WO2002051822A2

WO2002051822A2 - Isothiazolecarboxamides as microbicides

Info

Publication number: WO2002051822A2
Application number: PCT/EP2001/014447
Authority: WO
Inventors: Yoshinori Kitagawa; Haruko Sawada; Lutz Assmann
Original assignee: Nihon Bayer Agrochem K.K.
Priority date: 2000-12-22
Filing date: 2001-12-10
Publication date: 2002-07-04
Also published as: AU2002216086A1; WO2002051822A3; JP2002193956A

Abstract

Novel isothiazolecarboxamides of the formula (I) wherein R1 represents a hydrogen atom or cyanomethyl, R2 represents a hydrogen atom or methyl, and R3 represents a hydrogen atom, C¿7-10? alkyl or methoxycarbonylphenoxymethyl, provided that R?1, R2 and R3¿ are not simultaneously a hydrogen atom, a process for the preparation of the new compounds and their use as microbicides

Description

Isothiazolecarboxamides

The present invention relates to novel isomiazolecarboxamides, to a process for their preparation and to their use as microbicides.

It has already been known that certain isothiazolecarboxamides can be employed for the control of plant pests (cf. JP-A 119 463-1988, JP-A 121 263-1989, JP-A 199 963- 1989 and JP-A 149 572-1990). Further, it has already been described that some isothiazolecarboxamides can be used as intermediates and as a agrochemical agents for the control of fungi (cf. JP-A 139 672-1985). The fungicidal activity of such known compounds, however, is not always satisfactory.

There have now been found novel isothiazolecarboxamides of the formula

wherein

R¹ represents a hydrogen atom or cyanomethyl,

R² represents a hydrogen atom or methyl, and

R³ represents a hydrogen atom, C -₁₀ alkyl or methoxycarbonylphenoxymethyl,

provided that R , R² and R³ are not simultaneously a hydrogen atom.

Further, it has been found that the isothiazolecarboxamides of the formula (I) can be prepared by reacting 3,4-dichloro-isothiazole-5-carbonyl chloride of the formula

with amines of the formula

wherein

R¹, R² and R³ have the above-mentioned meanings,

in the presence of an inert diluent and, if appropriate, in the presence of an acid- binding agent and, if appropriate, in the presence of a phase transfer catalyst.

Finally, it has been found that the isothiazolecarboxamides of the formula (I) are outstandingly active as microbicides in agriculture and horticulture, particularly as fungicides for the direct control of plant diseases or for causing resistance in plants against plant pathogens.

Surprisingly, the isothiazolecarboxamides of the formula (I) according to the invention have a much better microbicidal activity than the already known compounds, which are structurally most similar and have the same type of action.

In the present context, "alkyl" preferably represent straight-chain groups, such as n- heptyl, n-octyl, n-nonyl and n-decyl. Formula (I) provides a general definition of the isothiazolecarboxamides according to the invention. Preferred compounds of the formula (I) are those, in which

R¹ represents a hydrogen atom or cyanomethyl,

R² represents a hydrogen atom or methyl, and

R³ represents a hydrogen atom, n-heptyl, n-octyl, n-nonyl, n-decyl or 4-methoxy- carbonylphenoxymethyl,

provided that R¹, R²and R³ are not simultaneously a hydrogen atom.

A particularly preferred sub-group of the compounds according to the invention are those isothiazolecarboxamides of the formula (I) wherein

R¹ represents a hydrogen atom or cyanomethyl,

R² represents a hydrogen atom, and

provided that R , R and R are not simultaneously a hydrogen atom.

If 3,4-dichloro-isothiazole-5-carbonyl chloride and 1-cyano-n-octyl-amine are used as starting materials, the process according to the invention can be illustrated by the following formula scheme.

Formula (II) characterizes the 3,4-dichloro-isothiazole-5-carbonyl chloride, which is required as starting material for carrying out the process according to the invention. The 3,4-dichloro-isothiazole-5-carbonyl chloride is known (cf. JP-A 59 024-1993).

Formula (III) provides a general definition of the amines, which are required as reaction components for carrying out the process according to the invention. In this formula, R¹, R² and R³ preferably have those meanings, which have already been mentioned as preferred for these radicals.

The following compounds may be mentioned as examples of amines of the formula

(III):

[(cyanomethyl)amino]acetonitrile, 2-aminononanenitrile,

2-aminodecanenitrile,

2-aminoundecanenitrile,

2-aminododecanenitrile,

2-amino-3-(4-methoxycarbonylphenoxy)propiononitrile, 2-amino-3-(4-methoxycarbonylphenoxy)-2-methylpropiononitrile and so on.

The amines of the formula (III) are known or can be prepared by known processes [cf. JIKKEN KAGAKU KOUZA (Lecture on Experimental Chemistry) 4^th Edition, Nol. 22, pages 193-195 (published by Maruzen on November 30, 1992)]. The amines can also be synthesized by the Strecker reaction.

Suitable diluents for conducting the process according to the invention are all customary inert organic solvents as well as water. The following can preferably be used: Water, aliphatic, alicyclic and aromatic hydrocarbons (which may optionally be chlorinated), for example, pentane, hexane, cyclohexane, petroleum ether, ligroine, benzene, toluene, xylene, dichloromethane, chloroform, carbon tetrachloride, 1,2- dichloroethane, chlorobenzene, dichlorobenzene etc.; ethers, for example, ethyl ether, methyl ethyl ether, isopropyl ether, butyl ether, dioxane, dimethoxyethane (DME), tetrahydrofuran (THF), diethylene glycol dimethyl ether (DGM) etc.; ketones, for example, acetone, methyl ethyl ketone (MEK), methyl isopropyl ketone, methyl isobutyl ketone (MIBK) etc.; nitriles, for example, acetonitrile, propionitrile, acrylonitrile etc.; alcohols, for example, methanol, ethanol, isopropanol, butanol, ethylene glycol etc.; esters, for example, ethyl acetate, amyl acetate etc.; acid amides, for example, dimethylformamide (DMF), dimethylacetamide (DMA), N-methyl- pyrrolidone, l,3-dimethyl-2-imidazolidinone, hexamethylphosphoric triamide (HMPA) etc.; sulfones and sulfoxides, for example, dimethyl sulfoxide (DMSO), sulfolane etc.; as well as bases, for example, pyridine etc.

