WO2000029398A1 - Isothiazolecarboxylic acid derivatives - Google Patents

Abstract

Novel isothiazolecarboxylic acid derivatives of formula (I) in which X and Y have the meanings given in the specification, processes for the preparation of the new compounds and their use as biocides. New isothiazolecarboxylic acid chlorides of formula (II) in which X has the meanings given in the specification, and a process for the preparation of these compounds.

Description

Isothiazolecarboxylic Acid Derivatives

The present invention relates to novel isothiazolecarboxylic acid derivatives, to processes for their preparation and to their use as biocides.

It has already been known that certain isothiazolecarboxylic acid derivatives have plant growth regulating properties (see JP-A 21 432/1968 and JP-A 301 730/1988). Moreover, it has already been described that certain isothiazolecarboxylic acids can be employed for the control of plant pests (see JP-A 1 995/1968, JP-A 59 024/1993, JP-A 9 313/1994, JP-A 277 276/1996 and JP-A 277 277/1996). After all, a process for the preparation of isothiazolecarboxylic acids and the use of such compounds as agrochemicals or as intermediates have also been disclosed already (see JP-A 196 637/1995). The fungicidal activity of such known compounds, however, is not always satisfactory.

There have now been found novel isothiazolecarboxylic acid derivatives of the formula

in which

X represents halogen, Cj.4 alkyl or Cj_4 haloalkyl and

Y represents -O-Z, S-Z¹ or

in which Z represents hydrogen, Cμ₆ alkyl, C_]_4 haloalkyl, C3.8 cycloalkyl, optionally substituted C3.6 alkenyl, optionally substituted C3.6 alkynyl, substituted C_j.₄ alkyl, optionally substituted phenyl, optionally substituted naphthyl or optionally substituted heterocyclyl with 5 or 6 ring-members,

Z¹ represents hydrogen, C3-8 cycloalkyl or optionally substituted C_j-galkyl,

Z² represents hydrogen, Cι_₁₆ alkyl, C₃_8 cycloalkyl, C₃.₆ alkenyl, C₃.₆ alkynyl, substituted Cj-g alkyl, optionally substituted phenyl or optionally substituted 5- or 6-membered heterocyclyl with 1 to 3 heteroatoms selected from nitrogen, oxygen and sulphur,

Z³ represents hydrogen, C1..4 alkyl, C3.6 alkenyl or optionally substituted phenyl, or

Z² and Z³, together with the nitrogen atom to which they are bonded, form an optionally substituted 5- to 7-membered heterocyclic group, which in addition to the nitrogen atom may contain one or two more heteroatoms selected from nitrogen and oxygen.

Furthermore, it has been found that the isothiazolecarboxylic acid derivatives of the formula (I) can be prepared by

a) reacting isothiazolecarboxylic acid chlorides of the formula

in which

X has the above-mentioned meanings,

with compounds of the formula

H-Y (III)

in which

Y has 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,

or

b) reacting isothiazolecarboxylic acid derivatives of the formula

in which

X and Z have the above-mentioned meanings,

with amines of the formula

in which

Z² and Z³ have the above-mentioned meanings,

in the presence of an inert diluent,

or

c) reacting isothiazolecarboxylic acid derivatives of the formula

in which

X has the above-mentioned meanings,

with alcohols of the formula

in which

Z⁴ represents C_j_₁₆ alkyl, C₃_₈ cycloalkyl, C₃.₆ alkenyl, C₃.₆ alkynyl, substituted C_j.g alkyl, optionally substituted phenyl or optionally substituted 5- or 6-membered heterocyclyl with 1 to 3 heteroatoms selected from nitrogen, oxygen and sulphur, in the presence of an inert diluent and in the presence of an acid catalyst.

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

Surprisingly, the compounds according to the invention have a much better biocidal activity than the already known compounds, which are structurally most similar and have the same type of action.

In the present context, "halogen" represents fluoro, chloro, bromo or iodo.

"Alkyl" represents straight-chain or branched groups, such as methyl, ethyl, n- or isopropyl, n- iso-, sec- or tert-butyl, n-pentyl, iso-pentyl, tert-amyl, pentan-3-yl, neopentyl, n-hexyl, n-heptyl, n-octyl, n-nonyl, n-decyl, n-undecyl, n-dodecyl, n- tridecyl, n-tetradecyl, n-pentadecyl, n-hexadecyl etc.

"Alkoxy" represents straight-chain or branched groups, such as methoxy, ethoxy, n- or iso-propoxy, n-, iso-, sec- or tert-butoxy etc.

As examples of "cycloalkyl" there may be mentioned cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl and cyclooctyl.

The term"haloalkyl" represents straight-chain or branched alkyl groups, which are substituted by halogen, preferably fluorine, chlorine and/or bromine. As examples there may be mentioned trifluoromethyl, 2-fluoroethyl, 2-chloroethyl, 2-bromoethyl, 2,2,2-trifluoroethyl, 2,2,2 -trichloroethyl, 3-chloropropyl, 3-bromopropyl, 1- chloropropan-2-yl, l-bromopropan-2-yl, l,3-difluoropropan-2-yl, 2,3-dibromopropyl,

2,2-dichloro-3,3,3-trifluoropropyl etc. The term "optionally substituted phenyl" includes unsubstituted phenyl and phenyl that is substituted with one or more substituents, and in case it is substituted with a plurality of substituents, these substituents may be identical or different. As examples of such substituents there may be mentioned halogen such as fluoro, chloro, bromo and iodo; alkyl such as methyl, ethyl, n- or iso-propyl, n-, tert-, sec-, or iso-butyl etc.; alkoxy such as methoxy, ethoxy, n- or iso-propoxy, n-, tert-, sec- or iso-butoxy etc.; haloalkyl such as trifiuoromethyl, 2,2,2-trifluoromethyl, 2,2,2 -trichloroethyl etc.

The term "5- or 6-membered heterocyclic group" includes 5- or 6-membered saturated heterocyclic groups and 5- or 6-membered aromatic heterocyclic groups having 1 -4 hetero atoms selected from nitrogen, oxygen and sulphur.

As "5- or 6-membered aromatic heterocyclic group" there may be mentioned monovalent groups derived from, for example, pyrrolidine, tetrahydrofuran imidazolidine, pyrazolidine, piperidine, tetrahydropyran, piperidine, morpholine, 1 ,3- dioxolane etc. These heterocyclic groups may be substituted with, for example, hydroxy, halogen (for example, fluoro, chloro, bromo etc.), oxo, thioxo, alkyl, (for example, methyl, ethyl, n- or iso-propyl, n-, sec-, iso-, or tert-butyl etc.), alkoxy (methoxy, ethoxy, n- or iso-propoxy etc.), alkylthio (for example, methylthio, ethylthio, n- or iso-propylthio etc.), alkoxyalkyl (for example, methoxymethyl, ethoxymethyl etc.), alkylthioalkyl (for example, methylthiomethyl, ethylthiomethyl etc.), and in case a plurality of substituents are present, they may be identical or different.

As "5- or 6-membered aromatic heterocyclic group" there may be mentioned monovalent groups derived from, for example, furan, pyrrole, thiophene, imidazole, pyrazole, oxazole, isoxazole, thiazole, isothiazole, 1 ,2,4-triazole, 1,3,4-thiadiazole, pyridine, pyridazine, pyrimidine, pyrazine etc.

These heterocyclic groups may be substituted with, for example, cyano, nitro, halogen (for example, fluoro, chloro, bromo etc.), alkyl (for example, methyl, ethyl, WOKJO/29398 PCT/EP99/08355

- 7 -

n- or iso-propyl, n-, sec-, iso-, or tert-butyl etc.), alkoxy (methoxy, ethoxy, n- or iso- propoxy etc.), alkylthio (for example, methylthio, ethylthio, n- or iso-propylthio etc.), haloalkyl (for example, trifluoromethyl etc.), haloalkoxy (for example, trifluoro- methoxy etc.), cyanoalkyl (for example, cyanomethyl, 1-cyanoethyl, 1 -cyanopropyl etc.), alkoxycarbonyl (for example, methoxycarbonyl, ethoxycarbonyl etc.), alkoxyalkyl (for example, methoxymethyl, ethoxymethyl etc.), alkylthioalkyl (for example, methylthiomethyl, ethylthiomethyl etc.), and in case a plurality of substituents are present, they may be identical or different.

A "benzo condensed heterocyclic group with a 5- or 6-membered heterocyclic ring" is a benzo condensed cyclic group of a hetero as mentioned in the above in conjunction with "5- or 6-membered heterocyclic group" and its specific examples includes monovalent groups derived from benzo[b]thiophene, benzothiazole, benzoimidazole, benzotriazole, quinoline etc.

These condensed heterocyclic groups may be substituted with, for example, cyano, nitro, halogen (for example, fluoro, chloro, bromo etc.), alkyl (for example, methyl, ethyl, n- or iso-propyl, n-, sec-, iso-, or tert-butyl etc.), alkoxy (methoxy, ethoxy, n- or iso-propoxy etc.) alkylthio (for example, methylthio, ethylthio, n- or iso- propylthio etc.), alkoxyalkyl (for example, methoxymethyl, ethoxymethyl etc.), alkylthioalkyl (for example, methylthiomethyl, ethylthiomethyl etc.), and in case a plurality of substituents are present, they may be identical or different.

