the abovementioned meanings, is reacted with an azole of the general formula

J® (III), in which

Y has the abovementioned meaning, in the.presence of a diluent and of an acid-binding agent and, if appropriate, the azolyl-ketone thereby obtained is’ selectively reduced, in a manner which is in itself known, by means of a complex borohydride, if appropriate in the presence of a diluent.

Furthermore, the l-azolyl-4-hydroxy-butane derivatives obtainable according to the invention can be converted to the salts by reaction with acids.

Conversely, the acid addition salts can be converted into the free bases by treatment with suitable bases.

In some cases it has proved advantageous to trans

Le A 17 324

'־'6 esterify individual compounds, starting from the 4-acetoxy -i-azolyl-l-phenoxy-butan-2-ones obtainable according to the invention, via the corresponding l-azolyl-4-hydr.oxy-lphenoxy-butan-2-ones. For this purpose, the 4-acetoxyl-azolyl-l-phenoxy-butan-2-ones are first subjected to hydrolytic scission with concentrated hydrochloric acid in the presence of a diluent. The l-azolyl-4-hydroxy-lphenoxybutan-2-ones thereby produced are then subsequently reacted, if appropriate, with acid chlorides, isocyanates or sulphonyl chlorides in a generally known manner (see also the preparative Examples given later in this text).

Surprising, the active compounds according to the invention exhibit a substantially greater fungicidal activity, especially against cereal diseases, than the compounds triphenyl-(1,2,4-triazol-l-yl)-methane and 2,5-dichloroPhenoxy-J,3-dimethyl-l-(imidazol-l-yl)-butan-2-one known from the state of the art, which, chemically and in respect of their action, are closely related compounds. Their additional bactericidal action is equally surprising. The active compounds according to the invention thus represent an enrichment of the art.

If 4-acetoxy-l-bromo-l-(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 equation:

Le A 17 324

CHj Cl/T\0-CH-C0-C-CH. -O-CO-CH, + 1 11

Br CHj

<img file="IL52662A_D0002.tif" />

Base

- HBr

<img file="IL52662A_D0003.tif" />

<img file="IL52662A_D0004.tif" />

CHj 0-CH-C0-C-CH2 A CH₃N. Η

-O-CO-CHj

If 4-acetoxy-l-(4-chlorophenoxy)-3,3-dimethyl-l-(I, 2,4-triazol-l-yl)butan-2-one and sodium borohydride are used as starting materials, the course of the reaction can be represented by the following equation:

<img file="IL52662A_D0005.tif" />

NaBH₄

<img file="IL52662A_D0006.tif" />

OH CH, I I

Cl- -O-CH-CH-C-CH,-O-CO-CH,

II ⁵ ch,

The 1-bromo-4-(R-oxy)-butan-2-ones of' the formula (II) to be used as staring materials have not previously been described in the literature, but can be prepared in accordance with known processes by, for example, reacting known phenols of the general formula

<img file="IL52662A_D0007.tif" />

(IV), in which

Z and n have the above-mentioned meanings, with a bromoketone of the general formula

X¹

I

Br -CH₂ -CO - C - CH_? - K (V),

I .

CH₂X

Le A 17 324 in which

R, X and X¹ have the abovementioned meanings.

The active hydrogen atom which still remains is subsequently replaced by bromine in the usual manner (see also the preparative Examples).

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

X¹

I

CH₃ - CO ־ C - CH₂OH (VI), ' ‘ 2

CH₂X in which

X^ has the abovementioned meaning and 2

X represents hydrogen or hydroxyl, if appropriate, with acid chlorides, acid anhydrides, isocyanates or sulphonyl chlorides, in a generally known manner. The active hydrogen atom which still remains is then replaced by bromine in the usual manner.

The azoles of the formula (III) are well known compounds in organic chemistry.

From the point of view of phyto-toxicity, the preferred salts of the compounds of the formula (I) are physiologically tolerated salts, these being in general salts with physiologically tolerated acids. The preferred acids include the hydrogen halide acids (for example hydrobromic acid and especially hydrochloric acid), phosphoric acid, nitric acid, monofunctional or difunctional carboxylic acids and hydroxycarboxylic acids (for example acetic acid, maleic acid, succinic acid, fumaric acid, .־־// le A 17 324 q tartaric acid, salicylic acid, citric acid,sorbic acid and lactic acid) and 1,5-naphthalene-disulphonic acid.

