JP2001354657A - Substituted piperazine derivative and agricultural and horticultiral fungicide - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain a fungicide capable of efficiently controlling noxious fungi at a low concentration. SOLUTION: This substituted piperazine derivative represented by the general formula (I) [R1 denotes an alkyl, a cycloalkyl, phenyl group or the like which may be substituted with a halogen, an aryl group or the like; PZ ring denotes a (substituted) piperazine ring, an oxopiperazine ring, a dioxopiperazine ring or the like; X denotes a halogen, an alkyl, an alkoxy, an alkenyloxy, an alkylthio, phenyloxy, pyrimidyloxy, an alkoxycarbonyl, cyano, nitro, an acyl, an alkylaminocarbonyloxy, an alkanesulfonyloxy group or the like; and n denotes an integer of 0-3] and the agricultural or horticultural fungicide comprises the substituted piperazine derivative as an active ingredient.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

The present invention relates to a compound represented by the general formula (I):

Embedded image (The symbols in the formula are as described below.) The present invention relates to a substituted piperazine derivative represented by the formula (1) and a fungicide for agricultural and horticultural use containing the same as an active ingredient.

[0002]

2. Description of the Related Art Compounds having an amino acid amide structure have been known to be useful as pesticides.

For example, JP-A-3-153657, JP-A-4-153657
No. 230653, JP-A-4-283554, JP-A-4-308507
JP, JP-A-4-338372, JP-A-6-279405, JP-A-7-10825, JP-A-8-176115, JP-A-10-182616, European Patent Application No. 0672654 (A
1), Patent No. 286767 and the like disclose amino acid amide compounds having a pest control action or a bactericidal action.

However, the pesticidal activity of these compounds is still insufficient and unsatisfactory. In addition, when used repeatedly, fungicides may develop resistant bacteria to the drug and may not show sufficient bactericidal activity.Also, due to environmental problems, new fungicides that can efficiently control harmful bacteria at low concentrations are always available. It has been demanded.

[0005] Among the above prior art publications, Japanese Patent No. 286736 is disclosed.
No. 7 has a general formula (A)

Embedded image (Wherein R ^1A represents an alkyl group or the like, and R ^2A , R ^3A , R
^4A and R ^5A each represent a hydrogen atom, an alkyl group, or the like;
R ^6A represents a hydrogen atom, an alkyl group, a phenyl group, a heterocyclic group or the like (the above symbol definitions have been extracted as necessary), or R ^5A and R ^6A are further heterozygous together with the nitrogen atom to which they are bonded. Represents a 5- or 6-membered heterocyclic group which may contain oxygen or nitrogen as an atom. ) Describes that the substituted amino acid derivative has a pest control effect.

In the general formula (A), NR ^5A R ^6A is described in a broad definition as a 5- or 6-membered heterocyclic group which may further contain oxygen or nitrogen as a hetero atom together with the nitrogen atom to which it is attached. However, the specific disclosure is

Embedded image (Table 1, Compound No. 16 and Compound N
o. 18).

In the compound of the present invention, the heterocyclic ring at the corresponding position is a piperazine ring, and the nitrogen atom at the 4-position of the piperazine ring is substituted by n phenyl groups which may be substituted by X groups. However, such compounds are not substantially disclosed in Japanese Patent No. 286767, and are of such an extent that those skilled in the art cannot easily conceive based on the specific disclosure. It is.

[0008]

The present inventors have conducted various studies to develop compounds having excellent bactericidal activity. As a result, the novel substituted piperazine derivative represented by the general formula (I) has a low dose. The present invention has a wide spectrum of bactericidal spectrum, especially has excellent bactericidal activity against tomato late blight, potato late blight, grape downy mildew, and cucumber downy mildew, and has no harm to useful crops. Was completed.

That is, the present invention provides the following general formula (I)
And a fungicide for agricultural and horticultural use containing the derivative as an active ingredient.

[0010]

Embedded image

Wherein R ¹ is (1) an optionally substituted (i) lower alkyl group, (ii) lower alkenyl group,
Or (iii) a lower alkynyl group, (2) optionally substituted (i) cycloalkyl group, (ii) cycloalkenyl group, (iii) cyclic ether group, (iv) phenyl group,
Or (v) a heteroaryl group, (3) a dialkylamino group, or (4) a —N ＝ CR ² R ³ group (wherein R ² and R ³ are each independently (i) a hydrogen atom, (ii) An optionally substituted lower alkyl or phenyl group,
Or (iii) represents a cyano group. ) Represents a group represented by

Embedded image (In the group, m Ys each independently represent a lower alkyl group or a phenyl group which may be substituted, and m represents an integer of 0 to 4), and n Xs each represent Independently (1) halogen atom, (2) optionally substituted (i) lower alkyl group, (ii) lower alkenyl group, (ii)
i) lower alkynyl group, (iv) lower alkoxy group,
(V) lower alkenyloxy group, (vi) lower alkynyloxy group, or (vii) lower alkylthio group (3) optionally substituted phenyloxy group, (4) pyridyloxy group, or pyrimidyloxy group, (5) Hydroxyl group,
(6) alkoxycarbonyl group, (7) formyl group, or acyl group, (8) cyano group, (9) nitro group, (1
0) represents an amino group or a dialkylamino group, (11) an alkanesulfinyl group, an alkanesulfonyl group, or an alkanesulfonyloxy group, or (12) an alkylaminocarbonyloxy group, and n represents an integer of 0 to 3. ]

[0012]

[Compound of the Present Invention] R ¹ group: In the general formula (I), the lower alkyl group represented by R ¹ , R ² and R ³ is an alkyl group having 1 to 6 carbon atoms, and is methyl, ethyl, propyl or butyl. , Pentyl, hexyl or their isomeric groups. The lower alkenyl group represented by R ¹ is an alkenyl group having 2 to 6 carbon atoms having 1 to 3 double bonds,
Vinyl, propenyl, butenyl, butanedienyl, pentenyl, pentanedienyl, hexenyl, hexanedienyl, hexanetrienyl or isomers thereof. The lower alkynyl group represented by R ¹ is an alkynyl group having 2 to 6 carbon atoms having 1 to 3 triple bonds, and examples thereof include ethynyl, propynyl, butynyl, pentynyl, hexynyl and isomers thereof.

