Fungicidal derivative of phenyl(thio)urea or phenyl(thio) carbamate

Description: TECHNICAL FIELD [Detailed description of the invention]

【0001】

The present invention relates to novel bactericidal derivatives of phenyl (thio) urea and phenyl (thio) carbamate, methods for producing them, and bactericidal compositions containing such derivatives.

【0002】

International patent application WO 95/22532 describes phenyltriazolinone with herbicidal activity. In particular, the compound of formula (A) is shown, but the characteristics of this compound are not described at all.

【0003】

[Chemical 3]

<img file="JP2002114751A_D0001.tif" />【0004】

The abstract and claims of the above patent application are limited to the description of the composition and its use that such compounds can be used for herbicidal purposes. The detailed description of the invention only provides herbicidal activity data as a practical support for such a description. The patent application suggests that some compounds may have bactericidal activity. However, no data on bactericidal activity have been shown. There is no description that specifies the type of compound that can have bactericidal activity or proves the bactericidal activity of compound (A).

【0005】

Applicants have here found that certain novel carbamates, thiocarbamate, urea and thiourea and their derivatives have bactericidal activity. Therefore, the present invention is based on the general formula (I) :. [0006]

[Chemical 4]

<img file="JP2002114751A_D0002.tif" />With respect to the compounds of and their salts.

【0007】

In the formula, W stands for O or S; Y stands for group-NR¹R², -OR³Or-SR³Represents; R⁰Represents an alkyl, alkenyl, alkynyl, acyl, cyano, carbocyclyl or heterocyclyl group, each substituted or unsubstituted; or a hydrogen atom; or a single bond with Y; R¹And R²Is the same group or a different group and represents any one of the groups defined in R0; or -NR^aR^{b b}, -OR^a, -SR^a, -S (O) R^a, -S (O)₂R^aRepresents here the same or different R^aAnd R^{b b}Represents an alkyl, alkenyl, alkynyl, acyl, cyano, sulfonyl, carbocyclyl or heterocyclyl group, each substituted or unsubstituted; or a hydrogen atom; R³Is R⁰Represents one of the groups defined in; R¹And R², Or R¹And R⁰, Or R³And R⁰, Or R^aAnd R^{b b}And, together with the atoms that bind them, form an arbitrarily substituted ring to form a carbocyclyl group or a heterocyclyl group as a whole; R⁴Represents each substituted or unsubstituted alkyl, alkenyl, alkynyl, carbocyclyl or heterocyclyl group; hydroxy; mercapto; azide; nitro; halogen atom; cyano; acyl; substituted or unsubstituted amino; cyanato; Thiosianato;-SF₅;-OR^a;-SR^aOr-Si (R)^a)₃Represents and here is R^aIs synonymous with; m is an integer selected from 0, 1, 2 and 3; R⁵When is present, R⁵Is the other R⁵Can be the same or different from any one of the R⁴Represents one of the groups defined in; R⁶Represents a substituted or unsubstituted carbocyclyl group or heterocyclyl group; A represents a direct bond; or [0008]

[Chemical 5]

<img file="JP2002114751A_D0003.tif" />Represents, here, -n represents 0, 1 or 2 -k stands for 1-9 -A¹Is-CHR⁷-Represents -A²Represents -C (= X)- -A³Is -C (R⁸) = NO- -A⁴Is -ON = C (R)⁸)-Represents -X stands for O or S -X¹Is O, S, NR⁹Or represents a direct join, -X²Is O, NR⁹Or represents a direct join, -X³Is a hydrogen atom, -C (= O)-, -SO₂-Or represents a direct join R⁷Is the other R⁷Can be the same or different groups as any one of the groups, each representing an substituted or unsubstituted alkyl, alkenyl, alkynyl, cyano, acyl, hydroxy, alkoxy, haloalkoxy, alkylthio, cycloalkyl or phenyl group. Represents a hydrogen atom or a halogen atom; R⁸Is the other R⁸Can be the same or different groups as any one of the groups, each representing a substituted or unsubstituted alkyl, alkenyl, alkynyl, alkoxy, alkylthio, carbocyclyl or heterocyclyl group; or a hydrogen atom; R⁹Is the other R⁹Can be the same or different group as any one of the above, representing a substituted or unsubstituted alkyl group, a substituted or unsubstituted carbocyclyl or heterocyclyl group, a hydrogen atom or an acyl group; or two groups in A R⁹Form a 5-7-membered ring with the atoms that bind them; the right part of the divalent group -A- is R⁶Combined with;-AR⁶And R⁵Can form a substituted or unsubstituted fused ring system together with benzene nucleus M.

