WO1999008999A1

WO1999008999A1 - Arylacetamide derivatives and bacteriocides for agricultural and horticultural use

Info

Publication number: WO1999008999A1
Application number: PCT/JP1998/003598
Authority: WO
Inventors: Katsumi Masuda; Tsuyoshi Asahara; Junko Suzuki; Atsushi Yasuda; Katsumi Furuse; Kazuo Kumakura; Ichiro Miura; Norimichi Muramatsu
Original assignee: Kumiai Chemical Industry Co., Ltd.; Ihara Chemical Industry Co., Ltd.
Priority date: 1997-08-13
Filing date: 1998-08-12
Publication date: 1999-02-25
Also published as: AU8647998A

Abstract

Arylacetamide derivatives represented by general formula (1) and bacteriocides for agricultural and horticultural use (wherein A is Xn-substituted phenyl or the like; R1 is halogeno, C¿1?-C6 alkoxy or the like; R?2 and R3¿ are each alkyl or the like; Q is cyano or the like; X is alkyl, alkoxy, halogeno, haloalkyl or the like; and n is an integer of 1 to 3). The bacteriocides not only exhibit a high control effect against rice blast, apple scab and so on, but also are characterized by causing no chemical damage to crop plants and being excellent in residual effect and rain resistance, thus being suitable for agricultural and horticultural use.

Description

Specification

Aryl acetate amide derivatives and fungicides for agricultural and horticultural use

TECHNICAL FIELD The present invention relates to an aryl amide derivative which is a novel compound not described in any literature, and a fungicide for agricultural and horticultural use containing the same as an active ingredient.

Background art

Until now, 2- (1-bromophenylacetylacetylamino) isobutyric acid has been known as an intermediate for producing nitrogen-containing cyclic compounds (Japanese Patent Application Laid-Open No. 8-151364). Its usefulness as an agent is not known at all.

In recent years, the use of agricultural and horticultural fungicides has led to the emergence of drug-resistant bacteria, and existing drugs may not show sufficient fungicidal activity. In addition, new fungicides that can efficiently control harmful bacteria at a low concentration due to environmental problems are required.

The present inventors synthesized various novel aryl acetate amide derivatives to develop a drug having a bactericidal activity superior to conventionally known bactericides, and examined the physiological activities thereof. However, they have found that they have an excellent bactericidal activity against rice blast and the like and do not cause any harm to useful crops, and have completed the present invention.

Disclosure of the invention

That is, the present invention provides: (1) a general formula [1]

R ¹ 0 R ²

I II I " _n

A- CH-C-NH-CQ ^L1J

R3

[In the formula, A represents X _n phenyl group substituted by, which may be substituted also a 2-naphthyl group by 1 one naphthyl group or X _n but it may also be substituted by X _n, X is a halogen atom, C i-C6 alkyl group, C2-C6 alkenyl group, C2-C6 alkynyl group, C3-C6 cycloalkyl group, C1-C4 haloalkyl group, hydroxy group, Ci-C6 alkoxy Group, C2-C6 alkenyloxy group, C2-eg alkynyloxy group, C3-C6 cycloalkyloxy group, Ci-Czi halo Alkoxy group, phenoxy (in which the group C 1 through C ₆ alkyl group, C 1 through C 4 Haroa alkyl group, C i~C ₆ alkoxy group, Shiano group may be by connexion substituted nitro group or a halogen atom ), Ci-C6 alkylthio group, Ci-C4 haloalkylthio group, phenylthio group (the group is a Ci-C6 alkyl group, Ci-C4 haloalkyl group, CiC alkoxy group) , A cyano group, a nitro group or a halogen atom.), An amino group, a C 6 -C 6 alkylamino group, a C 丄 -C 6 dialkylamino group, a cyano group, a phenyl group (The group may be substituted by a C1-C6 alkyl group, a C1-C4 haloalkyl group, a Ci-C6 alkoxy group, a cyano group, a nitro group or a halogen atom.), An aralkyl group (the group Is a C 1 -C ₆ alkyl group, a C 1 -C 4 haloalkyl group, a C i -C ₆ alkoxy May be substituted by a cyano group, a cyano group, a nitro group or a halogen atom.), C; [-C ₆ alkylcarbonyl group, benzoyl group (the group is a C 1 -C 6 alkyl group, a C i -C 4 halo group) Alkyl, C i -C 6 alkoxy, cyano, nitro or halogen atoms.), Or C i -C 6 alkoxycarbonyl, wherein n is 1-3 Represents an integer, and R ¹ is a halogen atom, a CCe alkoxy group, a C3-C6 cycloalkoxy group, a C1-C4 haloalkoxy group, a C1-C6 alkylthio group, a C1-C6 alkylamino group or represents C 1 through C 6 Jiarukiruami amino group, R ² represents a C 1 through C fi alkyl group, C 3 to C 6 consequent opening alkyl or C i~C 4 haloalkyl group, R 3 is c 2 to C ₆ alkyl group, C ₂ -C 6 alkenyl group, the C ₃ -C ₆ cycloalkyl (in which the group C: -C ₆ alkyl group, By the androgenic atom connexion may be substituted.) Or C 1 through C 4 haloalkyl group, or R ² and R ³ are bonded to are 5- to 7-membered cycloalkyl group ring with the carbon atom (in which May be substituted by a C i Ce alkyl group or a halogen atom. Wherein Q is a cyano group or a group C OR ⁴ (R ⁴ is a C i -C 6 alkyl group, a C 3 -C 6 cycloalkyl group, a C 1 -C 4 haloalkyl group, a C i -C 6 alkoxy group , C 2 to C s Arukeniruokishi groups, C 2 to C 6 Arukiniruokishi groups, C 3 to C 6 cycloalkyl Ruokishi group, amino groups, C丄-C 6 alkylamino cyano group or a C 1 ~ C ₆ dialkyl amino Represents a group). And (2) an agricultural and horticultural killing agent containing these aryl amide derivatives as active ingredients. It is a fungicide.

First, terms used in the present specification will be described below. In this specification, for example, notations such as “C i to C ₆ ” indicate that the number of carbon atoms of the subsequent substituent is high, and in this case, it is 1 to 6.

The C〜 to C ₆ alkyl group refers to a linear or branched alkyl group, for example, a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a sec-butyl group. Group, tert-butyl group, n-pentyl group, isopentyl group, neopentyl group, n-hexyl group, isohexyl group, 3,3-dimethylbutyl group and the like.

The CQ-C6 cycloalkyl group includes, for example, a cyclopropyl group, a cyclopentyl group, a cyclohexyl group and the like.

The C-C4 haloalkyl group represents a linear or branched alkyl group substituted by a halogen atom, for example, a fluoromethyl group, a chloromethyl group, a difluoromethyl group, a dichloromethyl group, a trifluoromethyl group. And a pentafluoroethyl group.

The C 2 to C ₆ alkenyl group, a straight-chain or branched alkenyl group, for example if a vinyl group, 1. One propenyl group, Ariru group, isopropenyl group, 1 Buteniru group, 2-butenyl And the like.

The C 2 to C ₆ alkynyl group, a linear or branched alkynyl group, For example Echiniru group, 1 one propynyl group, 2 _ propynyl group, 1-Petit group, 2-Bed ethynyl group, Examples thereof include a 3-butynyl group, a 4-methyl-1-pentynyl group, and a 3-methyl-1-pentynyl group.

An aralkyl group is a linear or branched C ι ~ substituted by an aryl group.

Represents a C3 alkyl group, such as a benzyl group, a phenethyl group, a 1-naphthylmethyl group, and a 2-naphthylmethyl group.

Halogen atom means fluorine atom, chlorine atom, bromine atom and iodine atom.

The C丄~ C ₆ alkoxy group, a straight-chain or branched alkoxy group, for example if main butoxy group, an ethoxy group, n- propoxy group, isopropoxy group, n- butoxy sheet group, isobutoxy group, sec —Butoxy group, tert —butoxy group, n-pen Tiloxy, isopentyloxy, n-hexyloxy and the like can be mentioned.

The C2-C6 alkenyloxy group represents a linear or branched alkenyloxy group, and examples thereof include an aryloxy group, an isopropyloxy group, a 2-butenyloxy group and the like.

The C 2 -C ₆ alkynyloxy group represents a straight-chain or branched alkynyloxy group, and examples thereof include a 2-propynyloxy group, a 2-butynyloxy group, and a 3-butynyloxy group. .

Examples of the CQ-C6 cycloalkyloxy group include a cyclopropyloxy group, a cyclopentyloxy group, a cyclohexyloxy group, and the like.

The C-C4 haloalkoxy group represents a straight-chain or branched-chain alkoxy group substituted by a halogen atom, for example, a fluoromethoxy group, a difluoromethoxy group, a trifluoromethoxy group, a pentafluoroethoxy group. Group, etc.

C- _6- alkylthio refers to a linear or branched alkylthio, such as methylthio, ethylthio, n-propylthio, isopropylthio, n-butylthio, isobutylthio, sec-butylthio; Tert-butylthio group, n-hexylthio group and the like.

The C-C4 haloalkylthio group represents a straight-chain or branched-chain alkylthio group substituted by a halogen atom, such as fluoromethylthio, difluoromethylthio, trifluoromethylthio, and pentafluoro. And a loethylthio group.

C; [A -C ₆ Arukiruamino group, a linear or branched Arukiruami amino group and table, for example Mechiruamino group, Echiruami amino group, n - propyl group, isopropyl Piruami amino group, n- Puchiruami amino group, Examples include an isobutylamino group, a sec-butylamino group, a tert-butylamino group, and an n-hexylamino group.