The lower alkyl group, lower alkenyl group and lower alkynyl group include an alkoxy group, a halogen atom,
It may be substituted with one or more substituents selected from a cyano group, a nitro group, an aryl group, and a heteroaryl group. Examples of the aryl group include a phenyl group and a naphthyl group. The heteroaryl ring of the heteroaryl group is a monocyclic or bicyclic heterocyclic ring showing aromaticity having 1 to 3 heteroatoms such as an oxygen atom, a sulfur atom, and a nitrogen atom as a ring-forming atom. Examples include pyrrole, pyrazole, imidazole, triazole, pyridine, pyrimidine, triazine, furan, thiophene, thiazole, indole, quinoline, purine, and pteridine rings. The aryl group and the heteroaryl group may be further substituted with an alkyl group, an alkoxy group, a halogen atom, a haloalkyl group, a cyano group, a nitro group, or the like.

The cycloalkyl group represented by R ¹ is a cycloalkyl group having 3 to 8 carbon atoms, such as cyclopropyl,
Examples include cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, and cyclooctyl groups. The cycloalkenyl group R ¹ represents a cycloalkyl group having 3 to 8 carbon atoms, such as cyclopropyl propynyl, cyclobutenyl, cyclopentenyl, cyclohexenyl, cycloheptenyl, and cyclooctenyl or isomeric groups thereof. Examples of the cyclic ether group represented by R ¹ include a tetrahydrofuranyl group and a tetrahydropyranyl group. Examples of the heteroaryl group represented by R ¹ include pyrrole, pyrazole, imidazole, triazole, pyridine, pyrimidine, triazine, furan, thiophene, thiazole, indole, quinoline, purine, and pteridine rings.

The cycloalkyl group R ¹ represents cycloalkenyl group, cyclic ether group, a phenyl group phenyl and heteroaryl groups, and R ² and R ³ represents an alkyl group, an alkoxy group, a halogen atom, a haloalkyl group, It may be substituted with one or more substituents selected from a cyano group and a nitro group.

Preferred examples of R ¹ include a lower alkyl group, a lower alkenyl group, a lower alkynyl group and a cycloalkyl group, which are unsubstituted or substituted with a halogen atom, an alkoxy group, an aryl group or a heteroaryl group.

PZ ring group:

Embedded image Represents In the PZ ring, the lower alkyl group represented by Y is an alkyl group represented by R ^{1 or} an alkyl group having 1 to 6 carbon atoms, such as methyl, ethyl, propyl, butyl, pentyl, hexyl or an isomer thereof. Can be Examples of the substituent of the optionally substituted phenyl group include one or more substituents selected from an alkyl group, an alkoxy group, a halogen atom, a haloalkyl group, a cyano group, and a nitro group. Preferred Y is a lower alkyl group. The number m of the substituents is 0 to 4, preferably 0 or 1 to 2.

X group: The halogen atom represented by X is a fluorine, chlorine, bromine or iodine atom. As the lower alkyl group, lower alkenyl group and lower alkynyl group represented by X, those similar to the aforementioned R ¹ can be mentioned. X
The lower alkyl group in the lower alkoxy group and the lower alkylthio group, the lower alkenyl group in the lower alkenyloxy group, and the lower alkynyl group in the lower alkynyloxy group are the same as those described above for R ¹ . The lower alkyl (oxy, thio) group, lower alkenyl (oxy) group and lower alkynyl (oxy) group are substituted with one or more substituents selected from an alkoxy group, a halogen atom, a cyano group and a nitro group. Is also good.

The optionally substituted phenyl group is an unsubstituted phenyl group, an alkyl group, an alkoxy group,
A phenyl group which may be substituted with one or more substituents selected from a halogen atom, a haloalkyl group, a cyano group and a nitro group. Examples of the alkoxycarbonyl group include methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, butoxycarbonyl, pentyloxycarbonyl, hexyloxycarbonyl and isomers thereof. Examples of the acyl group include those having 2 to 5 carbon atoms, such as acetyl, ethylcarbonyl, propylcarbonyl, and isomers thereof. Examples of the dialkylamino group include a dimethylamino, diethylamino, and ethylmethylamino group. Examples of the alkylaminocarbonyloxy group include methylaminocarbonyloxy, ethylaminocarbonyloxy, propylaminocarbonyloxy, and the like.

The alkanesulfinyl (R-SO-) group includes methanesulfinyl, ethanesulfinyl, propanesulfinyl, butanesulfinyl and isomers thereof. Alkanesulfonyl (RS
Examples of the O ₂ —) group include methanesulfonyl, ethanesulfonyl, propanesulfonyl, butanesulfonyl and isomers thereof. The alkanesulfonyloxy (R-SO ₂ -O-) group, methanesulfonyloxy, ethanesulfonyloxy, propane sulfonyloxy include butane sulfonyloxy or isomeric groups thereof.