Preferred diluents for the reaction according to the invention are inert organic solvents׳, especially ketones, 5 such as diethyl ketone, and especially acetone and methyl ethyl ketone; nitriles, such as propionitrile and especially acetonitrile; alcohols, such as ethanol or isopropanol; ethers, such as tetrahydrofuran or dioxan; benzene; formamides, such as, in particular, dimethyl10 formamide; and halogenated hydrocarbons, such as methylene chloride, carbon tetrachloride or chlorform.

The reaction is carried out in the presence of an acid-binding agent. All inorganic or organic acid-binding agents which can usually be employed may be added, such as 15 alkali metal carbonates, for example sodium carbonate, potassium carbonate and sodium bicarbonate, or such as lower tertiary alkylamines, cycloalkylamines or aralkylamines, for example triethylamine, N,N-dimethylcyclohexylamine, dicyclohexylmethylamine, N,N-dimethylbenzylamine and also pyridine and diazabicyclo-octane. However, an appropriate excess of the azole (III) can also be used.

The reaction temperatures can be varied within a substantial range. In general, the reaction is carried out at from 20° to 150°C, preferably at from 60° to 120°0. 25 If a solvent is present, the reaction is advantageously carried out at the boiling point of the particular solvent.

In carrying out the process according to. the invention, preferably 1 to 2 moles of the azole and 1 to 2 moles of acid-binding agent are employed per mole of the 30 compounds of the formula (II). To isolate the compounds of the formula (I), the solvent is distilled off, the

־?/־

Le A 17 324 1° residue is taken up in an organic solvent and the solution is washed with water. The organic phase is dried over sodium'^,-.sulphate and freed from the solvent in vacuo. The residue is purified by distillation or recrystallisation.

I

For the selective reduction, polar organic solvents can be used- as diluents for the reaction according to the invention, especially alcohols, such as methanol, ethanol, butanol and isopropanol, and ethers, such as diethyl ether or tetrahydrofuran. The reaction is in general carried out at from 0° to 30°C, preferably at 0° to 20°C. For this reaction, about 1 mol of a borohydride, such as sodium borohydride or lithium borohydride, is employed per mol of the compound of the formula (11). To isolate the compounds of the formula (I), the residue is taken up in, 15 for example, dilute hydrochloric acid and the solution is then rendered alkaline and extracted with an organic solvent, or the residue is only mixed with water and the mixture is extracted by shaking.with an organic solvent.' The further working up is carried out in the usual manner.

״ 2 / 52662/2

The active compounds according to the invention exhibit a powerful fungitoxic action and a bacteriotoxic action. They do not damage crop plants in the concentrations required for combating fungi and bacteria. For these reasons they are suitable for use as .plant protection agents for combating fungi and bacteria. Fungitoxic agents are employed in plant protection for combating Plasmodiophoromycetes, Oomycetes,' Chytridiomycetes, Zygomycetes, Ascomycetes, Basidiomycetes and Deuteromycetes.

The active compounds according to the invention have a broad spectrum of action and can be used against parasitic fungi and bacteria which attack above-ground parts of plants or attack the plants through the soil, and also against seed-borrie pathogens.

They display a particularly good activity against parasitic fungi on above-ground parts of plants, such as 15 species of Brysiphe,־ species of Podosphaera and species of Venturia and also against species of Pyricularia and species of Pellicularia. Good actions are achieved against the pathogen of apple scab (Fusicladium dendriticum) Furthermore, the compounds exhibit a high activity against 20 cereal diseases, such as powdery mildew of cereals and powdery midlew of barley. An aspect to be singled out is that the active compounds according to the invention not only display a protective action but are also systemically active. Thus it proves possible to protect plants against fungal attack by supplying the active compound to the above-ground parts of the plant through the soil and the root or through the seed.

As plant protection agents, the compounds according to the invention can be used for the treatment of soil, for 50 the treatment of seed and for the treatment of above-ground pkwhe

The active compounds according to the invention can be converted into the usual formulations, such as solutions, emulsions, suspensions, powders, pastes and granules. These may be produced in known manner, for ex-ample by mixing the active compouds with extenders, ־!;hat is to say, liquid or solid or liquefied gaseous diluents or carriers, optionally with the use of surface-active agents, that is to say, emulsifying agents and/or dispersing Agents and/or foaming agents. In the case of the use of water as an extender, organic solvents can, for example, also be used as auxiliary solvents.

