Fungicide,bactericide or plant-growth regulating compositions containing triasole derivatives,and process for producing the active agents

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Patent Office (62) National application number (86) International filing date (86) Filing date for European patent application (30)

74-11-18 US 524587

84-05-28 Publication number 433 495

76-05-19

75-11-11

11/11/11 Application received as:

Ö Swedish patent application □ Completed international patent application with number

Q converted European patent application with number

10/10/09 US 620989 (71) Applicant: Janssen Pharmaceutics NV. (72) Inventor: G Van Reet, J Heeres, Vosselaar, Turnhout (74) Representative: AB Stockholm Patent Office

Beerse BE

L Waltz. Tessenderio, (54) Title: Triazole derivatives with fungicide, bactericidal or plant regulatory action for agricultural use (56) Other publications: SE 349 037 (CG7 d 55/06), DE 2 247 186 (A61k 27/00), US 3,575 999 (260-309), US 3 755 349 (260-309)

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POOR QUALITY

Prior to 1 invention intended · a non-fungal compound with fungicide, baked in ·. id cuer · plant regulaUe impact on agricultural use.

The compounds present differ from known triazole derivatives, among other things, by the nature of the side chain attached to the nitrogen atom of the triazole ring. The triazole derivatives disclosed in Dutch patent application 69.1302b and in French patent 2,200,012 are believed to be the derivatives most closely resembling the present triazole derivatives.

The present compound is characterized in that it consists of one ¹⁰ 1- (β-aryl) ethyl-1H-1,2, ^;1-triazole ketal of the formula

<img file="SE425246B_D0001.tif" />

IN

CH₇-> C - Ar ^z 0 0 ^xz^x or therapeutically active acid addition salts thereof, wherein Z represents the alkylene constituted by -CH 2 -C 3 -, -C 2 -CH 2 -C 3 -,

-CH (CH 2) -CH (CH 2 - or -CH -> - CH (alkyl) -, wherein the alkyl group has 10 carbon atoms, and Ar represents 2,4-dihaloethylene.

Therapeutically active acid addition salts of the present compounds are also included in the present invention.

The term alkyl herein is meant to include straight and branched hydrocarbon groups having 1-10 carbon atoms such as methyl, ethyl, 1-methylethyl, propyl, 1,1-dimethylethyl, butyl, pentyl, hexyl, heptyl, octyl, decyl and the like; lower alkyl in the present case means straight or branched saturated hydrocarbons having 1 to 6 carbon atoms, such as methyl, ethyl, propyl, 1-methylethyl, butyl, 1,1-dimethylethyl, pentyl, hexyl and similar alkyl groups; the term halo includes halogen atoms with atomic weights less than 127, ie fluorine, chlorine, bromine and iodine.

The ketals of formula I are readily obtained by transferring 1H-1,2,4-triazole (II) previously to a metal salt, e.g. by treatment with an alkali metal alkoxide, preferably sodium methoxide, is reacted with a halide of formula (III)

Y-CH 2 C-Ar (III) wherein Ar and Z have the meanings indicated and Y represents halogen, preferably bromine. The reaction between 1H-1,2,4-triazole (II) and (III) is advantageously carried out in a suitable non-reaction reaction inert organic

2 solvents such as Ν, Ν-dimethylformamide, Ν, Ν-dimethylacetamide, acetonitrile, benzonitrile or the like. Such solvents can be used in combination with other reaction-inert organic solvents such as benzene, methylbenzene, dimethylbenzene or the like. Where Y represents bromine or chlorine, it is appropriate to add an alkali metal iodide, e.g. sodium or potassium iodide. Slightly elevated temperatures increase the reaction rate and preferably the reaction is carried out at the reflux temperature of the reaction mixture.

The formed ketal of formula (I) is then isolated from the reaction mixture by conventional methods and optionally further purified by any conventional purification process, for example, by crystallization, extraction, trituration, chromatography, etc.

The procedure described can be further illustrated as follows:

<img file="SE425246B_D0002.tif" />

H (II)

NaOMe

-->

<img file="SE425246B_D0003.tif" />

(III) (I)

The compounds of formula (I) thus obtained_r in base form, can be converted into therapeutically useful acid addition salts by reaction with a suitable acid, such as an inorganic acid such as a hydrogen halide, i.e. , hydroxyacetic acid, Qi-hydroxypropionic acid, 2-oxopropionic acid, oxalic acid, malonic acid, succinic acid, maleic acid, fumaric acid, 2-hydroxy succinic acid, 2,3-dihydroxy succinic acid, 2-hydroxy-1,2,3-propane tricarboxylic acid, benzoic acid,

3-phenylpropionic acid, Af-hydroxybenzeneacetic acid, methanesulfonic acid, ethane ²5 sulfonic acid, hydroxyethanesulfonic acid, 4-methylbenzenesulfonic acid, Λτ-hydroxybenzoic acid, 4-amino-2-hydroxybenzoic acid, 2-phenoxybenzoic acid or 2-acetyloxybenzoic acid. The salts are in turn transferred to the corresponding free bases in the usual manner, e.g. by reaction with alkali, such as sodium or potassium hydroxide.