【0009】

According to a preferred embodiment, the present invention relates to compounds of general formula (I) having the following characteristics and salts thereof. That is, R in the formula⁰Are substituted or unsubstituted by alkyl, acyl, by alkoxy, haloalkoxy, alkylthio or halogen atoms, or by phenyl optionally substituted with alkyl, haloalkyl, alkoxy, haloalkoxy, alkylthio or halogen atoms. Or represents a cyano group; or represents a hydrogen atom; R¹, R²And R³Is synonymous with; R⁴Are substituted or unsubstituted by alkyl, haloalkoxy, alkylthio or halogen atoms, or by phenyl optionally substituted with alkyl, haloalkyl, alkoxy, haloalkoxy, alkylthio or halogen atoms, respectively. Represents an alkynyl, alkoxy or alkylthio group; hydroxy; halogen atom; cyano; acyl (preferably -C (= O) R^c, -C (= S) R^cOr -S (O)_pR^cAnd here p is 0, 1 or 2 and R^cRepresents alkyl, haloalkyl, alkoxy, haloalkoxy, alkylthio, amino, monoalkylamino or dialkylamino, or phenyl optionally substituted with alkyl, haloalkyl, alkoxy, haloalkoxy or alkylthio; or phenyl Represents oxy, phenylthio, carbocyclyl or heterocyclyl); m represents 0 or 1; R⁵When is present, R⁵Is R above⁴Represents one of the groups defined in; A represents a direct bond or the divalent group -O-, -S-, -NR⁹-,-CHR⁷-Or -O-CHR⁷-Represents, here, R⁹Are each substituted or unsubstituted by an alkoxy, haloalkoxy, alkylthio or halogen atom, or by a phenyl optionally substituted with an alkyl, haloalkyl, alkoxy, haloalkoxy, alkylthio or halogen atom. Or represents an alkynyl group; or represents a hydrogen atom; R⁷Is R above⁹Represents a group defined in or represents a hydroxy, halogen atom, cyano, acyl, alkoxy, haloalkoxy or alkylthio; R⁶Represents a phenyl group or aromatic heterocyclyl group (preferably thiazolyl, isothiazolyl, thiadiazolyl, pyridyl or pyrimidinyl) optionally substituted with one or more substituents, wherein the one or more substituents are the same group. Or it may be a different group, hydroxy, halogen atom, cyano, acyl (preferably -C (= O) R^c, -C (= S) R^cOr -S (O)_pR^c, Where p is 0, 1 or 2 and R^cRepresents alkyl, haloalkyl, alkoxy, haloalkoxy, alkylthio, amino, monoalkylamino or dialkylamino, or phenyl optionally substituted with alkyl, haloalkyl, alkoxy, haloalkoxy or alkylthio; or phenyl Oxy, phenylthio, carbocyclyl or heterocyclyl), amino, alkylamino, dialkylamino, alkyl, alkoxy, alkynyl, haloalkyl, R^aRepresents O-alkyl, acyloxyalkyl, cyano-oxyalkyl, alkoxy, haloalkoxy or alkylthio, or optionally substituted carbocyclyl (preferably cyclohexyl or cyclopentyl) with alkyl, haloalkyl, alkoxy, haloalkoxy or alkylthio; Represents a benzyl optionally substituted with alkyl, haloalkyl, alkoxy, haloalkoxy or alkylthio.

【0010】

According to a particularly preferred embodiment, the present invention has the following features: R⁴Is C₁-C₁₀Represents an alkyl group or halogen atom of; m represents 1; R⁵Is C₁-C₁₀Represents the alkyl or halogen atom of the benzene nucleus, preferably at the 5-position of the nucleus M; A represents the direct bond or divalent group -O- and is present at the 4-position of the benzene nucleus M; R⁶Represents a phenyl group optionally substituted with one or more substituents selected from halogen, alkyl, alkenyl, alkynyl, haloalkyl, alkoxyalkyl, hydroxyalkyl, haloalkoxyalkyl, alkoxy, alkylthio, acyl or cyano; It relates to a compound of the general formula (I) having the above-mentioned characteristics alone or in combination, and a salt thereof.

【0011】

Complexes of the compounds of the invention are of the formula NAn or NAn.₂It can be formed by a conventional method from the salt of. In the formula, N represents a metal cation such as copper, manganese, cobalt, nickel, iron or zinc cation, and An represents an anion such as chloride, nitrate or sulfate anion.

【0012】

When the compound of the present invention contains an oxidizable nitrogen atom, the N-oxide of the compound of the present invention is also included in the scope of the present invention.

【0013】

When the compounds of the invention are present in the form of geometric isomers of E and Z, the invention includes individual isomers and mixtures thereof in any proportion.

【0014】

When the compounds of the invention are present in the form of tautomers, the invention includes individual tautomers and mixtures thereof in any proportion.

【0015】

When the compounds of the invention are present in the form of optical isomers, the invention includes individual optical isomers and mixtures thereof in any proportion, including 50:50 mixtures called racemic mixtures.

【0016】

All alkyl groups defined above may be linear or branched, generally 1-10 carbon atoms, preferably 1-7 carbon atoms, more preferably 1-5 carbon atoms. Have.

【0017】

All alkenyl or alkynyl groups as defined above may be linear or branched, preferably having 2-7 carbon atoms and generally having 3 or less double or triple bonds. These bonds may be conjugated. For example, there are vinyl, allyl, butadienyl or propargyl.

【0018】

Carbocyclyl groups are saturated, unsaturated or aromatic 3-8 membered ring groups. Preferred saturated carbocyclyl groups are cyclopropyl, cyclopentyl and cyclohexyl. Preferred unsaturated carbocyclyl groups contain up to 3 double bonds. The preferred aromatic carbocyclyl group is phenyl. In the text, the term carbocyclyl is used synonymously with carbocyclyl. The term carbocyclyl further includes any type of condensed carbocyclyl group such as naphthyl, phenanthryl, indanyl and indenyl.

【0019】

A heterocyclyl group is a saturated, unsaturated or aromatic 3-7 membered ring group in which no more than 4 ring atoms can consist of heteroatoms such as nitrogen, oxygen and sulfur. Therefore, as the heterocyclyl group, for example, frill, thienyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, imidazolyl, dioxolanyl, oxazolyl, thiazolyl, imidazolinyl, imidazolidinyl, pyrazolyl, pyrazolinyl, pyrazolydinyl, isoxazolyl, isothiazolyl, octidiazolyl, isothiazolyl. There are piperidinyl, dioxanyl, morpholino, dithianyl, thiomorpholino, pyridadinyl, pyrimidinyl, pyrazinyl, piperazinyl, sulfolanyl, tetrazolyl, triazinyl, azepinyl, oxazepinyl, thiazepinyl, diazepinyl and thiazolinyl.

