JP2000351772A - Production of new oxide derivative - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain the subject compound free from any concern about chemical injury on useful plants and also exhibiting sufficient plant diseases injury- controlling activity by synthesis with a specific new hydroxime derivative as intermediate. SOLUTION: This new oxime derivative of formula V is obtained by the following process: an oximation agent is reacted with a ketone compound of formula I [X is H, a halogen, nitro or the like; n is 0-3; HetB is a ring structural group of formula II (Y is H, a halogen or the like) or the like] to form a hydroxime derivative of formula III, which, in turn, is reacted with an alkylating agent of formula IV (R1 is H or a lower alkyl; HetA is a six- membered aromatic ring or the like containing 1-2 N atom(s) and optionally substituted with 1-2 specific substituent(s); Z is an eliminable group) in the presence of a base; wherein the hydroxime derivative of formula III is e.g. (Z) or (E)-(5-methyl-1,2,3-thiadiazol-4-yl)phenylmethanoneoxime.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

TECHNICAL FIELD The present invention relates to a method for producing a novel oxime derivative and a novel hydroxyme derivative useful as an intermediate in the production method.

[0002]

2. Description of the Related Art An oxime derivative having an effect as a pesticide is disclosed, for example, in Japanese Patent Application Laid-Open No. 7-252242 according to the invention of the present inventors.
It is disclosed that 2,3-thiadiazole derivatives are effective as plant disease controlling agents. These compounds are
There is a need for the development of smaller and more potent drugs that exhibit significant efficacy.

[0003]

The problem to be solved by the present invention is to provide a method for industrially producing a novel oxime derivative which is free from phytotoxicity to useful plants and has a sufficient activity for controlling plant diseases. An object of the present invention is to provide a novel hydroxyme derivative useful as an intermediate used in a production method.

[0004]

Means for Solving the Problems The inventors of the present invention have intensively studied methods for producing various novel oxime derivatives in order to solve the above-mentioned problems. Industrially producing a novel oxime derivative having the same, and a hydroxyme derivative represented by the general formula (II) as an intermediate used in the production method,
The present invention has been completed.

That is, the present invention provides (1) the following general formula (I)

[0006]

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Wherein X is a hydrogen atom, a halogen atom, a nitro group, a hydroxy group, a cyano group, a carboxyl group, an alkoxycarbonyl group, a lower alkyl group, a lower alkyl group substituted with a halogen atom, a lower alkoxy group, Atom-substituted lower alkoxy group, lower alkylthio group, halogen atom-substituted lower alkylthio group, lower alkylsulfonyl group, halogen atom-substituted lower alkylsulfonyl group, aryl group, halogen atom or lower alkyl group Aryl group,
Represents an aryloxy group, an aryloxy group substituted with a halogen atom or a lower alkyl group, an amino group or an amino group substituted with a lower alkyl group, n represents an integer of 0 to 3, and HetB represents the following three formulas:

[0008]

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(Wherein, Y represents a hydrogen atom, a halogen atom, a lower alkyl group or a lower alkyl group substituted with a halogen atom). Wherein an oximation agent is reacted with the ketone compound represented by the following general formula (II):

[0010]

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(Wherein X, n and HetB are as defined in the general formula (I)), (2) a method for producing a hydroxyme derivative represented by the following general formula (II)

[0012]

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Wherein X is a hydrogen atom, a halogen atom, a nitro group, a hydroxy group, a cyano group, a carboxyl group, an alkoxycarbonyl group, a lower alkyl group, a lower alkyl group substituted by a halogen atom, a lower alkoxy group, Atom-substituted lower alkoxy group, lower alkylthio group, halogen atom-substituted lower alkylthio group, lower alkylsulfonyl group, halogen atom-substituted lower alkylsulfonyl group, aryl group, halogen atom or lower alkyl group Aryl group,
Represents an aryloxy group, an aryloxy group substituted with a halogen atom or a lower alkyl group, an amino group or an amino group substituted with a lower alkyl group, n represents an integer of 0 to 3, and HetB represents the following three formulas:

[0014]

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(Wherein, Y represents a hydrogen atom, a halogen atom, a lower alkyl group or a lower alkyl group substituted with a halogen atom). A hydroxyme derivative represented by the following general formula (III):

[0016]

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(Wherein R ¹ represents a hydrogen atom or a lower alkyl group; HetA represents a halogen atom, a lower alkyl group,
One or two nitrogen atoms which may be substituted with one or two substituents selected from the group consisting of lower alkylthio, lower alkylsulfonyl, lower alkoxy, trifluoromethyl and cyano Represents a 6-membered nitrogen-containing aromatic ring or a benzo-fused ring-type nitrogen-containing aromatic ring thereof,
Z represents a leaving group. Wherein the alkylating agent represented by the general formula (V) is reacted in the presence of a base.

[0018]

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(Where HetB, X and n represent the general formula (II)
HetA and R ¹Is the general formula (II
As defined in I). Oxime invitation represented by)
(3) HetA is a pyridyl group or one
Substituted with a halogen atom or lower alkyl group
The oxime derivative according to claim 2, which is a lysyl group.
Manufacturing method, (4) The following general formula (II)

[0020]

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Wherein X is a hydrogen atom, a halogen atom, a nitro group, a hydroxy group, a cyano group, a carboxyl group, an alkoxycarbonyl group, a lower alkyl group, a lower alkyl group substituted with a halogen atom, a lower alkoxy group, Atom-substituted lower alkoxy group, lower alkylthio group, halogen atom-substituted lower alkylthio group, lower alkylsulfonyl group, halogen atom-substituted lower alkylsulfonyl group, aryl group, halogen atom or lower alkyl group Aryl group,
Represents an aryloxy group, an aryloxy group substituted with a halogen atom or a lower alkyl group, an amino group or an amino group substituted with a lower alkyl group, n represents an integer of 0 to 3, and HetB represents the following three formulas:

[0022]

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(Wherein, Y represents a hydrogen atom, a halogen atom, a lower alkyl group or a lower alkyl group substituted with a halogen atom). A hydroxyme derivative represented by the following general formula (IV):

[0024]

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[Wherein, R ¹ represents a hydrogen atom or a lower alkyl group, and HetC contains one or more nitrogen atoms and may further contain a sulfur or oxygen atom. A 5-membered nitrogen-containing aromatic ring or a benzo-fused ring-type nitrogen-containing aromatic ring thereof which may be substituted with a group, wherein the substituent on the nitrogen atom of the 5-membered nitrogen-containing aromatic ring is a lower alkyl group,
A group selected from the group consisting of a lower alkylsulfonyl group, a triphenylmethyl group, a lower alkoxymethyl group, and an N, N-disubstituted sulfamoyl group substituted with a lower alkyl group; The substituent on the carbon atom includes a halogen atom, a cyano group, an alkyl group having 1 to 6 carbon atoms, an alkyl group having 1 to 6 carbon atoms substituted by a halogen atom, a cycloalkyl group having 3 to 6 carbon atoms, Two
6, an alkenyl group having 6 to 6 carbon atoms, an alkynyl group having 2 to 6 carbon atoms, an alkoxy group having 1 to 5 carbon atoms,

A C1-C5 alkoxy group substituted by a halogen atom, a lower alkylthio group, a lower alkylthio group substituted by a halogen atom, a lower alkylsulfonyl group, a lower alkylsulfonyl group substituted by a halogen atom, a lower alkyl A sulfinyl group, a lower alkylsulfinyl group substituted with a halogen atom, an amino group, an amino group substituted with a lower alkyl group or a cycloalkyl group having 3 to 6 carbon atoms or a triphenylmethyl group, a lower alkoxycarbonyl group, a carbamoyl group, A carbamoyl group substituted with a lower alkyl group, an aminomethyl group, an aminomethyl group substituted with a lower alkyl group, an acylaminomethyl group, an N-alkoxycarbonylaminomethyl group, an alkylthiomethyl group, an aryl group, and a halogen atom Allie Group, heteroaryl group or

A —N (R ² ) C (＝ O) R ³ group (where R
² represents a hydrogen atom or a methyl group, R ³ is a hydrogen atom, an alkyl group having 1 to 10 carbon atoms, an alkyl group having 1 to 10 carbon atoms substituted with a halogen atom, a cycloalkyl group having 3 to 8 carbon atoms, An alkenyl group having 2 to 6 carbon atoms, an alkynyl group having 2 to 4 carbon atoms, an aralkyl group, a lower alkyl group substituted with an amino group, an aralkyl group substituted with an amino group, a lower alkyl group substituted with an acylamino group, An aralkyl group substituted with an acylamino group, a lower alkyl group substituted with an alkoxycarbonylamino group, an aralkyl group substituted with an alkoxycarbonylamino group, an aryl group; a halogen atom and a lower alkyl group substituted with a halogen atom; The group consisting of alkyl, lower alkoxy, lower alkylthio, amino, nitro, and cyano Aryl group substituted with chosen group; a heteroaryl group, a lower alkoxy group, 3 carbon atoms
Represents a cycloalkyloxy group, a benzyloxy group, or an aryloxy group. ) And Z represents a leaving group. Wherein the alkylating agent represented by the general formula (VI) is reacted in the presence of a base.

