JP2015013811A - Arylamidine derivative and plant disease controlling agent containing salt thereof - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a plant disease controlling agent exhibiting a controlling effect against a wide range of plant pathogenic microbes without depending on the application site.SOLUTION: There is provided a plant disease controlling agent which contains a compound represented by the formula (I) [wherein, Aand Aeach independently are an amidino which may be protected; Xand Xeach independently are an alkylene which can be substituted with a halogen atom (methylene in the alkylene may be replaced by an oxygen atom or a sulfur atom); Z is a substitutable imino or a substitutable nitrogen-containing hetero ring; Rand Reach independently are a halogen atom, a substitutable alkyl, a substitutable cycloalkyl, a substitutable alkoxy, a substitutable alkylthio, a nitro, a substitutable amino, a substitutable alkylsulfinyl or a substitutable alkylsulfonyl; 1 and m each independently are an integer of 0 to 4] or a salt thereof as an active ingredient.

Description

  The present invention relates to a plant disease control agent comprising an arylamidine derivative or a salt thereof as an active ingredient, and a novel arylamidine derivative or a salt thereof.

  Patent Documents 1 and 2 describe arylamidine derivatives useful as medical antifungal agents and their pharmaceutical uses, but do not describe that the derivatives are useful for controlling plant diseases.

  In general, medical antifungal agents and plant disease control agents are used in different ways, so that the bactericidal spectrum and physical / chemical properties required for the drugs are greatly different. For this reason, examples of practical use for both medical and plant disease control include streptomycin, which is an antibiotic, but there is no practical example of antifungal agents.

International Publication WO 03/074476 Japanese Patent Laying-Open No. 2005-097298

  Conventionally, many drugs provided for controlling plant diseases are each characterized in their spectrum and plant pathogen control effect. For example, the effect on specific plant diseases is not sufficient, the treatment effect is slightly inferior to the preventive effect, or the rain resistance is inferior or the residual effect is relatively short, depending on the application scene, It may show only practically insufficient control effects against plant pathogens. Therefore, creation of a plant disease control agent that exhibits a high control effect on a wide range of plant pathogens regardless of the application situation 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) or a salt thereof as an active ingredient, an excellent control effect against various plant diseases. The present invention was completed by obtaining the knowledge that the compound also has useful properties as a plant disease control agent.

  That is, the present invention relates to the formula (I):

[Where:
A ¹ and A ² are each independently amidino which may be protected;
X ¹ and X ² are each independently alkylene which may be substituted with a halogen atom (methylene in the alkylene may be replaced with an oxygen atom or a sulfur atom);
Z is an optionally substituted imino or an optionally substituted nitrogen-containing heterocycle;
R ¹ and R ² are each independently a halogen atom, optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted alkoxy, optionally substituted alkylthio, nitro, or optionally substituted. Good amino, optionally substituted alkylsulfinyl, or optionally substituted alkylsulfonyl;
l and m are each independently an integer of 0 to 4]
The plant disease control agent which contains the compound represented by these, or its salt as an active ingredient, and the plant disease control method characterized by applying the said plant disease control agent to a plant.

  Moreover, this invention is a formula (I): among the active ingredients of the said plant disease control agent:

[Where:
A ¹ and A ² are each independently amidino which may be protected;
X ¹ and X ² are each independently alkylene which may be substituted with a halogen atom (methylene in the alkylene may be replaced with an oxygen atom or a sulfur atom);
Z is an optionally substituted imino or an optionally substituted nitrogen-containing heterocycle;
R ¹ and R ² are each independently a halogen atom, optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted alkoxy, optionally substituted alkylthio, nitro, or optionally substituted. Good amino, optionally substituted alkylsulfinyl, or optionally substituted alkylsulfonyl;
l and m are each independently an integer of 0 to 4;
(1) (i) both A ¹ and A ² are bonded in the para position to X ¹ and X ² and
(a) when both X ¹ and X ² are alkylenes replaced by oxygen atoms and the oxygen atoms are both bonded to a benzene ring, or (b) ^one of X ¹ and X ² is replaced by a sulfur atom Alkylene, the other is an alkylene substituted with an oxygen atom or a sulfur atom, the sulfur atom and the oxygen atom are both bonded to a benzene ring, and Z is an optionally substituted imino;
(ii) A ¹ is bonded to X ¹ in the para position, and ^one of X ¹ and X ² is an alkylene substituted with a sulfur atom, and the other is an alkylene substituted with an oxygen atom or a sulfur atom, and the sulfur atom And a nitrogen-containing heterocyclic ring in which both the oxygen atom and oxygen atom are bonded to a benzene ring and Z may be substituted, and the nitrogen atom constituting the heterocyclic ring is bonded to X ¹ , or
(iii) A ² is bonded to X ² at the para position, ^one of X ¹ and X ² is an alkylene substituted with a sulfur atom, and the other is an alkylene substituted with an oxygen atom or a sulfur atom, the sulfur atom And the oxygen atom is bonded to the benzene ring, and Z is a nitrogen-containing heterocyclic ring which may be substituted, and the nitrogen atom constituting the heterocyclic ring is bonded to X ² ,
At least one of R ¹ and R ² is selected from the group consisting of optionally substituted alkylthio, nitro, optionally substituted amino, optionally substituted alkylsulfinyl, and optionally substituted alkylsulfonyl;
(2) A nitrogen-containing complex in which A ² is bonded to X ² in the para position, X ¹ is alkylene, the alkylene is bonded to the benzene ring through a carbon atom, and Z may be substituted. In the case of a ring, the carbon atom constituting the heterocyclic ring is bonded to X ² ;
(3) A nitrogen-containing complex in which A ¹ is bonded to X ¹ in the para position, X ² is alkylene, the alkylene is bonded to the benzene ring through a carbon atom, and Z may be substituted. When it is a ring, the carbon atom constituting the heterocyclic ring is bonded to X ¹ ]
And a novel compound or a salt thereof.

The plant disease control agent of the present invention has a high control effect against a wide range of plant pathogens and also has high safety.
Furthermore, the plant disease control agent of the present invention has a so-called residual effect that maintains the plant disease control effect for a long time after spraying the drug, and can exhibit an excellent effect when the crop is subjected to rainfall after spraying the drug. The so-called rain resistance is excellent. Since the plant disease control agent of the present invention has useful properties as such a plant disease control agent, the number of times the drug is used or the amount used is increased in consideration of rainfall after the spraying of the drug and the duration of the control effect. It is not necessary and can protect crops from plant diseases at lower cost and less effort.

Examples of the optionally protected amidino represented by A ¹ or A ² include, in addition to an unprotected amidino, —COR ′ (R ′ is an optionally substituted alkyl, an optionally substituted arylalkyl, a substituted Optionally substituted aryl, optionally substituted alkoxy, optionally substituted arylalkoxy or optionally substituted aryloxy), —OH, or —OCOR ″ (R ″ may be substituted). Amidino protected with alkyl, optionally substituted arylalkyl or optionally substituted aryl) or the formula:

And a group represented by the formula (where R ″ is the same as above).
Although the substitution position of the amidino which may be protected represented by A ¹ or A ² is not particularly limited, it is preferably substituted at the meta position or para position with respect to X ¹ and X ² .

The alkylene in the X ¹ or X ^2, for example, methylene, ethylene, trimethylene, tetramethylene, pentamethylene, hexamethylene, heptamethylene, octamethylene, nonamethylene, decamethylene, undecamethylene, such as dodecamethylene C _1- There are ₁₂ examples. The alkylene may be substituted with one or more halogen atoms which are the same or different.
One or more methylenes in the alkylene may be replaced with an oxygen atom or a sulfur atom, and the position and number of the replacement are not particularly limited.

The imino in Z may be substituted with a substituent represented by R ³ .
The R ^3, optionally substituted alkyl, optionally substituted arylalkyl, aryl which may be substituted, -COR '(R' is as defined above), - OH, -OR '' (R '' Are the same as those described above, and -OCOR ″ (where R ″ is the same as described above).