【0020】

The term heterocyclyl further refers to condensed heterocyclyl groups such as benzimidazolyl, benzoxazolyl, imidazolypyridinyl, benzoxazinyl, benzothiadinyl, oxazolopyridinyl, benzofuranyl, quinolinyl, quinazolinyl, quinoxalinyl, dihydroquinazoli. Includes nyl, benzothiazolyl, phthalimide, benzofuranyl, benzodiazepinyl, indolyl and isoindrill. The term heterocyclic is also synonymous.

【0021】

The adjective "substituted" that modifies groups such as alkyl, alkenyl, alkynyl, carbocyclyl and heterocyclyl means that these groups are substituted with one or more of the same or different substituents. Substituents are hydroxy, alkenyl, alkynyl, mercapto, azide, nitro, halogen, cyano, acyl, alkoxycarbonyl, substituted or unsubstituted aminocarbonyl, substituted or unsubstituted amino, substituted or unsubstituted ammonio, substituted or unsubstituted. Substituted Carbocyclyls, Substituted or Unsubstituted Heterocyclyls, Cyanato, Thiosianato, -SF₅, -OR^a, -SOR^a, -SO₂R^aAnd -Si (R)^a)₃, Selected from, R here^aAre alkyl, alkenyl, alkynyl, carbocyclyl or heterocyclyl, each of which can be optionally substituted. For carbocyclyl and heterocyclyl groups, the list of substituents further includes alkyl, alkenyl and alkynyl, each of which can be optionally substituted. Preferred substituents on alkyl, alkenyl or alkynyl groups are alkoxy, haloalkoxy or alkylthio; halogens; substituted or unsubstituted phenyls, each having 1-5 carbon atoms. Preferred substituents for carbocyclyl and heterocyclyl groups are alkyl, haloalkyl, alkoxy, haloalkoxy or alkylthio; halogen; substituted or unsubstituted phenyl, each having 1-5 carbon atoms.

【0022】

Alkyl groups and carbon atoms of the carbocyclyl group and heterocyclyl group include oxo or imino, R optionally substituted with substituted or unsubstituted amino.^aOr -OR^a(R here^aIs synonymous with the above definition). Preferred groups are oxo, imino, alkylimino, oxymino, alkyloxymino or hydrazono.

【0023】

Substituted amino groups and amino groups in need of substitution are alkyl, alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted amino, -OR.^a(R here^aIs synonymous with the definition above), can be substituted with one or two identical or different substituents selected from carbocyclyl, heterocyclyl and acyl. In another embodiment, the two substituents can form a heterocyclyl group, preferably a 5-7 membered ring heterocyclyl group, together with the nitrogen atom to which they are attached, the heterocyclyl group may be substituted and another heteroatom. May include. Examples of this are morpholino, thiomorpholino or piperidinyl groups.

【0024】

The term acyl group includes sulfuric acid and phosphoric acid residues and carboxylic acid residues. Therefore, these residues have the general formula: -C (= X).^a) R^{b b}, -S (O)_pR^{b b}And -P (= X)^a) (OR^a) (OR^a), X in the formula^aRepresents O or S, R^{b b}Is the above R^aSynonymous with -OR^a, -SR^a, Substituted or unsubstituted amino or acyl, p represents 1 or 2. The preferred group is -C (= O) R^c, -C (= S) R^cAnd -S (O)_pR^cAnd here is R^cRepresents alkyl, C1-C5 alkoxy, C1-C5 alkylthio, phenyl, phenyloxy, phenylthio, carbocyclyl, heterocyclyl or amino, each of which can be optionally substituted.

【0025】

The compound of the present invention is effective as a fungicide (also called a fungicide), and is effective as a fungi imperfecti (Deuteromycetes), an oomycete (Oomycetes), an ascomycetes (Ascomycetes), a phycomycetes (Phycomycetes) and a basidiomycetes (Basidiomycetes). ) Family pathogens are controlled. For example, the antifungal activity against grain diseases such as: SEPTORIOSE (Leptosphaeria nodorum, Septoria tritici) of wheat, Erysiphe graminis f.sp hordei, Erysiphe graminis f.sp tritici, rust of wheat Diseases (Puccinia recondita, Pucciniastriiformis), wheat leaf rust (Pseudocercosporella herpotrichoides), barley HELMINTHOSPORIOSE (Drechslera teres), barley RHYNCHOSPORIOSE (Rhynchosporiose secalis).

【0026】

In addition, the following diseases are controlled: Solanaceae crops Phytophthora infestans, Plasmopara viticola, Botrytis cinerea, Rice diseases (PYRICULARIOSE, PELLICULARIOSE) , RHIZOCTONE).

【0027】

Accordingly, the present invention also provides a method for controlling phytopathogens in a field comprising applying one of the compounds of formula (I) or a salt thereof to a field contaminated with or susceptible to phytopathogens.

【0028】

The present invention also provides an agricultural composition comprising one of a compound of formula (I) or a salt thereof mixed with an agriculturally acceptable diluent or carrier.

【0029】

Of course, the composition of the present invention may contain two or more kinds of the compounds of the present invention.

【0030】

The composition further comprises one or more additional active ingredients, such as known compounds having properties such as plant growth regulators, herbicides, fungicides, insecticides, acaricides, fungicides or antibacterial agents. May contain. Thus, the compounds of the invention may be used sequentially or alternatively at the same time as another active ingredient (s).