[0028]

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(Wherein HetB, X and n represent the general formula (II)
HetC and R ¹Is the general formula (IV)
As defined in Oxime derivative represented by)
(5) In the general formula (VI), HetC is

[0030]

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[Wherein R ⁴ is a hydrogen atom, an amino group, an alkoxy group having 1 to 5 carbon atoms, an alkoxy group having 1 to 5 carbon atoms substituted with a halogen atom, a lower alkylthio group, or a halogen atom. A lower alkylthio group, a lower alkylsulfonyl group, a lower alkylsulfonyl group substituted with a halogen atom, a lower alkylsulfinyl group, a lower alkylsulfinyl group substituted with a halogen atom, or

—NHC (＝ O) R ³ group (wherein R ³ is a hydrogen atom, an alkyl group having 1 to 10 carbon atoms, an alkyl group having 1 to 10 carbon atoms substituted by a halogen atom, 8 cycloalkyl group, alkenyl group having 2 to 6 carbon atoms, alkynyl group having 2 to 4 carbon atoms, aralkyl group, lower alkyl group substituted with amino group, aralkyl group substituted with amino group, substitution with acylamino group Lower alkyl group,
An aralkyl group substituted with an acylamino group, a lower alkyl group substituted with an alkoxycarbonylamino group, an aralkyl group substituted with an alkoxycarbonylamino group,
Aryl group,

An aryl group substituted with a halogen atom, a lower alkyl group, a lower alkyl group substituted with a halogen atom, a lower alkoxy group, a lower alkylthio group, an amino group, a nitro group and a cyano group; A heteroaryl group, a lower alkoxy group,
Represents a cycloalkyloxy group, a benzyloxy group or an aryloxy group having 3 to 6 carbon atoms. ) Wherein R ⁵ is
Represents a hydrogen atom, a halogen atom, a lower alkyl group or a lower alkyl group substituted with a halogen atom. ] The method for producing an oxime derivative according to (4), which is a thiazolyl group represented by the formula:

(6) R ⁴ is a —NHC (＝ O) R ³ group (where R ³ is a hydrogen atom, an alkyl group having 1 to 6 carbon atoms, or an alkyl group having 1 to 6 carbon atoms substituted by a halogen atom) Selected from the group consisting of a halogen atom, a lower alkyl group, a lower alkyl group and a lower alkoxy group substituted with a halogen atom, an amino group, and a cyano group; a cycloalkyl group having 3 to 6 carbon atoms, an aralkyl group, an aryl group; An aryl group substituted with a group represented by the following formula: represents a heteroaryl group or a lower alkoxy group), wherein R ⁵ is a hydrogen atom, the method for producing an oxime derivative according to (5), (7) the following general formula: (II)

[0035]

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Wherein X is a hydrogen atom, a halogen atom, a nitro group, a hydroxy group, a cyano group, a carboxyl group, an alkoxycarbonyl group, a lower alkyl group, a lower alkyl group substituted with a halogen atom, a lower alkoxy group, a halogen atom, Atom-substituted lower alkoxy group, lower alkylthio group, halogen atom-substituted lower alkylthio group, lower alkylsulfonyl group, halogen atom-substituted lower alkylsulfonyl group, aryl group, halogen atom or lower alkyl group Aryl group,
Represents an aryloxy group, an aryloxy group substituted with a halogen atom or a lower alkyl group, an amino group or an amino group substituted with a lower alkyl group, n represents an integer of 0 to 3, and HetB represents the following three formulas:

[0037]

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(Wherein, Y represents a hydrogen atom, a halogen atom, a lower alkyl group or a lower alkyl group substituted with a halogen atom). A hydroxyme derivative,

(8) In the formula (II), X is a hydrogen atom, a halogen atom, a lower alkyl group, a lower alkyl group substituted with a halogen atom, a lower alkoxy group, an alkoxyl group substituted with a halogen atom, It is a cyano group or an aryl group, and provides the hydroxyme derivative according to (7), wherein n is 1 to 3.

[0040]

BEST MODE FOR CARRYING OUT THE INVENTION The general formula (I) of the present invention

[0041]

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And the general formula (II)

[0043]

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And the general formula (V)

[0045]

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And the general formula (VI)

[0047]

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In the formula, X represents a hydrogen atom, a halogen atom,
Nitro group, hydroxy group, cyano group, carboxyl group,
Alkoxycarbonyl group, lower alkyl group, lower alkyl group substituted by halogen atom, lower alkoxy group, lower alkoxy group substituted by halogen atom, lower alkylthio group, lower alkylthio group substituted by halogen atom, lower alkylsulfonyl group A lower alkylsulfonyl group substituted with a halogen atom, an aryl group, an aryl group substituted with a halogen atom or a lower alkyl group,
It represents an aryloxy group, an aryloxy group substituted with a halogen atom or a lower alkyl group, an amino group or an amino group substituted with a lower alkyl group.

Here, the halogen atom includes a chlorine atom, a bromine atom, an iodine atom and a fluorine atom, and the alkoxycarbonyl group includes a methoxycarbonyl group, an ethoxycarbonyl group and an n-propoxycarbonyl group. Lower alkyl groups, lower alkyl groups substituted with halogen atoms include methyl group, ethyl group, n-
A linear or branched lower alkyl group having 1 to 4 carbon atoms such as propyl group, isopropyl group, n-butyl group, isobutyl group, sec-butyl group, tert-butyl group; chloromethyl group; difluoromethyl group; Halogen-substituted lower alkyl groups such as fluoromethyl group, difluorochloromethyl group, pentafluoroethyl group, and 3,3,3-trifluoro-n-propyl group.

The lower alkoxy group and the lower alkoxy group substituted with a halogen atom include methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy, tert- -Butoxy group, cyclopropyloxy group, difluoromethoxy group, trifluoromethoxy group, etc., and the lower alkylthio group, and the lower alkylthio group substituted with a halogen atom include methylthio group, ethylthio group, n-propylthio group, isopropyl Thio group, n-butylthio group, isobutylthio group, sec-butylthio group, difluoromethylthio group, trifluoromethylthio group, cyclopropylthio group and the like,

The lower alkylsulfonyl group and the lower alkylsulfonyl group substituted by a halogen atom include methanesulfonyl group, ethanesulfonyl group, n-propanesulfonyl group, isopropanesulfonyl group, n-butanesulfonyl group and difluoromethanesulfonyl group. , A trifluoromethanesulfonyl group, and the like. Examples of the aryl group, an aryl group substituted with a halogen atom or a lower alkyl group include a phenyl group, a 4-chlorophenyl group, a 4-tolyl group, and a 3-fluorophenyl group. ,

Examples of the aryloxy group, the aryloxy group substituted with a halogen atom or a lower alkyl group include a phenoxy group and a 4-fluorophenoxy group.
Amino groups, amino groups substituted with lower alkyl groups include amino group, methylamino group, ethylamino group, n-propylamino group, isopropylamino group, n-butylamino group, isobutylamino group, sec-butylamino Group, tert
-Butylamino group, dimethylamino group, diethylamino group, di-n-propylamino group, di-n-butylamino group, ethylmethylamino group, methyl-n-propylamino group, ethyl-n-propylamino group, cyclo And a propylamino group.

The substitution position of X is not particularly limited.
Represents an integer of 0 to 3. When n is 2 or 3, X may be the same or different. X is preferably a hydrogen atom, a lower alkyl group having 1 to 2 carbon atoms, a fluoroalkyl group having 1 to 2 carbon atoms, or a halogen atom, and particularly preferably a hydrogen atom, a trifluoromethyl group, or a fluorine atom. Or a chlorine atom.

In the general formulas (V) and (VI), and in the general formulas (III) and (IV), R ¹ represents a hydrogen atom or a lower alkyl group. It may be branched or cyclic, for example, methyl group, ethyl group, n-propyl group, isopropyl group, n-butyl group,
Those having 1 to 4 carbon atoms such as an isobutyl group, a sec-butyl group and a cyclopropyl group are exemplified. Particularly preferred as R ¹ is a hydrogen atom or a methyl group.

In the general formulas (III) and (V), HetA
Represents a 6-membered nitrogen-containing aromatic ring containing one or two nitrogen atoms and optionally substituted with one or two substituents, or a benzo-fused ring-type nitrogen-containing aromatic ring thereof. The 6-membered nitrogen-containing aromatic ring includes a pyridine ring, a pyrimidine ring, a pyrazine ring and a pyridazine ring, and the benzo-fused ring-type nitrogen-containing aromatic ring includes a quinoline ring, a quinazoline ring and a quinoxaline ring.

The group which can be substituted on HetA is a halogen atom, a lower alkyl group, a lower alkylthio group, a lower alkylsulfonyl group, a lower alkoxy group, a trifluoromethyl group or a cyano group. Represents a chlorine atom, a bromine atom, a fluorine atom, and the lower alkyl group includes a methyl group, an ethyl group, and n-
A propyl group, an isopropyl group, a n-butyl group, an isobutyl group, a linear or branched lower alkyl group such as a sec-butyl group, and the like, and examples of the lower alkylthio group include a methylthio group, an ethylthio group, an n-propylthio group, and isopropyl. Examples thereof include a linear or branched lower alkylthio group such as a thio group, an n-butylthio group, an isobutylthio group, and a sec-butylthio group.

The lower alkylsulfonyl group includes
A methanesulfonyl group, an ethanesulfonyl group, a propanesulfonyl group, an isopropanesulfonyl group, a butanesulfonyl group, an isobutanesulfonyl group, a straight-chain or branched lower alkylsulfonyl group such as a sec-butanesulfonyl group. Is a straight-chain or branched lower alkoxy group such as a methoxy group, an ethoxy group, an n-propoxy group, an isopropoxy group, an n-butoxy group, an isobutoxy group, and a sec-butoxy group.

The preferred HetA is pyridine-2
Pyridine-2-yl substituted with an yl group or a lower alkyl group
Yl group, and among these, particularly preferred are
Examples include a pyridin-2-yl group and a 5-methylpyridin-2-yl group.

Formula (I), Formula (II), Formula (V)
And in general formula (VI), HetB is

[0060]

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Wherein Y represents a hydrogen atom, a halogen atom, a lower alkyl group or a lower alkyl group substituted with a halogen atom.
2,3-thiadiazol-4-yl group, 1,2,5-thiadiazol-3-yl group or 1,2,5-oxadiazol-3-yl group or a halogen derivative thereof,
Represents a halogen-substituted or unsubstituted lower alkyl derivative.

Examples of the halogen atom represented by Y include a fluorine atom, a chlorine atom and a bromine atom, and include a lower alkyl group,
Examples of the lower alkyl group substituted with a halogen atom include a methyl group, an ethyl group, an n-propyl group, an isopropyl group, a difluoromethyl group and a trifluoromethyl group.
Although lower alkyl groups of 4 to 4 are mentioned, a particularly preferable one is a methyl group.

