WO2004093544A1 - Substituted benzene derivative or salt thereof, process for producing these, and bactericide containing the same as active ingredient - Google Patents

Abstract

A bactericide containing a novel substituted benzene derivative or salt thereof as an active ingredient. The bactericide contains as an active ingredient either a substituted benzene derivative represented by the formula [I]: (wherein Z is a Y group or an optionally substituted heterocyclic group bonded in a position meta to A; X is halogeno, cyano, etc.; n is an integer of 0 to 4; A is -NR1-NR2-, -N=N-, or -D-NH-; G1 is oxygen, sulfur, or -NRa-; G2 is oxygen or sulfur; and R3 is alkyl, alkenyl, alkynyl, cycloalkyl, or haloalkyl) or a salt of the derivative.

Description

TECHNICAL FIELD The present invention relates to substituted benzene derivatives or salts thereof, methods for producing them, and fungicides containing them as active ingredients.

 The present invention relates to a novel substituted benzene derivative or a salt thereof, a method for producing the same, and a fungicide containing them as an active ingredient. Background art

 As the substituted benzene derivative, for example, the compounds described in WO 97/2257 can be mentioned. A compound having a structure similar to that of the phenylhydrazone derivative according to the present invention.

Examples of the compound include the compounds described in WO 0 1/17355 and WO 99/62869. However, these are different from the compounds of the present invention. Also, fungicides containing as an active ingredient a compound having a similar structural part to the substituted benzene derivative related to the present invention include those described in WO 99/13017, WO01 / 1355, etc. However, these are different from fungicides containing the substituted benzene derivative according to the present invention as an effective component. Furthermore, WO 03Z68230 describes substituted benzene derivatives for pharmaceutical use. Disclosure of the invention

 Many conventionally provided fungicides have characteristics in their plant disease control effects, and some have a slightly lower therapeutic effect than preventive effects, or have relatively short residual effects. However, depending on the application, it may show only a practically insufficient control effect on plant diseases. Therefore, creation of a novel compound having a strong plant disease control effect is desired.

 The present inventors have studied to solve the above-mentioned problems, and as a result, by using the compound represented by the formula [I] as an active ingredient, various diseases, especially oomycetes, ascomycetes, basidiomycetes, and the like. They have found that they exhibit excellent preventive and therapeutic effects on diseases caused by incomplete bacteria, and have completed the present invention.

 That is, the present invention provides a compound of the formula [I]:

Formula [I]:

[Wherein, z is a group from Y to ≡, where [γ is a hydrogen atom; an aryl group which may be substituted with halogen, hydroxy, alkyl, octaalkyl, alkoxy or haloalkoxy; substituted with halogen, hydroxy, aryl or alkoxy] An alkyl group which may be substituted with an aryl which may be substituted with halogen, alkyl or alkoxy; an alkoxyalkyl group which is substituted with an aryl which may be substituted with halogen, alkyl or alkoxy; Alkenyl group optionally substituted by halogen; alkynyl group optionally substituted by halogen, hydroxy, aryl or alkoxy; cycloalkyl group optionally substituted by halogen, hydroxy or alkoxy; cycloalkenyl group; cycloalkyl alkyl group; a halogen, alkyl or optionally Ariru alkyl group optionally substituted by alkoxy; halogen, alkyl or optionally Fuenoki Shiarukiru group optionally substituted by alkoxy; C (O) R ⁴ group; COOR ⁵ group; S i R ⁶ R ⁷ R ^{8 is} an alkyl group or a Si R ⁶ R ⁷ R ⁸ group, and R ⁴ , R ⁵ , R ⁶ , R ⁷ and R ⁸ are the same or different and are a hydrogen atom or an alkyl group} or A And X is a halogen atom, a cyano group, a hydroxyl group, an alkyl group, an alkoxy group, or An alkyl group or a haloalkoxy group; n is an integer of 0 to 4; A is a hydrogen atom each independently one NR ¹ -NR ² one group (R ¹ and R ^2; alkyl; alkenyl; § Rukiniru Group; alkoxyalkyl group; alkylcarbonyl group; haloalkylcarbonyl group; haloalkoxycarbonyl group; alkylthioalkyl group; haloalkyl group; phenylcarbonyl group; alkoxycarbonyl group; or substituted with halogen, alkyl or alkoxy. A good arylalkyl group), —N = N— group or one D—NH— group (D is an alkylene group optionally substituted by octogen, hydroxy or alkoxy); G ¹ is oxygen atom, a sulfur atom or one NR ^a - a group (R ^a is a hydrogen atom or an alkyl group), G ² is an oxygen atom or a sulfur atom (G ¹ and G ² are Be may be different even one); R ³ is an alkyl group, an alkenyl group, an alkynyl group, a cycloalkyl group or a haloalkyl group, provided that but aヽ^ ≡ "one group, A gar D-NH A bactericide comprising, as an active ingredient, a substituted benzene derivative represented by the formula:

 Further, the present invention provides a compound of the formula [I ′]:

(In the formula, Het ′ is an optionally substituted phenyl group, an optionally substituted benzophenyl group, an optionally substituted furanyl group, an optionally substituted benzofuranyl group, an optionally substituted A pyridyl group, an optionally substituted pyrimidinyl group or an optionally substituted pyridazinyl group; X is a halogen atom, an alkyl group, an alkoxy group, a haloalkyl group or a haloalkoxy group; n is an integer of 0 to 4 A "is one NH—NH group or —D—NH— group (D is an alkylene group optionally substituted by halogen, hydroxy or alkoxy); G ¹ is an oxygen atom, a sulfur atom Or — NR ^a _ group ( ^Ra is a hydrogen atom or an alkyl group); R ³ is an alkyl group, an alkenyl group, an alkynyl group, a cycloalkyl group or a haloalkyl group (provided that (1) Het ' An optionally substituted phenyl group or an optionally substituted pyridyl group, wherein A "is -NH-NH-, and when n of Xn is 1, X in the ortho position to A" is an alkyl group or an alkoxy group, and (2) Me t 'is 2 hydroxy Shipirijiru group, a "is alkylene - NH- is a group, G ¹ Gar NR ^a - Motodea Ri, R ³ is alkyl Group)) or a substituted benzene derivative represented by And a method for producing the same.

Further, the present invention provides a compound of formula [1 "]:

{In the formula, X eight androgenic atom; Shiano group, a hydroxyl group, alkyl group, alkoxy group, halo alkyl group or haloalkoxy group, n is an integer of 0 ~ 4, A '''one NR ¹ - An NR ² group (R ¹ and R ² are each independently a hydrogen atom; an alkyl group; an alkenyl group; an alkynyl group; an alkoxyalkyl group; an alkyl carbonyl group; an octaalkyl carbonyl group; a haloalkoxycarbonyl group; A haloalkyl group; a phenylcarbonyl group; an alkoxyl group or an arylalkyl group which may be substituted by halogen, alkyl or alkoxy) or one N = N group, and R ³ ′ is an alkyl group. There, G ¹ 'and G ² are each independently an oxygen atom or a sulfur atom, Y is a hydrogen atom, a halogen, hydroxy, alkyl, haloalkyl, alkoxy Or an aryl group optionally substituted with haloalkoxy; an alkyl group optionally substituted with halogen, hydroxy, aryl or alkoxy; an alcohol substituted with an aryl group optionally substituted with halogen, alkyl or alkoxy. An alkenyl group which may be substituted with halogen, hydroxy, aryl or alkoxy; an alkynyl group which may be substituted with halogen, hydroxy, aryl or alkoxy; cycloalkyl which may be substituted with halogen, hydroxy or alkoxy. Alkyl group; cycloalkenyl group; cycloalkylalkyl group; arylalkyl group optionally substituted with halogen, alkyl or alkoxy; phenoxyalkyl group optionally substituted with halogen, alkyl or alkoxy.

C (O) R ⁴ groups; COOR ⁵ groups; Si R ⁶ R ⁷ R ⁸ —alkyl groups or S i R ⁶ R ⁷ R ⁸ groups; R ⁴ , R ⁵ , R ⁶ , R ⁷ and R ⁸ is the same or different and is a hydrogen atom or an alkyl group}, and relates to a phenylhydrazine derivative or a salt thereof, and a production method thereof. BEST MODE FOR CARRYING OUT THE INVENTION

 In the present invention, the heterocyclic moiety of the heterocyclic group which may be substituted in the formula includes phenyl, dihydrophenyl, tetrahydrophenyl, benzophenyl, furanyl, dihydrofuranyl, tetrahydrofuranyl, benzofuranyl, pyridyl, dihydropyran. Lysyl, Tetrahydropyridyl, Piperidinyl, Pyrimidyl, Dihydropyrimidyl, Tetrahydropyrimidyl, Hexahydropyrimidyl, Pyridazinyl, Dihydropyridazinyl, Tetrahydropyridazinyl, Hexahydropyridazinyl, Virazinyl, Dihydropyrazinyl , Tetrahydropyrazinyl, quinolyl, quinoxalyl, isothiazolyl, benzocenyl and the like. Of these, chenyl, benzochenyl, furanyl, benzofuranyl, pyridyl, pyrimidinyl, pyridazinyl, pyrazinyl, quinolyl, quinoxalyl, isotizazolyl or benzozonitil are preferred, and chenyl, benzochenyl, furanyl, benzofuranyl, pyridyl groups , Pyrimidinyl or pyridazinyl are more preferred.

As the substituent of the above-mentioned optionally substituted heterocyclic group, a halogen atom; Alkyl group which may be substituted with gen, cyano, hydroxy, alkoxy or alkoxyl alkoxyl group; alkoxy group which may be substituted with halogen; alkylthio group which may be substituted with halogen; cyano group; Group; an alkylthiocarbonyl group or a cycloalkyl group which may be substituted with alkyl, halogen or cyano, and the like. A halogen atom, an alkyl group, a haloalkyl group, an alkylthio group or an alkoxy group is preferable. The number of the substituents may be one or two or more. When the number of the substituents is two or more, the substituents may be the same or different.

 In the formula, the halogen atom or the halogen moiety of each substituent substituted with halogen includes fluorine, chlorine, bromine or iodine.

The alkyl moiety of the alkyl group or various substituents substituted with an alkyl, a straight-chain or branched-chain are mentioned, C Among them, _ _{1 D} alkyl is preferable, C, - ₆ alkyl is further desirable. C, as the _ ₆ alkyl, for example methyl, cyclohexyl Echiru, n one-propyl, isopropyl, n- heptyl, isobutyl, sec-butyl, tert-butyl, n- pentyl, isopentyl, neopentyl, to n-, 1, 1 one-dimethylpropyl , 1,1-dimethylbutyl and the like. As the C ^ _{1 ()} Al kill, other C doctor ₆ alkyl, heptyl to e.g., Okuchiru, 1, 1 one Jechi Rubuchiru, nonyl, decyl, and the like.

Alkenyl groups include straight-chain or branched ones, among which C _2- ,. Alkenyl is preferably, C ₂ - ₆ alkenyl is more desirable. C _{2 -} The ₆ alkenyl, for example Biel, 1 one propenyl, 2-propenyl, isopropenyl, 1 Buteniru, 2-butenyl, hexenyl, and the like to one scratch. Also, C _{2 -} Examples _{1 Q} an alkenyl, C _{2 -} Other ₆ alkenyl, such as 1-Okuteniru the like. Examples of the alkynyl group include straight-chain or branched-chain alkynyl groups. Among them, C ₂ , 0 alkynyl is desirable, and C ₂ -6 alkynyl is more desirable. C _{2 - 6} The alkynyl, for example Eteniru, 1 one Puropieru, 2-propynyl, 1 one heptynyl, 2 - butynyl, 3-butynyl, 4-methyl-1 _ pentynyl, 3-methyl-1 one pen ethynyl, and the like. Also, C ₂ - Examples _{1 D} alkynyl, C _{2 -} Other ₆ alkynyl include for example 1 one year old Kuchiniru the like.

 As the cycloalkyl group or the cycloalkyl part of the cycloalkylalkyl group,

, C _{3. 6} cyclo alkyl is preferred, for example cyclopropyl, Shikuropuchiru, shea Kuropenchiru, hexyl and the like cyclohexylene.

The cycloalkenyl group, C ₃ - ₆ shea Kuroarukeniru is desirable, for example 1 - cyclopentene one 1 one I le, 2- cyclopentene one 1 one I le, xenon Hmm 1 one I le to 1 Shikuro, cyclohexene 2-cyclopropyl — 1-yl, etc.