The C-C ₆ dialkylamino group includes, for example, a dimethylamino group, a getylamino group, a dipropylamino group, a dibutylamino group and the like. The C i -C ₆ alkylcarbonyl group refers to a linear or branched alkyl carbonyl group, and examples thereof include an acetyl group, a propionyl group, a butyryl group, and an isoptyryl group.

The C 1 -C 6 alkoxycarbonyl group represents a linear or branched alkoxycarbonyl group, such as a methoxycarbonyl group, an ethoxyquin carbonyl group, an n-propoxycarbonyl group, an isopropoxycarbonyl group, —Butoxycarbonyl group, isobutoxycarbonyl group, sec —butoxycarbonyl group, tert —butoxycarbonyl group, n—pentyloxycarbonyl group, n-hexyloxy group, etc. it can.

Some of the compounds of the present invention represented by the general formula [1] have one or more asymmetric carbon atoms in the molecule, and such compounds have optical isomers. Exists. Pure individual diastereomers, enantiomers and mixtures thereof are also included in the compounds of the present invention.

Preferred compounds of the present invention compound represented by the general formula [1], A is at Therefore substituted Fuweniru group or a 2-naphthyl group X _n, R ¹ is a chlorine atom, bromine atom, main butoxy group or R ² is a methyl, ethyl or n-propyl group, and R 3 is an ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-methylthio group. Butyl, cyclopropyl, 1-methylcyclopropyl, cyclobutyl, cyclopentyl or dichloromethyl; Q is cyano, methoxycarbonyl, ethoxycarbonyl or acetyl; X is fluorine; Chlorine atom, bromine atom, iodine atom, methyl group, ethyl group, isopropyl group, isobutyl group, tert-butyl group, trifluoromethyl group, methoxy group, ethoxy group Group, n-propoxy group, isopropoxy group, difluoromethyoxy group, trifluoromethyoxy group, phenoxy group, methylthio group, ethylthio group, isopropylthio group, dimethylamino group, getylamino group or phenyl group, and n is 1 to Compounds that are integers of 2 can be mentioned.

Next, specific examples of the compound of the present invention represented by the general formula [1] are shown in Tables 1 to 22, and are not limited thereto. O

(Table 2)

11 Rl R2 R3 Q

2-OCF 0Q Br CHQ C3H7-1- COCH

2-OCF oQ OCHQ 0 CHQ C4H9-t CN

2-OCFQ OCH 0Q CH ₃ CqH ₇ -i COOCHQ

2-OCFQ OCHQ CH3 C3H7-1 COCH3

2-OCHQ Br CH3 C3H7- 1 COOCHQ

2-OCHQ Br 0 CH ₇ -i COCHQ

2-OCH3 OCH3 CH ₃ C ₃ H ₇ -i COOCH3

2-OCH3 OCH3 CH ₃ C ₃ H ₇ -i COCH3

3, 4, 5- (OCHQ) Q OCHQ 0 CHQ C3H7— i CN

3.4- (OCHQ) OCHQ CHQ C3H7-1 CN

3, 4- (CI) 2 OCH3 CH3 C3H7-I COOCH 0Q

3, 4- (CI) 2 OCHQ CH 0Q C3H ₇ -i CN

3, 4- (CD? OCHQ CH 0Q C4Hq-t CN

3, 4-(CI) 2 OCHQ 0 CHQ CqH ₇ -i COCHQ

3- Br Br CH3 C3H7-1 COOCHQ

3- Br Br CH ₃ C3H7-1 COCH3

3- Br OCH3 CH ₃ C4H9- t CN

3-Br OCH3 CH ₃ C ₃ H ₇ -i COOCH3

3-Br OCH3 CH ₃ C3H7- i COCH3

3-CF3 Br CH ₃ C4H9- t CN

3-CF3 Br CH ₃ C ₃ H ₇ -i CN

3-CF3 Br CH ₃ C ₃ H ₇ -i COCH3

3-CF3 OCH3 CH ₃ C ₄ H ₉ -t CN

3-CF3 OCH3 CH ₃ C3H7-1 CN Fine

GO

o o 2 x

M 3 s s Q s s s s s s s s s s s s s s s s s s s s s s s s s s

^§ § Q § ^S 8 § o ^S S § o § cz § § SS 8 § QQSSQ § SS o Q § SS § S

(Table 4)

C3H7-1 COOCH

3-0CH ₃ Br CH CqH ₇ -i COCH

3-0CH ₃ OCH3 CHo C ₄ Hg-t CN

3-OCH3 OCH3 CHQ CQHT- I COOCH3

3-OCH3 OCH3 CH ₃ C3H7-i COCH3

4- Br Br CH ₃ C4H9-t CN

4-Br Br CHQ CQH ₇ -I COOCHQ

4-Br Br CH ₃ C3H7-1 COCH3

4-Br ^{υ 1} b CHo CoH7-i CN

4-Br OCH3 CHo CH ₂ CH = CH ₂ CN

4-Br OCH CHQ CN

CQH ₇ -I COOCpHc

4-Br 0CH3 CH ₃ C ₃ H ₇ -i COCH3

4-Br 0C ₃ H ₇ CH ₃ C3H7- i CN

4-Br SCH3 CH ₃ C ₄ Hg-t CN

4-Br OCH3 C2H5 C2H5 COCH3

4-C4H9-1 F CH ₃ C3H7-i CN

4-C4H9- 1 OCH3 CH ₃ C ₃ H _r i CN

4-C ₄ Hg-t OCH3 (CH ₂ ) ₅ -CN

4-C ₄ Hg-t OCH3 CH ₃ C ₂ H ₅ CN

4-C ₄ Hg-t OCH3 CH ₃ C3H7 CN

(Table 5)

R2 R3

4-C ₄ Hg-t OCH3 CH ₃ CF ₃ C

4-C ₄ Hg-t OCH3 CH ₃ C4H9-s CN

4-C ₄ Hg-t OCH3 CH ₃ C ₄ -i CN

4-C ₄ Hg-t OCH3 CH ₃ C4H9-t CN

4-C ₄ Hg-t OCH3 C2H5 C3H7 CN

4-C ₄ Hg-t OCH3 C2H5 C3H7-i CN

4-C ₄ Hg-t OCH3 CH ₃ C ₃ H ₇ -i COCH3

4-C ₄ Hg-t OCH3 C2 C ₂ H ₅ COCH3

4-CF3 Br CH ₃ C ₄ Hg-t CN

4-CF3 Br CH ₃ CHC1 ₂ CN

4-CF3 Br ^C 2 ^H 5 ^C 2 ^H 5 CN -CF3 Br (CH ₂ ) ₅ -CN -CF3 Br CH ₂ C1 C3H7-i CN -CF3 Br CH ₃ CH ₂ CH = CH ₂ CN

4-CF3 Br CH ₂ C1 2H5 CN

4-CF3 Br CH ₃ -O CN

4-CF3 Br CH ₃ CF ₃ CN

CHq

4-CF ₃ Br CH ₃ CN

_{_{4- F3 Br CH 3 C 4 -i}} CN -CF3 Br CH 3 - 1 CN

F

4-CF3 Br CH ₃ CN

4-CF3 Br-(CH ₂ ) ₄ -CN

4-CF3 Br CN 4-CF3 Br CH ₃ C ₃ H ₇ -i COOCH3

4-CF ₃ Br CH ₃ C ₃ H ₇ -i COCH3 (Table 6)

R1 _R 2 R3 Q

^Λ π

4-ti ci CH ₇ -i CN

4-CF M (C * ^-1 H ¹ * Q) O CHQ C H7-i CN

4-CFQ NHCH CHQ C / iHq-t CN

4-CFo 0 CHQ CN

4-CF ₃ 0C ₂ H ₅ CH ₃ C3H7-1 CN

4-CF ₃ OCH3 CH ₃ C3H7-i CN

4-CFQ OCHQ CHQ C lHo-t CN

4-CFQ O υCHQ CHQ CHC12 CN

4- CF ₃ OCH3 ^C 2 ^H 5 ^C 2 ^H 5 then N

-CF ₃ 0CH ₃ CH ₂ C1 C ₃ H ₇ -i CN

4-CF3 OCH3 CH ₃ CH ₂ CH = CH ₂ CN

4-CF3 OCH3 CH ₃ CF ₃ CN

4-CF3 OCH3 CH ₃ C4H9-1- CN

4-CF3 OCH3 CH ₃ CN

F

4-CF3 OCH3 CH ₃ CN

4-CF ₃ OCH3-(CH ₂ ) ₄ -CN 4-CF ₃ OCH3 CN

4-CF3 OCH3 CH ₃ C ₃ H ₇ -C00CH ₂ C≡CH (Table 7)

χ _η Rl R2 R3 Q

4-CF3 OCH3 CH ₃ C ₃ H ₇ -i C00CH2CH = CH ₂

4-CF3 OCH3 CH ₃ C ₃ H ₇ -i COOCH3

4-CF3 OCH3 CH ₃ C ₃ H ₇ -i COCF3

4-CF3 OCH3 C ₂ H ₅ C2H5 COCH3

4-CF3 OCH3 CH ₃ C ₃ H ₇ -i COCH3

4-CF3 OCH3 CH ₃ C ₃ H ₇ -i CO (CH ₃ ) ₂

4-CF3 OCH3 CH ₃ C ₃ H ₇ -icco]