In the general formulas (IV) and (VI), HetC
Contains one or more nitrogen atoms, and may further contain a sulfur or oxygen atom, and may be a 5-membered nitrogen-containing aromatic ring or a benzo-fused ring-type nitrogen-containing ring thereof, which may be substituted with one or two substituents. Shows an aromatic ring. Examples of the 5-membered nitrogen-containing aromatic ring include a pyrrole ring, an imidazole ring, an oxazole ring, a thiazole ring, a pyrazole ring, an isoxazole ring, an isothiazole ring, a 1,2,3-triazole ring, a 1,2,4-triazole ring, 1,2,3-oxadiazole ring,

A 1,2,4-oxadiazole ring,
2,5-oxadiazole ring, 1,3,4-oxadiazole ring, 1,2,3-thiadiazole ring, 1,2,4
-A thiadiazole ring, a 1,3,4-thiadiazole ring,
A 1,2,5-thiadiazole ring and a tetrazole ring; examples of the benzo-fused ring type nitrogen-containing aromatic ring include a benzimidazole ring, a benzoxazole ring, a benzothiazole ring, an imidazo [1,2-a] pyridine ring, [1,
2,4] triazo [1,5-a] pyridine ring.

The group which can be substituted on the nitrogen atom of HetC is a lower alkyl group, a lower alkylsulfonyl group, a triphenylmethyl group, a lower alkoxymethyl group, or an N, N-disubstituted sulfamoyl group substituted by a lower alkyl group. However, as the lower alkyl group, a methyl group, an ethyl group,
n-propyl group, isopropyl group, n-butyl group, isobutyl group, sec-butyl group, and as the lower alkylsulfonyl group, methanesulfonyl group, ethanesulfonyl group, n-propanesulfonyl group, isopropanesulfonyl group, n -Butanesulfonyl group and isobutanesulfonyl group; lower alkoxymethyl group includes methoxymethyl group and ethoxymethyl group; N, N-disubstituted sulfamoyl group substituted by lower alkyl group includes dimethylsulfonyl group; A famoyl group and a diethylsulfamoyl group.

The group which can be substituted on the carbon atom of HetC includes a halogen atom, a cyano group, an alkyl group having 1 to 6 carbon atoms, an alkyl group having 1 to 6 carbon atoms substituted by a halogen atom, and a 3 to 6 carbon atoms. Cycloalkyl group, alkenyl group having 2 to 6 carbon atoms, alkynyl group having 2 to 6 carbon atoms, alkoxy group having 1 to 5 carbon atoms, 1 to 5 carbon atoms substituted with a halogen atom
An alkoxy group, a lower alkylthio group, a lower alkylthio group substituted with a halogen atom, a lower alkylsulfonyl group, a lower alkylsulfonyl group substituted with a halogen atom, a lower alkylsulfinyl group, a lower alkylsulfinyl group substituted with a halogen atom, An amino group, an amino group substituted with a lower alkyl group, a cycloalkyl group having 3 to 6 carbon atoms or a triphenylmethyl group,

Lower alkoxycarbonyl group, carbamoyl group, carbamoyl group substituted by lower alkyl group, aminomethyl group, aminomethyl group substituted by lower alkyl group, acylaminomethyl group, N-alkoxycarbonylaminomethyl group, alkylthio group A methyl group, an aryl group, an aryl group substituted with a halogen atom, a heteroaryl group, or

--N (R ² ) C (＝ O) R ³ group (wherein R ²
Represents a hydrogen atom or a methyl group, and R ³ represents a hydrogen atom, an alkyl group having 1 to 10 carbon atoms, preferably an alkyl group having 1 to 8 carbon atoms, and a carbon atom having 1 to 10 carbon atoms, preferably 1 to 10 carbon atoms. 8, an alkyl group having 8 to 8 carbon atoms, preferably a cycloalkyl group having 3 to 6 carbon atoms, an alkenyl group having 2 to 6 carbon atoms, an alkynyl group having 2 to 4 carbon atoms, an aralkyl group,
A lower alkyl group substituted with an amino group, an aralkyl group substituted with an amino group, a lower alkyl group substituted with an acylamino group, an aralkyl group substituted with an acylamino group, a lower alkyl group substituted with an alkoxycarbonylamino group, An aralkyl group substituted with an alkoxycarbonylamino group,

An aryl group; substituted with a group selected from the group consisting of a halogen atom, a lower alkyl group, a lower alkyl group and a lower alkoxy group, a lower alkylthio group, an amino group, a nitro group, and a cyano group substituted with a halogen atom. An aryl group; a heteroaryl group, a lower alkoxy group, a cycloalkyloxy group having 3 to 6 carbon atoms,
It represents a benzyloxy group or an aryloxy group. ).

More specifically, as the halogen atom,
A chlorine atom, a fluorine atom, and a bromine atom;
To 6 alkyl groups, 1 carbon atom substituted with a halogen atom
Examples of the alkyl group of (6) to (6) include a methyl group, an ethyl group, a n-propyl group, an isopropyl group, a n-butyl group, an isobutyl group, a n-hexyl group, a difluoromethyl group, and a trifluoromethyl group. Examples of the 3 to 6 cycloalkyl group include a cyclopropyl group, a cyclopentyl group, and a cyclohexyl group, and examples of the C2 to C6 alkenyl group include a vinyl group, an allyl group, a butenyl group, and a hexenyl group.

Examples of the alkynyl group having 2 to 6 carbon atoms include an ethynyl group, a propargyl group and a butynyl group.
Examples of the lower alkoxy group having 1 to 5 carbon atoms and the lower alkoxy group having 1 to 5 carbon atoms substituted with a halogen atom include a methoxy group, an ethoxy group, an n-propoxy group, an isopropoxy group, an n-butoxy group and an isobutoxy group. , Sec-butoxy group,
n-pentyloxy group, difluoromethoxy group, trifluoromethoxy group and the like, and a lower alkylthio group, as a lower alkylthio group substituted with a halogen atom,
Methylthio, ethylthio, propylthio, isopropylthio, butylthio, isobutylthio, sec-
Examples thereof include a butylthio group, a difluoromethylthio group, and a trifluoromethylthio group.

The lower alkylsulfonyl group and the lower alkylsulfonyl group substituted with a halogen atom include methanesulfonyl, ethanesulfonyl, propanesulfonyl, isopropanesulfonyl, butanesulfonyl, difluoromethanesulfonyl, trifluoromethanesulfonyl and the like. And a lower alkylsulfinyl group, and examples of the lower alkylsulfinyl group substituted with a halogen atom include a difluoromethanesulfinyl group and a trifluoromethanesulfinyl group.

An amino group, a lower alkyl group or a compound having 3 to 3 carbon atoms
Examples of the amino group substituted with the cycloalkyl group 6 include:
Amino group, methylamino group, ethylamino group, propylamino group, isopropylamino group, butylamino group, isobutylamino group, sec-butylamino group, dimethylamino group, diethylamino group, dipropylamino group, dibutylamino group, ethyl Examples include a methylamino group, a methylpropylamino group, an ethylpropylamino group, a cyclopropylamino group, a cyclopentylamino group, and a cyclohexylamino group.

Examples of the lower alkoxycarbonyl group include a methoxycarbonyl group, an ethoxycarbonyl group, and a propoxycarbonyl group. Examples of the carbamoyl group substituted with a lower alkyl group include N-methylcarbamoyl and N-ethyl. Carbamoyl group, N-
Isopropylcarbamoyl group, N, N-diethylcarbamoyl group, and the like. Examples of the aminomethyl group substituted with an aminomethyl group or a lower alkyl group include an aminomethyl group, an N-methylaminomethyl group, and an N-ethylaminomethyl group. , N-propylaminomethyl group, N-isopropylaminomethyl group, N-butylaminomethyl group, N, N-
Examples include a dimethylaminomethyl group and an N, N-diethylaminomethyl group.

Examples of the acylaminomethyl group include formylaminomethyl, acetylaminomethyl, propionylaminomethyl, butyrylaminomethyl, isobutyrylaminomethyl, benzoylaminomethyl, N-
Examples of the acetyl-N-isopropylaminomethyl group include N-alkoxycarbonylaminomethyl groups such as methoxycarbonylaminomethyl group, ethoxycarbonylaminomethyl group, t-butoxycarbonylaminomethyl group, N- (t-butoxycarbonyl group). ) -N-isopropylaminomethyl group and the like; and the alkylthiomethyl group include an isopropylthiomethyl group and the like.

The aryl group and the aryl group substituted with a halogen atom include phenyl, 2-fluorophenyl, 3-fluorophenyl, 4-fluorophenyl, 2-chlorophenyl, 3-chlorophenyl,
-Chlorophenyl group, 2,4-dichlorophenyl group,
A 3,4-dichlorophenyl group, a 2,6-dichlorophenyl group, a naphthyl group, a biphenyl group and the like, and the heteroaryl group includes a pyridin-2-yl group, a pyridin-4-yl group, a pyrimidin-3-yl group A 2-furyl group, a 3-furyl group, a 2-thienyl group, a 3-thienyl group,
Examples include a quinoyl group, an indolyl group, a benzofuranyl group, a benzothienyl group, a benzothiazolyl group, a benzoisoxazolyl group, and a benzoisothiazoyl group.

Specific examples of R ^{3 in the} —N (R ² ) C (＝ O) R ³ group include an alkyl group having 1 to 10, preferably 1 to 8 carbon atoms, which is substituted with a halogen atom. Examples of the alkyl group having 1 to 10 carbon atoms, preferably 1 to 8 carbon atoms, include a methyl group, an ethyl group, an n-propyl group, an isopropyl group, a t-butyl group, an n-butyl group, an isobutyl group, and a sec-butyl group. Group, n-pentyl group, 1-ethylpropyl group, n-decyl group, chloromethyl group, trifluoromethyl group, trichloromethyl group, 1-bromoisopropyl group, chlorodifluoromethyl group, 1-chloromethyl-1-methyl Ethyl group etc. are mentioned, C3-8, Preferably C3-3.
6 as the cycloalkyl group, a cyclopropyl group, a cyclobutyl group, a cyclopentyl group, a cyclohexyl group,
A cyclooctyl group.

The alkenyl group having 2 to 6 carbon atoms includes vinyl group, allyl group, butenyl group, hexenyl group and the like, and the alkynyl group having 2 to 4 carbon atoms includes ethynyl group, propargyl group, butynyl group and the like. Examples of the aralkyl group include a benzyl group and a 2-phenylethyl group. Examples of the lower alkyl group substituted with an amino group include an aminomethyl group and a 1-aminoisobutyl group. As the aralkyl group substituted with
Examples include a 1-amino-2-phenylethyl group and the like, and examples of the lower alkyl group substituted with an acylamino group include an acetylaminomethyl group and a 1-acetylaminoisobutyl group.