The nitrogen-containing heterocycle in Z contains one or more non-aromatic nitrogen atoms, and in some cases contains one or more heteroatoms other than nitrogen atoms (for example, oxygen atoms, sulfur atoms, etc.). Saturated or unsaturated 3 to 7 membered or polycyclic heterocyclic ring may be mentioned. In addition, the heterocyclic ring may be monocyclic or polycyclic, and may be substituted with an oxo group (═O).
Specific examples thereof include a 3-membered heterocyclic ring such as aziridin; a 4-membered heterocyclic ring such as azetidine; pyrrolidine, pyrroline, imidazolidine, imidazoline, pyrazolidine, pyrazoline, oxazolidine, oxazoline, isoxazolidine, isoxazoline, thiazolidine, thiazoline. , Isothiazolidine, isothiazoline, and the like; 6-membered heterocycles such as piperidine, piperazine, morpholine, thiomorpholine, perhydropyrimidine, perhydropyridazine; 7-membered heterocycles such as azepane and diazepane; And polycyclic heterocycles such as isoindoline, quinuclidine, 7-azabicyclo [2.2.1] heptane, 2,5-diazabicyclo [2.2.1] heptane, 2,5-diazabicyclo [2.2.2] octane; It is done.

  The nitrogen-containing heterocycle may have 1 to 8 substituents at substitutable positions. When the number of substituents is 2 or more, the substituents may be the same or different. Such substituents include halogen, alkyl, haloalkyl, alkoxy, haloalkoxy, alkylthio, haloalkylthio, nitro, thiocyanato, -COR '(R' is the same as above), -CSR '(R' is the same as above) ), -C (= S) SR "(R" is the same as above), -OH, -OCOR "(R" is the same as above), and the like.

The alkyl, alkoxy, alkylthio, alkylsulfinyl or alkylsulfonyl represented by R ¹ or R ² may have 1 to 7 substituents at substitutable positions, and when the substituent is 2 or more The substituents may be the same or different. Such substituents include halogen, alkoxy, haloalkoxy, aryl, aryloxy, arylalkoxy, alkylthio, haloalkylthio, alkylsulfinyl, haloalkylsulfinyl, alkylsulfonyl, haloalkylsulfonyl, nitro, -COR '(where R' ), -OH, -OCOR "(R" is the same as above), and the like.
Examples of the amino substituent represented by R ¹ or R ² include optionally substituted alkyl, optionally substituted arylalkyl, optionally substituted aryl, —COR ′ (R ′ is the same as above), — OR ″ (R ″ is the same as above) and the like.
The cycloalkyl represented by R ¹ or R ² may have 1 to 11 substituents at substitutable positions, and such a substituent includes the above-described nitrogen-containing heterocyclic ring. Examples of the substituent are the same as those described above.

Each substituent in the amino substituents represented by R ³ , R ′, R ″, and R ¹ or R ² may have a substituent at a substitutable position. Examples of the substituent on the alkyl or alkyl moiety include halogen, alkoxy, haloalkoxy, alkylthio, haloalkylthio, alkylsulfinyl, haloalkylsulfinyl, alkylsulfonyl, haloalkylsulfonyl, nitro, trimethylsilyl, thiocyanate and the like. Examples of the substituent on the aryl or aryl moiety include halogen, alkyl, haloalkyl, alkoxy, haloalkoxy, alkylthio, haloalkylthio, alkylsulfinyl, haloalkylsulfinyl, alkylsulfonyl, haloalkylsulfonyl, nitro, trimethylsilyl, thiocyanate and the like.

  In the present specification, unless otherwise specified, examples of the halogen atom or the halogen as a substituent include fluorine, chlorine, bromine and iodine atoms. The number of halogen atoms as a substituent may be 1 or 2 or more, and in the case of 2 or more, each halogen atom may be the same or different. Further, the halogen atom may be substituted at any position.

In the present specification, unless otherwise specified, examples of the alkyl or alkyl moiety include C _1-6 such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl, pentyl, hexyl and the like.
In the present specification, unless otherwise specified, examples of cycloalkyl include C _3-6 such as cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl.
In the present specification, unless otherwise specified, examples of the aryl or aryl moiety include C _6-10 such as phenyl and naphthyl.

  The salt of the compound of the formula (I) includes any salt that is acceptable in the technical field. For example, a salt with an inorganic acid such as hydrochloric acid, hydrobromic acid, sulfuric acid, phosphoric acid or the like. Salts with organic carboxylic acids such as tartaric acid, formic acid, acetic acid, citric acid, fumaric acid, maleic acid, trichloroacetic acid and trifluoroacetic acid; methanesulfonic acid, benzenesulfonic acid, p-toluenesulfonic acid, mesitylenesulfonic acid and naphthalene And salts with sulfonic acids such as sulfonic acids.

  The compound of the formula (I) may have isomers such as geometric isomers, tautomers, and optical isomers. In the present invention, both isomers and isomer mixtures are present. Is included. In the present specification, unless otherwise specified, isomers are described as a mixture. The present invention also includes various isomers other than those described above within the scope of technical common sense in the technical field.

  Depending on the type of isomer, the chemical structure may differ from the described structural formula, but those skilled in the art can fully recognize that these are related to the isomer, and therefore are within the scope of the present invention. Obviously.

  Some desirable embodiments of the substituent in the formula (I) will be described below. These aspects can also be combined with each other.

As A ¹ or A ² an unprotected amidino is preferred.

X ^{1 and} X ² are each independently preferably an alkylene (particularly C _2-8 alkylene) in which methylene in the alkylene may be substituted with oxygen or sulfur.

  Z is preferably an imino which may be substituted or a nitrogen-containing saturated heterocyclic ring (especially a 5- to 6-membered heterocyclic ring) which may be substituted.

R ¹ and R ² are each independently preferably an optionally substituted alkylthio (particularly methylthio), an optionally substituted amino or nitro.

  l and m are each preferably 1.

  The compound of the above formula (I) or a salt thereof (hereinafter also referred to as the compound of the present invention) can be produced according to the following production method, ordinary salt production method and usual amidino protection method. It is not limited to.

(Production method 1)
Compound (Ia), in which Z is an optionally substituted imino and A ¹ and A ² are unprotected amidino, can be produced, for example, by the following production method 1.

Wherein Z ¹ is an imino optionally substituted with R ³ ;
When Y ¹ is L, Y ² is amino or NHR ³ ; when Y ¹ is amino or NHR ³ , Y ² is L;
L is halogen (chlorine, bromine, iodine, etc.), —OSO ₂ R ⁴ (R ⁴ is alkyl optionally substituted with fluorine or the like, or aryl optionally substituted with alkyl, etc.), —OP ( A leaving group such as ═O) (OR ⁵ ) ₂ (R ⁵ is alkyl);
R ¹ , R ² , R ³ , X ¹ , X ² , l and m are the same as described above.

  Compound (IV) can be produced by reacting compound (II) with compound (III) in the presence of a base and a solvent.

  As the solvent used in this reaction, any solvent can be used as long as it does not adversely influence the reaction. For example, N, N-dimethylformamide, N, N-dimethylacetamide, 1-methyl-2-pyrrolidone, Examples include polar aprotic solvents such as acetonitrile and dimethyl sulfoxide; ethers such as tetrahydrofuran, dioxane and ethylene glycol diethyl ether; and the like.

Bases used in this reaction include alkali metal hydrides such as sodium hydride and potassium hydride; alkali metal carbonates such as sodium carbonate and potassium carbonate; alkali metals such as sodium hydrogen carbonate and potassium hydrogen carbonate. Bicarbonates; alkyllithiums such as n-butyllithium and t-butyllithium; organic bases such as triethylamine, diisopropylethylamine and pyridine;
The amount of the base used is equimolar or more, preferably 1.1 to 2.2 times the molar amount of compound (II) or compound (III).

  The reaction temperature is usually about 0 to 150 ° C., preferably about 10 to 100 ° C., and the reaction time is usually about 1 to 2 hours.

  Compound (II) and compound (III) can be produced by the methods described in WO 96/16947, WO 03/74476 and the like.

Conversion from compound (IV) to compound (Ia) can be carried out using Organic Functional Group Preparation (Vol. III), Academic Press (1970), WO 95/1168, WO 97/36862, WO 98/10763, WO 02/60861, JP-A-2-76843 and the like.
Hereinafter, the production method 2 to the production method 6 will be specifically described.

(Production method 2)
Compound (Ia) can be produced from compound (IV) via compound (V).

_Where R ⁶ is C _1-8 alkyl, or benzyl optionally substituted with alkyl, alkoxy, etc .;
R ¹ , R ² , X ¹ , X ² , Z ¹ , l and m are the same as described above.

Compound (V) can be produced by reacting compound (IV) with R ⁶ OH in the presence of an acid.