The starting materials of formula (III), some of which are known compounds, can be prepared according to known methods. Such compounds wherein Z represents a group -C 2 -CH 2 -, -CH 2 CH 2 -CH 2 -, -CH (CH 2) -CH (CH-j) - and -CH 2 -CH 2 -CH 3 - and methods for preparing these compounds is disclosed in U.S. Patent No. 3,557,999

The compounds of formula (III) are prepared by catalysing a suitable ketone of formula (IV) wherein Ar and Y are designated by a suitable diol of formula (V) according to known ketalization methods described in the literature. (see, e.g., Synthesis, 1974 (1), 23).

According to a preferred method, the two reactants are refluxed together for several hours, whereby water is azeotropically removed in a suitable organic solvent, preferably in the presence of a simple alcohol such as ethanol, propanol, butanol, pentanol or the like, and in the presence of a suitable strong acid. , such as 4-methylbenzenesulfonic acid. Suitable organic solvents which may be used for this purpose are, for example, aromatic hydrocarbons such as benzene, methylbenzene, dimethylbenzene and the like, and saturated hydrocarbons such as cyclohexane.

il

Ar-C-CHgY + HO-Z-OH 4-methylbenzenesulfonic acid (III) butanol ¹7 (IV) (V) benzene

The ketones of formula (IV) are known and can be prepared by methods known to those skilled in the art.

From formula (I), it is apparent that several of the compounds of the present invention have asymmetric carbon atoms in the structure and, consequently, they may exist under various stereochemical optical isomeric forms. When an alkyl group is in the 4-position of the dioxolane nucleus, the carbon atom to which the alkyl group is attached and the carbon atom in the 2-position of the dioxolane nucleus are asymmetrical. The stereochemical and optical isomers of the compounds of formula (I) can be separated and isolated by methods known to those skilled in the art. The indicated isomers fall within the scope of the invention.

The compounds of formula (I) and the acid addition salts thereof are useful agents in the control of fungi and bacteria. The compounds of the invention are valuable in treating plants attacked by pathogenic microorganisms, as well as for the destruction of microorganisms on materials.

The compounds of the invention are very strong fungicides which can be used in agriculture. They are very active against a large number of fungi, e.g. against the fungi responsible for the appearance of apple mildew on various plants, against Erysiphe graminis, Erysiphe polygon !, Erysiphe cichoracearum, Erysiphe polyphaga, Podosphaera leuchotricha, Sphaerotheca pannosa, Sphaerotheca rnors-uvae, Uncinula

<img file="SE425246B_D0004.tif" />

&lt;ι necator, etc, and other fungi, e.g. Venturia maequalis, Colletotrichum lindemuthianura, Fusarium oxysporum, Alternaria tenius, Thielaviopsis basicola, Helminthosporium gramineuni, Penicillium degitatum, etc.

They are particularly useful because of their prophylactic as well as curative and systemic effects. Their strong effect on phytopathogenic fungi is illustrated more clearly by the results obtained in the following experiments.

In several of these experiments, the compound 1- [2- (2,4-dichlorophenyl) -1,3-dioxolan-2-ylmethyl-1H-1,2,4-triazole, (Ia) was used as a representative type of the compounds of formula (I).

.Cl (Ia)

The compounds for which test results are given have not been given to limit the invention to these compounds but merely to exemplify the strong action against fungi of all the compounds of formula (I).

A. Prophylactic effect of compounds of formula (I) against Erysiphe cichoracearum on cucumber in leaf treatment.

Young cucumber plants, about 10 days old, were sprayed with an aqueous solution containing 250, 100 or 10 ppm of the compound to be tested, while the comparison plants were untreated. When the plants had dried, they were artificially infected with spores of Erysiphe cichoracearum by rubbing heavily infected leaves against the plants. On the 15th day after the artificial infection, the degree of fungal infestation is evaluated by counting the number of spots per plant. The results given in Table I are averages for two plants and are expressed according to the following scoring system.

0 = 0 spots per plant = 1-5 spots per plant = 6-10 spots per plant = more than 10 spots per plant

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Table I

Prophylactic action of compound (I) against Erysiphe chichora oarum on gux plants in leaf treatment

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<img file="SE425246B_D0006.tif" />