Examples of the aralkyl group substituted with an acylamino group include a 1-acetylamino-2-phenylethyl group, and the lower alkyl group substituted with an alkoxycarbonylamino group is t-butoxycarbonylaminomethyl. Group, a 1- (t-butoxycarbonylamino) isobutyl group and the like, and an aralkyl group substituted with an alkoxycarbonylamino group include a 1- (benzyloxycarbonylamino) -2-phenylethyl group and the like.

An aryl group; and a group selected from the group consisting of a halogen atom, a lower alkyl group, a lower alkyl group and a lower alkoxy group, a lower alkylthio group, an amino group, a nitro group, and a cyano group substituted with a halogen atom. Aryl group; phenyl group,
2-fluorophenyl group, 3-fluorophenyl group, 4
-Fluorophenyl group, 2-chlorophenyl group, 3-chlorophenyl group, 4-chlorophenyl group, 2,4-dichlorophenyl group, 3,4-dichlorophenyl group, 2,6
-Dichlorophenyl group, 4-methylphenyl group, 2-methylphenyl group, 2,4-dimethylphenyl group, 4-trifluoromethylphenyl group, 2-methoxyphenyl group, 3-methoxyphenyl group, 4-methoxyphenyl group, 2-methylthiophenyl group, 4-aminophenyl group, 4-acetylaminophenyl group, 2-cyanophenyl group, 3-cyanophenyl group, 4-cyanophenyl group,
Examples thereof include a 4-nitrophenyl group and a naphthyl group.

The heteroaryl groups include 2-furyl, 2-thienyl, pyridin-4-yl, pyridin-2-yl, thiazol-4-yl, oxazol-4-yl, pyrazol-3 and the like. -Yl group, imidazol-4-yl group, isothiazol-5-yl group, isoxazol-5-yl group, pyrazinyl group, pyrimidine-2-
Yl, pyridazin-3-yl, (1,2,3-thiadiazole) -4-yl, (1,2,5-thiadiazole) -3-yl, furazanyl, benzothiazol-2-yl Benzoimidazol-2-yl group, quinolin-2-yl group, isoquinolin-1-yl group, quinoxalin-2-yl group and the like.

The lower alkoxy group includes a methoxy group,
An ethoxy group, an n-propoxy group, an isopropoxy group, a butoxy group, a t-butoxy group, a 1-ethylpropoxy group and the like are mentioned. As the cycloalkyloxy group having 3 to 6 carbon atoms, a cyclopropyloxy group, a cyclopentyloxy group Group, cyclohexyloxy group and the like, and the aryloxy group include a phenoxy group and the like. HetC
Two or more of these substituents which may be substituted on the nitrogen atom and the carbon atom may be present simultaneously.

Preferred as HetC are an optionally substituted thiazol-2-yl group, an optionally substituted thiazol-4-yl group and an optionally substituted thiazol-5-yl group. Of these, particularly preferred are a thiazol-2-yl group, a thiazol-4-yl group, a 2-aminothiazol-4-yl group,
-Acylaminothiazol-4-yl group, 2-alkoxycarbonylaminothiazol-4-yl group, 2-alkoxythiazol-4-yl group, 2-alkylthiothiazol-4-yl group, 2-alkylsulfinylthiazole-4- An yl group, a 2-alkylsulfonylthiazol-4-yl group, a 2-arylthiazol-4-yl group,
A 2-bromothiazol-4-yl group is exemplified.

The oxime moiety present in the oxime derivatives represented by the general formulas (V) and (VI) has a stereostructure of (E) -form or (Z) -form. Are also included in the present invention. Usually, synthetic products are:
It is obtained as a mixture of the (E) -form and the (Z) -form, and these can be isolated by separation and purification.

The (Z) form is more excellent in plant disease control activity than the (E) form, but the (Z) form changes to the (E) form by light or the like in a natural environment, and a certain (E) form. Stabilizes as a mixture at the ratio of the isomer to the (Z) isomer. The stabilized ratio between the (E) -form and the (Z) -form differs for each compound.

The method for producing the oxime derivatives represented by the general formulas (V) and (VI) of the present invention will be described in detail below.

The following general formula (I)

[0088]

Embedded image

(Where HetB, X, and n are as defined above) and an oximation agent are reacted with the ketone compound represented by the following general formula (II):

[0090]

Embedded image

(Where HetB, X, and n are as defined above) are prepared. Further, the hydroxyme derivative is represented by the following general formula (III)

[0092]

Embedded image

(Wherein HetA and R ¹ are as defined above, and Z represents a leaving group) or the following general formula (IV)

[0094]

Embedded image

(Wherein HetC and R ¹ are as defined above, and Z represents a leaving group) by reacting in the presence of a base with an alkylating agent represented by the general formula ( The oxime derivative represented by V) or the general formula (VI) can be produced.

The ketone compound represented by the general formula (I) is
Raw materials used in the production method of the present invention, for example, ethyl 5-methyl (1,2,3-thiadiazoyl-4-yl) carboxylate (Acta Pharm. Suecica, 10, 297 (197)
3)), 5-methyl (1,2,3-thiadiazoyl-4-)
Il) Carboxylic acid (Acta Pharm. Suecica, 10, 297
(1973)), 3-formyl-4-methyl-1,2,5-oxadiazole (J. Org. Chem., 32, 3865 (196
7)), 3-formyl-4-methyl-1,2,5-thiadiazole (Heterocyclic Chem., 22, 325 (1985))
And other methods described in the literature (eg, New Experimental Chemistry Course 1
Synthesis and reaction of four organic compounds II, 1997, Maruzen Co., Ltd.
CA Buehler, DE Pearson, Survey of Organic Sy
ntheses, John Wiley and Sons, New York, 532, 197
6) can be synthesized.

Examples of the oximation agent used in this reaction include hydroxylamine or hydroxylamine salts such as hydroxylamine hydrochloride, hydroxylamine sulfate, and hydroxylamine acetate.
The amount of the oximation agent to be used is generally in the range of 1 to 10 moles, preferably 1 to 2 moles, relative to the ketone.

When a hydroxylamine salt is used, the reaction is carried out in the presence of a base. As the base, for example, an inorganic base such as sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, cesium carbonate, sodium hydrogen carbonate, pyridine, triethylamine, tripropylamine, tributylamine, diisopropylethylamine,
Trioctylamine, N, N-dimethylaniline, N-
Organic bases such as methylpyrrolidine, N-methylmorpholine, N-ethylmorpholine, and 1,8-diazabicyclo [5.4.0] undec-7-ene are exemplified. The amount of the base used is at least equimolar to the hydroxylamine salt.

This reaction can be carried out in the presence or absence of a solvent. The solvent that can be used is not particularly limited as long as it is inert to the reaction.For example, pentane, hexane, heptane, petroleum ether, benzene, toluene,
Hydrocarbon solvents such as xylene, dichloromethane, 1,2
-Halogenated solvents such as dichloroethane, chloroform, carbon tetrachloride, methanol, ethanol, propanol,
2-propanol, alcohol solvents such as trifluoroethanol, acetonitrile, nitrile solvents such as propionnitrile, diethyl ether, diisopropyl ether, dimethoxyethane, dioxane, tetrahydrofuran, ether solvents such as diglyme,

N, N-dimethylformamide, N, N-
Non-protic polar solvents such as dimethylacetamide and dimethylsulfoxide, water, and a mixed solvent system of two or more thereof, preferably, methanol, ethanol, dioxane, tetrahydrofuran and the like, and a mixed solvent of these solvents and water is there. The proportion of water is between 1% and 99%, preferably between 10% and 90%.

The reaction temperature is in the range of -78 to 250 ° C, preferably in the range of -10 to 120 ° C. The reaction time varies depending on the amount of the reaction reagent and the reaction temperature, but ranges from 30 minutes to 24 hours. After the completion of the reaction, if the product needs to be purified, it can be easily purified by a known and commonly used production method such as distillation, recrystallization or column chromatography.

The hydroxyme derivative represented by the general formula (II) and the general formula (III) and the general formula (I
In the reaction with the alkylating agent represented by V), the amount of the alkylating agent to be used is generally in the range of 1 to 5 moles, preferably 1 to 2 moles.

As the base, for example, sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate,
Inorganic bases such as cesium carbonate, sodium hydrogen carbonate and potassium hydrogen carbonate, pyridine, triethylamine, tripropylamine, tributylamine, diisopropylethylamine, trioctylamine, N, N-dimethylaniline, N-methylpyrrolidine, N-methylmorpholine; N
-Ethyl morpholine,

Organic bases such as 1,8-diazabicyclo [5.4.0] undec-7-ene; alkoxides such as sodium methoxide, sodium ethoxide, potassium tert-butoxide and sodium isopentanate; sodium hydride And alkali metal hydrides such as potassium hydride, and organic lithiums such as methyllithium, butyllithium, and phenyllithium. The amount of the base to be used is generally 1 to 10 mol, preferably 1 to 3 mol, per mol of the hydroxyme derivative.

This reaction can be carried out in the presence or absence of a solvent. The solvent that can be used is not particularly limited as long as it is inert to the reaction.For example, pentane, hexane, heptane, petroleum ether, benzene, toluene,
Hydrocarbon solvents such as xylene, dichloromethane, 1,2
-Halogenated solvents such as dichloroethane, chloroform, carbon tetrachloride, methanol, ethanol, propanol,
Alcohol solvents such as 2-propanol and trifluoroethanol; nitrile solvents such as acetonitrile and propionnitrile; ether solvents such as diethyl ether, diisopropyl ether, dimethoxyethane, dioxane, tetrahydrofuran and diglyme; N, N-dimethylformamide; An aprotic polar solvent such as N, N-dimethylacetamide, dimethylsulfoxide and the like, or a mixed solvent system of two or more thereof are exemplified. Preferably, dioxane, tetrahydrofuran, acetonitrile, N, N-
Dimethylformamide, N, N-dimethylacetamide, dimethylsulfoxide and the like. The reaction temperature is-
In the range of 78 to 250 ° C, preferably -10 to 100
It is in the range of ° C. The reaction time varies depending on the amount of the reaction reagent and the reaction temperature, but ranges from 30 minutes to 24 hours. After the completion of the reaction, if the product needs to be purified, it can be easily purified by a known and commonly used production method such as distillation, recrystallization or column chromatography.