4-CF3 CI CH ₃ C3H7-1 CN

4-CF3 CI CH ₃ C ₃ H _r i COCH3

4-CF3 o CH ₃ C ₃ H ₇ -i CN

4-CF3 OC3H7 CH ₃ C3H7-i CN

4-CF3 SC2H5 CH ₃ C3H7- i CN

4-CF3 SC2H5 CH ₃ C4H9- t CN

4-CF3 SCH ₃ CH ₃ C ₃ H ₇ -i CN

4-CF3 SCH3 C2H5 C2H5 CN

4-CH2-0CH3 CH ₃ C ₃ H ₇ -i CN

_{_{4-C1 Br C 2 H 5}} C2H5 CN

4- CI Br (CH ₂ ) ₅ -CN

4- CI Br CH ₃ C ₃ H ₇ -i CN

4- CI Br CH ₃ CH ₂ CH = CH ₂ CN

4-Cl Br CH2CI C2 ^H 5 CN

4-CI Br CH ₃ Ό CN

4-Cl Br CH ₃ CF3 CN

4-Cl Br CH ₃ C4H9-t CN

4-Cl Br CH ₃ CN (Table 8)

Rl R2 R3

F

4-CI Br CH ₃ CN 4-CI Br. (CH ₂ ) ₄ -CN

4-CI Br CN

4-C1 Br CH ₃ C3H7- i C00CH ₃

4-CI Br CH ₃ C ₃ H ₇ -i COCH3

4- CI CI CH ₃ C ₃ H ₇ -i CN

4-C1 F CH ₃ C ₃ H ₇ -i CN

4-then i (then J 2

3H7 1

4-CI NHCH ₃ CH ₃ C ₃ H ₇ -i CN

4- CI NHCH ₃ CH ₃ C4H9-t CN

4-C1 o CH ₃ C ₃ H ₇ -i CN

4- CI 0CHF2 CH ₃ C ₃ H ₇ -i LN

4-CI 0C ₂ H ₅ CH ₃ C ₃ H ₇ -i CN

4 4 1 n ⁿ 3 CQH7-1 CN

4- CI 0CH ₃ CH ₃ C ₄ H ₉ -t CN

4- CI 0CH3 CH ₃ CHC1 ₂ CN

4-C1 0CH3 C2 C2H5 CN

4- CI 0CH3 (CH ₂ ) ₅ -CN

4- CI 0CH3 CH ₂ C1 C ₃ H ₇ -i CN

4- CI 0CH3 CH ₃ CH ₂ CH = CH ₂ CN

4-C1 0CH3 CH ₂ C1 C2H5 CN

4-CI 0CH3 CH ₃ CN

O

4-CI 0CH3 CH ₃ CF ₃ CN

CH

4- CI 0CH3 CH ₃ CN

4- CI 0CH3 CH ₃ C4H9-1 CN

4- CI 0CH3 CH ₃ CN (Table 9)

, N R2 R3

F

4-C1 0CH ₃ CH ₃ CN 4-CI OCH3. (CH ₂ ) ₄ -CN

4-CI OCH3 CH ₃ C ₃ H ₇ -i C00CH ² C≡CH

4- CI OCH3 CH ₃ C ₃ H ₇ -i C00CH ₂ CH = CH ₂

4-C1 OCH3 CH ₃ C ₃ H ₇ -i COOCH3

4- CI OCH3 CH ₃ C ₃ H ₇ -i COCF3

4-CI OCH3 C2 C ₂ H ₅ COCF3

4-C1 OCH3 CH ₃ C ₃ H ₇ -i COCH3

4- CI OCH3 CH ₃ C ₃ H ₇ -i C0N (CH ₃ ) ₂

4-C1 U shi 3 ^H 7 ¹ shi

Three

4-CI 0 CH ₃ C ₃ H ₇ -i CN

4- CI 0C ₃ H ₇ CH ₃ C ₃ H ₇ -i CN

_{_{_{4- CI SC 2 H 5 CH 3}}} C3H7 - i CN

4-CI OCH3 CH ₃ C4H9- COCH3

4- CI SCH ₃ CH ₃ C ₃ H ₇ -i CN

4- CI SCH3 CH ₃ C ₄ H ₉ -t CN

4-C1 OCH3 C2H5 C2H5 COCH3

4-CN Br CH ₃ C ₃ H ₇ -i CN

4-CN OCH3 CH ₃ C ₃ H ₇ -i CN

4-CN SCH3 CH ₃ C ₃ H ₇ -i CN

4-COOCH3 OCH3 CH ₃ C ₃ H ₇ -i CN

O H3 H ₃ C3H7- i CN

4-COCH3 OCH3 CH ₃ C ₃ H ₇ -i CN

4-CO-^ OCH3 CH ₃ C3H7-i CN Five

Fifteen

(Table 10)

χ _η Rl R2 R3 Q

OCH3 CH ₃ C3H7— i CN

\ = /

4-1 OCH3 CH ₃ C ₃ H ₇ -i COCH3

_{_{_{4-1 OCH3 2 H 5 C 2 H}}} 5 COCH3

4-1 OCH3 CH ₃ C3H7-1 CN

4-1 OCH3 CH ₃ C ₄ Hg-t CN

4-CH ₃ N (CH ₃ ) _{2 2} H ₅ C2¾ CN

4-CH3 NHCH3 CH ₃ C4H9-t CN

-CH3 OCH3 CH ₃ C ₃ H ₇ -i CN

4-CH3 OCH3 CH ₃ C4H9- t CN

-CH3 OCH3 CH ₃ CF ₃ CN

-CH3 OCH3 CH ₃ C4H9-S CN

4-CH3 OCH3 CH ₃ C4H9-1 CN

-CH3 OCH3 C ₂ H ₅ COCH3

4-CH3 OCH3 CH ₃ C3H7-1 COCH3

4-CH3 OCH3 CH ₃ C ₃ H ₇ -i COOCH3

4-CH3 OCH3 CH _{3 4} H ₉ -t COOCH3

4-N (C ₂ H ₅ ) ₂ OCH3 CH ₃ C ₃ H ₇ -i CN

4- (CH _{3) 2} OCH3 CH ₃ C3H7-1 CN

4- HCH3 OCH3 CH ₃ C4H9-t CN

4- H2 OCH3 CH ₃ C ₃ H ₇ -i CN

4-OC4H9 OCH3 CH ₃ C ₃ H _r i CN

4-OCF3 Br H ₃ C ₃ H ₇ -i CN

4-OCF3 Br CH ₃ C ₃ H ₇ -i COOCH3

4-OCF3 Br CH ₃ C ₃ H ₇ -i COCH3

4-OCF3 Br CH ₃ C4H9- t CN

4-OCF3 OCH3 CH ₃ C ₄ H ₉ -t CN

4-OCF3 OCH3 CH ₃ CF ₃ CN

]. ]

¾] 02]

¾] Re ¾

.

? S? P P.

I

0) 0]

]. 0]

¾. . ]

]

Q. ]-. ¾

0-to

] 〇 ½ ½ i.

]] l

(Table 12)

Rl R2 R3 Q

^Λ η

OCH3 CH3 C ₄ H ₉ -t CN

OCH 0Q ώ 0 CN

0CH ₃

OCH3 CH ₃ C3H7- i CN

₄ OCH3 CH ₃ C3H7-1 CN

, OCH

⁴ \ = / υ 3 3 3 ^N 7 ¹ n n

^¾ \ _y-ll then ^N 3 then 3 ^N 7 ¹ ,

4 ~ "Shi H3 rw, S ^N 3 ^Υ 3 ^Π 7 ¹

A- Shi to ~% ~ nru rw Li ⁿ 3 teeth 3 ⁿ Ryo ¹

4-C ₃ H ₇ -i-i Γ

^N 3 f H7,

4-C3H7-1 0CH ₃ CH ₃ 3H7-1 CN

4-SCH3 0CH3 CH ₃ C3H7-1 CN

4-SCH3 0CH3 CH ₃ C4H9- t CN

_{_{4-SCH3 0CH3 C 2 H 5}} C2H5 CN

0CH3 CH ₃ C ₃ H ₇ -i CN

4-CH = CH ₂ 0CH3 CH ₃ C ₃ H ₇ -i CN

4-0CH ₂ CH = CH ₂ 0CH3 CH ₃ C ₃ H ₇ -i CN

4-0CH ₂ C≡CH 0CH3 CH ₃ C ₃ H ₇ -i CN

Ο

(Table 14)

Br CH ₃ CN

Br-(CH ₂ ) ₄ -CN

Br ¾ CN

(Table 15)

R2 R

0CH ₃ CH ₃ C ₄ Hg-t CN

0CH3 H ₃ CF ₃ C

0CH3 CH3 CHC1 ₂ CN

0CH3 CH ₃ CH ₂ CH = CH2 CN

0CH3 CH ₃ CN

Cl

0CH3 CH ₃ CN 0CH3 ■ (CH ₂ ) ₄ CN 0CH3 CN

-CH

0CH3 CH ₃ C ₃ H ₇ -i COOCH3

0CH3 CH ₃ C ₃ H ₇ -i C00CH ₂ CH = CH ₂

0CH3 CH ₃ C ₃ H ₇ -i C00CH ² C≡CH

0CH3 CH ₃ C ₃ H ₇ -i COOHQ

0CH3 CH ₃ C ₃ H ₇ -i C00- <]