Formula (I) provides a general definition of the isothiazolecarboxylic acid derivatives according to the invention. Preferred compounds of the formula (I) are those, in which

X represents fluoro, chloro, bromo, methyl, ethyl, trifluoromethyl

or pentafluoroethyl, and Y represents -O-Z, -S-Z¹, or

^"N* , in which

represents hydrogen, Cj.₆ alkyl, Cj.3 haloalkyl, C3. cycloalkyl, C3.6 alkenyl which may be substituted with halogen, C₃_6 alkynyl which may be substituted with halogen,

or

Z represents substituted alkyl having 1 to 4 carbon atoms and 1 or 2 substituents selected from the group consisting of

C3-8 cycloalkyl, dialkylamino with 1 to 4 carbon atoms in each of the alkyl groups, C_j-4 alkylthio, alkylcarbonyl with 1 to 4 carbon atoms in the alkyl group, alkoxycarbonyl with 1 to 4 carbon atoms in the alkoxy group, cyano, nitro, trialkylsilyl with 3 to 6 carbon atoms in the alkyl groups,

-OR¹, in which

R¹ is hydrogen, C_j.g alkyl, C3.6 alkenyl, C_]_ haloalkyl, phenyl

(which may be substituted by halogen, C_j.4 alkyl and/or Cj_4 haloalkyl), benzyl, N-alkyl-N-phenyl-aminoalkyl with 1 to 4 carbon atoms in each of the alkyl groups or optionally substituted 5- or 6-membered heterocyclyl,

phenyl optionally substituted by 1 to 3 substituents selected from the group consisting of halogen, C_j_ alkyl, C_]_₄ alkoxy, C1.4 haloalkoxy, C]_₄ haloalkyl, benzyl, alkoxycarbonyl with 1 to 4 carbon atoms in the alkoxy group, sulfamoyl, nitro, cyano and/or carboxyl,

naphthyl

5- or 5-membered heterocyclyl with 1 to 3 heteroatoms selected from nitrogen, oxygen and/or sulphur, which heterocyclyl groups may be substituted by 1 to 3 substituents selected from halogen, C_j.₄ alkyl, oxo and/or thioxo,

and benzo-condensed heterocyclyl with 5- or 6-ring members in the heterocyclyl group and 1 to 3 heteroatoms selected from nitrogen, oxygen and/or sulphur, which heterocyclyl group may be substituted by Cμ₄ alkyl,

or

represents phenyl optionally substituted by 1 to 3 substituents selected from the group consisting of halogen, C . alkyl, Cj_4 haloalkyl, Cj_₄ haloalkoxy, phenoxy, phenyl, carboxy, alkoxycarbonyl with 1 to 4 carbon atoms in the alkoxy group, cyano, nitro and dialkylamino with 1 to 4 carbon atoms in each of the alkyl groups,

or

represents naphtyl,

or Z represents 5- or 6-membered heterocyclyl with 1 to 3 heteroatoms selected from nitrogen, oxygen and/or sulphur, which heterocyclyl groups may be substituted by 1 to 4 Cμ alkyl groups,

Z¹ represents hydrogen, C₅.₇ cycloalkyl or Cι_6 alkyl, which may be substituted by methoxycarbonyl, ethoxycarbonyl, phenyl or chlorophenyl,

Z² represents hydrogen, C_]._{] 6} alkyl, C3-8 cycloalkyl, C3.₄ alkenyl, C3.4 alkynyl,

or

Z² represents substituted alkyl having 1 to 5 carbon atoms and up to 4 substituents selected from the group consisting of

halogen, hydroxy, Cι_₄ alkoxy, Cj. alkylthio, N-Acyl Cj_₄ alkyl-amino, phenyl optionally substituted by 1 to 3 substituents selected from the group consisting of halogen, C_j.g alkyl, Cι-6- alkoxy, C₁.4 haloalkyl, Cj-4 haloalkoxy, sulfamoyl, dialkylaminomethyl with 1 to 4 carbon atoms in each alkyl group, phenyl or phenoxy, wherein the two last-mentioned radicals may be substituted by 1 or 2 substituents selected from the group consisting of halogen, C_j.g alkyl, C_j.₄ haloalkyl, C_]_ alkoxy, C1.4 alkylthio and cyano,

or 5- or 6-membered heterocyclyl with 1 or 2 heteroatoms selected from the group consisting of nitrogen, oxygen and sulphur, wherein said heterocyclyl group may be substituted by up to three substituents selected from halogen,

Cj.6 alkyl, C_j_ haloalkyl, C1.4 alkoxy, C_j_4 alkylthio and cyano,

or

Z² represents phenyl optionally substituted by 1 to 3 substituents selected from the group consisting of halogen, C_].₈ alkyl, C₃.g cyloalkyl, hydroxy, Cj-4 alkoxy, Cj_₄ haloalkyl, Cι_ haloalkyl, C_]. haloalkylthio, Cι_ haloalkyl- sulfonyl, C}_4 alkylthioalkyl, carboxyl, nitro, cyano, alkyloxycarbonyl with 1 to 4 carbon atoms in the alkoxy group, phenyl, phenoxy, benzoyl, phenylthiomethyl which may be substituted in the phenyl part by C_j.4 alkyl, and in case there are two substituents they may form a hydrocarbon ring,

or

Z² represents 5- to 6-membered heterocyclyl with 1 to 3 heteroatoms selected from nitrogen, oxygen, and/or sulphur, which heterocyclyl groups may be substituted by 1 or 2 substitutents selected from the group consisting of halogen, C1.4 alkyl, Cι_₄ alkoxy and Cι_4 haloalkyl,

and

Z³ represents hydrogen, methyl, ethyl, n-propyl, isopropyl, allyl, 2-butenyl or phenyl,

or

Z² and Z³, together with the nitrogen atom to which they are bonded, form a 5- or 6- membered heterocyclyl group, which in addition to the nitrogen atom may contain one or two more heteroatoms selected from nitrogen and oxygen, which heterocyclyl oxygen, which heterocyclyl groups may be substituted by up to 3 Cj-4 alkyl groups.

Particularly preferred are compounds of the formula (I), in which

X represents chloro, methyl or trifluoromethyl, and Y represents -O-Z, -S-Z¹,

, in which

Z represents hydrogen, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec- butyl, tert-butyl, 2-fluoroethyl, 2-chloroethyl, 2-bromoethyl, 3-chloropropyl, 3-bromopropyl, 1 -chloropropan-2-yl, 1 -bromopropan-2-yl, 2,3-dibromo- propyl, 2,2,2-trichloroethyl, 2,2-dichloro-3,3,3-trifluoropropyl, cyclopropyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, allyl, 4-pentenyl, 3-chloro- 2-butenyl, 2-cyanoethyl, propargyl, 3-hexynyl, 4-iodo-2-butynyl, 3-iodo- propinyl,

or

Z represents substituted alkyl having 1 to 3 carbon atoms and 1 or 2 substituents selected from the group consisting of

cyclopropyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, dimethyl- amino, diethylamino, dipropylamino, N-ethyl-N-methyl-amino, methylthio ethylthio, acetyl, propionyl, butyryl, pentylcarbonyl, 2,2-dimethyl-propionyl, methoxycarbonyl, ethoxycarbonyl, cyano, nitro, trimethylsilyl,

-OR¹, in which

R¹ is hydrogen, methyl, ethyl, n-propyl, isopropyl, n-butyl, allyl, 2- butenyl, 2,2,2-trifluoroethyl, l,3-difluoro-2-propyl, phenyl, 3-tri- fluoromethylphenyl, benzyl, N-methylanilinoethyl, N-ethylanilino- ethyl or 2-(l-pyrrolyl)ethyl, phenyl optionally substituted by 1 or 2 substituents selected from the group consisting of fluoro, chloro, methyl, methoxy, trifluoromethyl, trifluoromethoxy, benzyl, methoxy- carbonyl, sulfamoyl, nitro and cyano, 1-naphthyl, 2-naphthyl, 2- tetrahydrofuryl, 2-tetrahydropyranyl, 3-tetrahydrofuryl, l-methyl-4- piperidinyl, 2,2-dimethyl-l ,3-dioxolan-4-yl, 2-oxo-l ,3-dioxolan-4-yl, 2-thioxo-l,3-dioxolan-4-yl, 1 -piperidinyl, 2,6-dimethyl-4-morpholin- yl, 2-furyl, 2-thienyl, 1-pyrroyl, l-methyl-2-pyrrolyl, 1 -imidazolyl, 1- (1,2,4-triazolyl), 2-pyridyl, 3-pyridyl, 4-pyridyl, and 1 -benzotriazolyl,

or

Z represents phenyl optionally substituted by 1 or 2 substituents selected from the group consisting of fluoro, chloro, bromo, methyl, ethyl, n-propyl, tert- butyl, trifluoromethyl, trifluoromethoxy, tetrafluoroethoxy, phenoxy, phenyl, carboxy, methoxycarbonyl, ethoxycarbonyl, cyano, nitro, dimethylamino and diethylamino,

or

represents 1-naphthyl, 2-naphthyl or 2,2,6,6-tetramethyl-4-piperidinyl,

Z¹ represents hydrogen, cyclopropyl, cyclopentyl, cyclohexyl, methyl, ethyl or phenyl,

Z² represents hydrogen, methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, n- pentyl, n-hexyl, n-heptyl, n-octyl, n-nonyl, n-decyl, n-undecyl, n-dodecyl, n- tetradecyl, n-hexadecyl, cyclopropyl, cyclopentyl, cyclohexyl, cycloheptyl, allyl, 2-butenyl, propargyl,

or Z² represents substituted alkyl having 1 to 4 carbon atoms and 1 to 4 substituents selected from the group consisting of fluoro, chloro, hydroxy, methoxy, methylthio, N-formylmethylamino, N-formylethylamino, N-formylpropyl- amino, N-acetylmethylamino, N-benzoylmethylamino, phenyl optionally substituted by 1 to 2 substituents selected from the group consisting of fluoro, chloro, methyl, ethyl, n-propyl, isopropyl, tert-butyl, trifluoromethyl, trifluoromethoxy, sulfamoyl, dimethylaminomethyl, diethylamino-methyl, phenyl and phenoxy, wherein the two last-mentioned radicals may be substituted by 1 or 2 substituents selected from the group consisting of fluoro, chloro, methyl, ethyl, n-propyl, isopropyl, tert-butyl, trifluoromethyl, trifluoromethoxy, methylthio and cyano,

or

5- or 6-membered heterocyclyl with 1 or 2 heteroatoms selected from the group consisting of nitrogen, oxygen and sulphur,

or

Z² represents phenyl optionally substituted by 1 to 3 substituents selected from the group consisting of fluoro, chloro, methyl, ethyl, n-propyl, isopropyl, n- butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, pentan-3-yl, cyclopropyl, cyclopentyl, cyclohexyl, cycloheptyl, hydroxy, methoxy, ethoxy, trifluoromethyl, trifluoromethoxy, trifluoromethylthio, trifluoromethylsulfonyl, methylthiomethyl, ethylthiomethyl, n-propylthiomethyl, n-butylthiomethyl, neo-pentylthiomethyl, 4-tert-butylphenylthiomethyl, carboxyl, methoxy- carbonyl, ethoxycarbonyl, cyano, nitro, phenyl, phenoxy, benzyl and benzoyl, and in case there are 2 substituents they together may form a hydrocarbon ring,

or Z² represents 5- or 6-membered heterocyclyl with 1 to 3 heteroatoms selected from nitrogen, oxygen and sulphur, which heterocyclyl groups may be substituted by 1 or 2 substituents selected from the group consisting of fluoro, chloro, methyl, methoxy and trifluoromethyl,

and

Z³ represents hydrogen, methyl, ethyl, allyl or phenyl,

or

Z² and Z³ , together with the nitrogen atom to which they are bonded, form a 5- or 6- membered heterocyclic ring selected from the group consisting of pyrrolidino, piperidino, 2-methylpiperidino, morpholino, 2,6-dimethylmorpholino, 1- pyrrolyl, 1-imidazolyl and 1,2,4-triazol-l-yl.