Suitable acid-binding agents for conducting the process according to the invention are all customary inorganic and organic bases. The following can preferably be used: Inorganic bases, such as hydrides, hydroxides, carbonates, bicarbonates etc. of alkali metals and alkaline earth metals, for example, sodium hydride, lithium hydride, sodium hydrogen carbonate, potassium hydrogen carbonate, sodium carbonate, potassium carbonate, lithium hydroxide, sodium hydroxide, potassium hydroxide, calcium hydroxide etc.; and as organic bases, for example, tertiary amines, dialkyl- aminoanilines and pyridines, for example, triethylamine, 1,1,4,4-tetramethyl- ethylenediamine (TMEDA), N,N-dimethylaniline, N,N-diethylaniline, pyridine, 4- dimethylaminopyridine (DMAP), l,4-diazabicyclo[2,2,2]octane (DABCO), 1,8- diazabicyclo[5,4,0]undec-7-ene (DBU) etc. The process according to the invention can also be conducted in the presence of a phase transfer catalyst in the presence of a diluent. As examples of suitable diluents to be used in that case there can be mentioned water; aliphatic, alicyclic and aromatic hydrocarbons (which may optionally be chlorinated), for example, pentane, hexane, cyclohexane, petroleum ether, ligroine, benzene, toluene, xylene, dichloromethane, chlorobenzene, dichlorobenzene etc.; ethers, for example, ethyl ether, methyl ethyl ether, isopropyl ether, butyl ether, dioxane, dimethoxyethane (DME), tetrahydrofuran (THF), diethylene glycol dimethyl ether (DGM) etc.; nitriles, for example, aceto- nitrile, propionitrile, acrylonitrile etc.

As suitable of phase-transfer catalysts there can be mentioned quaternary ions, for example, tetramethylammonium bromide, tetrapropylammonium bromide, tetrabutyl- ammonium bromide, tetrabutylammonium hydrogen sulfate, tetrabulylarnmonium iodide, trioctylmethylammonium chloride, benzyltriethylaiximonium bromide, butyl- pyridinium bromide, heptylpyridinium bromide, benzyltriethylarnmonium chloride etc.; crown ethers, for example, dibenzo-18-crown-6, dicyclohexyl-18-crown-6, 18- crown-6 etc.; cryptands, for example, [2.2.2]-cryptate, [2JJ]-cryptate, [2.2J]- cryptate, [2.2.B]-cryptate, [3.2.2]-cryptate etc.

Upon carrying out the process according to the invention, the reaction temperatures can be varied within a substantially wide range. The reaction is generally carried out at a temperature between about -30°C and about +150°C, preferably between about 0°C and about +80°C.

The process according to the invention is generally carried out under atmospheric pressure but, if desired, can also be carried out under elevated or reduced pressure.

Upon carrying out the process according to the invention, in general 1 mole of 3,4- dichloro-isothiazole-5-carbonyl chloride of the formula (II) is reacted with 1.0 to 1.2 moles of an amine of the formula (III) in the presence of a diluent, such as dichloro- methane, and in the presence of 1 to 2 moles of an acid-binding agent, such as triethylamine.

The compounds according to the invention prepared by the above-mentioned process can in each case be isolated from the reaction mixture by customary procedures and can be purified by known methods, such as crystallization, chromatography etc.

The compounds according to the present invention exhibit a strong microbicidal activity. Thus, they can be used for combating undesired microorganisms, such as phytopathogenic fungi and bacteriae, in agriculture and horticulture. The compounds are suitable for the direct control of undesired microorganisms as well as for generating resistance in plants against attack by undesired plant pathogens.

Resistance-inducing substances in the present context are to be understood as those substances which are capable of stimulating the defence system of plants such that the treated plants, when subsequently inoculated with undesirable microorganisms, display substantial resistance to these microorganisms.

Undesirable microorganisms in the present case are to be understood as phytopatho- genie fungi and bacteriae. The substances according to the invention can thus be employed to generate resistance in plants against attack by the harmful organisms mentioned within a certain period of time after the treatment. The period of time within which resistance is brought about in general extends from 1 to 10 days, preferably 1 to 7 days, after treatment of the plants with the active compounds.

Generally, the compounds according to the invention can be used as fungicides for combating phytopathogenic fungi, such as Plasmodiophoromycetes, Oomycetes, Chytridiomycetes, Zygomycetes, Ascomycetes, Basidiomycetes and Deutero- mycetes, and can also be used as bactericides for combating bacteriae, such as Pseudomonadaceae, Rhizobiaceae, Enterobacteriaceae, Corynebacteriaceae, Stre- ptomycetaceae, Proteobacteriae and Gram-positive groups. Some pathogens causing fungal diseases which come under the generic names listed above are mentioned as examples, but not by way of limitation:

Erwinia species, such as, for example, Erwinia amylovora;

Pythium species, such as, for example, Pythium ultimum;

Phytophthora species, such as, for example, Phytophthora infestans;

Pseudoperonospora species, such as, for example, Pseudoperonospora humuli or

Pseudoperonospora cubensis; Plasmopara species, such as, for example, Plasmopara viticola;

Bremia species, such as, for example, Bre ia Lactucae;

Peronospora species, such as, for example, Peronospora pisi or P. brassicae;

Erysiphe species, such as, for example, Erysiphe graminis;

Sphaerotheca species, such as, for example, Sphaerotheca fuliginea; Podosphaera species, such as, for example, Podosphaera leucotricha;

