SE433496B - PROCEDURE FOR PREPARING A 1- (BETA-ARYL) ETHYL-1H-1,2,4-TRIAZOLKETAL - Google Patents

Description

10 15 20 25 30 8305128-4 -CH-CH- and -CH 2 -CH H54 m5 alkyl , wherein the alkyl group has from 1 to about 10 carbon atoms, and Ar represents 2,4-dihalophenyl.

The therapeutically active acid addition salts of the indicated the purifications (I) are also encompassed by the present invention.

The term "alkyl", as used in the definition given herein, of Z, is intended to include straight and branched chain hydrocarbon groups of 1 to about 10 carbon atoms, such as methyl, ethyl, 1-methylethyl, propyl, 1,1-dimethyl ylethyl, butyl, pentyl, hexyl, heptyl, octyl, decyl and the like; "lower alkyl" in the present case refers to straight or branched saturated carbon hydrogen having 1 to about 6 carbon atoms, such as methyl, ethyl, propyl, 1-methyl- ethyl, butyl, 1,1-dimethylethyl, pentyl, heiyl and similar alkyl groups per; the term "halo" includes halogen atoms with smaller atomic weights than 127, i.e. fluorine, chlorine, bromine and iodine.

The ketals of formula I are readily obtained according to the present invention. by 1H-1,2, Ä-triazole (II), previously converted to a metal salt, e.g. by treatment with an alkali metal alkoxide, preferably sodium methoxide, is reacted with a halide with the formula (III) Y-CHër; C <~ Ar O O \ Z / (III) wherein Ar and Z have the meanings given and Y represents halogen, tread bromine. The reaction between lñ-1,2,2-triazole (II) and (III) is advantageously carried out in a suitable zero reaction inert organic solvents such as N, N-dimethylformamide, N, N-dimethylacetamide, aceto- nitrile, 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. When Y bromine or chlorine, it is advisable to add an alkali metal talliodide, e.g. sodium or potassium iodide. Slightly elevated tempe- temperatures increase the reaction rate and preferably the reaction is carried out at the reflux temperature of the reaction mixture.

. The ketal formed of formula (I) is then isolated from the reaction medium. mixture by conventional methods and optionally purified further by any conventional purification procedure, for example by crystallization, extraction, trituration, chromatography, etc. 3 8305128-4 The specified procedure may be further impaired by way: N Y-csï- c-Ar I '' o \ o (111) * Å Nasr / le \ Z / H>> (II) Dnr, NaI (I) The compounds of formula (I) thus obtained, in basic form, can be transferred to therapeutically useful acid addition salts by reaction with a suitable acid, such as an inorganic acid, such as as a hydrogen halide, ie hydrogen chloride, hydrogen bromide or hydrogen iodide, sulfuric acid, nitric acid or thiocyanic acid, a phosphoric acid, an organic acid, such as acetic acid, propionic acid, hydroxyacetic acid, oxypropionic acid, 2-oxopropionic acid, oxalic acid, malonic acid, succinic acid Elic acid, maleic acid, fumaric acid, 2-hydroxy-succinic acid, 1,2,3-dihydroxy- succinic acid, 2-hydroxy-1,2,3-propanetricarboxylic acid; benzoic acid, Phenylpropionic acid, Hydroxybenzeneacetic acid, methanesulfonic acid, ethane sulfonic acid, hydroxyethanesulfonic acid, U-methylbenzenesulfonic acid, ßk = hydro- ,,., W9; iQçn§9ê $ ï§â ,, l: §m; n9; 3; hydroxihenS9ssyna ,, 2; iengxibanSQesyralellerr 2-acetyloxybenzoic acid. The salts are in turn transferred to the corresponding the free bases in the usual way, e.g. by reaction with alkali, so- 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 Z g, wherein Z represents a group -CH 2 -CH 2 -, -CH (CH 3) -CH 2 -, § -CH (CH3) -CH (CH3) - and -CH2-CH2-CH2- and methods of preparation of these compounds are described in U.S. Pat. No. 3,575,999 the compounds of formula (III) are prepared by a suitable One tone of formula (IV), wherein Ar and Y have the meanings given, ketalized With a suitable diol of formula (V) according to known ketalization methods. methods, which are described in the literature (see eg Synthesis, 1974 (1), 23) - According to a preferred method, the two reactants are refluxed together for several hours, azeotropically removing water in (39 a suitable organic solvent, preferably in the presence of a simple alcohol, such as ethanol, propanol, butanol, pentanol or similar and in the presence of a suitably strong acid, such as 4-methylbenzene- "sulfonic acid. Suitable organic solvents which may be used for for this purpose, for example, aromatic hydrocarbons such as benzene, methyl > Benzene, dimethylbenzene and the like, and saturated hydrocarbons such as cyclohexane. 9305126-4 CIO ' Ar- -CHZY + ε0-Z-OH U-methylbenzenesulfonic acid (III) butanol 477 (IV) (V) benzene The ketones of formula (IV) are known and can be prepared according to methods known to those skilled in the art.