2,4-(^Br) 2-^c6^hrs₃

2, 4- (Cl)₂-C₆hrs₃

2, 4- (Cl)₂-C₆hrs₃

2,4- (Cl)₂-C₆hrs₃

2,4- (Cl)₂-C₆hrs₃

I 2, 4- (Cl)₂C ~ H₃j '' 2 o 3

2,4- (Cl)₂-C₆hrs₃ί 2.4- (CI)₂-C₆hrs₃

<img file="SE425246B_D0007.tif" />

<td>Base-</td><td>Effect</td><td colspan="2">against fungus. '</td>

<td>or</td><td colspan="2">point</td><td></td>

<td>salt form</td><td>250 ppm</td><td>100 ppm</td><td>10 ppm</td>

<td>base</td><td> -</td><td> 0</td><td> 0</td>

<td>(COOH)₂</td><td> -</td><td> 1</td><td> -</td>

<td>HNO₃</td><td> 0</td><td> -</td><td> -</td>

<td>HNO₃</td><td> -</td><td> 0</td><td> 0</td>

<td>HNO₃</td><td> -</td><td> 0</td><td> 0</td>

<td>U / 2 (COOH)₂</td><td></td><td> 2</td><td> -</td>

<td>HNO₃</td><td> -</td><td> 0</td><td> 0</td>

<td>HNO₃</td><td> 0</td><td> -</td><td> -</td>

<td>HNO₃</td><td> -</td><td> 2</td><td> -</td>

<td>HNO₃</td><td> 0</td><td> -</td><td> -</td>

P Ilf i in WMNW

Profyl.1 Prophylactic action against Erysiphe polyphaga on cucumber during leaf treatment.

Young cucumber plants in the single-leaf stage were sprayed with an aqueous solution containing 500, 250 or 125 ppm of (Ia), while the comparison plants were untreated. An artificial infection with spores of Erysiphe polyphaga was carried out by rubbing heavily infected leaves against the plants on the 4th, 6th or 8th day after treatment. On the 18th and 34th days after the treatment, the proportion of leaf surfaces, which were attacked by the fungus separately for infected leaves and newly formed leaves, was determined. The results given in Table 1.1 are averages for 5 plants and expressed as a percentage of attack compared to the untreated plants.

Table 1.1

Prophylactic effect of (Ia) against Erysipe polyphaga on cucumber during leaf treatment

<td>Utvärderingsdag</td><td colspan="6">18 days after treatment</td><td colspan="6">34 days after treatment</td>

<td>Infected on specified day eft. treatment</td><td colspan="2"> 4</td><td colspan="2"> 6</td><td colspan="2"> 8</td><td colspan="2"> 4</td><td colspan="2"> 6</td><td colspan="2"> 8</td>

<td>Infected leaves (a) or newly formed leaves (B)</td><td>^A</td><td>b</td><td>A</td><td>b</td><td>A</td><td>b</td><td>A</td><td>b</td><td>A</td><td>b</td><td>A</td><td>b</td>

<td>Concentration of (Ia) in spray solution in Untreated</td><td> 100</td><td> 100</td><td> 100</td><td> 100</td><td> 100</td><td> 100</td><td> 100</td><td> 100</td><td> 100</td><td> 100</td><td> 100</td><td> 100</td>

<td>500 ppm</td><td> 0</td><td> 0</td><td> 0</td><td> 0</td><td> 0</td><td> 0</td><td> 0</td><td> 0</td><td> 0</td><td> 0</td><td> 0</td><td> 0</td>

<td>250 ppm</td><td> 0</td><td> 0</td><td> 0</td><td> 0</td><td> 0</td><td> 0</td><td> 0</td><td> 0</td><td> 0</td><td> 0</td><td> 0</td><td> 0</td>

<td>125 ppm</td><td> 0</td><td> 0</td><td> 0</td><td> • 0</td><td> 0</td><td> 0</td><td> 0</td><td> 0</td><td> 0</td><td> 0</td><td> 0</td><td>Ί</td>

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B. Prophylactic pathway against Eiysiphe graminis on grain during soil treatment.

Barley plants were treated by irrigating each plant with 100 ml of an aqueous solution containing 1000, 100 or 10 ppm (Ia). Comparative plants received the same volume of solution, which however did not contain (Ia). The natural infection, which usually occurs when the plants are kept in greenhouses near infected plants, was evaluated 16 days after treatment by counting the number of spots on the leaves. 5 seedlings were used per experimental series 10 and the results in Table II are averages, expressed as a percentage of attack relative to the comparison plants.

Table II

Phylphylactic effect of (Ia) against Erysiphe graminis on barley during soil treatment

<td>Dose in mg (Ia) per plant</td><td>Attack in% relative to comparison plant</td>

<td>comparison Plantation</td><td> 100</td>

<td>100 mg</td><td> 0</td>

<td>10 mg</td><td> 0</td>

<td>1 mg</td><td> 53</td>

C. Healing effect against Erysiphe graminis on barley during leaf treatment.

Barley plants infested by Erysiphe graminis were sprayed with an aqueous solution containing (Ia) at the indicated concentration. On the 16th day after treatment, the number of spots per plant was determined. Five seedling test series were used and the results given in Table III are averages, expressed as a percentage of attack relative to the comparison plants.

Table III

Healing effect of (Ia) against Erysiphe graminis on barley during leaf treatment

<td>Concentration of (Ia) in the spray solution</td><td>Attack holding seedlings</td><td>i? in advance for comparison</td>

<td> 0</td><td></td><td> 100</td>

<td>1000 ppm</td><td></td><td> 0</td>

<td>100 ppm</td><td></td><td> 1,5</td>

<td>| 10 ppm</td><td></td><td> 25</td>

D. Prophylactic effect of (Ia) riot Podospaera leuchotricha η; spiked apple plants when sprouting.

One year old apple seedlings were sprayed with an aqueous solution containing (Ia) at the indicated concentration. The plants were artificially infected as described in Sample A with spores of Podosphaera leuchotricha 1 day after treatment and incubated for 36 hours. The degree of fungal infestation was evaluated 25 days after treatment by counting the number of spots. Two seedlings per experimental series were used and the residuals given in Table IV constitute averages, expressed as a percentage of attack relative to the comparison plants.