Nenturia species, such as, for example, Nenturi inaequalis;

Pyrenophora species, such as, for example, Pyrenophora teres or P. graminea

(conidia form: Drechslera, syn: Helminthosporium);

Cochliobolus species, such as, for example, Cochliobolus sativus (conidia form: Drechslera,syn: Helminthosporium);

Uromyces species, such as, for example, Uromyces appendiculatus;

Puccinia species, such as, for example, Puccinia recondita;

Sclerotinia species, such as, for example, Sclerotinia sclerotiorum;

Tilletia species, such as, for example, Tilletia caries; Ustilago species, such as, for example, Ustilago nuda or Ustilago avenae;

Pellicularia species, such as, for example, Pellicularia sasakii;

Pyricularia species, such as, for example, Pyricularia oryzae;

Fusarium species, such as, for example, Fusarium culmorum;

Botrytis species, such as, for example, Botrytis cinerea; Septoria species, such as, for example, Leptosphaeria nodorum;

Cercospora species, such as, for example, Cercospora canescens; Alternaria species, such as, for example, Alternaria brassicae; and Pseudocercosporella species, such as, for example, Pseudocercosporella herpo- trichoides.

The compounds according to the present invention are particularly suitable for causing resistance against infection of plants by plant pathogens, such as Pyricularia oryzae, Phythophthora infestans etc.

The good toleration, by plants, of the active compounds, at the concentrations required for combating plants diseases, permits treatment of above-ground parts of plants, of vegetative propagation stock and seeds, and of the soil.

The compounds according to the present invention have a low toxicity against warmblooded animals and therefore can be used safely.

The active compounds can be converted into the customary formulations, such as solutions, emulsions, wettable powders, suspensions, powders, foams, pastes, granules, tablets, aerosols, natural and synthetic materials impregnated with active compound, very fine capsules in polymeric substances, coating compositions for use on seed, and formulations used with burning equipment, such as fumigating cartridges, fumigating cans and fumigating coils, as well as ULN cold mist and warm mist formulations.

These formulations may be produced in known manner, for example by mixing the active compounds with extenders, that is to say liquid or liquefied gaseous or solid diluents or carriers, optionally with the use of surface-active agents, that is to say emulsifying agents and/or dispersing agents and/or foam-forming agents. In the case of the use of water as an extender, organic solvents can, for example, also be used as auxiliary solvents. As liquid solvents diluents or carriers, there are suitable in the main, aromatic hydrocarbons such as xylene, toluene or alkyl naphthalenes, chlorinated aromatic or chlorinated aliphatic hydrocarbons, such as chlorobenzenes, chloroethylenes or methylene chloride, aliphatic hydrocarbons, such as cyclohexane or paraffins, for example mineral oil fractions, alcohols, such as butanol or glycol as well as their ethers and esters, ketones, such as acetone, methyl ethyl ketone, methyl-isobutyl ketone or cyclohexanone, or strongly polar solvents, such as dimethylformamide and dimethyl-sulphoxide, as well as water.

By liquefied gaseous diluents or carriers are meant liquids which would be gaseous at normal temperature and under normal pressure, for example aerosol propellants, such as halogenated hydrocarbons as well as butane, propane, nitrogen and carbon dioxide.

As solid carriers there may be used ground natural minerals, such as kaolings, clays, talc, chalk, quartz, attapulgite, montmorillonite or diatomaceous earth, and ground synthetic minerals, such as highly-dispersed silicic acid, alumina and silicates. As solid carriers for granules there may be used crushed and fractionated natural rocks such as calcite, marble, pumice, sepiolite and dolomite, as well as synthetic granules of inorganic and organic meals, and granules of organic material such as sawdust, coconut shells, maize cobs and tobacco stalks.

As emulsifying and/or foam-forming agents there may be used non-ionic and anionic emulsifiers, such as polyoxyethylene-fatty acid esters, polyoxyethylene-fatty alcohol ethers, for example alkylaryl polyglycol ethers, alkyl sulphonates, alkyl sulphates, aryl sulphonates as well as albumin hydrolysis products.

Dispersing agents include, for example, lignin sulphite waste liquors and methyl- cellulose. Adhesives such as carboxymethylcellulose and natural and synthetic polymers in the form of powders, granules or latices, such as gum arabic, polyvinyl alcohol and poly- vinyl acetate, can be used in the formulation.

It is possible to use colorants such as inorganic pigments, for example iron oxide, titanium oxide and Prussian Blue, and organic dyestuffs, such as alizarin dyestuffs, azo dyestuffs or metal phthalocyanine dyestuffs, and trace nutrients, such as salts of iron, manganese, boron, copper, cobalt, molybdenum and zinc.

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

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

In many cases, synergistic effects are achieved, i.e. the activity of the mixture exceeds the activity of the individual components.

Examples of co-components in mixtures are the following compounds:

Fungicides: aldimorph, ampropylfos, ampropylfos potassium, andoprim, anilazine, azaconazole, azoxystrobin, benalaxyl, benodanil, benomyl, benzamacril, benzamacril-isobutyl, bialaphos, binapacryl, biphenyl, bitertanol, blasticidin-S, bromuconazole, bupirimate, buthiobate, calcium polysulphide, capsimycin, captafol, captan, carbendazim, carboxin, carvon, quinomethionate, chlobenthiazone, chlorfenazole, chloroneb, chloropicrin, chloro- thalonil, chlozolinate, clozylacon, cufraneb, cymoxanil, cyproconazole, cyprodinil, cyprofuram, carpropamide, debacarb, dichlorophen, diclobutrazole, diclofluanid, diclomezine, dicloran, diethofencarb, difenoconazole, dimethirimol, dimethomorph, diniconazole, diniconazole-M, dinocap, diphenylamine, dipyrithione, ditalimfos, dithianon, dodemorph, dodine, drazoxolon, edifenphos, epoxiconazole, etaconazole, ethirimol, etridiazole, famoxadon, fenapanil, fenarimol, fenbuconazole, fenfuram, fenitropan, fenpiclonil, fenpropidin, fenpropimorph, fentin acetate, fentin hydroxide, ferbam, ferimzone, fluazinam, flumetover, fluoromide, fluquinconazole, flurprimidol, flusilazole, flusulfamide, flutolanil, flutriafol, folpet, fosetyl-aluminium, fosetyl-sodium, fthalide, fuberidazole, furalaxyl, furametpyr, furcarbonil, fiirconazole, furconazole-cis, furmecyclox, fenhexamide, guazatine, hexachlorobenzene, hexaconazole, hymexazole, imazalil, imibenconazole, iminoctadine, iminoctadine albesilate, iminoctadine triacetate, iodocarb, ipconazole, iprobenfos (IBP), iprodione, irumamycin, isopro- thiolane, isovaledione, iprovalicarb, kasugamycin, kresoxim-methyl, copper preparations, such as: copper hydroxide, copper naphthenate, copper oxychloride, copper sulphate, copper oxide, oxine-copper and Bordeaux mixture, mancopper, mancozeb, maneb, meferimzone, mepanipyrim, mepronil, metalaxyl, metconazole, methasulfocarb, methfuroxam, metiram, metomeclam, metsulfovax, mildiomycin, myclobutanil, myclozolin, nickel dimethyldithiocarbamate, nitrothal-isopropyl, nuarimol, ofurace, oxadixyl, oxamocarb, oxolinic acid, oxycarboxim, oxyfenthiin, paclobutrazole, pefurazoate, penconazole, pencycuron, phosdiphen, pimaricin, piperalin, polyoxin, polyoxorim, probenazole, prochloraz, procymidone, propamo- carb, propanosine-sodium, propiconazole, propineb, pyrazophos, pyrifenox, pyrimethanil, pyroquilon, pyroxyfur, quinconazole, quintozene (PCNB), quinoxyfen, sulphur and sulphur preparations, spiroxamine, tebuconazole, tecloftalam, tecnazene, tetcyclacis, tetraconazole, thiabendazole, thicyofen, thifluzamide, thiophanate-methyl, thiram, tioxymid, tolclofos-methyl, tolylfluanid, triadimefon, triadimenol, triazbutil, triazoxide, trichlamide, tricyclazole, tridemorph, triflumizole, triforine, triticonazole, trifloxystrobin, uniconazole, validamycin A, vinclozolin, viniconazole, zarilamide, zineb, ziram and also Dagger G, OK-8705,

OK-8801, α-(l , 1 -dimethylethyl)-β-(2-phenoxyethyl)- 1 H- 1 ,2,4-triazole- 1 -ethanol, -(2,4-dichlorophenyl)-β-fluoro-β-propyl-lH-l,2,4-triazole-l-ethanol, α-(2,4-dichlorophenyl)-β-methoxy-α-methyl-lH-l,2,4-triazole-l-ethanol, -(5 -methyl- 1 ,3 -dioxan-5 -yl)- β - [[4-(trifluoromethyl)-phenyl] -methylene] - 1 H- 1 ,2,4- triazole- 1 -ethanol,

(5RS,6RS)-6-hydroxy-2,2,7,7-tetramethyl-5-(lH-l,2,4-triazol-l-yl)-3-octanone, (E)-α-(methoxyimino)-N-methyl-2-phenoxy-phenylacetamide, 1 -(2,4-dichlorophenyl)-2-(l H- 1 ,2,4-triazol- 1 -yl)-ethanone O-(phenylmethyl)-oxime, 1 -(2-methyl- 1 -naphthalenyl)- 1 H-pyrrol-2,5-dione, l-(3,5-dichlorophenyl)-3-(2-propenyl)-2,5-pyrrolidinedione, l-[(diiodomethyl)-sulphonyl]-4-methyl-benzene, l-[[2-(2,4-dichlorophenyl)-l,3-dioxolan-2-yl]-methyl]-lH-imidazole, 1 -[[2-(4-chlorophenyl)-3-phenyloxiranyl]-methyl]- 1 H- 1 ,2,4-triazole, l-[l-[2-[(2,4-dichlorophenyl)-methoxy]-phenyl]-ethenyl]-lH-imidazole,

1 -methyl-5 -nonyl-2-(phenylmethyl)-3 -pyrrolidinole,

2',6'-dibromo-2-methyl-4'-trifluoromethoxy-4-trifluoro-methyl-l,3-tlιiazole-5- carboxanilide, 2,6-dichloro-5-(methylthio)-4-pyrimidinyl thiocyanate, 2,6-dichloro-N-(4-trifluoromethylbenzyl)-benzamide,

2,6-dichloro-N-[[4-(trifluoromethyl)-phenyl]-methyl]-benzamide, 2-(2,3 ,3 -triiodo-2-propenyl)-2H-tetrazole,

2- [( 1 -methylethyl)-sulphonyl] -5-(trichloromethyl)- 1 ,3 ,4-thiadiazole,

2-[[6-deoxy-4-O-(4-O-methyl-β-D-glycopyranosyl)-α-D-glucopyranosyl]-amino]-4- methoxy-lH-pyrrolo[2,3-d]pyrimidine-5-carbonitrile, 2-aminobutane,

2-bromo-2-(bromomethyl)-pentanedinitrile,

2-chloro-N-(2,3-dihydro- 1 , 1 ,3 -trimethyl- 1 H-inden-4-yl)-3 -pyridinecarboxamide,

2-chloro-N-(2,6-dimethylphenyl)-N-(isothiocyanatomethyl)-acetamide,

2-phenylphenol (OPP), 3 ,4-dichloro- 1 -[4-(difluoromethoxy)-phenyl] - 1 H-pyrrol-2,5-dione,