From formula (I) it appears that several of the compounds according to The present invention has asymmetric carbon atoms in the structure and Consequently, they may exist under different stereochemical, optical isomeric forms. When an alkyl group is present in the U-position of the dioxolane nucleus is the carbon atom to which the alkyl group is attached, and the carbon but in the 2-position of the dioxolane nucleus asymmetric. The stereochemicals and the optical isomers of the compounds of formula (I) may be separated And isolated according to methods known to those skilled in the art. The specified iso- the merits 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. Before- The compounds of the invention are valuable in the treatment of 15 animals and humans¿_surpassed_by_pathogenic microorganisms, _together for the destruction of microorganisms on materials.

They are particularly useful because of their prophylactic similarity. as a curative and systemic effect. Their strong action against phyto- pathogenic fungi are more clearly illustrated by the results obtained 20 lits in the following experiments.

In several of these experiments the compound 1 - [? ~ (2, U-dichloro- phenyl) -1,3-dioxolan-2-ylmethyl] -1H-1,2,2-triazole, (I-a), such as a .representative type of the compounds of formula (I). .___ N I \ [Ry Cl ¿”2? ° \ @ - Ö ° 1 L__J (I-a) The compounds for which experimental results are given have not been given to limit the invention to these compounds but only for to exemplify the strong antifungal activity of all compounds within the scope of formula (I). in /// '{»' ši \ 1“ ä \ .Y '| 10 20 25 8305128-4 The compounds of formula (I) are also very active esters against large: number of fungi, which are pathogenic to humans and animals. Smile is for example, active against fungi such as fi icrosporum canis, Trichopnyton mentagrophytes, Trichophyton rubrum, Aspergillus fumigatus, Phialo- phora verucosa, Cryptococcus neoformans, Candida albicans, Candide tropicalis, etc. Late extraordinary beneficial effect against Candide albicans is clearer from the results obtained in the following experiments.

A. Effect of (I-a) on Candide attack on the demand of limes.

Young turkeys (lä days old) were artificially infected by that the requirement was forcibly added to a suspension containing 4,106 C.F.U. (colony forming units) of Candida albicans.

When the animals became infected, they either received their normal diet ( group), or a medicated feed, which contained 125 ppm off (I-a). Two weeks later all the turkeys were killed, cultures were made_of the requirement and the number of Candide colonies per gram require was calculated. ' The results are summarized in Table VI.

Table VI Number of colonies of Candida_albiçans per gram required by the turkeys treated with (I-a) - (125 ppm) or placebo.

Treatment Number of animals Number of Candida colonies I down grams require Comparison - 1,520,000 dj “r 2 âvë 700 3 3 132 000 U 1 909 D00 (I-a) 1 0 (125 ppm) 2U7 200 6 7U2 O In Table VI, the compound (I-a) i a concentration of 125 ppm particularly effective against attack so As can be seen from the results in relation to the corresponding untreated animals.

B. Effect of (I-a) on vaginal Candida infestation in rats In female rats weighing 100 g, eggs were removed. _ the toks and the uterus. the requirement About 3 weeks later, all animals were given a weak subcutaneous injection of 100 mg estradiolundecylate and the was injected intravaginally with a suspension containing 5,103 C.F.U. 15 20 3305128-4 6 of Candide albicans.

