JPH1192456A - New 3-substituted phenyl-4-halopyridazine derivative and agrochemical containing the same as active ingredient and its intermediate - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain the subject new compound having high herbicidal effects and capable of manifesting sufficient safety in several important crops and useful as agrochemicals, especially a herbicide. SOLUTION: This compound is a 3-substituted phenyl-4-halopyridazine derivative represented by formula I [X is a halogen; Y is H or a halogen; R<1> is H, a halogen or cyano; (n) and (m) are each independently 0 or 1; R<1> is H, a halogen or a 1-6C (halo)alkyl; R<2> is H, a 1-6C alkyl or the like; R<3> is H, nitro or the like], e.g. 3-(4-chloro-2-fluoro-5-cyclopentyloxyphenyl)-6,7-dihydro-4-hydroxy-[5 H]-cyclopenta[c]pyridazine represented by formula II. The compound represented by formula I can be obtained by reacting, e.g. a compound represented by formula III (R<3> ' is H, nitro, an alkoxy or the like; R<17> is a lower alkyl) with a compound represented by formula IV in the presence of a base at 0-200 deg.C.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

The present invention relates to a novel 3-substituted phenyl-4-halopyridazine derivative, a pesticide containing the same as an active ingredient and an intermediate effective for producing the derivative, and particularly as a herbicide. It provides effective pesticides.

[0002]

BACKGROUND OF THE INVENTION Many herbicides have been used in the cultivation of important crops such as wheat, corn, soybean, rice and the like. Desirable herbicide conditions include having a high herbicidal effect at a low dose, having a broad herbicidal spectrum, having an appropriate residual effect, and having sufficient safety for crops. However, many existing herbicides do not fully satisfy these conditions at present.

On the other hand, 3-substituted phenyl-4-halopyridazines such as 4-chloro-3-phenyl-6,7-dihydro-5H-cyclopenta [c] pyridazine and 4-chloro-3
Although the method for synthesizing -phenyl-5,6,7,8-tetrahydrocinnoline is described in Tetrahedron Letters, 37 , 1351 (1996), the above reference discloses 4-chloro-3-
There is no description that phenyl-6,7-dihydro-5H-cyclopenta [c] pyridazine or 4-chloro-3-phenyl-5,6,7,8-tetrahydrocinnoline has herbicidal activity. Furthermore, there is no description about a compound having a substituent at the phenyl group at the 3-position of a pyridazine ring or a cinnoline ring.

Further, the synthesis method and herbicidal activity of 3-substituted phenylpyridazines are described in US Pat. Nos. 5,623,072 and 5,616,789. However,
The substituent of the phenyl group at the 3-position of the pyridazine ring in the above document is characterized by having a hydrogen atom at the 2-position, a haloalkyl at the 3-position, a hydrogen atom, a nitro group, or an amino group at the 4-position. No description is given on the herbicidal activity of a compound having a phenyl group at the 4-position having a halogen or cyano group at the 4-position.

[0005]

DISCLOSURE OF THE INVENTION The present inventors have proposed a 3-substituted phenyl-4-in order to solve the above-mentioned problems of herbicides.
As a result of intensive studies on the synthesis of halopyridazine derivatives and their herbicidal activity, a 3-substituted phenyl-4-halopyridazine derivative having a halogen or cyano group at the 4-position of the phenyl group at the 3-position of the pyridazine ring has a high herbicidal effect. In addition to having sufficient safety for some important crops, the present invention has been completed. That is, the gist of the present invention is represented by the following general formula [I]

[0006]

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(In the above formula, X represents a halogen atom;
Represents a hydrogen atom or a halogen atom, and Z represents a halogen atom.
And n and m are each independently
Represents 0 or 1;¹Is a hydrogen atom, a halogen atom,
C₁-C₆Alkyl group or C₁-C₆Halo archi
And R represents^TwoIs a hydrogen atom, C₁-C₆Alkyl group
Or R¹Together with -KLM- (where K is
Is CR^FourR^Five, CR^FourR^FiveCR⁶R⁷, Oxygen atom, sulfur
Yellow atom or C₁-C₆Substituted with an alkyl group of
L represents CR⁸R⁹, Oxygen atom, sulfur atom or
Is C₁-C₆Indicates a nitrogen atom substituted with an alkyl group
And M is CR^TenR¹¹, Oxygen atom, sulfur atom or C₁−
C₆Represents a nitrogen atom substituted with an alkyl group of
Substituent R^Four~ R¹¹Each independently represent a hydrogen atom or
Or C₁-C₆Represents an alkyl group). However, K, L
And M simultaneously represent an oxygen atom, a sulfur atom or C₁-C₆of
It cannot be a nitrogen atom substituted with an alkyl group. )
Represents that a ring represented by^ThreeIs hydrogen
Atom, nitro group or -QR¹²(Wherein Q is an oxygen atom,
Sulfur atom, sulfinyl group, sulfonyl group or -NR
¹³-(Where R¹³Is a hydrogen atom, C ₁-C₆The alkyl of
Group, C_Two-C₆An alkenyl group of C_Two-C₆Alkini
Group, C₁-C₆Haloalkyl group of C_Two-C₆Halo of
Alkenyl group, C_Two-C₆An alkoxyalkyl group of C
_Two-C₆An acyl group of C₁-C₆Alkylsulfonyl of
Group, C₁-C₆Haloalkylsulfonyl group, C_Two-C
₆An alkenylsulfonyl group of C_Two-C₆The alkoxy of
Substituted with a carbonyl group, a phenyl group or a phenyl group
C₁-C_ThreeRepresents an alkyl group. ) And R¹²Is water
Elementary atom, C₁-C_TenAn alkyl group of C_Two-C_TenArche of
Nyl group, C_Two-C_TenAlkynyl group, C _Three-C₈No shiku
Loalkyl group, C_Four-C_TenSubstituted with an alkyl group
Chloroalkyl group, C_Four-C_Ten(Cycloalkyl) al
Kill group, C_Three-C₈A cycloalkenyl group of C₁-C_Ten
Haloalkyl group of C_Two-C_TenHaloalkenyl group of C
_Three-C₈Halocycloalkyl group, C_Two-C₇The cyano
Alkyl group, C_Two-C_TenAn alkoxyalkyl group of C_Two
-C_TenAn alkylthioalkyl group of C_Two-C_TenArchi
Rusulfonylalkyl group, C_Two-C₆An acyl group of C_Three
-C₆An oxoalkyl group, C₁-C₆Alkyl sulf
Honyl group, C₁-C₆Haloalkylsulfonyl group, C
_Two-C₆Alkenylsulfonyl group, phenyl group,
C substituted with a nyl group₁-C_ThreeAlkyl group of 3-6 members
A heterocyclic group having 1 to 2 oxygen atoms, sulfur atoms and
And / or containing a nitrogen atom), 3-6 membered heterocycle
Groups (the ring may have 1-2 oxygen atoms, sulfur atoms and / or
Or a nitrogen atom-containing C)₁-C_ThreeNo
Alkyl group, the following general formula [II]

[0008]

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Or a group represented by the following general formula [II
I]

[0010]

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(Where R¹⁴Is a hydrogen atom or C₁-C_Four
W is an oxygen atom, a sulfur atom or-
NR¹⁶(Where R¹⁶Is a hydrogen atom or C₁-C_FourAl
Represents a kill group. ) And R^FifteenIs a hydrogen atom, C₁-C₆
An alkyl group of C_Two-C₆An alkenyl group of C_Two-C₆
Alkynyl group, C_Three-C₆A cycloalkyl group, C _Four
-C_TenA cycloalkyl group substituted with an alkyl group
_Three-C₆A cycloalkenyl group of C₁-C₆No haloal
Kill group, C_Two-C₆Haloalkenyl group of C_Three-C₆of
Halocycloalkyl group, C_Two-C_FiveOf cyanoalkyl
Group, C_Two-C₆An alkoxyalkyl group of C_Two-C₆of
Alkylthioalkyl group, C_Two-C₆Alkylsulfo
Nylalkyl group, C_Three-C₆An oxoalkyl group, C_Three
-C₇An acyloxyalkyl group of C_Three-C₇Arco
Xycarbonylalkyl group, phenyl group, phenyl group
Replaced C₁-C_ThreeAn alkyl group of 3-6 members
Groups (the ring may have 1-2 oxygen atoms, sulfur atoms and / or
Or a nitrogen atom) or a 3-6 membered heterocyclic ring
Groups (the ring may have 1-2 oxygen atoms, sulfur atoms and / or
Or a nitrogen atom-containing C)₁-C_ThreeNo
Represents a alkyl group. Also, R^FifteenIs that W is -NR¹⁶Indicates-
In some cases, together with W, 1-2 nitrogen atoms and / or
Represents a 5-6 membered heterocyclic group containing 0-1 oxygen atoms.
It may be formed. ).

R ¹² , R ¹³ or R ¹⁵ is a phenyl group, a C ₁ -C ₃ alkyl group substituted by a phenyl group, 3-6
Membered heterocyclic group, wherein the ring contains 1-2 oxygen, sulfur and / or nitrogen atoms, or 3-6
C-substituted by a membered heterocyclic group, wherein the ring contains 1-2 oxygen, sulfur and / or nitrogen atoms
If an alkyl group having ₁ -C _3, the phenyl group and the heterocyclic group, 1-3 identical or different halogen atoms, alkyl groups of C ₁ -C _4, a trifluoromethyl group,
C ₁ -C ₄ alkoxy, C ₂ -C ₅ acyloxy, C ₁ -C ₄ alkylthio, C ₁ -C ₄ alkylsulfonyl, nitro, cyano or C ₂ -C ₅
May be substituted with an alkoxycarbonyl group. )
Represents a group represented by 3-substituted phenyl-
A 4-halopyridazine derivative, an agricultural chemical containing the 4-halopyridazine derivative as an active ingredient, and an effective intermediate for producing the derivative.
Especially in herbicides.

Hereinafter, the present invention will be described in more detail. In the present invention, the 3-substituted phenyl-4-halopyridazine derivative used as a herbicide is represented by the above general formula [I]. In the above general formula [I], X includes a halogen atom such as a fluorine atom, a chlorine atom, a bromine atom or an iodine atom, and among them, a chlorine atom is preferable. Examples of Y include a hydrogen atom; a halogen atom such as a fluorine atom, a chlorine atom, a bromine atom, or an iodine atom. Among them, a chlorine atom or a fluorine atom is preferable, and a fluorine atom is particularly preferable. Examples of Z include a halogen atom such as a fluorine atom, a chlorine atom, a bromine atom, and an iodine atom; or a cyano group, with a chlorine atom being preferred.

N and m are each independently 0 or 1
And preferably m = 0, and particularly preferably n
= 0 and m = 0.

R ¹ is a hydrogen atom; a halogen atom such as a fluorine atom, a chlorine atom, a bromine atom or an iodine atom; a methyl group, an ethyl group, a propyl group, an isopropyl group, a butyl group, an isobutyl group and a sec-butyl group. , T-butyl group, pentyl group, isopentyl group, neopentyl group, t-
Pentyl group, 1-methylbutyl group, 2-methylbutyl group, 1-ethylpropyl group, 1,2-dimethylpropyl group, 1,3-dimethylpropyl group, hexyl group, isohexyl group, 1-methylpentyl group, 2-methyl Pentyl group, 3-methylpentyl group, 1,1-dimethylbutyl group, 1,2-dimethylbutyl group, 1,3-dimethylbutyl group, 3,3-dimethylbutyl group, 1-ethylbutyl group, 2-ethylbutyl group A C ₁ -C ₆ alkyl group such as 1,1,1,2-trimethylpropyl group, 1-ethyl-1-methylpropyl group, 1-ethyl-2-methylpropyl group;

Fluoromethyl, chloromethyl, bromomethyl, difluoromethyl, trifluoromethyl, 2-fluoroethyl, 2-chloroethyl, 2-
Bromoethyl group, 2,2,2-trifluoroethyl group,
1,1,2,2,2-pentafluoroethyl group, 2-fluoropropyl group, 2-chloropropyl group, 2-bromopropyl group, 3-fluoropropyl group, 3-chloropropyl group, 3-bromopropyl group , 2,2,3,3,3-
Pentafluoropropyl group, 1,1,2,2,3,3
3-heptafluoropropyl group, 2,2,2-trifluoro-1-methylethyl group, 4-fluorobutyl group,
-Chlorobutyl group, 4-bromobutyl group, 2,2,3
C ₁ -C such as 3,4,4,4-heptafluorobutyl group
₆ haloalkyl groups, of which a hydrogen atom, an alkyl group or a haloalkyl group is preferable.

R ² is a hydrogen atom; methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, t-butyl, pentyl, isopentyl, neopentyl, t-pentyl, Pentyl group, 1-methylbutyl group, 2-methylbutyl group, 1-ethylpropyl group, 1,2-dimethylpropyl group, 1,3-dimethylpropyl group, hexyl group, isohexyl group, 1-methylpentyl group, 2-methyl Pentyl group, 3-methylpentyl group, 1,1-dimethylbutyl group, 1,2-dimethylbutyl group, 1,3-dimethylbutyl group, 3,3-dimethylbutyl group, 1-ethylbutyl group, 2-ethylbutyl group ,
1,1,2-trimethylpropyl group, 1-ethyl-1-
Methylpropyl group, an alkyl group of C ₁ -C _6, such as 1-ethyl-2-methylpropyl group.

Further, R ¹ and R ² combine to form -K-LM-
May be formed. In this equation, K is CR ⁴
A group represented by R ⁵ or CR ⁴ R ⁵ CR ⁶ R ⁷ ; an oxygen atom; a sulfur atom; or a nitrogen atom substituted by a C ₁ -C ₆ alkyl group such as a methyl group, an ethyl group, a propyl group, and an isopropyl group. L is a group represented by CR ⁸ R ⁹ ; an oxygen atom; a sulfur atom; or a methyl group, an ethyl group,
A nitrogen atom substituted by a C ₁ -C ₆ alkyl group such as a propyl group or an isopropyl group; M is a group represented by CR ¹⁰ R ¹¹ ; an oxygen atom; a sulfur atom; And a nitrogen atom substituted by a C ₁ -C ₆ alkyl group such as a propyl group and an isopropyl group.

The substituents R ^{4 to} R ¹¹ each independently represent a hydrogen atom; a methyl group, an ethyl group, a propyl group,
Isopropyl, butyl, isobutyl, sec-butyl, t-butyl, pentyl, isopentyl, neopentyl, t-pentyl, 1-methylbutyl, 2-methylbutyl, 1-ethylpropyl, 1 , 2-dimethylpropyl, 1,3-dimethylpropyl, hexyl, isohexyl, 1-methylpentyl, 2-methylpentyl, 3-methylpentyl, 1,1-dimethylbutyl, 1,2 -Dimethylbutyl, 1,3-dimethylbutyl, 3,3-dimethylbutyl, 1-ethylbutyl, 2-ethylbutyl, 1,1,2-trimethylpropyl, 1-ethyl-1-methylpropyl , 1
- alkyl group of C ₁ -C _6, such as ethyl-2-methylpropyl group.

When R ¹ and R ² combine to form a ring represented by -KLM-, preferably, K is a group represented by CR ⁴ R ⁵ or CR ⁴ R ⁵ CR ⁶ R ⁷ ; Or L is a group represented by CR ⁸ R ⁹ or an oxygen atom, and M is a group represented by CR ¹⁰ R ¹¹ or an oxygen atom, and particularly preferably K is CR ⁴ R ⁵ Or a group represented by CR ⁴ R ⁵ CR ⁶ R ⁷ , wherein L is CR
A group represented by ⁸ R ⁹ , wherein M forms a hydrocarbon group having 5 to 6 ring members which is a group represented by CR ¹⁰ R ¹¹ , and more preferably, K, L and M are Each is the case of a methylene group.

R ³ is a hydrogen atom, a nitro group or —QR ¹²
Is a group represented by Q in -QR ¹² represents an oxygen atom,
Sulfur atom, sulfinyl group, sulfonyl group or -NR
¹³ - group represented by an oxygen atom or -NR ¹³ - preferably a group represented by, in particular an oxygen atom.