As liquid diluents or carriers, especially solvents, there are suitable in the main, aromatic hydrocarbons, such as xylene, toluene, benzene or alkyl-naphthalenes, chlorinated aromatic' or chlorinated aliphatic hydrocarbons, such as chlorobenzenes, chloroethylenes or methylene chloride, aliphatic or alicyclic hydrocarbons, such as cyclohexane or paraffins, for example mineral!oil fractions, alcohols, such as butanol or glycol as well as their ethers and esters, ketones, such as acetone, methyl ethyl ketone, methyl isobutyl ketone or cyclohexanone, or strongly polar solvents, such as dimethylformamide and dimethylsulphoxide, as well as water. '

By liquefied gaseous diluents or carriers are meant liquids which would be gaseous at normal temperature and under normal pressure, for example aerosol propellants, such as dichlorodifluoromethane or trichlorofluoromethane.

As solid carriers there are preferably used ground natural minerals, such as kaolins, clays, talc, chalk, quartz, attapulgite, montmorillonite or diatomaceous earth, and ground synthetic minerals, such as highly

-?/־ le A 1 7 324 !3 *

dispersed silicic acid, alumina and silicates.

Preferred examples of emulsifying and foam-forming agents include nonionic and anionic emulsifiers, such as polyoxyethylene-fatty acid esters, polyoxyethylene-fatty

I alcohol ethers, for example alkylaryl polyglycol ethers, alkyl sulphonates,alkyl sulphonates, alkyl sulphates and aryl sulphonates as well as albumin hydrolysis products;

' I and preferred examples of dispersing agents including lignin sulphite waste liquors and methylcellulose.

¹⁰ The active compounds according to the invention can be present in the formulations as a mixture with other active compounds such as fungicides, insecticides, acaricides, nematicides, herbicides, bird repellants, growth factors, plant nutrients and agents for improving soil structure.

The formulations in general contain from 0.1 to 95 per cent by weight of active compound, preferably from 0.5 to 90 per cent.

The active compounds can be used as such, as their formulations or as the use forms prepared therefrom by further dilution, such as ready-to-use solutions, emulsions, suspensions, powders, pastes and granules. They may be used in the customary manner, for example by watering, spraying, atomising, dusting, scattering, dry dressing, moist dressing, wet dressing, slurry dressing or encrusting. Especially when used as leaf fungicides, the active compound concentrations in the use forms can be varied within a substantial range. They are, in general, from

0.1 to 0.00001 per cent by weight, preferably from 0.05 to

0.0001 per cent.

In the treatment of seed, amounts of active compound ־ H ־ y/

Le A 17 524 of 0.001 to 50 g per kilogram of seed, preferably 0.01 to 10 g, are generally employed.

For the treatment of soil, amounts of active compound of 1 to 1,000 g per cubic metre of soil, preferably 10 to

200 g, are generally employed.

The present invention also provides a fungicidal or bactericidal composition containing as active ingredient a compound of the present invention in admixture with a solid or liquefied gaseous diluent or carrier or in admixture with a liquid diluent or carrier containing a surface-active agent.

The present invention also provides a method of combating fungi or bacteria which comprises applying to the fungi or bacteria, or to a habitat thereof, a compound of

15. the present invention alone or in the form of a composition containing as active ingredient a compound of the present invention in admixture with a diluent or carrier.

The present invention further provides crops protected from damage by fungi or bacteria by being grown in areas 20 in which immediately prior to and/or during the time of the growing a compound of ths present invention was applied alone or in admixture with a diluent or carrier.

It will be seen that the usual methods of providing a harvested crop may be improved by the present invention.

²5 The fungicidal and bactericidal activity of the compounds of this invention is illustrated by the following biotest Examples.

In these Examples, the active compounds according to the present invention are each identified by' the number of the corresponding preparative Example given later in this text.

- Z/ le A 17 ?24 /f

The known comparison compounds are identified as follows:

N ,Cl ^0-CH-C0-C(CH₃ ),

Example A:

Shoot treatment test/powdery mildew of cereals/protective (leaf-destructive mycosis)

To produce a suitable preparation of active compound, 0.25 g part by weight of active compound was taken up in

25 parts by weight of dimethylformamide and 0.06 part by weight of alkylaryl polyglycol ether; then 975 parts by weight of water were added. The concentrate was diluted with water to the desired final concentration of the spray liquor.

