# Patent

## Title
1,2,4-oxadiazolyl-phenoxyalkylisoxazoles and their use as antiviral

## Abstract

The invention relates to the use of certain 1-[2-pyri(mi)dyl]-5-hydroxy-pyrazoles which are characterized by formula (I) given in the description, as microbicides for the protection of industrial materials, and to certain novel 1-[2-pyri(mi)dyl]-5-hydroxy-pyrazoles which are characterized by formula (II) given in the description.

## Background
The invention relates to the use of certain 1-[2-pyri(mi)dyl]-5-hydroxy-pyrazoles as microbicides for the protection of industrial materials, and to certain novel 1-[2-pyri(mi)dyl]-5-hydroxy-pyrazoles.

U.S. Pat. No. 4,663,327 discloses 1-hetaryl-4-aryl-pyrazolin-5-ones, for example 1-[2-pyri(mi)dyl]-4-phenyl-pyrazolin-5-ones, and their microbicidal properties. However, since the compounds are coloured and result in discolourations when incorporated into industrial materials, for example paints and plastics, they cannot be used in the protection of materials in spite of their good microbicidal properties.

In Japanese Application J.A-A 62/149,617 (CA Vol. 108, 11 247 k) which has been published, there are furthermore described 1-hetaryl-pyrazolin-5-ones, for example 1-[2-pyri(mi)dyl]-pyrazolin-5-ones, and their use as pharmaceuticals.

Other compounds which are still used to date for imparting fungicidal properties to plastics are organoarsenic compounds, even though the replacement of these compounds and also of the organomercury compounds which are still used in paints is highly desirable for ecotoxicological reasons. However, no ecotoxicologically more favourable compounds have been found to date which meet the high demands which must be made of microbicides which can be used for imparting microbicidal properties to plastics. Indeed, such microbicides must have resistance to high temperatures, besides a good microbicidal activity, and must furthermore not adversely affect the properties of the plastics.

It has now been found that 1-[2-pyri(mi)dyl]-5-hydroxypyrazoles of a particular formula have a microbicidal action in plastics and paints which equals that of the organoarsenic and organomercury compounds and which furthermore have the required thermal stability and which moreover meet the demands of being ecotoxicologically acceptable and do not adversely affect the properties, for example colour and elasticity, of the plastics, paints and coatings to which these compounds have been added.

The invention therefore relates to the use of 1-[2-pyri(mi)dyl]-5-hydroxy-pyrazoles of the formula ##STR1## in which R represents hydrogen, or an optionally substituted alkyl, aralkyl or alkoxy group, alkinyl, cycloalkyl, aralkyl, alkoxy, alkylmercapto, aralkoxy, aralkylmercapto, aryloxy, arylmercapto, alkoxycarbonyl or aminocarbonyl group, or R.sub.1 together with R forms a divalent alk(en)ylene radical which has 3 to 6 C atoms in the chain, alkyl, alkoxy, alkylmercapto, alkoxycarbonyl or aminocarbonyl group, identical or different radicals when n is 2 or 3, and materials.

Preferably used 1-[2-pyri(mi)dyl]-5-hydroxy-pyrazoles of the formula (I) are those in which aralkyl, alkoxy, aralkylmercapto or alkoxycarbonyl.

Particularly preferred 1-[2-pyri(mi)dyl]-5-hydroxypyrazoles of the formula (I) are those in which -cycloalkyl, C.sub.1 -C.sub.6 -alkoxy, optionally substituted benzyl, C.sub.1 -C.sub.6 -alkoxycarbonyl or benzylmercapto.

Very particularly preferred are the 1-[2-pyri(mi)dyl]-5-hydroxy-pyrazoles of the formula (I) when, in this formula, ethoxycarbonyl.

Novel compounds from amongst the 1-[2-pyri(mi)dyl]-5-hydroxy-pyrazoles to be used according to the invention are those of the formula (II).

The invention therefore also relates to novel 1-[pyri(mi)dyl]-5-hydroxy-pyrazoles of the formula ##STR2## in which X represents CH or N, -aralkyl or alkoxy group, and -alkyl, alkenyl, alkinyl, cycloalkyl, aralkyl, alkoxy, alkylmercapto, aralkoxy, aralkylmercapto, aryloxy, arylmercapto, alkoxycarbonyl or aminocarbonyl group, or R.sub.1 ' together with R' forms a divalent alk(en)ylene radical which has 3 to 6 C atoms in the chain,

with the proviso that R' and R.sub.1 ' do not simultaneously represent hydrogen.

Typical representatives of the pyrazoles of the formula (I) which can be used according to the invention and of the pyrazoles of the formula (II) according to the invention are listed in the examples.

The pyrazoles of the formula (I) which are to be used according to the invention and the novel pyrazoles of the formula (II) according to the invention can also exist in their tautomeric pyrazolin-5-one form.

The following may be mentioned as optionally substituted alkyl radicals for R and R.sub.1 : C.sub.1 -C.sub.12 -alkyl groups such as methyl, ethyl, n- and i-propyl, n-butyl, i-pentyl, hexyl, i-octyl, n-decyl and n-dodecyl; suitable substituents for these alkyl radicals are mainly halogen atoms, preferably chlorine or fluorine, furthermore C.sub.1 -C.sub.4 -alkoxy and C.sub.1 -C.sub.6 -alkoxycarbonyl groups. Examples of representatives of the substituted alkyl radicals are the difluoromethyl, trifluoromethyl and monochlorodifluoromethyl radical, furthermore the methoxymethyl and the methoxycarbonylmethyl and the ethoxycarbonylmethyl radical.