 Examples of the aryl moiety include, in addition to phenyl, a condensed polycyclic group such as naphthyl.

Examples of the alkylene group include those having 1 to 6 carbon atoms, such as methylene, ethylene, propylene, butylene, pentylene, and hexylene. A methylene group is preferable. Among the compounds of the present invention, a compound of the formula [I-10]

(Wherein, Het is an optionally substituted heterocyclic group; X, n, A, G ¹ , G ² and R ³ are the same as those described above) The salt can be produced according to a known method, for example, by the methods shown in the following Production Methods 11 to 13.

[Manufacturing method 1 1 1]

Het-B (OH) ₂

 [1-H] P-i]

In the formula, A ′ represents one NR ¹ —NR ² — group (R ¹ and R ² are each independently a hydrogen atom; an alkyl group; an alkenyl group; an alkynyl group; an alkoxyalkyl group; an alkyl propylon group; a haloalkyl propylonyl group; A haloalkoxy group; an alkylthioalkyl group; an haloalkyl group; a phenylcarbonyl group; an alkoxycarbonyl group or an arylalkyl group optionally substituted with halogen, alkyl or alkoxy) or —D—NH— group ( D is halogen, substituted with hydroxy or alkoxy located at also alkylene group); L is a bromine atom, an iodine atom or OS_〇 ₂ CF ₃ group,; H et, X, n , GG 2 and R ³ is as described above)

 As shown in the above scheme, by reacting the compound of the formula [11-II] with the compound of the formula [1-III] in the presence of a palladium complex and a base, the compound of the formula [I-11] is Can be manufactured. This method is a known method (for example, a method described in Tetrahedron Letters 35 (42) p77 19 (1994), Tetrahedron Letters 37 (7) pl043 (1996), Journal of the American Chemical Society 124 pl3662 (2002), etc.). It is based on. The compound of the formula [111] is generally used in a ratio of 1.0 to 10.0 equivalents, preferably 1.0 to 2.0 equivalents, relative to the compound of the formula [111].

In the production method 111, a solvent can be used in some cases. The solvent may be any solvent that does not hinder the progress of this reaction. For example, ketones such as acetone, methyl ethyl ketone and cyclohexanone; ethers such as getyl ether, diisopropyl ether, tetrahydrofuran, dioxane, dimethoxyethane, diethylene dalicol dimethyl ether; ethyl acetate, acetic acid Esters such as methyl; aromatic hydrocarbons such as benzene and toluene; nitriles such as acetonitrile; N, N-dimethylformamide; N, N-dimethylacetamide; dimethylsulfoxide; and water. The base used in the reaction of the production method 11-11 is, for example, potassium t-butoxide. Metal alkoxides; alkali metal carbonates such as sodium carbonate and potassium carbonate; alkaline earth metal carbonates such as calcium carbonate; alkali metal hydroxides such as sodium hydroxide and potassium hydroxide; And inorganic bases such as hydroxides of alkaline earth metals such as calcium. The base is used usually in a proportion of 1.0 to 20.0 equivalents, preferably 1. (! To 3.0 equivalents) to the compound of the formula [111].

 The palladium complex to be used in the production method 1-11 is tetrakistriphenyl phosphine palladium (0), bis (dibenzylideneacetone) palladium (0), tris (dibenzylideneacetone) palladium (0), palladium acetate-triphenyl Examples include phosphine and palladium acetate-tricyclohexylphosphine. The palladium complex is used in a proportion of 0.001 to 1.0 equivalent, preferably 0.01 to 0.2 equivalent, relative to the compound of the formula [111].

 The reaction temperature of the production method 11 is from 70 to 200, preferably from 0 to 150. The reaction time is not fixed depending on the reaction temperature, the reaction amount and the like, but may be generally selected from the range of 1 hour to 72 hours. After completion of the reaction, the desired product is isolated from the reaction system by a conventional method, and if necessary, purified by column chromatography, recrystallization, or the like. Formula I I,

(Wherein L, X, n, A ″, G ¹ and R ³ are as described above), and a compound represented by the formula [111]: Het′-B (OH) ₂ ( Wherein He is as defined above) in the presence of a base and a palladium complex.

[Method 1-2

WR ¹ WR G ¹ R ³

1-nc TJP2004 / 005900

7

(Wherein, Het, L, X, n, G ¹ , G ² and R ³ are as described above, and R ¹ ′ and R ² ′ are each independently an alkyl group; an alkenyl group; an alkynyl group; an alkoxyalkyl Alkyl carbonyl group; Haloalkyl carbonyl group; Haloalkoxycarbonyl group; Alkylthioalkyl group; Noroalkyl group; Phenylcarbonyl group; Alkoxycarbonyl group or arylalkyl which may be substituted with halogen, alkyl or alkoxy. And W is halogen)

As shown in the above scheme, a compound of the formula [1-1a] or a compound of the formula [1-1 Ia] is reacted with a compound of the formula [IV-1] in an inert solvent in the presence of a base. By doing so, a compound of the formula [I-1b] or a compound of the formula [1-1-b] can be obtained. Further, by reacting a compound of the formula [1-1b] or a compound of the formula [1-1 II-b] with a compound of the formula [IV-2] in an inert solvent in the presence of a base. The compound of the formula [I-lc] or the compound of the formula [1-1-c] can be obtained. On the other hand, when R and R ² ′ are each independently a C _1-6 alkyl group, (R ^b 〇) may be used instead of the compound of the formula [IV-1] and / or the compound of the formula [IV-2〗]. a compound represented by the ₂ S 〇 ₂ (R ^b is an is CI- _s alkyl group) can be used. Moreover, R ¹ 'and R ^2' are each independently 〇 Bok ₆ alkyl force Ruponiru group or C -! In the case of ₆ Haroaruki Rukaruponiru group, compound and Z or of the formula [IV- 1] [IV- 2] A compound represented by (R ^e CO) ₂ O (R ^e is a Ci-6 alkyl group or a Ct- ₆ haloalkyl group) can be used in place of the compound of the formula (1).

 Examples of the inert solvent that can be used in the production method 1-2 include the solvents exemplified in the production method 11-11. The base used in the production method 1-2 includes an inorganic base or an organic base. Examples of the inorganic base include carbonates of alkali metals such as sodium carbonate and potassium carbonate; hydrogen carbonates of alkaline metals such as sodium hydrogen carbonate; carbonates of alkaline earth metals such as calcium carbonate; sodium hydroxide; Hydroxides of alkaline metals such as hydroxide hydroxide; hydroxides of alkaline earth metals such as calcium hydroxide; hydrides of alkali metals such as lithium hydride and sodium hydride. Examples of the organic base include amines such as triethylamine and diisopropylethylamine; and pyridines such as pyridine and dimethylaminopyridine. The base is generally used in a proportion of 0.5 to 3.0 equivalents, preferably 0.8 to 2.0 equivalents, to the compound of the formula [I-a] or the compound of the formula [1-1-a]. The base is similarly used in a proportion of usually 0.5 to 3.0 equivalents, preferably 0.8 to 2.0 equivalents to the compound of [Ib] or the compound of formula [1-1-b].

 The reaction temperature of each step of the production method 1-2 is -70 to 200, preferably -20 to 150 ° C. The reaction time is not fixed depending on the reaction temperature and the reaction amount, but may be generally selected from the range of several tens of minutes to 48 hours. After completion of the reaction, the desired product is isolated from the reaction system by a conventional method, and if necessary, purified by column chromatography, recrystallization, or the like.

Wherein Het, X, n, GG ² and R ³ are as described above: TJP2004 / 005900

As shown in the above scheme, the compound of the formula [I-Id] can be produced by oxidizing the compound of the formula [I-la] in the presence of an oxidizing agent and an inert solvent. Palladium catalysts such as palladium carbon, palladium oxide, and Lindlar catalysts; manganese dioxide; sodium periodate; sodium benzene diacetate; mercury oxide; hydrogen peroxide; bromine; Sodium acid salt; N-bromosuccinimide (NBS); azodicarboxylic acid getyl sulfonate; nitric acid; 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) It is desirable to use a palladium catalyst. Examples of the inert solvent that can be used in the production method 13 include those that do not inhibit the progress of this reaction, such as the inert solvent used in the production method 1-1. The reaction temperature of the production method 13 is -70 ^ C ~ 20 (TC, preferably 0 ~ 150 ° C. The reaction time is not fixed depending on the reaction temperature and the reaction amount, but is generally 10 minutes. After completion of the reaction, the desired product is isolated from the reaction system by a conventional method, and if necessary, purified by column chromatography, recrystallization, or the like.

[Intermediate manufacturing method 1

 1-V 1-Π

(Wherein L, X, n, A ″, G ¹ , G ² , R ³ and W are the same as those described above) of the formula [1—II] which is an intermediate of the compound of the formula [I-11] The compound is obtained by reacting a compound of the formula [1-V] with a compound of the formula [1-1 VI] in an inert solvent in the presence of a base by a known method, for example, as shown in the above scheme. In the compounds of the present invention, the compound of the formula [1 "] or a salt thereof may be produced according to a known method, for example, by the following production method 2-1. It can be manufactured by the method shown in Manufacturing method 2-3.

[Method 2

H two Y

 Pd complex

 241-1

^{{Wherein, G 1 ', G 2,} RR 2, R 3', X, Y and n are as defined above; Y 'is hydroxy, C _{1 - s} alkyl, C physician ₆ Ha Roarukiru, C _{l -} . ₆ an alkoxy or Ji ₆ Ha port alkoxy optionally substituted § Li Ichiru group or a halogen be, hydroxy, Ariru or C, _s alkoxy optionally substituted by C ₂ - be _{1 D} an alkenyl group; L is chlorine atom, a bromine atom, an iodine atom or 0s0 ₂ CF ₃ group; L 'is a halogen atom; Q is a hydrogen atom or a C, _ ₆ alkyl group}

As a method for producing a compound of the formula [1 "—1], as shown in the above scheme, (1) a compound of the formula [2-II] and a compound of the formula [2-III-a] are converted to a palladium complex and A method of reacting in the presence of a base, and reacting a compound of the formula [2-1-1-1] with a compound of the formula [2-III-e] in the presence of a palladium complex and a base to obtain a compound of the formula [1 "-1 [Method for obtaining compound of formula [I] [Method according to known method described in Tetrahedron Letters, Vol. 37, p. 5527 (1996)], (2) Formula [2- A method of reacting a compound of the formula [2] with a compound of the formula [2-III-b] in the presence of a palladium complex, and (3) a compound of the formula [2-II] and a compound of the formula [2 -—- c] And (4) reacting a compound of the formula [2-II] with a compound of the formula [2-III-d] in the presence of a palladium complex and a base [Journal Bed Organic Chemistry one (Journal of Organic Clie mistry) Vol. 61, pp. 5169 (1996) method] is exemplified et al is that according to a known method described in such as. For the compound of the formula [2-II], the compound of the formula [2-III-a], the compound of the formula [2-III-b], the compound of the formula [2-III-c] or [2- The compound of III-d] is usually used in a ratio of 1.0 to 10 equivalents, preferably 1.0 to 3.0 equivalents. For the compound of the formula [2— II— 1〗 The compound of the formula [2—Ι Π-e] is generally used in a ratio of 1. (! To 10.0 equivalents, preferably 1.0 to 3.0 equivalents.

 In production method 2-1, a solvent can be used in some cases. Any solvent may be used as long as it does not hinder the progress of this reaction. Examples thereof include ketones such as acetone, methyl ethyl ketone, and cyclohexanone; getyl ether, diisopropyl ether, tetrahydrofuran, dioxane, dimethoxyethane. Ethers such as diethylene glycol dimethyl ether; esters such as ethyl acetate and methyl acetate; octogenated hydrocarbons such as dichloromethane, chloroform, and carbon tetrachloride; aromatic hydrocarbons such as benzene and toluene; Nitriles such as acetonitrile; Ν, Ν-dimethylformamide; Ν, Ν-dimethylacetamide; dimethyl sulfoxide; water and the like can be used. Base used in the reaction of Production method 2-1 (1) includes, for example, inorganic bases such as sodium carbonate and potassium carbonate; propylamine, butylamine, diisopropylamine, triethylamine, triptylamine, diisopropylethylamine, pyrrolidine And organic amines such as piperidine. The base is used usually in a proportion of 1. (! To 20.0 equivalents, preferably 1.0 to 3.0 equivalents, to the compound of the formula [2-II].