Preferred X is a halogen atom, a lower alkyl group, a lower alkoxy group, a lower alkenyloxy group, a lower alkylthio group, a phenyloxy group, a pyrimidyloxy group, an alkoxycarbonyl group, a cyano group, a nitro group, an acyl group, an alkylamino group. Carbonyloxy group,
Alkanesulfonyloxy groups are exemplified. Substituent number n
Is 0 to 3, preferably 0 or 1 to 2.

Next, typical examples of the compounds of the present invention represented by the general formula (I) and their physical properties are shown in Tables 1 to 5, but the compounds of the present invention are not limited thereto (compound numbers are , Use the same number throughout the specification.) In the table, Me represents a methyl group, Et represents an ethyl group, i-Pr represents an isopropyl group, and sec-Bu
Represents a secondary butyl group, t-Bu represents a tertiary butyl group, Ac represents an acetyl group, and P represents
h represents a phenyl group. In addition, ¹ H-NMR shows that tetramethylsilane is used as an internal standard, and CDCl _{3 is used} as a solvent.
And the value measured with a Hitachi R-1900 type spectrum meter (90 MHz) was shown as a δ value (ppm).

[0023]

[Table 1]

[0024]

[Table 2]

[0025]

[Table 3]

[0026]

[Table 4]

[0027]

[Table 5]

[0028]

[Table 6]

[0029]

[Table 7]

[0030]

[Table 8]

[0031]

[Table 9]

[0032]

[Table 10]

[0033]

[Table 11]

[0034]

[Table 12]

[0035]

[Table 13]

[0036]

[Table 14]

[0037]

[Table 15]

[0038]

[Production method of the compound of the present invention] The compound of the present invention represented by the general formula (I) can be produced, for example, according to the following production step A or production step B.

(1) Manufacturing process A

Embedded image (In the formula, R ¹ , PZ ring, X and n represent the same meaning as described above.)

According to the production step A, an amino acid derivative represented by the general formula (II) or a derivative having its carboxyl group activated is converted to a cyclic second derivative represented by the general formula (III) in the presence of a catalyst and / or a base. The compound (I) of the present invention can be produced by reacting with a secondary amine.

The general formula (II) used in this reaction
Examples of the derivative in which the carboxyl group of the amino acid derivative represented by the formula is activated include an acid halide such as an acid chloride, an acid anhydride obtained by dehydration-condensation of two amino acid derivatives of the formula (II), and a formula (II) Mixed acid anhydrides obtained by condensing an amino acid derivative with another acid or O-alkyl carbonic acid, and activated esters such as p-nitrophenyl ester, 2-tetrahydropyranyl ester and 2-pyridyl ester. it can.

The reaction is carried out by N, N'-dicyclohexylcarbodiimide, 1-ethyl-3- (dimethylaminopropyl) -carbodiimide hydrochloride, N, N'-carbonyldiimidazole, 2-chloro-1,3-dimethylimidazolium It can also be carried out using a condensing agent such as chloride.

The reaction is usually performed in a solvent. As a solvent that can be used, any solvent that does not inhibit the reaction may be used.
For example, pentane, hexane, heptane, cyclohexane, petroleum ether, ligroin, benzene, toluene,
Hydrocarbons such as xylene, halogenated hydrocarbons such as dichloromethane, dichloroethane, chloroform, carbon tetrachloride, chlorobenzene, dichlorobenzene, ethers such as diethyl ether, diisopropyl ether, ethylene glycol dimethyl ether, tetrahydrofuran, dioxane, acetone, methyl ethyl ketone , Ketones such as methyl isobutyl ketone, acetates such as methyl acetate and ethyl acetate, nitriles such as acetonitrile, propionitrile and benzonitrile, and non-protons such as dimethyl sulfoxide, N, N-dimethylformamide and sulfolane A mixed solvent obtained by combining an apolar solvent and a solvent selected from these may be used.

As the base, those generally used in this type of reaction can be used without any particular limitation. For example, alkali metal hydroxides such as sodium hydroxide and potassium hydroxide, alkaline earth metal hydroxides such as calcium hydroxide, alkali carbonates such as sodium carbonate and potassium carbonate, furthermore, triethylamine, trimethylamine, N, N -Dimethylaniline, pyridine, N-methylpiperidine, 1,5
-Diazabicyclo [4.3.0] non-5-ene (DB
N), organic bases such as 1,8-diazabicyclo [5.4.0] undec-7-ene (DBU) and the like, and preferably tertiary amines such as triethylamine, pyridine and N-methylpiperidine. is there.

Examples of the catalyst include 4-dimethylaminopyridine, 1-hydroxybenzotriazole, N,
N-dimethylformamide and the like can be used.

The reaction is carried out at a temperature ranging from -75 ° C to 100 ° C, preferably from -60 ° C to 40 ° C. The reaction time is preferably 1 to 20 hours.

Next, a method for producing a starting compound will be described. The compound represented by the general formula (II) can be produced by a known method. For example, in the general formula (II), R
^The compound in which ¹ is tert-butyl can be produced by reacting L-valine with di (tert-butyl) dicarbonate in the presence of sodium hydrogen carbonate. In the general formula (II), the compound wherein R ¹ is a benzyl group is L-
It can be produced by reacting valine with carbobenzoxycyclolide in the presence of sodium bicarbonate [Methoden del Organischen Chemie
oden der Organischen Chemie), Volume 15, Issue 2,
2nd page, Georg Thieme Verlag Stuttgart (1974); Chemistryof Am
ino Acids), Vol. 2, p. 891, John Wily & Sons, New York (John Wily &; Son)
s, NY) (1964); Journal of the Ameri
86, p. 1839 (1969).
Year)〕.