3 ,5 -dichloro-N- [cyano [( 1 -methyl-2-propinyl)-oxy] -methyl] -benzamide,

3 -( 1 , 1 -dimethylpropyl- 1 -oxo- 1 H-indene-2-carbonitrile,

3-[2-(4-chlorophenyl)-5-ethoxy-3-isoxazolidinyl]-pyridine,

4-chloro-2-cyano-N,N-dimethyl-5-(4-methylphenyl)- 1 H-imidazole- 1 -sulphonamide, 4-methyl-tetrazolo[l ,5-a]quinazolin-5(4H)-one,

8-hydroxyquinoline sulphate,

9H-xanthene-2-[(phenylamino)-carbonyl]-9-carboxylic hydrazide, bis-(l-methylethyl)-3-methyl-4-[(3-methylbenzoyl)-oxy] 2,5-thiophenedicarboxylate, cis- 1 -(4-chlorophenyl)-2-( 1 H- 1 ,2,4-triazol- 1 -yl)-cycloheptanol, cis-4-[3-[4-(l,l-dimethylpropyl)-phenyl-2-methylpropyl]-2,6-dimethyl- mo holinehydrochloride, ethyl [(4-chlorophenyl)-azo]-cyanoacetate, potassium hydrogen carbonate, methanetetrathiol sodium salt, methyl 1 -(2,3-dihydro-2,2-dimethyl- 1 H-inden- 1 -yl)- 1 H-imidazole-5-carboxylate, methyl N-(2,6-dimethylphenyl)-N-(5-isoxazolylcarbonyl)-DL-alaninate, methyl N-(chloroacetyl)-N-(2,6-dimethylphenyl)-DL-alaninate,

N-(2,6-dimethylphenyl)-2-methoxy-N-(tetrahydro-2-oxo-3-furanyl)-acetamide,

N-(2₅6-dimethylphenyl)-2-methoxy-N-(tetrahydro-2-oxo-3-thienyl)-acetamide, N-(2-chloro-4-nitrophenyl)-4-methyl-3 -nitro-benzenesulphonamide,

N-(4-cyclohexylphenyl)- 1 ,4,5,6-tetrahydro-2-pyrimidineamine, N-(4-hexylphenyl)-l,4,5,6-tetrahydro-2-pyrimidineamine, N-(5-chloro-2-methylphenyl)-2-methoxy-N-(2-oxo-3-oxazolidinyl)-acetamide, N-(6-methoxy)-3-pyridinyl)-cyclopropanecarboxamide, N-[2,2,2-trichloro-l-[(chloroacetyl)-amino]-ethyl]-benzamide, N- [3 -chloro-4,5 -bis(2-propinyloxy)-phenyl] -N' -memoxy-methanimidamide,

N-formyl-N-hydroxy-DL-alanine-sodium salt,

O,O-diethyl [2-(dipropylamino)-2-oxoethyl]-ethylphosphoramidothioate, O-methyl S-phenyl phenylpropylphosphoramidothioate, S-methyl 1 ,2,3 -benzothiadiazole-7-carbothioate, spiro [2H]- 1 -benzopyran-2, 1' (3 ' H)-isobenzofuran] -3 ' -one,

Bactericides: bronopol, dichlorophen, nitrapyrin, nickel dimethyldithiocarbamate, kasugamycin, octhilinone, furancarboxylic acid, oxytetracyclin, probenazole, streptomycin, tecloftalam, copper sulphate and other copper preparations.

Insecticides / acaricides / nematicides: abamectin, acephate, acetamiprid, acrinathrin, alanycarb, aldicarb, aldoxycarb, alpha- cypermethrin, alphamethrin, amitraz, avermectin, AZ 60541, azadirachtin, azamethiphos, azinphos A, azinphos M, azocyclotin,

Bacillus popilliae, Bacillus sphaericus, Bacillus subtilis, Bacillus thuringiensis, baculoviruses, Beauveria bassiana, Beauveria tenella, bendiocarb, benfuracarb, bensultap, benzoximate, betacyfluthrin, bifenazate, bifenthrin, bioethanomethrin, biopermethrin, BPMC, bromophos A, bufencarb, buprofezin, butathiofos, butocarboxim, butylpyridaben, cadusafos, carbaryl, carbofuran, carbophenothion, carbosulfan, cartap, chloethocarb, chlorethoxyfos, chlorfenapyr, chlorfenvinphos, chlorfluazuron, chlormephos, chlorpyrifos, chlorpyrifos M, chlovaporthrin, cis-resmethrin, cispermethrin, clocythrin, cloethocarb, clofentezine, cyanophos, cycloprene, cycloprothrin, cyfluthrin, cyhalothrin, cyhexatin, cypermethrin, cyromazine, deltamethrin, demeton M, demeton S, demeton-S-methyl, diafenthiuron, diazinon, dichlorvos, diflubenzuron, dimethoat, dimethylvinphos, diofenolan, disulfoton, docusat-sodium, dofenapyn, eflusilanate, emamectin, empenthrin, endosulfan, Entomopf hora spp., esfenvalerate, ethiofencarb, ethion, ethoprophos, etofenprox, etoxazole, etrimphos, fenamiphos, fenazaquin, fenbutatin oxide, fenitrothion, fenothiocarb, fenoxacrim, fenoxycarb, fenpropathrin, fenpyrad, fenpyrithrin, fenpyroximate, fenvalerate, fipronil, fluazuron, flubrocythrinate, flucycloxuron, flucythrinate, flufenoxuron, flutenzine, fluvalinate, fonophos, fosmethilan, fosthiazate, fubfenprox, furathiocarb, granulosis viruses, halofenozide, HCH, heptenophos, hexaflumuron, hexythiazox, hydroprene, imidacloprid, isazophos, isofenphos, isoxathion, ivermectin, lambda-cyhalothrin, lufenuron, malathion, mecarbam, metaldehyde, methamidophos, Metharhizium anisopliae, Metharhizium flavoviride, methidathion, methiocarb, methomyl, methoxyfenozide, metolcarb, metoxadiazone, mevinphos, milbemectin, monocrotophos, naled, nitenpyram, nithiazine, novaluron, nuclear polyhedrosis viruses, omethoat, oxamyl, oxydemethon M, Paecilomyces fumosoroseus, parathion A, parathion M, permethrin, phenthoat, phorat, phosalone, phosmet, phosphamidon, phoxim, pirimicarb, pirimiphos A, pirimiphos M, profenofos, promecarb, propoxur, prothiofos, prothoat, pymetrozine, pyraclofos, pyresmethrin, pyrethrum, pyridaben, pyridathion, pyrimidifen, pyriproxyfen, quinalphos, ribavirin, salithion, sebufos, silafluofen, spinosad, sulfotep, sulprofos, tau-fluvalinate, tebufenozide, tebufenpyrad, tebupirimiphos, teflubenzuron, tefluthrin, temephos, temivinphos, terbufos, tetrachlorvinphos, theta-cypermethrin, thiamethoxam, thiapronil, thiatriphos, thiocyclam hydrogen oxalate, thiodicarb, thiofanox, thuringiensin, tralocythrin, tralomethrin, triarathene, triazamate, triazophos, triazuron, trichlophenidine, trichlorfon, triflumuron, trimethacarb, thiacloprid, vamidothion, vaniliprole, Nerticillium lecanii, YI 5302, zeta-cypermethrin, zolaprofos,