Tables 1 to 66 show specific structures of the compounds represented by formulas (V) and (VI). However, in the table, HetA, HetB, HetC, X,
Y, n and R ¹ correspond to the definitions in general formula (II), general formula (V) and general formula (VI), and Me is a methyl group, Et
Is an ethyl group, Pr is a propyl group, Bu is a butyl group, Ph
Represents a phenyl group.

[0107]

[Table 1]

[0108]

[Table 2]

[0109]

[Table 3]

[0110]

[Table 4]

[0111]

[Table 5]

[0112]

[Table 6]

[0113]

[Table 7]

[0114]

[Table 8]

[0115]

[Table 9]

[0116]

[Table 10]

[0117]

[Table 11]

[0118]

[Table 12]

[0119]

[Table 13]

[0120]

[Table 14]

[0121]

[Table 15]

[0122]

[Table 16]

[0123]

[Table 17]

[0124]

[Table 18]

[0125]

[Table 19]

[0126]

[Table 20]

[0127]

[Table 21]

[0128]

[Table 22]

[0129]

[Table 23]

[0130]

[Table 24]

[0131]

[Table 25]

[0132]

[Table 26]

[0133]

[Table 27]

[0134]

[Table 28]

[0135]

[Table 29]

[0136]

[Table 30]

[0137]

[Table 31]

[0138]

[Table 32]

[0139]

[Table 33]

[0140]

[Table 34]

[0141]

[Table 35]

[0142]

[Table 36]

[0143]

[Table 37]

[0144]

[Table 38]

[0145]

[Table 39]

[0146]

[Table 40]

[0147]

[Table 41]

[0148]

[Table 42]

[0149]

[Table 43]

[0150]

[Table 44]

[0151]

[Table 45]

[0152]

[Table 46]

[0153]

[Table 47]

[0154]

[Table 48]

[0155]

[Table 49]

[0156]

[Table 50]

[0157]

[Table 51]

[0158]

[Table 52]

[0159]

[Table 53]

[0160]

[Table 54]

[0161]

[Table 55]

[0162]

[Table 56]

[0163]

[Table 57]

[0164]

[Table 58]

[0165]

[Table 59]

[0166]

[Table 60]

[0167]

[Table 61]

[0168]

[Table 62]

[0169]

[Table 63]

[0170]

[Table 64]

[0171]

[Table 65]

[0172]

[Table 66]

Agrochemicals, particularly plant disease controlling agents, containing the oxime derivative produced by the method of the present invention as an active ingredient are effective against various plant diseases caused by phytopathogenic viruses, bacteria and fungi, and particularly effective against fungal diseases. It is effective against various plant diseases. Examples of plant diseases caused by filamentous fungi include a wide range of plant diseases caused by oomycetes and plant diseases caused by blast fungi (Pyricularia oryzae).

These include downy mildew on various plants (do
wny mildew and plague (late blightor Phytophthora rot)
etc.), for example, grape downy mildew (Plasmopara v
iticola), downy mildew of cucumber (Pseudoperonospora cubensi)
s), dead blight (Phytophthora melonis), tomato gray blight (Phytophthora capsici), plague (Phytophthora infe
stans), downy mildew of cruciferous vegetables (Peronospora brassic
ae), downy mildew of leek (Peronospora destructor), downy mildew of spinach (Peronospora spinaciae), downy mildew of soybean (Peronospora manshurica),

Downy mildew of broad bean (Peronospora viciae),
Tobacco plague (Phytophthora nicotianae var.nicotian
ae), potato blight (Phytophthora infestans), hop downy mildew (Pseudoperonospora humuli), pineapple blight (Phytophthora cinnamomi), bell pepper blight (P
hytophthora capsici), root rot of strawberries (Phytophthoraf
ragariae), damping-off of various crops (due to Pythium spp., etc.),
It has an excellent control effect on a wide range of plant diseases caused by oomycetes (Oomycetes) such as red blight (Pythium aphanidermatum) of bentgrass and rice blast (Pyricularia oryzae).

Although the present drug can use the active ingredient alone, it is generally known and commonly used solid and liquid carriers used in the preparation of agricultural chemicals, as well as dispersants, diluents, emulsifiers, spreading agents, and the like. It can be mixed with an auxiliary agent such as a thickener and formulated into a dosage form such as a wettable powder, a liquid preparation, an oil preparation, a powder preparation, a granule preparation, a sol preparation (flowable) and the like.

Examples of solid and liquid carriers include talc, clay, bentonite, kaolin, diatomaceous earth, montmorillonite, mica, vermiculite, gypsum, calcium carbonate, white carbon, wood powder, starch, alumina, silicate, and sugar polymer. , Waxes, water, alcohols (methyl alcohol, ethyl alcohol, n-propyl alcohol, isopropyl alcohol, n-butyl alcohol, ethylene glycol, benzyl alcohol, etc.), petroleum fractions (petroleum ether, kerosene, solvent naphtha, etc.), Aliphatic or alicyclic hydrocarbons (n-hexane, cyclohexane, etc.),

Aromatic hydrocarbons (benzene, toluene,
Xylene, ethylbenzene, chlorobenzene, cumene,
Methyl naphthalene, etc.), halogenated hydrocarbons (chloroform, dichloromethane, etc.), ethers (isopropyl ether, ethylene oxide, tetrahydrofuran, etc.), ketones (acetone, methyl ethyl ketone, cyclohexanone, methyl isobutyl ketone, etc.), esters (ethyl acetate, Butyl acetate, ethylene glycol acetate, amyl acetate, etc.), acid amides (dimethylformamide, dimethylacetanilide, etc.), nitriles (acetonitrile, propionitrile, acrylonitrile, etc.), sulfoxides (dimethylsulfoxide, etc.), alcohol ethers ( Ethylene glycol monomethyl ether, ethylene glycol monoethyl ether, etc.).

Examples of the auxiliary include nonionic surfactants (polyoxyethylene alkyl ether, polyoxyethylene alkyl ester, polyoxyethylene alkyl phenyl ether, polyoxyethylene sorbitan alkyl ester, sorbitan alkyl ester, etc.),
Anionic surfactants (alkylbenzenesulfonate, alkylsulfosuccinate, polyoxyethylene alkylsulfate, arylsulfonate, etc.), and cationic surfactants (alkylamines, polyoxyethylenealkylamines, quaternary) Ammonium salts), amphoteric surfactants (alkylaminoethylglycine, alkyldimethylbetaine, etc.), polyvinyl alcohol, hydroxypropylcellulose, carboxymethylcellulose, gum arabic, tragacanth gum, xanthan gum, polyvinyl acetate, gelatin, casein, sodium alginate, etc. Is mentioned.

Further, the present medicament can be used in combination with various known and commonly used agricultural and horticultural fungicides, herbicides, plant growth regulators, pesticides such as insecticides, acaricides, and fertilizers. The active ingredient content of this drug varies depending on the form of preparation, application method and other conditions, but is usually 0.5 to 95%.
(Weight), preferably 2 to 70% (weight). The method of application of this chemical can be applied to plants (foliage application), application to plant growing soil (soil application), application to paddy water (water application), application to seeds (seed treatment), etc. It is.

The application rate of this drug varies depending on the plant to be applied, the disease to be applied, and the like. In the case of foliar application, the concentration of the active ingredient is 1 to 10,000 ppm, preferably 10 to 10,000 ppm.
~ 1000 ppm solution per 10 ares
It is preferable to apply 0 L, and in the case of soil application and surface application, 0.1 to 100 per 10 ares in the amount of the active ingredient.
It is preferable to apply 0 g, particularly preferably 10 to 100 g. In the case of seed treatment, 0.001 to 50 g of the active ingredient is preferably applied to 1 kg of seed.

[0182]

EXAMPLES Next, the present invention will be described with reference to Production Examples, Preparation Examples and Test Examples, but the present invention is not limited to these. The compound number is (number in the table) −
(Symbol of HetB)-(compound number in the table).

(Production Example 1) (5-Methyl-1,2,3-
Thiadiazol-4-yl) phenylmethanone (0.2
Hydroxylamine hydrochloride (0.20 g, 2.82 m) was added to a solution of 9 g, 1.41 mmol) in ethanol (20 ml).
mol) and triethylamine (0.4 ml, 2.8 m
mol), and the mixture was heated under reflux for 48 hours. After concentrating the reaction solution, the residue was dissolved in ethyl acetate, washed with water, and dried over magnesium sulfate. The solvent was distilled off, and the residue was purified by column chromatography to give (Z)-(5-methyl-
1,2,3-Thiadiazol-4-yl) phenylmethanone oxime (0.16 g) and (E)-(5-methyl-1,2,3-thiadiazol-4-yl) phenylmethanone oxime (0. 04g) (Compound No. 102-
(A) -14) was obtained.

(Z)-(5-methyl-1,2,3-thiadiazol-4-yl) phenylmethanone oxime; ¹
H-NMR (CDCl ₃ ): δ 2.54 (s, 3
H), 7.30 to 7.50 (m, 5H), 8.30 to
8.45 (brd, 1H). MS (m / e): 219 (M +). (E)-(5-methyl-1,2,3-thiadiazole-
4-Hyl) phenylmethanone oxime; ¹ H-NMR
(CDCl ₃ ): δ 2.67 (s, 3H), 7.35
~ 7.60 (m, 5H), 8.00 to 8.20 (br
d, 1H). MS (m / e): 219 (M +).

(Production Example 2) (Z)-(5-methyl-1,
2,3-Thiadiazol-4-yl) phenylmethanone oxime (9.31 g, 0.04 mol) was dissolved in acetonitrile (677 ml), and potassium carbonate (9.98) was dissolved.
g, 0.07 mol) and the hydrochloride of 2-picolyl chloride (10.40 g, 0.06 mol) were added, and the mixture was stirred with heating under reflux for 5 hours. After concentrating the reaction solution, the residue was extracted with ethyl acetate, washed with water and dried over magnesium sulfate. The solvent was distilled off, the residue was purified by column chromatography, and (Z)-(5-methyl-1,2,3-thiadiazol-4-yl) phenylmethanone O- (2-pyridyl) methyloxime ( 9.67 g) (Compound No. 1-
(a) -1 (Z)).