To test for protective activity, single—leaved young barley plants of the Amsel variety were sprayed with the preparation of active compound until dew-moist. After drying, the young barley plants were dusted with spores of Erysiphe graminis var. hordei.

- it (6

Le A 17 324

After 6 days’ dwell time of the plants at a temperature of 21-22°C and 80-90¢ atmospheric^ humidity the occurrence of mildew pustules of the plants was evaluated. The degree of infection was expressed as a percentage of the infection of the untreated control plants. 0¢ denoted no infection and 100¢ denoted the same degree‘of infection as in the case of the untreated control. The active compound was the more active, the lower was the degree of mildew infection.

The active compounds, active compound concentrations in the spray liquor and the degrees of infection can be seen from the table which follows:

Table A

Shoot treatment test/powdery mildew of cereals/protective

Active compound Infection concentration in in % of the

Active compounds the spray liquor untreated in %.by weight control

<td> untreated</td><td> -</td><td> 100.0</td>

<td> (A)</td><td> 0.025</td><td> 100.0</td>

<td> (1)</td><td> 0.025</td><td> 0.0 1</td>

<td> (5)</td><td> 0.025</td><td> 50.0</td>

<td> (6)</td><td> 0.025</td><td> 50.0</td>

<td> (7)</td><td> 0.025</td><td> 1 32.5</td>

<td> (8)</td><td> 0.025</td><td> 0.0</td>

<td> (10)</td><td> 0.025</td><td> 0.0</td>

<td> (11)</td><td> 0.025</td><td> 16.3</td>

<td> (12)</td><td> 0.025</td><td> 0.0</td>

<td></td><td> ־#־</td><td></td>

<td> le A 17 524</td><td> //</td><td></td>

dhoot treatment test/powdery mildew of cereals/protective .Table A (Continuation)

<td> 5</td><td> Active compounds</td><td> Active compound concentration in the spray liquor in % by weight</td><td> Infection ' in of the untreated .control</td>

<td></td><td> (13)</td><td> 0.025</td><td> 50.0</td>

<td> 10</td><td> (14)</td><td> 0.025</td><td> 13.8</td>

<td></td><td> (15)</td><td> 0.025</td><td> 0.0</td>

Example

Powdery mildewcf barley (Erysiphe graminis var. horde!)/ systemic (fungal disease of cereal shoots) . The active compounds were used as pulverulent seed treatment agents. They were prepared by extending the particular active compound with a mixture of equal parts by weight of talc and kieselguhr to give a finely pulverulent mixture of the desired concentration of active compound.

For the treatment of seed, barley seed was shaken with i

the mixture of active compound and extender in a closed glass bottle. The seed was sown at the rate :of 3 x 12 grains in flowerpots , 2 cm deep in a mixture of one part by volume of Fruhstorfer standard soil and one part by volume of quartz sand. The germination and emergence took place under favourable conditions in a greenhouse. 7 days after sowing, when the barley plants had developed their first leaf, they were dusted with fresh spores of Erysiphe

- «ί -

Le A 17 324 ./¢.

C

I I graminis var. hordei and grown on at 21-22°0|and 8090%־ 1 relative atmospheric humidity and 16 hours' exposure to light. The typical mildew pustules formed on the leaves over the course of 6 days. j

The degree of infection was expressed as a percentage i

of. the infection of the untreated control pleats. Thus, 0% denoted no infection and 100% denoted the !same degree of infection as in the case of the untreated control. The active compound was the more active, the lower was the degree of mildew infection.

The active compounds and concentrations of active compound in the seed treatment agent, as well as the amount ' used of the latter, and the percentage infection with mildew can be seen.from the table which follows:

Table B

Powdery mildew of barley test (drysiphe graminis var. hordei)/ systemic

<td> 20</td><td colspan="2"> Active compound Active concent:compounds ration in the dressing in % by weight</td><td> Amount of dressing used in g/kg of seed</td><td> Infection in % of the antreated control</td>