Table IV

Prophylactic effect of (Ia) against Podosphaera leucotricha on dilute apple plants when sprayed

<td>Concentration of (Ia)</td><td>Attack in% of ratio</td>

<td>in the spray solution</td><td>for comparison plants</td>

<td> 0</td><td> 100</td>

<td>100 ppm</td><td> 0</td>

<td>10 ppm</td><td> 6</td>

E. Effect on Thielaviopsis sp.

mm thick slices of potato and leek were dipped in an aqueous sample solution containing (Ia) at indicated concentrations.

The plates were placed after dipping on filter paper on a large plastic tray and the tray was covered with glass. An artificial infection was performed on the day of treatment by spraying the slices with a concentrated suspension of spores of Thielaviopsis sp. and the slices were incubated at room temperature.

The growth of fungi on the slices is evaluated 6 days after treatment by estimating the fungal infestation on the surface. The results j given in Table V are expressed as a percentage of attack relative to the comparison plants.

Table V

The effect of (Ia) on Thielaviopsis sp.

<td rowspan="2">Concentration of (Ia) in the sample solution in ppm</td><td colspan="2">Attack in% relative to comparison plants</td>

<td>Potato</td><td>Puree onion</td>

<td> 0</td><td> 100</td><td> 100</td>

<td> 1000</td><td> 0</td><td> 0</td>

<td> 100</td><td>⁰</td><td> 0</td>

<td> 10</td><td> 0</td><td> 42,0’</td>

<td> 1</td><td> 11</td><td> 100</td>

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The compounds of formula (I) have, apart from wounds. le antimicrobial effects, valuable plant regulating properties. Bercend · on various factors, such as the nature of the plants under treatment and, in the dose of the active ingredient added, the observed effect may be either growth stimulant or growth inhibitory. The present compounds, as such, are useful in regulating the growth of plants. In particular, they can be used as plant inhibitors or as plant retardants, especially as inhibitors for growth of root shoots, e.g. on tobacco plant. However, under certain circumstances, ce can also be used as growth stimulants for plants.

The plant regulating properties of the compounds of formula (I), which are naturally intended to fall within the scope of the present invention, are more clearly illustrated by the results obtained in the following experiments, wherein the compound (Ia) is used as representative of the compounds of the invention. The results obtained with (Ia) are not intended to limit the invention but merely to exemplify the useful plant regulating properties of all compounds within the scope of formula (I).

F. Plant-regulating effect on tomato plants during soil treatment.

Young tomato plants, 3.5 to 4 cm tall, were planted in separate pots. Each pot was watered with a test solution, which

<img file="SE425246B_D0008.tif" />

contained the specified amount of (Ia). The plant was evaluated by determining the length and weight of the plants 28 days after treatment.

The results given in Table IX are averages for fern plants and are expressed as a percentage of the comparison plants. Tahel1 TX

Plant regulating effect of (Ia) on tomato plants during soil treatment

<td>Dose of (Ia) in mg / plant</td><td>The length of the plants in% in relation to the comparison plants</td><td>The weight of the plants in $ relative to the comparison plants</td>

<td>No</td><td> 100</td><td> 100</td>

<td> 10</td><td> 114</td><td> 118</td>

<td> 1</td><td> 127</td><td> 134</td>

<td> 0,1</td><td> 122</td><td> 116</td>

G. Plant regulating effect on barley in leaf processing.

Young seedlings in the 3-4 leaf stage were sprayed with a test solution containing (Ia) of the indicated concentrations. The effect on plant growth was evaluated 24 days after treatment by determining the weight of the plants. The results given in Table X are averages for 10 plants and are expressed as a percentage in relation to the comparison plants.

Table X

Plant-regulating effect of (Ia) on barley during leaf treatment

<td>Conc. of (Ia) in the sample solution (Ppm)</td><td>The average weight of the plants in ίί of the comparison plants</td>

<td>No</td><td> 100</td>

<td> 125</td><td> 126</td>

<td> 60</td><td> 116</td>

H. The effect of the growth of root shoots on tobacco plants.

Tobacco Plant, var. Xanthi, was raised in greenhouses and peaked in the early bud stage.

After 5 days, a leaf spray treatment was carried out with an aqueous suspension of compound (Ia) in amounts corresponding to 3 and 1.5 kg ai / ha.

Each treatment was repeated three times. Twelve days after the treatment, the growth of the root, cotter, was estimated in comparison with the topped and untreated corn leaves.

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The recorded reductions of rootstock growth were 10 'at 3.0 SEK / ha and 90 3 at

I. V-'ix inhibition on. sojaplar.tor.

Soybean plant, var. Hark was grown in crude cox at 23 0, 20,000 Lux and a day length of 14 hours.

a cultivating chamber

When the third trifoliate mixture had been unfolded, the plants were sprayed with an aqueous suspension of compound (Ia) at concentrations of 1000, 500, 100 and 50 ppm active ingredient.