【0031】

The diluent or carrier in the composition of the invention may be a solid or a liquid associated with a surfactant such as a dispersant, emulsifier or wetting agent. Anionic compounds are suitable surfactants. Examples of anionic compounds are carboxylates such as metal carboxylates of long chain fatty acids; N-acylsarcosineates; monoesters or diesters of fatty alcohol esterates or phenolalkylethylates with phosphates or such esters. Salts; sulfate esters of fatty alcohols such as dodecyl sodium sulfate, octadecyl sodium sulfate or cetyl sodium sulfate; sulfate esters of ethoxylated fatty alcohols; sulfate esters of ethoxylated alkylphenols; lignin sulfonates; petroleum sulfonates; alkyl-benzene sulfonates or lower Alkyl-naphthalene sulfonates Alkyl-aryl sulfonates such as butyl-naphthalene sulfonates; Condensations of naphthalene sulfonates-formaldehyde; Condensations of phenol sulfonates-formaldehyde; More complex sulfonates such as sulfonamides, eg olein Condensation of acid with sulfonated N-methyltaurin; dialkyl-sulfosuccinate, eg sodium sulfonate of dioctyl succinate; acid derivatives of alkyl glycoside compounds and alkyl polyglycoside compounds and their metal salts, eg alkyl citrate Polyglycosides or alkyl polyglycosides of tartrate; mono-, di- and tri-esters of sulfonic acids and their metal salts.

【0032】

Nonionic surfactants include fatty acid esters, fatty alcohols, fatty acid amides or condensates of phenol substituted with aliphatic alkyl or aliphatic alkenyl with ethylene oxide and / or propylene oxide; fatty esters of polyhydric alcohol ethers, For example, sorbitan fatty acid esters; condensates of such esters with ethylene oxide, such as polyoxyethylene sorbitan fatty acid esters; alkyl glycosides, alkyl polyglycosides; block copolymers of ethylene oxide and propylene oxide; 2,4,7,9- Acetylene glycols such as tetramethyl-5-decine-4,7-diol; ethoxylated acetylene glycols; graft copolymers with acrylic side chains; alkoxylated siloxane surfactants; or imidazoline-type surfactants such as 1-hydroxy There is ethyl-2-alkylimidazolin.

【0033】

Examples of cationic surfactants are monoamines, diamines or polyamines in the form of acetate, naphthenate or oleate; oxygen-containing amines such as amine oxides, polyoxyethylene-alkylamines or polyoxypropylene-alkylamines; carboxylic acids and diamines. Or an amine bound to an amide obtained by condensation with a polyamine; a quaternary ammonium salt.

【0034】

The compositions of the present invention are solutions, aerosols, dispersions, aqueous emulsions, microemulsions, dispersible concentrates, spray concentrates, seed coating or film coating compositions, smoke or smoke compositions, dispersions. It can be formed into any form used in the field of formulation of agrochemical compounds such as sex powders, emulsions (emulsified concentrates), granules or impregnated ribbons. The composition may also be in a form suitable for direct application, or in the form of a concentrate or original composition that needs to be diluted with an appropriate amount of water or another diluent prior to application.

【0035】

The dispersible concentrate contains the compound of the present invention, which is completely or partially dissolved in one or more water-soluble solvents, and one or more surfactants and / or polymerization agents. The addition of the formulation to water induces crystallization of the active ingredient, so this process is controlled by surfactants and / or polymers to give a fine dispersion.

【0036】

The powder for spraying contains the compound of the present invention in the form of a mixture that is homogeneously mixed and ground with a finely ground solid diluent such as kaolin.

【0037】

The emulsion comprises the compound of the present invention dissolved in a water immiscible solvent. The compound forms an emulsion or microemulsion when added to water in the presence of an emulsifier.

【0038】

The solid granules consist of the compounds of the invention associated with diluents similar to those used in spray powders. The mixture is granulated by a known method. Alternatively, the solid granules consist of an active ingredient absorbed or coated on a preformed granular carrier such as acid clay, atapulsite, silica or coarse limestone (limestone grit).

【0039】

Wettable powders, granules or granules generally contain the active ingredient as a mixture of a suitable surfactant and a powdered Inactive Diluent such as clay or diatomaceous earth.

【0040】

Other suitable concentrates are fluid concentrated suspensions formed by grinding the compound with water or another liquid, surfactant and suspending agent.

【0041】

The concentration of the active ingredient in the composition of the present invention for application to plants is preferably in the range of 0.0001-1.0% by weight, particularly 0.0001-0.01% by weight. The amount of active ingredient in the original composition can be adjusted in a wide range, for example in the range of 5-95% by weight of the composition.

【0042】

When the compound of the present invention is used, the compound of the present invention is generally applied to seeds, plants or their growing areas. The compounds can be applied directly to the soil before, during or after sowing so that the presence of the active ingredient in the soil controls the growth of fungi that attack the seeds. When treating the soil directly, the active ingredient is homogeneously mixed with the soil, such as spraying, spraying solid form granules, or applying the active ingredient at the same time as sowing using the same seeder as the seed. The active ingredient can be applied in some way. A suitable application dose is 5-1000 g / hectare, more preferably 10-500 g / hectare.

【0043】

Alternatively, the active ingredient may be applied directly to the plant at the time the fungus begins to appear on the plant, or as a precautionary measure before the appearance of the fungus, for example by spraying or spraying. The preferred method of application in both cases is foliar spray. Since plants are most severely damaged during the seedling stage, it is generally important to effectively control fungi during the seedling stage of the plant. If necessary, pre-germination herbicides or post-germination herbicides may be used as appropriate during spraying or spraying. It is also often possible to treat roots, bulbs, rhizomes or other tubers of plants before or under planting, for example by immersing the roots in a suitable composition in liquid or solid form. Suitable doses for direct application of the active ingredient to plants are in the range of 0.025-5 kg / hectare, preferably 0.05-1 kg / hectare.

【0044】

In addition, the compounds of the invention may be applied to harvested fruits, vegetables or grains to prevent infection during storage.

【0045】

Further, the compound of the present invention may be applied to a genetically modified plant or portion of a plant.

【0046】

In addition, the compounds of the invention may be used to treat fungal infections of building wood or to carry out public health. The compounds of the present invention can also be used to treat fungal infections in livestock or pastoralism.

【0047】

The compounds of the present invention can be prepared by many routes using known methods.