<td> 25</td><td> without dressing ׳</td><td> -</td><td></td><td> 100.0</td>

<td></td><td> (A)</td><td> 25</td><td> 10</td><td> 88.8</td>

<td></td><td> (B)</td><td> 25</td><td> 10</td><td> 100.0</td>

<td></td><td> (1)</td><td> 25</td><td> ' 10</td><td> 0.0</td>

<td> 30</td><td> (5)</td><td> 25</td><td> 10</td><td> 0,0 ־</td>

<td></td><td> (8)</td><td> 25</td><td> 10</td><td> 0.0</td>

<td></td><td> (10)</td><td> 25</td><td> 10</td><td> 0.0</td>

<td></td><td> (12)</td><td> 25</td><td> 10</td><td> 27.5</td>

Le A 17 324

Table B (Continuation)

Powdery mildew of barley test (Erysiphe ^raminis var. hardei)/ systemic ~

<td> Active compounds</td><td> Active compound concentration in the dressing in % by weight</td><td> Amount of dressing used in g/kg of seed</td><td> Infection in % of the antreated control</td>

<td> (13)</td><td> 25</td><td> 10</td><td>^! 3.8</td>

<td> (14)</td><td> 25</td><td> 10</td><td> 1 ' 0.0</td>

<td> (15)</td><td> 25</td><td> 10</td><td> 155.0 l</td>

<td> Example C Bacteria test</td><td> / Xanthomonas</td><td> oryzae</td><td> i 1</td>

Solvent: 11.75 parts by weight of acetone

Dispersing agent: 0.75 part by weight of alkylaryl polyglycol ether

Water: 987.50 parts by weight ^!

The amount of active compound required for the desired active compound concentration in the spray liquor

I was mixed with the stated amount of the solvent and of the dispersing agent and the concentrate was diluted with the stated amount of water.

JO rice plants which were about 40 days old were sprayed with the spray liquor until dripping wet. The plants remained in a greenhouse, at temperatures of 22 to 24°C and a relative atmospheric humidity of about 70%, until they had dried. Needles were then dipped into an aqueous bacterial suspension of Xanthomonas oryzae and the plants

־#־

Le A 17 324 were inoculated by pricking the leaves. After the inoculation, the leaves stood for 24 hours at 100% relative atmospheric humidity and thereafter in a room, at 26 to 28°C and 80% relative atmospheric humidity.

days after the inoculation, the infection of all 1 pricked inoculated leaves of plants which had beforehand been treated with the preparation was evaluated, using a scale of from 1 to 9. 1 denoted 100% action, 3 denoted good action, 5 denoted moderate action and 9 denoted no action.

The active compounds, active compound concentrations and results can be .seen from the table which follows:

Table C

Bacteria test

Xanthomonas oryzae

Active compound

Infection rating at an active compound concentration of 0.025% untreated control9 (12)5 (8)5 (11)3

The process of this invention is illustrated by the following preparative Examples.

Example it n

Le A 17 324

<img file="IL52662A_D0008.tif" />

SO, Η

A solation of 36*3 g (0.2 mol) of crude 4-acetoxy1-bromo-l-(4-chlorophenoxy)-3,3-d imethyl-batan-2-one in 50 ml of acetone was added dropwise, at the boil, to a suspension of 21 g'(0.3 mol) of triazole and !JO g (0.2 mol) of potassium carbonate in 200 ml of acetone. After heating for 15 hours under reflux, the mixture was filtered and the filtrate was concentrated by' distilling off the solvent in vacuo. The residue was taken up in 200 ml of methylene chloride and the solution was washed three times with 50 ml of water at a time, dried over sodium sulphate and concentrated. The residue was dissolved in 100 ml of acetone and J6 g (0.1 mol) of 1,5naphthalenedisulphonic acid octahydrate in 100 ml of acetone were added. The crystalline precipitate which resulted I was filtered off and dried. 45 g (45¢ _of theory) of

4-acetoxy-l-(4-chloro-phenoxy)-3,3-dime thyl-1-(1,2,4triazol-l-yl)-butan-2-one 1,5-naphthalenedisulphonate of melting point 155 - 160°C were obtained. Preparation of the starting material /־־Λ ^CHj^C1־O‘ ⁰ ־ ™ ־ CO - C - CH₂ - co - CH,

Br CH,

Le A 17 324

170 g (0.72 mol) of 4-acetoxy-l-bromo-3,3-dimethylbutan-2-one in 200 ml of acetone were added dropwise, over the course of 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 1,000 ml of acetone. ' After heating for 15 hours whilst stirring under reflux, thb mixture was filtered and the filtrate was concentrated by distilling off the solvent in vacuo. The residue was taken up in 200 ml of methylene chloride and the solution was washed three times with 50 ml of water at. a time, dried over sodium sulphate and concentrated. The oily residue was distilled. 153 g.(72¢ of theory) of 4-acetoxy-l-(4chlorophenoxy )-3,3־-dimethyl-butan—2-one of melting point 140 - 145°C/0.2 nun Hg was obtained.