As R ⁶ OH, methanol and ethanol are usually used, but propanol, butanol, isobutanol, octanol, benzyl alcohol and the like can also be used.

As the solvent, R ⁶ OH is usually used, but ethers such as diethyl ether, tetrahydrofuran and dioxane; halogenated hydrocarbons such as methylene chloride and chloroform; aromatic hydrocarbons such as benzene and toluene. Etc. can also be used alone or in combination.

  As the acid, hydrogen chloride and hydrogen bromide are usually used, but perchloric acid, sulfonic acids such as methanesulfonic acid, p-toluenesulfonic acid, and the like can also be used.

  The reaction temperature is usually about -20 to 50 ° C, preferably about -10 to 20 ° C, and the reaction time is usually about 1 hour to 24 hours, preferably about 2 hours to 12 hours.

  Compound (Ia) can be produced by reacting compound (V) with ammonia or an ammonium salt in a solvent.

  As the ammonia, ammonia water or ammonia gas can be used as appropriate.

  Examples of ammonium salts include ammonium chloride, ammonium bromide, and ammonium acetate.

  As the solvent, alcohols such as methanol, ethanol and propanol are usually used, but ethers such as diethyl ether, tetrahydrofuran and dioxane; halogenated hydrocarbons such as methylene chloride and chloroform; N, N- Polar aprotic solvents such as dimethylformamide, N, N-dimethylacetamide, 1-methyl-2-pyrrolidone, acetonitrile, methyl sulfoxide; and the like can be used alone or in admixture.

  The reaction temperature is usually about −20 to 100 ° C., preferably about −10 to 80 ° C., and the reaction time is usually about 1 hour to 48 hours, preferably about 2 hours to 24 hours.

(Production method 3)
Compound (Ia) can be produced from compound (IV) via compound (VI) and compound (VII).

In which R ⁷ is C _1-4 alkyl;
R ¹ , R ² , X ¹ , X ² , Z ¹ , l and m are the same as described above.

  Compound (VI) can be produced by reacting compound (IV) with hydrogen sulfide in the presence of a base and a solvent.

  Examples of the base include ammonia, triethylamine, diisopropylethylamine, pyridine, 2-picoline and the like.

  As the solvent, alcohols such as methanol, ethanol and isopropanol, and bases such as pyridine and 2-picoline can also be used as the solvent.

  The reaction temperature is usually about 0 to 120 ° C., preferably about 20 to 100 ° C., and the reaction time is usually about 1 to 48 hours, preferably about 2 to 24 hours.

  Compound (VII) can be produced by alkylating compound (VI) with an alkylating agent in a solvent.

  Examples of the alkylating agent include alkyl halides such as methyl iodide, ethyl iodide, and ethyl bromide; dialkyl sulfates such as dimethyl sulfate and diethyl sulfate.

  Examples of the solvent include ketones such as acetone and 2-butanone; halogenated hydrocarbons such as methylene chloride and chloroform; and the like can be used alone or as a mixture.

  The reaction temperature is usually about 0 to 100 ° C., preferably about 10 to 80 ° C., and the reaction time is usually about 1 to 48 hours, preferably about 2 to 24 hours.

  Compound (Ia) can be produced by reacting compound (VII) with ammonia or an ammonium salt in a solvent.

  As the ammonia, ammonia water or ammonia gas can be used as appropriate.

  Examples of ammonium salts include ammonium chloride, ammonium bromide, and ammonium acetate.

  As the solvent, alcohols such as methanol, ethanol and propanol are usually used, but ethers such as diethyl ether, tetrahydrofuran and dioxane; halogenated hydrocarbons such as methylene chloride and chloroform; N, N- Polar aprotic solvents such as dimethylformamide, N, N-dimethylacetamide, 1-methyl-2-pyrrolidone, acetonitrile, methyl sulfoxide; and the like can be used alone or in admixture.

  The reaction temperature is usually about −20 to 100 ° C., preferably about −10 to 80 ° C., and the reaction time is usually about 1 to 24 hours, preferably about 2 to 12 hours.

(Production Method 4)
Compound (Ia) can be produced from compound (IV) via compound (Ia-1) in which amidino is protected.

In the formula, R ¹ , R ² , X ¹ , X ² , Z ¹ , l and m are the same as described above.

  Compound (Ia-1) can be produced by reacting compound (IV) with hydroxylamine or a hydroxylamine salt in a solvent.

  Examples of the hydroxylamine salt include hydrochloride and sulfate.

  Examples of the solvent include alcohols such as methanol, ethanol and isopropanol; polar aprotic solvents such as dimethyl sulfoxide and N, N-dimethylformamide; and the like can be used alone or in combination.

  When a hydroxylamine salt is used in this reaction, an inorganic base such as sodium acetate, potassium acetate, sodium carbonate or potassium carbonate or an organic base such as triethylamine, diisopropylethylamine or pyridine is used to adjust the pH of the reaction solution. Is usually used.

  The reaction temperature is usually about 0 to 120 ° C., preferably about 20 to 80 ° C., and the reaction time is usually about 1 to 24 hours, preferably about 2 to 12 hours.

  Compound (Ia-1) can be converted to compound (Ia) by a hydrogenation reaction using a metal catalyst such as Raney nickel, palladium, rhodium or the like, or a reduction reaction with zinc in acetic acid.

  Examples of the solvent used in the hydrogenation reaction include carboxylic acids such as formic acid and acetic acid; ethers such as tetrahydrofuran and dioxane; alcohols such as methanol and ethanol; and the like.

  The reaction temperature of the hydrogenation reaction is usually about 0 to 120 ° C., preferably about 20 to 80 ° C., and the reaction time is usually about 1 to 24 hours, preferably about 2 to 12 hours.

  The reaction temperature for the reduction with zinc in acetic acid is usually about 10 to 110 ° C., preferably about 30 to 80 ° C., and the reaction time is usually about 1 to 24 hours, preferably about 2 to 12 hours. is there.

(Production method 5)
Compound (Ia) can also be produced from compound (Ia-1) via compound (Ia-2) in which amidino is protected.

Wherein R ⁸ is alkyl optionally substituted with halogen or the like, or arylalkyl optionally substituted with alkyl, alkoxy or the like;
R ¹ , R ² , X ¹ , X ² , Z ¹ , l and m are the same as described above.

  Compound (Ia-2) can be produced by reacting compound (Ia-1) with an acid halide or acid anhydride in the presence of an acid or a base catalyst in a solvent.

Examples of the acid catalyst include carboxylic acids such as acetic acid and trifluoroacetic acid; inorganic acids such as hydrochloric acid and sulfuric acid; sulfonic acids such as methanesulfonic acid and p-toluenesulfonic acid; and the like.
Examples of the base catalyst include organic bases such as triethylamine, diisopropylethylamine, and pyridine.

  Examples of the acid halide include acetyl chloride, propionyl chloride, butyryl chloride, phenylacetic acid chloride and the like. Examples of the acid anhydride include acetic anhydride and propionic anhydride.

  Examples of the solvent include ethers such as diethyl ether, tetrahydrofuran and dioxane; halogenated hydrocarbons such as methylene chloride and chloroform, and these can be used alone or as a mixture.

  The reaction temperature is usually about 0 to 100 ° C., preferably about 10 to 60 ° C., and the reaction time is usually about 1 to 24 hours, preferably about 2 to 12 hours.

  Compound (Ia-2) can be converted to Compound (Ia) by a hydrogenation reaction using a metal catalyst such as Raney nickel, palladium, or rhodium in a solvent.

  Examples of the solvent include carboxylic acids such as formic acid and acetic acid; ethers such as tetrahydrofuran and dioxane; alcohols such as methanol and ethanol;

  The reaction temperature is usually about 0 to 120 ° C., preferably about 20 to 80 ° C., and the reaction time is usually about 1 to 24 hours, preferably about 2 to 12 hours.

(Production method 6)
Compound (Ia) can also be produced by reacting compound (IV) with lithium bis (trimethylsilyl) amide in a solvent.

In the formula, R ¹ , R ² , X ¹ , X ² , Z ¹ , l and m are the same as described above.

  Examples of the solvent include ethers such as diethyl ether and tetrahydrofuran; polar aprotic solvents such as N, N-dimethylformamide and hexamethylphosphoric triamide; and the like can be used alone or in combination. .