 The palladium complex used in Production Method 2-1 includes tetrakistriphenylphosphine palladium (0), dichlorobis (triphenylphosphine) palladium (II) -triphenylphosphine, palladium acetate-triphenylphosphine, palladium (II) acetate —Tricyclohexylphosphine, palladium (II) chloride—triphenylbutylphosphine, dichloro-1, Γ-pisdiphenylphosphinophenocene palladium (II), etc., and a compound of the formula [2-Ι Ι] The palladium complex is used in a ratio of 0.001 to 0.1 equivalent, and the tertiary phosphine is used in a ratio of 2.0 to 4.0 equivalents to the palladium complex. The catalyst used may be ammonium salts such as tetrabutylammonium bromide and tetrabutylammonium hydrogen sulfate. Ani Gerare used in a ratio of 0.1 001-0. 1 equiv to the compound of the formula [2-I I],

In the case of using the compound of the formula [2-Ι Ι Ι-a] or the compound of the formula [2-Ie] in the production method 2-1, in addition to the palladium complex, a copper halide such as copper (I) iodide It is common to use The copper halide is used usually in a ratio of 0.01 to 0.5 equivalent to the compound of the formula [2-III-a] or the compound of the formula [2-III-e]. The reaction temperature of production method 2-1 is -70 to 200, preferably 0 to 150. The reaction time is not fixed depending on the reaction temperature, the reaction amount and the like, but may be generally selected from the range of 1 hour to 72 hours. After completion of the reaction, the desired product is isolated from the reaction system by a conventional method, and if necessary, purified by column chromatography, recrystallization, or the like. 05900

11

[Formulation 2—2]

WR ¹

I "-la Γ-1-

 -1-c

 2 I-a base, inert solvent

2-ab

 Base, inert solvent

(Wherein, G ¹ ′ G ² , R ³ ′, X, Y, L and n are as described above; R ¹ ′ and R ² ′ are each independently an alkyl group; an alkenyl group; an alkynyl group; an alkoxyalkyl Alkyl carbonyl group; Haloalkyl alkenyl group; Haloalkoxy alkenyl group; Alkylthioalkyl-group; Octaalkyl-group; Phenylcarbonyl group; Alkoxy alkenyl group; Alkoxy alkenyl group or may be substituted with halogen, alkyl or alkoxy. An arylalkyl group; W is a halogen)

As shown in the above scheme, a compound of the formula [Γ-1-1-a] or a compound of the formula [2—II-a] and a compound of the formula [IV-1] are prepared in an inert solvent in the presence of a base. By reacting, the compound of the formula [1 "—1-b] or the compound of the formula [2-II-b] can be obtained. -b] is reacted with a compound of the formula [IV-2] in the presence of a base to obtain a compound of the formula [1 "-1-1-c" or a compound of the formula [2-II-c] Further, according to the method of Production Method 1, a compound of the formula [I "-11" can be obtained from a compound of the formula [II-b] or a compound of the formula [2-II-c]. On the other hand, C is independently R and R ² 'are each, in the case of _ ₆ alkyl group, in place of the compound of the compound and / or of the formula [IV- 1] [IV- 2] (R b O) 2 S0 ₂ a compound represented by the (R ^b are 〇 ₆ alkyl group) can be used. In the case of C Bok ₆ alkyl force Ruponiru group or 〇 les ₆ haloalkyl Cal Poni Le group independently R ¹ 'and R ^2' are each of the formula - compound and Z or the formula [IV 1] [IV- 2] of Represented by (R ^e CO) ₂₀ instead of compound Compound (R ^e is C, - ₆ alkyl group or a C i-6 haloalkyl group) Using. As the inert solvent that can be used in Production Method 2-2, the solvents exemplified in Production Method 2-1 can be used. As the base used in Production method 2-2, an inorganic base or an organic base can be used. As the inorganic base, for example, sodium carbonate or carbonate of an alkali metal atom such as carbon dioxide; Carbonates of alkaline metals such as aluminum, lime, carbonates of alkaline earth metals such as calcium carbonate, hydroxides of alkaline metals such as sodium hydroxide, hydroxide limes, etc .; Hydroxides of lithium earth metals; hydrides of alkaline metals such as lithium hydride and sodium hydride can be used. As the organic base, for example, amines such as triethylamine and diisopropylethylamine; pyridines such as pyridine and dimethylaminopyridine can be used. The base is usually 1.0 to 3.0 equivalents, preferably 1.0 to 2.0, equivalent to the compound of the formula [1 "-1-1-a] or the compound of the formula [2- [-a]. It is used in an equivalent ratio, and is usually 1.0 to 3.0 equivalents, preferably L 0 to 0, based on the compound of the formula [1-1-b] or the compound of the formula [2-I I-b]. Used at a rate of 2.0 equivalents.

 The reaction temperature of Preparation Method 2-2 is -70 to ~ 200 ^, preferably 20 to 150 ° C. The reaction time is not fixed depending on the reaction temperature and the reaction amount, but generally, may be selected from the range of 10 minutes to 48 hours. After completion of the reaction, the desired product is isolated from the reaction system by a conventional method, and if necessary, purified by column chromatography, recrystallization, or the like.

[Formulation 2-3]

(Wherein, G ¹ ′ G ² , R ³ ′, X, Y and n are as described above)

 As shown in the above scheme, by oxidizing the compound of the formula [Γ1-1-a] in the presence of an oxidizing agent and an inert solvent, a compound of the formula [I "1-2] can be produced. Examples of the oxidizing agent include palladium catalysts such as palladium carbon, palladium oxide, and Linda catalyst; manganese dioxide; sodium periodate; iodobenzene diacetate; mercury oxide; hydrogen peroxide; Sodium bromate; N-bromosuccinimide (NBS); azodicarboxylic acid getyl sulfonate; nitric acid; 2,3-dichloro mouth-5,6-disocyano-1,4-benzoquinone (DDQ) It is desirable to use a palladium catalyst Examples of the inert solvent that can be used in Production Method 2-3 include those that do not inhibit the progress of this reaction, such as the inert solvent used in Production Method 2-1. twenty three The reaction temperature is -70 to 200, preferably 0 T: to 150 ° C. The reaction time is not fixed depending on the reaction temperature and the reaction amount, but is generally selected from the range of 10 minutes to 48 hours. After completion of the reaction, the desired product is isolated from the reaction system by a conventional method, and if necessary, column chromatography.

1. Purify by recrystallization.

Shi ((((

 Base 4235 1 13

 , Ϊ

[Intermediate manufacturing method 2]

2-V 2-n-a

(Where G ¹ G ² , RX, L, n and W are as described above:

The compound of the formula [2-II-a], which is an intermediate of the compound of [1 "-1-1-a], can be prepared by a known method, as shown in the above scheme, by a known method. Alternatively, it can be produced by reacting a salt thereof with a compound of the formula [2-VI] in an inert solvent in the presence of a base, but is not limited thereto. The compound (hydrazine derivative) of the formula [2-V], which is a precursor of the compound of the formula [2-Π-a], is obtained by, for example, converting the corresponding aniline with sodium nitrite. It can be synthesized by diazotizing and then reducing with tin (II) chloride, etc. Next, among the compounds of the formula [II] or salts thereof, examples of desirable compounds as fungicides are listed below. The present invention is not limited to the above-mentioned compound [1 ′] or a salt thereof.

 A compound of the above formula [I "} or a salt thereof.

 A compound of the above formula [1 "-11" or a salt thereof.

 A compound of the above formula [Γ'-2] or a salt thereof.

X is a halogen atom, Shiano group, hydroxyl group, _alkyl group, C, _ ₆ alkoxy C, be. ₆ c port alkyl group or ₆ C port alkoxy group

Each independently represent a hydrogen atom, C _{1 -. 6} alkyl group, C _{2 6} alkenyl, C _{2 6} alkynyl group, C -! ₆ alkoxy C, - ₆ alkyl group, C, ₆ alkyl Cal Poni Le group, C -! ₆ Ha . mouth alkylcarbonyl group, C, - ₆ alkoxy force Ruponiru group or ₆ C outlet alkoxymorphinan aryloxycarbonyl group; R ³ is C, ₆ compound or its salt of (2) or (3) an alkyl group.

(6) Y is hydrogen atom;! Halogen, hydroxy, C _{l - 6} alkyl, C _{1 - 6} C Roaru kill, C - ₆ alkoxy or C, - ₆ Ha port alkoxy which may be substituted with § Li

- Le group; a halogen, hydroxy, Ariru or C, which may be substituted by _ ₆ alkoxy C, - i. .. Alkyl group; halogen, C, _[delta] alkyl or C, ₆ alkoxy C substituted with which may be Ariru substituted - ₆ alkoxy Ci _ _1Q alkyl group;! Halogen, hydroxy, Ariru or C, in _ ₆ alkoxy C which may be substituted

.. _{2 1 ()} alkenyl group; a halogen, hydroxy, § Li Ichiru or C, ₆ alkoxy optionally substituted C ₂ _ ₁ be ₍₎ alkynyl; halogen, hydroxy or C, - ₆ alkoxy substituted which may C ₃ - ₆ cyclo alkyl group;. C ₃ down Kuroarukeni Le group; C ₃ - ₆ a cycloalkyl C - alkyl group;! halogen, C, - ₆ alkyl Wakashi Ku is substituted with C Bok ₆ alkoxy Aryl C! _ ₆ alkyl group; halogen,

Phenoxy C! _ ₆ alkyl group optionally substituted with C,. ₆ alkyl or C ₆ alkoxy; C (0) R ⁴ group; COOR ⁵ group: Si R ⁶ R ⁷ R ⁸ — Ci- ₆ alkyl Group or S a i R ⁶ R ⁷ R ^{8 group, R 4, R 5, R} 6, R 7 and R ⁸ are identical or different, a hydrogen atom or a C, - ₆ alkyl group wherein the compound of (5) or its salt.

(7) Y is halogen, hydroxy, C! -. ₆ alkyl, C, s Ha port alkyl, C, -

₆ alkoxy or C ₆ C port alkoxy which may be substituted with § Li Ichiru group or C androgenic, hydroxy, § Li Ichiru or may be substituted by ₆ alkoxy C ₂ -. A _1D alkenyl group (5) Compound.

(8) The compound according to (5), wherein R ¹ is a hydrogen atom or a C, ₆ alkyl group.

(8) The compound according to (5), wherein R ³ is a methyl group or an ethyl group.

(9) The compound according to (5), wherein both G ¹ and G ² are oxygen atoms. The substituted benzene derivative represented by the formula (I) of the present invention (hereinafter abbreviated as the compound of the present invention) or a salt thereof is useful as an active ingredient of a fungicide, particularly an active ingredient of an agricultural and horticultural fungicide. Examples of agricultural and horticultural fungicides include rice blast, sesame leaf blight, and coat blight; wheat powdery mildew, red mold, rust, snow rot, naked smut, eye spot, leaf Blight, Fusarium wilt; Black spot on citrus, Scab; Apple morilia, Powdery mildew, Spot scab, Black scab; Pear scab, Black scab; Peach ash, Scab, Phomopsis rot; Bud ド Black rot, 晚 Rot, powdery mildew, downy mildew; Anthracnose of blight, deciduous disease; Anthracnose of mildew, powdery mildew, vine wilt Disease, downy mildew; tomato leaf spot, leaf mold, late blight; black spot on brassica vegetables, summer blight on potatoes, late blight; strawberry powdery mildew; gray mold on various crops, sclerotia It is effective for controlling diseases such as diseases. In particular, it is useful for controlling diseases caused by bacteria belonging to algae (Oomycetes), ascomycetes (Ascomycetes), incomplete fungi (Deuteromycetes), and basidiomycetes (Bas idiomycetes). Next, specific bacterial names are given as non-limiting examples. The genus Pseudoperonospora, for example, Pseudoperonospora cubensis, the genus Erysipe, for example, the wheat powdery mildew (Erysiphe graminis), the genus Benturia (Venturis), e.g. , Genus Pyricularia (Pyricidaria oryzae), genus Potrytis (Botrytis), such as Botrytis cinerea, Rhizoctonia (Rhizoctonia), such as Rhizoctonia solani It is also effective in controlling soil diseases caused by phytopathogenic bacteria such as Fusarium, Pichidium, Rhizoctonia, Verticillium, and Brasmodiophora.