¹ H-NMR (CDCl ₃ ): δ 2.53
(S, 3H), 5.40 (s, 2H), 7.19 (d
d, J = 4.9 Hz, J = 7.6 Hz, 1H), 7.3
0 to 7.42 (m, 3H), 7.35 (d, J = 7.8
Hz, 1H), 7.44 to 7.50 (m, 2H), 7.
7. 67 (J = 7.8 Hz, J = 7.6 Hz, 1H);
56 (d, J = 4.9 Hz, 1H). MS (m / e): 310 (M +).

(Production Example 3) (E)-(5-methyl-1,
2,3-Thiadiazol-4-yl) phenylmethanone oxime (0.30 g, 1.40 mmol) was dissolved in acetone (20 ml), and potassium carbonate (0.32 g,
2.0 mmol) and hydrochloride of 2-picolyl chloride (0.34 g, 2.0 mmol) were added, and the mixture was stirred at room temperature for 3 days. After concentrating the reaction solution, the residue was extracted with ethyl acetate, washed with water and dried over magnesium sulfate. The solvent was distilled off and the residue was purified by column chromatography,
(E)-(5-methyl-1,2,3-thiadiazole-
4-yl) phenylmethanone O- (2-pyridyl) methyl oxime (0.07 g) (Compound No. 1- (a) -1 (E))
I got

¹ H-NMR (CDCl ₃ ): δ 2.59
(S, 3H), 5.40 (s, 2H), 7.21 (d
d, J = 4.83, 8.70 Hz, 1H), 7.31-
7.72 (m, 7H), 8.58 (d, J = 4.88H)
z, 1H). MS (m / e): 310 (M +).

(Production Example 4) (3-Methyl-1,2,5-
Thiadiazol-4-yl) phenylmethanone (3.2
Hydroxylamine hydrochloride (4.48 g, 63.1 m) was added to a solution of 2 g, 15.7 mmol) in ethanol (85 ml).
mol) and triethylamine (8.8 ml, 63.1).
mmol) and heated under reflux for 8 hours. After concentrating the reaction solution, ethyl acetate / water was added to the residue and extracted. After drying over magnesium sulfate, the solvent was distilled off. The residue was purified by column chromatography, and (Z)-(3-
Methyl-1,2,5-thiadiazol-4-yl) phenylmethanone oxime (2.18 g) (Compound No. 1
02- (b) -14).

¹ H-NMR (CDCl ₃ ): δ 2.53
(S, 3H), 7.27 to 7.56 (m, 5H), 8.
52-8.78 (brd, 1H). MS (m / e): 219 (M +).

(Production Example 5) DMF (150 ml) was mixed with 6
0% sodium hydride (2.41 g, 60.0 mmol
l), ice-cooled, and (Z)-(3-methyl-1,2,2,
5-Thiadiazol-4-yl) phenylmethanone oxime (6.0 g, 27.0 mmol) was added, and the mixture was stirred for 40 minutes. 4-Chloromethyl-2-iso was added to the reaction mixture.
-Propionylaminothiazole (7.76 g, 35.
6 mmol) in DMF (110 ml) was added dropwise.
The reaction solution was gradually returned to room temperature and then stirred for 20 hours.
The solvent was distilled off from the reaction solution under reduced pressure, and the residue was extracted with ethyl acetate / water. The extract was washed with water and dried over magnesium sulfate. The solvent was distilled off, and the residue was purified by column chromatography to give (Z)-(3-methyl-1,
2,5-thiadiazol-4-yl) phenylmethanone O- (2-iso-propionylaminothiazole-
4-yl) methyl oxime (9.08 g) (Compound No. 8
-(b) -7 (Z)).

¹ H-NMR (CDCl ₃ ): δ 1.22
(D, J = 6.91 Hz, 6H), 2.41 (s, 3
H), 2.47 to 2.76 (m, 1H), 5.21.
(S, 2H), 6.89 (s, 1H), 7.28-7.
60 (m, 5H), 9.50 to 9.90 (brd, 1
H). MS (m / e): 401 (M +).

(Production Example 6) (3-Methyl-1,2,5-
Oxadiazol-4-yl) phenylmethanone (3.
Hydroxylamine hydrochloride (5.19 g, 73.0 m) was added to a solution of 43 g (18.0 mmol) in pyridine (55 ml).
mol), and the mixture was heated and stirred at 70 ° C. for 21 hours. After concentrating the reaction solution, the residue was dissolved in ethyl acetate, washed with dilute hydrochloric acid, then with water, and dried over magnesium sulfate. The solvent was distilled off, the residue was purified by column chromatography, and (Z)-(3-methyl-1,2,5-oxadiazol-4-yl) phenylmethanone oxime (2.13 g), and (E)-(3-methyl-1,2,2
5-oxadiazol-4-yl) phenylmethanone oxime (0.79 g) (Compound No. 102- (c)-
14) was obtained.

(Z)-(3-methyl-1,2,5-oxadiazol-4-yl) phenylmethanone oxime;
¹ H-NMR (CDCl ₃ ): δ 2.38 (s, 3
H), 7.30-7.48 (m, 3H), 7.48-
7.62 (m, 2H), 7.89 to 8.00 (brd,
1H). MS (m / e): 219 (M +). (E)-(3-methyl-1,2,5-oxadiazol-4-yl) phenylmethanone oxime; ¹ H-NMR
(CDCl ₃ ): δ 2.55 (s, 3H), 7.30
To 7.48 (m, 3H), 7.48 to 7.62 (m, 2
H), 7.89-8.00 (brd, 1H). MS (m / e): 219 (M +).

(Production Example 7) DMF (16 ml) was added to 60
% Sodium hydride (0.43 g, 10.6 mmol)
And cooled on ice to give (Z)-(3-methyl-1,2,5-
Oxadiazol-4-yl) phenylmethanone oxime (0.94 g, 4.63 mmol) in DMF (20 m
l) The solution was added and stirred for 40 minutes. 4-
Chloromethyl-2-triphenylmethylaminothiazole (2.71 g, 6.94 mmol) in DMF (15 m
l) The solution was added dropwise. The reaction solution was gradually returned to room temperature and then stirred for 4 days. The solvent was distilled off from the reaction solution under reduced pressure, and the residue was extracted with ethyl acetate / water. The extract was washed with water and dried over magnesium sulfate. The solvent was distilled off and the residue was purified by column chromatography,
(Z)-(3-methyl-1,2,5-oxadiazol-4-yl) phenylmethanone O- (2-triphenylmethylaminothiazol-4-yl) methyl oxime (0.59 g) (compound No. 9- (c) -6 (Z)).

¹ H-NMR (CDCl ₃ ): δ 2.23
(S, 3H), 5.11 (s, 2H), 6.27 (s,
1H), 6.80-6.97 (brd, 1H), 7.1.
3 to 7.60 (m, 20H). MS (m / e): 557 (M +).

(Production Example 8) (Z)-(3-methyl-1,
2,5-oxadiazol-4-yl) phenylmethanone O- (2-triphenylmethylaminothiazole-
4-yl) methyl oxime (0.43 g, 0.77 mm
ol) in acetone (15 ml).
ml) and heated under reflux for 8 hours. The solvent was distilled off from the reaction solution under reduced pressure, and the residue was added with ethyl acetate / saturated sodium hydrogen carbonate solution to adjust the pH to 7, followed by extraction. The extract was washed with water and dried over magnesium sulfate. The solvent was distilled off and the residue was purified by column chromatography,
(Z)-(3-Methyl-1,2,5-oxadiazol-4-yl) phenylmethanone O- (2-aminothiazol-4-yl) methyloxime (0.05 g) (Compound No. 8 -(c) -1 (Z)).

¹ H-NMR (CDCl ₃ ): δ 2.31
(S, 3H), 4.85 to 5.10 (brd, 1H),
5.14 (s, 2H), 6.46 (s, 1H), 7.3
2 to 7.66 (m, 5H). MS (m / e): 315 (M +).

(Production Example 9) (Z)-(3-methyl-1,
2,5-oxadiazol-4-yl) phenylmethanone To O- (2-aminothiazol-4-yl) methyl oxime (0.053 g, 0.168 mmol) was added trifluoroacetic anhydride (7 ml), and The mixture was heated and stirred for an hour. The reaction solution was concentrated, the residue was purified by column chromatography, and (Z)-(3-methyl-1,2,5-oxadiazol-4-yl) phenylmethanone O- (2
-Trifluoroacetylaminothiazol-4-yl)
Methyl oxime (0.063 g) (Compound No. 8- (c) -14
(Z)).

¹ H-NMR (CDCl ₃ ): δ 2.26
(S, 3H), 5.26 (s, 2H), 7.07 (s,
1H), 7.28 to 7.56 (m, 5H), 7.68 to
8.10 (brd, 1H). MS (m / e): 411 (M +).

Tables 67 to 81 collectively show physicochemical data such as ¹ H-NMR spectrum and mass spectrum of the oxime derivative produced in the same manner as in these Production Examples. The indication of the compounds in the table indicates, for example, that the compound of 1- (a) -1 is the compound of Table 1 and the compound of No. 1 in which HetB is (a).

[0202]

[Table 67]

[0203]

[Table 68]

[0204]

[Table 69]

[0205]

[Table 70]

[0206]

[Table 71]

[0207]

[Table 72]

[0208]

[Table 73]

[0209]

[Table 74]

[0210]

[Table 75]

[0211]

[Table 76]

[0212]

[Table 77]

[0213]

[Table 78]

[0214]

[Table 79]

[0215]

[Table 80]

[0216]

[Table 81]

Next, preparation examples using the oxime derivative produced by the method of the present invention will be described. Formulation Examples and the compounds of the present invention used in the control test, unless otherwise specified,
It is a mixture of the (Z) form and the (E) form. (Formulation Example 1) Dust Compound No. 2 parts by weight of the oxime derivatives represented by 1- (a) -1 to 66- (b) -10 were each mixed and pulverized with 98 parts by weight of clay to obtain a powder.

(Formulation Example 2) Wettable powder Compound No. 20 parts by weight of the oxime derivatives represented by 1- (a) -1 to 66- (b) -10 were each mixed and pulverized with 68 parts by weight of clay, 8 parts by weight of white carbon and 4 parts by weight of polyoxyethylene nonylphenyl ether. , A wettable powder.