Specific examples of isothiazolecarboxylic acid derivatives according to the invention are listed in the following Tables 1 and 2.

Table 1

X chloro hydrogen atom methyl hydrogen atom chloro methyl methyl methyl chloro ethyl chloro n-propyl chloro isopropyl chloro isobutyl chloro sec-butyl chloro tert-butyl chloro 2-bromoethyl chloro 2-chloroethyl chloro 2-fiuoroethyl chloro 2-cyanoethyl chloro 2-methoxyethyl chloro 2-n-butoxyethyl chloro 2-allyloxyethyl chloro 2,2,2 -trichloroethyl chloro 3-ethoxypropyl chloro 4-oxopentan-l-yl chloro 3-chloropropyl chloro 3-bromopropyl chloro 1 -chloropropan-2-yl Table 1 (continuation)

X Z chloro 1 -bromopropan-2-yl chloro 2,3-dibromopropyl chloro 2-nitroethyl chloro cyclopropylmethyl chloro 1 -cyclopropylethyl chloro cyclohexylmethyl chloro cyclooctylmethyl chloro 3-phenylpropyl chloro 2-phenylethyl chloro benzyl chloro 2-chlorobenzyl methyl 2-chlorobenzyl chloro 3-chlorobenzyl methyl 3-chlorobenzyl chloro 4-chlorobenzyl chloro 4-methylbenzyl chloro 4-methoxybenzyl chloro 4-nitrobenzyl chloro 2-(4-methoxyphenyl)ethyl chloro phenoxyethyl chloro 2-(4-chlorophenoxy)ethyl chloro allyl methyl allyl chloro 4-pentenyl chloro 2-propynyl chloro 3-hexynyl chloro 3 -chloro-2-buten- 1 -yl Table 1 (continuation)

X Z chloro cyclopropyl chloro cyclopentyl chloro cyclooctyl chloro phenyl chloro 2-chlorophenyl chloro 3-bromophenyl chloro 2,4-dichlorophenyl chloro 3,4-dichlorophenyl chloro 4-chloro-2-methylphenyl chloro 4-tert-butylphenyl chloro 3-nitrophenyl chloro 4-nitrophenyl chloro 3-cyanophenyl chloro 2-cyanophenyl chloro 3 -trifluoromethylphenyl chloro 2-trifluoromethylphenyl methyl 2-trifluoromethylphenyl chloro 3 -(N,N-dimethy lamino)phenyl chloro 2-methoxycarbonylphenyl methyl 2-methoxycarbonylphenyl chloro 3 -iodopropin-2-yl chloro methoxycarbonylmethyl chloro ethoxycarbonylmethyl chloro 1 -methoxycarbonylethyl chloro 1 -ethoxycarbonylethyl chloro 2-(N,N-dimethylamino)ethyl chloro 3-(N,N-dimethylamino)propyl Table 1 (continuation)

X Z chloro 3 -hy droxypropy 1 chloro 2-hydroxyethyl chloro 4-trifluoromethylbenzyl chloro furan-2-ylethyl chloro pyridin-2-ylethyl chloro pyrrol- 1-yl ethyl chloro 2-fluorobenzyl chloro 4-fluorobenzyl chloro 4-methylphenyl chloro 2-carboxyphenyl methyl 2-carboxyphenyl chloro tetrahydrofuran-2-ylmethyl methyl tetrahydrofuran-2-ylmethyl chloro tetrahy drofuran-3 -ylmethyl chloro 1 -methylpiperidin-4-ylmethyl chloro furan-2-ylmethyl chloro thiophen-2 -ylmethyl chloro 1 -methylpyrrol-2-ylmethyl chloro imidazol- 1 -ylmethyl chloro 1 ,2,4-triazol- 1 -ylmethyl chloro pyridin-2 -ylmethyl chloro pyridin-3 -ylmethyl chloro trimethylsilylmethyl chloro trimethylsilylethyl chloro naphth- 1 -ylmethyl chloro naphth-2 -ylmethyl chloro naphth-2-ylethyl Table 1 (continuation)

X Z chloro 1-phenethyl chloro 2-phenylpropan-2-yl chloro 4-cyanophenyl chloro 2-sulfamoylbenzyl chloro 2-methylthioethyl chloro cyclohexyl chloro pyridin-4-ylmethyl chloro 2,6-difiuorobenzyl chloro 2,2-dichloro-3,3,3-trifluoropropyl chloro 2-nitrobenzyl chloro 2-methylbenzyl chloro 2-methoxybenzyl methyl 2-methoxybenzyl chloro 2,2-dimethoxypropyl chloro 3-methyl-2-nitrobenzyl chloro cycloheptyl chloro 3 -methoxy benzyl chloro 2,4-dichlorobenzyl chloro 2,2-dimethyl- 1 ,3-dioxolan-4-ylmethyl chloro 2,3-dihydroxypropyl chloro 2-hydroxy-3 -methoxypropy 1 chloro 2,2,6,6-tetramethylpiperidin-4-yl chloro 2-oxo- 1 ,3 -dioxolan-4-ylmethyl chloro 2,3-dimethoxypropyl chloro 2-thioxo- 1 ,3-dioxolan-4-ylmethyl chloro 3 ,3 -dimethyl -2 -oxobutyl chloro 3 -ethoxy-2-hydroxypropy 1 Table 1 (continuation)

X Z chloro 2-( 1 -piperidinyl)ethy 1 chloro 2-(2,6-dimethylmorpholin-4-yl)ethyl chloro 2-(pyridin-3 -y l)ethyl chloro 2-diethylaminoethyl chloro 2-(pyridin-4-yl)ethyl chloro 2-(imidazol-l -yl)ethyl chloro 4-trifluoromethoxybenzyl chloro 2-( 1 -methylpyrrol-2-yl)ethyl chloro 1 -(pyridin-3-yl)ethyl chloro 3-trimethylsilylpropyl chloro 4-phenoxyphenyl chloro 3-phenylphenyl chloro 1 -(pyridin-2-yl)ethyl chloro 4-benzylbenzyl chloro acetonyl chloro 2-oxoheptyl chloro l-(furan-2-yl)ethyl chloro 1 -(pyridin-4-yl)ethyl chloro 2-trifluoromethoxyphenyl chloro 3-( 1 , 1 ,2,2-tetrafluoroethoxy)phenyl chloro 2-naphthyl chloro 2-(2-pyrrol- 1 -ylethoxy)ethyl chloro 2-(3 -trifluoromethylphenoxy)ethy 1 chloro 2-benzyloxyethyl chloro 2-(4-methoxycarbonylphenyl)ethyl chloro 2-[2-(N-ethyl-N-phenylamino)ethoxy]ethyl chloro 2-(2,2,2-trifluoroethoxy)ethyl Table 1 (continuation)

X Z chloro 2-( 1 ,3 -difluoropropan-2-yloxy)ethyl chloro 2-(benzotriazol- 1 -yl)ethyl chloro 2-(4-chlorophenyl)ethyl chloro 2-(4-tolyl)ethyl chloro l-(4-tolyl)ethyl chloro 1 -(4-chlorophenyl)ethyl methyl 1 -(4-chlorophenyl)ethyl chloro cyclopentyl chloro methoxycarbonylmethyl trifluoromethyl hydrogen atom trifluoromethyl methyl

Table 2

chloro ammo chloro methylamino methyl methylamino chloro isopropylammo methyl isopropylammo chloro piperidino chloro morpholino methyl morpholino chloro sec-butylamino chloro anilino chloro dimethylamino methyl dimethylamino chloro pyrrolidino chloro hexamethyleneimmo chloro 2,6-dimethylmorpholino chloro 2-methoxyethylamino chloro pyrrol- 1-yl chloro imidazol-1-yl chloro chloro 1,2,4-triazol-l-yl chloro chloro thiazol-2-ylamino methyl thiazol-2-ylamino chloro 1 ,3,4-thiadiazol-2-ylamino Table 2 (continuation)

X NZ²Z³ chloro pyridin-2-ylamino chloro pyrimidin-2-ylamino chloro pyridin-4-ylamino chloro 5-methylisoxazol-3-ylamino chloro propargylamino chloro diallylamino chloro benzylamino chloro 4-chlorobenzylamino methyl 4-chlorobenzylamino chloro 3 -chlorobenzy la ino chloro 2-chlorobenzylamino methyl 2-chlorobenzylamino chloro 2,4-dichlorobenzylamino chloro 3 ,4-dichlorobenzylamino chloro 2-fluorobenzylamino chloro 4-fluorobenzylamino chloro 2-methylbenzylamino chloro 1 -(imidazol- 1 -yl)ethylamino chloro 2-methylpiperidino chloro 4-methylbenzylamino chloro N-methylbenzylamino chloro imidazol- 1 -ylmethylamino chloro 4-benzoylanilino chloro n-hexadecylamino chloro n-tetradecylamino chloro n-decylamino chloro 2-fτjrfurylamino chloro cyclohexylamino Table 2 (continuation)

X NZ Z³ chloro n-octylamino chloro n-heptylamino chloro n-hexylamino chloro n-pentylamino chloro n-butylamino chloro 2,2,2-tri chloro- 1 -hydroxyethylamino chloro (4-aminosulfonylphenyl)ethylamino chloro ethylamino chloro N-methylamlino chloro 2,N-dimethylanilino chloro 4,N-dimethylanilino chloro 4-methoxy-N-methyl-anilino chloro 4-chloro-N-methyl-anilino chloro 3 -chloro-N-methyl-anilino chloro 2-chloro-N-methyl-anilino chloro 3 ,4-dichloro-N-methyl-anilino chloro N-ethyl-anilino chloro diphenylamino chloro N-benzyl-anilino chloro 3 -trifluoromethy lanilino chloro 2-trifluoromethylanilino chloro 4-nitroanilino methyl 4-nitroanilino chloro 2-nitroanilino methyl 2-nitroanilino chloro 4-cyanoanilino methyl 4-cyanoanilino Table 2 (continuation)