A method for producing a compound in which the carboxyl group of an amino acid derivative is activated is also known. For example, a mixed acid anhydride with a chloroformate can be produced by reacting an amino acid derivative represented by the general formula (II) with isobutyl chloroformate in the presence of an organic base. The p-nitrophenyl ester is represented by the general formula (I
It can be produced by reacting the amino acid derivative of the formula (I) with p-nitrophenol in the presence of a condensing agent [Methoden der Organischen Chemie, Vol. 15, No. 2, No. 2, page 2, Georg Thieme Verlag Stuttgart (1974)
Year); Chemische Berichte,
38, 605 (1905); Journal of
The American Chemical Society (Journal of
the American Chemical Society), Vol. 74, 67
Page 6 (1952); Journal of the American
Chemical Society (Journal of the American Ch
emical Society), Vol. 86, p. 1839 (1964)].

The cyclic secondary amines represented by the general formula (III) can also be produced by a known method or a method similar thereto (Journal of Medicinal Chemistry, No. 21).
Volume 1301 (1978); Recueil des Travaux Chimiq
ues des Pays-Bas, Volume 107, Page 303 (1988
Year); Tetrahedron Letters
s), 39, 7459 (1998); Synthesis (Syn)
thesis), Vol. 10, p. 925 (1990); Journal of M. Chemistry (Journal of M)
edicinal Chemistry), Vol. 33, p. 1344 (1990)
Year)).

(2) Manufacturing process B

Embedded image (In the formula, R ¹ , a PZ ring, X and n have the same meanings as described above, and L represents a halogen atom, a group R ¹ OC (O) O—, a group R ¹ O—, or an imidazolyl group.)

According to the production step B, the compound represented by the general formula (IV) is converted into an inorganic acid salt such as an amine represented by the general formula (V) or a hydrochloride thereof or a tosylate in the presence or absence of a base. By reacting with an organic acid salt such as a salt, the compound of the present invention represented by the general formula (I) can be produced.

The reaction is carried out in the presence or absence of a solvent. The solvent may be any one that does not inhibit the reaction,
For example, pentane, hexane, heptane, cyclohexane, petroleum ether, ligroin, benzene, toluene,
Hydrocarbons such as xylene, halogenated hydrocarbons such as dichloromethane, dichloroethane, chloroform, carbon tetrachloride, chlorobenzene, dichlorobenzene, ethers such as diethyl ether, diisopropyl ether, ethylene glycol dimethyl ether, tetrahydrofuran, dioxane, acetone, methyl ethyl ketone , Ketones such as methyl isobutyl ketone, acetates such as methyl acetate and ethyl acetate, nitriles such as acetonitrile, propionitrile and benzonitrile, and non-protons such as dimethyl sulfoxide, N, N-dimethylformamide and sulfolane A mixed solvent obtained by combining an apolar solvent and a solvent selected from these may be used.

As the base, those generally used in this type of reaction can be used without any particular limitation. For example, alkali metal hydroxides such as sodium hydroxide and potassium hydroxide, alkaline earth metal hydroxides such as calcium hydroxide, alkali carbonates such as sodium carbonate and potassium carbonate, furthermore, triethylamine, trimethylamine, N, N -Dimethylaniline, pyridine, N-methylpiperidine, 1,5
-Diazabicyclo [4.3.0] non-5-ene (DB
N), organic bases such as 1,8-diazabicyclo [5.4.0] undec-7-ene (DBU) and the like, and preferably tertiary amines such as triethylamine, pyridine and N-methylpiperidine. is there. The reaction temperature is -20
C. to 100.degree. C., preferably 0.degree. The reaction time is preferably from 30 minutes to 20 hours.

Formula (V) which is an intermediate of the compound of the present invention
The amines represented by the formula (I) can be used, for example, to remove a carbamate of the compound (I) synthesized by the method of the production step A from a generally known method for removing an amino protecting group of an amino acid, for example, a catalytic reduction method And liquid hydrogen fluoride, sulfonic acids, hydrogen chloride, hydrogen bromide, formic acid and the like.

[0055]