The fungicide containing the compound of the present invention is usually prepared by mixing the compound with various agricultural auxiliaries, powder, granule, water dispersible granule, wettable powder, aqueous suspension, oil suspension. It is used in various forms such as water, solvent, emulsion, liquid, paste, aerosol, micro-spray, etc., as long as it meets the purpose of the present invention. It can be in any formulation form. Auxiliaries used in the formulation include diatomaceous earth, slaked lime, silica sand, ammonium sulfate, urea, calcium carbonate, talc, white carbon, vermiculite, kaolin, bentonite, a mixture of kaolinite and sericite, clay, sodium carbonate, baking soda Solid carriers such as sodium sulfate, sodium sulfate, zeolite, starch, and carboxymethyl cellulose; water, toluene, xylene, solvent naphtha, dioxane, acetone, isophorone, methyl isobutyl ketone, benzene, cyclohexane, cyclohexanone. , Methylnaphthylene, dimethylsulfoxide, dimethylformamide, dimethylacetamide, N-methyl-2-pyrrolidone, alcohol and other solvents; fatty acid salts, benzoates, alkylsulfosuccinates, dialkylsulfosuccinates Acid salts, polycarboxylates, alkyl sulfates, alkyl sulfates, alkyl aryl sulfates, alkyl diglycol ether sulfates, alcohol sulfates, alkyl sulfonates, alkyl aryl sulfonates, aryl sulfonates Salt, lignin sulfonate, alkyl diphenyl ether disulfonate, polystyrene sulfonate, alkyl phosphate ester, alkyl aryl phosphate, styryl aryl phosphate, polyoxyethylene alkyl ether sulfate, polyoxy Ethylene alkyl aryl ether sulfate, polyoxyethylene alkyl aryl ether sulfate, polyoxyethylene alkyl ether phosphate, polyoxyethylene alkyl aryl phosphate, Anionic surfactants and spreading agents, such as salts of phthalenesulfonic acid formalin condensate; sorbitan fatty acid esters, glycerin fatty acid esters, fatty acid polydalicelide, fatty acid alcohols, polyglycol esters, acetylene glycol, acetylene alcohol Polyoxyalkylene block polymer, Polyoxyethylene alkyl ether, Polyoxyethylene alkyl aryl ether, Polyoxyethylene styryl alcohol, Polyoxyethylene glycol alkyl ether, Polyoxyethylene fatty acid ester Nonionics such as polyoxyethylene sorbitan fatty acid ester, polyoxyethylene glycerin fatty acid ester, polyoxyethylene hydrogenated castor oil, and polyoxypropylene fatty acid ester Surfactants and spreading agents: olive oil, potato oil, castor oil, palm oil, camellia oil, coconut oil, sesame oil, corn oil, rice bran oil, peanut oil, cottonseed oil, soybean oil, rapeseed oil, linseed oil, cutting oil, liquid Vegetable oils such as paraffin and mineral oils. These adjuvants can be selected from those known in the art without departing from the purpose of the present invention. In addition, various commonly used auxiliary agents such as a bulking agent, a thickening agent, an anti-settling agent, an anti-freezing agent, a dispersion stabilizer, a safener, and a fungicide can be used. The mixing ratio of the compound of the present invention to various adjuvants is generally 0.005: 99.995 to 95: 5, preferably 0.2: 99.8 to 90:10. In the actual use of these preparations, they can be used as they are, or they can be diluted to a predetermined concentration with a diluent such as water, and added with various spreading agents as necessary. The use concentration of the compound of the present invention varies depending on the target crop, the method of use, the formulation form, the application rate, and the like, and cannot be unconditionally specified, but in the case of foliage treatment, it is usually 0.1 to 10,000 ppm per active ingredient, preferably. Is 1 to 3,000 ppm. In the case of soil treatment, it is usually 1 to 100,000 g / lia, preferably 10 to 20,000 g / ha.

 The application of various preparations of the fungicide containing the compound of the present invention, or a dilution thereof, is usually carried out by a general application method, that is, spraying (for example, spraying, spraying, misting, atomizing, dusting, water surface) Application), soil application (mixing, irrigation, etc.), surface application (coating, dressing, coating, etc.). It can also be applied by the so-called ultra-high concentration small volume spray method (ultra low volume). In this method, it is possible to contain 100% of the active ingredient.

 The fungicide of the present invention may be used, if necessary, with other pesticides, such as insecticides, acaricides, nematicides, fungicides, antiviral agents, attractants, herbicides, plant growth regulators, etc. Can be used in combination, and in this case, even better effects may be exhibited.

Examples of the active ingredient compound of the fungicide (generic name; including some applications) in the above other pesticides include, for example, mepanipyrim (Mepanipyr im), pyrimesanil (Pyr ime thani 1), cyprodinil (Cyprod inil) Pyrimidinamine-based compounds such as fluazinam (F 1 uaz inai); Triadimeion, Bitertanol, Triflumizole, Etaconazole, Epiconazole, Propiconazole, Penconazole, Penconazole, Flusilazole, Microbutanil ), Cyproconazole, Tebuconazole, Hexaconazole, Hexaconazole, Furconazole-cis, Prochloraz ', Metoconazole, Epoxyconazole Azole compounds such as, for example, Tetraconazole, Oxpoconazole fumarate, Oxpoconazole fumarate, Sipconazole and Prothioconazole;

 Quinoxaline-based compounds such as quinomethionate; diamines such as Maneb, Zineb, Mancozeb, Polycarbamate, Metiram, and Propineb Thiocarbamate compounds;

 Organochlorine compounds such as Fthalide, Chlorothalonil, Qu intozene;

 Imidazole compounds such as benomyl, thiophanate-methyl, carbendazim, and cyazofamid;

 Cyanoacetamide compounds, such as Cymoxanil;

 Compounds such as metallaxyl, metallaxyl M, oxadixyl, offurase, benalaxyl, furalaxyl, and cyprofuram (Cyproiuram) compounds such as metalaxyl M, metalaxyl M, oxadixyl, offurace, benalaxyl

 Sulfenic acid-based compounds such as dichloiluanide; copper-based compounds such as cuprichydroxide and organic copper (Oxine Copper);

 Isoxazole compounds such as Hymexazol;

 Josetyl aluminum (Fosetyl—A1), Turkish phos-methyl (Tolcofos—Methyl)

), S-benzyl, O-diisopropyl phosphorothioate, O-ethyl S

, S-diphenyl phosphorodithioate, organophosphorus compounds such as aluminum ethyl hydrogen phosphonate;

 N-halogenothioalkyl compounds such as Captan, Captafol, and Folpet;

 Procymidone (Procymidone), Iprodione (Iprodione), Pink Mouth Zolin (

Diclopoxyimide compounds such as Vinclozolin);

 Flutolanil, Mepronil, Zoxamid

), Benzanilide compounds such as tiadinil;

 Piperazine-based compounds such as Triforine;

 Pyridine compounds such as Pyrifenox;

 Carbinol compounds such as Fenarimol and Flutriafol;

 Piperidine-based compounds such as Fenpropidine;

Morpholinic compounds such as fenpropimorpli; Organotin compounds such as Fentin Hydroxide and Fentin Acetate;

 Urea compounds such as Pencycuron:

 Synamic acid-based compounds such as Dimethomorph and Flumorph;

 Phenylcarbamate compounds such as Diethofencarb; Cyanobilol compounds such as Fludioxonil, Fenpiclonil 1;

 Azoxystrobin (Azoxystrobin), Kresoxim—Methyl, Metominophen (Metominofen), Trifloxystrobin (Trif loxystrobin), Picoxystrobin (Picoxystrobin), Oryzastrobin (Dimoxystrobin) ), Stoline virulin compounds such as Fluoxastrobin; oxazolidinone compounds such as Famoxadone;

 Thiazole carboxamide compounds such as Ethaboxam; silylamide compounds such as Siltiophani;

 Amino acid amide carbamate compounds such as iprovalicarb and benthiaval icarb;

 Imidazolidine compounds such as fenamidone;

 Hydopenid compounds such as fenhexamid: benzenesulfonamide compounds such as Flusuliamid; oxime ether compounds such as Cyflufenamid; compounds such as Fenoxanil Phenoxyamide compounds;

 Triazole compounds such as Simeconazole;

 Atraquinone compounds;

 Crotonic acid compounds;

 Antibiotics and other compounds include Isoprothiolane, Tricyclazole, Pyroquilon, Pycluilon, Diclomezine, Probenazole, Quinoxyfen, Propamocap salt (Propamocarb Hydrochloride), Spiroxamine (Spirox amine), Chloropicr (Chloropicr in), Dazomet (Dazomet), Lithium Bamuna Thorium salt (Me m-sodium), Nicobifen (Nicobifen), Metrafenone, UTF-753 — 307, including Diclocymet and ProQuinazid.

 Examples of the pesticides, acaricides, or nematicides in the other pesticides, that is, the active ingredient compounds of the pesticides (generic names; including some applications) include, for example, Profenofos, Dic lorvos, Fenamiplios, Fenitrothion, EPN, Diazinon, Chlorpyrifos-niethyl, Acephate, Prothiophos Organic phosphoric ester compounds such as Fosthiazate, Phosphocarb, Cadusafos, Dislufoton;

Carbaryl, Propoxur, Aldicarb ), Carbofuran, Thiodicarb, Mesomyl (Metti omyl), Oxamyl, Oxamyl, Ethioiencarb, Pirimicarb, Fenobu carb, Fenobu carb Carbamate compounds such as Benfuracarb; Nepalistoxin derivatives such as Cartap and Thiocyclam;

 Organochlorinated compounds such as Dicofol, Tetradiion Organometallic compounds such as fenbutatin oxide (Fenbutatin Oxide); Fenvalerate, Permethrin, Cypermetrin, Pyreth compounds such as deltamethrin (Del tamethrin), cyhalothrin (Cyhalo thrin), tefluthrin (Eflufenprox), flufenprox (Fluienprox) and imidate (Imidate);

 A compound such as diflubenzuron, chlorfluazuron, teflubenzuron, teflubenzuron, flufenoxuron, bistrifluuron, or a compound such as noviilumuron;

 Juvenile hormone-like compounds such as methoprene;

 Pyridazinone compounds such as pyridaben;

 Pyridyl-based compounds such as fenpyroximate, fipronil, tebufenpyrad, ethiprole, tolfenpyrad, acetoprol (Acetoprole), and the like; Neonicotinoids such as Nitenpyram), Ace miprid, Thiacloprid, Thiamethoxam, Clothianidin, Clotiiianidin, Nidinoteiuran, Dinoteiuran, etc.

 Hydrazine compounds such as Tebufenozide, Methoxyfenozide and Chromafenozide;

 Pyridine compounds such as Pyridaryl and Flonicamid;

 Tetronic acid-based compounds such as Spirodiclofen, etc. Stomatovirin-based compounds such as Fluacrypyrin; Pyridinamine-based compounds such as Fluienerin;

Dinitro compounds, organic sulfur compounds, urea compounds, triazine compounds, hydrazone compounds, and other compounds such as buprofezin, hexthiazox, amitraz, chlordimimeform, and silafluofen (Si laf luof en), triazamate (Triazama te), pymetrozine (Pymetrozine), pyrimidifen (Pyrimidi fen), chlorfenapyr (Chlorfenapyr), indoxacarb (Indoxacarb), asequinoxazole (E equitoxazole, E equitoxazole) Cyromazine), 1,3-diclopropene (1,3-dicloropropene), verbutin (Verbutin), spiromesifen (Spiromesiien), thiazolylcinanonitrile (Thiazolylciimanoni) Compounds such as triaryl) and amidoflumet (Amidolumet); AKD-102, IA-1200, and the like. Furthermore, microbial pesticides such as BT agents, entomopathogenic virus agents, etc., Avermectin, Milbemica

It can also be mixed or used in combination with antibiotics such as ilbemycin, spinosad, and emamectin benzoate. Example

 Examples of the present invention will be described below, but the present invention should not be construed as being limited to only these examples.