The following may be mentioned for R, R.sub.1, R' and R.sub.1 ':

As optionally substituted aralkyl groups, the benzyl, .alpha.-methylbenzyl, .alpha.,.alpha.-dimethylbenzyl, 2-phenylethyl and the .alpha.- and .beta.-naphthylmethyl radical, and benzyl radicals which are substituted by halogen, in particular chlorine and fluorine, C.sub.1 -C.sub.4 -alkyl, in particular methyl, ethyl, trifluoromethyl, difluorochloromethyl, difluoromethyl and trichloromethyl, and by C.sub.1 -C.sub.4 -alkoxy, in particular methoxy, ethoxy, trifluoromethoxy, difluorochloromethoxy and difluoromethoxy, C.sub.1 -C.sub.4 -alkylmercapto such as methylmercapto, trifluoromethylmercapto, difluorochloromethylmercapto, nitro and/or cyano.

As optionally substituted alkoxy groups: C.sub.1 -C.sub.12 -alkoxy groups such as the methoxy, ethoxy, butoxy and hexoxy group.

The following may be mentioned for R.sub.1 and R.sub.1 ':

As an optionally substituted alkenyl group, the allyl group;

as optionally substituted alkinyl groups, the propinyl, 1-iodo-propinyl and the 3,3-dimethylpropinyl group; as optionally substituted cycloalkyl groups, C.sub.3 -C.sub.7 -cycloalkyl groups, in particular cyclohexyl radicals which are substituted by C.sub.1 -C.sub.4 -alkyl groups or by halogen, such as the cyclohexyl radical, the methylcyclohexyl, the dimethylcyclohexyl and the 1,3,3-trimethylcyclohexyl and the 3-chlorocyclohexyl radical;

as optionally substituted alkylmercapto groups, C.sub.1 -C.sub.2 -alkylmercapto groups which are substituted by halogen, such as the methylmercapto, trifluoromethylmercapto, difluoromethylmercapto and the difluorochloromethylmercapto group;

as aralkoxy groups, the benzyloxy group and benzyloxy groups which are substituted by halogen and C.sub.1 -C.sub.4 -alkyl radicals;

as aralkylmercapto groups, the benzylmercapto group and the benzylmercapto groups which are substituted by halogen and/or C.sub.1 -C.sub.4 -alkyl;

as aryloxy groups, the phenoxy group and phenoxy groups which are substituted by halogen, C.sub.1 -C.sub.4 -alkyl, C.sub.1 -C.sub.2 -halogenoalkyl, cyano, nitro, trifluoromethyl and difluoromethyl;

as arylmercapto groups, the phenylmercapto group and the phenylmercapto groups which are substituted by halogen, C.sub.1 -C.sub.4 -alkyl, C.sub.1 -C.sub.2 -halogenoalkyl, cyano and nitro;

as alkoxycarbonyl groups, C.sub.1 -C.sub.6 -alkoxycarbonyl groups, such as the methoxycarbonyl and ethoxycarbonyl group; as aminocarbonyl group, the carboxamido, N-methylcarboxamido and N,N-dimethylaminocarboxamido group;

as alk(en)ylene radicals which have 3 to 6 C atoms in the chain, the ethylene, 1,3-propylene, 1,4-butylene and the 1,4-butadiene-(1,4)ylene radical.

Optionally substituted alkyl radicals for R.sub.2 which may be mentioned are C.sub.1 -C.sub.4 -alkyl and C.sub.1 -C.sub.2 -halogenoalkyl radicals, such as the methyl, trifluoromethyl, difluoromethyl and difluorochloromethyl radical.

The pyrazoles of the formula (I) which are to be used according to the invention and the novel pyrazolines of the formula (II) according to the invention can be prepared by condensation reactions which are known per se, for example those described in Chem. Ber. 38 (1905) 2104; Bull. Soc. Chim. France 1967, 3780-92. These condensation reactions proceed following the reaction scheme below: ##STR3## If appropriate, the condensation can be carried out in the presence of a solvent; solvents which have proved suitable are mainly alcohols, such as ethanol, or aromatic hydrocarbons, such as toluene.

To facilitate the cyclisation reaction, it is advantageous to add bases, such as sodium hydroxide, potassium hydroxide or potassium tert.-butylate.

The condensation reaction can be carried out within a substantial temperature range. Hydrazone formation, which proceeds first, can be carried out at temperatures from 20 to 110.degree. C., preferably between 60 and 90.degree. C. The cyclocondensation reaction, which proceeds after the base has been added, can be effected at temperatures from 20 to 100.degree., preferably 20 to 40.degree. C. Since the addition of bases proceeds exothermally in some cases, cooling may be necessary in this reaction step.