0CH3 CH ₃ C ₃ H ₇ -i C0NH ₂

0CH3 CH ₃ C ₃ H ₇ -i CONHCH3

0CH3 CH ₃ C ₃ H ₇ -i C0N (CH ₃ ) ₂

0CH3 CH ₃ C ₃ H ₇ -i COCH3

0CH3 CH ₃ C ₃ H ₇ -i COCF3

0CH3 C2H5 C2H5 CN

0CH3 ₂ H ₅ C ₃ H ₇ -i CN

0CH3 (CH ₂ ) ₅ -CN

OC2H5 CH ₃ H ₇ -i CN

OC3H7 CH ₃ C ₃ H ₇ -i CN

0CHF ₂ CH ₃ C ₃ H ₇ -i CN

CH ₃ C3H7-i CN

CH ₃ C ₃ H ₇ -i CN

SCH3 CH ₃ C ₃ H ₇ -i CN (Table 16)

Rl R2 R3 Q

SCH ₃ CH ₃ C ₄ H ₉ -t CN

SCH ₃ C2H5 C2H5 CN

SC ₂ H ₅ CH ₃ C3H7-i CN

SC ₂ H ₅ CH ₃ C4H9-t CN

NHCH3 CH ₃ C3H7-i CN

NHCH3 CH ₃ C4H9- t CN

N (CH ₃ ) ₂ CH ₃ C3H7-i CN

O

(Table 18)

Xn R ¹ R ² R3 Q

6- CH ₃ Br CH ₃ C ₃ H ₇ -i COCH3

6-CHQ OCHq CHQ C / iHq- t CN

_{6-CH3 OCH3 CH 3 C3H7- 1} COOCH3

6-CH3 OCH3 CH ₃ C3H7-i COCH3

5-Cl, 6-OCH3 Br CH ₃ c -t CN

5-Cl, 6-OCH3 Br CH ₃ C ₃ H ₇ -i COOCH3

5-Cl, 6-OCH3 Br CH ₃ C3H7-i COCH3

5-Cl, 6-OCH3 OCH3 CH ₃ C ₄ H ₉ -t CN

5-Cl, 6-OCH3 OCH3 CH ₃ C3H7- i COOCH3

5-Cl, 6-OCH3 OCH3 CH ₃ C ₃ H ₇ -i COCH3

(Table 19)

R2 R3 Q

F CH ₃ C3H7- i CN

CI CH ₃ C ₃ H ₇ -i CN

JJ ΓΜ

η3 C2H5

Br CH 0 3H7 CN

Br C ₄ H ₉ -i CN

Br CH 0Q CF ₃ CN

Br CH 0Q CHC1 ₂ CN

Br-(c) ₄ -CN

Br CN

Br CH3 C3H7-1 COOCH3

Br CH ₃ C3H7- i COCH3

Br 2H5 C2H5 CN

Br 2H5 C3H7-i CN

Br (CH ₂ ) ₅ -CN

OH ₃ H ₃ CN

OCH3 CH ₃ C ₃ H ₇ CN

O H3 CH ₃ C3H7-i CN

OCH3 CH ₃ C4H9-i CN (Table 20)

Rl R2 R3

0CH ₃ CH ₃ C4H9- t CN

0CH3 CH ₃ CF ₃ CN

0CH3 CH ₃ CHC1 ₂ CN

0CH3 CH ₃ CH ₂ CH = CH ₂ CN

0CH3 CH ₃ CN

CH

0CH3 CH ₃ CN

F

0CH3 CH ₃ CN

CI

0CH3 CH ₃ -<'CN 0CH3 (CH ₂ ) ₄ -CN 0CH3 CN

0CH3 CH ₃ C ₃ H ₇ -i COOCH3

0CH3 CH ₃ C ₃ H ₇ -i C00CH ₂ CH = CH ₂

0CH3 CH ₃ C ₃ H ₇ -i C00CH ² C≡CH

0CH3 CH ₃ C ₃ H ₇ -i COO

0CH3 CH ₃ C ₃ H ₇ -i C00- <|

0CH3 CH ₃ C ₃ H ₇ -i C0NH ₂

0CH3 H ₃ C3H7-i CONHCH3

0CH3 CH ₃ C ₃ H ₇ -i C0N (CH ₃ ) ₂

0CH3 CH ₃ C ₃ H ₇ -i COCH3

0CH3 CH ₃ C ₃ H ₇ -i COCF3

0CH3 C2H5 C2H5 CN

0CH3 C2H5 C ₃ H ₇ -i CN

0CH3 (CH ₂ ) ₅ -CN

OC2H5 CH ₃ C ₃ H ₇ -i CN

OC3H7 H ₃ C3H7-i CN

SCH3 CH ₃ C ₃ H ₇ -i CN (Table 21)

R2 R3 Q

SCH ₃ CH ₃ C ₄ H ₉ -t C

SCH ₃ C2 «5 C2H5 CN

SC ₂ H ₅ CH ₃ C3H7- i CN

_{_{_{_{SC 2 H 5 CH 3 C 4}}}} Hg-t CN

NHCH ₃ CH ₃ C3H7- i CN

NHCH ₃ CH ₃ C4H9- t CN

N (CH ₃ ) ₂ CH ₃ C3H7- i CN

P T JP98 / 03598

27

(Table 22)

X (n I Rl R2 R3 Q

4-CH3 Br CH ₃ C ₄ H ₉ -t CN

4-CH3 Br CH ₃ C3H7-i COOCH3

4-CH3 Br CH ₃ C ₃ H ₇ -i COCH3

C3H7- i COOCH3

4-CHQ 0CH3 CH ₃ C3H7-1 COCH3

4-Br Br CH ₃ C ₃ H ₇ -i CN

4- Br Br CH ₃ C ₄ H ₉ -t CN

4- Br Br CH ₃ C3H7- 1 COOCH3

4-Br Br CH ₃ C ₃ H ₇ -i COCH3

4-Br OCH3 CH ₃ C ₃ H ₇ -i CN

4-Br OCH3 CH ₃ C ₄ H ₉ -t CN

4- Br OCH3 CH ₃ C3H7-i COOCH3

4-Br OCH3 CH ₃ C3H7-i COCH3

7-OCH3 Br CH ₃ C3H7- i CN

7-OCH3 Br CH ₃ C ₄ H ₉ -t CN

7-OCH3 Br CH ₃ C ₃ H ₇ -i COOCH3

7-OCH3 Br H ₃ C ₃ H ₇ -i COCH3

7-OCH3 OCH3 CH ₃ C ₃ H ₇ -i CN

7-OCH3 OCH3 CH ₃ C4H9-t CN

7-OCH3 OCH3 CH ₃ C ₃ H ₇ -i COOCH3

7-OCH3 OCH3 CH ₃ C3H7-i COCH3

The compound of the present invention represented by the general formula [1] can be produced, for example, according to the following production method. Manufacturing method 1

2 R ¹ o R

R ^] 0 R

II I II

A- CH-C-OH + H? N-C-Q A- CH-C- H-C-Q

I condensing agent

[twenty three] ]

(Wherein, R1, R2, R3, A and Q represent the same meaning as described above.)

The compound of the present invention [1] is prepared by converting an aryl acetic acid derivative represented by the general formula [2] to an amide represented by the general formula [3] by using a condensing agent, if necessary, in the presence of a catalyst and a catalyst or a base. It can be produced by reacting with carboxylic acids.

This reaction is usually performed in a solvent. As a solvent that can be used, any solvent that does not inhibit the reaction may be used.Examples include pentane, hexane, heptane, cyclohexane, petroleum ether, rigoin, hydrocarbons such as benzene, toluene, xylene, dichloromethane, dichloromethane, and the like. Halogenated hydrocarbons such as dichloroethane, chloroform, carbon tetrachloride, carbon benzene, and dichlorobenzene; ethers such as getyl ether, diisopropyl ether, ethylene glycol dimethyl ether, tetrahydrofuran, and dioxane Ketones such as aceton, methylethyl ketone, methyl isobutyl pyrketone, and methyl isobutyl ketone; acetate esters such as methyl acetate and ethyl acetate; nitritols such as acetonitrile and propionitol; or dimethyl sulfoxide , N, N Can have use dimethylformamidine de, a non-pro ton polar solvent or a mixed solvent combining solvents selected from these sulfolane.

Examples of the condensing agent include 1-ethyl-3- (3-dimethylaminopropyl) force rubodiimid hydrochloride, N, Ν'-dicyclohexylcarbodiimide, carbonyldiimidazole, and 2-chloro-1,3-dimethylimidazolyl.ゥ Muclide, etc.

Examples of the catalyst include 4-dimethylaminopyridine, 1-hydroxybenzotriazole, dimethylformamide and the like.

As the base, those generally used in this type of reaction can be used. For example, sodium hydroxide, alkaline metal hydroxides such as hydroxide Alkaline earth metal hydroxides such as shim, sodium carbonate, alkaline metal carbonates such as carbonated lime, or triethylamine, trimethylamine, N, N-dimethylaniline, pyridine, N Organic bases such as —methylbiperidine, 1,5-diazabicyclo [4. And tertiary amines such as triethylamine, pyridine and N-methylbiperidine. The reaction is carried out at a temperature of -50 ° C (: to 150 ° C, preferably 0 to 60 ° C. The reaction time is preferably 1 to 30 hours.

Next, a method for producing a starting compound used in this production method will be described.