(lR-cis)-[5-(phenylmethyl)-3-furanyl]-methyl-3-[(dihydro-2-oxo-3(2H)- furanylidene)-methyl] 2,2-dimethylcyclopropanecarboxylate,

(3-phenoxyphenyl)-methyl 2,2,3,3-tetramethylcyclopropanecarboxylate, 1 - [(2-chloro-5-thiazolyl)methyl]tetrahydro-3 ,5-dimethyl-Ν-nitro- 1 ,3 ,5-triazine-

2(lH)-imine,

2-(2-chloro-6-fluorophenyl)-4-[4-(l,l-dimethylethyl)phenyl]-4,5-dihydro-oxazole,

2-(acetyloxy)-3 -dodecyl- 1 ,4-naphthalenedione,

2-chloro-N-[[[4-(l-phenylethoxy)-phenyl]-amino]-carbonyl]-benzamide, 2-chIoro-N- [[[4-(2,2-dichloro- 1 , 1 -difluoroethoxy)-phenyl]-amino]-carbonyl]- benzamide,

3-methylphenyl propylcarbamate

4-[4-(4-ethoxyphenyl)-4-methylpentyl] - 1 -fluoro-2-phenoxy-benzene,

4-chloro-2-(l , 1 -dimethylethyl)-5-[[2-(2,6-dimethyl-4-phenoxyphenoxy)ethyl]thio]- 3(2H)-pyridazinone,

4-chloro-2-(2-chloro-2-methylpropyl)-5 - [(6-iodo-3 -pyridmyl)methoxy] -3 (2H)-pyri- dazinone,

4-chloro-5-[(6-chloro-3-pyridinyl)methoxy]-2-(3,4-dichlorophenyl)-3(2H)-pyri- dazinone, Bacillus thuringiensis strain EG-2348,

[2-benzoyl- 1 -( 1 , 1 -dimethylethyl)-hydrazinobenzoic acid,

2,2-dimethyl-3-(2,4-dichlorophenyl)-2-oxo-l-oxaspiro[4.5]dec-3-en-4-yl butanoate,

[3 - [(6-chloro-3 -pyridinyl)methyl] -2-tniazolidinylidene]-cyanamide, dihydro-2-(nitromethylene)-2H-l,3-thiazine-3(4H)-carboxaldehyde, ethyl [2-[[ 1 ,6-dihydro-6-oxo- 1 -(phenylmethyl)-4-pyridazinyl]oxy]ethyl]-carbamate,

N-(3 ,4,4-trifiuoro- 1 -oxo-3 -butenyl)-glycine, N-(4-chlorophenyl)-3-[4-(difluoromethoxy)phenyl]-4,5-dihydro-4-phenyl-lH-pyra- zole- 1 -carboxamide,

N-[(2-chloro-5-thiazolyl)methyl]-N'-methyl-N"-nitro-guanidine, N-methyl-N'-(l-methyl-2-propenyl)-l,2-hydrazinedicarbothioamide, N-methyl-N'-2-propenyl- 1 ,2-hydrazinedicarbothioamide,

O,O-diethyl [2-(dipropylamino)-2-oxoethyl]-ethylρhosphoramidothioate.

The active compounds can be used as such or in the form of their formulations or the use forms prepared therefrom by further dilution, such as ready-to-use solutions, emulsions, suspensions, powders, tablets, pastes, microcapsules and granules. They are used in the customary manner, for example by watering, immersion, spraying, atomising, misting, vaporizing, injecting, forming a slurry, brushing on, dusting, scattering, dry dressing, moist dressing, wet dressing, slurry dressing or encrusting.

In the treatment of parts of plants, the active compounds concentration in the use forms can be varied within a substantial range. They are, in general, from 1 to 0.0001% by weight, preferably from 0.5 and 0.001%.

For the treatment of seed, amounts of active compound of 0.001 to 50 g, especially 0.01 to 10 g, are generally employed per kilogram of seed.

For the treatment of soil, active compound concentrations, at the point of action, of 0.00001 to 0.1% by weight, especially of 0.0001 to 0.02%, are generally employed.

As already mentioned above, all plants and parts of plants can be treated according to the invention. In a preferred embodiment naturally occurring plant species and plant varieties or those obtained by conventional biological breeding methods, such as crossbreeding or protoplast fusion as well as parts of such plants are treated. In an additional preferred embodiment transgenic plants and plant varieties which have been obtained by genetic engineering methods, possibly in combination with conventional methods (genetically modified organisms) and parts of such plants are treated. The term "parts" or "parts of plants" or "plant parts" is explained above.