  The reaction temperature is usually about −78 to 50 ° C., preferably about −30 to 30 ° C., and the reaction time is usually about 1 to 24 hours, preferably about 2 to 12 hours.

(Production method 7)
Compound (Ib-1) in which Z is a nitrogen-containing saturated heterocyclic ring and X ¹ is substituted with a saturated heterocyclic nitrogen atom can be produced by the following production method 7.

In the formula, Z ² is a nitrogen-containing heterocycle, and a nitrogen atom constituting the heterocycle is bonded to X ¹ or R ⁹ ;
R ⁹ is an amino protecting group;
R ¹ , R ² , X ¹ , X ² , L, l and m are the same as described above.

Examples of the amino protecting group represented by R ⁹ include t-butoxycarbonyl, benzyloxycarbonyl, benzyl and the like.

  Compound (VIII) can be produced by a method described in WO 03/74476, WO 06/3881, or the like.

By reacting compound (VIII) in which R ⁹ is a t-butoxycarbonyl group with an inorganic acid or organic acid such as hydrochloric acid, sulfuric acid, nitric acid, trifluoroacetic acid, methanesulfonic acid, p-toluenesulfonic acid and the like in a solvent. Can be converted to compound (IX).

  Examples of the solvent include halogenated hydrocarbons such as methylene chloride and chloroform; ethers such as tetrahydrofuran and dioxane; alcohols such as methanol and ethanol; polar aprotic solvents such as acetonitrile and dimethylformamide; Or can be used in combination.

  The reaction temperature is usually about −20 to 120 ° C., preferably about 0 to 100 ° C., and the reaction time is usually about 1 to 24 hours, preferably about 2 to 12 hours.

Compound (VIII) in which R ⁹ is a benzyloxycarbonyl group or a benzyl group can be converted to compound (IX) by catalytic hydrogenation in a solvent using a catalyst such as palladium, palladium chloride, Raney nickel or the like.

  Examples of the solvent include alcohols such as methanol and ethanol; carboxylic acids such as formic acid and acetic acid; ethers such as tetrahydrofuran and dioxane; and the like. These can be used alone or in combination.

  The reaction temperature is usually about −20 to 120 ° C., preferably about 0 to 100 ° C., and the reaction time is usually about 1 to 24 hours, preferably about 2 to 12 hours.

  Compound (XI) can be obtained by reacting compound (IX) with compound (X) under the same reaction conditions as the reaction between compound (II) and compound (III) in Production Method 1.

  The method for converting compound (XI) to compound (Ib-1) can be appropriately selected from the methods for converting compound (IV) in production method 2 to production method 6 to compound (Ia). .

(Production method 8)
The compound (Ib-2) in which Z is a nitrogen-containing heterocycle and X ¹ ′ and X ² ′ are bonded to the carbon atom of the heterocycle can be produced by the following production method 8.

In the formula, X ¹ ′ and X ² ′ are each independently alkylene which may be substituted with a halogen atom (provided that methylene to which L in the alkylene is not bonded represents an oxygen atom or a sulfur atom) May be substituted);
Each W is independently an oxygen atom or a sulfur atom;
Z ³ is a nitrogen-containing heterocycle, and the carbon atom constituting the heterocycle is bonded to X ¹ ′ and X ² ′;
R ¹ , L and l are the same as described above.

  Compound (XII) can be produced according to the method described in WO 09/61879, WO 05/26165, Chemistry Letters, 1996, 747 and the like.

  Compound (XIV) can be obtained by reacting compound (XII) with compound (XIII) under the same reaction conditions as in the reaction between compound (II) and compound (III) in Production Method 1.

  The method for converting compound (XIV) to compound (Ib-2) can be appropriately selected from the methods for converting compound (IV) in production method 2 to production method 6 to compound (Ia). .

  The compound of the present invention can be applied to, for example, Mastigomycotina, Ascomycotina, Basidiomycotina, Deuteromycotina, Zygomycotina, etc. It can control phytopathogenic fungi belonging to them, and is particularly effective for controlling phytopathogenic fungi belonging to Ascomycotina or Deuteromycotina.

More specific examples of the plant pathogenic bacteria include the following.
As the flagellum subfamily, potato or tomato plague (Phytophthora infestans), tomato gray plague (Phytophthora capsici) genus Phytophthora genus; cucumber downy mildew (Pseudoperonospora cubensis) Pseudoperonospora; Plasmopara, such as Plasmopara viticola; Pythium, such as Pythium graminicola, Pythium iwayamai, Pythium And so on.

  As a subfamily of Aspergillus oryzae, genus Erysiphe such as wheat powdery mildew (Erysiphe graminis); genus Sphaerotheca such as Sphaerotheca fuliginea and Sphaerotheca humuli ; Uncinula genus such as Uncinula necator; Podosphaera genus such as Podosphaera leucotricha; Mycosphaerella pinodes, Mycosphaerella pomi ), Banana Black Sigatoka (Mycosphaerella musicola), Mycosphaerella nawae, Mycosphaerella fragariae, Mycosphaerella, Venturia inaequalis, Pear Venturia genus such as Venturia nashicola; Barley reticulum (Pyrenophora teres), Pyrenophora genus such as Pyrenophora graminea; Sclerotinia genus such as Sclerotinia sclerotiorum; Cochliobolus miyabeanus Cochliobolus genus such as; Didymella genus such as Didymella bryoniae; Gibberella genus such as Gibberella zeae; Elsinoe ampelina), Elsinoe genus such as Elsinoe fawcettii; Diaporthe citri, Diaporthe genus such as Diaporthe sp .; Apple Moniria (Monilinia mali), Monilinia genus like Monilinia fructicola; Grape rot fungus (Glom and genus Glomerella, such as erella cingulata.

  As a basidiomycete, the genus Rhizoctonia such as Rhizoctonia solani; the genus Ustilago such as Ustilago nuda; Puccinia coronata; Puccinia recondita, Puccinia genus such as wheat yellow rust fungus (Puccinia striiformis);

  As an imperfect subgenus, the genus Septoria such as Septoria nodorum, Septoria tritici; the genus Botrytis such as Botrytis cinerea; Pyricularia genus such as rice blast fungus (Pyricularia oryzae); Cercospora genus such as Cercospora beticola, Cercospora kakivola; Colletotrichum orbiculare Colletotrichum genus such as; Alternaria alternata apple pathotype, Alternaria alternata Japanese pear pathotype, potato summer or Alternaria solani, cabbage black spot fungus ( Alternaria genus such as Alternaria brassicae; Pseudocercosporella herp genus Pseudocercosporella such as otrichoides; genus Pseudocercospora such as Pseudocercospora vitis; Rhynchosporium such as Rhynchosporium secalis Genus; genus Cladosporium such as Cladosporium carpophilum; genus Phomopsis such as Phomopsis sp .; grouse such as Gloeosporium kaki Examples include the genus Gloeosporium; the genus Fulvia such as tomato leaf mold fungus (Fulvia fulva); and the genus Corynespora such as Corynespora cassiicola.

  Examples of the zygomycota include genus Rhizopus such as strawberry soft rot fungus (Rhizopus stronifer) and peach black mold fungus (Rhizopus nigricans).

  The compound of the present invention is useful as an active ingredient of a plant disease control agent. For example, rice blast, sesame leaf blight, coat blight; wheat powdery mildew, red mold, rust, snow rot, Bare scab, eye rot, leaf blight, dry blight; citrus black spot disease, scab; apple monilia disease, powdery mildew, spotted leaf disease, black star disease, anthracnose disease, brown spot disease, circle Herb disease, soot spot disease, soot spot disease, black spot disease; pear black spot disease, black spot disease, powdery mildew, plague; pear ring-shaped ring disease, powdery mildew; peach ash star disease, black star disease, fomopsis Rot disease; grape black rot, late rot, powdery mildew, downy mildew, gray mold, brown spot, branch swelling; oyster anthracnose, deciduous, powdery mildew, soot spot; cucumber Anthracnose, powdery mildew, vine blight, downy mildew, plague, brown spot; tomato ring-rot, leaf mold, plague, gray mold, powdery mildew; Brassicaceae Vegetable downy mildew, black spot disease; Potato summer plague, plague; Strawberry powdery mildew, gray mold, anthracnose; various crops downy mildew, plague, gray mold, mycorrhizal disease, powdery mildew Although it is effective for controlling diseases such as mildew, it exhibits an excellent control effect especially for plagues of fruit trees and vegetables, downy mildew, and blight of wheat. It is also effective for controlling soil diseases caused by phytopathogenic fungi such as Fusarium, Psium, Rhizoctonia, Verticillium, and Plasmodiohora.