First, a compound represented by the general formula [2] can be synthesized by a known method [for example, Journal of Pharmaceutical Chemical Society, Vol. 82, pp. 4062 (1960); 0 rganic Synthesis, The method can be produced by the method described in Vol. 6, page 403 (1988) :) or a method analogous thereto.

Further, the compound represented by the general formula [3] can be synthesized by a known method [for example, 0 rganic Synthesis, Vol. 3, p. 88 (1955); Journal of Medicinal Chemistry, Brother 9, Vol. 11 (1966); the method described in Tetrahedron Letters, vol. 17, p. 1455 (1977)] or a method analogous thereto. Manufacturing method 2

R ¹ 0 R

R ¹ 0 II

I II A-CH-C-NH-CQ A- CH-CL + H ₂ NCQ

R3

[4] [3] R ³ [1]

(In the formula, R i, R ² , R ³ , A and Q represent the same meaning as described above, and L represents a halogen atom.)

The compound of the present invention [1] is obtained by converting an aryl acetate hydride represented by the general formula [4] to a salt. It can be produced by reacting with an amine represented by the general formula [3] in the presence of a group.

This reaction is usually performed in a solvent. Any solvent that does not inhibit the reaction may be used, for example, hydrocarbons such as pentane, hexane, heptane, cyclohexane, petroleum ether, lignin, benzene, toluene, xylene, and the like. Dicro. Halogenated hydrocarbons such as methane, dichloroethane, chloroform, carbon tetrachloride, carbon benzene, dichlorobenzene, ethers such as dimethyl ether, diisopropyl ether, ethylene glycol dimethyl ether, tetrahydrofuran, and dioxane; Ketones such as acetone, methyl ethyl ketone, methyl isobutyl ketone, methyl isobutyl ketone, acetates such as methyl acetate and ethyl acetate, nitriles such as acetonitrile and propionitrile, or N Non-protonic polar solvents such as N, N-dimethylformamide, sulfolane and the like, or a mixed solvent combining solvents selected therefrom can be used. As the base, those generally used in this type of reaction can be used. For example, alkaline metal hydroxides such as sodium hydroxide and hydroxylated lime, alkaline earth metal hydroxides such as calcium hydroxide, and alkaline metal carbonates such as sodium carbonate and carbonated lime Salts, or tertiary amines such as triethylamine and trimethylamine; organic bases such as pyridine and picoline; and the like, preferably, metal salts of alkali metal and tertiary amines. .

The reaction is carried out at a temperature in the range of 150 to 150 ° C, preferably in the range of 0 to 60 ° C. The reaction time is preferably 1 to 30 hours.

The aryl acetic acid halides represented by the general formula [4] can be obtained by converting the aryl acetic acid represented by the general formula [2] produced by the above-mentioned method into, for example, thionyl chloride, phosphorus pentachloride, It can be produced by reacting with a halogenating agent such as phosphorus bromide. Manufacturing method 3 0 RH— ^{R l} 'R l ₀ R ²

I II I [5] I II I

A- CH-C-N'H-C-Q ^ A- CH-C-NH-C-Q

R 3 R3

[i-1 J Cl]

(Wherein, R ² , R ³ , A, Q and L represent the same meaning as described above, and R ¹ ′ represents an alkoxy group, a cycloalkoxy group, a haloalkoxy group, an alkylthio group, an alkylamino group or a dialkylamino group. Represents a no group.)

The compound [1] of the present invention is obtained by converting a monohalogenoaryl acetic acid amide represented by the general formula [1-1] into an alcohol, mercaptan or amine represented by the general formula [5] in the presence of a base. Can be produced by reacting with

This reaction is usually performed in a solvent. Solvents that can be used may be any solvents that do not inhibit the reaction, for example, pentane, hexane, heptane, cyclohexane, petroleum ether, rig-mouth, hydrocarbons such as benzene, toluene, xylene, and dichloromethane. Halogenated hydrocarbons such as dichloroethane, chloroform, carbon tetrachloride, carbon benzene, dichlorobenzene, ethers such as acetyl ether, diisopropyl ether, ethylene glycol dimethyl ether, tetrahydrofuran, dioxane, acetone, Ketones such as methyl ethyl ketone, methyl isobutyl ketone, and methyl isobutyl ketone; acetates such as methyl acetate and ethyl acetate; nitriles such as acetonitrile and propionitrile; alcohols such as methanol and ethanol. Le ethers or dimethyl sulfoxide, N, N-dimethyl Chiruhorumuami de, can be used non-pro ton polar solvent or a mixed solvent combining ¾ medium is selected from these sulfolane.

As the base, those generally used in this type of reaction can be used. For example, alkaline metal hydroxides such as sodium hydroxide and hydroxyladium, alkaline earth metal hydroxides such as calcium hydroxide, and alkaline metal carbonates such as sodium carbonate and lithium carbonate Salts, sodium bicarbonate, alkaline metal hydrogencarbonates such as sodium bicarbonate, sodium hydride, alkaline metal hydrides such as sodium hydride, sodium methylate, sodium ethylate Metal alkoxides such as tertiary amines such as triethylamine and trimethylamine or organic compounds such as pyridine Bases and the like are preferred, and preferred are alkali metal carbonates, alkali metal hydrides and alkali metal alcoholates.

The reaction temperature is 150. (: Up to 150 ° C., preferably 0 to 60 ° C.) The reaction time is preferably 1 to 30 hours.

[Best Mode for Carrying Out the Invention]

Next, the production method, formulation method and use of the compound of the present invention will be specifically described with reference to examples. Production Example 1

Production of N- (1-cyano 1,2,2-trimethylpropyl) -1-2-methoxy-2- (4-methoxyphenyl) acetamide (Compound No. A-37)

a) 5.0 g of ethyl 2-methoxy-2- (4-methoxyphenyl) acetate was dissolved in 30 ml of ethanol. To this solution, 15 ml of a 10% aqueous sodium hydroxide solution was added dropwise. After stirring at room temperature for 12 hours, the reaction solution was poured into water, diluted hydrochloric acid was added, and the mixture was extracted with getyl ether. After drying over anhydrous magnesium sulfate, the dimethyl ether was distilled off under reduced pressure to give 3.6 g of 2-methoxy-2- (4-methoxyphenyl) acetic acid with a melting point of 55 to 57 ° C (yield). 8 2%).

b) To 30 Om1 of 25% aqueous ammonia, 15.4 g of sodium cyanide and 24.0 g of ammonium chloride were added. To this mixture, 3,0.0 g of 3,3-dimethyl-2-butanone was added dropwise under ice cooling. After stirring at room temperature for 24 hours, the reaction solution was poured into water and extracted with ethyl acetate. After drying over anhydrous magnesium sulfate, ethyl acetate was distilled off under reduced pressure, and 28.2 g of 2-amino-2,3,3-trimethylbutyronitrile having a melting point of 107 to 110 ° C (28.2 g) Rate of 74%).

c) To 20 ml of dichloromethane was added 0.4 g of 2-methoxy-2- (4-methoxyphenyl) acetic acid and 1.1 g of 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride. Was. After stirring for 10 minutes, 0.5 g of 2-amino-2,3,3-trimethylbutyronitrile was added. After stirring at room temperature for 3 hours, the reaction solution was poured into water and extracted with dichloromethane. After drying over anhydrous magnesium sulfate, methane at the dichloromethane outlet was distilled off under reduced pressure. Residue is used for gel gel power The residue was purified by luffy to obtain 0.5 g (yield: 79%) of the desired product having a refractive index of 1.522.3 (20 ° C). Production Example 2

Preparation of 2-bromo-1- (4-chlorophenyl) -1-N- (1-cyano-1,2-dimethylpropyl) acetamide (Compound No. A-1)

a) To a mixture of 3.0 g of 2- (4-chlorophenyl) acetic acid and 3.5 g of phosphorus tribromide, 5.8 g of bromine was added dropwise at room temperature. After stirring for 30 minutes, the mixture was heated and stirred at 80 to 90 ° C for 6 hours. The reaction solution was poured into ice water and extracted with toluene. After drying over anhydrous magnesium sulfate, the toluene was distilled off under reduced pressure to obtain 5.3 g (yield 96%) of 2-bromo-2- (4-phenylphenyl) acetyl bromide as a yellow liquid. Was.

b) To 50 ml of tetrahydrofuran, 2.2 g of 2-amino 2,3-dimethylbutyroni trinole and 2.4 g of triethylamine were added. To this mixture, 6.2 g of 2-bromo-2- (4-chlorophenyl) acetyl bromide was added dropwise under ice cooling. After stirring at room temperature for 5 hours, the reaction solution was poured into water and extracted with ethyl acetate. After drying over anhydrous magnesium sulfate, ethyl acetate was distilled off under reduced pressure. The residue was purified by silica gel column chromatography and had a melting point of 110-113. 5.6 g of C

(83% yield). Production Example 3

Preparation of 2- (4-chlorophenyl) -N- (1-cyano 1,2-dimethylpropyl)-2-methoxyacetamide (Compound No. A-2)

Methanol 30 m Π2-promo 2- (4-chlorophenyl) -1-N- (1-cyano-1,2-dimethylpropyl) acetamide 1.0 g, sodium methylate (28 (0.6% methanol solution). After stirring under heating and refluxing for 3 hours, the reaction solution was poured into water and extracted with chloroform. After drying over anhydrous magnesium sulfate, chloroform was distilled off under reduced pressure. The residue was purified by silica gel column chromatography to obtain a refractive index of 1.5105 (0.6 g of the target compound at 20 ° (yield: 70%)). Production Example 4