Groups of R rats were treated in shelters alternately the following days with either a solvent (PEG 205) or The administered dose of the compound was 39 mg / SEK in) (I-a). orally. Vaginal samples were taken from all animals at the end of treatment. (ie 1 days), and these were grown on Sabouraud agar medium, containing penicillin (20 I.U./ml) and Streptomycin (U0.pg/ml) and the number of Candida colonies was then counted.

Table VII summarizes the results obtained with (I-a) against vaginal Candide attacks in rats.

Table VII Number of animals per cultural population Treatment Number Day After Culture Assessment X) | animals, treatment line O l 2 3 H- Comparison ' (PEG 200) Ä 14 0 0 0 1 3 (I-a) (H0 mg / kg U lü 3 1 0 0 0 ~ .. w,. . -. --__- --- -. ,,.;.; ';' .., _ _ x) Culture assessment: 0 = no plant 1 = 1-25 colonies 2 = 26-100 colonies 3 => l00 colonies - H = countless colonies As can be seen from the results in Table VII, (I-a) is very ' effective against vaginal Candide anárepg in rats.

C, Effect of (I-a) on systemic Candida infestations in guinea pigs.

Male adult guinea pigs were infected intravenously with Candide albicans, which causes a general systemic candidiasis.

Subsequently, 7 guinea pigs were treated orally in shelter one after the other days with either solvent (PEG 200) or (I-a). The the dose used was H0 mg / kg body weight.

Four days after the last day of treatment, everyone was killed the animals, the kidneys were removed and grown on Sabouraud agar medium, containing penicillin (20 I.U./ml) and Streptomycin (NO / ug / ml) and the number of isolated colonies of Candida albicans per gram of kidney Table VIII shows the detailed results obtained with (I-a) against systemic deep mycosity in guinea pigs.i was counted. 10 15 20 8305128-4 7 Tahell Till l Treatment I Number in Number-Candide Coloniesq animal e per: rem kidney = Comparisons l 182 (PEG 209) 2 É 2335 3 '25220 U 385 5 19800 6_ 113 7 BUS (I-a) 1 0 (NO mg / kg 2 18 (orally) 3 0 Ä 0 S 0 6 53 7 0 From the results in Table VIII it can be concluded that (I-a) is an extremely potent agent against systemic deep mycosity 'in guinea pigs.

Due to the stated fungicidal and / or anti-fungal bacterial properties, according to the present invention provide valuable compositions comprising the present ketals (I) or acid addition salts thereof as the active ingredient in a solvent or a solid, semi-solid or liquid diluent agent or carrier material. In addition, the invention comprises an effective effective method of controlling fungal or bacterial growth by using of an effective bactericidal or fungicidal amount of such catheters clays (I) or salts thereof. The present compounds can be used in suitable solvents or diluents, in the form of emulsions, suspensions, dispersions or ointments, on suitable solids or semi-solid carriers, in natural or synthetic soaps, detergents or dispersion media, optionally together with other compounds with arachidicides, insecticides, ovicides, fungicides and / or bactericidal properties or together with inactive additives.

Solid carriers which are suitable for the manufacture of compositions in powder form, include various inert, porous and powdered dispersants of inorganic or organic nature. 10 20 25 '50 35 w 8305128-4 8 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 carriers. for example by grinding them thereby; alternatively, the inert is impregnated the carrier substance 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 preparations may also easily wettable with water, so that suspensions are held.

The inert solvents used in the preparation of liquids preparations should not be flammable and should be so far may be odorless and non-toxic to warm-blooded animals or for plants in the surrounding environment. Solvents, as appropriate for this purpose, high-boiling oils, e.g. of vegetable origin and low boiling point solvents with a flash point of at least 30 ° C, such as polyethylene glycol, visopropanol, dimethyl sulfoxide, hydrogenated naphtha alenes and alkylated naphthalenes. Of course it is also possible to use mixtures of solvents. in the usual way and, if necessary, use solution promoters Other liquid forms which may be used consist of The solutions can be prepared funds. emulsions or suspensions of the active compound in water or suitable inert solvents, or concentrates for the preparation of positioning of such emulsions, which can be directly adjusted to the desired concentration. For this purpose you can, for example, mix it active ingredient with a dispersant or emulsifier agent._ The active component can also be dissolved or dispersed l a suitable inert solvent and simultaneously or thereafter mixed with a dispersant or emulsifier.