The 1-[2-pyri(mi)dyl]-5-hydroxy-pyrazoles are isolated from the reaction mixtures using known methods. In general, a procedure is followed in which the reaction mixtures are freed from the solvent and the residue is treated with aqueous hydrochloric acid. The pyrazoles which precipitate during this process are separated off by filtration by suction. However, it is also possible to pour the reaction mixture directly into a large excess of dilute hydrochloric acid and to filter off the pyrazoles which separate out as a precipitate.

The starting compounds required for the condensation reaction, optionally .alpha.-substituted .beta.-ketocarboxylic esters or .alpha.-formylcarboxylic esters and 2-hydrazinopyri(mi)dines, are either known compounds or can be prepared analogously to known compounds by above-described processes.

The industrial materials to be protected according to the invention are non-living materials which have been prepared for use in industry. For example, industrial materials which are intended to be protected by active compounds according to the invention from microbial change or destruction can be glues, sizes, paper and board, textiles, leather, wood, paints, plastics and plastic articles, cooling lubricants and other materials which can be infested with, or destroyed by, microorganisms. Parts of production plants, for example cooling-water circuits, whose function may be impaired by the multiplication of microorganisms, may also be mentioned within the scope of the materials to be protected. Industrial materials which may be mentioned within the scope of the present invention are preferably paints, plastics and plastic articles.

Microorganisms, capable of bringing about degradation of, or change in, the industrial materials, which may be mentioned are, for example, bacteria, fungi, yeasts, algae and slime organisms. The active compounds according to the invention preferably act against fungi, in particular moulds, and against fungi which discolour and destroy wood permanently.

Microorganisms of the following genera may be mentioned as examples:

Depending on the field of application, the active compounds which are to be used according to the invention can be converted into the customary formulations, such as solutions, emulsions, suspensions, powders, pastes and granules.

These can be prepared in a manner known per se, for example by mixing the active compounds with an extender which consists of liquid solvent and/or solid carriers, optionally with the use of surface-active agents, such as emulsifiers and/or dispersants, it being possible, if appropriate, for organic solvents such as alcohols to be used as auxiliary solvents in the event that water is used as the extender.

Liquid solvents for the active compounds can be, for example, water, alcohols, such as lower aliphatic alcohols, preferably ethanol or isopropanol, or benzyl alcohol, ketones, such as acetone or methyl ethyl ketone, liquid hydrocarbons, such as petroleum fractions, or halogenated hydrocarbons, such as 1,2-dichloroethane.

The microbicidal agents used for the protection of industrial materials contain the active compounds in general in an amount from 1 to 100% by weight, preferably from 10 to 90% by weight.

The use concentrations of the active compounds which are to be used according to the invention depend on the nature and the occurrence of the microorganisms to be controlled, and on the composition of the material to be protected. The optimum amount for use can be determined by serial tests. In general, the use concentrations are in the range from 0.001 to 5% by weight, preferably from 0.05 to 1.0% by weight, relative to the material to be protected.

The active compounds which are to be used according to the invention can also be used as a mixture with other known active compounds. The following active compounds may be mentioned by way of example: benzyl alcohol mono(poly)hemiformal and other formaldehyde-releasing compounds, benzimidazolyl-methylcarbamates, tetramethylthiuram disulphide, zinc salts of dialkyldithiocarbamates, 2,4,5,6-tetrachloroisophthalonitrile, thiazolylbenzimidazole, mercaptobenzothiazole, 2-thiocyanatomethylthiobenzothiazole, methylene bisthiocyanate, and phenol derivatives such as 2-phenylphenol, (2,2' -dihydroxy-5,5'-dichloro)-diphenylmethane and 3-methyl-4-chloro-phenol, organotin compounds, N-trihalogenomethylthio compounds, such as folpet, fluorofolpet and dichlofluanid, azole fungicides such as triadimefon, triadimenol and bitertanol, tebuconazole, propiconazole and prochloraz, and also iodopropargyl compounds such as jodpropargylbutyl-carbamat.

Moreover, the active compounds according to the invention in particular those of the examples listed, can be present as a mixture with other active compounds, such as insecticides, attractants, sterilants, acaricides, nematicides, fungicides, growth-regulating substances or herbicides, in their commercially available formulations and in the use forms prepared from these formulations.

The insecticides include, for example, phosphates, carbamates, carboxylates, formamidines, tin compounds, substances produced by microorganisms, etc. Preferred components for mixtures are the following:

azinphos-ethyl, azinophos-methyl, 1-(4-chlorophenyl)-4-(O-ethyl, S-propyl)phosphoryloxypyrazole (TIA-230), chlorpyrifos, coumaphos, demeton, demeton-S-methyl, diazinon, dichlorvos, dimethoate, ethoprophos, etrimfos, fenitrothion, fenthion, heptenophos, parathion, parathion-methyl, phosalone, pirimiphos-ethyl, pirimiphosmethyl, profenofos, prothiofos, sulprofos, triazophos and trichlorphon.

aldicarb, bendiocarb, BPMC (2-(1-methylpropyl)phenylmethylcarbamate), butocarboxim, butoxicarboxim, carbaryl, carbofuran, carbosulfan, cloethocarb, isoprocarb, methomyl, oxamyl, pirimicarb, promecarb, propoxur and thiodicarb.