Preparation of 2- (4-chlorophenyl) -1-N- (1-cyano-1,2-dimethylpropyl) -2-methylthioacetamide (Compound No. A-9)

2-Bromo-2- (4-chlorophenyl) -N- (1-cyano 1,2-dimethylpropyl) acetamide in 30 ml of methanol 1.O g, methyl mercaptan sodium salt (15% aqueous solution) 1.4 g was added. After stirring at room temperature for 12 hours, the reaction solution was poured into water and extracted with black hole form. After drying over anhydrous magnesium sulfate, the chloroform was distilled off under reduced pressure. The residue was purified by silica gel column chromatography to obtain 0.7 g (yield: 78%) of the desired product having a melting point of 121-124 ° C. Production Example 5

2 _ bromo one? Preparation of ^-(1-cyan-1,2,2-trimethylpropyl) -1- (2-naphthyl) acetamide (Compound No. B-8)

To 30 ml of tetrahydrofuran was added 5.5 g of 2-amino 2,3,3-trimethylbutyronitrile and 6.1 g of triethylamine. To this mixture, 16.4 g of 2-bromo-12- (2-naphthyl) acetyl bromide was added dropwise under ice cooling. After stirring at room temperature for 5 hours, the reaction solution was poured into water and extracted with ethyl acetate. After drying over anhydrous magnesium sulfate, ethyl acetate was distilled off under reduced pressure. The residue was purified by silica gel column chromatography to obtain 13.5 g (yield: 83%) of the desired product having a melting point of 128 to 131 ° C. Production Example 6

Production of N- (1-cyano 1,2,2-trimethylpropyl) -1-2-methoxy-2- (2-naphthyl) acetamide (Compound No. B-4, B-5)

2-promo N- (1-Cyan-1,2,2-trimethylpropyl) 1-2- (2-naphthyl) acetamide in 30 ml of methanol 3.5 g, sodium methylate (28 % Methanol solution) 1.9 g was added. Stir under reflux for 3 hours After that, the reaction solution was poured into water and extracted with black-mouthed form. After drying over anhydrous magnesium sulfate, chloroform was distilled off under reduced pressure. The residue was purified by silica gel column chromatography, and 1.3 g (43% yield) of diastereomer A (low-polar substance) of the target compound having a melting point of 117-119 and a refractive index of 1.5574 (20 ° 1.lg (36%) of diastereomer B (highly polar substance) of the target compound of C) was obtained. Production example— (

2-Promo N- (1-Isopropyl-1-methyl-1-oxopropyl) -1-2- (4-Trifluoromethylphenyl) acetamide (Compound No.A_65) a) 6N hydrochloric acid To 300 ml, 12.5 g of N— (1-isopropyl-11-methyl_2-oxopropyl) acetamide was added. After stirring under reflux for 5 hours, the mixture was concentrated under reduced pressure. The residue was washed with acetone to obtain 5.7 g (yield 36%) of 3-amino-3,4-dimethyl-12-pentanonone hydrochloride having a melting point of 202.

b) To 20 ml of acetonitrile, 1.O g of 3-amino-3,4-dimethyl-12-pentanone hydrochloride and 1.8 g of potassium carbonate were added. To this mixture, 2.0 g of 2-bromo-12- (4-trifluoromethylphenyl) acetyl bromide was added dropwise under ice cooling. After stirring at room temperature for 7 hours, the reaction solution was poured into water and extracted with ethyl acetate. After drying over anhydrous magnesium sulfate, ethyl acetate was distilled off under reduced pressure. The residue was purified by silica gel chromatography to obtain 1.0 g (yield: 40%) of the target substance having a melting point of 165 to 167 ° C. Production Example 8

Production of N- (1-isopropyl-1-methyl-1-oxopropyl) -1-2-methoxy-2- (4-trifluoromethylphenyl) acetamide (Compound Nos. A-66, A-67)

2-promo N- (1-isopropyl-1-1-methyl-2 in 30 ml of methanol —Oxopropyl) —2— (4-trifluoromethylphenyl) acetamide (0.8 g) and sodium methylate (28% methanol solution) (0.6 g) were added. After stirring under reflux with heating for 3 hours, the reaction solution was poured into water and extracted with ethyl acetate. After drying over anhydrous magnesium sulfate, ethyl acetate was distilled off under reduced pressure. The residue was purified by silica gel column chromatography, and 0.2 g (yield 29%) of diastereomer A (low polarity) of the desired compound having a melting point of 120 to 122 g and a melting point of 79 Diastereomer B (highly polar) 0.2 (yield 29%) of the target compound at ~ 81 ° C was obtained. Production Example 9

(S) 1 (+) — 2— (4-promophenyl) 1 N— (1 isopropyl-11-methyl-12-oxopropyl) 12-methoxyacetamide (Compound No. A—95, A-96) ) Manufacturing of

a) In 200 ml of ethyl acetate, 7.2 g of 2- (4-bromophenyl) -12-methoxyacetic acid was dissolved. To this solution, 3.6 g of (S)-(-)-phenethylamine was added, and the mixture was stirred under reflux for 2 hours. After cooling to room temperature, the precipitated diastereomer salt was collected by filtration and recrystallized three times with water. Dilute hydrochloric acid was added to this salt, and extracted with black-mouthed form. After drying over anhydrous magnesium sulfate, the chlorophyll form was distilled off under reduced pressure. (S) — (+) — 2- (4-Promophenyl) — 2-Methoxy at 87-89 ° C Acetic acid 1.6 g (yield 32%) was obtained. Specific rotation: [Hi] _D ^{2 4} = +1 0 3.3 °

(c = 0. 1 3, CHC 1 3)

b) In 30 ml of dichloromethane, (S)-(+)-2- (4-bromophenyl) -l- 2-methoxyacetic acid 1.0 g, 1-ethyl-3- (3-dimethylaminopropyl) carbopimid hydrochloride 0.8 g of salt was added. After stirring for 30 minutes, 0.63 g of 3-amino-3,4-dimethyl-2-pentanone was added. After stirring at room temperature for 5 hours, the reaction solution was poured into water and extracted with dichloromethane. After drying over anhydrous magnesium sulfate, dichloromethane was distilled off under reduced pressure. The residue was purified by silica gel column chromatography, and 0.36 g (yield 25%) of diastereomer A (low-polar substance) of the target compound having a melting point of 71-72 ° C and a refractive index of 1. 5 3 2.1 (2 0 3f

(° C), 0.17 g (yield: 12¾) of diastereomer B (highly polar substance) of the target compound was obtained. Optical purity: diastereomer A = 97.0% e.e., diastereomer B-99.296 e.e. (high-performance liquid chromatography, Daicel chiral cell OD)

Examples of the compound of the present invention produced according to the methods shown in Production Examples 1 to 9 are shown in Tables 23 to 26 together with the compounds shown in the above Production Examples.

In addition, isomer A indicates diastereomer A, isomer B indicates diastereomer B, and isomer M indicates diastereomer mixture. Isomer RA refers to diastereomer A whose acid moiety is optically active (R), isomer RB refers to diastereomer B whose acid moiety is optically active (R), and isomer RM The diastereomer mixture in which the acid moiety is the optically active substance (R) is shown. Isomer SA indicates diastereomer A in which the acid moiety is optically active (S), isomer SB indicates diastereomer B in which the acid moiety is optically active (S), and isomer SM indicates acid. The diastereomer mixture in which the site is the optically active form (S) is shown. Diastereomer A refers to low-polarity diastereomer separated by silica gel column chromatography or high-performance liquid chromatography, and diastereomer B refers to a high-polarity diastereomer similarly separated. Show.

(Table 23)

39

(Table 24)

99/08999

PCT / JP98 / 03598

40

(Table 25)

41

(Table 26)

42

(Table 27)

Compound x _n R ¹ R2 R3 Q isomer Melting point (° c) No. "^ or refractive index _n 20

A- 110 3-Cl. 4-CH ₃ OCH3 CH ₃ C ₃ H ₇ -i C0CH ₃ M 105-108

A- 111 4-Br OCH3 CH ₃ C3H7-i CO M 1.5333

A- 112 4-CI OCH3 CH ₃ C ₃ H ₇ -i C00CH ₃ M 1.5097

A-113 4-CI Br CH ₃ C3H7-i COOCH3 M 104-107

A-114 3, 4-C12 OCH3 CH ₃ C3H7- i COOCH3 M1.5299

A - 115 4-Br OCH3 CH 3 C 3 H 7 - i C00C 2 H 5 M 1. 5193

(Table 28)

Compound R2 R3 Q isomer Melting point (T) No. or refractive index n

Bl OCH3 CH ₃ C3H7- -i CN A 1.5556

B-2 O H3 CH ₃ C3H7- -i CN B 1.5585

B-3 OCH3 CH ₃ C3H7- -i CN M 1.5562

B-4 OCH3 CH ₃ 4H9- -t CN A 117-119

B-5 OCH3 CH ₃ C4H9- -t CN B 1.5574

B-6 OCH3 CH ₃ C4H9- t CN M 72-75

B-7 Br CH ₃ ¾H7- i CN 117-119

B-8 Br CH ₃ C4H9- t CN 128-131

B-9 OCH3 CH ₃ C3H7- i COCH3 M 88-91 The agricultural and horticultural fungicide of the present invention comprises an aryl amide derivative represented by the general formula [1] as an active ingredient. When the compound of the present invention is used as an agricultural and horticultural fungicide, the active ingredient can be used in an appropriate dosage form depending on the purpose. Usually, the active ingredient is diluted with an inert liquid or solid carrier, and if necessary, a surfactant and the like can be added to the active ingredient. Suitable carriers include, for example, solid carriers such as talc, bentonite, clay, kaolin, diatomaceous earth, white carbon, vermiculite, slaked lime, silica sand, ammonium sulfate, and urea, isopropyl alcohol, xylene, cyclohexanone, and methyl naphthalene. And liquid carriers such as Surfactants and dispersants include, for example, dinaphthyl methanesulfonate, alcohol sulfate, alkylaryl sulfonate, lignin sulfonate, polyoxyethylene glycol ether, polyoxyethylene alkylaryl ether, Examples include polyoxyethylene sorbitan monoalkylate. Examples of the auxiliary include carboxymethylcellulose and the like. These preparations are diluted to an appropriate concentration and sprayed or applied directly.