[Synthesis Example 1 1] Synthesis of N- [2-chloro-5- (2-Chenyl) benzyl] methylrubamate (Compound No. 1-2) In a nitrogen atmosphere, toluene was added to 20 ml of N- ( An aqueous solution (10 ml) of 0.5 g of methyl 5-bromo-2-chlorobenzyl) carbamate, 0.05 g of tetrakis (triphenylphosphine) palladium (0> 0.05 g, and 0.19 g of sodium carbonate) was added. A solution of 0.28 g of 2-thiophenpolonic acid in ethanol (20 ml) was added to the mixture, the mixture was heated under reflux for 4 hours, and then cooled to room temperature, and water was added to the reaction solution, followed by extraction with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate, filtered, and the solvent was distilled off under reduced pressure.The residue was purified by silica gel column chromatography (eluent: n-hexane / ethyl acetate = 80/20) to give N- [2-chloro-5- (2-Chenyl) benzyl] methyl methylbamate (Compound No. 1-2) 0.19 g (yield 38%) was obtained as an oil.

_{Ή-NMR (CDC 1 3,} 400MHz) δ 7. 60 (s, 1H), 7. 45 (dd, 1H / = 2. 4Hz, 8Hz), 7. 34 (d, 1H / = 8 Hz), 7 28 (in, 2H) 7.07 (t, 1H / = 4Hz), 5.17 (br, 1H), 4.47 (d, 2H 7 = 4Hz), 3.64 (s, 3H)

[Synthesis Example 1-2] Synthesis of methyl N- [2-chloro-5- (5-pyrimidinyl) benzyl] carbamate (Compound No. 1-19)

(1) Synthesis of 5-bromo-2-chloro-methoxymethoxymethylbenzene

 To 0.28 g of 60% sodium hydride was added 15 ml of tetrahydrofuran, and after cooling to 0 ° C, a solution of 1.17 g of 5-bromo-2-chlorobenzylbenzene in 15 ml of tetrahydrofuran was added dropwise. Stir for 30 minutes. 0.55 g of chloromethyl methyl ether was added, and the mixture was stirred at room temperature for 9 hours. After the completion of the reaction, the reaction solution was poured into water and extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate, filtered, and the solvent was distilled off under reduced pressure. The residue was purified by silica gel column chromatography (eluent: n-hexane / ethyl acetate = 95/5) to give 1.25 g (90% yield) of 5-bromo-2-chloro-methoxymethoxymethylbenzene as an oil. Obtained as a product.

(2) Synthesis of 1- (4-chloro-3-methoxymethoxymethyl) phenylporonic acid

Under a nitrogen atmosphere, to a solution of 1.25 g of 5-bromo-2-chloro-methoxymethoxymethylbenzene in tetrahydrofuran (30 ml) at -78 ^ 0 was added 4.47 ml of n-butyllithium (1.58 M). Stir for 30 minutes. 0.98 g of trimethyl borate was added, and the mixture was stirred at -78 ° C for 1 hour and at room temperature for 2 hours. 20 ml of 10% hydrochloric acid was added to this solution, and the mixture was stirred overnight. This solution was extracted with a jetilter. The organic layer was dried over anhydrous sodium sulfate, filtered, and the solvent was distilled off under reduced pressure. The residue was washed with hexane to obtain 0.82 g (75) of a crude product of 4-chloro-3-methoxymethoxymethylphenylporonic acid.

(3) Synthesis of 5- (4-chloro-3-methoxymethoxymethylphenyl) pyrimidine Under a nitrogen atmosphere, 0.37 g of 5-bromopyrimidine and 0.13 g of tetrakis (triphenylphosphine) palladium (0) in 20 ml of toluene An aqueous solution (10 ml) of 0.25 g of sodium carbonate was added. To this solution, an ethanol solution (10 ml) of 0.82 g of a crude product of 4-chloro-3-methoxymethoxymethylphenylporonic acid was added, and the mixed solution was heated under reflux for 4 hours and then cooled to room temperature. Water was added to the reaction solution, which was extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate, filtered, and the solvent was distilled off under reduced pressure. The residue was purified by silica gel column chromatography (eluent: n-hexane / ethyl acetate = 50/50), and 0.43 g of 5- (4-methoxy-3-methoxymethoxymethylphenyl) pyrimidine (yield: Rate 70%).

(4) Synthesis of 2-chloro-5- (5-pyrimidinyl) benzyl alcohol

 To 0.43 g of 5- (4-chloro-3-methoxymethoxymethylphenyl) pyrimidine was added 10 ml of 10 mM concentrated hydrochloric acid in ethanol, and the mixture was refluxed for 4 hours. After the reaction solution was cooled to room temperature, the solution was made basic with a sodium hydroxide solution, and extracted with getyl ether. The organic layer was dried over anhydrous sodium sulfate, filtered, and the solvent was distilled off under reduced pressure. The residue was purified by silica gel column chromatography (eluent: n-hexane / ethyl acetate = 30/70) to obtain 0.20 g of 2-chloro-5- (5-pyrimidinyl) benzyl alcohol (55% yield). Was.

(5) Methyl N- [2-chloro-5- (5-pyrimidinyl) benzyl] carbamate

 0.25 g of 2-chloro-5- (5-pyrimidinyl) benzyl alcohol was dissolved in ethylene dalicol dimethyl ether, 0.24 g of thionyl bromide was added to this solution at 0 ° C, and the mixture was stirred at room temperature for 4 hours. did. Water was added to the reaction solution, and extracted with toluene. The organic layer was washed with an aqueous solution of sodium carbonate, dried over anhydrous sodium sulfate and filtered, and the solvent was distilled off under reduced pressure. 10 ml of dimethylformamide, 0.14 g of potassium cyanate and 3 ml of methanol were added to the residue, and the mixture was stirred at room temperature overnight and at 100 at 3 hours. After cooling the reaction solution to room temperature, water was added and extracted with getyl ether. The organic layer was dried over anhydrous sodium sulfate, filtered, and the solvent was distilled off under reduced pressure. The residue was purified by silica gel column chromatography (eluent: n-hexane / ethyl acetate = 50/50) to give N- [2-octanol-5- (5-pyrimidinyl) benzyl] methyl methylbamate ( Compound No. 1-19) 0.05 g (melting point 126.5; yield 19%) was obtained. Ή-NMR (CDC 13, 400MHz) 59.22 (s, 1H), 8.94 (s, 2Η), 7.60 (s, 1Η), 7.52 (d, 1H 7 = 8.4 Hz) 7.43 (dd, 1H / = 2Hz 8.4Hz), 5.25 (br, 1H), 4.52 (d, 2H 7 = 8.8Hz), 3.72 (s, 3H

[Synthesis Example 13] Synthesis of methyl 5- (5-methyl-2-phenyl) -2-chlorophenylcarbazate (Compound No. 1-57)

(1) Synthesis of methyl 5-promo-2-chloromethylcarbamate

20 ml of water and 20 ml of concentrated hydrochloric acid were added to 2.00 g of 5-bromo-2-chloroaniline, and the mixture was cooled to 0 and stirred. Then, while maintaining the temperature at 0, 0.66 g of an aqueous solution of sodium nitrite (10 ml) was added dropwise. After adding the sodium nitrite solution, stir the mixture at 0 for 1 hour did. Next, a solution of 4.37 g of tin (II) chloride dihydrate in 10 ml of concentrated hydrochloric acid was added to the mixture, and the mixture was stirred at 0 for 1 hour. Washed. The crystals were added to 200 ml of a 10% aqueous sodium hydroxide solution, stirred for 10 minutes, and then extracted with getyl ether. The ether layer was dried over sodium sulfate and filtered, and the solvent was distilled off under reduced pressure to obtain 2.96 g of crude crystals of 5-bromo-12-chlorophenylphenylhydrazine. This was dissolved in 20 ml of toluene, 1.23 g of triethylamine was added to the toluene solution, and the mixture was cooled to 0. Then, 0.66 g of methyl chloroformate was added, and the mixture was stirred at 0 for 30 minutes. The mixture was washed with water, dried over anhydrous sodium sulfate, filtered, and the solvent was distilled off under reduced pressure. The residue was purified by silica gel column chromatography (eluent: n-hexane / ethyl acetate = 80/20) to obtain 0.43 g (yield 17%) of methyl 5-bromo-2-chlorophenylcarbazinate Was.

(2) Synthesis of methyl 5- (5-methyl-2-phenyl) -2-chlorophenylcarbazate 0.25 g of methyl 5-bromo-2-chlorophenylcarbazinate obtained in the above example was obtained. 0.02 g of palladium acetate, 0.04 g of tricyclohexylphosphine, 0.24 g of potassium t-butoxide and 1 ml of water were added to the solution dissolved in 8 ml of dioxane with stirring, and 5-methylthiophene- A solution of 0.15 g of 2-boronic acid dissolved in 2iiil of dioxane was added, and the mixture was stirred at 100 ° C for 4 hours. After cooling to room temperature, the reaction solution was poured into water and extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate, filtered, and the solvent was distilled off under reduced pressure. The residue was purified by silica gel column chromatography (eluent: n-hexane / ethyl acetate = 80/20), and yellow oily methyl 5- (5-methyl-2-thenyl) -2-chlorophenylcarbamate was obtained. (Compound No. 1-57) 0.08 g (38% yield) was obtained.

'' H-NMR (CDC13, 400MHz) δ 7.23 (d, 1H 7 = 8Hz), 7.08 (d, 1H 7 = 2.4Hz), 7.05 (d, 1H / = 3.6Hz), 7.00 (dd, 1H J = l. 4Hz 8Hz) 6.69 (d, 1H /=2.4Hz), 6.51 (br, 1H), 6.23 (br, 1H), 3.76 ( s, 3H), 2.48 (s, 3H)

[Synthesis Example 1-4] Synthesis of methyl N- [2-chloro-5- (2-thenyl) benzyl] -N-methylcarbamate (Compound No. 1-76)

(1) Synthesis of methyl N- [5-bromo-2-chlorobenzyl] -N-methylcarbamate 2 ml of tetrahydrofuran was added to 0.08 g of 60% sodium hydride, and the mixture was cooled to 0.

A solution of 0.55 g of methyl N- [5-bromo-2-chlorobenzyl] carbamate in 6 ml of tetrahydrofuran was added dropwise, and the mixture was stirred for 30 minutes. 0.30 g of methyl iodide was added, and the mixture was stirred at room temperature for 4 hours. After the completion of the reaction, the reaction solution was poured into water and extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate, filtered, and the solvent was distilled off under reduced pressure. The residue was purified by silica gel column chromatography (eluent: n-hexane / ethyl acetate = 80/20), and 0.40 g (76% yield) of methyl N--promo-2-cyclobutamate) -N-methylcarbamate was obtained. Was obtained as an oil.

(2) Synthesis of N- [2-culo-5- (2-Chenyl) benzyl] -methyl N-methylcarbamate N- [5-bromo-2] synthesized in the above synthesis example in 5 ml of toluene under a nitrogen atmosphere. -Cloth benzyl] An aqueous solution (2 ml) of 0.30 g of methyl methylcarbamate, 0.06 g of tetrakis (triphenylphosphine) palladium (0), and 0.24 g of sodium carbonate was added. An ethanol solution (2 ml) of 0.19 g of 2-thiophenboronic acid was added to this solution, and the mixed solution was refluxed and heated for 4 hours, and then cooled to room temperature. Water was added to the reaction solution, which was extracted with ethyl acetate. Organic The layer was dried over anhydrous sodium sulfate, filtered, and the solvent was distilled off under reduced pressure. The residue was purified by silica gel column chromatography (eluent: n-hexane / ethyl acetate = 90/10), and methyl N- [2-chloro-5- (2-thenyl) benzyl] -N-methylmethylcarbamate (compound 0.116 g (53% yield) of Nol-76) was obtained as an oil.