allethrin, alphamethrin, bioallethrin, bioresmethrin, cycloprothrin, cyfluthrin, cyhalothrin, cypermethrin, deltamethrin, alpha-cyano-3-phenyl-2-methylbenzyl 2,2-dimethyl-3-(2-chloro-2-trifluoromethylvinyl) cyclopropanecarboxylate (FMC 54800), fenpropathrin, fenfluthrin, fenvalerate, flucythrinate, flumethrin, fluvalinate, permethrin, resmethrin, tralomethrin.

amitraz and chlordimeform

azocyclotin, cyhexatin and fenbutatin oxide

abamectin, Bacillus thuringiensis, bensultap, binapacryl, bromopropylate, buprofecin, camphechlor, cartap, chlorobenzilate, chlorfluazuron, 2-(4-chlorophenyl)-4,5-diphenylthiophene (UBI-T 930), chlofentezine, 2-naphthylmethyl cyclopropanecarboxylate (Ro 12-0470), cyromacin, DDT, dicofol, N-(3,5-dichloro-4-(1,1,2,2-tetrafluoroethoxy)phenylamino)carbonyl)-2,6-dif luorobenzamide (XRD 473), diflubenzuron, N-(2,3-dihydro-3-methyl-1,3-thiazol-2-ylidene)2,4-xylidine, dinobuton, dinocap, endosulfan, fenoxycarb, fenthiocarb, flubenzimine, flufenoxuron, gamma-HCH, hexythiazox, hydramethylnon (AC 217 300), ivermectin, 2-nitromethyl-4,5-dihydro-6H-thiazine (SD 52618), 2-nitromethyl-3,4-dihydrothiazole (SD 35651), 2-nitromethylene-1,3-thiazinan-3-yl-carbamaldehyde (WL 108 477), propargite, teflubenzuron, tetradifon, tetrasul, thiocyclam, triflumaron, and nuclear polyhedrosis and granulosis viruses.

A mixture of 7.2 g of ethyl propionylacetate, 5.4 g of 2-hydrazinopyridine and 200 ml of ethanol is refluxed for 3 hours, with stirring. The reaction mixture is then cooled to 20 to 30.degree. C., and, with stirring, treated with 5.8 g of potassium tert.-butylate. After the mixture has been stirred for 10 hours, the solvent is removed in vacuo, the residue is treated with 200 ml of water, and a pH of 1 is established by adding hydrochloric acid. The precipitate is filtered off with suction, dried, and then recrystallised from alcohol.

5.2 g (=55.1% of theory) of 1-[2-pyridyl]-3-ethyl-5-hydroxy-pyrazole are obtained.

M.p.: 189.degree. C.

The 3-substitutedl-[pyri(mi)dyl-(2)]-5-hydroxy-pyrazoles listed in Table 1 below were obtained in the same manner from the corresponding ethyl acylacetates.

The pyrazoles, which were obtained in the form of oils, were characterised by the .delta.-value of the pyrazole H, determined by NMR. ______________________________________ Physical Example R (R.sub.1, R.sub.2 = H) X      characteristics ______________________________________ 2     CH.sub.3        N      .delta. = 5.38 ppm 3     CF.sub.3        CH     .delta. = 5.85 ppm 4     t-butyl         CH     .delta. = 5.47 ppm 5     CH.sub.3 OCH.sub.2 CH     .delta. = 5.57 ppm 6     iC.sub.3 H.sub.7 CH     .delta. = 5.42 ppm 7     C.sub.8 H.sub.14 CH     .delta. = 5.42 ppm 8     C.sub.10 H.sub.21 CH     .delta. = 5.42 ppm 9 ##STR4##       CH     .delta. = 5.92 ppm 10 ##STR5##       CH     m.p. = 124-125.degree. C. 11 ##STR6##       CH     .delta. = 5.96 ppm 12 ##STR7##       CH     .delta. = 6.06 ppm 13 ##STR8##       CH     .delta. = 6.06 ppm 14 ##STR9##       CH     .delta. = 5.32 ppm 15     CH.sub.3        N      M.sup..sym.  = 176 16 ##STR10##      N      m.p. = 146-49.degree. C. ______________________________________

A mixture of 24.9 g of ethyl .alpha.-formyl-octanoate (73%), 9.8 g of 2-hydrazinopyridine and 200 ml of ethanol is refluxed for 3 hours, with stirring. The reaction mixture is then cooled to 20 to 30.degree. C. and, with stirring, treated with 10.4 g of potassium tert.-butylate, in portions. After the mixture has been stirred for 10 hours, the solvent is removed in vacuo. The residue is treated with 200 ml of water, and a pH of 1 is established using hydrochloric acid. The oil which separates out is extracted using methylene chloride. After the methylene chloride solution has been dried over sodium sulphate, the solvent is removed in vacuo.

12.1 g (=54.8% of theory) of 1-[2-pyridyl]-4-hexyl-5-hydroxy-pyrazole are obtained in the form of a yellow oil which crystallises slowly.

M.p.: 37-38.degree. C.