The fungicide for agricultural and horticultural use of the present invention can be used by foliage application, soil application or water surface application. The compounding ratio of the active ingredient is appropriately selected according to need, but it is appropriate to use 0.1 to 20% (by weight) for powders and granules, and 5 to 80% (by weight) for emulsions and wettable powders. is there.

The application rate of the agricultural and horticultural fungicide of the present invention varies depending on the type of the compound used, the target disease, the tendency to occur, the degree of damage, the environmental conditions, the dosage form used, and the like. For example, when used as such as powders and granules, the active ingredient may be appropriately selected from the range of O.lg to 5 kg, preferably lg to 1 kg, per 10 liter. When used in liquid form, such as emulsions and wettable powders, it is appropriate to appropriately select from the range of 0.1 ppm to 10,000 ppm, preferably 1 to 3, OOO ppm.

The compound according to the present invention can control plant diseases caused by fungi belonging to algal fungi (Oomycetes), ascomycetes (Ascomycetes), incomplete fungi (Deuteromycetes), and basidiomycetes (Basidiomycetes) by the above-mentioned application forms. Next, specific bacterial names are given as non-limiting examples. Genus Pseudoperonospora, Pseudoperonospora cubensis; genus Sphaerotheca, for example, Sphaerotheca fuliginea :, genus Venturia, for example, Venturis inaequalis, Genus Pyricularia, such as blast (Pyricularia oryzae), genus Gipera (Gibberella), such as blight seedling (Gibberella fujikuroi), botrytis (Botrytis), such as Botrytis cinerea, Altanaria Genus Alternaria, for example, Komatsuna black spot (Alternaria brassicicola), Rhizoctonia (Rhizoctonia), for example, Rhizoctonia solani, Puccinia, for example, rust! ! (Puccinia recondita).

Further, the compound of the present invention may be mixed with an insecticide, another fungicide, a herbicide, a plant growth regulator, a fertilizer *, etc., if necessary. Next, the formulation method will be specifically described with reference to typical examples of the agricultural and horticultural fungicides of the present invention. In the following description, “%” indicates weight percentage.

Formulation Example 1 Powder

2% of compound (B-3), 5% of diatomaceous earth and 93% of clay were uniformly mixed and pulverized to obtain a powder.

Formulation Example 2 wettable powder

50% of the compound (A-31), 45% of diatomaceous earth, 2% of sodium dinaphthylmethanedisulfonate and 3% of sodium ligninsulfonate were uniformly mixed and pulverized to obtain a wettable powder.

Formulation Example 3 Emulsion

An emulsion was prepared by uniformly dissolving 30% of the compound (A-65), 20% of cyclohexanone, 11% of polyoxyethylene alkylaryl ether, 4% of calcium alkylbenzenesulfonate and 35% of methylnaphthalene.

Formulation Example 4 Granules

5% of compound (A-21), 2% of sodium salt of lauryl alcohol sulfate, 5% of sodium ligninsulfonate, 2% of carboxymethylcellulose and 86% of creme are uniformly mixed and pulverized. The mixture was kneaded with 20% of water, kneaded, processed into granules of 14 to 32 mesh using an extruder, and dried to obtain granules. / 08999

PCT / JP98 / 03598

45

Next, the effects of the fungicide for agricultural and horticultural use of the present invention will be specifically described with reference to test examples.

Test example 1 Rice blast prevention effect test

Approximately 15 rice seeds (variety: Asahi Aichi) were sown in a 7 cm diameter unglazed pot and grown in a greenhouse for 2 to 3 weeks. A wettable powder prepared according to Formulation Example 2 was diluted with water so that the active ingredient concentration became SOOppm, and the rice seedling having the fourth leaf completely developed was sprayed with 10 ml per pot. After air-drying, a conidia suspension of rice blast fungus (Pyricularia oryzae) was spray-inoculated and immediately placed in a humidity chamber at 25 ° C for 24 hours. Then, they were transferred to a greenhouse, and the number of lesions on the fourth leaf was examined 5 days after inoculation. The control values were determined by Equation 1 and evaluated according to the criteria in Table 29. The results are shown in Tables 30-33.

(Equation 1) Number of lesions in the treatment area

Control value (%) = (1) 100

Lesion count in untreated area

(Table 29) Evaluation control

A 100% control value

B 100% to less than 800%

C 80.0% to 50.0% or more

Control value less than D 50.0%

(Table 30) Compound number Evaluation

A 1 A

A-2 B

A- 3 A

A- 4 A

A-5 A

A- 6 A

A- 7 A

A-8 A

A- 9 B

A-10 B

A-1 1 A

A-1 2 A

A- 1 3 A

A-14 A

A-15 A

A- 1 6 B

A 1 7 A

A- 1 8 B

A-1 9 A

A-20 A

A- 2 1 A

A-22 A

A- 23 B

A- 24 B

A- 25 B

A

A- 27 A

A- 28 B

A- 29 B

A-30 A

A-3 1 A

A- 32 B a 9 V a ε 9-va 29 -V e Τ 9-V a 09-V a 6 S-V a 89-V

9 9-V e 99 -V ag 9-V a S—V a ε -ves S ~ V e T 9-V e 09 -V e 6 Ρ -V a 8 ー V ef ⁷ — V v 9 to V a Q p -V g-V g S-V e Z ~ va I p-V a 0-V a 6 S-V a 8 ε-va ε-va 9 ε-ν a Q ε-ν e ε-ves ε -ν Meng

(ΐ Halla) SC0 / 86if / lDd

66680/66 OM s

<<<<Q <<<<<_;<;; _{m <;<;} l_ D OO COM CO LO CD OO CD O CM CO LO CO OO COC CO ^ L CD CO CD CO CD CO OO 00 00 oo CO oo 00 CO CO 00 CD DC CD

<<<<<<<<<<<<<<<<<<<

(Table 33) Compound number Evaluation

A-97 A

A-98 A

A-99 A

A-100 A

A-01 A

A-102 A

A- 03 A

A- 104 A

A- 1 05 A

A-1 06 B

A- 1 07 B

A-108 B

A- 1 09 A

A- 1 10 A

A 1 1 1 B

A-1 1 2 A

A 1 1 3 A

A 1 14 A

A- 1 1 5 A

B-1 A

B-2 A

B-3 A

B-4 B

B-5 B

B-6 A

B-7 B

B-8 B

B 9 A Test example 2 Rice blast surface application test

Rice seedlings of 1.5 foliage stage (variety: Aichi Asahi) were transplanted into four white spots in 9 cm diameter white porcelain pots and grown in a greenhouse. The wettable powder prepared according to Formulation Example 2 at the 2.5 leaf stage was subjected to water application to the pot such that the active ingredient concentration was 300 g per 10 ares. Ten days after the treatment, a conidia suspension of rice blast fungus (Pyricu 1 ariaoryzae) was spray-inoculated and immediately placed in a moist chamber at 25 ° C for 24 hours. Then, they were transferred to a greenhouse, and 5 days after the inoculation, the number of lesions on the highest leaf at the time of the inoculation was examined. The control value was determined by Equation 1, and the results of evaluation based on the criteria in Table 29 are shown in Tables 34 to 35.