【0048】

For example, a compound of general formula (I) can be prepared from a compound of general formula (II) according to the following reaction scheme 1: [0049]

[Chemical 6]

<img file="JP2002114751A_D0004.tif" />【0050】

The reaction for converting the compound of formula (II) to the compound of formula (I) is carried out under the following conditions: -Universally react with Cl (CW) Y, that is, W stands for O and Y stands for -NR¹R²Carbamoyl chloride, W for S and Y for -NR¹R²When is represented by thiocarbamoyl chloride, W stands for O and Y stands for -OR.³Chloroformate, W for S and Y for -OR³Chlorthionoformate, W for O and Y for -SR³When, represents chlorothiol formate, W stands for S, and Y stands for -SR.³When expressing, react with chlorodithioformate; -R⁰When is a hydrogen atom and W is O, it reacts with phosgene, diphosgene or triphosgene to form an isocyanate and then treats with HY; -R⁰When is a hydrogen atom and W is S, it reacts with thiophosgene to form isothiocyanate, which is then treated with HY; -Y is -NHR¹When representing, R¹React with N = (CW); -W stands for S and Y stands for -SR³Represents R⁰If is not a hydrogen atom, then carbon disulfide and R³React with X, where X represents a halogen atom or any other leaving group.

【0051】

Further, the compound of the general formula (I) has a group R.⁰Or R¹Or R²Or R³By derivatization of; or W represents O and R⁰, R¹Or R²Or R³When represents a hydrogen atom, it can be converted to another compound of general formula (I) by acylation, cyanation or alkylation.

【0052】

R⁰If is not a hydrogen atom, the compound of general formula (II) can be prepared from the compound of general formula (III) according to the following reaction scheme 2.

【0053】

[Chemical 7]

<img file="JP2002114751A_D0005.tif" />【0054】

The reaction that causes the conversion is performed under the following conditions: -R⁰If represents an alkyl group, formylate or acylate with anhydride and then reduce with dimethyl sulfide borane; -R⁰If represents a cyano group, cyanide with chlorocyan or bromocyan; -R⁰When represents an acyl group, it is acylated with an acyl halide.

【0055】

The compound of general formula (III) can be prepared by reducing the nitro group of the compound of (IV) according to the reaction scheme 3. Preferred reaction conditions include reaction with hydrated hydrazine in ethanol catalyzed by palladium or platinum.

【0056】

[Chemical 8]

<img file="JP2002114751A_D0006.tif" />【0057】

The compound of formula (IIIa), that is, the compound of general formula (III) in which A in the formula represents a direct bond, is X in the formula.^VCan be prepared according to Reaction Scheme 4, which represents a leaving group.

【0058】

[Chemical 9]

<img file="JP2002114751A_D0007.tif" />【0059】

Compound of formula (IIIb), i.e. R in formula⁴The compound of the general formula (III) in which is a halogen atom is X in the formula.^TCan be produced according to the reaction scheme 5 in which is a halogen atom. X^TWhen represents bromine, preferred reaction conditions include stirring with bromine in a suitable solvent.

【0060】

[Chemical 10]

<img file="JP2002114751A_D0008.tif" />【0061】

The compound of formula (IIIc), that is, the compound of general formula (III) in which A in the formula represents NHC (= O)-; the compound of formula (IIId), that is, A in the formula represents a direct bond R⁶Compounds of formula (III); compounds of formula (IIIe), where is a substituted or unsubstituted phthalimide group and the curve connecting the 3- and 4-positions of the phthalimide group represents a substituted or unsubstituted carbocyclic chain. That is, A in the equation represents a direct bond and R⁶Compounds of general formula (III) representing a pyrrolyl group in which is optionally substituted with one or more identical or different groups R at the 2- or 5-position are according to the procedure shown in Reaction Scheme 6 from the compound of formula (V). Can be manufactured. For some compounds of general formula (V), the group R to improve yield⁴It may be necessary to protect / deprotect the amino group at the ortho position of.

【0062】

[Chemical 11]

<img file="JP2002114751A_D0009.tif" />【0063】

The compound of formula (IVa), that is, A in the formula is the group A^ZThe compound of the general formula (IV) representing the above can be produced by reacting the compound of the formula (VI) with the compound of the formula (VII) according to the reaction scheme 7. A^ZRepresents a group in compound (VI) that forms an anion under basic conditions. Alternatively, A^ZRepresents a primary or secondary basic nitrogen atom, X^ZRepresents a leaving group, preferably a halogen atom. A^ZWhen is representing an oxygen atom, preferred reaction conditions include treatment of (VI) with sodium hydride followed by addition of (VII). A^ZWhen is representing a sulfur atom, preferred reaction conditions include the reaction of (VI) and (VII) in the presence of a tertiary amine base such as ethyldiisopropylamine. A^ZIs-CHR⁷Preferred reaction conditions include treatment of (VI) with potassium tert-butyrate in cold dimethylformamide. A^ZWhen is representing a basic nitrogen atom, no base is needed.

【0064】

[Chemical 12]

<img file="JP2002114751A_D0010.tif" />【0065】

The compound of formula (IVb), that is, A in the formula is the group A^WThe compound of the general formula (IV) representing the above can be produced by reacting the compound of the formula (VIII) with the compound of the formula (IX) according to the reaction scheme 8. A^WRepresents a group in compound (VIII) that forms an anion under basic conditions. X^WRepresents a leaving group, preferably a halogen atom. Preferred basic conditions include the reaction of (VIII) with potassium carbonate or sodium hydride, followed by the addition of (IX).

【0066】

[Chemical 13]

<img file="JP2002114751A_D0011.tif" />【0067】

A compound of formula (IVc), i.e. a compound of general formula (IV) in which A represents O, is prepared by reacting a compound of formula (X) with a boronic acid of formula (XI) according to reaction scheme 9. it can. Preferred reaction conditions include the reaction of copper acetate with triethylamine.