-NR¹³R in-¹³As a hydrogen source
Child; methyl group, ethyl group, propyl group, isopropyl
Group, butyl group, isobutyl group, sec-butyl group, t-butyl
Group, pentyl group, isopentyl group, neopentyl group, t-
Pentyl group, 1-methylbutyl group, 2-methylbutyl
Group, 1-ethylpropyl group, 1,2-dimethylpropyl
Group, 1,3-dimethylpropyl group, hexyl group,
Xyl group, 1-methylpentyl group, 2-methylpentyl
Group, 3-methylpentyl group, 1,1-dimethylbutyl
Group, 1,2-dimethylbutyl group, 1,3-dimethylbutyl
Group, 3,3-dimethylbutyl group, 1-ethylbutyl
Group, 2-ethylbutyl group, 1,1,2-trimethylpro
Pill group, 1-ethyl-1-methylpropyl group, 1-ethyl
C such as 2-methylpropyl group₁-C₆The alkyl of
Groups; vinyl, allyl, 1-propenyl, isoprop
Phenyl, 1-butenyl, 2-butenyl, 3-butenyl
Nyl, 1-methylallyl, 2-methylallyl, 1
-Pentenyl group, 2-pentenyl group, 3-pentenyl
Group, 4-pentenyl group, 1-methyl-2-butenyl group,
1-methyl-3-butenyl group, 2-methyl-3-butenyl
Group, 3-methyl-2-butenyl group, 3-methyl-3-
Butenyl group, 1,1-dimethylallyl group, 1-ethylamine
Ryl, 1-hexenyl, 2-hexenyl, 3-hexyl
Xenyl, 4-hexenyl, 5-hexenyl, 4
-Methyl-3-pentenyl group, 1-propylallyl group,
C such as 1-ethyl-1-methylallyl group_Two-C₆Al
Kenyl group; ethynyl group, 1-propynyl group, 2-propynyl group
Nyl, 1-butynyl, 2-butynyl, 3-butynyl
Group, 1-methyl-2-propynyl group, 1-pentynyl
Group, 2-pentynyl group, 3-pentynyl group, 4-pentyne
Nyl group, 1-methyl-3-butynyl group, 1,1-dimethyl
2-propynyl group, 1-hexynyl group, 2-hexyl
N-yl, 3-hexynyl, 4-hexynyl, 5-he
C such as xynyl group_Two-C₆An alkynyl group;
Tyl group, chloromethyl group, bromomethyl group, difluoro
Methyl group, trifluoromethyl group, 2-fluoroethyl
Group, 2-chloroethyl group, 2-bromoethyl group, 2,
2,2-trifluoroethyl group, 1,1,2,2,2-
Pentafluoroethyl group, 2-fluoropropyl group, 2
-Chloropropyl group, 2-bromopropyl group, 3-fur
Oropropyl group, 3-chloropropyl group, 3-bromoprop
Ropyl group, 2,2,3,3,3-pentafluoropropyl
Group, 1,1,2,2,3,3,3-heptafluorop
Ropyl group, 2,2,2-trifluoro-1-methylethyl
Group, 4-fluorobutyl group, 4-chlorobutyl group, 4
-Bromobutyl group, 2,2,3,3,4,4,4-hep
C such as tafluorobutyl group₁-C ₆A haloalkyl group;
C such as 3,3-dichloroallyl group_Two-C₆No halo arque
Nyl group: methoxymethyl group, ethoxymethyl group, propo
Xymethyl group, isopropoxymethyl group, butoxymethy
A 2-methoxyethyl group, a 2-ethoxyethyl group,
2-propoxyethyl group, 2-isopropoxyethyl
Group, 2-butoxyethyl group, 3-methoxypropyl group,
C such as 4-methoxybutyl group and 5-methoxypentyl group
_Two-C₆Alkoxyalkyl group; acetyl group, piropi
Onyl group, butyryl group, isobutyryl group, valeryl group,
Isovaleryl group, 2-methylbutyryl group, hexanoyl
Group, 2,2-dimethylbutyryl group, 2-ethylbutyryl
Group, 2-methylvaleryl group, 3-methylvaleryl group, 4
-C such as methylvaleryl group_Two-C ₆Acyl group of methyl
Sulfonyl group, ethylsulfonyl group, propylsulfonyl
Group, isopropylsulfonyl group, butylsulfonyl
Group, pentylsulfonyl group, hexylsulfonyl group, etc.
C₁-C₆Alkylsulfonyl group; trifluoromethyl
C such as rusulfonyl group₁-C₆Haloalkylsulfoni
C; such as vinylsulfonyl group and allylsulfonyl group
_Two-C₆An alkenylsulfonyl group of the formula:
Rubonyl group, ethoxycarbonyl group, propyloxyca
Rubonyl group, isopropylcarbonyl group, butoxycal
C such as bonyl group and pentyloxycarbonyl group_Two-C₆
An alkoxycarbonyl group; a phenyl group and 4-chlorofu
Phenyl, 3-chlorophenyl, 2-chlorophenyl
Phenyl group such as a group; or benzyl group, phenethyl group, etc.
Substituted with a phenyl group of₁-C_ThreeAlkyl group
And preferably a hydrogen atom, C_Two-C₆An acyl group of
C₁-C₆Alkylsulfonyl group or C_Two-C₆of
An alkoxycarbonyl group, particularly preferably a hydrogen atom
Child, C₁-C₆Alkylsulfonyl group or C_Two-C
₆Is an alkoxycarbonyl group.

R ¹² is a hydrogen atom; methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, t-butyl, pentyl, isopentyl, neopentyl, t-butyl, Pentyl group, 1-methylbutyl group, 2-methylbutyl group, 1-ethylpropyl group, 1,2-dimethylpropyl group, 1,3-dimethylpropyl group, hexyl group, isohexyl group, 1-methylpentyl group, 2-methyl Pentyl group, 3-methylpentyl group, 1,1-dimethylbutyl group, 1,2-dimethylbutyl group, 1,3-dimethylbutyl group, 3,3-dimethylbutyl group, 1-ethylbutyl group, 2-ethylbutyl group ,
1,1,2-trimethylpropyl group, 1-ethyl-1-
C ₁ -C ₁₀ such as methylpropyl group, 1-ethyl-2-methylpropyl group, heptyl group, octyl group, nonyl group, etc.
Alkyl, vinyl, allyl, 1-propenyl, isopropenyl, 1-butenyl, 2-butenyl, 3-butenyl, 1-methylallyl, 2-methylallyl, 1-pentenyl, 2 -Pentenyl group, 3-
Pentenyl group, 4-pentenyl group, 1-methyl-2-butenyl group, 1-methyl-3-butenyl group, 2-methyl-
3-butenyl group, 3-methyl-2-butenyl group, 3-methyl-3-butenyl group, 1,1-dimethylallyl group, 1
-Ethylallyl, 1-hexenyl, 2-hexenyl, 3-hexenyl, 4-hexenyl, 5-hexenyl, 4-methyl-3-pentenyl, 1-propylallyl, 1-ethyl-1- methylallyl group, an alkenyl group of C ₂ -C _10, such as a geranyl group; ethynyl, 1-propynyl, 2-propynyl, 1-butynyl group, 2-
Butynyl, 3-butynyl, 1-methyl-2-propynyl, 1-pentynyl, 2-pentynyl, 3-pentynyl, 4-pentynyl, 1-methyl-3-butynyl, 1,1- Dimethyl-2-propynyl, 1-hexynyl, 2-hexynyl, 3-hexynyl, 4
-Alkynyl group of C ₂ -C ₁₀ such as hexynyl group, 5-hexynyl group; cyclopropyl group, cyclobutyl group, cyclopentyl group, cyclohexyl group, cycloheptyl group,
Cycloalkyl groups C ₃ -C _8, such as cyclooctyl;
1-methylcyclopropyl group, 2-methylcyclopropyl group, 1,2-dimethylcyclopropyl group, 2,2-dimethylcyclopropyl group, 2,3-dimethylcyclopropyl group, 1-ethylcyclopropyl group, 2- Ethylcyclopropyl group, 1,2,3-trimethylcyclopropyl group, 2,2,3-trimethylcyclopropyl group, 1,
2,2,3-tetramethylcyclopropyl group, 1-methylcyclobutyl group, 2-methylcyclobutyl group, 3-methylcyclobutyl group, 1,2-dimethylcyclobutyl group, 1,3-dimethylcyclobutyl group A 2,3-dimethylcyclobutyl group, a 2,2-dimethylcyclobutyl group,
1-ethylcyclobutyl group, 2-ethylcyclobutyl group, 3-ethylcyclobutyl group, 1-methylcyclopentyl group, 2-methylcyclopentyl group, 3-methylcyclopentyl group, 1,2-dimethylcyclopentyl group,
1,3-dimethylcyclopentyl group, 2,2-dimethylcyclopentyl group, 2,3-dimethylcyclopentyl group, 3,3-dimethylcyclopentyl group, 1-ethylcyclopentyl group, 1-methylcyclohexyl group, 2-methylcyclohexyl group, 3-methylcyclohexyl group,
4-methylcyclohexyl group, 1,2-dimethylcyclohexyl group, 1,3-dimethylcyclohexyl group, 1,
4-dimethylcyclohexyl group, 2,2-dimethylcyclohexyl group, 2,3-dimethylcyclohexyl group,
2,4-dimethylcyclohexyl group, 3,3-dimethylcyclohexyl group, 3,4-dimethylcyclohexyl group, 4,3- dimethylcyclohexyl group, substituted by an alkyl group of C ₄ -C _10, such as 1-ethyl cyclohexyl group A cycloalkyl group; a (cyclopropyl) methyl group,
(Cyclobutyl) methyl group, (cyclopentyl) methyl group, (cyclohexyl) methyl group, (cycloheptyl)
Methyl group, (cyclooctyl) methyl group, (cyclopropyl) ethyl group, (cyclobutyl) ethyl group, (cyclopentyl) ethyl group, (cyclohexyl) ethyl group,
(Cycloheptyl) ethyl group, (cyclooctyl) ethyl group, (cyclopropyl) Purochiru group, (cyclobutyl) Purochiru group, (cyclopentyl) Purochiru group, (cyclohexyl) Purochiru group, C _4, such as (cycloheptyl) Puroru group - C ₁₀ (cycloalkyl) alkyl group, 2-
Cyclopropenyl group, 2-cyclobutenyl group, 2-cyclopentenyl group, 3-cyclopentenyl group, 2-cyclohexenyl group, 3-C ₃ -C cyclohexenyl group ₈
Cycloalkenyl group; fluoromethyl group, chloromethyl group, bromomethyl group, difluoromethyl group, trifluoromethyl group, 2-fluoroethyl group, 2-chloroethyl group, 2-bromoethyl group, 2,2,2-trifluoroethyl Group, 1,1,2,2,2-pentafluoroethyl group, 2-fluoropropyl group, 2-chloropropyl group,
2-bromopropyl group, 3-fluoropropyl group, 3-
Chloropropyl group, 3-bromopropyl group, 2,2,
3,3,3-pentafluoropropyl group, 1,1,2,2
2,3,3,3-heptafluoropropyl group, 2,2
2-trifluoro-1-methylethyl group, 4-fluorobutyl group, 4-chlorobutyl group, 4-bromobutyl group,
A C ₁ -C ₁₀ haloalkyl group such as a 2,2,3,3,4,4,4-heptafluorobutyl group; a C ₂ -C ₁₀ haloalkenyl group such as a 3,3-dichloroallyl group; 2-difluorocyclopentyl halocycloalkyl group C ₃ -C _8, such as a group; cyanomethyl group, 1-cyanoethyl group, 2
A C ₂ -C ₇ cyano such as a cyanoethyl group, a 1-cyanopropyl group, a 2-cyanopropyl group, a 3-cyanopropyl group, a 1-cyanobutyl group, a 2-cyanobutyl group, a 3-cyanobutyl group, or a 4-cyanobutyl group; Alkyl group; methoxymethyl group, ethoxymethyl group, propoxymethyl group, isopropoxymethyl group, butoxymethyl group, 2-
C ₂ such as methoxyethyl group, 2-ethoxyethyl group, 2-propoxyethyl group, 2-isopropoxyethyl group, 2-butoxyethyl group, 3-methoxypropyl group, 4-methoxybutyl group, and 5-methoxypentyl group alkoxyalkyl groups -C _10; methylthiomethyl group, ethylthiomethyl group, propyl thio methyl group, isopropylthio methyl group, butylthiomethyl group, 2- (methylthio) ethyl, 2- (ethylthio) ethyl group, 2- (Propylthio) ethyl group, 2- (isopropylthio) ethyl group, 2
- (butylthio) ethyl group, 3- (methylthio) propyl, 4- (methylthio) butyl group, 5- (methylthio) alkylthioalkyl group C ₂ -C _10, such as a pentyl group, methylsulfonylmethyl group, ethylsulfonyl methyl Group, propylsulfonylmethyl group, isopropylsulfonylmethyl group, butylsulfonylmethyl group, 2- (methylsulfonyl) ethyl group, 2- (ethylsulfonyl)
Ethyl group, 2- (propylsulfonyl) ethyl group, 2-
C ₂ -C ₁₀ such as (isopropylsulfonyl) ethyl group, 2- (butylsulfonyl) ethyl group, 3- (methylsulfonyl) propyl group, 4- (methylsulfonyl) butyl group and 5- (methylsulfonyl) pentyl group Alkylsulfonylalkyl group; acetyl group, pyropionyl group, butyryl group, isobutyryl group, valeryl group, isovaleryl group, 2-methylbutyryl group, hexanoyl group, 2,2-
Dimethyl butyryl group, 2-ethylbutyryl group, 2-methylvaleryl group, 3-methylvaleryl group, an acyl group of C ₂ -C ₆ such as 4-methylvaleryl group, a 2-oxopropyl group, 1-methyl-2-oxo-propyl , 1-methyl-
2-oxobutyl group, 1-ethyl-2-oxobutyl group, C ₃ -C and 1-propyl-2-oxo-propyl
₆ oxoalkyl groups; C ₁ -C ₆ alkylsulfonyl groups such as methylsulfonyl group, ethylsulfonyl group, propylsulfonyl group, isopropylsulfonyl group, butylsulfonyl group, pentylsulfonyl group, and hexylsulfonyl group; trifluoromethylsulfonyl group Etc. C ₁
Haloalkylsulfonyl group -C _6; vinylsulfonyl groups, alkenylsulfonyl groups C ₂ -C ₆ such as allyl sulfonyl group; a phenyl group, 4-chlorophenyl group, 3-
A phenyl group such as a chlorophenyl group or a 2-chlorophenyl group; or a C ₁ -C ₃ alkyl group substituted with a phenyl group such as a benzyl group or a phenethyl group; a 2-pyridinyl group, a 3-pyridinyl group, a 4-pyridinyl group; 1-furyl group, 2-furyl group, 1-pyranyl group, 2-pyranyl group,
3-pyranyl group, 1-dihydrofuryl group, 2-dihydrofuryl group, 1-dihydropyranyl group, 2-dihydropyranyl group, 3-dihydropyranyl group, 1-tetrahydrofuryl group, 2-tetrahydrofuryl group, A 3-6 membered heterocyclic group such as a 1-tetrahydropyranyl group, a 2-tetrahydropyranyl group, a 3-tetrahydropyranyl group (the ring is 1-
A 3- to 6-membered heterocyclic group such as a 1-tetrahydromethyl group or a 2-tetrahydromethyl group (containing 2 oxygen atoms, a sulfur atom and / or a nitrogen atom); , alkyl group of C ₁ -C ₃ substituted with a sulfur atom and / or nitrogen atom); 1-gamma-butyrolactonyl group represented by the following general formula, such as 2-gamma-butyrolactonyl [II]

[0024]

Embedded image

Or a group represented by the following general formula [II
I]

[0026]

Embedded image

The group represented by

[0028] In the general formula [III], R ¹⁴ is a hydrogen atom; or a methyl group, an ethyl group, a propyl group, an isopropyl group, butyl group, isobutyl group, sec- butyl groups, C ₁ -C of a t- butyl group and the like _And W represents an oxygen atom, a sulfur atom or a group represented by —NR ¹⁶ —.