(Table 34) Compound number Evaluation

A- 2 B

A- 7 B

A- 1 2 B

A-14 B

A-20 B

A- 2 1 B

A-22 B

A-30 B

A- 3 1 B

A-43 B

A- 45 B

A- 46 B

A- 52 B

A- 53 B

A- 54 B

A- 55 B

A- 56 B

A- 57 B

A- 65 B

A- 66 B

A- 67 B

A- 68 A

A- 69 B

A- 70 A

A- 72 A

A-73 A

A-74 A

A-75 A

A- 76 A

A- 77 A

A-78 B

A- 79 A (Table 35)

Test Example 3 Apple scab prevention effect test

Five apple seeds (variety: Kodama) were sown in a 9 cm X 9 cm PVC bowl and grown in a greenhouse for 20 days. A wettable powder prepared according to Formulation Example 2 was diluted with water to a seedling seedling having four true leaves developed so that the active ingredient concentration would be 500 ppm, and 20 m1 per pot Sprayed. After air-drying, a spore suspension of the scab of apple scab (Venturiainaequa 1 is) was inoculated by spraying and immediately placed in a moist chamber at 22 ° C for 48 hours. Then, the apple seedlings were transferred to a greenhouse to cause disease, and 14 days after inoculation, the diseased area of the top two leaves at the time of breeding was investigated. The disease severity was evaluated based on the criteria shown in Table 36. The disease severity was calculated from the disease severity and the number of leaves according to Equation 2, and the control value was calculated from Equation 3. The resulting control values were evaluated according to the criteria in Table 29, and the results are shown in Table 37. (Table 36)

(Equation 2)

∑ (Disease degree X number of leaves) Damage degree (%) = X 100 Number of survey leaves X 4

(Equation 3) Damage degree of treated area Control value (%) = (1) 100 Damage degree of untreated area

(Table 37)

<

Compound number Evaluation

A-1 inch 9 A

A-2 1 A

A-34 B

A-36 B

A-74 A

A- 75 A

A-76 A

A- 77 B

A-79 B

A-82 B

A— 83 B

B

A- 95 B

A-97 A

A- 99 A

A 1 00 B

Claims

The scope of the claims

1. General formula [1] R ¹ 0 R ²

II

A— CH-C-NH-C-Q [1]

R 3

[In the formula, A represents a Fuweniru group, which may be substituted also 2-naphthyl group by which do good also 1-naphthyl group or X _n replaced by X _n substituted by X _n, X is a halogen atom, C i Cs alkyl group, C2- 26 alkenyl group, C2-C6 alkynyl group, C3-C6 cycloalkyl group, C1-C4 haloalkyl group, hydroxy group, Ci-C6 alkoxy group, C 2 to C 6 Arukeniruokishi group, C. 2 to C ₆ Arukiniruokishi groups, C 3 to C 6 cycloalkyl O alkoxy group, C i~C 4 halo alkoxy group, phenoxy group (said group C i -C ₆ alkyl groups, C I～C ₄ Haroa alkyl groups, C i C e alkoxy group, Shiano group may be by connexion substituted nitro group or a halogen atom.), C i~C 6 alkylthio groups, C I～C ₄ Haroaruki thio group, phenylene thioether (in which the group C i~C ₆ alkyl group, C i~C 4 Haroaru Or a C 1 -C 6 alkoxy group, a cyano group, a nitro group or a halogen atom.), An amino group, a C 1 -C 6 alkylamino group, a C 1 -C 6 dialkyl Amino group, cyano group, phenyl group (the group may be substituted by a C1-C6 alkyl group, a C1-C4 haloalkyl group, a C1-C6 alkoxy group, a cyano group, a nitro group or a halogen atom) good.), Ararukiru (in which the group C i~C ₆ alkyl group, C 1 through C 4 haloalkyl group, C i~C s alkoxy group, Shiano group may be substituted by a two-Toro group or a halogen atom. ), C -C ₆ alkylcarbonyl group, Benzoiru (in which the group C 1 through C 6 alkyl group, C i ~ C 4 Haroa alkyl group, C i~C ₆ alkoxy group, Shiano group, a nitro group or a halogen atom Or C i -C 6 alkoxy Represents carbonylation Le group, n represents an integer of 1 to 3, R l represents a halogen atom, C i~C 6 alkoxy groups, C ₃ ~ C 6 cycloalkoxy groups, C 1 through C 4 haloalkoxy groups, C Represents a C 1 to C ₆ alkylthio group, a C 1 to C ₆ alkylamino group or a C 丄 to C 6 dialkylamino group, R 2 represents a C i~C 6 alkyl group, C 3 to C 6 consequent opening alkyl or C i~C 4 haloalkyl group, R 3 is C 2 to C 6 alkyl group, C ₂ -C 6 alkenyl group , C 3 to C 6 cycloalkyl group (said group C 1 through C ₆ alkyl group, may be by connexion substituted with halogen atoms.) or an C 1 through C 4 haloalkyl group, or R ² and R 3 May form a 5- to 7-membered cycloalkyl group together with the carbon atom to which it is attached (the group may be substituted by a C: [to C6 alkyl group, which may be substituted by a halogen atom). A cyano group or a group—C〇R ⁴ (R ⁴ is a C i -C 6 alkyl group, a C ₃ -cycloalkyl group, a C 1 -C 4 haloalkyl group, a C i -C s alkoxy group, a C 2 -C β alkenyl Okishi group, C 2 to C 6 Arukiniruokishi group, Ji 3～〇 6 cyclo alkyl O alkoxy group, amino group, C 1 through C ₆ alkylamino cyano group or a C 1 through C 6 dialkyl Represents a Ruami amino group.) Represents the. ], An aryl acetate amide derivative represented by the formula:

2. general formula [1], A represents a Fuweniru group, X _n by substitution which may be substituted by may be 1 one naphthyl group or X _n are 2-naphthyl group substituted by X _n, X halogen atoms, C i~C ₆ alkyl group, C ₃ -C 6 Shikuroaruki Le group, C 1 through C 4 haloalkyl group, C i~C s alkoxy groups, C 3 to C e cycloalkyl Arukiruokishi group, C 1 through C 4 haloalkoxy groups, C 1 through C 6 alkylthio groups, C E -C 4 haloalkylthio group or a phenyl group (said group C i~C ₆ alkyl groups, C E -C 4 haloalkyl groups, C I～C ₆ alkoxy , A cyano group, a nitro group or a halogen atom.), N represents an integer of 1 to 3, R 1 represents a halogen atom, a C i -C s alkoxy group, a C 3 -C 6 Cycloalkoxy group, C1-C4 haloalkoxy group, C1-C6 alkylthio group, Ci-C6 alkyla It represents a cyano group or a C 1 ~ C ₆ dialkyl § amino group, R ² represents a C i C e al kill groups, C 3 to C 6 consequent opening alkyl or C 1 through C 4 haloalkyl group, R 3 is C 2 to C ₆ alkyl group, C ₂ -C 6 alkenyl group, C ₃ -C ₆ a cycloalkyl group (said group C i ~ C 6 alkyl group, but it may also be substituted by a halogen atom.) or C. 1 to Represents a C 4 haloalkyl group, or R ² and R ³ are a 5- to 7-membered cycloalkyl group together with a bonding carbon atom (the group may be a C 1 to C 6 alkyl group, May be formed, and Q is S 5f

Group or group COR ⁴ (R ⁴ is a C 丄 -C 6 alkyl group, a C ₃ -C 6 cycloalkyl group, C))-C, 1 haloalkyl group, a C i -C ₆ alkoxy group, a C 2 -C 6 alkenyl Ruokishi group, a C Ri ~ C 6 Arukiniruokishi groups, C 3 to C 6 cycloalkyl O alkoxy group, amino group, C 1 through C ₆ alkylamino cyano group or a C 1 through C 6 dialkyl amino group. ) Is an aryl amide derivative.

3. In the general formula [1], A represents a phenyl group, 1-naphthyl group or 2-naphthyl group substituted by X _n , X represents a halogen atom, a C i -C 6 alkyl group, C 3 -C 6 Cycloalkyl group, C1-C4 haloalkyl group, Ci-C6 alkoxy group, C3-Cfi cycloalkyloxy group, C1-C4 haloalkoxy group, Ci-C6 alkylthio group, C- C4 haloalkylthio group or phenyl group (the group may be substituted by a C1-C6 alkyl group, a C1-C4 haloalkyl group, a C1-Cs alkoxy group, a cyano group, a nitro group or a halogen atom And n represents an integer of 1 to 3, and R ¹ represents a halogen atom, a C ^{1 to} C 6 alkoxy group, a C 3 to C 6 cycloalkoxy group, a C 1 to C 4 haloalkoxy group, or a C 1. represents ~ C 6 alkylthio group, R ² represents a C 1 through C 6 alkyl group, R ³ is C 2 to C 6 alkyl group, C 3 to C ₆ cycloalkyl Represents an alkyl group (the group may be substituted by a C 1 -C ₆ alkyl group or a halogen atom) or a C 1 -C 4 haloalkyl group, or R ² and R 3 represent a bonding carbon atom with 5-membered to 7-membered cycloalkyl group (. said group C] _~C ₆ alkyl group, which may be substituted by a halogen atom) in the ring may be formed, Q is Shiano group or a group - COR ⁴ (R ⁴ represents a Ci-C 6 alkyl group, a C ₃ -C 6 cycloalkyl group, a C 丄 -C 4 haloalkyl group or a C 丄 -C ₆ alkoxy group.)

4. In the general formula [1], A represents a phenyl group or a 2-naphthyl group substituted by X _n , and X represents a halogen atom, a C i -C 6 alkyl group, a C i -C 4 haloalkyl group, a C i -C s alkoxy group, C1-C4 haloalkoxy group or phenyl group (the group is a C1-C6 alkyl group, a C1-C4 haloalkyl group, a C1-C6 alkoxy group, a cyano group, a nitro group or And n represents an integer of 1 to 3, R ¹ represents a halogen atom or a C ^{1 to} C ₆ alkoxy group, and R ² represents a C 丄 to C 6 alkyl group. R ³ is a C2-C6 alkyl group, C 3 to C 6 cycloalkyl group (said group C丄-C 6 alkyl group, may be by connexion substituted with a halogen atom., Or an C 1 through C 4 haloalkyl group, or R ² and R ³ A 5- to 7-membered cycloalkyl group (the group may be substituted by a C i Cs alkyl group or a halogen atom) may be formed together with the bonding carbon atom, and Q is a cyano group or C 一 R ⁴ (R 4 is C: [to C ₆ alkyl group or C

Represents a -C6 alkoxy group. ) Is an aryl amide derivative.

5. A fungicide for agricultural and horticultural use containing the aryl acetate derivative of claim 1, 2, 3, or 4 as an active ingredient.