It is also possible to use semi-solid carriers ointment-like, paste-like or wax-like nature, in which the active the component is incorporated, if necessary, by means of solution-promoting agents and / or emulsifiers. Vaselín and other ointment bases are _examples of semi-solid carriers. oIt is also possible to use the active ingredient in form of aerosols. For this purpose, it is dissolved or dispersed active ingredient, if necessary by means of appropriate inert 10 15 20 25 STAY 35 H0 8305128-4 solvents such as carrier liquids, e.g. difluorodichloromethane, as in atmospheric pressure boils at a temperature below room temperature, or in other volatile solvents. In this way, solutions are obtained pressures which, when sprayed, produce aerosols which are particularly suitable for for the regulation or control of fungi, bacteria, e.g. in enclosed spaces and storage rooms, The present compounds and their compositions can be applied as with conventional methods. Fungi or bacteria or one materials to be treated or protected against fungal attack or bacteria, can be treated with the present compounds and com- its positions by dusting, sprinkling, spraying, brushing dipping, dipping, lubrication, impregnation or other suitable means.

When the present compounds are used together with suitable carrier, tlex. in solution, suspension, powder, powder, ointment, emulsion and similar forms, high activity is observed within a_much large dilution range. So, for example, have concentrations of it active ingredient of 0.1 to 10% by weight, by weight of the composition used, has been shown to be effective in controlling fungi or bacteria. Of course, higher concentrations can also can be used if a certain situation gives rise to it.

The following examples are intended to illustrate, but not to limit, present invention. Unless otherwise stated, this applies to all parts parts by weight. _ Example 1. A stirred and cooled (0 ° C) solution of 30 parts of 1- (N-amino- -2-methoxyphenyl) ethanone in 360 parts of concentrated hydrochloric acid solution, 75 parts of water and 30 parts of acetic acid are diazotized with a solution of 17.25 parts of sodium nitrite in 200 parts of water. After stirring for 30 minutes at 0 ° C, pour the whole into a solution of 50 parts copper (I) - chloride in 2H0 parts of concentrated hydrochloric acid solution with stirring.

The mixture is heated for 1 hour at 60 ° C. When the product has cooled down at room temperature it is extracted twice with 2,2'-oxybispropane. The the combined extracts are washed successively with water, a dilute sodium hydroxide solution and then again twice with water, dried, filtered and evaporated to give 28 parts (76 2) 1- (N-chloro-2-methoxyphenyl) ethanone, mp 55 ° C.

Example 2. 57 parts of 1- (2,1H-dibromophenyl) -1-ethanone are dissolved in 220 parts 1,2-ethanediol at 50 ° C. While stirring, add dropwise over one 1-hour period 6ü divides bromine without external heating. After stirring for 1 hour at room temperature, H parts of β-methylbenzenesulfonate are added. 8305128-4 10 15 20 25 30 35 HO 10 acid and 360 parts benzene. The whole is stirred and refluxed over at night during separation of water. The reaction mixture is evaporated and the residue is taken up in 2,2'-oxybispropane. The solution formed wash successively once with dilute sodium hydroxide solution and three times with water, dried, filtered and evaporated, 73.3 parts (6.5.5%) of 2- (bromomethyl) -2- (2,1-dibr phenyl) -1,3-dioxolane; mp 9600.

Example 3.

A. A stirred solution of 2.3 parts of sodium in 120 parts of methanol was added with 6.9 parts of 1H-1,2,4-triazole in 150 parts of dimethylformamide. the ethanol is removed at normal pressure until the internal temperature rises goes to 13000. Then 25 parts 2- (bromomethyl) -2- (2, H- dichlorophenyl) -1,3-dioxolane. The reaction mixture is stirred and returned boiled for 3 hours. It is allowed to cool to room temperature and read in 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-1,2,1-triazole, sm; 90.9 ° C.

B. 6 parts 1- [2- (2,0-dichlorophenyl) -1,5-dioxolan-2-ylmethyl] -1H- 1,2, α-triazole was converted to the nitrate salt in 2,2'-oxybispropane. Ef- After cooling, the salt is filtered off and crystallized twice 2-propanone to give 3 parts of 1- [2- (2, H-dichlororenyl) -1,3- dioxclan-2-ylmethyl] -la-1,2,1-thiazole nitrate, mp 172.7 ° C. c. 6 parts of 1- [2- (2,1-cyclophenyl) -1,3-cycloalan-2-ylmenyl] -15- 1,2, N-triazole is converted to the sulphate salt in 2,2'-oxybispropane. The The sulphate formed is filtered off and crystallized from 2-propanol.