The percentage plant inhibition of the treated plants relative to the comparison plants was determined after 14 days. The following results were obtained:

<td>Treatment</td><td>% plant inhibition</td>

<td>(Ia) 1000 ppm ai</td><td> 70 %</td>

<td>500 ppm ai</td><td> 40 2</td>

<td>100 ppm ai</td><td>25 "k</td>

<td>50 ppm ai</td><td> 0 3</td>

<td>Järnförelseplantor</td><td>0 g</td>

At the concentration of 1000 ppm, a more intense green color of the foliage could be observed.

Due to the stated fungicidal, antibacterial and plant regulatory properties of the compounds, according to the present invention, valuable compositions comprising the ketals (I) or acid addition salts thereof can be prepared such as the active ingredient in a solvent or a solid, semi-solid or liquid diluent or carrier material. In addition, the invention discloses an effective method for controlling fungal or bacterial growth using an effective bactericidal or fungicidal amount of such ketals (I) or salts thereof. The present compounds may be used in suitable solvents or diluents, in the form of emulsions, suspensions, dispersions or ointments, on suitable solid or semi-solid carrier substances, in natural or synthetic soaps, detergents or dispersion media, optionally in conjunction with other compounds with arachicidal, insecticidal, ovicidal, fungicidal and / or bactericidal properties or together with inactive additives.

Solid carrier substances suitable for the preparation of powder form compositions include various inert, porous and powdery dispersants of inorganic or organic nature.

<img file="SE425246B_D0009.tif" />

<img file="SE425246B_D0010.tif" />

such as tricalcium phosphate, calcium carbonate, in the form of processed chalk or limestone, kaolin, tree trunks, bentonite, talc, diatomaceous earth or boric acid, which is ground; powdered cork, sawdust and other fine powder materials of vegetable origin can also be used as carrier substances,

The active ingredient is mixed with these carrier substances, e.g. by painting them; alternatively, the inert carrier substance is impregnated with a solution of the active component in a volatile solvent and the solvent is then removed by heating or suction filtration at reduced pressure. By adding wetting agents and / or dispersants, such powder formulations can also be easily wetted with water so that suspensions are obtained.

The inert solvents used in the preparation of liquid preparations should not be flammable and should, as far as possible, be odorless and non-toxic to warm-blooded animals or to plants in the surrounding environment. Solvents suitable for this purpose are high boiling oils, e.g. of vegetable origin, and low boiling solvents having a flash point of at least JO ° C, such as polyethylene glycol, isopropanol, dimethyl sulfoxide, hydrogenated naphthalenes and alkylated naphthalenes. Of course, it is also possible to use mixtures of solvents. The solutions can be prepared in the usual manner and, if necessary, solution-promoting agents are used. Other liquid forms which may be used consist of emulsions or suspensions of the active compound in water or suitable inert solvents, or also concentrates for preparing such emulsions which can be directly adjusted to the desired concentration. For this purpose, for example, the active ingredient may be mixed with a dispersant or emulsifier. The active component may also be dissolved or dispersed in a suitable inert solvent and simultaneously or subsequently mixed with a dispersant or emulsifier.

It is also possible to use semi-solid carrier substances of the ointment-like, paste-like or wax-like nature, wherein the active component is incorporated, if necessary, by means of solvent-promoting agents and / or emulsifiers. Vaseline and other ointment bases are examples of semi-solid carrier substances.

It is further possible to use the active ingredient in the form of aerosols. For this purpose, the no active ingredient is dissolved or dispersed, if necessary with the aid of appropriate additives.

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solvents such as carrier liquids, e.g. difluorodichloromethane, which at atmospheric pressure boils at a temperature below room temperature, or in other volatile solvents. In this way, pressurized solutions are obtained which, when sprayed, provide aerosols which are particularly suitable for controlling or controlling fungi, bacteria, e.g. in enclosed rooms and storage rooms, as well as for application to vegetation for the eradication or prevention of infections by fungi or bacteria.

The present compounds and compositions thereof can be applied by conventional methods. Fungi or bacteria or a material to be treated or protected against attack by fungi or bacteria may be treated with the present compounds and their compositions by dusting, sprinkling, spraying, frosting, lubricating, impregnating or otherwise suitable.

When the present compounds are used in conjunction with suitable carriers, e.g. in solution, suspension, powders, powders, ointments, emulsions and similar forms, high activity is observed within a very large dilution range. For example, concentrations of the active ingredient of 0.1 to 10% by weight, based on the weight of the composition used, have been found to be effective in controlling fungi or bacteria. Of course, higher concentrations can also be used if a particular situation gives rise to this.

The following examples are intended to illustrate, but not to limit, the present invention. Unless otherwise indicated, all parts refer to 25 parts by weight.