X NZ Z³ chloro 2,6-dichloroanilino chloro 2-methylthioethylamino chloro cycloheptylamino chloro 4-tert-butylanilino chloro 2-(4-tert-butylphenyl)ethylamino chloro 2-[4-(4-chlorophenoxy)phenyl]ethylamino chloro 2-[3-(4-chlorophenoxy)phenyl]ethylamino chloro 2,4-dimethylanilino chloro 2-hydroxyanilino chloro 4-(4-tert-butylphenylthiomethyl)anilino chloro 4-neo-pentylthiomethylanilino chloro 4-(N,N-diethylaminomethyl)benzylamino chloro 4-(pentan-3 -yl)anilino chloro 4-sec-butylanilino chloro 2-(3,4-dimethoxyphenyl)ethyl chloro 4-cyclohexylanilino chloro 2,3-dichloroanilino chloro 4-cycloheptylanilino chloro 2-phenylanilino chloro 1 , 1 ,3-trimethyl-2,3-dihydroinden-4-ylamino chloro 2-[4-(4'-chlorophenyl)phenyl]ethylamino chloro 1 -(4-chlorophenyl)ethylamino chloro 3-cyanoanilino chloro 2-cyanoanilino methyl 2-cyanoanilino chloro N-formyl-N-methylaminomethylamino methyl N-formyl-N-methylaminomethylamino Table 2 (continuation)

X NZ Z³ chloro 2-methoxycarbonylanilino methyl 2-methoxycarbonylanilino chloro 4-cyano-2,5-difluoroanilino methyl 4-cyano-2 , 5 -difluoroanilino chloro isopropy lamino methyl isopropylammo chloro 2,6-dichloro-4-trifluoromethylanilino methyl 2,6-dichloro-4-trifluoromethylanilino chloro diethylamino methyl diethylamino chloro 2-cyano-N-methylanilino chloro 4-(3-trifluoromethylphenoxy)benzylamino chloro 4-(4-trifluoromethoxyphenoxy)benzylamino chloro 4-(4-cyanophenoxy)benzylamino chloro 2-carboxyanilino methyl 2-carboxyanilino chloro 4-ethoxycarbonylanilino methyl 4-ethoxycarbonylanilino chloro 3 -trifluoromethylbenzylamino methyl 3 -trifluoromethylbenzylamino chloro 1 -(4-trifluoromethoxyphenyl)ethylamino methyl l-(4-trifluoromethoxyphenyl)ethylamino chloro 2-cyano-4-trifluoromethylanilino methyl 2-cyano-4-trifluoromethylanilino chloro 3 -chloro-5 -trifluoromethylpyridin-2-y lamino methyl 3-chloro-5-trifluoromethylpyridin-2-ylamino chloro 3 -methylisothiazol-5-ylamino Table 2 (continuation)

X NZ²Z³ chloro 4-(4-methylthiophenoxy)benzylamino methyl 4-(4-methylthiophenoxy)benzylamino chloro cyclopropylamino methyl cyclopropylamino chloro 4-trifluoromethylanilino methyl 4-trifluoromethylanilino chloro 4,6-dimethoxypyrirnidin-2-ylamino methyl 4,6-dimethoxypyrimidin-2-ylamino chloro 5-trifluoromethylpyridin-2-ylamino methyl 5-trifluoromethylpyridin-2-ylamino chloro 2-cyclohexylanilino chloro 4-carboxyanilino methyl 4-carboxyanilino chloro 6-chloropyridin-3-ylamino methyl 6-chloropyridin-3-ylamino chloro 1 -methyl-4-phenylpropylamino methyl 1 -methyl-4-phenylpropylamino chloro l-methyl-4-(3,4-difluorophenyl)propylamino methyl 1 -methyl-4-(3 ,4-difluorophenyl)propy lamino chloro 4-phenoxy-2-trifluoromethylanilino methyl 4-phenoxy-2-trifluoromethylanilino chloro 2-chloro-4-trifluoromethylsulfonylanilino methyl 2-chloro-4-trifluoromethylsulfonylanilino chloro 2-chloro-4-trifluoromethylthioanilino methyl 2-chloro-4-trifluoromethylthioanilino chloro 3-chloro-4-trifluoromethylthioanilino methyl 3-chloro-4-trifluoromethylthioanilino Table 2 (coi ntinuation)

X NZ Z³ chloro 2-chloro-4-trifluoromethoxyanilino methyl 2-chloro-4-trifluoromethoxyanilino chloro 2-chloro-4-nitroanilino chloro 4-cyano-2,5-difluoro-N-methylanilino methyl 4-cyano-2,5-difluoro-N-methylanilino chloro pyrrolidino methyl pyrrolidino chloro 2-hydroxyethylamino chloro 2-cyano-6-nitro-4-trifluoromethylanilino methyl 2-cyano-6-nitro-4-trifluoromethylanilino chloro 4-cyano-2-trifluoromethylanilino methyl 4-cyano-2-trifluoromethylanilino chloro 4-cyano-2,5-difluoro-N-methylanilino methyl 4-cyano-2,5-difluoro-N-methylanilino chloro 2-chloro-4-cyanoanilino methyl 2-chloro-4-cyanoanilino chloro 2-chloro-4-trifluoromethylanilino methyl 2-chloro-4-trifluoromethylanilino chloro 4-nitro-2-trifluoromethylanilino methyl 4-nitro-2-trifluoromethylanilino chloro 2-nitro-4-trifluoromethylanilino methyl 2-nitro-4-trifluoromethylanilino chloro 2,4-dinitroamlino methyl 2,4-dinitroanilino chloro 2,6-dinitroanilino methyl 2,6-dinitroanilino chloro 2,4,6-trichloroanilino Table 2 (continuation)

X NZ²Z³ methyl 2,4,6-trichloroanilino chloro 2,4-dichloro-6-nitroanilino methyl 2,4-dichloro-6-nitroanilino chloro 2,4-dichloro-6-cyanoanilino methyl 2,4-dichloro-6-cyanoanilino chloro 2,4-dichloro-6-trifluoromethylanilino methyl 2,4-dichloro-6-trifluoromethylanilino trifluoromethyl 2-chloro4-trifluoromethylsulfonylanilino trifluoromethyl 2-trifluoromethyl-4-trifluoromethylsulfonylanilino trifluoromethyl 2,5-difluoro-4-cyanoanilino trifluoromethyl 2-trifluoromethyl-4-phenoxyanilino trifluoromethyl 3-chloro-4-trifluoromethylthioanilino trifluoromethyl 2-chloro-4-cyanoanilino trifluoromethyl 4-trifluoromethyl-2-nitroanilino

If 3-chloro-4-cyano-5-isothiazolecarbonyl chloride and allylalcohol are used as starting materials, process (a) according to the invention can be illustrated by the following formula scheme.

If methyl 4-cyano-3-methyl-5-isothiazolecarboxylate and methylamine are used as starting materials, process (b) according to the invention can be illustrated by the following scheme.

If 3-chloro-4-cyano-5-isothiazolecarboxamide and N-formyl-N-hydroxymethyl- methylamine are used as starting materials, process (c) according to the invention can be illustrated by the following formula scheme.

Formula (II) provides a general definition of the isothiazolecarboxylic acid chlorides, which are required as starting materials for carrying out process (a) according to the invention. In this formula, X preferably has those meanings, which have already been mentioned as preferred for this substituent.

The following compounds may be mentioned as examples of isothiazolecarboxylic acid chlorides of the formula (II):

3-chloro-4-cyano-5-isothiazolecarbonyl chloride,

4-cyano-3-methyl-5-isothiazolecarbonyl chloride, 4-cyano-3-trifluoromethyl-5-isothiazolecarbonyl chloride.

The isothiazolecarboxylic acid chlorides of the formula (II) are novel. They can be prepared by

d) reacting isothiazolecarboxylic acids of the formula

in which

X has the above-mentioned meanings,

with chlorinating agents, such as thionyl chloride, phosphoryl chloride, phosphorous pentachloride etc.

Process (d) can be carried out according to principally known methods (see "SHIN JIKKEN KAGAKU KOUZA" (New lecture on experimental chemistry), Vol. 14 "Syntheses and reactions of organic compounds II" pp. 1106-1111 (published by Maruzen Co. Ltd. on December 20, 1977).

The isothiazolecarboxylic acids of the formula (Id), which are required as starting materials in process (d), are compounds according to the invention, which have not been described in the literature until now. They can be prepared by

e) reacting isothiazole derivatives of the formula

in which

X has the above-mentioned meanings, with compounds of the formula

HO-Z (IIIc)

in which

Z has the above-mentioned meanings,

and, if Z is different from hydrogen, hydrolyzing the esters of the formula (la) thus obtained.

Process (e) can be carried out according to principally known methods (see "SHIN JIKKEN KAGAKU KOUZA" (New lecture on experimental chemistry), Vol. 14 "Syntheses and reactions of organic compounds II" pp. 930-943 and 1022-1023

(published by Maruzen Co. Ltd. on December 20, 1977), Organic Functional Group Preparations, Vol. 3, pp. 276-281 (Academic Press New York and London, 1972), Journal Organic Chemistry, Vol. 26, pp. 412-418 (1961), etc.).

The isothiazole derivatives of the formula (IV) are known or can be prepared according to the principally known methods. Thus, they can be prepared by

f) reacting 4,5-dichloro-l,2,3-dithiazolium chloride with malonitrile or with compounds of the formula

in which X has the above-mentioned meanings,

Process (f) can be carried out according to known methods (see Journal of Chemistry Society, Perkin Trans. 1, 1997, pp. 3345-3349 or Journal of Chemistry Society, Perkin Trans. 1 , 1998, pp. 77-81 ).

The afore-mentioned 4,5-dichloro-l,2,3-dithiazolium chloride can be easily synthesized according to the process described in Chemische Berichte, 1985, Vol. 1 18, pp. 1632-1643.

Formula (III) provides a general definition of the compounds, which are required as reaction components for carrying out process (a) according to the invention. In this formula, Y preferably has those meanings, which have already been mentioned as preferred for this substituent.

The following compounds may be mentioned as example of the reaction components of the formula (III): methanol, isopropanol, cyclopentyl alcohol, phenol, benzyl alcohol, allyl alcohol, ethyl mercaptan, benzyl mercaptan, piperidine, aniline propargylamine, 1 -amino- 1 ,2,4-triazole.

The compounds of the formula (III) are known or can be prepared according to known methods (see "SHIN JIKKEN KAGAKU KOUZA" (New lecture on experimental chemistry), Vol. 14 "Syntheses and reactions of organic compounds I" pp. 451-566 (published by Maruzen Co. Ltd. on November 20, 1977), "SHIN JIKKEN KAGAKU KOUZA" (New lecture on experimental chemistry), Vol. 14

"Syntheses and reactions of organic compounds III" pp. 1332-1398 (published by Maruzen Co. Ltd. on February 20, 1978), "SHIN JIKKEN KAGAKU KOUZA" (New lecture on experimental chemistry), Vol. 14 "Syntheses and reactions of organic compounds III" pp. 1699-1712 (published by Maruzen Co. Ltd. on February 20, 1978) etc.) Formula (la) provides a general definition of the isothiazolecarboxylic acid derivatives, which are required as starting materials for carrying out process (b) according to the invention. In this formula, X and Z preferably have those meanings, which have already been mentioned as preferred for these radicals. Particularly preferred are the isothiazolecarboxylic acid derivatived of the formula (la), in which Z denotes a radical different from hydrogen.