[Application as a fungicide for agricultural and horticultural use] The compound represented by the general formula (I) has a pest controlling effect and can be used as a fungicide for agricultural and horticultural use. Examples of the plant disease in which the compound of the present invention exhibits excellent control effects include rice blast (Pyri
cularia oryzae) and sesame leaf blight (Cochliobolus miyabea)
nus), sheath blight (Rhizoctonia solani), stupid seedling disease (Gib
berella fujikuroi); powdery mildew of wheat (Erysiphe)
graminis f.sp.hordei, Erysiphe graminis f.sp.tri
tici), rust (Puccinia striiformis, Puccinia gra
minis, Puccinia recondita f.sp.tritici, Puccinia
hordei), Fusarium head blight (Gibberella zeae), Nettle spot (Pyr)
enophorateres, snow rot (Typhula incarnata, Typhul)
a ishikariensis, Sclerotiniaborealis, Micronectri
ell a nivalis), naked smut (Ustilago nuda), black smut (Tilletia caries, Tilletia toetida), eye spot disease (Tapesia yallundea), scald disease (Phynchosporium)
secalis f.sp. hordei, leaf blight (Septoria tritic)
i), blight (Lentosphaeria nodorum); citrus black spot (Diaporthe citri), scab (Elsinoe fawcett)
ii), brown rot (Phytophthora citrophthora), green mold (Penicillium digitatum), blue mold (Penici)
llium italicum); Monilinia ma in apples (Monilinia ma)
li), rot (Valsa ceratosperma), powdery mildew (Podosphaera leucotricha), spot leaf spot (Alternari)
a alternata apple pathotype, scab (Venturia in)
aequalis), scab (Gymnosporangium yamadae), ring spot (Botriophaeria berengeriana f.sp. piricol)
a), soot spot disease (Zygophiala jamaicensis), soot spot disease (Gloeodes pomigena), black spot disease (Mycosphaerella pom)
i), anthracnose (Glomerella cingulata), brown spot (Diplo
carpon mali); Pear scab (Venturia nashicol)
a), Black spot (Alternaria alternata japanese pear pa
thotype), ring spot (Physalospora piricola), scab (Gymnosporangium asiaticum); peach scab (Monil)
inia fructicola), scab (Cladosporium carpophilu)
m), Phomopsis sp .; Grape downy mildew (Plasmopara viticola), brown spot (Pseudocerco)
spora vitis), ring spot (Marssonina viticola), black rot (Elsinoe ampelina), late rot (Glomerella cingu)
lata), powdery mildew (Uncinula necator), rust (Ph
akopsora ampelopsidis), branch swelling (Phomopsis sp.);
Oyster powdery mildew (Phyllactinia kakicola), anthracnose (Colletotrichum gloeosporioides), corn leaf spot (Ce)
rcospora kaki,), round star deciduous disease (Mycosphaerella n awa)
e); scab of ume (Cladosporium carpophilum); scab of peach (Monilinia fructicola); powdery mildew of cucumber (Sphaerotheca fuliginea), downy mildew (Pseudo)
peronospora cubensis, vine blight (Didymella bryoni)
ae), Anthracnose (Colletotorichum legenarium), Seedling blight (Pythium cucurbitacearum, Pythium debaryanum, R
hizoctonia solani); Tomato ring spot (Alternaria so
lani), leaf mold (Cladosporium fulvum), plague (Phy
tophthora infestans; eggplant brown spot (Phomopsis vex)
ans), powdery mildew (Erysiphe cichoracearum); black spot on cruciferous vegetables (Alternaria japonica, Alternari)
a bracicae, Alternaria brassicicola, white spot (Cer
cosporella brassicae); downy mildew of spinach (Pero
nospora spinaciae), plague (Phytophthora sp.); onion downy mildew (Peronospora destructor), plague (Ph
ytophthora nicotiana, gray rot (Botrytis alli)
i); rust on green onion (Puccinia allii); rhizome rot on ginger (Pyrhium ultimum, Pythium zigiberis); powdery mildew on strawberry (Sphaerotheca humuli), anthracnose (G
lomerella cingulata); soybean purpura (Cercospora)
kikuchii), downy mildew (Peronospora manshurica), black rot (Elsinoe glycines), black spot (Diaporthe phaseo)
lorum var.sojae); Brown spot of adzuki bean (Cercospora cane)
scens), rust (Uromyces phaseoli var. azukicol)
a); Bean anthracnose (Colletotrichum lindemuthian)
um); Black rot of peanut (Cercosporidium personatu)
m), brown spot (Cercospora arachidicola), scab (Shaceloma arachidis); powdery mildew of pea (Ery
siphe pisi); Potato summer blight (Alternaria solan)
i), plague (Phytophthora infestans); tea net blast (Exobasidium reticulatum), scab (Elsinoe leu)
cospila), ring spot disease (Pestalotiopsis theae, Pestaloti)
opsis longiseta); Tobacco scab (Alternaria long)
ipes), powdery mildew (Erysiphe cichoracearum), anthracnose (Colletotrichum gloeosporioides); brown spot of sugar beet (Cercospora beticola);
solani), pseudo blight (Ceratobasidium spp.), Pythium disease (Pythium periplocum, Pythium graminicola, P
ythium vanterpoolii); Rose scab (Diplocarpon r)
osae), powdery mildew (Shaerotheca pannosa); brown spot of chrysanthemum (Septoria obesa), white rust (Puccinia horia)
na); gray mold of various crops (Botrytis cinerea),
Sclerotinia sclerotiorum and the like.

In order to use the compound of the present invention as a fungicide for agricultural and horticultural use, the compound of the present invention is applied to plants by spraying, spraying, applying, or the like, or the seeds of the plant or the soil or soil around the plant are treated. It can be carried out by treating the soil for seed sowing, paddy fields, or water for hydroponics with the compound of the present invention. The treatment can be performed before or after the plant is infected with the pathogen.

The compound of the present invention may be used in the form of conventional preparations, for example, for pesticides such as liquids, wettable powders, emulsifiers, suspensions, liquid concentrates, tablets, granules, aerosols, pastes, powders, and smokers. It can be used as a drug suitable for a bactericide. Such agents comprise at least one compound of the present invention and suitable solid or liquid carriers, and, if desired,
Auxiliaries suitable for improving the dispersibility and other properties of the active ingredient (eg surfactants, spreading agents, dispersants, stabilizers)
It can be manufactured by an ordinary method of mixing with the above.

Examples of solid carriers or diluents include plant substances, fibrous substances, artificial plastic powders, clays (eg, kaolin, bentonite, clay), talc and inorganic substances (pumice, sulfur powder), chemical fertilizers, etc. Is mentioned. Liquid carriers and diluents include water, alcohols,
Examples include ketones, ethers, aromatic hydrocarbons, aliphatic hydrocarbons, esters, nitriles, amides (N, N-dimethylformamide, dimethyl sulfoxide), halogenated hydrocarbons, and the like.

Examples of the surfactant include alkyl sulfates, alkyl sulfonates, polyethylene glycol ethers, polyhydric alcohol esters and the like. Spreading or dispersing agents include casein, gelatin, starch powder, carboxymethylcellulose, gum arabic,
Alginic acid, lignin, bentonite, polyvinyl alcohol, pine oil, molasses, agar and the like.

Examples of the stabilizer include isopropyl phosphate mixture, tricresyl phosphate, true oil, epoxy oil, surfactants, fatty acids and esters thereof. In addition to the above ingredients, the formulations of the present invention may contain other fungicides,
It can be used in admixture with pesticides, herbicides or fertilizers.