56.9 g (0.2 mbl) of 4-acetoxy-l-(4-chlorophenoxy)-3,

3-dimethyl-butan-2-one were dissolved in 350 ml of carbon tetrachloride. 10.3 g (0.2 mol)of bromine were added dropwise, at room temperature, in such a way that the bromine was steadily consumed. Thereafter, the mixture was stirred for 30 minutes at room temperature. After distilling off the solvent in vacuo. 4-acetoxy-l-bromo-l(4-chlorophenoxy)-3,3־dimethyl-butan-2-one was obtained quantitatively and could be directly reacted further. Example 2

CHj

I

CO - C - CH, - 0 - CO - CH₃ ch₃ u-----N

<img file="IL52662A_D0009.tif" />

־- ft

Le A 17 324 . 22 g (0.05 mol) of 4-acetoxy-l-bromo-l-/4-(4'-chlorophenyl)-phenoxy73«3־-dimethyl-butan-2-one were dissolved in 20 ml of acetone and the solution was added dropwise, at the boil, to 5-5 g (0.08 mol) of imidazole and 7.5 g (0.05 mol) of potassium carbonate in 80 ml of acetone. After heating for 15 hours under reflux, the mixture was filtered and the filtrate was concentrated by distilling off the solvent in vacuo. The oil which remained was washed with

I ml of water and was crystallised, or recrystallised, from ether. 9 g (42.2¢ of theory) of 4-acetoxy-l-/4-(4'chlorophenyl)-phenoxy7-5,5-dimethyl-l-(imidazol-l-yl)-butan-

2-one of melting point 110 - 112°C were obtained.

Example 3 :

<img file="IL52662A_D0010.tif" />

ml of concentrated hydrochloric acid were added to

42.8 g (0. 1 mol) of 4-acetoxy-l-/^-(4'-chlorophenyl)phenoxy7“3,3-dimethyl-1-(imidazol-l-yl)-butan-2-one (see Example 2) in 200 ml of methanol and the mixture was heated for 8 hours under reflux. The solvent was then distilled off in vacuo and 50 ml of saturated sodium bicarbonate solution and 50 ml of pentane were added to the residue. After 2 hours, the crystalline product was filtered off.

58.9 g (100% of theory) of l-/“4-(4'-chlorophenyl)-phenoxy7 -3,3-dimethyl-4-hydroxy-l-(imidazol-l-yl)-butan-2-one of melting point 135 - 135°C were obtained.

Le A 17 324

2¢

Example 4 .

. ... . י i ' . . '¹ : י

'. CH^ » .GO⁰ ־ i® -⁰⁰-;-™i4) ,(,™)⁰־“-⁰־)

X^NX| ⁰¹ל

.... IL___N ;

7.72 g (0.02 mol) of 1-/4-(4¹ -chlorophenyl)-phenoxx/־־ 3,3-dimethyl-4-hydroxy-l-(imidazol-l-yl)-butan-2-one (see Example 3) were dissolved in 50 ml of methylene chloride, 5 ml of pivalic acid chloride were added and the mixture was heated for 5 hours;under reflux. The solvent was then distilled off in vacuo. the residue was taken up in methylene chloride and the solution was washed twice with 50 ml of saturated sodium bicarbonate solution at a time and was concentrated. The residue׳ was taken up in 50 ml of pentane, whereupon it crystallised. 5.3 g (60¢ of theory) of 1-/4-(4’-chlorophenyl)-phen0xx7-3,3-dimethyl-l(imidazol-l-yl)-4-p.iva10yloxy-butan-2-one of melting point 98 - 103°C were obtained.

The following examples of the general formula

ס ®CH-A-C-CHa - 0 - R (!) ^Zn CHgX were obtained analogoulsy to the abovementioned examples:

־ // Le A 17 324 t-i (D

H

[י.