The following compounds may be mentioned as examples of isothiazolecarboxylic acid derivatives of the formula (la):

methyl-3-chloro-4-cyano-5-isothiazolecarboxylate, methyl-4-cyano-3-methyl-5-isothiazolecarboxylate, methyl-4-cyano-3-trifluoromethyl-5-isothiazolecarboxylate.

The isothiazolecarboxylic acid derivatives of the formula (la) are compounds according to the invention, which can be prepared according to process (a) mentioned above.

Formula (Ilia) provides a general definition of the amines, which are also required as starting materials for carrying out process (b) according to the invention. In this formula, Z² and Z³ 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 (Ilia):

methylamine, n-butyl-amine, aniline, benzylamine, propargylamine, 1 -amino- 1 ,2,4-triazole.

The amines of the formula (Ilia) are known or can be prepared by known methods.

Formula (lb) provides a general definition of the isothiazolecarboxylic acid derivatives, which are required as starting materials for carrying out process (c) according to the invention. In this formula, X preferably has those meanings, which have already been mentioned as preferred for this radical.

The following compounds may be mentioned as examples of isothiazolecarboxylic acid derivatives of the formula (lb):

3-chloro-4-cyano-5-isothiazolecarboxamide,

4-cyano-3-methyl-5-isothiazolecarboxamide, 4-cyano-3-trifluoromethyl-5-isothiazolecarboxamide.

The isothiazolecarboxylic acid derivatives of the formula (lb) are compounds according to the invention, which can be prepared by process (a).

Formula (Illb) provides a general definition of the alcohols, which are also required as starting materials for carrying out process (c) according to the invention. In this formula, Z⁴ preferably has those meanings, which have already been mentioned as preferred for Z², excluding hydrogen.

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

(Illb): methanol, ethanol, benzyl alcohol, 4-chlorobenzyl alcohol, 3-trifluoromethyl- benzyl alcohol, N-formyl-N-hydroxylmethylmethylamine.

The alcohols of the formula (Illb) are known or can be prepared by known methods. All inert organic solvents customary for such reactions can be used as diluents for carrying out process (a) according to the invention. Suitable solvents preferably include 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, such as ethyl ether, methyl ethyl ether, isopropyl ether, butyl ether, dioxane, dimethoxyethane (DME), tetrahydrofuran (THF), diethylene glycol dimethyl ether (DGM) etc.; ketones, such as acetone, methyl ethyl ketone (MEK), methyl isopropyl ketone, methyl isobutyl ketone (MIBK) etc.; nitriles, such as acetonitrile, propionitrile, acrylnitrile etc.; esters, such as ethyl acetate, amyl acetate etc.; acid amides, such as dimethylformamide (DMF), dimethylacetamide (DMA), N-methylpyrrolidone, 1,3- dimethyl-2-imidazolidinone, hexamethylphosphoric triamide (HMPA) etc.; sulfones, sulfoxides, such as dimethyl sulfoxide (DMSO), sulfolane etc.; and bases, such as pyridine etc.

Suitable acid-binding agents for carrying out process (a) according to the invention are all customary inorganic and organic acid acceptors. The following can preferably be used hydrides, hydroxides, carbonates and bicarbonates of alkali metals and alkaline earth metals, such as sodium hydride, lithium hydride, sodium hydrogen carbonate, potassium hydrogen carbonate, sodium carbonate, potassium carbonate, lithium hydroxide, sodium hydroxide, potassium hydroxide, calcium hydroxide etc.; inorganic alkali metal amides, such as lithium amide, sodium amide, potassium amide etc.; alcoholates, tertiary amines, dialkylaminoanilines and pyridines, such as triethylamine, 1,1,4,4-tetramethylethylenediamine (TMEDA), N,N-dimethylaniline,

N,N-diethylaniline, pyridine, 4-dimethylaminopyridine (DMAP), 1 ,4-diazabicyclo- [2,2,2]octane (DABCO) and l,8-diazabicyclo[5,4,0]undec-7-ene (DBU) etc., organo- lithium compounds, such as methyl lithium, n-butyl lithium, sec-butyl lithium, tert- butyl lithium, phenyl lithium, dimethyl copper lithium, lithium diisopropylamide, lithium cyclohexyl isopropylamide, lithium dicyclohexylamide, n-butyl lithium.DBACO, n-butyl lithium.DBU, n-butyl lithium.TMEDA etc. Process (a) according to the invention can also be carried out in the presence of a phase-transfer catalyst. As examples of diluents used in that case there may be mentioned water, aliphatic, alicyclic and aromatic hydrocarbons (which may optionally be chlorinated), such as pentane, hexane, cyclohexane, petroleum ether, ligroine, benzene, toluene, xylene, dichloromethane, chlorobenzene, dichlorobenzene etc.; ethers, such as ethyl ether, methyl ethyl ether, isopropyl ether, butyl ether, dioxane, dimethoxyethane (DME), tetrahydrofuran (THF), diethylene glycol dimethyl ether (DGM) etc.; nitriles, such as acetonitrile, propionitrile, acrilonitrile etc.

As example of phase-transfer catalysts there may mentioned quaternary ions, such as tetramethylammonium bromide, tetrapropylammonium bromide, tetrabutyl- ammoniurn bromide, tetrabutylammonium hydrogen sulfate, tetrabutylammonium iodide, trioctylmethylammonium chloride, benzyltriethylammonium bromide, butyl- pyridinium bromide, heptylpyridinium bromide, benzyltriethylammonium chloride etc.; crown ethers, such as dibenzo-18-crown-6, dicyclohexyl-18-crown-6, 18-crown- 6-etc; cryptands, such as [2.2.2]-cryptate, [2.1.1]-cryptate, [2.2.1]-cryptate, [2.2.B]- cryptate, [20202S]-cryptate, [3.2.2]-cryptate etc.

When carrying out process (a) 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 -78°C and about +100°C, preferably between about -78°C and about +40°C.

Process (a) according to the invention is generally carried out under atmospheric pressure but, if desired, can also be carried out under elevated or reduced pressure.

When carrying out process (a) according to the invention, in general 1 mole of an isothiazolecarboxylic acid chloride of the formula (II) is reacted 1.0 to 2.5 moles of a compound of the formula (III) in the presence of a base and a diluent, such as dichloromethane.

Process (b) according to the invention can also be carried out in the presence of a diluent. Suitable diluents are all customary inert organic solvents as well as water.

The following can preferably be used: water, aliphatic, alicyclic or aromatic hydrocarbons (which may optionally bechlorinated), such as pentane, hexane, cyclohexane, petroleum ether, ligroine, benzene, toluene, xylene, dichloromethane, chloroform, carbon tetrachloride, 1,2-dichloroethane, chlorobenzene, dichloro- benzene etc., ethers, such as ethyl ether, methyl ethyl ether, isopropyl ether, butyl ether, dioxane, dimethoxyethane (DME), tetrahydrofuran (THF), diethyleneglycol dimethyl ether (DGM) etc.; ketones, such as acetone, methyl ethyl ketone (MEK), methyl isopropyl ketone, methyl isobutyl ketone (MIBK) etc.; nitriles, such as acetonitrile, propionitrile, acrylonitrile etc.; alcohols, such as methanol, ethanol, isopropanol, butanol, ethylene glycol etc.; esters such as ethyl acetate, amyl acetate etc.; acid amides, such as dimethylformamide (DMF), dimethylacetamide (DMA), N- methylpyrrolidone, l,3-dimethyl-2-imidazolidinone, hexamethylphosphoric triamide (HMPA) etc.; sulfones, sulfoxides, such as dimethyl sulfoxide (DMSO), sulfolane etc.; and bases, such as pyridine etc.

When carrying our process (b) 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 -78°C and about +100°C, preferably between about 0°C and about +30°C.

Process (b) according to the invention is generally carried out under atmospheric pressure but, if desired, can also be carried out under elevated or reduced pressure.

When carrying out process (b) according to the invention, in general 1 mole of an isothiazolecarboxylic acid derivative of the formula (la) is reacted with 1 to 2.2 moles of an amine of the formula (Ilia) in the presence of a diluent, such as dichloromethane.

Process (c) according to the invention can also be carried out in the presence of a diluent. As examples of suitable diluents there may be mentioned formic acid, acetic acid, propionic acid, trifluoroacetic acid etc.

Process (c) according to the invention can also be conducted in the presence of an acid catalyst.

As examples of such acid catalysts there may be mentioned mineral acids, such as sulfuric acid etc.; organic acids, such as methane sulfonic acid, benzene sulfonic acid, p-toluene sulfonic acid etc.

When carrying out process (c) 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 0°C and about +150°C, preferably between about 0°C and about +130°C.

Process (c) according to the invention is generally carried out under atmospheric pressure but, if desired, can also be carried out under elevated or reduced pressure.

When carrying out process (c) according to the invention, in general 1 mole of an isothiazolecarboxylic acid derivative of the formula (lb) is reacted with 1 to 2 moles of an alcohol of the formula (Illb) in the presence of 2 to 6 moles of an acid catalyst and in the presence of a diluent, such as acetic acid.

The isothiazolecarboxylic acid derivatives according to the present invention exhibit a strong biocidal 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 undesirable 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 Pseudomonoadaceae, Rhizobiaceae, Enterobacteriaceae, Corynebacteriaceae and

Streptomycetaceae.

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.

After all, the compounds according to the invention do also have insecticidal and/or herbicidal properties.

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 ULV 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.

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 compound 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.

The preparation and use of the active compounds according to the invention can be seen from the following examples. Synthesis Example 1

(Compound No. 29)

Process (a):

After thionyl chloride (5 ml) and dimethylformamide (3 drops) had been added to a solution of 3-chloro-4-cyano-5-isothiazolecarboxylic acid (1.0 g) in chloroform (50 ml), the mixture was refluxed by heating for 5 hours.

After cooling to room temperature, the solvent and the excess of thionyl chloride were distilled off under reduced pressure to obtain the objective 3-chloro-4-cyano-5- isothiazolecarbonyl chloride (1.0 g).

A solution of the 3-chloro-4-cyano-5-isothiazolecarbonyl chloride (1.0 g) obtained in dichloromethane (30 ml) was added drop by drop to a solution of allyl alcohol (0.4 g) and triethylamine (0.6 g) in dichloromethane (50 ml) at room temperature. After the addition, the mixture was stirred at room temperature for 2 hours, and the reaction mixture was then washed with water.