Example 1. A stirred and cooled (0 ° C) solution of 30 parts of 1- (4-amino-2-methoxyphenyl) ethanone in 360 parts of concentrated hydrochloric acid solution, 75 parts of water and 30 parts of acetic acid is diazotized with a solution of 17.25 parts sodium nitrite in 200 parts of water. After stirring for 30 minutes at 0 ° C, the whole is poured into a solution of 30 parts of copper (I) chloride in 240 parts of concentrated hydrochloric acid solution with stirring. The mixture is heated for 1 hour at 60 ° C. When the product is cooled to room temperature, it is extracted twice with 2,2'-oxybispropane. The combined extracts are washed successively with water, a dilute sodium hydroxide solution and then twice again with water, dried, filtered and evaporated to give 28 parts (76 µl) of 1- (4-chloro-2-methoxyphenyl) ethanone, m.p. ° C.

ί'ί 2643-3

WE

Example 2. 57 parts of 1- (2,4-dibromethylphenyl) -1-ethanone are dissolved in MU parts 1,2-ethanedicl at 10 ° C. With stirring, drone pv .: urides are added for a 1-hour period 64 parts · well without external heating. After stirring for 1 hour at room temperature, 4 parts are added

4-methylbenzenesulfonic acid and 360 parts of benzene. The whole is stirred and refluxed overnight during separation of water. The reaction mixture is evaporated and the residue is taken up in 2,2'-oxybispropane. The resulting solution is successively washed once with dilute sodium hydroxide solution and three times with water, dried, filtered and evaporated to give 73.3 parts (64.5 2- (bromomethyl) -2- (2,4-dibromophenyl) -1 3-dioxolane, mp 96 ° C.

Example 3 ·

A. A stirred solution of 2.3 parts of sodium in 120 parts of methanol is added with 6.9 parts of 1H-1,2,4-triazole in 150 parts of dimethylformamide.

The methanol is removed under normal pressure until the internal temperature reaches 130 ° C. Then 25 parts of 2- (bromomethyl) -2- (2,4dichlorophenyl) -1,3-dioxolane are added. The reaction mixture is stirred and refluxed for 3 hours. It is allowed to cool to room temperature and poured into water. The precipitated product is filtered off and crystallized in isopropyl ether (activated carbon) to give 12 parts

1- [2- (2,4-dichlorophenyl) -1,3-dioxolan-2-ylmethyl] -1H-1,2,4-triazole, mp 109.9 ° C.

B. 6 parts of 1- [2- (2,4-dichlorophenyl) -1,3-dioxolan-2-ylmethyl] -1H-

1,2,4-Triazole was transferred to the nitrate salt in 2,2'-oxybispropane. After cooling, the salt is filtered off and crystallized twice

2-propanone to give 3 parts of 1- [2- (2,4-dichlorophenyl) -1,2-dioxolan-2-ylmethyl] -1H-1,2,4-triazole nitrate, mp 172.7 ° C.

C. 6 parts 1- / 2- (2,4-dichlorophenyl) -1,3-dioxolan-2-ylmethyl-7H-1H

1,2,4-Triazole is transferred to the sulfate salt in 2,2'-oxybispropane. The resulting sulfate is filtered off and crystallized from 2-propanol. The product is filtered off and recrystallized from ethanol (activated carbon) to give, after drying, 6 parts of 1- / 2- (2,4-dichloro-phenyl) -1,3-dioxolan-2-ylmethyl-7H-1,2,4-triazole sulfate, m.p. 207.1 ° C. Example 4. A stirred solution of 2.3 parts of sodium in 80 parts of methanol is added with 6.9 parts of 1H-1,2,4-triazole and 2 parts of sodium iodide in 100 parts of Ν, amid-dimethylformamide. The methanol is removed under normal pressure until the internal temperature reaches 130 ° C. Then 34.4 parts of 2- (bromomethyl) -2- (2,4-dichlorophenyl) -4-methyl-1, 3dioxolane are added and the whole is stirred and refluxed for 3 hours. The reaction mixture is poured into water and the product is extracted twice

7512643-3> 5 with diisopropyl ether. Wash the extract of a conc. Nitric acid solution with water and an excess' in 11 o'clock. r.es. The_r^_A The nitrate salt is filtered off and crystallized from a mixture of 2-propanol and diisopropyl ether to give 15 parts of 1- [2- (2, A-dichlorophenyl) 5β-methyl-1,3-dioxolan-2-ylmethyl] -1H-1,2 , A-triazole nitrate, mp 137.8 ° C.

Example 5. A stirred sodium methoxide solution prepared from 2.8 parts of sodium in 56 parts of methanol is added with a mixture of 8.3 parts of 1H-1, 2,4-triazole and 135 parts of N, N-dimethylformamide. The methanol is removed under normal pressure until its internal temperature reaches 130 ° C. Then a mixture of 27.8 parts of 2- (bromomethyl) -2- (2-chlorophenyl) -1,3-dioxolane and 3 parts of potassium iodide is added. The whole is stirred and refluxed for 6 hours. The reaction mixture is allowed to cool to room temperature, after which it is poured into water and the product is extracted three times with 1,1'-oxybisethane. The combined extracts are washed twice with water, dried, filtered and evaporated. The residue is transferred to the ethane diode salt of 4-methyl-2-pentanone. The salt is filtered off and crystallized in 3-methyl-5-pentan to give 16 parts of 1- [2- (2-chlorophenyl) -1,3-dioxolan-2-ylmethyl] -1H-1,2, A triazole ethanedioate, mp 156.5 ° C.