-NR¹⁶-R¹⁶As a hydrogen atom;
Or methyl, ethyl, propyl, isopropyl
Group, butyl group, isobutyl group, sec-butyl group, t-butyl
C such as a group₁-C_FourIs an alkyl group. R^Fifteenas,
Hydrogen atom: methyl group, ethyl group, propyl group, isopropyl
Pill, butyl, isobutyl, sec-butyl, t-butyl
Tyl group, pentyl group, isopentyl group, neopentyl
Group, t-pentyl group, 1-methylbutyl group, 2-methylbutyl
Tyl group, 1-ethylpropyl group, 1,2-dimethylpro
Pill, 1,3-dimethylpropyl, hexyl, i
Sohexyl group, 1-methylpentyl group, 2-methylpen
Tyl group, 3-methylpentyl group, 1,1-dimethylbutyi
Group, 1,2-dimethylbutyl group, 1,3-dimethylbutyl
Butyl, 3,3-dimethylbutyl, 1-ethylbutyl
Group, 2-ethylbutyl group, 1,1,2-trimethylpro
Pill group, 1-ethyl-1-methylpropyl group, 1-ethyl
C such as 2-methylpropyl group₁-C₆The alkyl of
Groups; vinyl, allyl, 1-propenyl, isoprop
Phenyl, 1-butenyl, 2-butenyl, 3-butenyl
Nyl, 1-methylallyl, 2-methylallyl, 1
-Pentenyl group, 2-pentenyl group, 3-pentenyl
Group, 4-pentenyl group, 1-methyl-2-butenyl group,
1-methyl-3-butenyl group, 2-methyl-3-butenyl
Group, 3-methyl-2-butenyl group, 3-methyl-3-
Butenyl group, 1,1-dimethylallyl group, 1-ethylamine
Ryl, 1-hexenyl, 2-hexenyl, 3-hexyl
Xenyl, 4-hexenyl, 5-hexenyl, 4
-Methyl-3-pentenyl group, 1-propylallyl group,
C such as 1-ethyl-1-methylallyl group_Two-C₆Al
Kenyl group; ethynyl group, 1-propynyl group, 2-propynyl group
Nyl, 1-butynyl, 2-butynyl, 3-butynyl
Group, 1-methyl-2-propynyl group, 1-pentynyl
Group, 2-pentynyl group, 3-pentynyl group, 4-pentyne
Nyl group, 1-methyl-3-butynyl group, 1,1-dimethyl
2-propynyl group, 1-hexynyl group, 2-hexyl
N-yl, 3-hexynyl, 4-hexynyl, 5-he
C, such as a xynyl group_Two-C₆Alkynyl group; cyclopropyl
Group, cyclobutyl group, cyclopentyl group, cyclohexyl
C such as a sil group_Three-C ₆A cycloalkyl group of 1-methyl
Cyclopropyl group, 2-methylcyclopropyl group, 1,
2-dimethylcyclopropyl group, 2,2-dimethylcycl
Propyl group, 2,3-dimethylcyclopropyl group, 1
-Ethylcyclopropyl group, 2-ethylcyclopropyl
Group, 1,2,3-trimethylcyclopropyl group, 2,
2,3-trimethylcyclopropyl group, 1,2,2,3
-Tetramethylcyclopropyl group, 1-methylcyclobut
Tyl group, 2-methylcyclobutyl group, 3-methylcyclo
Butyl group, 1,2-dimethylcyclobutyl group, 1,3-
Dimethylcyclobutyl group, 2,3-dimethylcyclobuty
Group, 2,2-dimethylcyclobutyl group, 1-ethyl
Cyclobutyl group, 2-ethylcyclobutyl group, 3-ethyl
Cyclobutyl group, 1-methylcyclopentyl group, 2-methyl
Tylcyclopentyl group, 3-methylcyclopentyl group,
1,2-dimethylcyclopentyl group, 1,3-dimethyl
Cyclopentyl group, 2,2-dimethylcyclopentyl
Group, 2,3-dimethylcyclopentyl group, 3,3-dimethyl
Tylcyclopentyl group, 1-ethylcyclopentyl group,
1-methylcyclohexyl group, 2-methylcyclohexyl
Group, 3-methylcyclohexyl group, 4-methylcyclo
Hexyl group, 1,2-dimethylcyclohexyl group, 1,
3-dimethylcyclohexyl group, 1,4-dimethylcycl
Rohexyl group, 2,2-dimethylcyclohexyl group,
2,3-dimethylcyclohexyl group, 2,4-dimethyl
Cyclohexyl group, 3,3-dimethylcyclohexyl
Group, 3,4-dimethylcyclohexyl group, 4,3-dimethyl
Tylcyclohexyl group, 1-ethylcyclohexyl group, etc.
C_Four-C_TenCycloalkyl substituted with an alkyl group
Groups: 2-cyclopropenyl group, 2-cyclobutenyl group, 2
-Cyclopentenyl group, 3-cyclopentenyl group, 2-
C such as cyclohexenyl group and 3-cyclohexenyl group_Three
-C₆A cycloalkenyl group; a fluoromethyl group,
Romethyl group, bromomethyl group, difluoromethyl group,
Trifluoromethyl group, 2-fluoroethyl group, 2-chloro
Roethyl group, 2-bromoethyl group, 2,2,2-trif
Fluoroethyl group, 1,1,2,2,2-pentafluoro
Ethyl group, 2-fluoropropyl group, 2-chloropropyl
Group, 2-bromopropyl group, 3-fluoropropyl
Group, 3-chloropropyl group, 3-bromopropyl group,
2,2,3,3,3-pentafluoropropyl group, 1,
1,2,2,3,3,3-heptafluoropropyl group,
2,2,2-trifluoro-1-methylethyl group, 4-
Fluorobutyl group, 4-chlorobutyl group, 4-bromobu
Tyl group, 2,2,3,3,4,4,4-heptafluoro
C such as butyl group₁-C₆A haloalkyl group of 3,3-di
C such as chloroallyl group_Two-C₆A haloalkenyl group;
C such as 2,2-difluorocyclopentyl group_Three-C₆of
Halocycloalkyl group; cyanomethyl group, 1-cyanoe
Tyl group, 2-cyanoethyl group, 1-cyanopropyl group,
2-cyanopropyl group, 3-cyanopropyl group, 1-cy
Anobutyl group, 2-cyanobutyl group, 3-cyanobutyl
C, a 4-cyanobutyl group, etc._Two-C_FiveCyano Archi
Methoxy group, ethoxymethyl group, propoxy group
Cimethyl group, isopropoxymethyl group, butoxymethyl
Group, 2-methoxyethyl group, 2-ethoxyethyl group, 2
-Propoxyethyl group, 2-isopropoxyethyl group,
2-butoxyethyl group, 3-methoxypropyl group, 4-
C such as methoxybutyl group and 5-methoxypentyl group_Two−
C₆Alkoxyalkyl group; methylthiomethyl group, d
Tylthiomethyl, propylthiomethyl, isopropyl
Luthiomethyl group, butylthiomethyl group, 2- (methylthio
E) ethyl group, 2- (ethylthio) ethyl group, 2- (p
Ropirthio) ethyl group, 2- (isopropylthio) ethyl
Group, 2- (butylthio) ethyl group, 3- (methylthio)
E) propyl group, 4- (methylthio) butyl group, 5-
C such as (methylthio) pentyl group_Two-C₆Alkyl
Oalkyl group; methylsulfonylmethyl group, ethylsulfur
Phonylmethyl group, propylsulfonylmethyl group, isop
Propylsulfonylmethyl group, butylsulfonylmethyl
Group, 2- (methylsulfonyl) ethyl group, 2- (ethyl
Sulfonyl) ethyl group, 2- (propylsulfonyl) e
Tyl group, 2- (isopropylsulfonyl) ethyl group, 2
-(Butylsulfonyl) ethyl group, 3- (methylsulfo
Nyl) propyl group, 4- (methylsulfonyl) butyl
Group such as a 5- (methylsulfonyl) pentyl group_Two-C
₆Alkylsulfonylalkyl group of 2-oxopropy
Group, 1-methyl-2-oxopropyl group, 1-methyl
-2-oxobutyl group, 1-ethyl-2-oxobutyl
Group such as 1-propyl-2-oxopropyl group_Three-C
₆An oxoalkyl group of 2- (acetyloxy) ethyl
Group, 2- (propionyloxy) ethyl group, 2- (butyi)
Ryloxy) ethyl group, 2- (isobutyryloxy) e
Tyl group, 2- (valeryloxy) ethyl group, 2- (iso
Valeryloxy) ethyl group, 2- (pivaloyloxy)
Ethyl group, 2- (acryloyloxy) ethyl group, 2-
(Propioloyloxy) ethyl group, 2- (methacryloyl)
Yloxy) ethyl group, 2- (crotonoyloxy) e
Tyl group, 3- (acetyloxy) propyl group, 4- (A
Cetyloxy) butyl group, 5- (acetyloxy) pen
C such as tyl group_Three-C₇Acyloxyalkyl group; meth
Oxycarbonylmethyl group, ethoxycarbonylmethyl
Group, propoxycarbonylmethyl group, isopropoxy
Rubonylmethyl group, butoxycarbonylmethyl group, iso
Butoxycarbonylmethyl group, sec-butoxycarbonyl
Methyl group, t-butoxycarbonylmethyl group, pentyl
Xycarbonylmethyl group, isopentyloxycarboni
Methyl group, hexyloxycarbonylmethyl group, 2-
(Methoxycarbonyl) ethyl group, 2- (ethoxycal
Bonyl) ethyl group, 2- (propoxycarbonyl) ethyl
Group, 2- (isopropoxycarbonyl) ethyl group, 2
-(Butoxycarbonyl) ethyl group, 2- (isobutoxy)
(Cyclocarbonyl) ethyl group, 2- (sec-butoxycarbonyl)
L) ethyl group, 2- (t-butoxycarbonyl) ethyl
Group, 2- (pentyloxycarbonyl) ethyl group, 2-
(Isopentyloxycarbonyl) ethyl group, 1- (meth
Ethoxycarbonyl) ethyl group, 1- (ethoxycarbonyl)
L) ethyl group, 1- (propoxycarbonyl) ethyl
Group, 1- (isopropoxycarbonyl) ethyl group, 1-
(Butoxycarbonyl) ethyl group, 1- (isobutoxy)
Carbonyl) ethyl group, 1- (sec-butoxycarbonyl)
L) ethyl group, 1- (t-butoxycarbonyl) ethyl
Group, 1- (pentyloxycarbonyl) ethyl group, 1-
(Isopentyloxycarbonyl) ethyl group, 3- (me
Toxylcarbonyl) propyl group, 3- (ethoxycarbo
Nyl) propyl group, 3- (propoxycarbonyl) pro
Pill group, 3- (isopropoxycarbonyl) propyl
Group, 3- (butoxycarbonyl) propyl group, 1- (meth
Toxylcarbonyl) propyl group, 1- (ethoxycarbo)
Nyl) propyl group, 1- (propoxycarbonyl) pro
Pill group, 1- (isopropoxycarbonyl) propyl
Group, 1- (butoxycarbonyl) propyl group, 1- (meth
(Toxicarbonyl) -1-methylethyl group, 1- (ethoxy
(Xycarbonyl) -1-methylethyl group, 1-methyl-1
-(Propoxycarbonyl) ethyl group, 1- (isopro
Oxycarbonyl) -1-methylethyl group, 1- (but
Xycarbonyl) -1-methylethyl group, 4- (methoxy)
(Cyclocarbonyl) butyl group, 4- (ethoxycarbonyl)
Butyl group, 4- (propoxycarbonyl) butyl group, 3
C (such as-(isopropoxycarbonyl) butyl group)_Three-C
₇An alkoxycarbonylalkyl group; a phenyl group;
Methyl, ethyl, propyl substituted with phenyl
Groups such as isopropyl and isopropyl₁-C_ThreeAn alkyl group of 1-
Containing two oxygen, sulfur and / or nitrogen atoms
A 3-6 membered heterocyclic group; or 1-2 oxygen atoms
3-6 containing an atom, a sulfur atom and / or a nitrogen atom
Methyl, ethyl, and propyl substituted with a membered heterocyclic group
C, e.g.₁-C_ThreeAlkyl group
I can do it.

Examples of the 3-6 membered heterocyclic group containing 1-2 oxygen, sulfur and / or nitrogen atoms include:
Oxiranyl group, oxetanyl group, tetrahydrofuryl group, furyl group, thienyl group, pyrrolyl group, pyrrolidinyl group, oxazolyl group, thiazolyl group, imidazolyl group,
Examples include an isoxazolyl group, an isothiazolyl group, a pyrazolyl group, a tetrahydropyranyl group, a pyridyl group, a piperidyl group, a pyrimidinyl group, a pyridazinyl group, a morpholinyl group, and a piperazinyl group, which may have a substituent.

R ¹⁵ may form a ring together with W when W represents —NR ¹⁶ . And if R ¹⁵ to form a W and ring indicates that to form a 5-6 membered heterocyclic group R ¹⁵ may contain 1-2 nitrogen atoms and 0-1 oxygen atoms with W . 1-2 nitrogen atoms and 0-
A 5-6 membered heterocyclic group containing one oxygen atom is defined as 1
-Pyrrolidinyl group, 1-pyrrolyl group, 2-isoxazolidinyl group, 1-pyrazolyl group, 1-imidazolyl group,
1-piperidyl group, 4-morpholinyl group, perhydro-
Examples thereof include a 1,2-oxazin-2-yl group and a 1-piperazinyl group, which may have a substituent.

R ¹² , R ¹³ and R ¹⁵ are a phenyl group,
A C ₁ -C ₃ alkyl group substituted with a phenyl group, 3-
A 6-membered heterocyclic group, wherein the ring contains 1-2 oxygen, sulfur and / or nitrogen atoms, or 3-
When a C ₁ -C ₃ alkyl group substituted with a 6-membered heterocyclic group (the ring contains 1-2 oxygen atoms, sulfur atoms and / or nitrogen atoms) is used, The phenyl group and the heterocyclic group may have a substituent. Specific examples of the substituent include 1-3 identical or different halogen atoms such as a fluorine atom, a chlorine atom, a bromine atom and an iodine atom; a methyl group, an ethyl group, a propyl group, an isopropyl group, a butyl group and an isobutyl group. , sec- butyl group, an alkyl group of C ₁ -C ₄ in a t- butyl group and the like; trifluoromethyl group; methoxy group, an ethoxy group, a propoxy group, isopropoxy group, butoxy group, isobutoxy group, sec- butoxy group, a C ₁ -C ₄ alkoxy group such as t-butoxy group; acetyloxy group, propionyloxy group, butyryloxy group, isobutyryloxy group, valeryloxy group, isovaleryloxy group, pivaloyloxy group, acryloyloxy group, propioloyl methylthio group; oxy group, methacryloyloxy group, an acyloxy group of C ₂ -C _5, such as a crotonoyloxy group Ethylthio group, propylthio group, isopropylthio group, butylthio group, isobutylthio, sec- butylthio groups, C ₁ -C such t- butylthio group
₄ alkylthio groups; C ₁ -C ₄ alkylsulfonyl such as methylsulfonyl, ethylsulfonyl, propylsulfonyl, isopropylsulfonyl, butylsulfonyl, isobutylsulfonyl, sec-butylsulfonyl, t-butylsulfonyl, etc. group; a nitro group; a cyano group; or a methoxycarbonyl group, an ethoxycarbonyl group, propoxycarbonyl group, isopropoxycarbonyl group, butoxycarbonyl group, isobutoxycarbonyl group, sec- butoxycarbonyl group, C ₂ etc. t- butoxycarbonyl group —C ₅ alkoxycarbonyl group and the like.

Of these, R^ThreeAs a hydrogen source
, A nitro group or -QR¹²(Wherein Q is an oxygen atom or
Is -NR¹³− (R¹³Is a hydrogen atom, C_Two-C₆Acyl
Group, C₁-C₆Alkylsulfonyl group or C_Two-C
₆Represents an alkoxycarbonyl group of the formula:¹²Is water
Elementary atom, C₁-C_TenAn alkyl group of C_Two-C_TenArche of
Nyl group, C_Two-C_TenAlkynyl group, C_Three-C₈No shiku
Loalkyl group, C_Three-C₈A cycloalkenyl group of C₁
-C_TenHaloalkyl group of C_Two-C_TenHaloalkenyl of
Group, C_Two-C_TenHalocycloalkyl group, C_Two-C₇of
Cyanoalkyl group, C_Two-C_TenThe alkoxyalkyl
Group, C_Three-C₆An oxoalkyl group, C₁-C ₆Al
C substituted with a killsulfonyl group or a phenyl group₁-C_Three
And a 3-6 membered heterocyclic group (the ring has 1-2
A 3-6 membered heterocyclic group (the ring
Contains 1-2 oxygen atoms).₁
-C_ThreeAn alkyl group of the following general formula [II]

[0034]

Embedded image

A group represented by the following general formula [II]
I]

[0036]

Embedded image

(Where R¹⁴Is a hydrogen atom or C₁-C_Four
W is an oxygen atom or -NR¹⁶−
(Where R¹⁶Is a hydrogen atom or C₁-C_FourAlkyl group
And R)^FifteenIs a hydrogen atom or C₁-C₆No
Represents a alkyl group. )). R^ThreeAs
Particularly preferably, a hydrogen atom, a nitro group or -QR
¹²(Wherein Q is an oxygen atom or -NR¹³− (R¹³Is hydrogen
Atom, C₁-C₆Alkylsulfonyl group or C_Two−
C₆Represents an alkoxycarbonyl group of the formula)¹²Is
Hydrogen atom, C₁-C_TenAn alkyl group of C_Two-C_TenAl
Kenyl group, C_Two-C_TenAlkynyl group, C_Three-C₈No
Chloroalkyl group, C₁-C_TenHaloalkyl group of C_Two−
C _TenHaloalkenyl group of C_Two-C₇Of cyanoalkyl
Group, C_Two-C_TenAn alkoxyalkyl group of C_Three-C₆of
Oxoalkyl group, C₁-C₆Alkylsulfonyl of
Group substituted with a phenyl group₁-C_ThreeAn alkyl group of
3-6 membered heterocyclic group (the ring contains 1-2 oxygen atoms)
Has), a 3-6 membered heterocyclic group (the ring is
Substituted with a carbon atom)₁-C_ThreeThe alkyl of
A group represented by the general formula [II],
A group represented by the general formula [III] is shown. )
Preferably -QR¹²(Wherein Q represents an oxygen atom;¹²
Is C₁-C_TenAn alkyl group of C_Two-C_TenThe alkenyl of
Group, C_Two-C_TenAlkynyl group, C _Three-C₈Cycloa
Alkyl group, C₁-C_TenHaloalkyl group of C_Two-C_Tenof
Haloalkenyl group, C_Two-C₇A cyanoalkyl group of C
_Two-C_TenAn alkoxyalkyl group of C_Three-C₆Oxo
An alkyl group, a 3-6 membered heterocyclic group (the ring comprises 1-2
A 3-6 membered heterocyclic group (containing an oxygen atom)
Substituted with 1 to 2 oxygen atoms)₁-C
_ThreeOr a group represented by the above general formula [II]
Is shown. ).

As a combination of the substituents, R ¹ and R ² are preferably bonded together to form a ring;
³ are hydrogen atoms, in a nitro group or -QR ¹² (wherein, Q is an oxygen atom, -NR ¹³ - (wherein, R ¹³ is a hydrogen atom, C ₁ -C
Shows a ₆ alkylsulfonyl group or an alkoxycarbonyl group having C ₂ -C ₆ for. ) Wherein R ¹² is a hydrogen atom, C
Alkyl group of ₁ -C _10, alkenyl group of C ₂ -C _10, C
An alkynyl group of ₂ -C _10, C cycloalkyl group ₃ -C _8, a haloalkyl group of C ₁ -C _10, C ₂ -C haloalkenyl group _10, cyanoalkyl group C ₂ -C _7, C ₂ - C
₁₀ alkoxyalkyl group, oxoalkyl group of C ₃ -C _6, an alkylsulfonyl group having C ₁ -C _6, alkyl group of C ₁ -C ₃ substituted with a phenyl group, 3-6-membered Hajime Tamaki ( The ring contains 1-2 oxygen atoms), 3-
A C ₁ -C ₃ alkyl group substituted by a 6-membered heterocyclic group (the ring contains 1-2 oxygen atoms), the following general formula [II]

[0039]

Embedded image

Or a group represented by the following general formula [II
I]

[0041]

Embedded image

(Wherein R ¹⁴ is a hydrogen atom or C ₁ -C ₄
W represents an oxygen atom or —NR ¹⁶ (wherein, R ¹⁶ represents a hydrogen atom or a C ₁ -C ₄ alkyl group), and R ¹⁵ represents a hydrogen atom or C ₁ -C _6. Represents an alkyl group. ). ), And particularly preferably, R ¹ and R ² are bonded together to form a carbocyclic ring, and R ³ is —QR ¹² (wherein Q represents an oxygen atom, and R ¹² is C ₁ alkyl -C _10, C ₂ -C ₁₀
Alkenyl group, C ₂ -C ₁₀ alkynyl group, C ₃ -C
₈ cycloalkyl groups, C ₁ -C ₁₀ haloalkyl groups,
C ₂ -C ₁₀ haloalkenyl group, cyanoalkyl group C ₂ -C _7, an alkoxyalkyl group C ₂ -C _10, C ₃ -
A C ₆ oxoalkyl group, a 3-6 membered heterocyclic group (the ring contains 1-2 oxygen atoms), a 3-6 membered heterocyclic group (the ring is A C ₁ -C ₃ alkyl group substituted with an oxygen atom) or a compound of the above general formula [I
And a group represented by I]. ). Of these, Y is more preferably a halogen atom.

The compound of the above general formula [I] may form a salt at the pyridazine ring portion and, when the substituent R ³ contains a hydroxyl group or a nitrogen atom, at that portion. Specifically, an alkali metal salt such as a sodium salt, a potassium salt, or a calcium salt, or a halogen such as an alkaline earth metal salt, hydrofluoride, hydrochloride, hydrobromide, or hydroiodide is used. Inorganic acid salts such as nitrates, perchlorates, sulfates and phosphates; sulfonates such as methanesulfonate, trifluoromethanesulfonate and p-toluenesulfonate Can be

Further, represented by the following general formula (V) or (V ')

[0045]

Embedded image

(Wherein Y, Z, R ¹ , R ² and R ³
Is the same as defined in claim 1), is an important intermediate for synthesizing the compound (I) of the present invention, and is a novel compound. Compounds (V) and (V ') are structural isomers, and are easily isomerized in the presence of an acid or an alkali. For example, when chlorinated by a reagent such as phosphorus oxychloride, the reaction proceeds via compound (V), and when alkylation is performed in the presence of a base such as sodium hydride, the reaction proceeds via (V ′). The reaction proceeds.