After drying the organic layer with anyhdrous sodium sulfate, the solvent was distilled off under reduced pressure and the residue was purified by silica gel column chromatography (eluent : toluene) to obtain the objective allyl 3-chloro-4-cyano-5- isothiazolecarboxylate (0.8 g). (Colorless crystals, mp.41-44°C). Synthesis Example 2

(Compound No. 74)

Process (a):

Thionyl chloride (5 ml) and dimethylformamide (3 drops) were added to a solution of 4-cyano-3-methyl-5-isothiazolecarboxylic acid (1.0 g) in chloroform (50 ml), and the mixture was refluxed by heating for 5 hours. After cooling to room temperature, the excess of thionyl chloride was distilled off under reduced pressure to obtain the objective 4-cyano-3-methyl-5-isothiazolecarbonyl chloride (1.0 g).

In another vessel, sodium hydride (0.25 g, 60% in oil) was added to a solution of 2,6- dichloro-4-(trifluoromethyl)aniline (1.4 g) in tetrahydrofuran (50 ml), and the mixture was stirred at room temperature for 1 hour. To this solution, the solution of the previously obtained 4-cyano-3-methyl-5-isothiazolecarbonyl chloride (1.0 g) in dichloromethane (30 ml) was added drop by drop at room temperature. After the addition, the mixture was stirred at room temperature for 10 hours. After that, dichloromethane (100 ml) was added and the reaction mixture was washed with water. After drying the organic layer with anhydrous sodium sulfate, the solvent was distilled off under reduced pressure and the residue was purified by silical gel column chromatography (eluent: ethyl acetate hloroform = 1 :20) to obtain the objective N- [2,6-dichloro-4-(trifluoromethyl)phenyl]-4-cyano-3-methyl-5-isothiazolecarboxa- mide (0.6 g). (Colorless crystals, mp. 216-217°C). Synthesis Example 3

(Compound No. 62)

Process (b):

Under ice cooling ammonia gas was introduced into methanol (100 ml) up to a saturation. To this solution, there was added methyl 3-chloro-4-cyano-5-isothiazole- carboxylate (4.0 g) under ice cooling, and the mixture was stirred for 30 minutes under ice cooling. The excess of solvent and ammonia gas were then distilled off under reduced pressure, and the residue was purified by silica gel column chromatography (eluent: ethyl acetatexhloroform = 1 :10) to obtain 3-chloro-4- cyano-5-isothiazolecarboxamide (3.2 g). (Colorless crystals, mp. 152-153°C).

Synthesis Example 4

(Compound No. 65)

Process (b):

A solution of methyl 4-cyano-3-methyl-5-isothiazolecarboxylate (1.0 g) in dichloro- methane (30 ml) was added drop by drop to a solution of methylamine (5.0 g, 40% methanol solution) in dichloromethane (50 ml) at room temperature. After the addition, the mixture was stirred at room temperature for 3 hours and the reaction mixture was washed with water. After drying the organic layer with anhydrous sodium sulfate, the solvent was distilled off under reduced pressure and the residue was purified by silica gel column chromatography (eluent: ethanolxhloroform = 1 :20) to obtain the objective N-methyl-4-cyano-3-methyl-5-isothiazolecarboxamide (0.9 g). (Colorless crystals, mp. 111-112°C).

Synthesis Example 5

(Compound No. 61)

Process (c):

N-formyl-N-hydroxylmethylmethylamine (1.78 g) was added to a solution of 3- chloro-4-cyano-5-isothiazolecarboxamide (3.74 g) in acetic acid (30 ml) and the mixture was stirred at room temperature for 1 hour. The reaction mixture was then cooled to 10°C and concentrated sulfuric acid (4.3 g) was added drop by drop to the mixture at a temperature of 10°C. After the mixture was stirred at the same temperature for 15 minutes, the reaction mixture was brought to the room temperature, stirred for 24 hours and extracted with dichloromethane (50 ml, twice).

After the organic layers were put together and dried with anhydrous sodium sulfate, the solvent was distilled off under reduced pressure and the residue was purified by silical gel column chromatography (eluent: dichloromethane:ethanol = 96:4) to obtain the objective N-(N'-formyl-N^,-methylaminomethyl)-3-chloro-4-cyano-5- isothiazolecarboxamide (2.1 g). (Colorless crystals, mp. 115-118°C)

The following Tables 3 to 5 show the compounds, the syntheses of which were disclosed in the Synthesis Examples 1 to 5, and other compounds which were synthesized in the same manner. Table 3

Compound

No. Y (Melting point °C)

1 hydroxy 108-114

2 methoxy 75-77

3 2-trifluoromethylphenoxy 105-106

2-cyanoanilino 188-189

5 isopropylammo 124

6 methylamino 154-156

7 4-cyano-2,5-difluoroanilino 148-149

8 4-(4-methylthiophenoxy)benzylamino 126-127

2-methoxycarbonylphenoxy 128-130

10 2-methoxycarbonylanilino 178-180

11 2-carboxyanilino 171

12 2-nitroanilino 186-188

13 4-nitroanilino 235-236

14 4-chlorobenzylamino 158-159

15 3 -trifluoromethylbenzylamino 158-159

16 l-(4-trifluoromethoxyphenyl)ethylamino 112-113

17 2-methoxybenzyloxy 162-163

18 2-chlorobenzyloxy 130-131 9 3 -chlorobenzyloxy 116-117 0 1 -(4-chlorophenyl)ethoxy 78-79 1 dimethylamino 72-73 Table 3 (continued)

Compound

No. Y (Melting point °C)

22 diethylamino 40-43

23 4-ethoxycarbonylanilino 213

24 2-carboxyphenoxy 179-180

25 thiazol-2-ylamino 250

26 2-cyano-4-trifluoromethylanilino 188

27 2,6-dichloro-4-trifluoromethylanilino 198-199

28 cyclopropylamino 152-153 9 allyloxy 41-44

30 morpholino n^D ₂₀ 1.5903*)

31 4-cyanoanilino 207-209

32 4-trifluoromethylanilino 248-249 3 4,6-dimethoxypyrimidin-2-ylamino 172-173 4 5-trifluoromethylpyridin-2-ylamino 186 5 3-chloro-5-trifluoromethylpyridin-2-ylamino 178 6 4-carboxyanilino 250 7 6-chloropyridin-3 -ylamino 191-192 8 1 -methyl-3-phenylpropylamino 113 9 l-methyl-3-(3,5-difluorophenyl)propylamino 122-124 0 4-phenoxy-2-trifluoromethylanilino 129-130 1 2-chloro-4-trifluoromethylsulfonylanilino 140-142 2 3 -chloro-4-trifluoromethylthioanilino 180-181 3 2-chloro-4-trifluoromethoxyanilino 141 4 methoxycarbonylmethyloxy 107-110 5 cyclopentyloxy 53-54 6 pyrrolidino 91-92 Table 3 (continued)

Compound

No. Y (Melting point °C)

47 2-cyano-6-nitro-4-trifluoromethylanilino 208-210

48 4-cyano-2-trifluoromethylanilino 197-199

49 2-chloro-4-nitroanilino 170- 174 50 4-cyano-2,5-difluoro-N-methylanilino 182-185

51 2-chloro-4-cyanoanilino 185-187

52 2-chloro-4-trifluoromethylanilino 165-166

53 4-nitro-2-trifluoromethylanilino 177-179

54 2-nitro-4-trifluoromethylanilino 134-138 55 2,4-dinitroanilino 174-175

56 2,6-dinitroanilino 182-184

57 2,4,6-trichloroanilino 212-213

58 2,4-dichloro-6-nitroanilino 193-194

59 2,4-dichloro-6-cyanoanilino 204-205 60 2,4-dichloro-6-trifluoromethylanilino 157-158

61 N-formyl-N-methylaminomethylamino 115-1 18

62 amino 152-153

*) Refractive index Table 4

Compound

No. Y (Melting point °C)

63 hydroxy 150-155

64 methoxy 55-57

65 methylamino 111-112

66 2-cyanoanilino 232-233

61 2-methoxycarbonylphenoxy 133-134

68 2-methoxycarbonylanilino 198-200

69 2-chlorobenzyloxy 98-101

70 1 -(4-chlorophenyl)ethoxy 65-66

71 2-chlorobenzylamino 150-152

72 4-chlorobenzylamino 151-153

73 2,5-difluoro-4-cyanoanilino 201-202

74 2,6-dichloro-4-trifluoromethylanilino 216-217

75 2-chloro-4-nitroanilino 153-154

76 2-chloro-4-trifluoromethylsulfonylanilino 153-155

Table 5

Compound

No. Y (Melting point °C)

77 hydroxy 82-86

78 methoxy 78-79

79 2-chloro-4-trifluoromethylsulfonylanilino 130

80 2-trifluoromethyl-4-trifluoromethylsulfonylanilino 113-115

Synthesis Example 6

(Compound No. 1)

Water (150 ml) was added to a solution of methyl 3-chloro-4-cyano-isothiazole- carboxylate (9.5 g) in methanol (150 ml) under ice cooling, and then potassium hydrogen carbonate (10 g) was added. The reaction mixture was brought to the room temperature and stirred for 100 hours at room temperature. After that the reaction mixture was cooled with ice, and 2N-hydrochloric acid (100 ml) was added thereto drop by drop. It was then extracted with ethyl acetate (100 ml, three times). After the organic layers were put together and dried with anhydrous sodium sulfate, the solvent was distilled off under reduced pressure and the deposit was washed with cold hexane to obtain 3-chloro-4-cyano-5-isothiazolecarboxylic acid (8.0 g). Colorless crystals, mp. 108-114°C). Synthesis Example 7

(Compound No.2)

To a solution of 3-chloro-4,5-dicyanoisothiazole (10 g) in methanol (200 ml) a solution of 28% sodium methoxide in methanol (1 g) was added drop by drop under stirring with ice cooling. The reaction mixture was brought to room temperature and stirred for 1 hour at room temperature. Ice (100 g), dichloromethane (100 ml) and 2N-hydrochloric acid (100 ml) were added to the reaction mixture, which was then stirred for 1 hour at room temperature. The organic layer was separated, and the aqueous layer was extracted with dichloromethane (50 ml, twice). After the combined organic layers were dried with anhydrous sodium sulfate, the solvent was distilled off under reduced pressure and the residue was purified by silica gel column chromatography (eluent: toluene) to obtain methyl 3-chloro-4-cyano-5-isothiazole- carboxylate (9.5 g). (Colorless crystals, mp. 75-77°C).