The product is filtered off and recrystallized from ethanol (activated carbon) whereby after drying 6 parts of 1- [2- (2,1-dichlorophenyl) - 1,3-dioxolan-2-ylmethyl-1H-1,2,2H-triazole sulfate, mp 207,1 ° C.

Ekemnel U. A stirred solution of 2.3 parts of sodium in SO nol is added with 6.9 parts of 1H-1,2,2-triazole and 2 parts of sodium iodide in 100 parts N, N-dimethylformamide. the ethanol is removed at ground pressure until the internal temperature reaches 130 ° C. Then 3a, u parts 2- (bromomethyl) -2- (2,1-N-dichlorophenyl) -N-methyl-1,3- IIEâL-í * dioxolane and the whole is stirred and refluxed for 3 hours. The ionic mixture is poured into water and the product is extracted twice The extract is washed with water and an excess is added. with diisopropyl ether. of a concentrated nitric acid solution The crude nitrate salt filtered off and crystallized from a mixture of 2-propanol and 10 15 20 25 8305128-4 11 Example 5. A stirred sodium methoxide solution, prepared starting from from 2.8 parts of sodium in 56 parts of methanol, was added with one mixture of 8.3 parts of lä-1,2, U-triazole and 135 parts of N, N-dimethyl- The methanol is removed at normal pressure until its internal Then a mixture is added formamide. the temperature is 130 ° C. of 27.8 parts of 2- (bromomethyl) -2- (2-chlorophenyl) -1,3-dioxolane and 3 parts of lar potassium iodide. The whole is stirred and refluxed for 5 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'-oxibis- The combined extracts are washed twice with water, dried, the remainder is transferred to ethandicdatsal- of U-methyl-2-pentanone. The salt is filtered off and crystallized from U-methyl-2-pentanone to give 16 parts of 1- [2- (2-chlorophen- yl) -1,3-dioxolan-2-ylmethyl] -1H-1,2,3-triazole ethanediodate, mp 125.5 ° C.

Example 6, Following the procedure described in Examples 5, _ and uses equivalent amounts of suitable starting material, ethane. filtered and evaporated. the following 1,2, H-triazolethane diode salt can be prepared; Ü ' A N \ N IN ° "2? <Â * ' .___ L Ar Acid salt Melting point 2, u- (Br) 2-c6H5 (cooH) 2 19o.3 ° c Example 7¿ A stirred mixture of 9.5 parts of 1H-1,2, β-triazole and 225 parts of N, N-dimethylformamide were added portionwise with ,2 parts of a sodium hydride dispersion (78 Z). The mixture is stirred until then the evolution of smoke ceases, after which 16 parts of 2 ~ (bromine methyl) -2- (2,0-dichlorophenyl) -U-Pbopyl, 1,5-dioxolane and stirring 5 hours at reflux temperature. Reaction mixture one is cooled and poured into water. The product is extracted three times The combined extracts are washed with water, dried, continued in 2,2'-oxybispropane. filtered and evaporated. the residue is purified by column chromatography l .- See" over silica gel with a mixture of trichloromethane and 2 2 methano 10 15 20 25 30 8305128-4 12 as eluent {'The first fraction is collected and eluted the agent evaporates. the residue is transferred to the nitrate salt in 2,2'-oxi- bispropane. The salt is filtered off and crystallized from a mixture of 2-propanone and petroleum ether to give 8.2 parts (RS 2) III - (2,1H-dichlorophenyl) -N-propyl-1,3-dioxolan-2-ylmethyl] -1H-1,2, H- mp 152.6 ° C. stirred sodium methoxide solution prepared triazole nitrate S; c- (N , Example 8. En from 3.8 parts of sodium in HO parts of methanol, was added with 11.5 parts 1H ~ 1,2, U-triazole and 225 parts Methano- The mixture is distilled off until the internal temperature reaches 150 ° C.