The compound of the present invention is usually prepared by mixing the compound with various agricultural adjuvants, powders, granules, granule wettable powders, wettable powders, aqueous suspensions, oily suspensions, aqueous solvents, emulsions, It can be used in various forms such as liquids, pastes, aerosols, microdispersions, etc., but it can be made into any conventional form used in the art as long as it meets the purpose of the present invention. it can. Adjuvants used in the formulation include solid carriers such as diatomaceous earth, slaked lime, calcium carbonate, talc, white carbon, kaolin, bentonite, kaolinite, sericite, clay, sodium carbonate, sodium bicarbonate, sodium sulfate, zeolite, starch; water , Toluene, xylene, solvent naphtha, dioxane, acetone, isophorone, methyl isobutyl ketone, chlorobenzene, cyclohexane, dimethyl sulfoxide, N, N-dimethylformamide, N, N-dimethylacetamide, N-methyl-2-pyrrolidone, alcohol, etc. Solvent; fatty acid salt, benzoate, alkylsulfosuccinate, dialkylsulfosuccinate, polycarboxylate, alkylsulfate, alkylsulfate, alkylarylsulfate, alkyldiglycolethersulfate, a Cole sulfate ester salt, alkyl sulfonate salt, alkyl aryl sulfonate salt, aryl sulfonate salt, lignin sulfonate salt, alkyl diphenyl ether disulfonate salt, polystyrene sulfonate salt, alkyl phosphate ester salt, alkyl aryl phosphate salt, styryl Aryl phosphate, polyoxyethylene alkyl ether sulfate, polyoxyethylene alkyl aryl ether sulfate, polyoxyethylene alkyl aryl ether sulfate, polyoxyethylene alkyl ether phosphate, polyoxyethylene alkyl aryl phosphate Anionic surfactants such as salts, salt of naphthalene sulfonic acid formalin condensate; sorbitan fatty acid ester, glycerin fatty acid ester, fatty acid polyglyceride Fatty acid alcohol polyglycol ether, acetylene glycol, acetylene alcohol, oxyalkylene block polymer, polyoxyethylene alkyl ether, polyoxyethylene alkyl aryl ether, polyoxyethylene styryl aryl ether, polyoxyethylene glycol alkyl ether, polyoxyethylene fatty acid ester, Nonionic surfactants such as polyoxyethylene sorbitan fatty acid ester, polyoxyethylene glycerin fatty acid ester, polyoxyethylene hydrogenated castor oil, polyoxypropylene fatty acid ester; olive oil, kapok oil, castor oil, palm oil, palm oil, palm Oil, sesame oil, corn oil, rice bran oil, peanut oil, cottonseed oil, soybean oil, rapeseed oil, linseed oil, persimmon oil, liquid paraffin And vegetable oils and mineral oils. Each component of these adjuvants can be used by appropriately selecting one or two or more types without departing from the object of the present invention. Further, in addition to the above-mentioned adjuvants, it can also be used by appropriately selecting from those known in the art, a bulking agent, a thickener, an anti-settling agent, an antifreezing agent, a dispersion stabilizer, a safener, Various commonly used adjuvants such as antifungal agents can also be used. The compounding ratio of the compound of the present invention and various adjuvants is generally 0.005: 99.995 to 95: 5, preferably 0.2: 99.8 to 90:10. In actual use of these preparations, use them as they are, or dilute them to a predetermined concentration with a diluent such as water, and add various spreading agents (surfactants, vegetable oils, mineral oils, etc.) as necessary. Can be used.

  The concentration of the compound of the present invention varies depending on the target crop, method of use, formulation, application rate, etc., and cannot be generally defined. However, in the case of foliage treatment, it is usually 0.1 to 10,000 ppm, preferably 1 ~ 2,000 ppm. In the case of soil treatment, it is usually 10 to 100,000 g / ha, preferably 200 to 20,000 g / ha. In the case of seed treatment, it is usually 0.01 to 100 g / Kg seed, desirably 0.02 to 20 g / Kg seed.

  The compound of the present invention is generally applied for application of its various preparations or dilutions thereof, that is, spraying (eg spraying, spraying, misting, atomizing, dusting, water surface application, etc.), soil application (Mixing, irrigation, etc.), surface application (application, powder coating, coating, etc.) can be performed. It can also be applied by the so-called ultra low volume application method. In this method, it is possible to contain 100% of the active ingredient.

  The compound of the present invention may contain other agricultural chemicals as necessary, such as fungicides, insecticides, acaricides, nematicides, soil insecticides, antiviral agents, attractants, herbicides, plant growth preparations, etc. Can be mixed and used together. In this case, a more excellent effect may be exhibited.

In the above-mentioned other agricultural chemicals, as an active ingredient compound of a bactericide (generic name; including some pending applications or Japan Plant Protection Association test code), for example,
Anilinopyrimidine compounds such as mepanipyrim, pyrimethanil, cyprodinil;
Tria such as 5-chloro-7- (4-methylpiperidin-1-yl) -6- (2,4,6-trifluorophenyl) [1,2,4] triazolo [1,5-a] pyrimidine Zolopyrimidine compounds;
Pyridinamine compounds such as fluazinam;
Triadimefon, bitertanol, triflumizole, etaconazole, propiconazole, penconazole, flusilazole, microbutanil, cyproconazole cyproconazole, tebuconazole, hexaconazole, furconazole-cis, prochloraz, metconazole, epoxiconazole, tetraconazole, o Oxpoconazole fumarate, prothioconazole, triadimenol, flutriafol, difenoconazole, fluquinconazole azole), fenbuconazole, bromuconazole, diniconazole, tricyclazole, probenazole, simeconazole, pefazoate, ipconazole, imibenconazole Azole compounds such as (imibenconazole), azaconazole, triticonazole, imazalil;
Quinoxaline compounds such as quinomethionate;
Dithiocarbamate compounds such as maneb, zineb, mancozeb, polycarbamate, metiram, propineb, thiram;
Organochlorine compounds such as fthalide, chlorothalonil, quintozene;
Imidazole compounds such as benomyl, thiophanate-methyl, carbendazim, thiabendazole, fuberiazole, cyazofamid;
Cyanoacetamide compounds such as cymoxanil;
Metalaxyl, metalaxyl-M (aka mefenoxam), oxadixyl, offurace, benalaxyl, benalaxyl-M, also known as kiralaylyl )), Fluralaxyl, cyprofuram, carboxin, oxycarboxin, thifluzamide, boscalid, bixafen, isothianil, tiadinil Anilide compounds such as sedaxane;
Sulfamide-type compounds such as dichlofluanid;
Copper-based compounds such as cupric hydroxide and oxine copper;
Isoxazole compounds such as hymexazol;
Fosetyl aluminum (fosetyl-Al), tolclofos-Methyl, S-benzyl O, O-diisopropyl phosphorothioate, O-ethyl S, S-diphenyl phosphorodithioate, aluminum ethyl hydrogen phosphonate, edifenphos, iprobenphos Organophosphorus compounds such as (iprobenfos);
Phthalimide compounds such as captan, captafol, folpet;
Dicarboximide compounds such as procymidone, iprodione, vinclozolin;
Benzanilide compounds such as flutolanil, mepronil, benodanil;
Amide compounds such as penthiopyrad, penflufen, furametpyr, isopyrazam, silthiopham, fenoxanil, fenfuram, fluxapyroxad;
Benzamide compounds such as fluopyram and zoxamide;
Piperazine compounds such as triforine;
Pyridine compounds such as pyrifenox;
Carbinol compounds such as fenarimol and nuarimol;
Piperidine compounds such as fenpropidin;
Morpholine compounds such as fenpropimorph and tridemorph;
Organotin compounds such as fentin hydroxide and fentin acetate;
Urea-based compounds such as pencycuron;
Synamic acid compounds such as dimethomorph, flumorph;
Phenyl carbamate compounds such as dietofencarb;
Cyanopyrrole compounds such as fludioxonil and fenpiclonil;
Azoxystrobin, kresoxim-methyl, metominostrobin, trifloxystrobin, picoxystrobin, oryzastrobin, dimoxystrobin ( strobilurin-based compounds such as dimoxystrobin, pyraclostrobin, fluoxastrobin, enestroburin, pyroxystrobin, pyrametostrobin;
Oxazolidinone compounds such as famoxadone;
Thiazole carboxamide compounds such as ethaboxam;
Valinamide compounds such as iprovalicarb, benchthiavalicarb-isopropyl;
Acylamino acid compounds such as methyl N- (isopropoxycarbonyl) -L-valyl- (3RS) -3- (4-chlorophenyl) -β-valaniphenate;
Imidazolinone compounds such as fenamidone;
Hydroxyanilide compounds such as fenhexamid;
Benzenesulfonamide compounds such as flusulfamide;
Oxime ether compounds such as cyflufenamid;
Anthraquinone compounds;
Crotonic acid compounds;
Antibiotics such as validamycin, kasugamycin, polyoxins;
Guanidine compounds such as iminoctadine and dodine;
Quinoline compounds such as tebufloquin;
Thiazolidine compounds such as flutianil;
Sulfur-based compounds such as sulfur;
Other compounds include pyribencarb, isoprothiolane, pyroquilon, diclomezine, quinoxyfen, propamocarb hydrochloride, chloropicrin, dazomet, and sodium metam Metam-sodium, metrafenone, nicobifen, UBF-307, diclocymet, proquinazid, amisulbrom (aka amibromdole), mandipropamid, fluicolide ), Carpropamid, meptyldinocap, N-[(3 ', 4'-dichloro-1,1-dimethyl) phenacyl] -3-trifluoromethyl-2-pyridinecarboxamide, N- [ (3 ', 4'-dichloro-1,1 -Dimethyl) phenacyl] -3-methyl-2-thiophenecarboxamide, N-[(3 ', 4'-dichloro-1,1-dimethyl) phenacyl] -1-methyl-3-trifluoromethyl-4-pyrazolecarboxamide N-[[2'-Methyl-4 '-(2-propyloxy) -1,1-dimethyl] phenacyl] -3-trifluoromethyl-2-pyridinecarboxamide, N-[[2'-methyl-4 '-(2-propyloxy) -1,1-dimethyl] phenacyl] -3-methyl-2-thiophenecarboxamide, N-[[2'-methyl-4'-(2-propyloxy) -1,1- Dimethyl] phenacyl] -1-methyl-3-trifluoromethyl-4-pyrazolecarboxamide, N-[[4 '-(2-propyloxy) -1,1-dimethyl] phenacyl] -3-trifluoromethyl-2 -Pyridinecarboxamide, N-[[4 '-(2-propyloxy) -1,1-dimethyl] phenacyl] -3-methyl-2-thiophenecarboxamide, N-[[4'-(2-propyloxy)- 1,1-dimethyl] phenacyl] -1 -Methyl-3-trifluoromethyl-4-pyrazolecarboxamide, N-[[2'-methyl-4 '-(2-pentyloxy) -1,1-dimethyl] phenacyl] -3-trifluoromethyl-2- Pyridinecarboxamide, N-[[4 '-(2-pentyloxy) -1,1-dimethyl] phenacyl] -3-trifluoromethyl-2-pyridinecarboxamide, pyriofenone, ferimzone, spiroxamine ), Fenpyrazamine, ametoctradin, valifenalate, S-2200, ZF-9646, BCM-061, BCM-062, NC-233, NK-1001, SB-4303, S-8606 DKF-1001, MF-1001, MF-1002, BAF-1107 and the like.