_{^{1 H-NMR (CDC1 3,}} 400MHz) δ 7. 45-7. 26 (m, 511), 7. 07 (t, III / = 4Hz), 4. 63 (d, 2H 7 = 25. 6 Hz) , 3.73 (d, 311 /-10.8 Hz), 2.97 (d, 3H 7 = 29.2 Hz) The compound of the present invention produced by the method according to the above synthesis example is shown in Table 11 below. And Tables 1-2. However, the compound of the present invention is not limited to these. In each table, Me represents methyl, Et represents ethyl, n-Pr represents normal-propyl, i-Pr represents iso-propyl, Bu (represents Yuichi Ichiri-butyl, c-Pr represents cyclopropyl, respectively. The melting points of the compounds described in Tables 11 and 12 other than Compound No. 1-1 are measured using an automatic melting point analyzer (METHOD). The measurement was carried out using METTLER FP62 manufactured by Latoledo.

o.Het X ¹ X ² X ³ X ⁴ DG ¹ G ² R ³ Physical properties -1- 3-Cenyl HHHH CH ₂ OO Me 71-73 ° C -2 2-Cenyl HHH CI CH2 OO Me Oil -3 3-Che two JHHH CI CH2 OO Me oil -4 2- thienyl _{HHHO e CH 2 OO Me 96.3 °} C -5 2- Choi Le _{HHHF CH 2 0 O Me 51.9 C} -6 2- thienyl _{HHH Me CH 2 0 O Me 102.3} C -7 2-Chenyl HHH CI CH ₂₀ O Et 73.3 ° C -8 2-Chenyl HHH CI CH ₂ 0 O CH2CCI3 114.0 C -9 2-Chenyl HHH CI CH ₂ 0 On-Pr 52.7 ° C -10 2- Chenyl HHH CI CH ₂₀ O i-Pr 152.3 ° C -11 2-Chenyl HHH CI CH ₂₀ O Bu (t) 98.3 ° C -12 2-furanyl HHH CI CH ₂₀ O Me 85 ° C -13 2- to 'Upushironganma thienyl _{HHH CI CH 2 0 O Me 230} C -14 to 2 "Nso" furanyl HHH CI CH ₂ 0 O Me oil -15 to 3' - down Γ thienyl _{HHH CI CH 2 0 O Me 98} ° C -16 5-Methyl-2-Chenyl HHH CI CH ₂₀ O Me 99.0 ° C -17 5-Ph-, π-M-2-Cenyl HHH CI CH 0 0 Me 113.3 "C -18 5-Chloro-2- thienyl _{HHH CI CH 2 0 0 Me 112.1} ° C -19 5- Pirimishi _{"El. HHH CI CH 2 0 0 Me} 126.5 ° C -20 4,5- 'U mode-2-thienyl HHH CI CH ₂ 0 0 Me

-21 3,5-Shif, Lomo -2-cell HHH CI CH ₂₀₀ Me

-22 4,5-Si * Black mouth- 2-Chenyl HHH CI CH ₂₀₀ Me

-23 3,5-Si, -Cu Chenyl HHH CI CH ₂ 0 0 Me

-24 2-Chenyl CI HHH CH ₂₀₀ Me

-25 2 -Chenyl H CI HH CH ₂ 0 0 Me

-26 2-Chenyl HH CI H CH ₂₀₀ Me

 ^ Ki j d ~ ichi— | n n

-28 2-Chenyl HHH CF ₃ CH ₂ 0 Me

-29 2-Chenyl HHH OCH ₂ CF ₃ CH ₂ 0 Me

-30 2-Chenyl HHH CI CH ₂ s 0 Me

-31 2-Chenyl HHH CI CH ₂ NH 0 Me

-32 2-thienyl _{HHH CI CH 2 N e 0 Me} 144.2 ° C -33 2- thienyl _{HHH CI CH 2 O 0 c-} Pr

-34 2 Pirishi 'Le HHH CI CH _2. O 0 Me

 -35 3-Piryl H H H CI CH2 0 0 Me

 -36 4-Piryl H H H CI CH2 0 0 Me

-37 2-Pyrimici'nyl HHH CI CH ₂ 0 0 Me

-38 4-Pyrimici "nil HHH CI CH ₂ O 0 Me

 -39 2-Quinolyl H H H CI CH 0 0 Me

-40 2-Quinoxaaryl.. HHH CI CH ₂ O 0 Me (Continued from Table 1-1)

(Table 1-1)

[Synthesis Example 2-1]

 Synthesis of methyl 3- (3,3-dimethyl-1-butynyl) phenylcarbazate (Compound No.2-1)

(1) Synthesis of methyl 3-bromophenylcarbazate

 Tetrahydrofuran lOml was added to 3-bromophenylhydrazine hydrochloride l.Og, the suspension was cooled to 0, triethylamine 1.13g was added, and the mixture was stirred at 0 ° C for 30 minutes. Thereafter, at 0, 0.46 g of methyl chloroformate was gradually added, followed by stirring at room temperature for 4 hours. 50 ml of water was added to the reaction solution, extracted with ethyl acetate, the organic layer was dried over anhydrous sodium sulfate, filtered, and the solvent was distilled off under reduced pressure. The residue was purified by silica gel column chromatography (eluent n-hexane / ethyl acetate = 60/40) to obtain 0.82 g (yield 78%) of methyl 3-bromophenylcarbazate.

(2) Synthesis of methyl 3- (3,3-dimethyl-1-butynyl) phenylcarbazate

 0.54 g of tetrakistriphenylphosphine palladium A (0) was added to a solution of 2.27 g of methyl 3-bromophenylcarbazate obtained in (1) above in 50 ml of toluene while stirring, and copper iodide (1) 0.09 g and piperidine 1.58 g were added, and the mixture was heated to 90 under a nitrogen atmosphere. 1.51 g of 3,3-dimethyl-1-butyne was added to this solution and stirred for 4 hours. After cooling to room temperature, the reaction solution was poured into water and extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate, filtered, and the solvent was distilled off under reduced pressure. The residue was purified by silica gel column chromatography (eluent: n-hexane / ethyl acetate = 70/30) and the oily methyl 3- (3,3-dimethyl-1-butynyl) phenylcarbazinate was obtained. (Compound No. 2-1) 1.20 g (52% yield) was obtained.

'H-NMRiCDCl ₃ , 400MHz) 57.13 (t, 1H / = 8Hz), 6.91 (d, 1H 7 = 8Hz), 6.84 (s, 1H), 6.71 (d, 1H 7 = 8Hz), 6.49 (br , 1H), 5.69 (br, 1H), 3.74 (s, 3H), 1.26 (s, 9H)

[Synthesis Example 2-2]

 Synthesis of methyl 5- (3,3-dimethyl-1-butynyl) -2-methylphenylcarbazate (Compound No. 2-55)

(1) Synthesis of methyl 5-bromo-2-methylphenylcarbazate

To 6.22 g of 5-bromo-2-methylaniline, 60 ml of water and 60 ml of concentrated hydrochloric acid were added, and the mixture was cooled to O: and stirred. Then, while maintaining the temperature at 0 ° C, a solution of 2.30 g of sodium nitrite dissolved in 30 ml of water was added dropwise. After adding sodium nitrite solution, the mixture Was stirred at 0 ° C for 1 hour. Next, a solution of 15.04 g of tin (II) chloride dihydrate in 30 ml of concentrated hydrochloric acid was added to the mixture, and the mixture was stirred for 1 hour at Ot, and the precipitated crystals were filtered by suction and washed with water. did. The crystals were added to 200 ml of a 10% aqueous sodium hydroxide solution, stirred for 10 minutes, and extracted with getyl ether. The ether layer was dried over sodium sulfate and filtered, and the solvent was distilled off under reduced pressure to obtain 2.96 g of crude crystals of 5-bromo-2-methylphenylhydrazine. This was dissolved in 50 ml of toluene, 1.40 g of pyridine was added to the toluene solution, and the mixture was cooled to 0 ° C. Then, 1.39 g of methyl chloroformate was added, and the mixture was stirred for 30 minutes with TC. The extract was washed with water, dried over anhydrous sodium sulfate, filtered, and the solvent was distilled off under reduced pressure.The residue was purified by silica gel column chromatography (eluent: n-hexane / ethyl acetate = 75/25) to give 5-bromo- 2.20 g (yield 26%) of methyl 2-methylphenylcarbazate were obtained.

(2) Synthesis of methyl 5- (3,3-dimethyl-1-butenyl) -2-methylphenylcarbazate 1-OOg of methyl 5-bromo-2-methylphenylcarbazate obtained in (1) above was added to 0.22 g of tetrakistriphenylphosphine palladium (0), 0.04 g of copper iodide (1) and 0.65 g of piperidine were added to the solution dissolved in 30 ml of ren under stirring, and the mixture was added at 90 ° C under a nitrogen atmosphere. Until heated. To this solution, 0.63 g of 3,3-dimethyl-1-putin was added, followed by stirring at 90 at 4 hours. After cooling to room temperature, the reaction solution was poured into water and extracted with ethyl acetate. The organic layer was dried over sodium sulfate, filtered, and the solvent was distilled off under reduced pressure. The residue was purified by silica gel column chromatography (eluent: n-hexane / ethyl acetate = 70/30) to give methyl 5- (3,3-dimethyl-1-butynyl) -2-methylphenylcarbazate having a melting point of 122. (Compound No. 2-55) 0.89 g (88% yield) was obtained.

'' H-NM (CDC l _{3 l} 400MHz) δ 6.96 (d, 1H 7 = 8Hz), 6.88 (s, 1H), 6.86 (d, 1H 7-8Hz), 6.45 (br , 1H), 5.59 (br, 1H), 3.75 (s, 3H), 2.17 (s, 3H), 1.28 (s, 9H)

[Synthesis Example 2-3]

 Synthesis of methyl 5- (3,3-dimethyl-1-butynyl) -2-methylphenyldiazocarbonate (Compound No. 2-120)

 A solution prepared by dissolving 0.20 g of methyl 5- (3,3-dimethyl-1-butynyl) -2-methylphenylcarbazinate obtained in Synthesis Example 2-2 in 10 ml of toluene was added with 10% palladium power. 0.05 g of one bon was added. After stirring at room temperature for 2 minutes, the reaction solution was filtered using celite. The solvent was distilled off under reduced pressure, and the oily methyl 5- (3,3-dimethyl-1-butynyl) -2-methylphenyldiazocarboxylate (Compound No. 2-120) 0.19 g (yield 95%).

_{'H-NMR (CDC 1 3} , 400MHz) δ 7. 58 (d, 1H / = 2Hz), 7. 45 (dd, 1H J = 2Hz, 8Hz), 7. 26 (s, 1H), 4. 05 (s, 3H), 2.64 (s, 3H), 1.29 (s, 9H)

[Synthesis Example 2-4]

 Synthesis of methyl 2-chloro-5- (4-ethylphenylethynyl) phenylcarbazate (Compound No. 2-173)

(1) Synthesis of methyl 2-butamate-5-trimethylsilylethynylphenylcarbazate (Compound No. 2-48)

Tetrakis was added to a solution prepared by dissolving 10.00 g of methyl 5-bromo-2-chloromethylcarbamate in 30 ml of dimethylformamide, which was prepared according to Synthesis Example 2-2, while stirring. 4 005900

27 2.07 g of triphenylphenylphosphine palladium (0), 0.35 g of copper (I) iodide and 50 ml of getylamine were added, and the mixture was heated to 60 ° C under a nitrogen atmosphere. To this solution, 7.04 g of trimethylsilylacetylene was added, and the mixture was stirred at 60 ° C. for 13 hours. After cooling to room temperature, the reaction solution was poured into water and extracted with getyl ether. The organic layer was dried over sodium sulfate, filtered, and the solvent was distilled off under reduced pressure. The residue was purified by silica gel column chromatography (eluent: n-hexane / ethyl acetate = 80/20), and 9.25 g (87% yield) of 2-methyl-5-trimethylsilylethynylphenylcarbazinate, melting point 142, was obtained. Got.

'' H-NM (CDC 13, 400MHz) <5 7.20 (d, 1H / = 8Hz), 7.02 (d, 1H / = 2Hz), 6.93 (dd, 1H J = 2 Hz, 8Hz) , 6.47 (br, 1H), 6.22 (br, 1H), 3.76 (s, 3H), 0.23 (s, 9H)

(2) Synthesis of methyl 2-chloro-5-ethynylphenylcarbazate (Compound No. 2-29) Methyl 2-chloro-5-trimethylsilylethynylphenylcarbazate obtained in (1) above 9. 25 g was dissolved in 200 ml of tetrahydrofuran and cooled to -10 ° C. Then, 32.7 ml of tetrabutylammonium fluoride (1M, tetrahydrofuran solution) was added, and the mixture was stirred for 30 minutes with TC. The reaction solution was poured into water and extracted with ethyl acetate. The organic layer was extracted with sodium sulfate. The residue was purified by silica gel column chromatography (eluent: n-hexane / ethyl acetate = 75/25), and the residue was purified by melting at 101 ° C. -5.19 g (yield 75%) of methyl ethylcarbamate

'' H-NMR iCDC ls, 400MHz) 57.21 (d, 1H / = 8Hz), 7.05 (d, 1H / = 2Hz), 6.95 (dd, 1H Jl Hz, 8Hz), 6.49 (br, 1H), 6.22 (br, 1H), 3.76 (s, 3H), 3.05 (s, 1H)

(3) Synthesis of Methyl 2- (4-ethylphenyl-2-ethynyl) phenylcarbazinate (Compound No. 2-173)

 In a solution of 0.25 g of 1-bromo-4-ethylbenzene dissolved in 2 ml of N, N-dimethylformamide and 1 ml of getylamine, 0.08 g of tetrakistriphenylphosphineparadium (0), 0.08 g of copper iodide (1 ) 0.02 g was added. To this solution was added a solution of 0.15 g of methyl 2-chloro-5-ethynylphenylcarbazate obtained in (2) above in 2 ml of N, N-dimethylformamide, and the mixture was stirred at 90 for 2 hours. After cooling to room temperature, the reaction solution was poured into water, and extracted with getyl ether. The organic layer was dried over sodium sulfate, filtered, and the solvent was distilled off under reduced pressure. The residue was purified by silica gel column chromatography (eluent n-hexane / ethyl acetate = 85/15), and the 2-chloro-5- (4-ethylphenylethyninyl) phenylcarbazate at melting point 21 1 was obtained. 0.20 g (91% yield) was obtained.