After addition of 19 parts of 2- (bromomethyl) -2- (2,1-dichlorophenyl) = U-ethyl- Reactive R, N-dimethylformamide. 1,3-dioxolane, the whole is stirred and refluxed for B hours. The mixture is cooled and poured into water. The product is extracted three times with 2,2'-okíbispropane. The combined extracts are washed evaporate. the residue is purified with with a mixture of trichloromethane with water, dried, filtered and column chromatography over silica gel and 2% methanol as eluent. The first fraction is and the eluent is evaporated. the residue is transferred to nitrate the salt in 2,2'-oxybispropane. The salt is filtered off and crystallized. in a mixture of U-methyl-2-pentanone and 2,2'-oxybispropane, to give 10.5 parts of (H9 5) 1- [2- (2, H-dichlorophenyl) -H-ethyl- 1,3-dioxolan-2-ylmethyl] -1H-1,2,3-triazole nitrate, mp 119.8 ° C. šxemnel 9- If you follow the procedure described in the example B and uses equivalent amounts of suitable starting material the following 1,2, U-triazolic acid addition salts can be prepared: 1- [U-butyl-2- (2,1-dichlorophenyl) -1,5-dioxolan-2-ylmethyl] 1H- 1,2, U-triazole sesquietanedioate, mp III, 6 ° C; 1- (2- (2,8-Aichloro-phenyl) -u-pentyl-1,3-oxo-ol-2-ylmethyl] -15- 1,2, U-triazole nitrate, mp 130.3 ° C; 1-12- (2,1-dichlorophenyl) -H-hexyl-1,3-dioxolan-2-ylmethyl] -1H- 1,2,2-triazole nitrate, mp 106.2 ° C; 1- [1- (2,1-Dichlorophenyl) -N-heptyl-1,3-dioxolan-2-ylmethyl] -1H- 1,2 H-triazole nitrate, mp 96.8 ° C, and 1-Lä IN - (2,1H-dichlorophenyl) -β-octyl-1,3-dioxolan-2-ylmethyl7-1H- 1,2,6-triazole nitrate, mp 110.6 ° C.

Eïêm fl el 10.f The procedure of Example 4 can be used to prepare compounds of formula (I), wherein Z represents -C 2 -CH (CH 5) - or -CH (CS3) -CE (CH5) -. Consequently, by inserting one equivalent amount of suitable 2-aryl-2- (bromomethyl) -α-methyl-1,3-dioxolane or 2'a? yl ~ 2 ~ (bromomethyl) -U, 5 ~ dimethyl-1,3-dioxolane prepare e.g. 10 15 20 25 30 35 8305128-4 15 the following compound in the form of the nitrate salt: 1- [W, 5-dimethyl-2- (2,0-dichlorophenyl) -1,5-dioxolan-2-ylmethyl] -leach 1,2,5 "tr1azole; Example 11. The procedure described in Example 3-A can be used for the preparation of the compounds of formula (I) wherein Z represents -c: '-.

I 2 “z amount of suitable 2-aryl-2- (bromomethyl) -1,3-dioxane as a starting material -C32-CH Consequently, by inserting an equivalent obtain the following compound: 1- [2- (2,1-dicaracinyl) -1,3-dioxan-2-ylmethyl] -1H-1,2,1-triazcyl; Example 12: The compositions of the present invention are used were in the forms commonly used to control fungi or bacteria, e.g. such as suspensions, powders, solutions, crystals more and the like. The following examples are intended to further illustrate the invention and the parts are by weight unless otherwise indicated: (1) Suspension: 1 kg 1-Z 2 - (2,1-dichlorophenyl) -1,1-dioxolan-2-ylmethyl] - 1H-1,2,2-triazole 2 lit. technically xylene 350 ml of surfactant water is diluted to the desired concentration of active stand. 1- [2- (2,4-dichlorophenyl) -1,3-dioxolan-2-ylmethyl] -1H-1,2,2-tri- the azole forms a stable aqueous suspension when dissolved in xylene and emulsified with a surfactant. (2) Becudri gsmedelz 20 parts of 1-Z 2 - (2,5-dichlorophenyl) -1,3-dioxolan-2-ylmethyl] -1- l} 2, U-triazole is ground with 560 parts of talc in a ball mill, after which 8 parts olein are added and grinding is continued and finally mixed The powder formed can das the mixture with ~ parts slaked lime. sprayed satisfactorily and has good adhesion. It can be used for powdering or for protecting plants. (3) Solution: 5 parts 1- [2- (2,0-dichlorophenyl) -1,3-dioxolan-2-ylmethyl] -1H- 95 parts of alkylated naphthalene con were thus used. 1, 2, ü-triazole is dissolved in as a spray for the treatment of fungal-infected objects or on the road floors, floors or other objects to prevent fungal infection.