Formulation Example 3 Granules Compound No. 5 parts by weight of the oxime derivatives represented by 1- (a) -1 to 66- (b) -10 were mixed and ground with 90 parts by weight of an equal mixture of bentonite and talc and 5 parts by weight of sodium alkylbenzenesulfonate, respectively. It was molded into an agent.

Next, Test Examples show that the oxime derivative obtained by the method of the present invention is useful as an active ingredient of various plant disease controlling agents. When the control effect was investigated, the diseased state of the test plant, that is, the degree of lesions appearing on foliage, etc., and the number of diseased individuals in the case of wilt disease, were visually observed, and no lesions or diseased individuals were observed. If not, "A", 1 compared to untreated area
The results are evaluated in four stages as "B" when about 0% is recognized, "C" when about 25% is recognized, and "D" when 50% or more is recognized, and shown in the table.

(Test Example 1) Tomato Blight Control Test A wettable powder prepared by the method of (Formulation Example 2) was effectively applied to 3 to 4 leaf stage tomatoes (variety: Toyofuku) grown in plastic pots having a diameter of 9 cm. It was diluted with water containing a surfactant (0.02%) so that the component concentration became 250 ppm, and sprayed with foliage. After air-drying, Phytophthora infestan
The spore suspension of s) was spray-inoculated, left in a moist chamber at 20 ° C. for 24 hours, then allowed to develop disease in a greenhouse, and 5 days after inoculation, the extent of the disease was investigated. Table 82 shows the test results of the tomato blight. In addition, 1250 ppm and 250 ppm of manzeb wettable powder were used as control drugs.

[0222]

[Table 82]

(Test Example 2) Cucumber downy mildew controlling effect test A wettable powder prepared by the method of (Formulation Example 2) was applied to a cucumber (cultivar: Tokiwa Shinchiro) at the 3 leaf stage grown in a plastic pot having a diameter of 9 cm. Was diluted with water containing a surfactant (0.02%) so that the active ingredient concentration became 50 ppm, and sprayed with foliage. After air drying, the cucumber downy mildew (Pseudoperonos
pora cubensis) was sprayed and inoculated, left in a moist room at 25 ° C. for 24 hours, then allowed to develop disease in a greenhouse, and 7 days after inoculation, the extent of the disease was investigated. Table 83 shows the test results of cucumber downy mildew. Manzeb wettable powder 1 was used as a control drug.
250 ppm and 50 ppm were used.

[0224]

[Table 83]

(Test Example 3) Cucumber downy mildew control test (leaf disk test) The first leaf of cucumber (variety: Tokiwa Shinjiro) at the 2nd to 3rd leaf stage was punched into a 10 mm diameter disc, It was immersed for 30 minutes in a chemical solution having an active ingredient concentration of 10 ppm prepared using a wettable powder prepared according to the method 2). After air-drying, a spore suspension of cucumber downy mildew (Pseudoperonospora cubensis, metalaxyl-resistant strain) was inoculated dropwise, placed in a moist chamber, and placed in an artificial weather device (14 hours daylength, day temperature 25 ° C, night temperature 18).
C) for 7 days, and the degree of disease development was investigated. Table 84 shows the results of the cucumber downy leaf leaf disk test. In addition, as a control drug, Manzeb wettable powder and metalaxyl wettable powder were used.
ppm was used.

[0226]

[Table 84]

Test Example 4 Test for Control of Grape Downy Mildew (Leaf Disk Test) Leaves of a grape leaf (cultivar: Neo Muscat) planted in the open field with a diameter of 1
A 0 mm disk was punched out, and the active ingredient concentration was adjusted using a wettable powder prepared according to the method of (Formulation Example 2).
It was immersed in a 10 ppm solution for 30 minutes. After air-drying, a spore suspension of a metalaxyl-sensitive strain A and a metalaxyl-resistant strain B of grape downy mildew (Plasmopara viticola) was inoculated dropwise, placed in a moist chamber, and placed in an artificial weather device (14 hours daylength, day temperature 25 days).
C., night temperature 18 ° C.) for 7 days, and the degree of onset was investigated.
Table 85 shows the results of the grape downy mildew leaf disk test.
In addition, 10 ppm of manzeb wettable powder and metalaxyl wettable powder were used as control drugs.

[0228]

[Table 85]

(Test Example 5) Cucumber seedling blight control test Pythium aphanidermatu cultivated by sterilizing soil and soil bran in a deep bottom petri dish having a diameter of 15 cm.
m) was mixed and packed. After sowing 10 cucumber seeds (variety: Dark Green Shin Tokiwa) per pot, the wettable powder prepared by the method of (Preparation Example 2) was used, and the active ingredient concentration was 1000 ppm.
And diluted with water to irrigate with soil. After the treatment, the cells were placed in an artificial weather device at 25 ° C. for 14 hours in a wet room as a wet chamber, and the disease severity was examined 4 days later. Table 86 shows the test results of the cucumber seedling blight. In addition, 1000 ppm of captan wettable powder was used as a control drug.

[0230]

[Table 86]

(Test Example 6) Rice blast control effect test A wettable powder prepared by the method of (Formulation Example 2) was applied to rice (cultivar: Aichi Asahi) at the 3-4 leaf stage grown in a plastic pot having a diameter of 9 cm. Was diluted with water containing a surfactant (0.02%) so that the active ingredient concentration became 250 ppm, and sprayed with foliage. After air drying, rice blast fungus (Pyricularia oryzae)
The spore suspension was spray-inoculated, left in a moist chamber at 25 ° C. for 24 hours, then allowed to develop disease in a greenhouse, and 7 days after inoculation, the extent of the disease was examined. Table 87 shows the results of the rice blast test. In addition,
500 ppm of Fusaride wettable powder and 2
50 ppm was used.

[0232]

[Table 87]

The specific structures of the compounds produced by the method of the present invention are further illustrated in Tables 88 to 90. However, in the table, HetB, HetC, X, Y and n correspond to the definitions in the general formulas (V) and (VI), and Me
Represents a methyl group.

[0234]

[Table 88]

[0235]

[Table 89]

[0236]

[Table 90]

Physical chemistry data such as ¹ H-NMR spectrum and mass spectrum of the oxime derivative produced in the same manner as in Production Examples 1 to 9 are further shown in Tables 91 to 97.

[0238]

[Table 91]

[0239]

[Table 92]

[0240]

[Table 93]

[0241]

[Table 94]

[0242]

[Table 95]

[0243]

[Table 96]

[0244]

[Table 97]

Test examples of the oxime derivative produced by the method of the present invention will be further described. In addition, the meaning of the evaluation of A to D is as follows.
The same as in Test Examples 1 to 6.

(Test Example 7) Cucumber downy mildew controlling effect test A cucumber downy mildew controlling effect test was carried out in the same manner as described in Test Example 2. The test results are shown in Table 98.

[0247]

[Table 98]

(Test Example 8) Cucumber downy mildew controlling effect test (leaf disk test) A cucumber downy mildew controlling effect test (leaf disk test) was carried out in the same manner as described in Test Example 3. The test results are shown in Table 99.

[0249]

[Table 99]

(Test Example 9) Grape downy mildew controlling effect test (leaf disk test) A grape downy mildew controlling effect test (leaf disk test) was performed in the same manner as described in Test Example 4. As the grape downy mildew (Plasmopara viticola), a resistant strain b was used. The test results are shown in Table 100.

[0251]

[Table 100]

Tables 101 to 102 show the specific structures of the compounds represented by the general formula (II) produced by the method of the present invention. However, in the table, Het
B, X, n and Y correspond to the definition in general formula (II),
Me represents a methyl group, Et represents an ethyl group, and Ph represents a phenyl group.

[0253]

[Table 101]

[0254]

[Table 102]

The physicochemical data such as ¹ H-NMR spectrum and mass spectrum of the hydroxyme derivative produced in the same manner as in Production Examples 1, 4 and 6 are shown in Tables 103-103.
As shown in Table 106.

[0256]

[Table 103]

[0257]

[Table 104]

[0258]

[Table 105]

[0259]

[Table 106]

[0260]

INDUSTRIAL APPLICABILITY The present invention can provide a method for producing a novel oxime derivative having a low phytotoxicity to useful plants and having a sufficient activity for controlling plant diseases, and an intermediate useful for the production method. .

──────────────────────────────────────────────────続 き Continued on the front page (51) Int.Cl. ⁷ Identification symbol FI Theme coat ゛ (Reference) C07D 413/12 C07D 417/12 417/12 417/14 417/14 471/04 101 471/04 101 108A 108 285/12 A // A01N 43/828 A01N 43/82 102 43/832 103 (72) Inventor Jin Kondo 1-25-16-205 Chikidaihigashi, Wakaba-ku, Chiba Chiba Prefecture (72) Inventor Hiroyuki Tsuboi Chiba Prefecture 10-12-4, Yachiyodainishi, Yachiyo-shi (72) Inventor Mika Iiyama 143-205, Misaki, Sakura-shi, Chiba (72) Inventor Takashi Asada 4-18-6, Chuodai, Shisui-cho, Inba-gun, Chiba (72) Inventor Takashi Goto 3-5-1-2-101 Osakidai, Sakura-shi, Chiba F-term (reference) 4C036 AD04 AD16 AD17 AD21 4C056 AA01 AB02 AC04 AD01 AE03 FA03 FA07 FA13 4C063 AA01 AA03 BB01 BB07 CC58 CC62 CC67 CC73 CC94 DD04 DD12 DD1 4 DD25 DD31 DD41 DD52 DD58 DD62 EE03 4C065 AA03 BB04 BB06 CC01 DD02 DD03 EE02 HH04 JJ01 KK01 LL01 PP16 PP17 QQ05 4H011 AA01 AA03 AA04 BB10 DA02 DA15 DD03

Claims (8)