【0068】

[Chemical 14]

<img file="JP2002114751A_D0012.tif" />【0069】

The compound of formula (IVd), that is, the compound of formula (IV) in which A in the formula represents a direct bond, is X in the formula.^ZCan be prepared from a compound of formula (XII) representing a leaving group, preferably a halogen atom, according to reaction scheme 10.

【0070】

[Chemical 15]

<img file="JP2002114751A_D0013.tif" />【0071】

A in the equation represents a direct bond R⁶Compounds of formula (IV) representing a heterocyclic group can be prepared using a number of methods known to those of skill in the art (see, eg, Comprehensive Heterocyclic Chemistry, Vols 1-7, ARK atritzky et CW Rees). For example, a compound of formula (IV) containing a 1,2,4-oxadiazole-3-yl group [Compound (IVe)] and a formula (IV) containing a 1,3,4-oxadiazole-2-yl group. ) Compound [Compound (IVf)] is shown in Reaction Schemes 11 and 12.

【0072】

[Chemical 16]

<img file="JP2002114751A_D0014.tif" />【0073】

[Chemical 17]

<img file="JP2002114751A_D0015.tif" />【0074】

The compound of formula (IIIf), i.e. A in the formula is -CHR⁷Represents this R⁷The compound of the general formula (III) representing a hydroxy or alkoxy group can be prepared from the compound of the formula (IIIg) by the procedure described in Reaction Scheme 13. R in reaction scheme 13 represents a substituted or unsubstituted alkyl group or hydrogen atom, and R⁶Represents a substituted or unsubstituted carbocyclic or heterocyclic group capable of forming an anion under basic conditions.

【0075】

Similarly, the amine functional group is its precursor, eg, group-NO.₂Or group-N (CW) R⁰For the compound of formula (IIIf) substituted by, the continuous reaction described in Reaction Scheme 13 can be carried out.

【0076】

[Chemical 18]

<img file="JP2002114751A_D0016.tif" />【0077】

Alternatively, using the same chemistry as above, structural unit-NR⁰R after the formation of (CW) Y⁶Can be produced by introducing the compound of the general formula (I).

【0078】

Other methods of making compounds of formula (I) and their intermediates and starting compounds will be apparent to those skilled in the art. Such methods are described, for example, in Brown, BR, The Organic Chemistry of Aliphatic Nitrogen Compouunds (Oxford Science Publications, 1994) and Patai, S. The chemistry of cyanates and their thio derivatives (John Wiley &amp; Sons, 1977). Has been done.

【0079】

Furthermore, the compounds of the present invention can be produced using known combinatorial chemistry methods.

【0080】

The present invention will be described in the following examples, but it should not be understood that the present invention is limited to these examples. The structure of the isolated novel compound was confirmed by NMR and / or another suitable analytical method. Proton NMR spectrum (¹H-NMR) is recorded in juuteriochloroform, and the chemical shift (δ) is expressed in ppm with reference to tetramethylsilane.

【0081】

Example 1 N'-(4-{[3- (1,1-dimethylethyl) phenyl] oxy} -2,5-dimethylphenyl) -N-ethyl-N-methylthiourea (Compound 27) Ethylmethylamine in a 0 ° C solution of 1-{[3- (1,1, -dimethylethyl) phenyl] oxy} -4-isothiocianato-2,5-dimethylbenzene (1.9 g) in tetrahydrofuran (6 mL) Drop (450 mg). The resulting reaction mixture is stirred at ambient temperature for 1 hour, then concentrated and polished with heptane. The title product is obtained in the form of a settling layer.

【0082】

Manufacture of starting material 1-Chloro-2,5-dimethyl-4-nitrobenzene A mixture of 2-chloro-1,4-xylene (1.4 g), acetic acid (17 mL) and 98% sulfuric acid (1 mL) cooled to 10 ° C, and a mixed acid consisting of sulfuric acid (3.8 mL) and nitric acid (1 mL). Is dropped at 0 ° C. The reaction mixture is poured into a water / ice mixture and then filtered. Recrystallization of the yellow precipitate from petroleum ether gives the title compound.

【0083】

1-{[3- (1,1-dimethylethyl) phenyl] oxy} -2,5-dimethyl-4-nitrobenzene A solution of 1-chloro-2,5-dimethyl-4-nitrobenzene (9.5 g) in dimethylformamide (60 mL) under an inert atmosphere with 3-t-butylphenol (7.5 g) and potassium carbonate (6.9 g). Is added. The resulting reaction mixture is heated to reflux for 5 hours and then partitioned into a water / diisopropyl ether mixture. The organic phase is washed with a basic aqueous solution and then with water at pH 7. Drying with magnesium sulphate, then adding carbon black and further filtering with Celite gives the title product after concentration.

【0084】

4-{[3- (1,1-dimethylethyl) phenyl] oxy} -2,5-dimethylaniline With 1-{[3- (1,1-dimethylethyl) phenyl] oxy} -2,5-dimethyl-4-nitrobenzene (8.65 g) and 5% palladium / carbon (100 mg) in n-propanol (60 mL) The mixture is heated to 90 ° C and hydrated hydrazine (4.3 mL) is added dropwise. The reaction mixture is maintained at 90 ° C for 2 hours and then filtered through Celite. Concentration gives the title compound.

【0085】

1-{[3- (1,1-dimethylethyl) phenyl] oxy} -4-isothiocianato-2,5-dimethylbenzene 4-((3- (1,1-Dimethylethyl) phenyl) oxy) -2,5-dimethylaniline (1.35 g) in toluene (6 mL) and sodium hydrogen carbonate (840 mg) in water (6 mL) Bring the two-phase mixture to ambient temperature and add thiophosgene (0.38 mL). The resulting reaction mixture is stirred for 2 hours and then tilted. The aqueous phase is extracted with toluene, then the organic phase is collected, washed with water, dried (magnesium sulphate) and then concentrated to give the title product.