W 10 parts of 1-Z 2 - (2,1-dichlorophenyl) -1,5-dioxolan-2-ylmethyl 1,2, H-triazole is dissolved in a hot liquid mixture of H00 parts of poly- 8-305128-4 leeward ethylene glycol 400 and 590 parts of polyethylene glycol 1500. The solution stirred under cooling and used as a cream for treating fungal infections. couples and bacteria. _

Claims (6)

IS '8305128-4 gatentkrav A process for the preparation of a chemical compound having fungicidal and / or bactericidal activity for medical use, which compound consists of 1- (β-aryl) ethyl-1H-1,2,4-triazole ketal of the formula NI \ N / 1 CH 2 Or therapeutically active acid addition salts thereof, wherein Z represents alkylene consisting of -CH 2 -CH 2 -, -CH 2 -CH 2 -CH 2 -, -CH (CH 3) -CH (CH 3) - or -CH 2 -CH (alkyl) -, wherein the alkyl group has 1 to 10 carbon atoms and Ar represents 2,4-dihalophenyl, characterized in that a metal salt of a compound of the formula § __: ï II \ NH is brought to reacting with a compound of the formula Y-CH2__1> 0¿__ Ar (M9 wherein Y represents the analogue, preferably in a suitable polar reaction inert solvent at elevated temperatures and that any therapeutically active acid addition salts of these products are prepared. 2. A process for the preparation of a compound consisting of 1-β- (2,4-dichlorophenyl) -1,3-dioxolan-2-ylmethyl] -1H-1,2,4-triazole or therapeutically active acid addition salts characterized in that 1H-1,2,4-triazole is reacted with a 2- (bromomethyl) -2- (2,4-dichlorophenyl) -1,3-dioxolane and that any therapeutically active acid addition salts thereof produced. Process for the preparation of 1- [2- (2,4-dichlorophenyl) -4-methyl-1,3-dioxolan-2-ylmethyl] -1H-1,2,4-triazole or therapeutically active acid addition salts thereof, characterized in from reacting 1H-1,2,4-triazole with 2- (bromomethyl) -2- (2,4-dichlorophenyl-4-methyl-1,3-dioxolane and therapeutically). »Av. -F .- sn. S. No - ~ -» g,..: Ua- | v nu.. 1 u 1 vvnu - un gnnnnn ~ ou - nn: n um: su 0: -. N ' a3øs12s-4, b active acid addition salts thereof may be prepared. A process for the preparation of 1- [E- (2,4-dichlorophenyl) -4-ethyl-1,3-dioxolan-2-ylmethyl] -1H-1,2,4-triazole or therapeutically active acid addition salts thereof characterized in that 1H-1,2,4-triazole is reacted with 2- (bromomethyl) -2- (2,4-dichlorophenyl) -4-ethyl-1,3-dioxolane and that therapeutically active acid addition salts thereof may be prepared. A process for the preparation of 1- [4- (2,4-dichlorophenyl) -4-propyl-1,3-dioxolan-2-ylmethyl] -1H-1,2,4-triazole or therapeutically active acid addition salts thereof, characterized in that 1H-1,2,4-triazole is caused to react with Z-bromomethyl) -Z- (2,4-dichlorophenyl) -4-propyl-1,3-dioxolane and that therapeutically active acid addition salts of which may be produced. Process for the preparation of 1- [E- (2,4-dichlorophenyl) -4-pentyl-1,3-dioxolan-2-ylmethyl] -1H-1,2,4-triazole or therapeutically active acid addition salts thereof , characterized in that 1H-1,2,4-triazole is caused to react with 2- (bromomethyl) -2- (2,4-dichlorophenyl] -4-pentyl-1,3-dioxolane and that therapeutically active acid addition salts thereof may be prepared.