The 4-substituted 1-[pyri(mi)dyl-(2)]-5-hydroxy-pyrazoles which are listed in Table 2 below were obtained in the same manner from the corresponding ethyl .alpha.-formylcarboxylates. ______________________________________ Ex-                               Physical am-                               character- ple  R.sub.1 (R, R.sub.2 = H) X       istics ______________________________________ 18   CH.sub.3             CH      .delta. = 7.35 ppm 19   C.sub.2 H.sub.5      CH      .delta. = 7.35 ppm 20   i-C.sub.3 H.sub.7    CH      .delta. = 7.48 ppm 21   n-C.sub.4 H.sub.9    CH      .delta. = 7.36 ppm 22   C.sub.10 H.sub.21    CH      .delta. = 7.50 ppm 23   i-C.sub.5 H.sub.11   CH      .delta. = 7.52 ppm 24   CH.sub.3             N       .delta. = 7.51 ppm 25   C.sub.2 H.sub.5      N       .delta. = 7.50 ppm 26   n-C.sub.4 H.sub.9    N       .delta. = 7.41 ppm 27 ##STR11##           CH      .delta. = 7.35 ppm 28 ##STR12##           CH      .delta. = 7.33 ppm 29 ##STR13##           CH      .delta. = 7.30 ppm 30 ##STR14##           CH      .delta. = 7.28 ppm 31 ##STR15##           CH      .delta. = 7.32 ppm 32 ##STR16##           CH      .delta. = 7.33 ppm 33 ##STR17##           CH      m.p.: 70-71.degree. C. 34 ##STR18##           CH      m.p.: 156-157.degree. C. 35 ##STR19##           CH      m.p.: 67-68.degree. C. 36 ##STR20##           CH      .delta. = 7.28 ppm 37 ##STR21##           CH       m.p.: 60-61.degree. C. 38 ##STR22##           CH      .delta. = 7.22 ppm 39 ##STR23##           N       m.p.: 110.degree. C. 40 ##STR24##           N       .delta. = 7.50 ppm 41 ##STR25##           N       .delta. = 7.42 ppm 42 ##STR26##           N       m.p.: 110-12.degree. C. 43 ##STR27##           N       m.p.: 102-103.degree. C. 44 ##STR28##           N       m.p.: 192-94.degree. C. 45 ##STR29##           N       .delta. = 7.37 ppm 46 ##STR30##           CH      .delta. = 7.86 ppm 47 ##STR31##           CH      .delta. = 7.84 ppm 48 ##STR32##           CH      .delta. = 7.85 ppm 49 ##STR33##           CH      .delta. = 7.70 ppm 50 ##STR34##           CH      .delta. = 7.87 ppm 51   C.sub.2 H.sub.5 OCO  N       m.p.: 155-58.degree. C. 52   C.sub.2 H.sub.5 OCOCH.sub.2 C       .delta. = 7.61 ppm 53   n-C.sub.4 H.sub.9 OCOCH.sub.2 C       .delta. = 7.50 ppm 54   n-C.sub.6 H.sub.13 OCOCH.sub.2 C       .delta. = 7.59 ppm 55   i-C.sub.4 H.sub.9 OCOCH.sub.2 C       .delta. = 7.86 ppm 56   C.sub.8 H.sub.17 OCOCH.sub.2 C       .delta. = 7.45 ppm 57   C.sub.2 H.sub.5 NHCOCH.sub.2 C       .delta. = 7.42 ppm 58   C.sub.2 H.sub.5 OCOCH.sub.2 N       .delta. = 7.62 ppm 59   C.sub.6 H.sub.13S    CH      .delta. = 7.30 ppm 60 ##STR35##           CH      .delta. = 7.20 ppm 61   CH.sub.3 O           CH      .delta. = 7.38 ppm 62   C.sub.4 H.sub.9 O    CH      .delta. = 7.32 ppm 63   CH.sub.2CHCH.sub.2   CH      .delta. = 7.35 ppm 64 ##STR36##           CH      .delta. = 7.47 ppm ______________________________________

A mixture of 14.1 g of ethyl .alpha.-benzyl-benzoylacetate, 5.5 g of hydrazinopyridine and 100 ml of ethanol is refluxed for 3 hours, with stirring. The reaction mixture is then cooled to 20 to 30.degree. C. and, with stirring, treated with 5.6 g of potassium tert.-butylate, in portions. The reaction mixture is stirred for 15 hours at 20 to 30.degree. C. The solvent is subsequently removed in vacuo. The residue is treated with 200 ml of water, and a pH of 1 is established using hydrochloric acid. The precipitate is filtered off with suction and stirred with isopropanol.

10 g (=61.1% of theory) of 2-[2-pyridyl]-3-phenyl-4-benzyl-5-hydroxy-pyrazole are obtained.

M.p.: 115-116.degree. C.