According to the invention plants of the plant varieties commercially available or used at any particular time are very preferably treated. Plant varieties are understood to be plants with specific properties ("traits") which have been obtained both by conventional breeding, by mutagenesis or by recombinant DNA techniques. They can be varieties, biotypes or genotypes.

Depending on the species or varieties of plants, their location and growth conditions

(the types of soil, climate, vegetation period and feed concerned), superadditive ("synergistic") effects can occur as a result of the treatment according to the invention. Effects such as for example reduced application rates and/or broadening of the activity spectra and/or increased activity of the compounds and compositions usable according to the invention, improved plant growth, increased tolerance of high or low temperatures, increased tolerance of dry conditions or water or ground salt contents, increased flowering capacity, facilitated harvesting, acceleration of maturity, increased crop yields, higher quality and/or increased nutritional value of the harvested crops and increased storing quality and/or processibility of the harvested crops are possible, which are greater than those actually expected.

Preferred transgenic plants or plant varieties (obtained by genetic engineering) to be treated according to the invention include all plants which as a result of the genetic modification concerned have received genetic material which provides them with particularly advantageous valuable properties ("traits"). Examples of such properties are improved plant growth, increased tolerance of high or low temperatures, increased tolerance of dry conditions or water or ground salt contents, increased flowering capacity, facilitated harvesting, acceleration of maturity, increased crop yields, higher quality and/or increased nutritional value of the harvested crops and increased storing quality and/or processibility of the harvested crops. Additional and particularly noteworthy examples of such properties are increased resistance of the plants to animal and microbial pests, such as to insects, mites, phytopathogenic fungi, bacteria and/or viruses as well as increased tolerance by the plants of certain herbicidal active compounds. Examples which may be mentioned of transgenic plants are the important crop plants such as cereals (wheat and rice), corn, soybeans, potatoes, cotton, rape and fruit plants (producing apples, pears, citrus fruits and grapes), the crop plants corn, soybeans, potatoes, cotton and rape being particularly noteworthy. Particularly significant properties ("traits") are increased resistance of the plants to insects due to the toxins forming in the plants, and in particular those which are produced in the plants (hereinafter referred to as "Bt plants") by the genetic material obtained from Bacillus Thuringiensis (e.g. by the genes CrylA(a), CrylA(b),

CrylA(c), CryllA, CryIIIB2, Cry9c Cry2Ab, Cry3Bb and CrylF and combinations thereof). Particularly significant properties ("traits") are the increased resistance of plants to fungi, bacteria and viruses due to systemically acquired resistance (SAR), systemin, phytoalexins, elicitors and resistance genes and correspondingly expressed proteins and toxins. Particulary significant properties ("traits") are also increased tolerance by the plants of certain herbicidal active compounds, such as for example imidazolinones, sulphonylureas, glyphosate or phosphinotricine (e.g. the "PAT" gene). The corresponding genes imparting the required properties ("traits") can also occur in the transgenic plants in combination with each other. Examples which may be mentioned of "Bt plants" are varieties of corn, cotton, soybeans and potatoes which are sold under the trade names YIELD GARD® (e.g. corn, cotton, soybeans), KnockOut® (e.g. corn), StarLink® (e.g. corn), Bollgard® (cotton), Nucotn® (cotton) and NewLeaf® (potatoes). Examples which may be mentioned of herbicide-tolerant plants are varieties of corn, cotton and soybeans which are sold under the trade names Roundup Ready® (tolerance of glyphosate, e.g. corn, cotton, soybeans), Liberty

Link® (tolerance of phosphinotricine, e.g. rape), IMI® (tolerance of imidazolinones) and STS® (tolerance of sulphonylureas, e.g. corn). Herbicide-resistant plants (bred for herbicide tolerance in the conventional manner) which may be mentioned are also the varieties (e.g. corn) sold under the name Clearfield®. The above statements do of course also apply to any plant varieties which may be developed in the future or launched onto the market in the future and which have the genetic properties ("traits") described above or developed in the future.

According to the invention the above-mentioned plants can be particularly advantageously treated with the compounds of the general formula I or the active compound mixtures according to the invention. The preferred ranges mentioned above for the active compounds or mixtures also apply to the treatment of these plants. Particularly advantageous is the treatment of plants with the compounds or mixtures specifically listed in the present text.

The preparation and the use of the compounds according to the invention is illustrated by the following examples. The invention, however, is not limited to said examples in any way.

Synthesis Example 1

Compound No.2

A solution of 3,4-dichloro-isothiazole-5-carbonyl chloride (1.0 g) in dichloromethane (5 ml) was added dropwise to a solution of 1-cyano-n-octyl-amine (0.78 g) and triethylamine (0.56 g) in dichloromethane (10 ml) whilst stirring under ice cooling.

After the addition was completed, the reaction mixture was warmed up to room temperature and was stirred for 3 hours at this temperature. The reaction mixture was then washed with water, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chroma- tography (eluent hexane : ethyl acetate = 9:1) to obtain N-(l-cyanooctyl)-3,4- dichloro-5-isothiazolecarboxamide (0.46 g). no²⁰ 1.5190 The following Table 1 shows compounds according to the invention, which were synthesized in the same manner as the compound of Synthesis Example 1. Said compound of Synthesis Example 1 is also listed in Table 1.

Table 1

Melting point (°C)

Compound or refractive index No. R¹ R" R³ (no²⁰)

1 CH₂CN H H 114-11

2 H H C₇H₁₅-n 1.5190

3 H H C₈H₁₇-n 1.5243

4 H H C H₁ -n 43-44

5 H H C₁₀H₂₁-n 55-57

Biological Test Example

Test Example A

Test for the effect of seed treatment against Pyricularia oryzae

Preparation of formulations of the compounds tested Active compound: 30 - 40 parts by weight

Carrier: mixture of diatomaceous earth and kaolin (1 :5), 55-65 parts by weight Emulsifϊer: polyoxyethylene alkyl phenyl ether, 5 parts by weight

The above-mentioned amounts of active compound, carrier and emulsifier are crushed and mixed to make a wettable powder. A portion of the wettable powder comprising the prescribed amount of active compound is diluted with water and used for testing.