Insecticides, acaricides, nematicides or soil pesticides in the above-mentioned other pesticides, that is, active ingredient compounds of pesticides (generic name; including some pending applications or Japan Plant Protection Association test code) ), For example,
Profenofos, dichlorvos, fenamiphos, fenitrothion, EPN, diazinon, chlorpyrifos, chlorpyrifos-methyl, acephate, prothiophos, prothiophos Fosthiazate, cadusafos, disulfoton, isoxathion, isofenphos, ethion, etrimfos, quinalphos, dimethylvinphos, dimethoate ), Sulprofos, thiometon, bamidothion, pyraclofos, pyridaphenthion, pirimiphos-methyl, propaphos, phosalone, Lumothione, malathion, tetrachlorvinphos, chlorfenvinphos, cyanophos, trichlorfon, methidathion, phenthoate, ESP, azinephosmethyl ( azinphos-methyl, fenthion, heptenophos, methoxychlor, parathion, phosphocarb, demeton-S-methyl, monocrotophos, methamidophos Organophosphate compounds such as (methamidophos), imimifafos, parathion-methyl, terbufos, phosphamidon, phosmet, phorate;
Carbaryl, propoxur, aldicarb, carbofuran, thiodicarb, methomyl, oxamyl, ethiofencarb, pirimicarb, fenobucarb, fenobucarb Carbamates such as carbosulfan, benfuracarb, bendiocarb, furathiocarb, isoprocarb, metolcarb, xylylcarb, XMC, fenothiocarb Compound;
Nereistoxin derivatives such as cartap, thiocyclam, bensultap, sodium thiosultap-sodium;
Organochlorine compounds such as dicophor, tetradifon, endosulfan, dienochlor, dieldrin;
Organometallic compounds such as fenbutatin oxide and cyhexatin;
Fenvalerate, permethrin, cypermethrin, deltamethrin, cyhalothrin, tefluthrin, etofenprox, flufenprox, cyfluthrin , Fenpropathrin, flucytrinate, fluvalinate, cycloprothrin, lambda-cyhalothrin, pyrethrin, esfenvalerate, tetramethrin (Tetramethrin), resmethrin, protrifenbute, bifenthrin, zeta-cypermethrin, acrinathrin, alpha-cypemethrin (alpha-cype) rmethrin, allethrin, gamma-cyhalothrin, theta-cypermethrin, tau-fluvalinate, tralomethrin, profluthrin, beta-si Pyrethroid compounds such as per-methrin (beta-cypermethrin), beta-cyfluthrin, mettofluthrin, phenothrin, flumethrin;
Diflubenzuron, chlorfluazuron, teflubenzuron, flufenoxuron, lufenuron, novaluron, triflumuron, hexaflumuron, hexaflumuron Benzoylurea compounds such as (bistrifluron), nobifluuron, fluazuron;
Juvenile hormone-like compounds such as metoprene, pyriproxyfen, fenoxycarb, diofenolan;
Pyridazinone compounds such as pyridaben;
Pyrazole compounds such as fenpyroximate, fipronil, tebufenpyrad, ethiprole, tolfenpyrad, acetoprole, pyrafluprole, pyriprole;
Imidacloprid, nitenpyram, acetamiprid, thiacloprid, thiamethoxam, clothianidin, nidinotefuran, dinotefuranit, dinotefurannit, dinotefurannit Nicotinoid compounds;
Hydrazine compounds such as tebufenozide, methoxyfenozide, chromafenozide, halofenozide and the like;
Pyridine compounds such as pyridalyl, flonicamid and the like;
Cyclic ketoenol compounds such as spirodiclofen, spiromesifen, spirotetramat, etc .;
Strobilurin-based compounds such as fluacrypyrim;
Pyrimidinamine compounds such as flufenerim;
Dinitro compounds;
Organic sulfur compounds;
Urea compounds;
Triazine compounds;
Hydrazone compounds;
Other compounds include buprofezin, hexythiazox, amitraz, chlordimeform, silafluofen, triazamate, pymetrozine, pyrimidifen, chloridmefen ), Indoxacarb, acequinocyl, etoxazole, cyromazine, 1,3-dichloropropene, diafenthiuron, benclothiaz , Bifenazate, propargite, clofentezine, metaflumizone, flubendiamide, cyflumetofen, chloranthra Lipant (chlorantraniliprole), cyantraniliprole (cyantraniliprole), cyenopyrafen (cyenopyrafen), pyrifluquinazone (pyrifluquinazone), fenazaquin (fenazaquin), amidoflumet (amidoflumet), sulfurramid (sulfluramid), hydramethylnon (hydramethylnon), aldehyde , Compounds such as sulfoxaflor, cypropene, fluensulfone, ryanodine, verbutin; and the like. Furthermore, Bacillus thuringiensis aizawai, Bacillus thuringiensis kurstaki, Bacillus thuringiensis israelensis, Bacillus thuringiensis japonensis, Bacillus thuringiensis tenebrionis or crystalline protein toxins produced by Bacillus thuringiensis, entomopathogenic fungi, nematode pathogenic fungi, etc. Microbial pesticides such as: avermectin, emamectin benzoate, milbemectin, milbemycin, spinosad, ivermectin, lepimectin, DE-175, abamectin ), Antibiotics such as emamectin, spinetoram and semi-synthetic antibiotics; natural products such as azadirachtin and rotenone; repellents such as deet; Mixed with, It is also possible to use.