In general, the above-mentioned preparation contains at least one compound of the present invention (I) in an amount of 1 to 95% by mass, preferably 0.5% by mass.
-50% by mass. These preparations can be used alone or in a diluted form.
g / ha, preferably about 2 g to 100 g / ha, usually about 1 to 50,000 ppm, preferably about 5
Used at a concentration of 0-1000 ppm.

[0062]

The present invention will now be described with reference to Production Examples of the compound of the present invention and Test Examples of the fungicide of the present invention, but the present invention is not limited to the following examples.

[Production Example] Production Example 1: 4- (4-chlorophenyl) -1- [N-
Production of (isopropoxycarbonyl) -L-valyl] piperazine (Compound No. 1) 1.34 g of N-isopropoxycarbonyl-L-valine was dissolved in 11 ml of dichloromethane, and N-methylpiperidine was dissolved.
0.65 g was added at -20 ° C and stirred at this temperature for 10 minutes. Then, 0.90 g of isobutyl chloroformate was added to this mixture.
Was added at -20 ° C, and the mixture was stirred at -20 ° C to -10 ° C for 1 hour. 1.30 g of 1- (4-chlorophenyl) piperazine
Was added at −60 ° C., and the mixture was stirred until the temperature reached room temperature except for the refrigerant. After completion of the reaction, the reaction solution was washed with water, a 5% aqueous sodium hydrogen carbonate solution and water in that order, dried over anhydrous magnesium sulfate, and then the solvent was distilled off under reduced pressure. The obtained residue was purified by silica gel column chromatography to obtain 0.96 g of the target substance as a yellow oily substance.

Production Example 2: 1- (4-chlorophenyl)-
Production of 4- [N- (isopropoxycarbonyl) -L-valyl] piperazinone (Compound No. 49) 0.35 g of N-isopropoxycarbonyl-L-valine and 0.43 g of 1- (4-chlorophenyl) piperazinone hydrochloride in 10 ml of chloroform. Is dissolved in triethylamine 0.18
g was added at 0 ° C. and stirred at this temperature for 10 minutes. next,
To this mixture, a chloroform solution 5 of 0.40 g of 1-ethyl-3- (dimethylaminopropyl) carbodiimide hydrochloride was added.
After adding ml at 0 ° C., the mixture was stirred until the temperature reached room temperature except for the refrigerant. After completion of the reaction, the reaction solution was washed with water, dried over anhydrous magnesium sulfate, and then the solvent was distilled off under reduced pressure. The obtained residue was purified by silica gel column chromatography to obtain 0.59 g of the target compound as a colorless amorphous substance.

Production Example 3: 1- (4-fluorophenyl)
-4- [N- (phenoxycarbonyl) -L-valyl]
Production of piperazine-2,6-dione (Compound No. 74) N-phenoxycarbonyl-L was added to 10 ml of chloroform.
0.46 g of -valine and 0.40 g of 1- (4-fluorophenyl) piperazine-2,6-dione were dissolved and stirred at 0 ° C for 10 minutes. Next, 5 ml of a chloroform solution of 0.55 g of 1-ethyl-3- (dimethylaminopropyl) carbodiimide hydrochloride was added to this mixture at 0 ° C., and the mixture was stirred until the temperature reached room temperature except for the refrigerant. After completion of the reaction, the reaction solution was washed with water, dried over anhydrous magnesium sulfate, and then the solvent was distilled off under reduced pressure. The obtained residue was purified by silica gel column chromatography to obtain 0.50 g of the target substance as a white amorphous substance.

Production Example 4: (1S, 4S) -2- (4-trifluoromethoxyphenyl) -4- [N- (isopropoxycarbonyl) -L-valyl] -2,5-diazabicyclo [2.2. 1] Production of heptane (Compound No. 89) N-isopropoxycarbonyl-
0.22 g of L-valine and 0.28 g of (1S, 4S) -2- (4-trifluoromethoxyphenyl) -2,5-diazabicyclo [2.2.1] heptane were dissolved and stirred at 0 ° C. for 10 minutes. Next, to this mixture was added 4 ml of a chloroform solution of 0.31 g of 1-ethyl-3- (dimethylaminopropyl) carbodiimide hydrochloride at 0 ° C., and the mixture was stirred until the temperature reached room temperature except for the refrigerant. After completion of the reaction, the reaction solution was washed with water, dried over anhydrous magnesium sulfate, and then the solvent was distilled off under reduced pressure. The obtained residue was purified by silica gel column chromatography to obtain 0.27 g of the target compound as a colorless amorphous substance
I got

Production Example 5: (1S, 4S) -2- (4-fluorophenyl) -4- [N- (isopropoxycarbonyl) -L-valyl] -2,5-diazabicyclo [2.
2.1] Production of heptane-3-one (Compound No. 94) N-isopropoxycarbonyl- was added to 3 ml of chloroform.
0.49 g of L-valine, (1S, 4S) -2- (4-fluorophenyl) -2,5-diazabicyclo [2.2.1]
0.50 g of heptane-3-one was dissolved and stirred at 0 ° C. for 10 minutes. Next, to this mixture was added 7 ml of a chloroform solution of 0.70 g of 1-ethyl-3- (dimethylaminopropyl) carbodiimide hydrochloride at 0 ° C, and the mixture was stirred until the temperature reached room temperature except for the refrigerant. After completion of the reaction, the reaction solution was washed with water, dried over anhydrous magnesium sulfate, and then the solvent was distilled off under reduced pressure. The obtained residue was purified by silica gel column chromatography to obtain 0.81 g of the target substance as a yellow amorphous substance.