_{'H-NM (CDC 1 3} , 400MHz) δ 7. 43 (d, 2H 7 = 8Hz), 7. 23 (d, 1H / = 8Hz), 7. 17 (d, 2H / = 8H z), 7 08 (d, 1H 7 = 2Hz), 6.99 (dd, 1H / = 2Hz, 8Hz), 6.51 (br, 1H), 6.28 (br, 1H), 3.77 (s, 3H ), 2.67 (α, 2H 7 = 7.2 Hz), 1.6 (t, 3H 7 = 7.2 Hz)

[Synthesis Example 2-5]

 Synthesis of N '-[2-chloro-5- (3,3-dimethyl-1-butynyl) phenyl] -methyl Ν'-methylcarbazate (Compound No. 2-225)

To 0.04 g of 60% sodium hydride was added 2 ml of tetrahydrofuran, and the mixture was cooled to 0, and then 0.25 g of methyl -5- (3,3-dimethyl-1-butynyl) phenylcarbazinate was added. A solution dissolved in trahydrofuran 6πι1 was added dropwise and stirred for 10 minutes. Dimethyl sulfate (0.1 Og) was added, and the mixture was stirred at room temperature for 1 hour. After the reaction is completed, pour the reaction solution into water, 0

28 extractions. The organic layer was dried over anhydrous sodium sulfate, filtered, and the solvent was distilled off under reduced pressure. The residue was purified by silica gel column chromatography (eluent: n-hexane / ethyl acetate = 85/15) to give N '-[2-cloro-5- (3,3-dimethyl) with a melting point of 95. 1-butynyl) phenyl] -Ν'-methylcarbazate (Compound No. 2-225) 0.04 g (20% yield) was obtained.

'' H-NMR (CDC l _{3 l} 300MHz) 57.16 (d, 1H / = 8Hz), 6.85 (dd, III / = 2Hz, 8Hz), 6.72 (d, 1H / = 2Hz), 6.33 (br, 1H), 3.72 (s, 3H), 3.25 (s, 311), 1.30 (s, 9H) The compounds of the present invention produced are shown in Tables 2-1, 2-2 and 2-3 below. However, the compounds of the present invention are not limited to these. In each table, Me is methyl, Et is ethyl, n-Pr is normal-propyl, i-Pr is isopropyl, c-Pr is cyclopropyl, and t-Bu is evening succinyl. , Ph represents phenyl, respectively. The immediate melting point in the physical properties column was measured using an automatic melting point measuring device (METTLER FP62 manufactured by Metra Toledo Co.).

(Continued from Table 2-1)

31

(Continued from Table 2-1)

(Continued from Table 2-1)

(Continued from Table 2-1)

(Continued from Table 21)

35

 Hereinafter, test examples of the agricultural and horticultural fungicide according to the present invention will be described. In each test, the control index was based on the following criteria.

 [Control index] [Degree of onset: Visual observation]

 5 No lesion or sporulation is observed.

4 Lesion area, number of lesions or sporulation area is less than 1 in untreated area 3 Lesion area, number of lesions or sporulation area is less than 40% of untreated area 2: Lesion area, number of lesions or sporulation area is less than 70% of the untreated area

 1: Lesion area, number of lesions or spore formation area is 70% or more of the untreated area Test Example 1-1 (Effectiveness test of cucumber powdery mildew)

 Cucumber (cultivar: four-leaf) was cultivated in a polypot having a diameter of 7.5 cm, and when the 1.5-leaf stage was reached, 10 ml of a drug solution adjusted to a predetermined concentration of the compound of the present invention was sprayed with a spray gun. After the drug solution was dried, a conidia suspension of powdery mildew was sprayed and inoculated, and kept in a constant temperature room of 20. Seven days after the inoculation, the spore-forming area of the first leaf was examined, and the control index was determined according to the evaluation criteria. As a result, among the above compounds, compound Nos. 1-2, 1-3, 1-5, 1-12, 1-15, 1-16, 1-17, 1-18, 1-57, 1-61 Compound No. 1-2, 1-12, 1-15, 1-16, Compound 17, 1-18, and 1-57 showed a control index of 4 or more at 125 ppm at 50 Oppm. Was. Test example 1–2 (Efficacy test of cucumber and disease prevention)

 Cucumber (cultivar: four-leaf) was cultivated in a polypot having a diameter of 7.5 cm, and when the 1.5-leaf stage was reached, 10 ml of a drug solution adjusted to a predetermined concentration of the compound of the present invention was sprayed with a spray gun. After the drug solution had dried, cucumber and zoosporangial suspension of the diseased bacteria were spray-inoculated and kept in a constant temperature room at 20 ° C. Seven days after the inoculation, the lesion area of the first leaf was examined, and the control index was determined according to the evaluation criteria. As a result, among the above compounds, Compound No. 1-2, 1-4, 1-5, 1-7, 1-12, 1-1

4, 500, 15-15, 1-16, 1-17, 1-19, 1-55, 1-56, 1-57, 1-58, 1-59, 1-61, 1-62, 1-76 Showed an effect of a control index of 4 or more.Compound No. 1-2, 4, 1-14, 1-15, 1-16, 4747, 1-55, 1-58, 1-59, 1-61 , 1-62 and U-76 showed an effect with a control index of 4 or more at 125 ppm. Test Example 2 — 1 (Evaluation of the preventive effect of powdery mildew on cucumber)

 Cucumber (cultivar: four-leaf) was cultivated in a polypot having a diameter of 7.5 cm, and when the 1.5-leaf stage was reached, 10 ml of a drug solution adjusted to a predetermined concentration of the compound of the present invention was sprayed with a spray gun. After the drug solution was dried, a conidia suspension of powdery mildew was sprayed and inoculated, and kept in a constant temperature room of 20. Seven days after the inoculation, the spore-forming area of the first leaf was examined, and the control index was determined according to the evaluation criteria. As a result, among the above compounds, Compound Nos. 2-1, 2-28, 2-55 and 2-120 showed an effect of a control index of 4 or more at 500 ppm. Compound Nos. 2--1, 2-28, 2-33, 2-34, 2-4

5, 2-47, 2-55, 2-61, 2-120, 2-121, 2-122, 2-123, 2-124, 2-129, 2-130, 2-13 4, 2-143 , 2-149, 2-158, 2-166, 2-168, 2-169, 2-170, 2-171, 2-173, 2-174, 2-175, 2-177, 2-178, 2 -179, 2-180, 2-181, 2-182, 2-184, 2-187, 2-188, 2-18 9, 2-191, 2-192, 2-195, 2-196, 2- 201, 2-202, 2-203, 2-204 and 2-224 showed an effect with a control index of 4 or more at 125 ppm. Test Example 2 — 2

A cucumber (variety: four leaves) was cultivated in a polypot having a diameter of 7.5 cm, and when the 1.5 leaf stage was reached, 1 Oml of a drug solution adjusted to a predetermined concentration of the compound of the present invention was sprayed with a spray gun. After the drug solution had dried, cucumber and zoosporangial suspension of the diseased fungus were spray-inoculated and kept in 20 thermostatic chambers. Seven days after the inoculation, the lesion area of the first leaf was examined, and the control index was determined according to the evaluation criteria. As a result, among the above compounds, Compound Nos. 2-1, 2-28, 2-55 and 2-120 exhibited an effect of a control index of 4 or more at 500 ppm. Compound Nos. 2-1, 2-29, 2-33, 2-34, 2-44, 2-45, 2-46, 2-47, 2-61, 2-75, 2-87, 2 -88, 2-120, 2-121, 2-122, 2-123, 2-124, 2-129, 2-130, 2-134, 2-143, 2-144, 2-149, 2-158, 2-161, 2-163, 2-16 5, 2-166, 2 -167, 2-168, 2-169, 2-170, 2-171, 2-173, 2-175, 2-176, 2-178, 2-179, 2-180, 2-181, 2-182 , 2-183, 2-184, 2-185, 2-187, 2-188, 2-189, 2-190, 2-191, 2-192, 2-193, 2-194, 2-195, 2-196, 2-201, 2-202, 2-203, 2-204, 2-215, 2-216, 2-224, 2-225, 2-242, 2-244, 2-255, 2- 256, 2-259, 2-260, 2-261 and 2-267 showed an effect with a control index of 4 or more at 125 ppm. Next, formulation examples of the present invention will be described. However, the formulation amount, dosage form, and the like in the present invention are not limited to the description examples only. Formulation Example 1

 (1) 20 parts by weight of the compound of the present invention

(2) Clay 72 parts by weight

(3) Sodium ligninsulfonate

The above components are uniformly mixed to form a wettable powder. Formulation Example 2

 (1) Compound of the present invention

 (2) 95 parts by weight or more of talc Mix uniformly to make a powder. Formulation Example 3

 (1) 20 parts by weight of the compound of the present invention

(2) N, N'-dimethylacetamide 20 parts by weight

(3) Polyoxyethylene alkyl phenyl ether 10 parts by weight

(4) Xylene 50 parts by weight or more is uniformly mixed and dissolved to form an emulsion. Formulation Example 4

 (1) 68 parts by weight of clay

(2) Sodium ligninsulfonate

 (3) Polyoxyethylene alkyl sulfate

 (4) Fine silica 25 parts by weight A mixture of the above components and the compound of the present invention are mixed in a weight ratio of 4: 1 to obtain a wettable powder. Formulation Example 5

 (1) 50 parts by weight of the compound of the present invention

(2) Talented X-rated hotel. Lialkylphenylphosphate-triethano-lamine

 (3) Silicone 0.

 (4) Water 47.8 parts by weight or more

 (5) 5 parts by weight of sodium polycarboxylate

(6) 42.8 parts by weight of anhydrous sodium sulfate And uniformly mixed, granulated and dried to obtain a wettable powder. Formulation Example 6

 (1) Compound of the present invention

 (2) Polyoxyethylene octyl phenyl ether

 (3) Polyoxyethylene phosphate ester 0.

 (4) Granular calcium carbonate93.

 (1) to (3) are uniformly mixed in advance, diluted with an appropriate amount of acetone, and then sprayed on (4) to remove acetone to form granules. Formulation Example 7

 (1) Compound of the present invention

(2) N-methyl-2-pyrrolidone 2.

 (3) 95.0 parts by weight or more of soybean oil are uniformly mixed and dissolved to give a fine powder; an ultra low volume formulation. Formulation Example 8

 (1) 20 parts by weight of the compound of the present invention

(2) Oxilated polyalkylphenol

Phosphate triethanolamine

 (3) Silicone 0

 (4) Xanthan gum 0

 (5) Ethylene glycol part

(6) Water 72 7 parts by weight or more uniformly mixed and ground to form an aqueous suspension, industrial applicability

 The substituted fin derivative represented by the formula [I] or a salt thereof exhibits an excellent effect as an active ingredient of a fungicide.