  Next, examples of the present invention will be described, but the present invention is not limited thereto. First, the synthesis example of this invention compound is described.

Synthesis example 1
Synthesis of 4- {4- [4- (4-amidinophenoxy) butylamino] butoxy} -3-nitrophenylcarboxamidine (Compound No. 2) (1) 4- (4-Bromobutoxy) -3-nitro Synthesis of benzonitrile
A 40 mL N, N-dimethylformamide solution of 7.5 g of 4-hydroxy-3-nitrobenzonitrile and 6.66 g of potassium carbonate was stirred at room temperature for 30 minutes in a nitrogen atmosphere, and then 18.9 g of 1,4-dibromobutane was added and 35 to 35 The reaction was carried out at 40 ° C. for 12 hours. After completion of the reaction, ethyl acetate and water were added for extraction, and dried over anhydrous magnesium sulfate. After evaporating the solvent under reduced pressure, the residue was purified by silica gel column chromatography (eluent; ethyl acetate / n-heptane = 1/3 to 1/2) to obtain 7.2 g of the desired product.

(2) Synthesis of t-butyl 4- (4-cyanophenoxy) butyl carbamate
To a 50 mL chloroform solution of 2.33 g of 4- (4-aminobutoxy) benzonitrile, 1.51 g of triethylamine was added under ice cooling, and then a 10 mL solution of 2.94 g of di-t-butyl dicarbonate was gradually added dropwise. After completion of dropping, the mixture was stirred for 12 hours while gradually returning to room temperature. After completion of the reaction, the solvent was distilled off under reduced pressure, and the residue was purified by silica gel column chromatography (eluent; ethyl acetate / n-heptane = 1/2) to obtain 2.55 g of the desired product.

(3) Synthesis of 4- (4- {t-butoxycarbonyl [4- (4-cyanophenoxy) butylamino] butoxy})-3-nitrobenzonitrile 0.51 g of sodium hydride (60% oil suspension) To 12 mL N, N-dimethylformamide suspension, 3.1 g of 4- (4-bromobutoxy) -3-nitrobenzonitrile synthesized in the above step (1) and t-butyl 4- (4 -Cyanophenoxy) A 12 mL N, N-dimethylformamide solution in which 2.47 g of butyl carbamate was dissolved was gradually added dropwise at room temperature, and reacted at 40 to 50 ° C. for 1 hour after completion of the addition. After completion of the reaction, ethyl acetate and water were added for extraction, and the organic layer was washed with water and dried over anhydrous magnesium sulfate. After evaporating the solvent under reduced pressure, the residue was purified by silica gel column chromatography (eluent; ethyl acetate / n-heptane = 1/1) to obtain 2.47 g of the desired product as an amorphous solid.

(4) Synthesis of 4- {4- [4- (4-amidinophenoxy) butylamino] butoxy} -3-nitrophenylcarboxamidine (hydrochloride) Lithium Bis (trimethylsilyl) amide tetrahydrofuran (1.8Mol / L) 4- (4- {t-butoxycarbonyl [4- (4-cyanophenoxy) butylamino] butoxy}) obtained in the above step (3) in 20 mL of the solution under a nitrogen atmosphere at −20 to −15 ° C. A 10 mL tetrahydrofuran solution of 1.0 g of -3-nitrobenzonitrile was gradually added dropwise. After completion of dropping, the reaction solution was allowed to react for 12 hours while gradually returning to room temperature. After completion of the reaction, the mixture was acidified with 25% hydrochloric acid under ice-cooling, washed with ethyl acetate, the aqueous layer was made alkaline with 10% aqueous sodium hydroxide solution, and allowed to stand at room temperature. The precipitate was dissolved in an ethanol (5.4 mol / L) solution of hydrogen chloride, and the solvent was concentrated under reduced pressure and then solidified to obtain 0.46 g of the desired product (hydrochloride) having a melting point of 208.0 ° C.

Synthesis example 2
Synthesis of 4- (3- {4- [3- (4-amidinophenoxy) propyl] -1-piperidinyl} propoxy) -3-methylthiophenylcarboxamidine (Compound No. 8) (1) 4- (3- Synthesis of bromopropyloxy) -3-methylthiobenzonitrile
To a 20 mL N, N-dimethylformamide solution of 2.1 g of 4-hydroxy-3-methylthiobenzonitrile, 1.93 g of potassium carbonate was added and stirred for 30 minutes in a nitrogen atmosphere. Then, 6 g of 1,3-dibromopropane was added, For 48 hours. After completion of the reaction, the solution was cooled, extracted with diethyl ether and water, and the organic layer was washed with water and saturated brine, and then dried over anhydrous magnesium sulfate. After evaporating the solvent under reduced pressure, the residue was purified by silica gel column chromatography (eluent; ethyl acetate / n-heptane = 1/2) to obtain 2.0 g of the desired product.

(2) Synthesis of 4- (3- {4- [3- (4-cyanophenoxy) propyl] -1-piperidinyl} propoxy) -3-methylthiobenzonitrile 4- (3- Bromopropyloxy) -3-methylthiobenzonitrile (0.773 g) and 4- [3- (4-piperidinyl) propoxy] benzonitrile (0.6 g) in 12 mL N, N-dimethylformamide solution was added with potassium carbonate (0.68 g) and reacted at room temperature for 12 hours. did. After completion of the reaction, ethyl acetate and water were added for extraction, and the organic layer was washed with water and dried over anhydrous magnesium sulfate. After evaporating the solvent under reduced pressure, the residue was purified with n-heptane to obtain 0.94 g of the desired product.

(3) Synthesis of 4- (3- {4- [3- (4-amidinophenoxy) propyl] -1-piperidinyl} propoxy) -3-methylthiophenylcarboxamidine Lithium bis (trimethylsilyl) amide tetrahydrofuran (1.8 mol) / L) 4- (3- {4- [3- (4-Cyanophenoxy) propyl] -1 obtained in the above step (2) in 17.8 mL of the solution at −20 to −15 ° C. in a nitrogen atmosphere. -Piperidinyl} propoxy) -3-methylthiobenzonitrile (0.94 g) in 5 mL tetrahydrofuran was gradually added dropwise. After completion of the dropwise addition, the reaction was continued for 12 hours while gradually returning the liquid temperature to room temperature. After completion of the reaction, the reaction solution was ice-cooled and acidified with 25% hydrochloric acid. After washing with a small amount of ethyl acetate, the aqueous layer was made alkaline with 10% aqueous sodium hydroxide under ice-cooling, and allowed to stand at room temperature, and the precipitated solid was collected by filtration. A solution of hydrogen chloride in ethanol (5.4 mol / L) was added to the filtered solid and stirred, and then the ethanol solution was concentrated to obtain 1.07 g of the desired product (melting point: 273.0 ° C.).

  Representative examples of the compounds of formula (I) are listed in Tables 1-2. In the formulas shown in Tables 1 and 2 and below, No. represents compound No., Me is methyl, Et is ethyl, Pr is propyl, iPr is isopropyl, Bu is butyl, and Ac is acetyl. Each is shown. The abbreviations used in Tables 1 and 2 represent the following substituents.

  In Tables 1 and 2, the numerical values shown as physical properties are melting points (° C.). These compounds can be synthesized based on the above synthesis examples or various production methods of the compound of the present invention described above.

For some of the compounds of the present invention, ¹ H-NMR data [measured by ¹ H-nuclear magnetic resonance spectroscopy. δ is a chemical shift value (ppm)] is shown in Table 3.

Below, the test example of this invention composition is described. In each test, the control index followed the following criteria.

Below, the test example of this invention composition is described. In each test, the control index followed the following criteria.
[Control index of various preventive effect tests] [Disease level: Visual observation]
5: No lesion or sporulation is observed.
4: The lesion area, the number of lesions, or the spore formation area is less than 10% of the untreated area.
3: The lesion area, the number of lesions, or the sporulation area is less than 40% of the untreated area.
2: The lesion area, the number of lesions, or the sporulation area is less than 70% of the untreated area.
1: The lesion area, the number of lesions, or the spore formation area is 70% or more of the untreated area.