【0086】

The above procedure for synthesizing N'-(4-((3- (1,1-dimethylethyl) phenyl) oxy) -2,5-dimethylphenyl) -N-ethyl-N-methylthiourea is universal to another amine. And diverted to different temperature and solvent conditions, especially acetonitrile, diethyl ether and dimethylformamide. This procedure was also used in the synthesis of thiosemicarbazide and thiohydroxyurea.

【0087】

In the case of 1-(4-{[3- (1,1-dimethylethyl) phenyl] oxy} -2,5-dimethylphenyl) -1,3-dihydro-2H-imidazol-2-thione (Compound 16) Cyclic thiourea was obtained by reacting dimethyl acetal aminoacetaldehyde with 4-{[3- (1,1-dimethylethyl) phenyl] oxy} -2,5-dimethylaniline by the above procedure.

【0088】

In addition, the above procedure for synthesizing 4-{[3- (1,1-dimethylethyl) phenyl] oxy} -2,5-dimethylaniline was used to produce the following aniline: 4-[(3-chlorophenyl). Oxy] -2,5-dimethylaniline, 4-{[4-chloro-3- (trifluoromethyl) phenyl] oxy} -2,5-dimethylaniline, 4-{[4-fluoro-3- (trifluoro) Methyl) phenyl] oxy} -2,5-dimethylaniline, 2,5-dimethyl-4-{[3- (trifluoromethyl) phenyl] oxy} aniline, 4-[(4-ethylphenyl) oxy] -2 , 5-Dimethylaniline, 4-[(4-chlorophenyl) oxy] -2,5-dimethylaniline and 4-{[3- (1,1-dimethylethyl) phenyl] oxy} -2- (trifluoromethyl) Aniline.

【0089】

Other anilines used as intermediates in the synthesis of the exemplified products were synthesized by the following methods.

【0090】

Production of 4- (5- (1,1-dimethylethyl) -1,3,4-oxadiazole-2-yl) -2-methylaniline Hydrazine hydrate (6.7 mL) is added to a solution of methyl 3-methyl-4-nitrobenzoate (25 g) in methanol (300 mL) at ambient temperature. The reaction mixture is heated to reflux for 15 minutes and then cooled. After filtration and drying, 3-methyl-4-nitrobenzohydrazide is obtained as a precipitate.

【0091】

A mixture of 3-methyl-4-nitrobenzohydrazide (3.9 g), triethylamine (3 mL) and 2,2-dimethylpropan acid chloride (2.6 mL) in dichloromethane (120 mL) was stirred for 2 hours and water was added. Added. Drying, evaporation and polishing of the organic phase with petroleum ether gives N'-(2,2-dimethylpropanoyl) -3-methyl-4-nidrobenzohydrazide in the form of a precipitate.

【0092】

Phosphorus pentoxide (10 g) is added to a suspension of N'-(2,2-dimethylpropanoyl) -3-methyl-4-nitrobenzohydrazide (5.1 g) in toluene (200 mL). After heating to reflux for 2 hours, the reaction mixture is poured into ice water and extracted with diethyl ether. The organic phase is collected, dried over magnesium sulphate, evaporated and purified by silica chromatography (eluting agent is 2: 1 diethyl ether / petroleum ether) and then 2- (1,1-dimethylethyl-5- (3-) Methyl-4-nitrophenyl) -1,3,4-oxadiazole is obtained.

【0093】

2- (1,1-Dimethylethyl-5- (3-Methyl-4-nitrophenyl) -1,3,4-oxadiazole (1.6 g) in a dimethylformamide / water mixture (1: 1, 25 mL) And FeCl₃.6H₂A mixture of O (5 g) and zinc powder (4 g) is heated at 100 ° C for 30 minutes and then filtered through Celite. After diluting with saturated aqueous sodium carbonate solution, the reaction mixture is extracted with diethyl ether. Drying with magnesium sulphate and evaporating the organic phase gives the title aniline.

【0094】

Production of 2,5-dimethyl-4-[(3-phenyl-1,2,4-thiadiazole-5-yl) oxy] phenylamine To a suspension of sodium hydride (60% dispersion in mineral oil, 3 g) in anhydrous dimethylformamide (300 mL) is added 4-amino-2,5-dimethylphenol (10.5) at ambient temperature. The reaction mixture is stirred for 30 minutes, then 5-bromo-3-phenyl-1,2,4-thiasiasol (18 g) prepared according to Chem. Ber. 1961, 94, 2043 is added slowly. After stirring for 15 hours, the reaction mixture is diluted with ice water and then extracted with diethyl ether. The title compound is obtained by drying with magnesium sulfate and then concentrating the collected organic phase.

【0095】

Production of 4- [3,4-dihydro-2 (1H) -isoquinolinyl] -2,5-dimethylaniline A mixture of 1-chloro-2,5-dimethyl-4-nitrobenzene (1.65 g) in N-methylpyrrolidine (5 mL) and 1,2,3,4-tetrahydroisoquinoline (5 mL) at 140 ° C for 15 hours. Stir. The organic phase diluted with water, then extracted with diethyl ether, dried and evaporated was purified by silica chromatography (eluting agent 1: 1 petroleum ether / diethyl ether) to give 2- (2,5-dimethyl-). 4-Nitrophenyl) -1,2,3,4-tetrahydro-isoquinoline is obtained.

【0096】

Reduction of 2- (2,5-dimethyl-4-nitrophenyl) -1,2,3,4-tetrahydro-isoquinoline by the method exemplified above gives the title aniline.