Claims

The scope of the claims

[Wherein ζ is a Υ = 'group {Y is a hydrogen atom; an aryl group which may be substituted with halogen, hydroxy, alkyl, octaalkyl, alkoxy or haloalkoxy; a halogen, hydroxy, aryl or alkoxy] An alkyl group which may be substituted; an alkoxyalkyl group which is substituted with aryl which may be substituted with halogen, alkyl or alkoxy; an alkenyl group which may be substituted with halogen, hydroxy, aryl or alkoxy; halogen, hydroxy, Alkynyl group optionally substituted by aryl or alkoxy; cycloalkyl group optionally substituted by halogen, hydroxy or alkoxy; cycloalkenyl group; cycloalkylalkyl group; optionally substituted by halogen, alkyl or alkoxy. Re Le alkyl group; a halogen, an alkyl or optionally Fuenoki Shiarukiru group optionally substituted by alkoxy; C (O) R ⁴ group; COOR ^{5 group; S i R s R 7 R} 8 - alkyl or S i R ⁶ R ⁷ R a ^{8 group, R 4, R 5, R} 6, R 7 and R ⁸ are identical or different, a hydrogen atom young properly may be substituted main evening position substituted for the a} or a group X is a halogen atom; a cyano group; a hydroxyl group; an alkyl group; an alkoxy group; a haloalkyl group or a haloalkoxy group, n is an integer of 0 to 4, and A is one NR ¹ -NR ^2. —Groups (R ¹ and R ² are each independently a hydrogen atom; an alkyl group; an alkenyl group; an alkynyl group; an alkoxyalkyl group; an alkyl group; a haloalkylcarbonyl group; a haloalkoxy group; an alkylthioalkyl group; a haloalkyl group ; Huenil A ruponyl group; an alkoxyl group, a ruponyl group or an arylalkyl group optionally substituted with halogen, alkyl or alkoxy), —N = N— group or —D—NH— group (D is halogen, hydroxy Or G ¹ is an oxygen atom, a sulfur atom or one NR ^a — group (R ^a is a hydrogen atom or an alkyl group); and G ² is an oxygen atom. Or a sulfur atom (G ¹ and G ² may be the same or different); R ³ is an alkyl group, an alkenyl group, an alkynyl group, a cycloalkyl group or an octaalkyl group. However,

A bactericide comprising, as an active ingredient, a substituted benzene derivative or a salt thereof represented by the following formula: Y is a single group, and A is a —D—NH group.

2. Formula [I -0]:

(Wherein, Het is an optionally substituted heterocyclic group, X, n, A, G ¹ , G ² and R ³ is as defined in claim 1) The fungicide according to claim 1, which contains a substituted benzene derivative represented by the formula or a salt thereof as an active ingredient.

 3. The germicidal according to claim 2, wherein the optionally substituted heterocyclic group represented by Het is a heterocyclic group optionally substituted with a halogen atom, an alkyl group, a haloalkyl group, an alkylthio group or an alkoxy group. Agent.

 4. The optionally substituted heterocyclic group represented by Het is an optionally substituted phenyl group, an optionally substituted benzothienyl group, an optionally substituted furanyl group, an optionally substituted benzofuranyl group. Group, optionally substituted pyridyl group, optionally substituted pyrimidinyl group, optionally substituted pyridazinyl group, optionally substituted quinolyl group, optionally substituted quinoxalyl group, optionally substituted isothiazolyl group 3. The fungicide according to claim 2, wherein the fungicide is a benzothienyl group which may be substituted.

 5. Formula []:

(In the formula, H et 'represents an optionally substituted phenyl group, an optionally substituted benzophenyl group, an optionally substituted furanyl group, an optionally substituted benzofuranyl group, and an optionally substituted A pyridyl group, an optionally substituted pyrimidinyl group or an optionally substituted pyridazinyl group; X is a halogen atom, an alkyl group, an alkoxy group, a haloalkyl group or a haloalkoxy group; n is an integer of 0 to 4 A "is one NH—NH— group or —D—NH— group (D is an alkylene group optionally substituted by halogen, hydroxy or alkoxy); G ¹ is an oxygen atom, a sulfur atom Or —NR ^a — group ( ^Ra is a hydrogen atom or an alkyl group); R ³ is an alkyl group, an alkenyl group, an alkynyl group, a cycloalkyl group or an octaalkyl group (provided that (1) H et 'is an optionally substituted phenyl group or an optionally substituted pyridyl group, and A "is -NH-NH-, and when n of Xn is 1, an ortho-position to A" When X is an alkyl group or an alkoxy group, and (2) Het ′ is a 2-hydroxypyridyl group, A ″ is an alkylene—NH— group, G ¹ is a —NR ^a — group, Except when R ³ is an alkyl group)} or a salt thereof.

{Wherein, X is a halogen atom; a cyano group; a hydroxyl group; an alkyl group; an alkoxy group; a haloalkyl group or a haloalkoxy group, n is an integer of 0 to 4, and A ′ ″ is 1 N Ri 1 NR ² — group (R ¹ and R ² are each independently a hydrogen atom; an alkyl group; an alkenyl group; an alkynyl group; an alkoxyalkyl group; an alkyl group; an octaalkyl group; a haloalkoxycarbonyl group; Haloal A kill group; a phenylcarbonyl group; an alkoxyl group or an arylalkyl group which may be substituted with halogen, alkyl or alkoxy) or —N = N one group, and R ³ ′ is an alkyl group; G ¹ ′ and G ² are each independently an oxygen atom or a sulfur atom; Y is a hydrogen atom; an aryl group which may be substituted with octagen, hydroxy, alkyl, octaalkyl, alkoxy or haloalkoxy; An alkyl group optionally substituted with hydroxy, aryl or alkoxy; an alkoxyalkyl group optionally substituted with aryl, optionally substituted with halogen, alkyl or alkoxy; even an alkyl group substituted with halogen, hydroxy, aryl or alkoxy Good alkenyl groups; halogen, hydroxy, aryl, or alk An alkynyl group optionally substituted with cycloalkyl; a cycloalkyl group optionally substituted with halogen, hydroxy or alkoxy; a cycloalkenyl group; a cycloalkylalkyl group; an arylalkyl optionally substituted with halogen, alkyl or alkoxy. group; iii androgenic, alkyl or optionally phenoxyethanol alkyl group optionally substituted by alkoxy; C (0) R ⁴ group; COOR ^{5 group; S i R 6 R 7 R} s alkyl or S i R ⁶ R ⁷ R ^A phenylhydrazine derivative or a salt thereof, which is represented by the formula: wherein there are ^eight groups, and R ⁴ , R ⁵ , R ⁶ , R ⁷ and R ⁸ are the same or different and are a hydrogen atom or an alkyl group. '

7. Formula [I "_ 1":

(Wherein, Y, G ′ \ G ² , R ¹ R ² , R ³ ′, X and n are as defined in the above-mentioned claim 6). Or a salt thereof.

8. Equation [1 "2]:

(Wherein, Y, G ′ \ G ² , R ³ ′, X and n are as defined in the aforementioned claim 6), or a phenylhydrazine derivative or a salt thereof according to claim 6.

9. X is a halogen atom, Shiano group, hydroxyl group, C ^ ₆ alkyl group, C ₆ alkoxy group 〇 I ₆ eight-necked alkyl group or C, be a _ ₆ eight-necked alkoxy group;! R ¹ and R ² are each independently hydrogen, C, to - ₆ alkyl groups, C _{2 6} alkenyl groups, C _{2 6} alkynyl groups, C WINCH ₆ alkoxy _d-6 alkyl groups, C ₆ alkyl Cal Poni Le groups, C,. _G a Roaruki Rukaruponiru groups, C ! be -e alkoxy force Ruponiru group or C -6 C port alkoxy force Lupo sulfonyl group;! Fueniruhidoraji emissions derivative or a salt thereof according to claim 6 R is C Les ₆ alkyl group.

1 0. Y is a hydrogen atom; !! halogen, hydroxy, C ₆ alkyl, C, - ₆ Nono Roaruki Le, C -e alkoxy or CI- 6 Ha port alkoxy optionally substituted with Ariru group; halogen, hydroxy, Aryl or C ₆ alkoxy Yes —,. Alkyl group;. Halogen, C ₆ alkyl or 〇 Bok ₆ alkoxy substituted substituted with good I § Li Ichiru also C ₆ alkoxy _d-1Q alkyl group;. A halogen, hydroxy, substituted with Ariru or C alkoxy May be C ₂ _i. Alkenyl group; a halogen, hydroxy, § Li Ichiru or ds alkoxy optionally substituted by C ₂ - _{1 Q} alkynyl; halogen, hydroxy or C) - in s alkoxy which may be substitution C ₃ _ ₆ sheet black alkyl group; C ₃ - ₆ shea Kuroarukeniru group; C ₃ - ₆ shea click port alkyl C, - ₆ alkyl group; a halogen, optionally substituted with C have _s alkyl or C Bok ₆ alkoxy Ariru. Bok ₆ alkyl group; a halogen, a good phenoxy _Ct-6 alkyl group optionally substituted by a C doctor ₆ alkyl or 〇 les ₆ alkoxy; C (O) R ⁴ group; COOR ^{5 group;! S i 6 7 1 ^} - Ji Bok ₆ Arukiru a group or 3 i R ⁶ R ⁷ R ^{8 group, R 4, R 5, R} s, R 7 and R ⁸ are identical or different, claim a hydrogen atom or a C! -e alkyl group 7. The phenylhydrazine derivative or a salt thereof according to 6.

11. The phenylhydrazine derivative or a salt thereof according to claim 9, wherein R ³ ′ is a methyl group or an ethyl group.

 12. A fungicide containing the substituted benzene derivative according to claim 5 or a salt thereof as an active ingredient.

 1 3. A fungicide comprising the phenylhydrazine derivative according to claim 6 or a salt thereof as an active ingredient.

 14. A method for controlling agricultural and horticultural crop diseases using a bactericidal effective amount of the substituted benzene derivative or a salt thereof according to claim 5.

 1 5. A method for controlling agricultural and horticultural crop diseases using a bactericidal effective amount of the X-nylhydrazine derivative or a salt thereof according to claim 6.

 16. Formula [I ']:

(In the formula, Het ′ is an optionally substituted phenyl group, an optionally substituted benzophenyl group, an optionally substituted furanyl group, an optionally substituted benzofuranyl group, an optionally substituted A pyridyl group, an optionally substituted pyrimidinyl group or an optionally substituted pyridazinyl group; X is a halogen atom, an alkyl group, an alkoxy group, a haloalkyl group or a haloalkoxy group; n is an integer of 0 to 4 by and; a "is _NH- NH - a group or one D-NH- group (D is halogen, hydroxy or alkoxy which may be substituted with an alkylene group); G ¹ is oxygen Harauma, sulfur atom Or one NR ^a — group (where ^Ra is a nitrogen atom or an alkyl group); R ³ is an alkyl group, an alkenyl group, an alkynyl group, a cycloalkyl group or an octaalkyl group (provided that (1 ) H et ' Is an optionally substituted phenyl group or an optionally substituted pyridyl group, A ”is —NH—NH—, and when n of X n is 1, X in the ortho position to A ″ Is an alkyl group or an alkoxy group, and (2) Het ′ is a 2-hydroxypyridyl group, A ″ is an alkylene—NH— group, G ¹ is a —NR ^a — group, and R ^A method for producing a substituted benzene derivative or a salt thereof represented by the formula:

(Wherein, L is a chlorine atom, a bromine atom, an iodine atom or OS0 ₂ CF ₃ group,, X, n, A " , G 1 and R ³ are as defined above) with a compound represented by, Equation [1—ΙΙΓ]

Wherein the substituted benzene derivative is reacted with a compound represented by Het'-B (OH) ₂ (where Het 'is as defined above) in the presence of a base and a palladium complex. Or a method for producing a salt thereof.

1 7. Formula [I "1 1":

(Wherein, Y, G ′ \ G ² , R ¹ R ² , R ³ ′, X and n are as defined in claim 6) or a method for producing the phenylhydrazine derivative or a salt thereof. And the equation [2-1 I]:

(Wherein, G, G ² , R ¹ , R ² , R ³ ′, X and n are as defined in the above claim 6; L is a bromine atom, an iodine atom or an OSO ₂ CF ₃ group) And a compound represented by the formula [2—

III-a]:

 H = Y

 (Wherein Y is as defined in claim 6), wherein the compound is reacted in the presence of a palladium complex and a base to produce the phenylhydrazine derivative or a salt thereof. Method.

1 8. Equation [1 "-1 2":

(Wherein, Y, G ′ \ G ² , R ³ ′, X and n are as defined in claim 6), wherein the phenylhydrazine derivative or a salt thereof is represented by the formula: [I "-1- a

(Wherein GG ² R ³ ′ X and n are as defined in the aforementioned claim 6), wherein the phenyl is oxidized in the presence of an oxidizing agent and an inert solvent. A method for producing a hydrazine derivative or a salt thereof.