The 3- and 4-substituted 1-[2-pyri(mi)dyl]-5-hydroxy-pyrazoles which are given in Table 3 below were obtained in the same manner from the correspondingly substituted ethyl acylacetates. __________________________________________________________________________ Example R         R.sub.1 (R.sub.2 = H) X  M.p. (.degree.C.) __________________________________________________________________________ 66   CH.sub.   CH.sub.3      CH 123.5-26.degree. C. 67   C.sub.2 H.sub.5 CH.sub.3      CH 50-53 68   i-C.sub.3 H.sub.7 CH.sub.3      CH 71-72 69   CH.sub.3  C.sub.2 H.sub.5 CH 107-08 70   CH.sub.3  n-C.sub.4 H.sub.9 CH 94-97 71   CH.sub.3  n-C.sub.6 H.sub.13 CH 42-43 72   CH.sub.3  n-C.sub.7 H.sub.15 CH 39-40 73   CH.sub.3  C.sub.12 H.sub.25 CH 47-48 74   CH.sub.3 ##STR37##    CH 82-83 75   CH.sub.3 ##STR38##    CH 121-24 76   CH.sub.3 ##STR39##    CH 84-87 77   CH.sub.3  HCCC(CH.sub.3).sub.2 CH 57-59 78   CH.sub.3 ##STR40##    CH 114-15 79   CH.sub.3 ##STR41##    CH 56-63 80   CH.sub.3 ##STR42##    CH 62-64 81   CH.sub.3 ##STR43##    CH 153-54 82   R + R.sub.1 = (CH.sub.2).sub.4 CH 125-26 83   R + R.sub.1 = (CH.sub.2).sub.5 CH 108-10 84   CH.sub.3  C.sub.2 H.sub.5 N  111-13 85   C.sub.2 H.sub.5 CH.sub.3      N  109-12 86   i-C.sub.3 H.sub.7 CH.sub.3      N  84-86 87   CH.sub.3  n-C.sub.4 H.sub.9 N  88-89 88   CH.sub.3  n-C.sub.7 H.sub.15 N  63-65 89   CH.sub.3  n-C.sub.12 H.sub.25 N  73-75 90   CH.sub.3 ##STR44##    N  121-24 91   CH.sub.3 ##STR45##    N  108-11 92   CH.sub.3 ##STR46##    N  78-83 93 ##STR47## ##STR48##    N  155-61 94   CH.sub.3 ##STR49##    N  198-201 95   CH.sub.3 ##STR50##    N  86-87 96   R + R.sub.1 = (CH.sub.2).sub.4 N  192-96 __________________________________________________________________________ Example R.sub.1   R.sub.2 (R = H) X  M.p. (.degree.C.) __________________________________________________________________________ 97   C.sub.2 H.sub.5 5-Cl, 6-CH.sub.3NH, N  172 98   C.sub.2 H.sub.5 5-Br          CH 119 99   C.sub.2 H.sub.5 6-CH.sub.3    CH .delta.(pyrazole H) = 7.37 ppm 100  C.sub.6 H.sub.13 4-CF.sub.3, 6-CH.sub.3 CH .delta.(pyrazole H) = 7.38 ppm 101  C.sub.6 H.sub.13 6-CH.sub.3    CH .delta.(pyrazole H) = 7.34 ppm 102  C.sub.6 H.sub.13 5-Cl, 6-CH.sub.3 NH N  .delta.(pyrazole H) = 7.45 ppm 103  C.sub.8 H.sub.17 5-Cl          CH 109 104 ##STR51## 4-Cl, 6-CH.sub.3 CH 80 105 ##STR52## 6-CH.sub.3    CH .delta.(pyrazole H) = 7.31 ppm 106 ##STR53## 6-Cl          CH 167-168 107 ##STR54## 5-Br          CH 143 108 ##STR55## 5-NO.sub.2    CH 170 __________________________________________________________________________

In order to demonstrate the effectiveness against fungi, the minimum inhibitory concentrations (MICs) of the active compounds according to the invention were determined:

Active compounds according to the invention are added at concentrations from 0.1 mg/1 to 5000 mg/1 to an agar which is prepared from brewer's wort and peptone. When the agar has solidified, it is contaminated with purebreed cultures of the test organisms listed in the table. The cultures are stored for 2 weeks at 28.degree. C. and 60 to 70% relative atmospheric humidity, and the MIC is then determined. MIC is the lowest concentration of active compound at which no growth whatsoever by the microbe species used takes place; it is given in Table 4 below. __________________________________________________________________________ MIC values of various 1-[pyri(mi)dyl-(2)]-5-hydroxy-pyrazoles on fungi, indicated in mg/l 1-[Pyri(mi)dyl-(2)]-5-hydroxy-pyrazoles of Example Test organisms 21 19 26 27 39 40 41 35 31 36 __________________________________________________________________________ Alternaria tenuis 5  50 25 50 20 20 20 35 50 10 Aspergillus niger 2  10 50 20 50 50 50 20 50 20 Aureobasidium pullulans 35 50 20 20 10 35 35 50 35 20 Chaetomium globosum 5  2  20 50 50 20 20 50 50 50 Cladosporium cladosporioides 10 5  -- -- -- -- -- -- -- -- Cladosporium herbarum -- -- 50 50 50 15 15 50 35 35 Lentinus tigrinus 1  2  75 50 75 100 100 50 50 50 Penicillium glaucum 2  20 -- -- -- -- -- -- -- -- Penicillium breviante -- -- 50 100 50 20 20 -- 20 20 Sclerophoma pityophila 7.5 2  50 5  20 35 35 20 75 10 Trichoderma viride 200 200 50 75 50 50 50 100 100 50 __________________________________________________________________________

The fungicidal action in paints is determined by testing the coatings obtained with the paints for resistance to moulds.

The test is carried out following Report 219 of the Defence Standards Laboratories Maribyrnong/Australia as follows:

A suitable substrate is painted on both sides with the paint to be tested.

To obtain results which are relevant to practice, some of the samples are treated with a warm stream of fresh air before being tested for resistance to mould (7 days; 40.degree. C.).