【0097】

Production of 4- (1-benzothiophen-2-yl) -2,5-dimethylaniline 1-Bromo-2,5-dimethyl-4-nitrobenzene (3.6 g), (1-benzothien-2-yl) boronic acid (3.6 g) and palladium tetraxtriphenylphosphine in ethanol (36 mL) and toluene (100 mL) The mixture of (0.4 g) and aqueous sodium (2M) solution (17 mL) is stirred for 18 hours until reflux. Partial evaporation, then extraction with ethyl acetate, drying of the organic phase and then evaporation again yields 2- (2,5-dimethyl-4-nitrophenyl) -1-benzothiophene.

【0098】

Reduction of 2- (2,5-dimethyl-4-nitrophenyl) -1-benzothiophene by the method described above gives the title aniline.

【0099】

Example 2 3- [4- (1-Benzothien-2-yl) -2,5-dimethylphenyl] -2-thioxo-1,3-thiazolidine-4-one (Compound 3) A solution of 2- (4-isothiocianato-2,5-dimethylphenyl) -1-benzothiophene (0.22 g) in diethyl ether (2 mL) and ethyl sulphenylacetate (0.09 g) is stirred at ambient temperature for 18 hours. .. The reaction medium is evaporated and then polished in petroleum ether to give the title compound.

【0100】

Example 3 N-(4-{[4-Chloro-3- (trifluoromethyl) phenyl] oxy} -2,5-dimethylphenyl) -N, N'-diethyl-N'-methylurea (Compound 116) Activated carbon spatula at 60 ° C under argon in a solution of 4-{[4-chloro-3- (trifluoromethyl) phenyl] oxy} -2,5-dimethylaniline (3 g) in acetic anhydride (50 mL). Add and then add diphosgene (2.07 g). The resulting reaction mixture is heated at 60 ° C. for 1 hour and then stirred at ambient temperature for 15 hours. Filter through Celite, then evaporate, pour into petroleum ether (50 mL), add N-ethylmethylamine (1.12 g) and after evaporation N'-(4-{[4-chloro-3- (trifluoro)) Methyl) phenyl] oxy} -2,5-dimethylphenyl) -N-ethyl-N'-methylurea is obtained. A 60% sodium hydride suspension (46 mg) and ethyl iodide (300 mg) in mineral oil are sequentially added to a solution of the obtained compound (380 mg) in tetrahydrofuran (2 mL). The reaction mixture is stirred at 50 ° C. for 2 hours, then diluted in water and extracted with diethyl ether. The organic phase is dried over magnesium sulphate and then evaporated to give the title compound.

【0101】

The above procedure for synthesizing N'-([4-chloro-3- (trifluoromethyl) phenyl] oxy} -2,5-dimethylphenyl) -N-ethyl-N-methylurea is universal to another amine. And diverted to different temperature and solvent conditions, especially acetonitrile, diethyl ether and dimethylformamide. Similar procedures were used for the synthesis of hydroxyurea, semicarbazide and carbamate.

【0102】

The following examples (Table 1) show, but are not limited to, some compounds of the invention synthesized by the above procedure.

【0103】

[table 1]

<img file="JP2002114751A_D0017.tif" /><img file="JP2002114751A_D0018.tif" /><img file="JP2002114751A_D0019.tif" /><img file="JP2002114751A_D0020.tif" /><img file="JP2002114751A_D0021.tif" /><img file="JP2002114751A_D0022.tif" /><img file="JP2002114751A_D0023.tif" /><img file="JP2002114751A_D0024.tif" /><img file="JP2002114751A_D0025.tif" /><img file="JP2002114751A_D0026.tif" /><img file="JP2002114751A_D0027.tif" /><img file="JP2002114751A_D0028.tif" /><img file="JP2002114751A_D0029.tif" /><img file="JP2002114751A_D0030.tif" />【0104】

The analytical characteristic values of the compounds in Table 1 are shown in the table below.

【0105】

[Table 2]

<img file="JP2002114751A_D0031.tif" /><img file="JP2002114751A_D0032.tif" /><img file="JP2002114751A_D0033.tif" /><img file="JP2002114751A_D0034.tif" /><img file="JP2002114751A_D0035.tif" /><img file="JP2002114751A_D0036.tif" /><img file="JP2002114751A_D0037.tif" />【0106】

Test Examples The activity of the compound against one or more of the following fungal diseases was tested: Phytophthora infestans: Tomato downy mildew; Erysiphe graminis f.sp.Tritici: Wheat Udonko disease; Pyricularia oryzae: Rice blast; Leptosphaeria nodorum: Septoria infection of nodorum species wheat; Mycosphaerella graminicola: Septoria infection of tritici species wheat; Puccinia recondita: grain rust; Pyrenophora teres: Helminthosporium infection in barley.

【0107】

An aqueous solution or aqueous dispersion of a compound containing one or more wetting agents at the desired concentration is used, and the solution is optionally applied by spraying or the stem base of the test plant is immersed in the solution. After a given time, the plant or part of the plant is inoculated with the appropriate test pathogen, stored under appropriate controlled environmental conditions to maintain plant growth and disease progression, and infection of the infected part of the plant. Visually evaluate the degree. The following compounds used at a concentration of 500 ppm (weight / volume) or less showed a control effect of 65% or more against specific fungal diseases as compared with the untreated control. Phytophthora infestans 44, 45 Erysiphe graminis f.sp.Tritici 1, 17, 18, 19, 20, 21, 22, 23, 24, 27, 28, 33, 42, 43, 45, 52, 53, 54, 55, 83, 84, 124, 170 Pyricularia oryzae 35 Leptosphaeria nodorum 18, 27, 45, 124, 169, 170, 171 Puccinia recondita 124, 127, 131, 140, 149, 157, 167, 169, 170 Pyrenophora teres 77, 93, 95, 113, 118, 119, 124, 128, 132, 140, 144, 145, 149, 150, 157, 164, 165.