Next, the novel 3-substituted phenyl-4 of the present invention
-A method for producing halopyridazine and derivatives thereof and intermediates thereof will be described. The compound of the present invention represented by the general formula [I] can be produced, for example, by any of the following production methods (1) to (13). Manufacturing method (1)

[0048]

Embedded image

(In the above reaction formula, X, Y, Z, R ¹ , R ²
Is the same as defined above. R ³ ′ represents a hydrogen atom, a nitro group,
It is an inert group which is not affected by the present reaction such as an alkoxy group, an alkylthio group, a dialkylamino group and the synthesis of the raw material [VII] shown below. R ¹⁷ represents a lower alkyl group such as a methyl group and an ethyl group. The above reaction is carried out in the absence of a solvent or in a solvent in the presence of a base, usually at a temperature of 0 to 200 ° C, preferably 50 to 100 ° C. The amount of the compound used in the reaction is usually such that [VIII] is 1.0 to 1.0 equivalent relative to 1 equivalent of [VII].
3.0 equivalents, preferably 1.0 to 1.5 equivalents, and 1.0 to 3.0 equivalents of the base, preferably 1.0 to 1.5 equivalents.

When a solvent is used, suitable solvents include aliphatic hydrocarbons (hexane, heptane, etc.), aromatic hydrocarbons (benzene, toluene, xylene, etc.), and halogenated hydrocarbons (dichloromethane, chloroform). ,
1,2-dichloroethane, chlorobenzene, dichlorobenzene, etc.), ethers (diethyl ether, tetrahydrofuran, dioxane, etc.), esters (ethyl acetate, butyl acetate, etc.), ketones (acetone, methyl ethyl ketone, etc.), aprotic polar solvents (N, N-dimethylformamide, N-methylpyrrolidone, dimethylsulfoxide,
Sulfolane, acetonitrile, etc.), alcohols (methanol, ethanol, 2-propanol, etc.), organic acids (formic acid, acetic acid, etc.), water, and mixtures thereof.

As the base to be used, triethylamine, diisopropylethylamine, pyridine, picoline, N, N-diethylaniline, 4- (dimethylamino) pyridine, 1,8-diazabicyclo [5,4,0] -7-undecene , 1,5-
Diazabicyclo [4,3,0] -5-nonene, 1,4-diazabicyclo
[2,2,2] organic bases such as octane, and sodium hydride, potassium hydride, sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, sodium hydrogencarbonate, potassium hydrogencarbonate, sodium acetate, potassium acetate, Inorganic bases such as sodium fluoride and potassium fluoride are exemplified.

Production method (2)

[0053]

Embedded image

In the above reaction formula, X, Y, Z, R ¹ and R ² are the same as defined above. R ³ ″ is an inert group such as a hydrogen atom, a nitro group, an alkoxy group, an alkylthio group, a dialkylamino group and the like which is not affected by the reaction and the synthesis of the intermediate [V] shown below.) The reaction is carried out without a solvent or in a solvent in the presence of a halogenating agent, usually at 0 to 200 ° C.
Preferably, it is carried out in a temperature range of 10 to 100 ° C. The amount of the compound used in the reaction is usually 1.0 to 3.0 equivalents, preferably 1.5 to 2.0 equivalents, to 1 equivalent of [V].

When a solvent is used, suitable solvents include aliphatic hydrocarbons (hexane, heptane, etc.), aromatic hydrocarbons (benzene, toluene, xylene, etc.), and halogenated hydrocarbons (dichloromethane, chloroform). ,
1,2-dichloroethane, chlorobenzene, dichlorobenzene, etc.), ethers (diethyl ether, tetrahydrofuran, dioxane, etc.), and mixtures thereof. The halogenating agents used include phosphorus trichloride, phosphorus oxychloride, phosphorus pentachloride, hydrogen chloride, phosphorus tribromide, hydrogen bromide, sulfur trifluoride diethylamine complex, tetrabutylammonium fluoride, hydrogen fluoride and the like. No.

Production method (3)

[0057]

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(In the above reaction formula, X, Y, Z, R ¹ ,
R ² , R ¹² and Q are the same as defined above. (However,
In [Ia], R ¹² excludes a hydrogen atom. ))

The above reaction is carried out in the absence of a solvent or in a solvent in the presence of an acid, usually at -20 to 200 ° C., preferably at 10 to 1 ° C.
It is performed in a temperature range of 00 ° C. When using a solvent,
Suitable solvents include aliphatic hydrocarbons (hexane, heptane, etc.) and aromatic hydrocarbons (benzene, toluene,
Xylene, halogenated hydrocarbons (dichloromethane, chloroform, 1,2-dichloroethane, chlorobenzene, dichlorobenzene, etc.), ethers (diethyl ether, tetrahydrofuran, dioxane, etc.), aprotic polar solvents (N, N- Examples include dimethylformamide, N-methylpyrrolidone, dimethylsulfoxide, sulfolane, acetonitrile, etc.), alcohols (methanol, ethanol, 2-propanol, etc.), water, and mixtures thereof.

Examples of the acid used include acids such as formic acid, acetic acid, trifluoroacetic acid, hydrochloric acid, hydrobromic acid, hydroiodic acid, sulfuric acid, phosphoric acid, methanesulfonic acid and p-toluenesulfonic acid. . The starting compound [I
a] can be synthesized by the above-mentioned production method (1) or production method (2) . In [Ia], R ¹² is preferably an alkyl group, a cycloalkyl group, an acyl group or an alkoxyalkyl group.

When R ¹² is expected to affect the cyclization reaction described in the above production method (1) as in the above general formula [III], the compound obtained in the above production method (3) is It can be produced by derivatization according to production method (4) or (5) .

Manufacturing method (4)

[0063]

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(In the above reaction formula, X, Y, Z, R ¹ ,
R ² , R ¹² and Q are the same as defined above. (However,
R ¹² excludes a hydrogen atom. ) V is a halogen atom such as a chlorine atom, a bromine atom and an iodine atom; a lower alkylsulfonyloxy group such as a methylsulfonyloxy group;
-Represents an arylsulfonyloxy group such as a toluenesulfonyloxy group. )

The above reaction is carried out without solvent or in a solvent in the presence of a base, usually at 0 to 200 ° C., preferably 10 to 10
It is performed in a temperature range of 0 ° C. The amount of the compound used for the reaction is usually 1.12 equivalents of R ¹² -V with respect to 1 equivalent of [Ib].
0 to 3.0, preferably 1.0 to 1.5 equivalents, and the base is 1.0 to 3.0, preferably 1.0 to 1.5 equivalents.

When a solvent is used, suitable solvents include aliphatic hydrocarbons (hexane, heptane, etc.), aromatic hydrocarbons (benzene, toluene, xylene, etc.), and halogenated hydrocarbons (dichloromethane, chloroform). ,
1,2-dichloroethane, chlorobenzene, dichlorobenzene, etc.), ethers (diethyl ether, tetrahydrofuran, dioxane, etc.), esters (ethyl acetate, butyl acetate, etc.), ketones (acetone, methyl ethyl ketone, etc.), aprotic polar solvents (N, N-dimethylformamide, N-methylpyrrolidone, dimethylsulfoxide,
Sulfolane, acetonitrile, etc.), alcohols (methanol, ethanol, 2-propanol, etc.), organic acids (formic acid, acetic acid, etc.), water, and mixtures thereof. As the base used, triethylamine,
Pyridine, picoline, N, N-diethylaniline, 4- (dimethylamino) pyridine, 1,8-diazabicyclo [5,4,0] -7-
Undecene, 1,5-diazabicyclo [4,3,0] -5-nonene, 1,
Organic bases such as 4-diazabicyclo [2,2,2] octane, and sodium hydride, potassium hydride, sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate,
Inorganic bases such as sodium hydrogen carbonate, potassium hydrogen carbonate, sodium acetate, potassium acetate, sodium fluoride, potassium fluoride and the like can be mentioned.

Manufacturing method (5)

[0068]

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(In the above reaction formula, X, Y, Z, R ¹ ,
R ² , R ¹² and Q are the same as defined above. (However,
R ¹² excludes a hydrogen atom. ) R ¹⁸ represents a lower alkyl group such as a methyl group and an ethyl group. The above reaction is carried out without solvent or in a solvent in the presence of triphenylphosphine and dialkyl azodicarboxylate, usually at a temperature of 0 to 100 ° C, preferably 0 to 50 ° C. The amount of the compound used in the reaction is usually the amount of R ¹² relative to 1 equivalent of [Ib].
-OH is 1.0 to 3.0 equivalents, preferably 1.0 to 1.
5 equivalents, 1.0 to 3.0 equivalents of triphenylphosphine, preferably 1.0 to 1.5 equivalents, and 1.0 to 3.0 equivalents of dialkyl azodicaarbonate, preferably 1.
0 to 1.5 equivalents.

When a solvent is used, suitable solvents include aliphatic hydrocarbons (hexane, heptane, etc.), aromatic hydrocarbons (benzene, toluene, xylene, etc.), and halogenated hydrocarbons (dichloromethane, chloroform). ,
1,2-dichloroethane, chlorobenzene, dichlorobenzene, etc.), ethers (diethyl ether, tetrahydrofuran, dioxane, etc.), esters (ethyl acetate, butyl acetate, etc.), ketones (acetone, methyl ethyl ketone, etc.), aprotic polar solvents (N, N-dimethylformamide, N-methylpyrrolidone, dimethylsulfoxide,
Sulfolane, acetonitrile, etc.), and mixtures thereof.

Manufacturing method (6)

[0072]

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(In the above reaction formula, X, Y, Z, R ¹ and R ² are the same as defined above.) The reaction is carried out without solvent or in a solvent, usually -10 to 1
The reaction is performed at a temperature of 50 ° C, preferably 20 to 60 ° C. The amount of the compound used in the reaction is usually [Ic] 1
1.0 to 3.0 equivalents, preferably 1.5 to
Use 2.0 equivalents of nitrating agent.

When a solvent is used, suitable solvents include inorganic acids (sulfuric acid, hydrochloric acid, etc.), organic acids (formic acid, acetic acid, etc.), and organic anhydrides (acetic anhydride, etc.). The nitrating agents used include inorganic acids (sulfuric acid, hydrochloric acid)
And nitric acid or nitrate (sodium nitrate, potassium nitrate, etc.)
And nitric acid, nitronium tetrafluoroborate, nitronium trifluoromethanesulfonate, and the like.

Manufacturing method (7)

[0076]

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(In the above reaction formula, X, Y, Z, R ¹ and R ² are the same as defined above.) The reduction reaction is carried out in the absence of a solvent or in a solvent, in the presence of a metal or metal compound and an acid. Below, it is usually performed in a temperature range of 50 to 100 ° C. The amount of the metal or metal compound used is usually 1 to 20 equivalents relative to 1 equivalent of [Id]. Preferably it is 2 to 10 equivalents. The amount of the acid used is usually 0.01 to 20 equivalents, preferably 0.01 to 10 equivalents, relative to 1 equivalent of [Id].

When a solvent is used, suitable solvents include aliphatic hydrocarbons (hexane, heptane, etc.), aromatic hydrocarbons (benzene, toluene, xylene, etc.), and halogenated hydrocarbons (dichloromethane, chloroform). ,
1,2-dichloroethane, chlorobenzene, dichlorobenzene, etc.), ethers (diethyl ether, tetrahydrofuran, dioxane, etc.), esters (ethyl acetate, butyl acetate, etc.), ketones (acetone, methyl ethyl ketone, etc.), aprotic polar solvents (N, N-dimethylformamide, N-methylpyrrolidone, dimethylsulfoxide,
Sulfolane, acetonitrile, etc.), organic acids (formic acid, acetic acid), water, and mixtures thereof. The amount of solvent used is usually between 1 and 100% by weight of [Id].
Times, preferably 1 to 20 times. The metals or metal compounds used include iron, zinc, tin, tin chloride (I
I) and the like. Examples of the acid used include hydrochloric acid, sulfuric acid, acetic acid and the like. Further, the above reaction is carried out by using sodium sulfide, sodium hydrosulfide,
It is also possible to use sodium dithionite, ammonium sulfide, a hydrogen / metal catalyst (palladium-carbon, platinum-carbon, rhodium-alumina, platinum, Raney nickel, etc.) and the like.

Production method (8)

[0080]

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(In the above reaction formula, X, Y, Z, R ¹ ,
R ² , R ¹² and R ¹³ are the same as defined above. (However, R ¹² excludes a hydrogen atom.) V is a halogen atom such as a chlorine atom, a bromine atom and an iodine atom; a lower alkylsulfonyloxy group such as a methylsulfonyloxy group; or
An arylsulfonyloxy group such as a p-toluenesulfonyloxy group is shown. )

The above reaction is carried out without solvent or in a solvent in the presence of a base, usually at 0 to 200 ° C., preferably at 10 to 10 ° C.
It is performed in a temperature range of 0 ° C. The amount of the compound used for the reaction is usually 1.13 equivalents of [If] and R ¹³ -V is 1.
0 to 3.0 equivalents, preferably 1.5 to 2.0 equivalents, and the base is 1.0 to 3.0 equivalents, preferably 1.5 to 3.0 equivalents.
2.0 equivalents.

When a solvent is used, suitable solvents include aliphatic hydrocarbons (hexane, heptane, etc.), aromatic hydrocarbons (benzene, toluene, xylene, etc.), and halogenated hydrocarbons (dichloromethane, chloroform, etc.). ,
1,2-dichloroethane, chlorobenzene, dichlorobenzene, etc.), ethers (diethyl ether, tetrahydrofuran, dioxane, etc.), esters (ethyl acetate, butyl acetate, etc.), ketones (acetone, methyl ethyl ketone, etc.), aprotic polar solvents (N, N-dimethylformamide, N-methylpyrrolidone, dimethylsulfoxide,
Sulfolane, acetonitrile, etc.), alcohols (methanol, ethanol, 2-propanol, etc.), organic acids (formic acid, acetic acid, etc.), water, and mixtures thereof. As the base used, triethylamine,
Pyridine, picoline, N, N-diethylaniline, 4- (dimethylamino) pyridine, 1,8-diazabicyclo [5,4,0] -7-
Undecene, 1,5-diazabicyclo [4,3,0] -5-nonene, 1,
Organic bases such as 4-diazabicyclo [2,2,2] octane, and sodium hydride, potassium hydride, sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate,
Inorganic bases such as sodium hydrogen carbonate, potassium hydrogen carbonate, sodium acetate, potassium acetate, sodium fluoride, potassium fluoride and the like can be mentioned.

Production method (9)

[0085]

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(In the above reaction formula, X, Y, R ¹ , R ² , R
³ , as defined above, X 'represents a halogen atom and Met represents a metal atom. The above reaction is carried out without solvent or in a solvent, usually from 0 to 250.
C., preferably at a temperature in the range of 100 to 200C. The amount of the compound used in the reaction is usually [Ih] 1
The cyanating agent (Met-CN) is 1.0 to
It is 3.0 equivalents, preferably 1.5 to 2.0 equivalents.

When a solvent is used, suitable solvents include aliphatic hydrocarbons (hexane, heptane, etc.), aromatic hydrocarbons (benzene, toluene, xylene, etc.), and halogenated hydrocarbons (dichloromethane, chloroform, etc.). ,
1,2-dichloroethane, chlorobenzene, dichlorobenzene, etc.), ethers (diethyl ether, tetrahydrofuran, dioxane, etc.), esters (ethyl acetate, butyl acetate, etc.), ketones (acetone, methyl ethyl ketone, etc.), aprotic polar solvents (N, N-dimethylformamide, N-methylpyrrolidone, dimethylsulfoxide,
Sulfolane, acetonitrile, etc.), alcohols (methanol, ethanol, 2-propanol, etc.), organic acids (formic acid, acetic acid, etc.), water, and mixtures thereof. As the cyanating agent used, copper cyanide,
Potassium cyanide, sodium cyanide and the like can be mentioned.

Manufacturing method (10)

[0089]

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(In the above reaction formula, X, Y, Z, R ¹ ,
R ² , R ³ , n and m are the same as defined above. However, n + m> 0) The above reaction is carried out without solvent or in a solvent, in the presence of an oxidizing agent, in the presence or absence of a metal or a metal complex.
The reaction is carried out at a temperature of 0 to 200C, preferably 10 to 100C. The amount of the compound used in the reaction is usually
[I] The oxidizing agent is used in an amount of 1.0 to 3.0 equivalents, preferably 1.5 to 2.5 equivalents, and 0.05 to 1.5 equivalents when a metal or a metal complex is required. , Preferably 0.1 to 1.0 equivalent.

When a solvent is used, suitable solvents include aliphatic hydrocarbons (hexane, heptane, etc.), aromatic hydrocarbons (benzene, toluene, xylene, etc.), and halogenated hydrocarbons (dichloromethane, chloroform, etc.). ,
1,2-dichloroethane, chlorobenzene, dichlorobenzene, etc.), aprotic polar solvents (N, N-dimethylformamide, N-methylpyrrolidone, dimethylsulfoxide,
Sulfolane, acetonitrile, etc.), alcohols (methanol, ethanol, 2-propanol, etc.), organic acids (formic acid, acetic acid, etc.), water, and mixtures thereof. Examples of the oxidizing agent used include m-chlorobenzoic acid, peracetic acid, hydrogen peroxide, t-butyl hydroperoxide and the like. Examples of the metal or metal complex used include vanadium, molybdenum, titanium tetraisopropoxide-diisopropyl tartrate complex, and the like.

Manufacturing method (11)

[0093]

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(In the above reaction formula, X, Y, Z, R ¹ ,
R ² and R ³ are the same as defined above. HU is an acid that forms a salt with the compound of the present application, and specifically, hydrohalic acids such as hydrofluoric acid, hydrochloric acid, hydrobromic acid, and hydroiodic acid; nitric acid, perchloric acid And inorganic acids such as sulfuric acid and phosphoric acid; and sulfonic acids such as methanesulfonic acid, trifluoromethanesulfonic acid and p-toluenesulfonic acid. )

The above reaction is carried out without solvent or in a solvent,
0 to 200 ° C, preferably 10 to 10 ° C in the presence of
It is performed in a temperature range of 0 ° C. The amount of the compound used in the reaction is usually from 1.0 to 1.0 in terms of HU relative to 1 equivalent of [I].
It is 3.0 equivalents, preferably 1.0 to 1.5 equivalents.

When a solvent is used, suitable solvents include aliphatic hydrocarbons (hexane, heptane, etc.), aromatic hydrocarbons (benzene, toluene, xylene, etc.), and halogenated hydrocarbons (dichloromethane, chloroform, etc.). ,
1,2-dichloroethane, chlorobenzene, dichlorobenzene, etc.), ethers (diethyl ether, tetrahydrofuran, dioxane, etc.), esters (ethyl acetate, butyl acetate, etc.), ketones (acetone, methyl ethyl ketone, etc.), aprotic polar solvents (N, N-dimethylformamide, N-methylpyrrolidone, dimethylsulfoxide,
Sulfolane, acetonitrile, etc.), alcohols (methanol, ethanol, 2-propanol, etc.), water, and mixtures thereof.