[Claims] [Claim 1] The following general formula (I) [In the formula, X is a hydrogen atom, a halogen atom, a nitro group, a hydroxy group, a cyano group, a carboxyl group, an alkoxycarbonyl group, a lower alkyl group, a lower alkyl group substituted with a halogen atom, a lower alkoxy group, or a halogen atom. Lower alkoxy group, lower alkylthio group, lower alkylthio group substituted with halogen atom, lower alkylsulfonyl group, lower alkylsulfonyl group substituted with halogen atom, aryl group, aryl substituted with halogen atom or lower alkyl group A group, an aryloxy group, an aryloxy group substituted with a halogen atom or a lower alkyl group, an amino group or an amino group substituted with a lower alkyl group; n represents an integer of 0 to 3;
B is the following three formulas: (Wherein, Y represents a hydrogen atom, a halogen atom, a lower alkyl group or a lower alkyl group substituted with a halogen atom.). ]
Wherein an oximation agent is reacted with a ketone compound represented by the following general formula (II): (Wherein X, n, and HetB are as defined in the general formula (I)). 2. The following general formula (II):[Wherein X represents a hydrogen atom, a halogen atom, a nitro group,
Roxy group, cyano group, carboxyl group, alkoxycal
Substituted with a bonyl group, a lower alkyl group, or a halogen atom
Lower alkyl, lower alkoxy, halogen atom
Substituted lower alkoxy group, lower alkylthio group, halo
A lower alkylthio group substituted with a gen atom, a lower alkyl
Rusulfonyl group, lower alkyl substituted with halogen atom
Rusulfonyl group, aryl group, halogen atom or low
Aryl group substituted with a secondary alkyl group, aryloxy
Group, substituted with a halogen atom or a lower alkyl group
Substituted with aryloxy group, amino group or lower alkyl group
N represents an integer of 0 to 3;
B is the following three formulas:(Where Y is a hydrogen atom, a halogen atom, a lower alkyl group
Or a lower alkyl group substituted with a halogen atom.
You. ) Is a group represented by any one of the ring structures. ]
And a hydroxyme derivative represented by the following general formula (III):(Where R¹Represents a hydrogen atom or a lower alkyl group;
A is a halogen atom, a lower alkyl group,
O group, lower alkylsulfonyl group, lower alkoxy group,
Selected from the group consisting of trifluoromethyl or cyano
Which may be substituted with one or two substituents,
6-membered nitrogen-containing aromatic ring containing 1 or 2 nitrogen atoms or
Represents a benzo-fused ring type nitrogen-containing aromatic ring, and Z represents a leaving group.
You. Is reacted in the presence of a base.
General formula (V), characterized in that:(Where HetB, X and n are as defined in general formula (II)
HetA and R ¹Is defined in general formula (III)
It is as follows. Method for producing oxime derivative represented by
Law. 3. The method for producing an oxime derivative according to claim 2, wherein HetA is a pyridyl group or a pyridyl group substituted with one halogen atom or lower alkyl group. 4. The following general formula (II):[Wherein X represents a hydrogen atom, a halogen atom, a nitro group,
Roxy group, cyano group, carboxyl group, alkoxycal
Substituted with a bonyl group, a lower alkyl group, or a halogen atom
Lower alkyl, lower alkoxy, halogen atom
Substituted lower alkoxy group, lower alkylthio group, halo
A lower alkylthio group substituted with a gen atom, a lower alkyl
Rusulfonyl group, lower alkyl substituted with halogen atom
Rusulfonyl group, aryl group, halogen atom or low
Aryl group substituted with a secondary alkyl group, aryloxy
Group, substituted with a halogen atom or a lower alkyl group
Substituted with aryloxy group, amino group or lower alkyl group
N represents an integer of 0 to 3;
B is the following three formulas:(Where Y is a hydrogen atom, a halogen atom, a lower alkyl group
Or a lower alkyl group substituted with a halogen atom.
You. ) Is a group represented by any one of the ring structures. ]
And a hydroxyme derivative represented by the following general formula (IV):[Wherein, R¹Represents a hydrogen atom or a lower alkyl group;
C contains one or more nitrogen atoms, and further contains sulfur or
It may contain an oxygen atom and may have one or two substituents
Optionally substituted 5-membered nitrogen-containing aromatic ring or benzo-condensed ring thereof
Represents a condensed nitrogen-containing aromatic ring;
Substituents on the atom are lower alkyl groups, lower alkyls
Ruphonyl group, triphenylmethyl group, lower alkoxymethyl
N, N-di-substitution substituted by a tyl group or a lower alkyl group
A group selected from the group consisting of substituted sulfamoyl groups,
The substituent on the carbon atom of the 5-membered nitrogen-containing aromatic ring is a halogen atom.
Atom, cyano group, alkyl group having 1 to 6 carbon atoms, halogen
Alkyl group having 1 to 6 carbon atoms,
3-6 cycloalkyl groups, alkenyl having 2-6 carbon atoms
Group, alkynyl group having 2 to 6 carbon atoms, alkynyl group having 1 to 5 carbon atoms
A C 1 -C 5 alkyl group substituted with a halogen atom
Substitute with alkoxy group, lower alkylthio group, halogen atom
Lower alkylthio group, lower alkylsulfonyl
Alkylsulfonyl substituted with a group or a halogen atom
Group, lower alkylsulfinyl group, substituted with halogen atom
Lower alkylsulfinyl group, amino group, lower
Alkyl group or cycloalkyl group having 3 to 6 carbon atoms
Amino group substituted by triphenylmethyl group, lower
Alkoxycarbonyl group, carbamoyl group, lower alkyl
Carbamoyl group, aminomethyl group,
Aminomethyl group substituted with a secondary alkyl group, acylamino
Nomethyl group, N-alkoxycarbonylaminomethyl
Group, alkylthiomethyl group, aryl group, halogen atom
An aryl group, a heteroaryl group, or -N
(R^Two) C (= O) R^ThreeGroup (where R^TwoIs a hydrogen atom or
Represents a methyl group;^ThreeIs a hydrogen atom, an atom having 1 to 10 carbon atoms
Alkyl group having 1 to 10 carbon atoms substituted with a halogen atom
Alkyl group, cycloalkyl group having 3 to 8 carbon atoms, carbon number
An alkenyl group having 2 to 6, an alkynyl group having 2 to 4 carbon atoms,
Aralkyl groups, lower alkyl groups substituted with amino groups,
An aralkyl group substituted with an amino group or an acylamino group
Substituted with a substituted lower alkyl group or an acylamino group
Substituted with an aralkyl group or an alkoxycarbonylamino group
Lower alkyl group and alkoxycarbonylamino group
An aralkyl group or an aryl group substituted with
Substituted with lower and lower alkyl groups and halogen atoms
Lower alkyl groups and lower alkoxy groups and lower alkyl groups
Group consisting of o group, amino group, nitro group and cyano group
An aryl group substituted with a group selected from the group consisting of: heteroaryl
Group, lower alkoxy group, cycloalkyl having 3 to 6 carbon atoms
Killoxy group, benzyloxy group or aryloxy group
Represents ) And Z represents a leaving group. A represented by
Reacting the alkylating agent in the presence of a base.
The general formula (VI)(Where HetB, X and n are as defined in general formula (II)
Het C and R ¹Is defined in general formula (IV)
It is a cage. )). 5. In the general formula (VI), HetC is [Wherein R ⁴ represents a hydrogen atom, an amino group, an alkoxy group having 1 to 5 carbon atoms, an alkoxy group having 1 to 5 carbon atoms substituted with a halogen atom, a lower alkylthio group, a lower alkylthio group substituted with a halogen atom. A lower alkylsulfonyl group, a lower alkylsulfonyl group substituted with a halogen atom, a lower alkylsulfinyl group, a lower alkylsulfinyl group substituted with a halogen atom, or -NHC (=
O) R ³ group (wherein, R ³ is a hydrogen atom, an alkyl group having 1 to 10 carbon atoms, an alkyl group having 1 to 10 carbon atoms substituted with a halogen atom, a cycloalkyl group having 3 to 8 carbon atoms, An alkenyl group having 2 to 6 carbon atoms, an alkynyl group having 2 to 4 carbon atoms,
Aralkyl groups, lower alkyl groups substituted with amino groups,
Aralkyl group substituted by amino group, lower alkyl group substituted by acylamino group, aralkyl group substituted by acylamino group, lower alkyl group substituted by alkoxycarbonylamino group, aralkyl group substituted by alkoxycarbonylamino group Aryl substituted with a group selected from the group consisting of a halogen atom, a lower alkyl group, a lower alkyl group substituted with a halogen atom, a lower alkoxy group, a lower alkylthio group, an amino group, a nitro group and a cyano group. A heteroaryl group, a lower alkoxy group, a cycloalkyloxy group having 3 to 6 carbon atoms, a benzyloxy group or an aryloxy group. R ⁵ represents a hydrogen atom, a halogen atom,
Represents a lower alkyl group or a lower alkyl group substituted with a halogen atom. The method for producing an oxime derivative according to claim 4, which is a thiazolyl group represented by the formula: 6. R ⁴ is a —NHC (4O) R ³ group, wherein R
³ is a hydrogen atom, an alkyl group having 1 to 6 carbon atoms, an alkyl group having 1 to 6 carbon atoms substituted with a halogen atom,
6, a cycloalkyl group, an aralkyl group, an aryl group,
A halogen atom, a lower alkyl group, a lower alkyl group substituted with a halogen atom, a lower alkoxy group, and an aryl group substituted with a group selected from the group consisting of an amino group and a cyano group; a heteroaryl group or a lower alkoxy group . The method for producing an oxime derivative according to claim 5, wherein R ⁵ is a hydrogen atom. 7. The following general formula (II): [In the formula, X is a hydrogen atom, a halogen atom, a nitro group, a hydroxy group, a cyano group, a carboxyl group, an alkoxycarbonyl group, a lower alkyl group, a lower alkyl group substituted with a halogen atom, a lower alkoxy group, or a halogen atom. Lower alkoxy group, lower alkylthio group, lower alkylthio group substituted with halogen atom, lower alkylsulfonyl group, lower alkylsulfonyl group substituted with halogen atom, aryl group, aryl substituted with halogen atom or lower alkyl group A group, an aryloxy group, an aryloxy group substituted with a halogen atom or a lower alkyl group, an amino group or an amino group substituted with a lower alkyl group; n represents an integer of 0 to 3;
B is the following three formulas: (Wherein, Y represents a hydrogen atom, a halogen atom, a lower alkyl group or a lower alkyl group substituted with a halogen atom.). ]
A hydroxyme derivative which is 8. In the general formula (II), X is a hydrogen atom, a halogen atom, a lower alkyl group, a lower alkyl group substituted with a halogen atom, a lower alkoxy group, an alkoxyl group substituted with a halogen atom, a cyano group, The hydroxyme derivative according to claim 7, which is a group or an aryl group, and n is 1 to 3.