Testing procedure

Seeds of paddy rice (variety: Kasabue) were drenched in a previously prepared diluted solution of an active compound having the prescribed concentration. 5 ml of such solution were used per 150 grains of seed. Drenching was conducted at a temperature of 20°C for 5 days. After the drenching, the air-dried seeds were sown in

2 plastic pots, each having a diameter of 9 cm, and the seeds were germinated by placing the pots in a warmed nursery box (32°C) for 3 days. After cultivating the seedlings for 2 weeks, the plants reached the 2 - 2.5 leaf stage. A spore suspension of artificially cultured Pyricularia oryzae was then sprayed on the test plants once, and the plants were kept at a temperature of 25°C and a relative atmospheric humidity of

100% for infection. Seven days after the inoculation, the infection rate per pot was classified and evaluated and the control value (%) was calculated. Phytotoxicity was tested at the same time. This test is an average of the results of 2 replications.

The evaluation of the infection rate and the calculation of the control value were conducted as follows:

Infection rate Percentage of lesion area in (%)

0 0

0.5 less than 2

1 2-less than 5

2 5-less than 10

3 10-less than 20

4 20-less than 40

5 more than 40

[ Infection rate of treated section x 100

Infection rate of untreated section

Test results

Compounds No. 1, 2, 3, 4, 5 and 7 showed control values of more than 90% at an active compound concentration of 500 ppm. No phytotoxicity was observed.

Formulation Examples

Formulation Example I (Granules)

25 parts by weight of water were added to a mixture of 10 parts by weight of Compound No. 1 according to the invention, 30 parts by weight of bentonite (mont- morillonite), 58 parts by weight of talc and 2 parts by weight of lignin sulphonic acid salt, and the mixture was kneaded thoroughly. The resulting product was granulated by means of an extrusion granulator to form granules having a size of from 10 to 40 meshes. The granules were dried at a temperature between 40 and 50°C. Formulation Example II (Granules)

95 parts by weight of a clay mineral having a particle size distribution within a range of from 0.2 to 2 mm were introduced into a rotary mixer. This product was uniformly wetted by spraying thereto under rotation a mixture of 5 parts by weight of Compound No. 2 according to the invention and a liquid diluent. The granules obtained in this manner were dried at a temperature between 40 and 50°C.

Formulation Example III (Emulsifiable Concentrate)

An emulsifiable concentrate was prepared by mixing 30 parts by weight of Compound No. 3 according to the invention, 55 parts by weight of xylene, 8 parts by weight of polyoxyethylene alkyl phenyl ether and 7 parts by weight of calcium alkylbenzene sulphonate with stirring.

Formulation Example IN (Wettable Powder)

A wettable powder was prepared by thoroughly mixing 15 parts by weight of Com- pound No. 5 according to the invention, 80 parts by weight of a mixture (1:5) of

White Carbon (fine powder of hydrated non-crystalline silicon oxide) and powdery clay, 2 parts by weight of sodium alkylbenzene sulphonate and 3 parts by weight of a condensate of sodium alkylnaphthalene sulphonate and formaldehyde in powdery state.

Formulation Example N (Wettable Granules)

20 parts by weight of Compound No. 7 according to the invention, 30 parts by weight of sodium lignin sulphonate, 15 parts by weight of bentonite and 35 parts by weight of calcined diatomaceous earth powder were thoroughly mixed with water. The resulting product was granulated by means of extrusion through a 0.3 mm screen. After drying the product, wettable granules were obtained.

Claims

Patent Claims

1. Isothiazolecarboxamides of the formula

wherein

R¹ represents a hydrogen atom or cyanomethyl,

R² represents a hydrogen atom or methyl, and

R represents a hydrogen atom, C₇.₁₀ alkyl or methoxycarbonylphenoxy- methyl,

provided that R , R and R are not simultaneously a hydrogen atom.

2. Isothiazolecarboxamides of the formula (I) according to claim 1, in which

R¹ represents a hydrogen atom or cyanomethyl,

R² represents a hydrogen atom or methyl, and

R³ represents a hydrogen atom, n-heptyl, n-octyl, n-nonyl, n-decyl or 4- methoxycarbonylphenoxymethyl,

provided that R¹, R² and R³ are not simultaneously a hydrogen atom.

3. Isothiazolecaboxamides of the formula (I) according to claim 1, in which R¹ represents a hydrogen atom or cyanomethyl,

R² represents a hydrogen atom, and

provided that R , R and R are not simultaneously a hydrogen atom.

4. Process for the preparation of isothiazolecarboxamides of the formula (I) according to claim 1, characterized in that 3,4-dichloro-isothiazole-5-carbonyl chloride of the formula

is reacted with amines of the formula

wherein

R , 1 , r R>2 and R have the above-mentioned meanings, in the presence of an inert solvent, and, if appropriate, in the presence of an acid binding agent and, if appropriate, in the presence of a phase transfer catalyst.

5. Microbicidal compositions, characterized in that they contain at least one isothiazolecarboxamide of the formula (I) according to claim 1 plus extenders and or surface-active agents.

6. Process for combating undesired microorganisms, characterized in that isothiazolecarboxamides of the formula (I) according to claim 1 are applied to the microorganisms and /or to their habitat.

7. Use of isothiazolecarboxamides of the formula (I) according to claim 1 for combating undesired microorganisms.

8. Process for the preparation of microbicidal compositions, characterized in that isothiazolecarboxamides of the formula (I) according to claim 1 are mixed with extenders and / or surface active agents.