Manufacturing method (12)

[0098]

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(In the above reaction formula, X, Y, Z, R ¹ ,
R ² and R ³ are the same as defined above. X ′ represents a halogen atom, and P represents —B (OH) ₂ or —Met′—X ″ (M
et 'represents a metal such as magnesium and zinc, and X "represents a halogen atom.)

The above reaction is carried out in the absence of a solvent or in a solvent, in the presence or absence of a metal or a metal complex, from 0 to 200
C., preferably in the temperature range of 10 to 100C. The amount of the compound used for the reaction is usually [IX] 1
[X] is 1.0 to 3.0 equivalents, preferably 1.0 to 1.5 equivalents, and the metal or metal complex is 0.01 to equivalents.
To 1.0 equivalent, preferably 0.05 to 0.5 equivalent.

When a solvent is used, suitable solvents include aliphatic hydrocarbons (hexane, heptane, etc.), aromatic hydrocarbons (benzene, toluene, xylene, etc.), and halogenated hydrocarbons (dichloromethane, chloroform, etc.). ,
1,2-dichloroethane, chlorobenzene, dichlorobenzene, etc.), ethers (diethyl ether, tetrahydrofuran, dioxane, etc.), aprotic polar solvents (N,
N-dimethylformamide, N-methylpyrrolidone, dimethylsulfoxide, sulfolane, acetonitrile, etc.), and mixtures thereof. When using a metal or metal complex, suitable metals or metal complexes include nickel, iron, ruthenium, cobalt, rhodium,
Metals such as iridium, palladium, platinum, etc., tetrakis (triphenylphosphine) palladium, tris (dibenzylideneacetone) dipalladium, dichlorobis (triphenylphosphine) palladium, dichloro [1,3
-Bis (diphenylphosphino) propane] nickel,
Bis (acetylacetonato) nickel, dichloro [1,
1'-bis (diphenylphosphino) ferrocene] The above-mentioned metal such as palladium, or a chloride of the above-mentioned metal and triphenylphosphine, tri (o-tolyl) phosphine, 1,2-bis (diphenylphosphino) Metal complexes formed with ligands such as ethane, 1,2-bis (diphenylphosphino) propane, 1,1′-bis (diphenylphosphino) ferrocene, dibenzylideneacetone, and acetylacetone.

Manufacturing method (13)

[0103]

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(In the above reaction formula, X, Y, Z, R ¹ ,
R ² and R ³ are the same as defined above. W is a halogen atom such as a chlorine atom, a bromine atom or an iodine atom; a lower alkylsulfonyloxy group such as a methylsulfonyloxy group; a lower haloalkylsulfonyloxy group such as a trifluoromethylsulfonyloxy group; or a p-toluenesulfonyloxy group or the like. It represents an arylsulfonyloxy group. )

The above reaction is carried out in the absence of a solvent or in a solvent, in the presence of a base, in the presence or absence of a metal or a metal complex, or in the absence of a metal at a temperature in the range of -50 to 200 ° C, preferably 0 to 100 ° C. . The amount of the compound used in the reaction is usually such that [XI] is 1.0 to 3 to 1 equivalent of [XII].
0 equivalents, preferably 1.0 to 1.5 equivalents,
To 3.0 equivalents, preferably 1.0 to 1.5 equivalents, and 0.01 to 1.0 equivalents, preferably 0.05 to 0.5 equivalents of metal or metal complex.

When a solvent is used, suitable solvents include aliphatic hydrocarbons (hexane, heptane, etc.), aromatic hydrocarbons (benzene, toluene, xylene, etc.), and halogenated hydrocarbons (dichloromethane, chloroform, etc.). ,
1,2-dichloroethane, chlorobenzene, dichlorobenzene, etc.), ethers (diethyl ether, tetrahydrofuran, dioxane, etc.), aprotic polar solvents (N,
N-dimethylformamide, N-methylpyrrolidone, dimethylsulfoxide, sulfolane, acetonitrile, etc.), and mixtures thereof. Bases used include triethylamine, pyridine, picoline, N, N-
Diethylaniline, 4- (dimethylamino) pyridine, 1,
8-diazabicyclo [5,4,0] -7-undecene, 1,5-diazabicyclo [4,3,0] -5-nonene, 1,4-diazabicyclo [2,2,2]
Organic bases such as octane, and sodium hydride, potassium hydride, butyllithium, sec-butyllithium, t-
Butyllithium, phenyllithium, sodium methoxide, potassium methoxide, sodium ethoxide, potassium ethoxide, lithium diisopropylamide, t
-Inorganic bases such as potassium butoxy, sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, sodium bicarbonate, potassium bicarbonate, sodium acetate, potassium acetate, sodium fluoride and potassium fluoride. Examples of the metal or metal complex to be used include copper chloride, copper bromide, copper iodide, iron chloride, iron bromide, iron iodide, and the like. In addition, the starting compound [VII] in the production method (1) is used. ] Can be produced, for example, according to the following reaction formula.

[0107]

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(In the above reaction formula, X, Y, Z, R ³ , R ¹⁷
Is the same as defined above. The raw material compound [V] in the production method (2) is
For example, it can be produced according to the following reaction formula.

[0109]

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(In the above reaction formula, X, Y, Z, R ¹ ,
R ² and R ³ are the same as defined above. V and W represent the same or different halogen atoms such as chlorine, bromine and iodine atoms. The compound of the present invention has isomers such as optical isomers and diastereomers depending on its structure, and the compound of the present invention includes all of these. When the compound of the present invention is used as a herbicide, each isomer separated according to a known method may be used alone, or may be used as a mixture of isomers.

When the compound of the present invention is used as a herbicide, the compound of the present invention (hereinafter sometimes referred to as “the drug substance”) may be applied as it is. It is used in the form of an agent, granule, emulsion, flowable agent and the like. Examples of the auxiliary agent include solid carriers such as kaolin, bentonite, talc, diatomaceous earth, white carbon, and starch; water, alcohols (methanol, ethanol, propanol, butanol, ethylene glycol, etc.), ketones (acetone, methyl ethyl ketone, cyclohexanone). Etc.), ethers (diethyl ether,
Dioxane, cellosolves, etc.), aliphatic hydrocarbons (kerosene, kerosene, etc.), aromatic hydrocarbons (benzene, toluene, xylene, solvent naphtha, methylnaphthalene, etc.), halogenated hydrocarbons (dichloroethane, carbon tetrachloride) Solvents such as acid amides (dimethylformamide, etc.), esters (ethyl acetate, butyl acetate, fatty acid glycerin esters, etc.), nitriles (acetonitrile, etc.); nonionic surfactants (polyoxygen, etc.) Ethylene alkyl allyl ether, polyoxyethylene sorbitan monolaurate, etc., cationic surfactants (alkyl dimethyl benzyl ammonium chloride, alkyl pyridinium chloride, etc.), anionic surfactants (alkyl benzene sulfonate, lignin sulfonate, etc.) Alcohol sulfates), amphoteric surfactants (alkyl dimethyl betaine, surfactant such as dodecyl aminoethyl glycine and the like). These solid carriers, solvents, surfactants and the like are each used as a single kind or a mixture of two or more kinds as necessary.

The application amount of the compound of the present invention varies depending on conditions such as the structure of the compound, the target weed, the treatment time, the treatment method, and the properties of the soil. However, the amount of the active ingredient per hectare is usually 2 to 2000 g, Preferably 5-1000
A range of grams is appropriate. As the target weeds of the compound of the present invention, in the field, for example, white fir, red sea bream, inadade, harutade, inuyubu, aoyuyu, hakobe, otokenosa, ichibi, onamimi, wild morning glory, Korean morning glory, wild mustard, yaemugra, yoshino violet, oroshaku , Cochinella, crabgrass, ohishiba, barnyardgrass, enokorogusa and the like.

Further, in paddy fields, there may be mentioned, for example, Kikasigusa, Azena, Konagi, Abnomome, Mizohakobe, Heramodaka, Tainubie, Tamagatsuri, Urikawa, Omodaka, Firefly and Sphagnum. The compound of the present invention can control the above weeds both in the pre-emergence soil treatment and in the foliage treatment during the growing season. Further, the compound of the present invention, for example, corn, wheat,
It has little effect on cultivated crops such as barley, rice, soybean and the like in both pre-emergence soil treatment and growing foliage treatment, and can be used as a selective herbicide.

Herbicides containing the compound of the present invention as an active ingredient include:
Other pesticides used in the same field, for example, insecticides, fungicides,
It can be mixed and applied with a plant growth regulator, a fertilizer and the like. In addition, it is possible to further stabilize the herbicidal effect by mixing and applying with other herbicides. When the compound of the present invention and another herbicide are mixed and applied, the respective preparations may be mixed at the time of application, or may be applied as a preparation containing both in advance. Examples of the herbicides that can be suitably mixed and applied with the compound of the present invention include the following.

Carbamate herbicide: 2-chloroallyl
Diethyldithiocarbamate, S-2,3-dichloroallyl
Diisopropylthiocarbamate, S-2,2,3-trichloroallyl diisopropylthiocarbamate, S-ethyl
Dipropyl thiocarbamate, S-ethyl diisobutyl thiocarbamate, S-benzyl 1,2-dimethylpropyl (ethyl) thiocarbamate, S-4-chlorobenzyl diethyl thiocarbamate, S-ethyl perhydroazepine-1-thiocarboxylate, S-isopropyl perhydroazepine-1-thiocarboxylate, S-1-methyl-1
-Phenylethyl piperidine-1-thiocarboxylate, O-3-t-butylphenyl 6-methoxy-2-pyridyl (methyl) thiocarbamate, 3- (methoxycarbonylamino) phenyl 3′-methylphenylcarbamate,
Isopropyl 3'-chlorophenyl carbamate, methyl (4-aminophenylsulfonyl) carbamate, etc.

Urea herbicides: 3- (3,4-dichlorophenyl) -1,1-dimethylurea, 3- (3,4-dichlorophenyl)-
1-methoxy-1-methylurea, 1,1-dimethyl-3- [3- (trifluoromethyl) phenyl] urea, 3- [4- (4-methoxyphenoxy) phenyl] -1,1-dimethylurea, 1 -(1−
Methyl-1-phenylethyl) -3-p-tolylurea, 3- (4-
(Isopropylphenyl) -1,1-dimethylurea, 3- (5-t-
(Butylisoxazol-3-yl) -1,1-dimethylurea, 1- (5-t-butyl-1,3,4-thiadiazol-2-yl)-
1,3-dimethylurea, 1- (benzothiazol-2-yl)-
1,3-dimethylurea, etc.

Amide herbicides: 2-chloro-2 ', 6'-diethyl-N- (methoxymethyl) acetanilide, N- (butoxymethyl) -2-chloro-2', 6'-diethylacetanilide, 2-
Chloro-2 ', 6'-diethyl-N- (2-propoxyethyl) acetanilide, 2-chloro-N- (ethoxymethyl) -6'-ethylaceto-o-toluidide, 2-chloro-6'-ethyl-N -(2-methoxy-1-methylethyl) aceto-o-toluidide, 2-chloro-N- (3-methoxy-2-thenyl) -2 ′, 6′-dimethylacetanilide, N- (chloroacetyl) -N -(2,6-diethylphenyl) glycine ethyl ester, 2-chloro-N- (2,4-dimethyl-3-thienyl) -N- (2-methoxy-1-methylethyl)
Acetamide, 3 ', 4'-dichloropropionanilide,
2 ', 4'-Difluoro-2- [3- (trifluoromethyl) phenoxy] nicotineanilide, 2- (1,3-benzothiazole-2
-Yloxy) -N-methylacetanilide, 2-bromo-N-
(a, a-dimethylbenzyl) -3,3-dimethylbutyramide, N
-[3- (1-Ethyl-1-methylpropyl) isoxazole-
5-yl] -2,6-dimethoxybenzamide, etc.

Dinitroaniline herbicide: 2,6-dinitro
-N, N-dipropyl-4- (trifluoromethyl) aniline,
N- butyl -N- ethyl-2,6-dinitro-4- (trifluoromethyl) aniline, 2,6-dinitro -N ^1, N ¹ - dipropyl -4
-(Trifluoromethyl) -m-phenylenediamine, 4- (dipropylamino) -3,5-dinitrobenzenesulfonamide, N-sec-butyl-4-t-butyl-2,6-dinitroaniline, N- (1-ethylpropyl) -2,6-dinitro-3,4-xylidine, etc.

Carboxylic acid herbicides: (2,4-dichlorophenoxy) acetic acid and its derivatives, (2,4,5-trichlorophenoxy) acetic acid and its derivatives, (4-chloro-2-methylphenoxy) acetic acid and its derivatives Derivative, 2- (2,4-dichlorophenoxy) propionic acid and its derivative, 4- (2,4
-Dichlorophenoxy) butyric acid and its derivatives, 2,3,6-
Trichlorobenzoic acid and its derivatives, 3,6-dichloro-2
-Methoxybenzoic acid and its derivatives, 3,7-dichloroquinoline-8-carboxylic acid, 7-chloro-3-methylquinoline-8
-Carboxylic acid, 3,6-dichloropyridine-2-carboxylic acid and its salt, 4-amino-3,5,6-trichloropyridine-2-
Carboxylic acid and its salts, (3,5,6-trichloro-2-pyridyloxy) acetic acid and its derivatives, (4-amino-3,5-
Dichloro-6-fluoro-2-pyridyloxy) acetic acid and its derivatives, (4-chloro-2-oxobenzothiazoline-3
-Yl) acetic acid and its derivatives, 2- [4- (2,4-dichlorophenoxy) phenoxy] propionic acid and its derivatives, 2- [4- [5- (trifluoromethyl) -2-pyridyloxy] phenoxy] Propionic acid and its derivatives, 2- [4
-[3-Chloro-5- (trifluoromethyl) -2-pyridyloxy] phenoxy] propionic acid and its derivatives, 2- [4
-(6-chloro-1,3-benzoxazol-2-yloxy)
Phenoxy] propionic acid and its derivatives, 2- [4- (6-
Chloroquinoxalin-2-yloxy) phenoxy] propionic acid and its derivatives, 2- [4- (4-cyano-2-fluorophenoxy) phenoxy] propionic acid and its derivatives, and the like

Phenolic herbicides: 3,5-dibromo-4-hydroxybenzonitrile and its salts, 4-hydroxy-
3,5-diiodobenzonitrile and its salts, 2-t-butyl-4,6-dinitrophenol and its salts, etc.

Cyclohexanedione herbicide: methyl
3- [1- (allyloxyimino) butyl] -4-hydroxy-6,6
-Dimethyl-2-oxo-3-cyclohexene-1-carboxylate and salts thereof, 2- [1- (ethoxyimino) butyl] -5- [2- (ethylthio) propyl] -3-hydroxy-2-cyclohexene- 1-one, 2- [1- (ethoxyimino) butyl] -3-hydroxy-5- (thian-3-yl) -2-cyclohexen-1-one, 2- [1- (ethoxyimino) propyl]- 3-hydroxy-5- (2,4,6-trimethylphenyl) -2-cyclohexen-1-one, 2- [1- (3-chloroallyloxyimino) propyl] -5- [2- (ethylthio) propyl ] -3-Hydroxy-2-
Cyclohexen-1-one, 2- [2-chloro-4- (methylsulfonyl) benzoyl] cyclohexane-1,3-dione, etc.

Diphenyl ether herbicides: 4-nitrophenyl 2,4,6-trichlorophenyl ether, 2- (2,4
-Dichlorophenoxy) -2-nitroanisole, 2-chloro
-4- (trifluoromethyl) phenyl 3-ethoxy-4-nitrophenyl ether, methyl 5- (2,4-dichlorophenoxy) -2-nitrobenzoate, 5- [2-chloro-4- (trifluoromethyl) Phenoxy] -2-nitrobenzoic acid and salts thereof, O- [5- [2-chloro-4- (trifluoromethyl) phenoxy] -2-nitrobenzoyl] ethyl glycolate, ethyl O- [5- [2- Chloro-4- (trifluoromethyl) phenoxy] -2-nitrobenzoyl] -DL-lactate, 5- [2-chloro-4- (trifluoromethyl) phenoxy] -N- (methylsulfonyl) -2-nitrobenzamide , 2-chloro-6-nitro-3-phenoxyaniline, etc.

Sulfonylurea herbicide: ethyl 2- (4
-Chloro-6-methoxypyrimidin-2-ylcarbamoylsulfamoyl) benzoate, methyl 2- (4,6-dimethylpyrimidin-2-ylcarbamoylsulfamoyl)
Benzoate, methyl 2- [4,6-bis (difluoromethoxy) pyrimidin-2-ylcarbamoylsulfamoyl] benzoate, methyl 2- (4,6-dimethoxypyrimidin-2-ylcarbamoylsulfamoylmethyl) benzoate, 1 -(2-chlorophenylsulfonyl) -3- (4-methoxy-6-methyl-1,3,5-triazin-2-yl) urea, methyl 2- (4-methoxy-6-methyl-1,3,5 -Triazin-2-ylcarbamoylsulfamoyl) benzoate, methyl 2- [4-methoxy-6-methyl-1,3,5-triazin-2-yl (methyl) carbamoylsulfamoyl]
Benzoate, 1- [2- (2-chloroethoxy) phenylsulfonyl] -3- (4-methoxy-6-methyl-1,3,5-triazine
-2-yl) urea, 1- (4,6-dimethoxy-1,3,5-triazin-2-yl) -3- [2- (2-methoxyethoxy) phenylsulfonyl] urea, methyl 2- [4 -Ethoxy-6- (methylamino) -1,3,5-triazin-2-ylcarbamoylsulfamoyl] benzoate, methyl 3- (4-methoxy-6-
Methyl-1,3,5-triazin-2-ylcarbamoylsulfamoyl) thiophen-2-carboxylate, ethyl
5- (4,6-dimethoxypyrimidin-2-ylcarbamoylsulfamoyl) -1-methylpyrazole-4-carboxylate, methyl 3-chloro-5- (4,6-dimethoxypyrimidine-2
-Ylcarbamoylsulfamoyl) -1-methylpyrazole-4-carboxylate, 1- (4,6-dimethoxypyrimidin-2-yl) -3- [3- (trifluoromethyl) -2-pyridylsulfonyl] urea , 1- (4,6-dimethoxypyrimidine-2-
Yl) -3- [3- (ethylsulfonyl) -2-pyridylsulfonyl] urea, 2- (4,6-dimethoxypyrimidin-2-ylcarbamoylsulfamoyl) -N, N-dimethylnicotinamino, 1- ( 2-chloroimidazo [1,2-a] pyridin-3-ylsulfonyl) -3- (4,6-dimethoxypyrimidin-2-yl) urea, 1- [2- (cyclopropylcarbonyl) phenylsulfamoyl] -3- (4,6-dimethoxypyrimidin-2-yl)
Urea, 1- (4-methoxy-6-methyl-1,3,5-triazine
-2-yl) -3- [2- (3,3,3-trifluoropropyl) phenylsulfonyl] urea and the like

Bipyridinium herbicide: 1,1'-dimethyl
-4,4'-bipyridinium dichloride, 1,1'-ethylene-
2,2'-bipyridinium dibromide, etc.