The samples which have been prepared in this manner are placed on an agar medium. Sample and medium are contaminated with fungal spores. The items are stored at 29.+-.1.degree. C. and 80 to 90% relative atmospheric humidity for 1 to 3 weeks, and samples are then taken. The coating is permanently mould-resistant when the sample remains free from fungus or shows not more than a slight infestation at the edge.

For contamination, fungal spores of the following nine moulds are used, these moulds being known as paint destructants or being found frequently on paints:

0 to 2% by weight, relative to the total solids content of the paint of the compound to be tested for its fungicidal activity, were incorporated into samples of a commercially available dispersion paint based on polyvinyl acetate. In this test, even those samples which only contained 0.3% by weight, relative to the total solids content of the paint, of 1-(2-pyridyl)-4-ethyl-5-hydroxy-pyrazole, described in Example 19, gave permanently mould-resistant paints. Have Been Imparted According to the Invention

The action which the plastics to which fungicidal properties have been imparted according to the invention take against microorganisms (various genera of fungi) was determined in accordance with Swiss Testing Procedure SNV No. 195,921 (1976; "Testing the antimycotic action of finished textiles and other materials with the aid of the agar diffusion test").

To carry out the determination, test samples (discs; diameter: 3 cm; thickness depending on the plastic to be tested: 250 .mu.m to 5 mm) of the plastics to which fungicidal properties had been imparted and, as a control, of the corresponding plain plastics were placed on 2-layer nutrient agar plates which had been inoculated with spores or hyphae of the test organism in question. The plates were incubated for 4 weeks at 29.+-.1.degree. C. Fungal growth on the test samples and in the contact zone under the test samples was then determined visually and, in the event that an inhibition zone had formed under the test samples, the size of this inhibition zone was measured.

Inhibition zone is understood as meaning the zone which is free from fungi, calculated using the following formula: ##EQU1## in which H=inhibition zone [mm]

Table 5 which follows gives the results, fungal growth and sizes of the inhibition zones, which were obtained when the amounts indicated in the table of the compounds also indicated in the table were used in the plastics also indicated in the table, when the tests were evaluated. __________________________________________________________________________ Action against various test organisms of the plastics to which fungicidal properties have been imparted __________________________________________________________________________ Test organisms used:  The abbreviations denote: (a) Aspergillus niger H = inhibition zone [mm] (b) Aspergillus terreus PB = fungal growth (4 scores: none, slight, (c) Chaetomium globosum medium, total) (d) Trichoderma viride (e) Cladosporium herbarium (f) Streptoverticilium reticulum __________________________________________________________________________ Compound used as fungicide, in accord- Amount used (a)  (b) (c) (d)  (e) (f) ance with Example [g/100 g of plastic] H/PB H/PB H/PB H/PB H/PB H/PB __________________________________________________________________________ 47        1.0/polyvinyl chloride 0/   0/  0/  0/   0-6 >25/ medium slight slight slight none none 19        1.0/polyvinyl chloride 20-25/ >25/ >25/ 0/   12-15/ 8-11/ none none none slight none none 18        1.0/polyvinyl chloride 0/   >25/ >25/ 0/   15-18/ 6-9/ slight none none slight none none 27        0.5/polyvinyl chloride 3-5/ 1-2/ 1-2/ 0/   1-3/ 8-10/ none none none medium none none Control   0/polyvinyl chloride 0/   0/  0/  0/   0/  0/ total total total total total total 19        0.15/polyurethane 4-6/ 2-4/ 0-1/ 10-12/ 8-10/ 15-20/ none none none none none none Control   0/polyurethane 0/   0/  0/  0/   0/  0/ total total total total total total __________________________________________________________________________ Polyvinyl chloride = PVC pastes (emulsion PVC) Polyurethane = polyester polyurethane (Bayflex .RTM.)

## Claims

1. A method of combating microbes which comprises applying to such microbes or to a microbe habitat a microbicidally effective amount of a 1-(2-pyridyl)-5-hydroxy-pyrazole of the formula ##STR56## in which R represents hydrogen, C.sub.1 -C.sub.12 -alkyl, optionally substituted with one or more substituents selected from the group consisting of chlorine, fluorine, C.sub.1 -C.sub.4 -alkoxy and C.sub.1 -C.sub.6 -alkoxycarbonyl, benzyl, .alpha.-methylbenzyl, .alpha.,.alpha.-dimethylbenzyl, 2-phenylethyl, .alpha.naphthylmethyl and .beta.-naphthylmethyl each of which is optionally substituted with a substituent selected from the group consisting of chlorine, fluorine, C.sub.1 -C.sub.4 -alkyl, C.sub.1 -C.sub.4 -alkoxy, C.sub.1 -C.sub.4 -alkylmercapto and cyano; substituted with one or more substituents selected from the group consisting of chlorine, fluorine, C.sub.1 -C.sub.4 -alkoxy and C.sub.1 -C.sub.6 -alkoxycarbonyl; -alkyl, fluorine or chlorine; .alpha.-methylbenzyl, .alpha.,.alpha.-dimethylbenzyl, 2-phenylethyl, .alpha.-naphthylmethyl and .beta.-naphthylmethyl each of which is optionally substituted with a substituent selected from the group consisting of chlorine, fluorine, C.sub.1 -C.sub.4 -alkyl, C.sub.1 -C.sub.4 -alkoxy, C.sub.1 -C.sub.4 -alkylmercapto and cyano; from the group consisting of halogen and C.sub.1 -C.sub.4 -alkyl; selected from the group consisting of halogen and C.sub.1 -C.sub.4 -alkyl; from the group consisting of halogen, C.sub.1 -C.sub.4 -alkyl, C.sub.1 -C.sub.2 -halogenoalkyl, cyano, nitro, trifluoromethyl and difluoromethyl; selected from the group consisting of halogen, C.sub.1 -C.sub.4 -alkyl, C.sub.1 -C.sub.2 -halogenoalkyl, cyano, and nitro; 3 to 6 c atoms in the chain, -C.sub.2 -halogenoalkyl, C.sub.1 -C.sub.4 -alkoxy, C.sub.1 -C.sub.4 -alkylmercapto, C.sub.1 -C.sub.4 -alkoxycarbonyl or aminocarbonyl, and identical or different radicals when n is 2 or 3.