Production Example 6: 4- (4-cyanophenyl)-
1- [N- (3,4-dimethylphenoxycarbonyl)
Preparation of -L-valyl] piperazine (Compound No. 10) 0.43 g of o-xylenol and 0.73 ml of diisopropylethylamine were dissolved in 30 ml of dichloromethane, and 20 ml of a dichloromethane solution of 0.71 g of p-nitrophenoxycarbonyl chloride was added at room temperature. For 1 hour. Next, 4- (4-cyanophenyl) is added to this mixture.
After adding 1.0 g of valylpiperazine and 0.73 ml of diisopropylethylamine in 50 ml of dichloromethane at room temperature, the mixture was stirred at this temperature overnight. After completion of the reaction, water was added, the mixture was extracted with ethyl acetate, dried over anhydrous magnesium sulfate, and then the solvent was distilled off under reduced pressure. The obtained residue was purified by silica gel column chromatography to obtain 1.1 g of the desired product as white crystals.

Production Example 7: 4- (4-cyanophenyl)-
Production of 1- [N- (phenethyloxycarbonyl) -L-valyl] piperazine (Compound No. 16) 0.43 g of 2-phenethyl alcohol and 3 drops of DMF (N, N-dimethylformamide) were dissolved in 20 ml of toluene, and triphosgene 0.51 was dissolved. After adding 20 ml of a toluene solution of g at room temperature, the mixture was heated under reflux for 3 hours. After evaporating the solvent under reduced pressure, 1.0 g of 4- (4-cyanophenyl) -1- (L-valyl) piperazine and diisopropylethylamine
40 ml of a 0.73 ml dichloromethane solution was added, and the mixture was stirred at room temperature overnight. After completion of the reaction, the solvent was distilled off under reduced pressure. The obtained residue was purified by silica gel column chromatography to obtain 0.49 g of the desired product as a colorless oily substance.

Production Example 8: 4- (4-cyanophenyl)-
Production of 1- [N- (4-fluorophenethyloxycarbonyl) -L-valyl] piperazine (Compound No. 17) 0.59 g of 4-fluorophenethyl alcohol was dissolved in 20 ml of tetrahydrofuran, and 0.68 g of N, N′-carbonyldiimidazole was dissolved. Was added at room temperature and stirred at this temperature for 4 hours. Next, 4- (4-cyanophenyl)-
A solution of 1- (L-valyl) piperazine (1.0 g) in tetrahydrofuran (10 ml) was added at room temperature, and the mixture was stirred under reflux with heating for 5 hours. After completion of the reaction, the solvent was distilled off under reduced pressure. The obtained residue was purified by silica gel column chromatography to obtain 1.07 g of the desired product as a colorless oily substance.

[Test Examples] Test examples of the compound of the present invention as a fungicide for agricultural and horticultural use will be described below. The control effect was evaluated by visually observing the diseased area ratio, disease length, and number of lesions at the time of the investigation, and the control index was evaluated on the following five levels.

Index 5: No lesion was found. Index 4: Diseased area rate, disease length, and number of lesions were 1 to 1 in the untreated plot.
Less than 10%, Index 3: Diseased area rate, disease length, number of lesions is 10 in the untreated plot
Index: less than 30%, index 2: disease area rate, disease length, number of lesions in untreated plots
<50%, Index 1: 50% of diseased area rate, disease length and number of lesions in untreated plot
未 満 <100%, Index 0: Diseased area rate, diseased length, and number of lesions are equivalent to the untreated plot.

As comparative drugs, No. 2 described in Table 1 of Japanese Patent No. 2867367 are used. Compound No. 16 (Compound A below) and No. 16 18 compounds (Compound B shown below) were used.

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Test Example 1 Test for Control of Downy Mildew of Cucurbits The active ingredient was diluted to 125 ppm with water containing 0.01% Tween20. This drug solution 200 liter / 10
An equivalent amount of a was sprayed with a spray gun on cucumber (variety: Hikari No. 3 P type) at the three leaf stage grown in a plastic pot having a diameter of 6 cm. The next day cucumber downy mildew (Pseudoperono
(spora cubensis) zoospore suspension was spray inoculated. After the pot was kept in a humidity chamber at 22 ° C. for 18 hours, it was left in a greenhouse for 3 days, and the diseased area ratio of the first and second true leaves was visually examined.
The control index was determined according to the evaluation criteria described above. As a result, the following compounds showed an index of 5 at 125 ppm. Compound number: 2,3,4,5,6,7,8,9,10,
11, 12, 13, 14, 15, 16, 17, 19, 2
0, 21, 22, 23, 24, 25, 33, 34, 3
5,36,37,38,39,40,41,42,4
3,44,45,46,47,48,49,50,5
1,52,53,54,55,56,57,58,5
9,60,61,62,63,64,65,66,6
7, 82, 83, 84, 85, 86, 87, 91. The index of Comparative Compounds A and B at 125 ppm was 0.

Test Example 2: Test for controlling tomato late blight The active ingredient compound was diluted to 125 ppm with water containing 0.01% Tween20. 200 L / 10 a equivalent of this drug solution was grown in a plastic pot having a diameter of 6 cm.
Sprayed to the leaf stage tomato (variety: sugar lamp) with a spray gun. The next day Phytophthora infesta
ns) The zoospore suspension was spray inoculated. After the pot was kept in a humidity chamber at 22 ° C. for 16 hours, the pot was allowed to stand in a greenhouse for 3 days, and the diseased area ratio of the third, fourth, and fifth leaves was visually inspected, and a control index was obtained according to the evaluation criteria described above. As a result, the following compounds showed an index of 5 at 125 ppm. Compound number: 1,2,3,4,5,6,7,8,9,1
0, 11, 12, 13, 14, 15, 16, 17, 1
9,20,21,22,23,24,25,33,3
4,35,36,37,38,39,40,41,4
2,43,44,45,46,47,48,49,5
0, 51, 52, 53, 54, 55, 56, 57, 5
8,59,60,61,62,63,64,65,6
6,67,68,82,83,84,85,86,8
8,90. Comparative compounds A and B showed an index of 0 at 125 ppm.