Synthesis Example 8

(Compound No. 77)

Water (100 ml) was added to a solution of methyl 4-cyano-3-trifluoromethyl-5- isothiazolecarboxylate (2.7 g) in methanol (100 ml) under ice cooling, and then potassium hydrogen carbonate (3.0 g) was added. The reaction mixture brought to the room temperature and stirred for 100 hours at room temperature. After that the reaction mixture was added to a mixture of ice (100 g), 2N-hydrochloric acid (100 ml) and ethyl acetate (100 ml). The organic layer was separated and the aqueous layer was extracted with ethyl acetate (100 ml, twice). After the combined organic layers were dried with anhydrous sodium sulfate, the solvent was distilled off under reduced pressure and the residue was purified by silica gel column chromatography (gradient elution: changing a solvent composition from chloroform to chloroform : ethyl acetate = 1 : 9) to obtain 4-cyano-3-trifluoromethyl-5-isothiazolecarb- oxylic acid (2.0 g). (Colorless crystals, mp. 82-86°C)

Synthesis Example 9

(Compound No. 78)

To as suspension of 4,5-dichloro-l,2,3-dithiazolium chloride (12.5 g) in dichloromethane (100 ml) a solution of 2-amino-3,3,3-trifluoropropenyl cyanide (6.8 g) in dichloromethane (50 ml) was added drop by drop under stirring with ice cooling. The reaction solution was stirred for 2 hours at room temperature. To the reaction mixture there was added a solution of pyridine (7.9 g) in dichloromethane (50 ml) drop by drop under stirring at room temperature in the course of 1 hour. The mixture was then stirred at room temperature for 2 hours. After the deposit was filtered off , the filtrate was concentrated under reduced pressure and the residue was purified by silica gel column chromatography (gradient elution: changing a solvent composition from toluene : hexane = 1 : 4 toluene : hexane = 1 : 1) to obtain 4,5-dicyano-3-tri- fluoromethylisothiazole (3.5 g). (brown oil). To a solution of the previous by prepared 4,5-dicyano-3-trifluoromethylisothiazole (3.5 g) in methanol (100 ml) a solution of 28% sodium methoxide in methanol (0.5 g) was added drop by drop under stirring with ice cooling. The reaction solution was brought to the room temperature and stirred for 30 minutes at room temperature. The reaction mixture was then added to a mixture of ice (100 g), dichloromethane

(50 ml) and 2N-hydrochloric acid (50 ml) and stirred for 1 hour at room temperature. The organic layer was separated and the aqueous layer was extracted with dichloromethane (50 ml, twice). After the combined organic layers were dried with anhydrous sodium sulfate, the solvent was distilled off under reduced pressure and the residue was purified by silica gel column chromatography (eluent: toluene) to obtain methyl 4-cyano-3-trifluoromethyl-5-isothiazolecarboxylate (2.7 g). (Colorless crystals, mp. 78-79°C).

Biological Test Examples

Test Example A

Test of foliar spray effect 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

Seedlings of paddy rice (cultivar: Kusabue) were cultured in plastic pots each having a diameter of 6 cm. The previously prepared solution of the prescribed concentration of active compound was sprayed over the seedlings in the 2-3 leaf stage, at a rate of 25 ml per 3 pots. 5 days after the application, a suspension of spores of artificially cultured Pyricularia oryzae was spray-inoculated once on the seedlings, and the seedlings were maintained at 25 °C and 100% relative humidity for infection. 7 days after the inoculation, the contraction rate per pot was classified and evaluated according to the following standard and the control value (%) was calculated. Phytotoxicity was tested at the same time. This test is an average of the results of 1 section 3 pots. The evaluation of the contraction rate and the calculation method of the control value are identical in each of the Test Examples 1-3. Contraction rate Percentage of lesion area in (%)

0 0

0.5 less than 2

1 2-less than 5

2 5-less than lO

3 10-less than 20

4 20-less than 40

5 more than 40

Control value (%) =

x 100 ontrac on ra e o untreate sect on

Test results

Compounds No. 1, 2, 3, 9 and 79 showed control values of more than 80% at an active compound concentration of 500 ppm.

Test Example B

Test of water surface application effect against Pyricularia oryzae.

Testing procedure

Seedlings of paddy rice (cultivar: Kusabue) in the 1.5 leaf stage were transplanted into irrigated plastic pots (30 cm²), one seedlings per pot. 7 days after the trans- planting (when the seedlings were in 3-4 leaf stage), the solution of the prescribed concentration of the active compound, which had been prepared in the manner similar to that of Test Example A, was dropped to the water surface with a pipette at a rate of 10 ml per pot. 7 days after the chemical treatment, a suspension of spores of artificially cultured Pryricularia oryzae (C race) was spray-inoculated once on the seedlings, and the seedlings were maintained in the inoculation box at 25°C and 100% relative humidity for 12 hours for infection. Thereafter, the seedlings were transferred to the greenhouse for management. 7 days after the inoculation, the contraction rate per pot was evaluated and further the control value (%) was calculated. Phytotoxicity was tested at the same time.

Test results

Compounds No. 1, 2, 3, 9, 17, 19, 20, 63, 64 and 67 showed control values of more than 80% at an active compound concentration of 8 kg/ha.

Test Example C

Spraying test against Phytophthora infestans.

Testing procedure

About 5 seeds of tomato (cultivar: Kurihara) were sown in each vinyl plastic pot of a diameter of 7 cm, and raised in a greenhouse (at 15-25°C). The solution obtained by diluting the prepared formulation of the test compound to the prescribed concentration as mentioned above, was sprayed at a rate of 25 ml per 3 pots over small seedlings reaching 4 leaf stage. Zoosporangia formed on the lesion of previously infected phytophthora infestans was washed down into distilled water through two layers of moslin to make a suspension. 10 days after the spraying, the suspension was inoculated by spraying to the plants to be treated and kept in a greenhouse of 15-20°C. 4 days after the inoculation, the contraction rate per pot was classified and the control value was calculated. The result is an average of 3 pots. Phytotoxicity was tested at the same time.

Test results

Compounds No. 1, 2, 9, 19, 20, 63, 64 and 67 showed control values of more than

80% at an active compound of 250 ppm. 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 tale 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 Com- pound 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. 20 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 IV (Wettable Powder) A wettable powder was prepared by thoroughly mixing 15 parts by weight of Compound No. 40 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 V (Wettable Granules)

20 parts by weight of Compound No. 67 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. Isothiazolecarboxylic acid derivatives of the formula

in which

X represents halogen, C_j.4 alkyl or C 1-4 haloalkyl and

Y represents -O-Z, S-Z¹ or

in which

Z represents hydrogen, Cj_₆ alkyl, C1.4 haloalkyl, C3. cycloalkyl, optionally substituted C^. alkenyl, optionally substituted C3.6 alkynyl, substituted Cj_4 alkyl, optionally substituted phenyl, optionally substituted naphthyl or optionally substituted heterocyclyl with 5 or 6 ring-members,

Z¹ represents hydrogen, C3- cycloalkyl or optionally substituted Cj-salkyl,

Z² represents hydrogen, Cj.jg alkyl, C3. cycloalkyl, C3.6 alkenyl, C3.6 alkynyl, substituted C_j_₆ alkyl, optionally substituted-phenyl or optionally substituted 5- or 6-membered heterocyclyl with 1 to 3 heteroatoms selected from nitrogen, oxygen and sulphur,

Z³ represents hydrogen, C_j.₄ alkyl, C₃.₆ alkenyl or optionally substituted phenyl, or

Z² and Z³, together with the nitrogen atom to which they are bonded, form an optionally substituted 5- to 7-membered heterocyclic group, which in addition to the nitrogen atom may contain one or two more heteroatoms selected from nitrogen and oxygen.

2. Isothiazolecarboxylic acid derivatives of the formula (I), according to claim 1, in which

X represents fluoro, chloro, bromo, methyl, ethyl, trifluoromethyl

or pentafluoroethyl, and

Y represents -O-Z, -S-Z¹, or

, in which

Z represents hydrogen C_j.g alkyl, C_j.3 haloalkyl, C3-8 cycloalkyl, C3-6 alkenyl which may be substituted with halogen, C3.6 alkynyl which may be substituted with halogen,

or represents substituted alkyl having 1 to 4 carbon atoms and 1 or 2 substituents selected from the group consisting of

C3-8 cycloalkyl, dialkylamino with 1 to 4 carbon atoms in each of the alkyl groups, C_j. alkylthio, alkylcarbonyl with 1 to 4 carbon atoms in the alkyl group, alkoxycarbonyl with 1 to 4 carbon atoms in the alkoxy group, cyano, nitro, trialkylsilyl with 3 to 6 carbon atoms in the alkyl groups,

-OR¹, in which

R¹ is hydrogen, C_j-g alkyl, C₃_6 alkenyl, C_j_ halolalkyl, phenyl

(which may be substituted by halogen, C_j_ alkyl and/or Cj.₄ haloalkyl), benzyl, N-alkyl-N-phenyl-aminoalkyl with 1 to 4 carbon atoms in each of the alkyl groups or optionally substituted 5- or 6-membered heterocyclyl,

phenyl optionally substituted by 1 to 3 substituents selected from the group consisting of halogen, Cj.4 alkyl, Cj.4 alkoxy, Cj.4 haloalkoxy, C_]_4 haloalkyl, benzyl, alkoxycarbonyl with 1 to 4 carbon atoms in the alkoxy group, sulfamoyl, nitro, cyano and/or carboxyl,

naphthyl

5- or 5-membered heterocyclyl with 1 to 3 heteroatoms selected from nitrogen, oxygen and/or sulphur, which heterocyclyl groups may be substituted by 1 to 3 substituents selected from halogen, Cj-4 alkyl, oxo and/or thioxo,

and benzo-condensed heterocyclyl with 5- or 6-ring members in the heterocyclyl group and 1 to 3 heteroatoms selected from nitrogen, oxygen and/or sulphur, which heterocyclyl group may be substituted by C}_4 alkyl,

or

Z represents phenyl optionally substituted by 1 to 3 substituents selected from the group consisting of halogen, C_j.^ alkyl, C_j.4 haloalkyl, Cj.4 haloalkoxy, phenoxy, phenyl, carboxy, alkoxycarbonyl with 1 to 4 carbon atoms in the alkoxy group, cyano, nitro and dialkylamino with 1 to 4 carbon atoms in each of the alkyl groups,

or

represents naphtyl,

or

Z represents 5- or 6-membered heterocyclyl with 1 to 3 heteroatoms selected from nitrogen, oxygen and/or sulphur, which heterocyclyl groups may be substituted by 1 to 4 C_]_₄ alkyl groups,

Z¹ represents hydrogen, C5.7 cycloalkyl or C_j. alkyl, which may be substituted by methoxycarbonyl, ethoxycarbonyl, phenyl or chlorophenyl,