Pyrazole herbicide: 4- (2,4-dichlorobenzoyl) -1,3-dimethylpyrazol-5-yl toluene
-4-sulfonate, 2- [4- (2,4-dichlorobenzoyl) 1,3
-Dimethylpyrazol-5-yloxy] acetophenone, 2- [4- (2,4-dichloro-3-methylbenzoyl) -1,3-dimethylpyrazol-5-yloxy] -4'-methylacetophenone, etc.

Triazine herbicide: 6-chloro-N ² , N ⁴ −
Diethyl-1,3,5-triazine-2,4-diamine, 6-chloro
-N ² - ethyl -N ⁴ - isopropyl-1,3,5-triazine -
2,4-diamine, 2- [4-chloro-6- (ethylamino) -1,3,5
-Triazin-2-ylamino] -2-methylpropionitrile, N ² , N ⁴ -diethyl-6- (methylthio) -1,3,5-triazin-2,4-diamine, N ^2- (1,2 −dimethylpropyl) -N ⁴ −
Ethyl-6- (methylthio) -1,3,5-triazine-2,4-diamine, 4-amino-6-t-butyl-3- (methylthio) -1,2,4-triazine-5 (4H) -ON, etc.

Imidazolinone herbicides: methyl 2- (4-
Isopropyl-4-methyl-5-oxo-2-imidazoline-2
-Yl) -4 (5) -methylbenzoate, 2- (4-isopropyl-4-methyl-5-oxo-2-imidazolin-2-yl) pyridine-3-carboxylic acid and salts thereof, 2- (4- Isopropyl-4-methyl-5-oxo-2-imidazolin-2-yl) quinoline-3-carboxylic acid and salts thereof, 5-ethyl-2- (4-isopropyl-4-methyl-5-oxo-2-imidazoline -2−
Yl) pyridine-3-carboxylic acid and salts thereof, 2- (4-isopropyl-4-methyl-5-oxo-2-imidazoline-2-
Yl) -5- (methoxymethyl) pyridine-3-carboxylic acid and its salts, etc.

Other herbicides: 1-methyl-3-phenyl-5
-[3- (trifluoromethyl) phenyl] -4-pyridone, 3-
Chloro-4- (chloromethyl) -1- [3- (trifluoromethyl)
Phenyl] -2-pyrrolidinone, 5- (methylamino) -2-phenyl-4- [3- (trifluoromethyl) phenyl] furan-3
(2H) -one, 4-chloro-5- (methylamino) -2- [3- (trifluoromethyl) phenyl] pyrazin-3 (2H) -one, N, N-
Diethyl-3- (2,4,6-trimethylphenylsulfonyl) -1H
-1,2,4-triazole-1-carboxamide, N- [2,4-dichloro-5- [4- (difluoromethyl) -4,5-dihydro-3-methyl-5-oxo-1H-1, 2,4-triazol-1-yl] phenyl] methanesulfonamide, 1- [4-chloro-3- (2,2,3,
3,3-pentafluoropropoxymethyl) phenyl] -5-phenyl-1H-1,2,4-triazole-3-carboxamide, 2-
(Chlorobenzyl) -4,4-dimethylisoxazolidine-3
-One, 5-cyclopropyl-4- [2- (methylsulfonyl)-
4- (trifluoromethyl) benzoyl] isoxazole, 5-t-butyl-3- (2,4-dichloro-5-isopropoxyphenyl) -1,3,4-oxadiazol-2 (3H) -one ,ethyl
[2-chloro-5- [4-chloro-5- (difluoromethoxy) -1-
Methylpyrazol-3-yl] -4-fluorophenoxy] acetate, S, S'-dimethyl 2- (difluoromethyl) -4-
Isobutyl-6- (trifluoromethyl) pyridine-3,5-dicarbothioate, methyl 2- (difluoromethyl) -5-
(4,5-dihydro-1,3-thiazol-2-yl) -4-isobutyl-6- (trifluoromethyl) pyridine-3-carboxylate, 2-chloro-6- (4,6-dimethoxypyrimidine- 2-ylthio) benzoic acid and its salts, methyl 2- (4,6-dimethoxypyrimidin-2-yloxy) -6- [1- (methoxyimino) ethyl] benzoate, 2,6-bis (4,6-dimethoxy) Pyrimidin-2-yloxy) benzoic acid and its salts, 5-
Bromo-3-sec-butyl-6-methylpyrimidine-2,4 (1H, 3
H) -dione, 3-t-butyl-5-chloro-6-methylpyrimidine-2,4 (1H, 3H) -dione, 3-cyclohexyl-1,5,6,7-tetrahydrocyclopentapyrimidine-2, 4 (3H) -dione,
Isopropyl 2-chloro-5- [1,2,3,6-tetrahydro-3-
Methyl-2,6-dioxo-4- (trifluoromethyl) pyrimidin-1-yl] benzoate, 1-methyl-4-isopropyl-2-[(2-methylphenyl) methoxy] -7-oxabicyclo [2.2. 1] heptane, N- (4-chlorophenyl) -3,4,5,6-
Tetrahydrophthalimide, pentyl [2-chloro-4-
Fluoro-5- (1,3,4,5,6,7-hexahydro-1,3-dioxo
-2H-isoindol-2-yl) phenoxy] acetate, 2- [7-fluoro-3,4-dihydro-3-oxo-4- (2-propynyl) -2H-1,4-benzoxazine-6- Il] -4,5,6,
7-tetrahydro-1H-isoindole-1,3 (2H) -dione,
N- (2,6-difluorophenyl) -5-methyl [1,2,4] triazolo [1,5-a] pyrimidine-2-sulfonamide, N- (2,6-
Dichloro-3-methylphenyl) -5,7-dimethoxy [1,2,4]
Triazolo [1,5-a] pyrimidine-2-sulfonamide, 2,
3-dihydro-3,3-dimethylbenzofuran-5-yl ethanesulfonate 2-ethoxy-2,3-dihydro-3,3-dimethylbenzofuran
-5-yl methanesulfonate methyl [[2-chloro-4-fluoro-5-[(tetrahydro-3
-Oxo-1H, 3H- [1,3,4] thiadiazolo [3,4a] pyridazine
1-ylidene) amino] phenyl] thio] acetate,
2- [2- (3-chlorophenyl) -2,3-epoxypropyl] -2-ethylindane-1,3-dione, etc.

[0129]

Next, the present invention will be described more specifically with reference to examples. However, the present invention is not limited to the following examples unless it exceeds the gist. Reference Example 1 ethyl 1- [4-chloro5- (cyclopentyloxy) -2-fur
Orophenyl] ethylidene carbazate

[0130]

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4'-chloro-5 '-(cyclopentyloxy)-
While heating and refluxing a mixture of 6.1 g of 2'-fluoroacetophenone, 2.5 g of ethyl carbazate and 20 mL of toluene for 10 hours, water is constantly removed from the system using an ester tube. After standing overnight, it was concentrated to obtain a crude product. Purification by column chromatography (developing solvent: hexane: ethyl acetate / 7: 1) gave 4.2 g of the title compound.
Physical property values and NMR spectrum data are as follows.

¹ H-NMR (CDCl ₃ ) δ (ppm): 7.93 (1H, br),
7.22 (1H, d, J = 6.0 Hz), 7.10 (1H, d, J = 10.5 H
z), 4.84 (1H, m), 4.32 (2H, q, J = 6.9 Hz), 2.22 (3
H, s), 1.98-1.80 (4H, m), 1.75-1.59 (2H, m), 1.
35 (3H, t, J = 6.9 Hz).

Reference Example 2 Ethyl 2,2,2-trichloro-1- [4-chloro5- (cyclopentene)
Tyloxy) -2-fluorophenyl] ethylidene carbaze
To

[0134]

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Ethyl 1- [4-chloro obtained in Reference Example 1
5- (cyclopentyloxy) -2-fluorophenyl] ethylidene carbazate 1.8 g, N-chlorosuccinimide
A mixture of 2.4 g and 30 mL of carbon tetrachloride is heated under reflux for 28 hours. The resulting crystals were allowed to stand at room temperature overnight, and the precipitated crystals were separated by filtration and washed with ethyl acetate. The obtained filtrate is concentrated and ethyl 2,2-dichloro-1- [4-chloro5- (cyclopentyloxy) -2-fluorophenyl] ethylidene carbazate
2.6 g were obtained. This crude product and sulfuryl chloride 4.5
The mixture of g is allowed to stir at 50 ° C. for 17 hours. Thereafter, the reaction solution is slowly dropped into stirred ice water. The precipitated crystals were separated by filtration, dissolved in ethyl acetate, washed with saturated saline, dried over anhydrous sodium sulfate, filtered and concentrated. The obtained crystals were filtered, washed with hexane and dried to obtain 1.8 g of the title compound. Physical property values and NMR spectrum data are as follows.

Mp 230.0-231.0 ° C. ¹ H-NMR (CDCl ₃ ) δ (ppm): 7.58 (1H, br), 7.32 (1H, d,
J = 9.3 Hz), 6.94 (1H, d, J = 5.7 Hz), 4.75 (1H,
m), 4.29 (2H, q, J = 6.9 Hz), 1.98-1.80 (4H, m), 1.
75-1.59 (2H, m), 1.33 (3H, t, J = 6.9 Hz) .IR (KBr) ν (cm ^-1 ): 2965, 1630, 1490, 1450, 1402, 1
341, 1190.

Reference Example 3 Ethyl 4-chloro-5-cyclopentyloxy-2-fluoro
Rophenylglyoxylate

[0138]

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A stirrer bar was placed in a 100 mL four-necked flask, and a Dimlow condenser and a thermometer were installed. 0.49 g of metallic magnesium, a piece of iodine, and 2 mL of THF
The mixture was stirred under a nitrogen stream for 15 minutes until the iodine color disappeared to activate magnesium. There, 1-bromo
A solution of 2.0 g of 4-chloro-5-cyclopentyloxy-2-fluorobenzene and 0.1 mL of dibromoethane in 6 mL of THF was added.
The solution was slowly dropped over 15 minutes while maintaining the internal temperature at 35 ° C or lower. After the addition, add 2 mL of dibromoethane in 0.1 mL of THF.
The L solution was slowly added dropwise over 5 minutes while maintaining the internal temperature at 35 ° C. or lower to prepare a Grignard reagent.

A stirrer bar was placed in a 2000 mL four-necked flask, and a Dimlow condenser and a thermometer were installed. 30.0 g of metallic magnesium, 1 spatula of iodine and THF
Remove 150 mL of the mixture under a stream of nitrogen until the iodine color disappears.
The mixture was stirred for a minute to activate the magnesium. Then, the Grignard reagent prepared above was added with a syringe, and THF220 was added.
After adding 1 mL of the solution, 181.94 g of 1-bromo-4-chloro-5-cyclopentyloxy-2-fluorobenzene and 180 mL of dibromoethane in 10.8 mL of THF were added thereto for 2 hours at an internal temperature of 30 mL.
The solution was slowly added dropwise at -36 ° C. After completion of the dropwise addition, 15 mL of a THF solution of 2.7 mL of dibromoethane was slowly added dropwise over 30 minutes while maintaining the internal temperature at 35 ° C or lower.

A stirrer bar was placed in a 3000 mL four-necked flask, and a Dimlow condenser and a thermometer were installed. There, 800 mL of ether of 184.0 g of diethyl oxalate
The solution was added and cooled to -30 ° C under a stream of nitrogen. there,
Keep the Grignard reagent prepared above at -30 ° C or lower.
The solution was slowly dropped over 1.5 hours. The temperature was further raised to -20 ° C and the mixture was stirred for 1 hour. A saturated aqueous ammonium chloride solution was slowly added to the reaction mixture to terminate the reaction, and the temperature was raised to room temperature. The reaction mixture was extracted with ethyl acetate, and the obtained organic phase was washed with brine, dried over anhydrous sodium sulfate, filtered and concentrated. Unreacted diethyl oxalate in the crude product was distilled off at 0.5 mmHg at a bath temperature of 70 ° C., and the resulting crude product was subjected to flash column chromatography (developing solvent: hexane: ethyl acetate / 20: 1- 15: 1) to give 101.1 g of the title compound. Physical property values and NMR spectrum data are as follows.

Mp 54.5-55.1 ° C. ¹ H-NMR (CDCl ₃ ) δ (ppm): 7.40 (1 H, d, J = 6.0 Hz),
7.22 (1H, d, J = 10.2Hz), 4.85 (1H, m), 4.43 (2H,
q, J = 6.9 Hz) 1.98-1.80 (4H, m), 1.75 -1.59 (2H,
m), 1.40 (3H, t, J = 6.9 Hz).

Reference Example 4 4-chloro-5-cyclopentyloxy-2-fluorophenyl
Glyoxylic acid

[0144]

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A mechanical stirrer and a thermometer were set in a 2000 mL three-necked flask, and sodium hydroxide 40.00 was added thereto.
g and water (500 mL) were added to prepare a 2N aqueous sodium hydroxide solution. After cooling to room temperature, 109.8 g of ethyl 4-chloro-5-cyclopentyloxy-2-fluorophenylglyoxylate obtained in Reference Example 3 was slowly added, and the mixture was stirred for 1.5 hours. After the reaction is completed, 1N hydrochloric acid aqueous solution 1000
The reaction solution was acidified by slow addition of mL. The reaction mixture was extracted three times with ether, and the obtained organic phase was washed twice with a saturated saline solution, dried over anhydrous sodium sulfate, filtered and concentrated to obtain 99.8 g of the title compound. Physical property value and NM
The R spectrum data is as follows.

Mp 94.2 −96.7 ° C. ¹ H-NMR (CDCl ₃ ) δ (ppm): 7.99 (1 H, t, J = 7.8 Hz),
7.33 (1H, dd, J = 1.5,8.4 Hz), 7.26 (1H, dd, J = 1.
5,9.9 Hz), 7.03 (1H, br) .IR (KBr) ν (cm ^-1 ): 2985, 1720, 1692, 1606, 1408, 1
250, 1215, 1080, 990, 900, 861, 540.

Example 1 3- (4-chloro-2-fluoro-5-cyclopentyloxyf
Enyl) -6,7-dihydro-4-hydroxy- [5H] -cyclopen
[C] Pyridazine

[0148]

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A 1000 mL flask was equipped with a stirrer bar, a salt tube and an alkali trap. Then, 99.8 g of 4-chloro-5-cyclopentyloxy-2-fluorophenylglyoxylic acid obtained in Reference Example 4 and thionyl chloride were obtained.
122.0 mL was added and the mixture was heated and stirred at 60 ° C. for 2.5 hours. Later, a distillation set was installed and the bath temperature was raised to 110 ° C,
Unreacted thionyl chloride was distilled off. Further benzene 120 m
After L was added and the residue was distilled off together with the remaining thionyl chloride, the residue was dried under reduced pressure with a vacuum pump to obtain crude glyoxylic acid chloride.

A 2000 mL four-necked flask was equipped with a stir bar, a salt tube and a thermometer. Thereto are added 54.2 g of N- (1-cyclopenten-1-yl) -morpholine, 66.6 g of triethylamine and 500 mL of methylene chloride, and the mixture is cooled to -5 ° C under a nitrogen stream. Thereto, the previously prepared solution of glyoxylic chloride in methylene chloride (200 mL) was slowly added dropwise over 1 hour while maintaining the solution temperature at 1 ° C or lower. Further, the reaction mixture was stirred at 1-10 ° C. for 1 hour. The reaction mixture was filtered and the residue (triethylamine hydrochloride) was washed with 150 mL of methylene chloride. The filtrate was transferred to a 2000 mL flask, 500 mL of 2-propanol was added, 19.8 g of hydrazine hydrate was added dropwise with stirring, the mixture was stirred at room temperature for 1 hour, and then left overnight. The reaction mixture was concentrated under reduced pressure, and the residue was suspended in ethanol. The suspension was filtered, the residue was washed with ethanol and hexane, and dried under reduced pressure to obtain 55.5 g of the title compound. The residue obtained by concentrating the filtrate under reduced pressure was suspended again in ethanol, filtered, washed and dried in the same manner.
3.6 g were obtained. Physical property values and NMR spectrum data are as follows.

Mp 300 ° C. over ¹ H-NMR (DMSO-d ₆ ) δ (ppm): 7.23 (1H, d, J = 6.3 Hz),
7.18 (1H, d, J = 9.6 Hz), 4.79 (1H, m), 3.05 (2H,
t, J = 7.5 Hz), 2.96 (2H, t, J = 7.5 Hz), 2.17 (2
H, qui, J = 7.5 Hz), 1.95-1.53 (8H, m) .IR (KBr) ν (cm ^-1 ): 3050, 2920, 1580, 1560, 1492, 1
465, 1401, 1187.

Example 2 4-chloro-3- [4-chloro5- (cyclopentyloxy) -2-fu
Fluorophenyl] -6,7-dihydro-5H-cyclopenta [c] pi
Redazin

[0153]

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To a solution of 1.50 g of ethyl 2,2,2-trichloro-1- [4-chloro5- (cyclopentyloxy) -2-fluorophenyl] ethylidenecarbazate obtained in Reference Example 2 in 10 mL of dichloromethane was added triethylamine. 0.42 g is slowly added dropwise. 1-morpholino-1-cyclopentene (0.64 g) is added to the mixture and heated to reflux for 7 hours. After standing overnight, the reaction mixture was extracted with ethyl acetate,
Washed sequentially with a saturated aqueous ammonium chloride solution, a saturated aqueous sodium bicarbonate solution, and a saturated saline solution, and dried over anhydrous sodium sulfate.
After filtration, concentrate. The crude product was purified by flash column chromatography (hexane: ethyl acetate / 9: 1-3: 1) to give 0.50 g of the title compound (Table 1, No. 18).