2. The method of claim 1, wherein with one or more substituents selected from the group consisting of chlorine, fluorine, C.sub.1 -C.sub.4 -alkoxy and C.sub.1 -C.sub.6 -alkoxycarbonyl; benzyl, .alpha.-methylbenzyl, .alpha.,.alpha.-dimethylbenzyl, 2-phenylethyl, .alpha.-naphthylmethyl and .beta.-naphthylmethyl each of which is optionally substituted with a substituent selected from the group consisting of chlorine, fluorine, C.sub.1 -C.sub.4 -alkyl, C.sub.1 -C.sub.4 -alkoxy, C.sub.1 -C.sub.4 -alkylmercapto and cyano, and substituted with one or more substituents selected from the group consisting of chlorine, fluorine, C.sub.1 -C.sub.4 -alkoxy and C.sub.1 -C.sub.6 -alkoxycarbonyl; -alkyl, fluorine or chlorine; .alpha.-methylbenzyl, .alpha.,.alpha.-dimethylbenzyl, 2-phenylethyl, .alpha.-naphthylmethyl and .beta.-naphthylmethyl each of which is optionally substituted with a substituent selected from the group consisting of chlorine, fluorine, C.sub.1 -C.sub.4 -alkyl, C.sub.1 -C.sub.4 -alkoxy, C.sub.1 -C.sub.4 -alkylmercapto and cyano; selected from the group consisting of halogen and C.sub.1 -C.sub.4 -alkyl;

3. The method according to claim 1, in which -cycloalkyl, C.sub.1 -C.sub.6 -alkoxy, benzyl, optionally substituted with a substituent selected from the group consisting of chlorine, fluorine, C.sub.1 -C.sub.4 -alkyl, C.sub.1 -C.sub.4 -alkoxy, C.sub.1 -C.sub.4 -alkylmercapto and cyano; C.sub.1 -C.sub.6 -alkoxycarbonyl or benzylmercapto.

4. A 1-(2-pyridyl)-5-hydroxy-pyrazole of the formula ##STR57## in which R.sup.1 represents hydrogen or C.sub.6 -C.sub.10 -alkyl, optionally substituted with one or more substituents selected from the group consisting of chlorine, fluorine, C.sub.1 -C.sub.4 -alkoxy and C.sub.1 -C.sub.6 -alkoxycarbonyl; benzyl, .alpha.-methylbenzyl, .alpha.,.alpha.dimethylbenzyl, 2-phenylethyl, .alpha.-naphthylmethyl and .beta.-naphthylmethyl each of which is optionally substituted with a substituent selected from the group consisting of chlorine, fluorine, C.sub.1 -C.sub.4 -alkyl, C.sub.1 -C.sub.4 -alkoxy, C.sub.1 -C.sub.4 -alkylmercapto and cyano; one or more substituents selected from the group consisting of chlorine, fluorine, C.sub.1 -C.sub.4 -alkoxy and C.sub.1 -C.sub.6 -alkoxycarbonyl; -alkyl, fluorine or chlorine; .alpha.-methylbenzyl, .alpha.,.alpha.-dimethylbenzyl, 2-phenylethyl, .alpha.-naphthylmethyl and .beta.-naphthylmethyl each of which is optionally substituted with a substituent selected from the group consisting of chlorine, fluorine, C.sub.1 -C.sub.4 -alkyl, C.sub.1 -C.sub.4 -alkoxy, C.sub.1 -C.sub.4 -alkylmercapto and cyano; from the group consisting of halogen and C.sub.1 -C.sub.4 -alkyl; selected from the group consisting of halogen and C.sub.1 -C.sub.4 -alkyl; from the group consisting of halogen, C.sub.1 -C.sub.4 -alkyl, C.sub.1 -C.sub.2 -halogenoalkyl, cyano, nitro, trifluoromethyl and difluoromethyl; selected from the group consisting of halogen, C.sub.1 -C.sub.4 -alkyl, C.sub.1 -C.sub.2 -halogenoalkyl, cyano, and nitro; has 3 to 6 c atoms in the chain.

5. A microbicidal composition comprising a microbicidally effective amount of a compound according to claim 4 and a diluent.