Z² represents hydrogen, Cj.j6 alkyl, C₃.₈ cycloalkyl, 03.4 alkenyl, 03.4 alkynyl,

or Z² represents substituted alkyl having 1 to 5 carbon atoms and up to 4 substituents selected from the group consisting of

halogen, hydroxy, C_j.₄ alkoxy, C_j.4 alkylthio, N-acyl Cj.4 alkyl - amino, phenyl optionally substituted by 1 to 3 substituents selected from the group consisting of halogen, C_j.g alkyl, Cj.5. alkoxy, Cj_4 haloalkyl, Cj.4 haloalkoxy, sulfamoyl, dialkylaminomethyl with 1 to 4 carbon atoms in each alkyl group, phenyl or phenoxy, wherein the two last-mentioned radicals may be substituted by 1 or 2 substituents selected from the group consisting of halogen, Cj. alkyl, Cj_4 haloalkyl, Cj.4 alkoxy, C_]_ alkylthio and cyano,

or 5- or 6-membered heterocyclyl with 1 or 2 heteroatoms selected from the group consisting of nitrogen, oxygen and sulphur, wherein said heterocyclyl group may be substituted by up to three substituents selected from halogen, C_j. alkyl, C .4 haloalkyl, Cj.4 alkoxy, Cj.4 alkylthio and cyano,

or

Z² represents phenyl optionally substituted by 1 to 3 substituents selected from the group consisting of halogen, Cj_8 alkyl, C3. cyloalkyl, hydroxy, C_j.4 alkoxy, C_j_₄ haloalkyl, Cj_ haloalkoxy, Cj-4 haloalkylthio, C_j_₄ haloalkyl-sulfonyl, C_j- alkylthio-alkyl, carboxyl, nitro, cyano, alkyloxycarbonyl with 1 to 4 carbon atoms in the alkoxy group, phenyl, phenoxy, benzoyl, phenylthiomethyl which may be substituted in the phenyl part by C_j.4 alkyl, and in case there are two substituents they may form a hydrocarbon ring,

or Z² represents 5- to 6-membered heterocyclyl with 1 to 3 heteroatoms selected from nitrogen, oxygen, and/or sulphur, which heterocyclyl groups may be substituted by 1 or 2 substitutents selected from the group consisting of halogen, C_j.4 alkyl, C_j_4 alkoxy and C_j.4 haloalkyl,

and

Z³ represents hydrogen, methyl, ethyl, n-propyl, isopropyl, allyl, 2- butenyl or phenyl,

or

Z² and Z³, together with the nitrogen atom to which they are bonded, form a 5- or 6-membered heterocyclyl group, which in addition to the nitrogen atom may contain one or two more heteroatoms selected from nitrogen and oxygen, which heterocyclyl oxygen, which heterocyclyl groups may be substituted by up to 3 Cj.4 alkyl groups.

Isothiazolecarboxylic acid derivatives of the formula (I) according to claim 1 in which

X represents chloro, methyl or trifluoromethyl, and

Y represents -0-Z. -S-Z¹,

, in which

Z represents hydrogen, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, 2-fluoroethyl, 2-chloroethyl, 2- bromoethyl, 3-chloropropyl, 3-bromopropyl, 1 -chloropropan-2-yl, 1- bromopropan-2-yl, 2,3-dibromo-propyl, 2,2,2-trichloroethyl, 2,2- dichloro-3,3,3-trifluoropropyl, cyclopropyl, cyclopentyl, cyclohexy, cycloheptyl, cyclooctyl, allyl, 4-pentenyl, 3-chloro-2-butenyl, 2- cyanoethyl, propargyl, 3-hexynyl, 4-iodo-2-butynyl, 3-iodo-propinyl,

or

Z represents substituted alkyl having 1 to 3 carbon atoms and 1 or 2 substituents selected from the group consisting of

cyclopropyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, dimethyl-amino, diethylamino, dipropylamino, N-ethyl-N-methyl- amino, methylthio ethylthio, acetyl, propionyl, butyryl, pentylcarbonyl, 2,2-dimethyl-propionyl, methoxycarbonyl, ethoxycarbonyl, cyano, nitro, trimethylsilyl,

-OR¹, in which

R¹ is hydrogen, methyl, ethyl, n-propyl, isopropyl, n-butyl, allyl, 2-butenyl, 2,2,2 -trifluoroethyl, l,3-difluoro-2-propyl, phenyl, 3-tri-fluoromethylphenyl, benzyl, N-methylanilinoethyl, N- ethylanilino-ethyl or 2-(l-pyrrolyl)ethyl, phenyl optionally substituted by 1 or 2 substituents selected from the group consisting of fluoro, chloro, methyl, methoxy, trifluoromethyl, trifluoromethoxy, benzyl, methoxy-carbonyl, sulfamoyl, nitro and cyano, 1-naphthyl, 2-naphthyl, 2-tefrahydrofuryl, 2- tetrahydropyranyl, 3 -tetrahy drofuryl, l-methyl-4-piperidinyl,

2,2-dimethyl- l,3-dioxolan-4-yl, 2-oxo-l,3-dioxolan-4-yl, 2- thioxo-l,3-dioxolan-4-yl, 1 -piperidinyl, 2,6-dimethyl-4- morpholin-yl, 2-furyl, 2-thienyl, 1-pyrroyl, l-methyl-2- pyrrolyl, 1 -imidazolyl, l-(l,2,4-triazolyl), 2-pyridyl,

3-pyridyl, 4-pyridyl, and 1 -benzotriazolyl,

or

Z represents phenyl optionally substituted by 1 or 2 substituents selected from the group consisting of fluoro, chloro, bromo, methyl, ethyl, n- propyl, tert-butyl, trifluoromethyl, trifluoromethoxy, tetrafluoro- ethoxy, phenoxy, phenyl, carboxy, methoxycarbonyl, ethoxycarbonyl, cyano, nitro, dimethylamino and diethylamino,

or

Z represents 1-naphthyl, 2-naphthyl or 2,2,6,6-tetramethyl-4-piperidinyl,

Z¹ represents hydrogen, cyclopropyl, cyclopentyl, cyclohexyl, methyl, ethyl or phenyl,

Z² represents hydrogen, methyl, ethyl, n-propyl, isopropyl, n-butyl, sec- butyl, n-pentyl, n-hexyl, n-heptyl, n-octyl, n-nonyl, n-decyl, n- undecyl, n-dodecyl, n-tetradecyl, n-hexadecyl, cyclopropyl, cyclopentyl, cyclohexyl, cycloheptyl, allyl, 2-butenyl, propargyl,

or

Z² represents substituted alkyl having 1 to 4 carbon atoms and 1 to 4 substituents selected from the group consisting of fluoro, chloro, hydroxy, methoxy, methylthio, N-formylmethylamino, N- formylethylamino, N-formyl-propylamino, N-acetylmethylamino, N- benzoylmethylamino, phenyl optionally substituted by 1 to 2 substituents selected from the group consisting of fluoro, chloro, methyl, ethyl, n-propyl, isopropyl, tert-butyl, trifluoro-methyl, trifluoromethoxy, sulfamoyl, dimethylaminomethyl, diethylamino- methyl, phenyl and phenoxy, wherein the two last-mentioned radicals may be substituted by 1 or 2 substituents selected from the group consisting of fluoro, chloro, methyl, ethyl, n-propyl, isopropyl, tert- butyl, trifluromethyl, trifluoromethoxy, methylthio and cyano,

or

5- or 6-membered heterocyclyl with 1 or 2 heteroatoms selected from the group consisting of nitrogen, oxygen and sulphur,

or

Z² represents phenyl optionally substituted by 1 to 3 substituents selected from the group consisting of fluoro, chloro, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, pentan-3- yl, cyclopropyl, cyclopentyl, cyclohexyl, cycloheptyl, hydroxy, meth- oxy, ethoxy, trifluoro-methyl, trifluoromethoxy, trifluoromethylthio, trifluoromethylsulfonyl, methylthiomethyl, ethylthiomethyl, n- propylthiomethyl, n-butylthiomethyl, neo-pentylthiomethyl, 4-tert- butylphenylthiomethyl, carboxy, methoxycarbonyl, ethoxycarbonyl, cyano, nitro, phenyl, phenoxy, benzyl and benzoyl, and in case there are 2 substituents they together may form a hydrocarbon ring,

or

Z² represents 5- or 6-membered heterocyclyl with 1 to 3 heteroatoms selected from nitrogen, oxygen and sulphur, which heterocyclyl groups may be substituted by 1 or 2 substituents selected from the group consisting of fluoro, chloro, methyl, methoxy and trifluoromethyl,

and

Z³ represents hydrogen, methyl, ethyl, allyl or phenyl,

or

Z² and Z³ , together with the nitrogen atom to which they are bonded, form a

5- or 6-membered heterocyclic ring selected from the group consisting of pyrrolidino, piperidino, 2-methylpiperidino, morpholino, 2,6- dimethylmorpholino, 1-pyrrolyl, 1-imidazolyl and 1,2,

4-triazol-l-yl.

Process for the preparation of isothiazolecarboxylic acid derivatives of the formula (I) according to claim 1 , characterized in that

a) isothiazolecarboxylic acid chlorides of the formula

in which

X has the above-mentioned meanings,

are reacted with compounds of the formula

H-Y (III) in which

Y has 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,

or

isothiazolecarboxylic acid derivatives of the formula

in which

X and Z have the above-mentioned meanings,

are reacted with amines of the formula

in which

Z² and Z³ have the above-mentioned meanings,

in the presence of an inert diluent, or

c) isothiazolecarboxylic acid derivatives of the formula

in which

X has the above-mentioned meanings,

are reacted with alcohols of the formula

HO-Z⁴ (Illb)

in which

Z⁴ represents Cj._jg alkyl, C₃.₈ cycloalkyl, C₃.₆ alkenyl, C₃.₆ alkynyl, substituted C_j. alkyl, optionally substituted phenyl or optionally substituted 5- or 6-membered heterocyclyl with 1 to 3 heteroatoms selected from nitrogen, oxygen and sulphur,

in the presence of an inert diluent and in the presence of an acid catalyst.

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

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

7. Use of isothiazolecarboxylic acid derivatives of the formula (I) according to claim 1 for combating undesired microorganism.

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

9. Isothiazolecarboxylic acid chlorides of the formula

in which

X is halogen, Cj. alkyl or Cj_₄ haloalkyl.

10. Process for the preparation of isothiazolecarboxylic acid chlorides of the formula (II) according to claim 9, characterized in that

d) isothiazolecarboxylic acids of the formula

in which X has the above-mentioned meanings,

are reacted with chlorinating agents.