Test Example 3: Test for Control of Grape Downy Mildew The active ingredient was diluted to 125 ppm with water containing 0.01% Tween20. A 200 L / 10a equivalent amount of this drug solution was sprayed with a spray gun on grape seedlings (variety: Kyoho) grown in a plastic pot having a diameter of 12 cm.
The next day, zoospore suspension of grape downy mildew (Plasmopara viticola) was spray-inoculated. After the pot was kept in a humidity chamber at 22 ° C. for 18 hours, the pot was allowed to stand in a greenhouse for 7 days, and the diseased area ratio of the third and fourth leaves was visually inspected, and a control index was obtained according to the evaluation criteria described above. As a result, the following compounds showed an index of 5 at 125 ppm. Compound number: 2,3,4,5,6,7,8,9,10,
11, 12, 13, 14, 15, 16, 17, 19, 2
0, 21, 22, 23, 24, 25, 33, 34, 3
5,36,37,38,39,40,41,42,4
3,44,45,46,47,48,49,50,5
1,52,53,54,55,56,57,58,5
9,60,61,62,63,64,65,66,6
7, 82, 83, 84, 85, 86, 87, 91. Comparative compounds A and B showed an index of 0 at 125 ppm.

Test Example 4: Test for controlling potato blight The active ingredient compound was diluted to 125 ppm with water containing 0.01% Tween20. A 200 L / 10a equivalent amount of this drug solution was sprayed on a potato (variety: baron) grown in a plastic pot having a diameter of 22 cm with a spray gun. The next day, a zoospore suspension of potato blight (Phytophthora infestans) was spray-inoculated. Place the pot in a 22 ° C
After holding for 6 hours, it was left in the greenhouse for 3 days, and the diseased area ratio of the fifth, sixth and seventh leaves was visually inspected, and the control index was determined according to the evaluation criteria described above. As a result, the following compound was obtained as 125
An index of 5 was shown in ppm. Compound number: 1,2,3,4,5,6,7,8,9,1
0, 11, 12, 13, 14, 15, 16, 17, 1
9,20,21,22,23,24,25,33,3
4,35,36,37,38,39,40,41,4
2,43,44,45,46,47,48,49,5
0, 51, 52, 53, 54, 55, 56, 57, 5
8,59,60,61,62,63,64,65,6
6,67,68,82,83,84,85,86,8
8,90. Comparative compounds A and B showed an index of 0 at 125 ppm.

[0078]

The novel substituted piperazine derivatives of the general formula (I) are effective in controlling (preventing and treating) a wide range of plant diseases at low doses, but are safe for crops. It is useful as a fungicide for agricultural and horticultural use.

──────────────────────────────────────────────────続 き Continued on the front page (51) Int.Cl. ⁷ Identification symbol FI Theme coat ゛ (Reference) C07D 241/08 C07D 241/08 295/18 295/18 A 307/20 307/20 487/08 487/08 (72) Inventor Noriko Shimozono 2-1-1 Midorigahara, Tsukuba, Ibaraki Pref. Inside SDS Biotech Tsukuba Research Laboratories (72) Inventor Hiroshi Wada 2-1-1 Midorigahara, Tsukuba-shi, Ibaraki Stock SDS Biotech Tsukuba Research Laboratory (72) Inventor Takuo Kimura 2-1-1 Midorigahara, Tsukuba-shi, Ibaraki FDS Term F-Term (Reference) 4C037 DA06 4C050 AA03 BB04 CC04 EE02 FF01 GG01 GG03 HH01 4H011 AA01 BA01 BB13 BC18 DA13 DD03 DE15

Claims (2)

[Claims] 1. A compound of the general formula (I) [Wherein, R ¹ represents (1) an optionally substituted (i) lower alkyl group, (ii) lower alkenyl group, or (ii)
i) lower alkynyl group, (2) optionally substituted (i) cycloalkyl group, (ii) cycloalkenyl group,
(Iii) a cyclic ether group, (iv) a phenyl group, or (v) a heteroaryl group, (3) a dialkylamino group,
Or (4) -N = CR ² R ³ group (in the group, R ² and R
³ independently represents (i) a hydrogen atom, (ii) an optionally substituted lower alkyl group or a phenyl group, or (iii) a cyano group. ) Represents a group represented by the following formula: (In the group, m Ys each independently represent a lower alkyl group or a phenyl group which may be substituted, and m represents an integer of 0 to 4), and n Xs each represent Independently (1) halogen atom, (2) optionally substituted (i) lower alkyl group, (ii) lower alkoxy group, (iii) lower alkenyloxy group, or (iv) lower alkylthio group, (3) ) An optionally substituted phenyloxy group, (4) pyridyloxy group or pyrimidyloxy group, (5) alkoxycarbonyl group, (6) acyl group, (7) cyano group, (8) nitro group, (9) Represents a dialkylamino group, (10) an alkanesulfinyl group, an alkanesulfonyl group, or an alkanesulfonyloxy group, or (11) an alkylaminocarbonyloxy group, and n is an integer of 0 to 3. Representing the. ] The substituted piperazine derivative shown by these. 2. A fungicide for agricultural and horticultural use containing the substituted piperazine derivative represented by the general formula (I) according to claim 1 as an active ingredient.