M £

H0₂

K)

4»SC«S»W׳״

4-Q-C1 2,4-Cl₂

2,4-Cl₂

114-C1 . 4-1¾

2,4-Cl₂

144-01 ^{16 4}.Q-Cl

<td> N</td><td> CO</td><td> H</td><td> CE_?</td><td> -CO-CHj</td><td> 110-111</td>

<td> N</td><td> . CO</td><td> H</td><td> CEj</td><td> -CO-CH₅</td><td> 115-114</td>

<td> N</td><td> CO</td><td> H</td><td> CE^</td><td> -CO-CH₅</td><td> 114-115</td>

<td> N</td><td> CO</td><td> H</td><td> CHj</td><td> -CO-CHj</td><td> ,,. viscous oil</td>

<td> N</td><td> CO</td><td> H</td><td> CE₅</td><td> -CO-CHj</td><td> 175-174 SO,⁰</td>

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

<td></td><td></td><td></td><td></td><td></td><td> SOjH</td>

<td> N</td><td> CO</td><td> H</td><td> CE^</td><td> -CO-CH₅</td><td> viscous oil</td>

<td> N</td><td> CO</td><td> -o-co 1</td><td> CE^</td><td> -CO-CHj</td><td> 85-86</td>

<td></td><td></td><td> CEj</td><td></td><td></td><td></td>

<td> CH</td><td> CO</td><td> H</td><td> ch₅</td><td> -C'O-CK₅</td><td> 148-151</td>

<td> CH'</td><td> CO</td><td> H</td><td> %</td><td> -CO-CHj</td><td> 69-70</td>

<td> CH</td><td> CO</td><td> H</td><td> CE₅</td><td> -CO-CHj</td><td> 72-74</td>

<td> CH</td><td> CO</td><td> H</td><td> CE, 5</td><td> -CO-CH^</td><td> viscous oil</td>

<td> CE</td><td> CO</td><td> H '</td><td> CH,</td><td> -co-(ch₂)₁₆</td><td> 58-68</td>

CE^

<td> (D &gt;</td><td> Example No.</td><td>^Zn</td><td> Y /</td><td> A</td><td> X</td><td> X¹</td><td> ft</td><td> Keltjnr point</td>

<td></td><td colspan="8"></td>

<td> bl טו</td><td> .17</td><td> 01־4</td><td> CH</td><td> CO</td><td> H</td><td> CH, נ</td><td> Η</td><td> 104-105</td>

<td></td><td> 18</td><td> 4-01</td><td> N</td><td> CO</td><td> H</td><td> CH, נ</td><td> H</td><td> 110-111</td>

<td></td><td> .19</td><td></td><td> CH</td><td> CHOH</td><td> H</td><td> ch₃</td><td> H</td><td> 138-143</td>

<td></td><td> 20</td><td> 01־4</td><td> CH.</td><td> CO</td><td> H</td><td> CH, נ</td><td> -CO-CHC1₂</td><td> 102-104 ί I</td>

<td> 1 X</td><td> 21</td><td> 01־4</td><td> N</td><td> CHOH</td><td> H</td><td> CHj</td><td> H</td><td> 96-105</td>

<td> M</td><td colspan="8"></td>

<td> 1 Ή</td><td> 22</td><td> 4-01</td><td> _N-</td><td> CO</td><td> H</td><td> CH, ג</td><td> 00 ^έ11^Η23</td><td> zShfl. Oel</td>

<td></td><td> 23</td><td> 4-C1 '</td><td> N</td><td> CO</td><td> H</td><td> CH, כ</td><td> -CO-CH₂C1</td><td> 69</td>

<td></td><td> 24</td><td> 2,4-C1₂</td><td> N</td><td> co.</td><td> H</td><td> ch₃</td><td> H</td><td> 110־104 - --I</td>

<td></td><td> 25</td><td> 4-C1</td><td> N</td><td> CO</td><td> H</td><td> CHj</td><td> -CO-CjH^</td><td> zahfl, Oel i I</td>

<td></td><td> . 26</td><td> #¹י</td><td> CH</td><td> CO</td><td> H</td><td> ch₃</td><td> ¥15</td><td> I 50-53 r</td>

Example No.

Meltinr point (°C) 'i bl N

4-C1 N CO H CH, ⁵⁸⁶⁰־ ¥5

4-01 N CO H CHj ¹־J^{0 6062}־

X 29 4-01 N CO H CH,

X כ ^נ^C17^H55

-CO 56-58 (CH2)₂-CH₂C1

4-C1 N CO H CHj -CO-y 75

4-01 N CO H CHj CO 85

72-75