²⁰ Example 6. If you follow the procedure described in Example

5 ,. and using equivalent amounts of suitable starting material, the following 1,2, 3-triazolethanedioate salt can be prepared:

<img file="SE425246B_D0011.tif" />

<img file="SE425246B_D0012.tif" />

Acid salt (COOH)₉

Melting point

19'3.3 ° C

Example 7. A stirred mixture of 9 5 parts of 1H-1,2,4-triazole and

225 parts Ν, Ν-dimethylformamide are added portionwise with A, 2 parts of a sodium hydride dispersion (78?). The mixture is stirred until stirring ceases, then 16 parts of 2- (bromomethyl 1) -2- (2,4-dichlorophenyl) -4-propyl1,1,3-dioxolane are added and stirring is continued for 5 hours at reflux temperature. The reaction mixture is cooled and poured into water. The product is extracted three times with

2,2'-oxybispropane. The combined extracts are washed with water, dried, filtered and evaporated. The residue is purified by column chromatography over silica gel with a mixture of trichloromethane and methanol as eluent. The first fraction is collected and eluted *. »Wk '>

<img file="SE425246B_D0013.tif" />

the agent is evaporated. The residue is transferred to the nitrate salt in 2,2'-oxybispropane. The salt is filtered off and crystallized from a mixture of 2-nropanone and petroleum ether to give 8.2 parts (45%) of 1- [2- (2,4-dichlorophenyl) -4-propyl] -1,3-dioxolane-2 ylmethyl7-1H-1,245 triazole nitrate, mp 132.6 ° C.

Example 8. A stirred sodium methoxide solution prepared from 3.8 parts of sodium in 40 parts of methanol is added with 11.5 parts of 1H-1, 2,4-triazole and 225 parts of Ν, Ν-dimethylformamide. The methanol is distilled off until the internal temperature reaches 150 ° C.

¹⁰ After the addition of 19 parts of 2- (bromomethyl) -2- (2,4-dichlorophenyl) -4-ethyl1,3-dioxolane, it is stirred and refluxed for 4 hours. The reaction mixture is cooled and poured into water. The product is extracted three times with 2,2'-oxybispropane. The combined extracts are washed with water, dried, filtered and evaporated. The residue is purified by column chromatography over silica gel with a mixture of trichloromethane and 2% methanol as eluent. The first fraction is collected and the eluent is evaporated. The residue is transferred to the nitrate salt in 2,2'-oxybispropane. The salt is filtered off and recrystallized in a mixture of 4-methyl-2-pentanone and 2,2'-oxybispropane to give 10.5 parts (49 2) of 1- [2- (2,4-dichlorophenyl) -4- ethyl, 3-dioxolan-2-ylmethyl-7H-1,2,4-triazole nitrate, mp 119.8 ° C.

Example 9. Following the procedure described in Example 17j and using equivalent amounts of suitable starting material, the following 1,2,4-triazoleic acid addition salts can be prepared: 1- / 4-butyl-2- (2,4-dichlorophenyl) - l, 3 "dioxolan-2-ylmetyl71H-

1.2.4- triazole sesquietanedioate, mp 111.6 ° C · ,Z^,2- (2,4-dichlorophenyl) -4-pentyl-l, 3-dioxolan-2-ylmetyl.7-LH

1.2.4- triazole nitrate, mp 13O₈3 ° C;

1- / 2- (2,4-dichlorophenyl) -4-hexyl-l, 3-dioxolan-2-ylmetyl7-LH

1,2,4-triazole nitrate, mp 106.2 ° C;

1- / 2- (2,4-dichlorophenyl) -4-heptyl-l, 3^-dioxolan-2-yImetyl7-1H-

1,2,4-triazole nitrate, mp 96.8 ° C, and 1-Z2- (2,4-dichlorophenyl) 4-octyl-1,3-dioxolan-2-ylmethyl-7H-1H

1,2,4-triazole nitrate, mp 110.6^islandC.

Example 10. The process of Example 4 can be used to prepare compounds of formula (I) wherein Z represents -CH₂-CH (CH 2) or -CH (CH 2) -CH (CH 2) -. Accordingly, by adding an equivalent amount of suitable 2-aryl-2- (bromomethyl) -4-methyl-1,3-dioxolane or 2-aryl-2- (bromomethyl) -4,5-dimethyl-1,3-methyl dioxolane produces the following compound in the form of the nitrate salt:

1- / 4,5-dimethyl-2- (2,4-dichlorophenyl) -1,3-dioxolan-2-ylmethyl-7H1,2,4 “triazole;

7512643-3

Example · The process described in Example YES can be used to employ the compounds of formula (I) wherein Z represents “CH₂-CH₉-CH_p-. Accordingly, by adding an equivalent amount of suitable 2-aryl-2- (bromomethyl) -1,3-dioxane as starting material, the following compound can be obtained:

b 1-Z2- (2,4-dichlorophenyl) -1,3-dioxan-2-ylmethyl] -1H-1,2,4-triazolo

Example ii. The compositions of the present invention are used in the forms commonly used to control fungi or bacteria, e.g. such as suspensions, powders, solutions, creams and the like. The following examples are intended to further illustrate the invention and the parts are by weight unless otherwise indicated:

(1) Suspension:

kg of 1-Z'2- (2,4-dichlorophenyl) -1,3-dioxolan-2-ylmethyl] -7

1H-1,2,4-triazole lit. technically xylene

j.5 550 ml of surfactant water is diluted to the desired concentration of active ingredient,

1- / 2- (2,4-dichlorophenyl) -1,3-dioxolan-2-ylmethyl7-1H-1,2,4-triazole forms a stable aqueous suspension when dissolved in 2G xylene and emulsified with a surfactant .

(2) Powder1:

parts 1- [2- (2,4-dichlorophenyl) -1,3-dioxolan-2-ylmethyl] -1H1_s2,4-triazole is milled with 560 parts of talc in a ball mill, after which 8 parts of olein are added and the painting is continued and finalized. The mixture is mixed with 4 parts quenched lime. The powder formed can be sprayed satisfactorily and has good adhesive ability. It can be used for germination or for plant protection.

(3) Solution:

parts 1- [2- (2,4-dichlorophenyl) -1,3-dioxolan-2-ylmethyl] -1H50 1,2,4-triazole is dissolved in 95 parts alkylated naphthalene and used as a spray for treating fungal infected objects or on walls , floor or other objects to prevent fungal infection.

(4) Cream:

parts 1- / 2- (2,4-dichlorophenyl) -1,3-dioxolan-2-ylmethyl-7H35 1,2,4-triazole is dissolved in a hot liquid mixture of 400 parts of polyethylene glycol 400 and 590 parts of polyethylene glycol 1500. The solution stirred under cooling and used as a cream for treating fungi and bacteria.

HOCH,! &lt;Χ

<img file="SE425246B_D0014.tif" />

4-methylbenzenesulfonic acid C methylbenzene D>

(HNO)

<img file="SE425246B_D0015.tif" />

A mixture of 1.7 parts of 1,3-propanediol, 1 part of 4-methylbenzenesulfonic acid and 90 parts of methylbenzene is stirred and refluxed for 30 minutes with water separator. Then 7.1 parts of 1 / 2- (2,4-dichlorophenyl) -2,2-dimethoxyethyl7-1H-1,2,4-triazole-4-methylbenzenesulfonate are added and stirring under reflux is continued for 4 hours. The reaction mixture is cooled, diluted with 1,1'-oxybisethane and the whole washed with a dilute sodium hydroxide solution and with water. A concentrated hydrochloric acid solution is added and the nitrate salt precipitates. It is filtered off and crystallized from a mixture of propanol and 2,2'-oxybispropane to give 2.2 parts (39/5) of 1- / 2- (2,4-dichlorophenyl) -1,3-dioxan-2-ylmethyl7 LH-l, 2,4-triazolnitrat; mp 143.1 ° C.

<img file="SE425246B_D0016.tif" />

7512643-3

Eyempcl 14.

N

<td colspan="5">j</td>

<td>and., 1 2 H, -C-OCH 1 ³</td><td> CH, - /</td><td>; + CH, /</td><td>OH l -CH-</td><td>OH -CH-CH j</td>

<td>· -ΓΊ Γ il</td><td></td><td></td><td>F</td><td></td>

<td>k J</td><td></td><td></td><td></td><td></td>

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

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

<td>A</td><td>r ~;</td><td></td><td></td><td></td>

<td></td><td>N '1</td><td>Cl</td><td></td><td></td>

<td></td><td>^XN ' 1</td><td>L</td><td></td><td></td>

<td></td><td>-a-</td><td></td><td>-Cl</td><td>HNO,</td>

<td></td><td> 1</td><td>Ό 1</td><td></td><td> 3</td>

<td></td><td>/ HJC</td><td>\ CH 3</td><td></td><td></td>

4-Methylbenzenesulfonic acid methylbenzene (HNO₅)

A mixture of 1.8 parts of 2,3-butanediol, 1 part of 4-methylbenzenesulfonic acid and 90 parts of methylbenzene is distilled aseotropically to dryness (1 hour). Then 7.1 parts of 1- / 2- (2,4-dichlorophenyl) 2,2-dimethoxyethyl / -1H-1,2,4-triazole-4-methylbenzenesulfonate are added and stirred overnight at reflux temperature. The reaction mixture is cooled and diluted with a sodium hydroxide solution. The product is extracted with .1,1'-oxybispropane. The extract is washed with water, dried, filtered and evaporated. The residue is transferred to the nitrate salt in the 2,2'oxybispropane. The salt is filtered off and crystallized from a mixture of acetonitrile and 2,2'-oxybispropane. The product is filtered off and dried to give 4.6 parts of 1- [2- (2,4-dichlorophenyl) -4,5-dimethyl-1,3] -oxoian-E-ylmethyl] -1H-1,2,4-triazole mononitrate; melting point 1. · '' c.

7512643-3 λ ©