Example 3 4-Chloro-3- (4-chloro-2-fluoro-5-hydroxyphen)
Nyl) -6,7-dihydro-5H-cyclopenta [c] pyridazine

[0156]

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A solution of 2.4 g of 4-chloro-3- (4-chloro-5-cyclopentyloxy-2-fluorophenyl) -6,7-dihydro-5H-cyclopenta [c] pyridazine in 2 mL of methylene chloride in 4 mL of 75% sulfuric acid Is slowly dropped. After stirring at room temperature for 30 minutes, the reaction mixture is added dropwise to crushed ice water and extracted with ethyl acetate. The aqueous layer is neutralized with a saturated aqueous solution of sodium bicarbonate, and then extracted with ethyl acetate. The combined organic layers are washed with saturated saline, dried over anhydrous sodium sulfate, filtered and concentrated.
The crude product was washed with a small amount of ethyl acetate and hexane to give 1.68 g of the title compound (Table 1, No. 12) as crystals.

Example 4 Ethyl 2- [2-chloro-4-fluoro-5- (4-chloro-6,7-
Dihydro-5H-cyclopenta [c] pyridazin-3-yl) f
Enoxy] Propionate

[0159]

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4-Chloro-3- (4-chloro-2-fluoro-5-hydroxyphenyl) -6,7-dihydro-5H-cyclopenta [c]
Pyridazine 0.40 g, ethyl α-bromopropionate
A mixture of 0.29 g, 0.22 g of potassium carbonate and 5 mL of acetone was heated to reflux for 5 hours while stirring. The reaction solution was cooled to room temperature, a saturated aqueous ammonia solution was added, and the mixture was extracted with ethyl acetate. The organic phase was washed with brine and dried over sodium sulfate. The crude product obtained by concentration under reduced pressure was subjected to flash column chromatography (hexane-ethyl acetate /
2: 1) and 0.44 g of the title compound (Table-2, No. 54)
I got

Example 5 4-chloro-3- [4-chloro-2-fluoro-5- (1-methyl-2-propyl)
Lopinyloxy) phenyl] -6,7-dihydro-5H-cyclope
[C] pyridazine

[0162]

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4-chloro-3- (4-chloro-2-fluoro-5-hydroxyphenyl) -6,7-dihydro-5H-cyclopenta [c]
0.61 g of pyridazine and triphenylphosphine (TPP) 0.
To a solution of 67 g and 1-buten-3-ol 0.21 g in 5 mL of tetrahydrofuran, diethyl azodicarboxylate (DEAD) 0.4
4 g are slowly added dropwise. Thereafter, the mixture is stirred at room temperature overnight.
The reaction solution was concentrated under reduced pressure, and the obtained crude product was purified by flash column chromatography (hexane / ethyl acetate /
The crystals obtained by purification according to 3: 1) were washed with hot water to obtain 0.46 g of the title compound (Table 1, No. 24).

Example 6 4-Chloro-3- [4-chloro5- (cyclopentyloxy) -2-fu
Fluorophenyl] -6,7-dihydro-5H-cyclopenta [c] pi
Redazin

[0165]

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The 3- (4-chloro-2- fury) obtained in Example 1
(Oro-5-cyclopentyloxyphenyl) -6,7-dihydro
4-Hydroxy- [5H] -cyclopenta [c] pyridazine 1.4
A toluene solution (10 mL) of 5 g and 3.00 g of phosphorus oxychloride was stirred at room temperature for 1 hour. The reaction mixture was added to ice-cold water (100 mL), extracted with ethyl acetate, and the obtained organic phase was washed with saturated aqueous sodium hydrogen carbonate and saturated brine, dried over anhydrous sodium sulfate, filtered and concentrated. The resulting crude product was purified by flash column chromatography (hexane-ethyl acetate /
2: 1) and 1.50 g of the title compound (Table-1, No. 18)
I got

Example 7 4-bromo-3- [4-chloro5- (cyclopentyloxy) -2-fu
Fluorophenyl] -6,7-dihydro-5H-cyclopenta [c] pi
Redazin

[0168]

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The 3- (4-chloro-2- fury) obtained in Example 1
(Oro-5-cyclopentyloxyphenyl) -6,7-dihydro
-4-Hydroxy- [5H] -cyclopenta [c] pyridazine 9.
A solution of 00 g of phosphorous tribromide in 30 mL was heated and stirred at 80-90 ° C. for 2 hours. After the completion of the reaction, the reaction mixture was cooled to room temperature, poured into ice water, and extracted with chloroform. The obtained organic layer was washed with a saturated aqueous solution of sodium bicarbonate and then with a saturated saline solution, dried over anhydrous sodium sulfate, filtered, and concentrated. The crude product was purified by flash column chromatography (developing solvent: hexane: ethyl acetate / 3: 1-5: 2) to give the title compound 3.0
0 g was obtained.

Example 8 4-chloro-3- (4-chloro-5-nitro-2-fluorophenyl)-
6,7-dihydro-5H-cyclopenta [c] pyridazine

[0171]

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4-chloro-3- (4-chloro-2-fluorophenyl) -6,7-dihydro-5H-cyclopenta [c] pyridazine 7.4
Add 35 mL of concentrated sulfuric acid to g, and stir while cooling to 7 ° C to make a homogeneous system. To this mixture, add mixed acid (2.5 mL concentrated sulfuric acid,
(2.5 mL of 60% nitric acid) is slowly added dropwise at 6-12 ° C over 10 minutes. The reaction mixture is poured into ice water (400 mL) and extracted with ethyl acetate. The obtained organic layer is washed successively with saturated aqueous sodium hydrogen carbonate and saturated brine, dried over anhydrous sodium sulfate, filtered and concentrated. The crude product was purified by flash column chromatography (hexane-ethyl acetate / 2: 1) to obtain 5.12 g of the title compound (Table 1, No. 8).

Example 9 4-chloro-3- (5-amino-4-chloro-2-fluorophenyl
Le) -6,7-dihydro-5H-cyclopenta [c] pyridazine

[0174]

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A mixture of 6.0 g of iron powder, 6 mL of water and 1.5 mL of acetic acid is heated under reflux for 30 minutes. After cooling to room temperature, isopropanol (20 mL) was added, and 4-chloro-3- (4-chloro-2-fluoro-5-nitrophenyl) -6,
5.05 g of 7-dihydro-5H-cyclopenta [c] pyridazine
Slowly add 20 mL of N-methylpyrrolidone (NMP) solution. Thereafter, the mixture was heated and stirred at 80 ° C. for 1.5 hours, cooled to room temperature, and subjected to an aqueous potassium carbonate solution (1.25 g of potassium carbonate,
0 mL) is added. The mixture is filtered through celite and the residue is washed with ethyl acetate. The filtrate is concentrated, the obtained crude product is extracted with ethyl acetate, and the obtained organic layer is washed successively with saturated aqueous sodium hydrogen carbonate and saturated brine, dried over anhydrous sodium sulfate, filtered and concentrated. The crude product is subjected to flash column chromatography (hexane-ethyl acetate / 2: 1)
And 4.59 g of the title compound (Table-1, No. 61) was obtained.

Example 10 Ethyl N- [4-chloro-5- (4-chloro-6,7-dihydro-5H-
Cyclopenta [c] pyridazin-3-yl) -2-fluorophen
Nil] Carbamate

[0177]

Embedded image

A solution of 1.50 g of 4-chloro-3- (5 amino-4-chloro-2-fluorophenyl) -6,7-dihydro-5H-cyclopenta [c] pyridazine and 0.57 g of ethyl chloroformate in pyridine (15 mL) ) Was allowed to stir for 8 hours. The reaction mixture was extracted with ethyl acetate, and the organic layer was washed successively with a 1N aqueous hydrochloric acid solution, a saturated aqueous sodium hydrogen carbonate solution and a saturated saline solution, dried over anhydrous sodium sulfate, filtered and concentrated. The crude product was purified by flash column chromatography (hexane-ethyl acetate / 2: 1) to obtain 1.10 g of the title compound (Table 1, No. 63).

Example 11 Ethyl N- [4-chloro-5- (4-chloro-6,7-dihydro-5H-
Cyclopenta [c] pyridazin-3-yl) -2-fluorophen
Nyl] -N-propargyl carbamate

[0180]

Embedded image

After washing 0.12 g of sodium hydride with hexane and removing the oil, 5 mL of dimethylformamide was used.
Was suspended. Ethyl N- [4-chloro-5-
(4-Chloro-6,7-dihydro-5H-cyclopenta [c] pyridazin-3-yl) -2-fluorophenyl] carbamate 1.0
g, and the mixture was stirred at room temperature for 30 minutes. Then, 0.35 g of propargyl bromide was added, and the mixture was further stirred for 2 hours. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed with a saturated aqueous solution of ammonium chloride, a saturated aqueous solution of sodium bicarbonate and a saturated aqueous solution of sodium chloride, dried over anhydrous sodium sulfate, filtered and concentrated. The crude product was purified by flash column chromatography (hexane-ethyl acetate / 2: 1) to obtain 0.75 g of the title compound (Table 1, No. 68).

Example 12 N- [4-Chloro-5- (4-chloro-6,7-dihydro-5H-cyclope
[C] pyridazin-3-yl) -2-fluorophenyl]
Lopansulfonamide

[0183]

Embedded image

4-Chloro-3- (5 amino-4-chloro-2-fluorophenyl) -6,7-dihydro-5H-cyclopenta [c] pyridazine 3.00 g, n-propanesulfonyl chloride 2.10
g, pyridine 1.6 g in methylene chloride solution 20 mL
Allowed to stir for hours. The reaction mixture was extracted with ethyl acetate, and the organic layer was washed successively with a 1N aqueous hydrochloric acid solution, a saturated aqueous sodium hydrogen carbonate solution and a saturated saline solution, dried over anhydrous sodium sulfate, filtered and concentrated. The crude product was purified by flash column chromatography (hexane-ethyl acetate / 2: 1) to obtain 2.95 g of the title compound (Table-1, No. 64).

Example 13 N- [5- (4-chloro-6,7-dihydro-5H-cyclopenta [c] pi
Lidazin-3-yl) -4-cyano-2-fluorophenyl] d
Tansulfonamide

[0186]

Embedded image

N- [4-bromo-5- (4-chloro-6,7-dihydro
-5H-cyclopenta [c] pyridazin-3-yl) -2-fluorophenyl] ethanesulfonamide 3.69 g, copper cyanide
Heat and reflux 10 mL of 0.91 g dimethylformamide solution for 2.5 hours. Then, the mixture was cooled to room temperature, and an aqueous solution of iron chloride (FeCl ₃
(3.5 g, 4 mL of water) and further stirred at room temperature for 20 minutes. Water was added to the reaction mixture, and the mixture was extracted three times with ethyl acetate. The obtained organic layer was washed with saturated saline, dried over anhydrous sodium sulfate, filtered, and concentrated. The crude product was purified by flash column chromatography (hexane-ethyl acetate / 2: 1) to give the title compound (Table 1, No. 86).
32 g were obtained.

Example 14 4-chloro-3- (4-chloro-2-fluoro-5-cyclopentyl
(Oxyphenyl) -6,7-dihydro-2-oxy- [5H] -cyclo
Penta [c] pyridazine

[0189]

Embedded image

4-chloro-3- (4-chloro-2-fluoro-5-cyclopentyloxyphenyl) -6,7-dihydro-1 H -cyclopenta [c] pyridazine 1.12 g, m-chloroperbenzoic acid
(mCPBA) 10 mL of a chloroform solution of 0.90 g was stirred at room temperature for 3 hours. The reaction was terminated by adding 15 mL of saturated aqueous sodium hydrogen carbonate. The reaction mixture was extracted with ethyl acetate, and the obtained organic layer was washed with saturated saline, dried over anhydrous sodium sulfate, filtered, and concentrated. The crude product was purified by flash column chromatography (hexane-ethyl acetate /
1: 1), and the title compound (Table-1, No. 93) 0.52 g
I got

Example 15 4-chloro-3- (4-chloro-2-fluoro-5-cyclopentyl
(Oxyphenyl) -6,7-dihydro- [5H] -cyclopenta [c]
Pyridazine hydrochloride

[0192]

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4-chloro-3- (4-chloro-2-fluoro-5-cyclopentyloxyphenyl) -6,7-dihydro-1 H -cyclopenta [c] pyridazine 0.60 g of a 5% hydrochloric acid / methanol solution 2.00 g The solution was allowed to stir at room temperature for 3 hours. The reaction mixture was concentrated under reduced pressure, and the obtained crystals were filtered. The crystals were washed with hexane and dried (Table-1, No. 88) to obtain 0.59 g.
Other compounds described in Tables 1 to 5 can also be produced according to any one of Examples 1 to 15. The structure of the obtained compound was confirmed by all various spectra. Table 6 shows the physical properties and spectral data of the compounds described in Tables 1 to 5.

[0194]

[Table 1]

[0195]

[Table 2]

[0196]

[Table 3]

[0197]

[Table 4]

[0198]

[Table 5]

[0199]

[Table 6]

[0200]

[Table 7]

[0201]

[Table 8]

[0202]

[Table 9]

[0203]

[Table 10]

[0204]

[Table 11]

[0205]

[Table 12]

[0206]

[Table 13]

[0207]

[Table 14]

[0208]

[Table 15]

[0209]

[Table 16]

[0210]

[Table 17]

[0211]

[Table 18]

[0212]

[Table 19]

Next, preparation examples of the compound of the present invention will be shown. In the following, “parts” and “%” mean “parts by weight” and “% by weight”, respectively.

Formulation Example 1 Wettable powder 40 parts of the compound of the present invention described in Tables 1 and 2, 20 parts of Curve Rex # 80 (trade name, Shionogi & Co., Ltd.), kaolin clay (trade name, Tsuchiya Kaolin Co., Ltd.) ) 35 parts and 5 parts of Solbor 8070 (trade name, Toho Chemical Co., Ltd.), a higher alcohol sulfate ester surfactant, were mixed and ground uniformly to obtain a wettable powder containing 40% of the active ingredient. .

Formulation Example 2 Emulsion 20 parts of the compound of the present invention of the compounds shown in Tables 1 to 5 were dissolved in a mixed solvent consisting of 35 parts of xylene and 30 parts of N, N-dimethylformamide. An emulsion containing 20% of the active ingredient was obtained by adding 15 parts of oxyethylene surfactant Solpol 3005X (trade name, Toho Chemical Co., Ltd.).

Formulation Example 3 Flowable agent 30 parts of the compound of the present invention described in Tables 1 to 5 were mixed in advance with 8 parts of ethylene glycol and Solpol AC.
5 parts of 3020 (trade name, Toho Chemical Co., Ltd.)
After mixing and dispersing in 1 part and 56.9 parts of water, this slurry-like mixture was wet-pulverized with a Dynomill (trade name, Shinmaru Enterprises) to obtain a flowable agent containing 30% of the active ingredient.

Formulation Example 4 Granules 1 part of the compound of the present invention described in Tables 1 to 5, 1 part of clay (manufactured by Nippon Talc), 43 parts of bentonite (manufactured by Toyojun Yoko Co., Ltd.) 55
Part, and succinate surfactant Eyallol CT-1
1 part (trade name, Toho Chemical Co., Ltd.) was blended and mixed and pulverized. Further, this was extruded from a hole having a diameter of 0.6 mm using an extrusion granulator, and was extruded at 60 ° C. for 2 hours.
After drying for 1 hour, cut into length of 1-2mm,
% Granules were obtained. Next, test examples of the compound of the present invention will be described.

Test Example 1 Flooded Soil Treatment Test A resin pot with an area of 200 cm ² was filled with alluvial clay loam in paddy fields, and after fertilization, an appropriate amount of water was added and scraping was performed. , Oak, kinkashigusa and firefly were mixed. Thereafter, water was introduced to maintain a flooding depth of 3.5 cm. On the 5th day of weed sowing, the flowable agent containing the compound of the present invention obtained in Formulation Example 3 as an active ingredient was diluted with water and adjusted with a predetermined amount so that the treatment amount of the active ingredient was 10 g per 1 are. Was dropped. After that, the cultivation management was continued in the greenhouse, and the herbicidal effect was investigated on the 28th day after the chemical treatment. The results are shown in Table-7. (Compound Nos. In Table 7 correspond to the compound Nos. Described in Tables 1 to 5).

[0219]

(Equation 1) Was calculated and expressed as a herbicidal effect coefficient according to the following criteria.

[0220]

[0221]

[Table 20]

Test Example 2 Upland Soil Treatment Test Upland 200 cm ² resin vat was filled with upland volcanic ash soil, and after fertilization, the soil surface was uniformly mixed with weed seeds such as crabgrass, enokorogosa, shiroza, and sylvestris. The wettable powder containing the compound of the present invention as an active ingredient obtained in Formulation Example 1 was diluted with water and adjusted, and a predetermined amount of a small power pressurized sprayer was used so that the treatment amount of the active ingredient was 10 g per are. Sprayed uniformly on the soil surface.
After that, the cultivation management was continued in the greenhouse, and the herbicidal effect was investigated on the 28th day after the chemical treatment. The results are shown in Table-8. (Compound Nos. In Table-8 correspond to the compound Nos. Described in Tables 1 to 5.) The evaluation of the herbicidal effect was expressed in the same manner as in Reference Example 1.

[0223]

[Table 21]

Test Example 3 Upland foliage treatment test Upland 200 cm ² resin vat was filled with upland volcanic ash soil, fertilized, and then seeded with common mustard, malva asagao, barnyardgrass, and locust, and uniformly covered the soil. Thereafter, cultivation management is continued in a greenhouse, and when the growing leaf age of the test weed reaches the 1.0 to 2.0 leaf stage, the wettable powder comprising the compound of the present invention obtained in Formulation Example 1 as an active ingredient is used. The dilution was adjusted with water, and a predetermined amount was uniformly sprayed with a small power pressurized sprayer so that the treatment amount of the active ingredient was 10 g per are. On day 21 after the chemical treatment, the herbicidal effect was investigated. The results are shown in Table-9. (Compound Nos. In Table 9 correspond to the compound Nos. Described in Tables 1 to 5.) The evaluation of the herbicidal effect was expressed in the same manner as in Test Example 1.

[0225]

[Table 22]

[Effects of the Invention] The compounds of the present invention exhibit a high herbicidal effect at a low dose and have few problems such as phytotoxicity, and are useful as herbicides.

 ──────────────────────────────────────────────────続 き Continuing on the front page (72) Inventor Masayuki Tomita 1000 Kamoshita-cho, Aoba-ku, Yokohama-shi, Kanagawa Prefecture Inside the Mitsubishi Chemical Research Institute (72) Inventor Osamu Ikeda 1000 Kamoshida-cho, Aoba-ku, Yokohama-shi, Kanagawa Mitsubishi Chemical Research Institute Yokohama Research Laboratory

Claims (16)

[Claims] [Claim 1] The following general formula [I](In the above formula, X represents a halogen atom, and Y represents a hydrogen atom.
Z represents a halogen atom or a cyano group, and n and m represent
Each independently represents 0 or 1;¹Is a hydrogen atom,
Halogen atom, C₁-C₆Alkyl group or C₁-C
₆A haloalkyl group of^TwoIs a hydrogen atom, C₁-C₆Represents an alkyl group of
Is R¹Together with -KL-M- (where K is CR
^FourR^Five, CR^FourR^FiveCR⁶R⁷, Oxygen and sulfur atoms
Or C₁-C₆Indicates a nitrogen atom substituted with an alkyl group
And L is CR⁸R⁹, Oxygen atom, sulfur atom or C₁−
C₆A nitrogen atom substituted by an alkyl group represented by
R^TenR¹¹, Oxygen atom, sulfur atom or C₁-C₆Al
A nitrogen atom substituted with a kill group (the above substituent R^Four~
R¹¹Are each independently a hydrogen atom or C₁−
C₆Represents an alkyl group). However, K, L and M are the same
Sometimes oxygen, sulfur or C₁-C₆Alkyl group
Is not a nitrogen atom substituted by )
Indicates that a ring is formed, R^ThreeIs a hydrogen atom, a nitro group or -QR¹²(Where Q
Is an oxygen atom, sulfur atom, sulfinyl group, sulfonyl group
Or -NR¹³-(Where R¹³Is a hydrogen atom, C ₁-C₆
An alkyl group of C_Two-C₆An alkenyl group of C_Two-C₆
Alkynyl group, C₁-C₆Haloalkyl group of C_Two−
C₆Haloalkenyl group of C_Two-C₆The alkoxyal
Kill group, C_Two-C₆An acyl group of C₁-C₆The alkyl of
Sulfonyl group, C₁-C₆Haloalkylsulfonyl
Group, C_Two-C₆An alkenylsulfonyl group of C_Two-C₆
An alkoxycarbonyl group, a phenyl group or phenyl
Substituted with a group₁-C_ThreeRepresents an alkyl group. )
Then R¹²Is a hydrogen atom, C₁-C_TenAn alkyl group of C_Two−
C_TenAn alkenyl group of C_Two-C_TenAlkynyl group, C _Three
-C₈A cycloalkyl group, C_Four-C_TenIn the alkyl group of
Substituted cycloalkyl group, C_Four-C_Ten(Cycloa
Alkyl) alkyl group, C_Three-C₈The cycloalkenyl of
Group, C₁-C_TenHaloalkyl group of C_Two-C_TenNo haloa
Lucenyl group, C_Three-C₈Halocycloalkyl group, C_Two
-C₇A cyanoalkyl group of C_Two-C_TenThe alkoxya
Alkyl group, C_Two-C_TenAn alkylthioalkyl group of C_Two
-C_TenAlkylsulfonylalkyl group of C_Two-C₆of
Acyl group, C_Three-C₆An oxoalkyl group, C₁-C₆
Alkylsulfonyl group of C₁-C₆The haloalkyls
Ruphonyl group, C_Two-C₆An alkenylsulfonyl group,
C substituted with a phenyl or phenyl group₁-C_ThreeArchi
Group, a 3-6 membered heterocyclic group (the ring is
Containing a hydrogen atom, a sulfur atom and / or a nitrogen atom), 3
A 6-membered heterocyclic group wherein the ring comprises 1-2 oxygen atoms, sulfur
Containing an atom and / or a nitrogen atom)
C₁-C_ThreeAn alkyl group represented by the following general formula [II]:Or a group represented by the following general formula [III]:(Where R¹⁴Is a hydrogen atom or C₁-C_FourAlkyl group
W is an oxygen atom, a sulfur atom or -NR¹⁶− (Expression
Medium, R¹⁶Is a hydrogen atom or C₁-C_FourRepresents an alkyl group of
You. ) And R^FifteenIs a hydrogen atom, C₁-C₆The alkyl of
Group, C_Two-C₆An alkenyl group of C_Two-C₆Alkini
Group, C_Three-C₆A cycloalkyl group, C_Four-C_TenNo
A cycloalkyl group substituted with an alkyl group,_Three-C₆of
Cycloalkenyl group, C₁-C₆Haloalkyl group of C
_Two-C₆Haloalkenyl group of C _Three-C₆Halocyclo
Alkyl group, C_Two-C_FiveA cyanoalkyl group of C_Two-C
₆An alkoxyalkyl group of C_Two-C₆The alkylthio
Alkyl group, C_Two-C₆Alkylsulfonylalkyl of
Group, C_Three-C₆An oxoalkyl group, C_Three-C₇Reed
Roxyalkyl group, C_Three-C₇Alkoxycarboni
Alkyl, phenyl, phenyl-substituted C
₁-C_ThreeAnd a 3-6 membered heterocyclic group (the ring is
1-2 oxygen, sulfur and / or nitrogen atoms
) Or a 3-6 membered heterocyclic group (the ring is
1-2 oxygen, sulfur and / or nitrogen atoms
C) substituted with₁-C_ThreeRepresents an alkyl group of
You. Also, R^FifteenIs that W is -NR¹⁶-Indicates W
Together with 1-2 nitrogen atoms and / or 0-1
It may form a 5-6 membered heterocyclic group containing an oxygen atom.
No. ). R¹², R¹³Or R^FifteenIs a phenyl group,
C substituted with a phenyl group₁-C_ThreeAn alkyl group of 3-
A 6-membered heterocyclic group (the ring may have 1-2 oxygen atoms,
Containing a hydrogen atom and / or a nitrogen atom), or 3-
6-membered heterocyclic group (wherein the ring has 1-2 oxygen atoms, sulfur
Containing an atom and / or a nitrogen atom)
C₁-C_ThreePhenyl group and
And heterocyclic groups are 1-3 identical or different halogen atoms.
Child, C₁-C_FourAn alkyl group, a trifluoromethyl group,
C₁-C_FourAn alkoxy group of C_Two-C_FiveAcyloxy
Group, C₁-C_FourAn alkylthio group of C₁-C_FourArchi
Rusulfonyl group, nitro group, cyano group or C_Two-C_Five
May be substituted with an alkoxycarbonyl group. )
Is shown. 3-substituted phenyl-4-halopypyr
Dazine derivatives. R ¹ represents a hydrogen atom, a C ₁ -C ₆ alkyl group or a C ₁ -C ₆ haloalkyl group; R ² represents a hydrogen atom, a C ₁ -C ₆ alkyl group; Together with ^{1 is} -KL-M- (where K is CR ⁴ R ⁵ , CR ⁴ R
⁵ CR ⁶ R ^{7 represents} an oxygen atom, a sulfur atom or a nitrogen atom substituted by a C ₁ -C ₆ alkyl group, and L represents CR ⁸ R
⁹ represents a nitrogen atom substituted with an oxygen atom, a sulfur atom or a C ₁ -C ₆ alkyl group, and M is CR ¹⁰ R ¹¹ , substituted with an oxygen atom, a sulfur atom or a C ₁ -C ₆ alkyl group. And a nitrogen atom (each of the substituents R ^{4 to} R ¹¹ independently represents a hydrogen atom or a C ₁ -C ₆ alkyl group). However, K, is not L and M are simultaneously oxygen atom, a nitrogen atom substituted by a sulfur atom or an alkyl group of C ₁ -C _6. 2. The 3-substituted phenyl-4 according to claim 1, which forms a ring represented by the formula:
-Halopyridazine derivatives. 3. A method according to claim 1, wherein R ² is -K-LM- together with R ¹ , wherein K is CR ⁴ R ⁵ or CR ⁴ R ⁵ CR ⁶ R ⁷ or an oxygen atom, and L is CR ⁸ R ⁹ or M represents a CR ¹⁰ R ¹¹ or an oxygen atom (each of the above substituents R ^{4 to} R ¹¹ independently represents a hydrogen atom or a C ₁ -C ₆ alkyl group), provided that K represents , L and M are not oxygen atoms at the same time.), The 3-substituted phenyl-4-halopyridazine derivative according to claim 1, wherein -K-L-M- (wherein with wherein R ² is R ^1, K represents a ^{CR 4 R 5, CR 4 R} 5 CR 6 R 7, L
Represents a CR ⁸ R ^9, M represents a CR ¹⁰ R ¹¹ (Examples of the substituents R ⁴ to R ^11, a hydrogen atom or an alkyl group of C ₁ -C ₆ independently). 3) wherein the carbon ring represented by the formula (3) is formed.
Substituted phenyl-4-halopyridazine derivatives. 5. R^ThreeIs a hydrogen atom, a nitro group or -Q
R¹²(Wherein Q is an oxygen atom or -NR¹³-(Where R
¹³Is a hydrogen atom, C_Two-C₆An acyl group of C₁-C₆No
Alkylsulfonyl group or C_Two-C₆The alkoxycal
Represents a bonyl group. ) And R¹²Is a hydrogen atom, C₁-C
_TenAn alkyl group of C_Two-C_TenAn alkenyl group of C_Two-C
_TenAlkynyl group, C_Three-C₈A cycloalkyl group, C
_Three-C₈A cycloalkenyl group of C₁-C_TenNo haloal
Kill group, C_Two-C_TenHaloalkenyl group of C_Two-C_Tenof
Halocycloalkyl group, C_Two-C₇Of cyanoalkyl
Group, C_Two-C_TenAn alkoxyalkyl group of C_Three-C₆of
Oxoalkyl group, C₁-C ₆Alkylsulfonyl of
Group substituted with a phenyl group₁-C_ThreeAn alkyl group of
3-6 membered heterocyclic group (the ring contains 1-2 oxygen atoms)
Has), a 3-6 membered heterocyclic group (the ring is
Substituted with a carbon atom)₁-C_ThreeThe alkyl of
A group represented by the following general formula [II]Or a group represented by the following general formula [III]:(Where R¹⁴Is a hydrogen atom or C₁-C_FourAlkyl group
W is an oxygen atom or -NR¹⁶-(Where R¹⁶Is
Hydrogen atom or C₁-C_FourRepresents an alkyl group. )
Then R^FifteenIs a hydrogen atom or C₁-C₆Represents an alkyl group of
You. ). )
The 3-substituted phenyl-4-halopyridazine of claim 1.
Derivatives. Wherein R ³ is a hydrogen atom, a nitro group or -Q
R ¹² (wherein, Q represents an oxygen atom or -NR ¹³ - (wherein, R
^{And 13} represents a hydrogen atom, a C ₁ -C ₆ alkylsulfonyl group or a C ₂ -C ₆ alkoxycarbonyl group. ) Wherein R ¹² is a hydrogen atom, a C ₁ -C ₁₀ alkyl group, C _2-
Alkenyl C _10, alkynyl group of C ₂ -C _10, C ₃
Cycloalkyl groups -C _8, C ₁ -C ₁₀ haloalkyl group, C ₂ -C haloalkenyl group _10, cyanoalkyl group _{C 2 -C 7, C 2 -C} 10 alkoxyalkyl group, C
₃ oxoalkyl group -C _6, an alkylsulfonyl group having C ₁ -C _6, alkyl group of C ₁ -C ₃ substituted with a phenyl group, 3-6-membered Hajime Tamaki (said ring, 1-2 3-6 membered heterocyclic group (containing 1-oxygen atom)
A C ₁ -C ₃ alkyl group substituted with 2 oxygen atoms), represented by the following general formula [II]: Or a group represented by the following general formula [III]: (Wherein, R ¹⁴ represents a hydrogen atom or a C ₁ -C ₄ alkyl group, W represents an oxygen atom or —NR ¹⁶ — (wherein, R ¹⁶ represents a hydrogen atom or a C ₁ -C ₄ alkyl group) ), And R ¹⁵ represents a hydrogen atom or a C ₁ -C ₆ alkyl group.). The 3-substituted phenyl-4-halopyridazine derivative according to claim 1, wherein 7. R^ThreeIs -QR¹²(Wherein Q represents an oxygen atom
And R¹²Is C₁-C _TenAn alkyl group of C_Two-C_TenNo
Lucenyl group, C_Two-C_TenAlkynyl group, C_Three-C₈of
Cycloalkyl group, C₁-C_TenHaloalkyl group of C_Two
-C_TenHaloalkenyl group of C_Two-C₇Cyano Archi
Group, C_Two-C_TenAn alkoxyalkyl group of C_Three-C₆
An oxoalkyl group, a 3-6 membered heterocyclic group (the ring is 1
-Containing 2 oxygen atoms), 3-6 membered heterocyclic group
(The ring contains 1-2 oxygen atoms)
C₁-C_ThreeOr an alkyl group represented by the following general formula [II]:Represents a group represented by )
3. The 3-substituted phenyl-4-halopyridazine derivative according to 1 above.
body. 8. R^TwoIs R¹Together with -KL-M- (formula
Medium, K is CR^FourR^FiveOr CR^FourR^FiveCR⁶R⁷Shows
And L is CR⁸R⁹And M is CR^TenR¹¹Indicates (on
The substituent R^Four~ R¹¹Are independent of each other
Child or C₁-C₆Represents an alkyl group). )
R^ThreeIs a hydrogen atom, a nitro group or -QR¹²(Where Q is
Oxygen atom or -NR ¹³-(Where R¹³Is a hydrogen atom, C
₁-C₆Alkylsulfonyl group or C_Two-C₆No
Indicates a alkoxycarbonyl group. ) And R¹²Is hydrogen field
Child, C₁-C_TenAn alkyl group of C_Two-C_TenThe alkenyl of
Group, C_Two-C_TenAlkynyl group, C_Three-C₈Cycloa
Alkyl group, C₁-C_TenHaloalkyl group of C_Two-C_Tenof
Haloalkenyl group, C_Two-C₇A cyanoalkyl group of C
_Two-C_TenAn alkoxyalkyl group of C_Three-C₆Oxo
Alkyl group, C₁-C₆Alkylsulfonyl group,
C substituted with a nyl group₁-C_ThreeAlkyl group of 3-6 members
A heterocyclic group having 1 to 2 oxygen atoms
), A 3-6 membered heterocyclic group (wherein the ring comprises 1-2 oxygen atoms)
Substituted with₁-C_ThreeAn alkyl group of
The following general formula [II]Or a group represented by the following general formula [III]:(Where R¹⁴Is a hydrogen atom or C₁-C_FourAlkyl group
W is an oxygen atom or -NR¹⁶-(Where R¹⁶Is
Hydrogen atom or C₁-C_FourRepresents an alkyl group. )
Then R^FifteenIs a hydrogen atom or C₁-C₆Represents an alkyl group of
You. ). )
The 3-substituted phenyl-4-halopyridazine of claim 1.
Derivatives. -K-L-M- (wherein with 9. R ² is R ^1, K represents a CR ⁴ R ⁵ or ^{CR 4 R 5 CR 6 R 7} , L represents a CR ⁸ R ^9, M Represents a CR ¹⁰ R ¹¹ (each of the above substituents R ^{4 to} R ¹¹ independently represents a hydrogen atom or a C ₁ -C ₆ alkyl group). ³ is -QR ¹² (wherein, Q is an oxygen atom, R ¹² is an alkyl group of C ₁ -C _10, C ₂ -C
₁₀ alkenyl groups, C ₂ -C ₁₀ alkynyl groups, C _3-
Cycloalkyl group C _8, C ₁ -C ₁₀ haloalkyl group, C ₂ -C haloalkenyl group _10, cyanoalkyl group _{C 2 -C 7, C 2 -C} 10 alkoxyalkyl group, C
₃ oxoalkyl group -C _6, 3-6 membered Hajime Tamaki (wherein the ring contains 1-2 oxygen atoms), 3-6 membered Hajime Tamaki (said ring, 1-2 A C ₁ -C ₃ alkyl group substituted with a compound of the formula [I
I] Represents a group represented by The 3-substituted phenyl-4-halopyridazine derivative according to claim 1, wherein 10. The 3-substituted phenyl-4-halopyridazine derivative according to any one of claims 1 to 9, wherein Y is a halogen atom. 11. The following general formula [V] or [V ′] (Wherein, Y, Z, R ¹ , R ² and R ³ are the same as defined in claim 1) or a 3-substituted phenyl-4-hydroxypyridazine derivative or 3-substituted phenylpyridazine-4- On derivatives. 12. The following general formula [VI] or [VI ′](In the above formula, k represents 1-2, R^ThreeIs a hydrogen atom, nitro
B group or -QR ¹²(Wherein Q is an oxygen atom or-
NR¹³-(Where R¹³Is a hydrogen atom, C₁-C₆Archi
Rusulfonyl group or C_Two-C₆Alkoxycarboni
Represents a hydroxyl group. ) And R¹²Is a hydrogen atom, C₁-C_Tenof
Alkyl group, C_Two-C_TenAn alkenyl group of C_Two-C_Tenof
Alkynyl group, C_Three-C₈A cycloalkyl group, C₁−
C_TenHaloalkyl group of C_Two-C_TenHaloalkenyl of
Group, C_Two-C₇A cyanoalkyl group of C_Two-C_TenAl
Coxyalkyl group, C_Three-C₆An oxoalkyl group, C
₁-C₆Substituted with an alkylsulfonyl group or a phenyl group
C₁-C_ThreeAnd a 3-6 membered heterocyclic group (the
The ring contains 1-2 oxygen atoms), 3-6 membered
A cyclic group (the ring contains 1-2 oxygen atoms)
Transformed C₁-C_ThreeRepresents an alkyl group. ). )
12. The 3-substitution according to claim 11, wherein
Phenyl-4-hydroxypyridazine derivative or 3-
Substituted phenylpyridazin-4-one derivatives. 13. The 3-substituted phenyl-4 according to claim 11, wherein Y is a halogen atom.
-Hydroxypyridazine derivatives or 3-substituted phenylpyridazin-4-one derivatives. 14. An agricultural chemical comprising the 3-substituted phenyl-4-halopyridazine derivative according to claim 1 as an active ingredient. 15. The pesticide according to claim 14, which is a herbicide. 16. The pesticide according to claim 15, which is a herbicide for paddy rice.