[Control index of various spore germination inhibition tests] [Sprouting rate and degree of germ tube elongation: macroscopic observation]
5: No germination is observed.
4: The germination rate or germ tube elongation is less than 20% of the untreated area.
3: The germination rate or germ tube elongation is less than 40% of the untreated area.
2: The germination rate or germ tube elongation is less than 70% of the untreated group.
1: Germination rate or germ tube elongation is 70% or more of the untreated group.

Test example 1 (wheat blight prevention effect test)
Wheat (variety: Norin 61) was cultivated in a plastic pot with a diameter of 7.5 cm, and when the 1.5 leaf stage was reached, a sufficient amount of chemical solution adjusted to a predetermined concentration of the compound of the present invention was sprayed with a spray gun. To (the same day) After the chemical solution dried, conidia suspension of glume blotch fungus (Septoria nodorum) was sprayed and inoculated, maintaining inoculation box about 1 day 20 ° C., it was maintained in a constant temperature chamber of subsequent 20 ° C. . The number of lesions was investigated 8 to 13 days after the inoculation, and the control index was determined according to the evaluation criteria.
Compound No. 1,8,9,10,11,12,13,14,15,16,18,23,24,25,26,27,28,1A and 2A were tested, and the effect of control index of 4 or more at 400 ppm showed that.

Test Example 2 (Cucumber downy mildew prevention effect test)
Cucumber (variety: Sagamihanjiro) was cultivated in a plastic pot with a diameter of 7.5 cm, and when the 1.5 leaf stage was reached, a sufficient amount of chemical 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 (on the day of treatment), a zoosporangium suspension of downy mildew ( Pseudoperonospora cubensis ) was spray-inoculated and kept in a constant temperature room at 20 ° C. The lesion area was examined 5 to 6 days after the inoculation, and the control index was determined according to the evaluation criteria. Compound No. When 1, 2, 4, 5, 8, 9, 10, 11, 12, 13, 14, 17, 18, 26 and 27 were tested, an effect of a control index of 4 or more was shown at 400 ppm.

Test Example 3 (Injury gray mold prevention effect test)
Green beans (cultivar: Taishokin) were cultivated in a plastic pot with a diameter of 12 cm, and a sufficient amount of a chemical solution prepared by adjusting the compound of the present invention to a predetermined concentration was sprayed with a spray gun when the 3-4 leaf stage was reached. After the chemical solution was dried (on the day of treatment or on the next day), a conidial spore suspension of Botrytis cinerea was soaked in a paper disk having a diameter of 8 mm, placed on the floor, and kept in a constant temperature room at 20 ° C. Three days after the inoculation, the lesion area was examined, and the control index was determined according to the evaluation criteria.
Compound No. 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 23, 24, 25, 26, 27, 28 and 1A When tested, an effect of controlling index 4 or more was shown at 400 ppm.

Test Example 4 (Tomato ring mold fungus spore germination inhibition test)
A conidial spore suspension of Alternaria solani to which a compound of the present invention was added to a predetermined concentration in a 96-well microplate was dispensed and kept in a constant temperature room at 20 ° C. One day after the culture, the degree of spore germination and germ tube elongation was examined with a microscope, and a control index was determined according to the above evaluation criteria.
The aforementioned compound No. 1, 2, 3, 4, 5, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 21, 23, 24, 25, 26, 27 and 1A tested However, the effect of controlling index 4 or more was shown at 20 ppm.

Test Example 5 (Swheat scab fungus spore germination inhibition test)
A conidial spore suspension of Fusarium graminearum to which a compound of the present invention was added to a predetermined concentration in a 96-well microplate was dispensed and kept in a constant temperature room at 20 ° C. One day after the culture, the degree of spore germination and germ tube elongation was examined with a microscope, and a control index was determined according to the above evaluation criteria.
The aforementioned compound No. 1, 2, 4, 5, 7, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 21, 23, 24, 26, 27, and 1A, the control index was 20 ppm. The effect of 4 or more was shown.

Test Example 6 (Action characteristic test)
(Rain resistance)
Cucumber (variety: Sagamihanjiro) is cultivated in a plastic pot with a diameter of 7.5cm, and when the 1.5 leaf stage is reached, a chemical solution prepared by adjusting the concentration of the compound of the present invention to a predetermined concentration is treated with a spray gun to cucumber cotyledons. did. After the chemical solution was dried, the specimen was treated with 10 mm / hr of rain for 1 hour using a rain apparatus and inoculated with a conidial spore suspension of Botrytis cinerea . After inoculation, it was kept in a constant temperature room at 20 ° C. Three days after the inoculation, the lesion area was examined and the rain resistance of the compound of the present invention was evaluated.
(Aftereffect)
A cucumber (variety: Sagamihanjiro) is cultivated in a 7.5 cm diameter plastic pot, and when the 1.5 leaf stage is reached, a sufficient amount of the medicinal solution in which the compound of the present invention is adjusted to a predetermined concentration is treated on the cucumber cotyledon, It was left in a greenhouse for 1 week. Subsequently, a conidial spore suspension of Botrytis cinerea was inoculated and kept in a constant temperature room at 20 ° C. The lesion area was examined 3 days after the inoculation, and the residual efficacy of the drug was evaluated.
When compounds No. 2, 8, and 27 were tested, it was confirmed that all had rain resistance and / or residual effect, which are desirable action characteristics as a plant disease control agent.

Formulation Example 1
(1) Compound of the present invention 20 parts by weight (2) 72 parts by weight of clay (3) Sodium lignin sulfonate 8 parts by weight or more is uniformly mixed to obtain a wettable powder.

Formulation Example 2
(1) Compound of the present invention 5 parts by weight (2) Talc 95 parts by weight or more is uniformly mixed to obtain a powder.

Formulation Example 3
(1) Compound of the present invention 20 parts by weight (2) N, N-dimethylacetamide 20 parts by weight (3) Polyoxyethylene alkylphenyl ether 10 parts by weight (4) Xylene 50 parts by weight or more are uniformly mixed and dissolved. To make an emulsion.

Formulation Example 4
(1) Clay 68 parts by weight (2) Lignin sulfonic acid soda 2 parts by weight (3) Polyoxyethylene alkylaryl ether sulfate 5 parts by weight (4) Fine powder silica A mixture of each component of 25 parts by weight or more and the compound of the present invention Are mixed at a weight ratio of 4: 1 to obtain a wettable powder.

Formulation Example 5
(1) Compound of the present invention 50 parts by weight (2) Oxidated polyalkylphenyl phosphate triethanolamine 2 parts by weight (3) Silicone 0.2 parts by weight (4) Water 47.8 parts by weight or more uniformly (5) 5 parts by weight of sodium polycarboxylate (6) 42.8 parts by weight of anhydrous sodium sulfate are further added to the mixed and pulverized stock solution, and the mixture is uniformly mixed, granulated and dried to obtain a granulated wettable powder.

Formulation Example 6
(1) Compound of the present invention 5 parts by weight (2) Polyoxyethylene octylphenyl ether 1 part by weight (3) Polyoxyethylene phosphate ester 0.1 part by weight (4) Granular calcium carbonate 93.9 parts by weight (1)- (3) is uniformly mixed in advance and diluted with an appropriate amount of acetone, and then sprayed onto (4) to remove the acetone and form granules.

Formulation Example 7
(1) Compound of the present invention 2.5 parts by weight (2) N-methyl-2-pyrrolidone 2.5 parts by weight (3) Soybean oil 95.0 parts by weight or more are uniformly mixed and dissolved to give a trace amount of spray. (ultra low volume formulation).

Formulation Example 8
(1) Compound of the present invention 20 parts by weight (2) Oxidated polyalkylphenyl phosphate triethanolamine 2 parts by weight (3) Silicone 0.2 part by weight (4) Xanthan gum 0.1 part by weight (5) Ethylene glycol 5 Part by weight (6) Water 72.7 parts by weight or more are uniformly mixed and pulverized to obtain an aqueous suspension.

Claims (3)

Formula (I):

[Where:
A ¹ and A ² are each independently amidino which may be protected;
X ¹ and X ² are each independently alkylene which may be substituted with a halogen atom (methylene in the alkylene may be replaced with an oxygen atom or a sulfur atom);
Z is an optionally substituted imino or an optionally substituted nitrogen-containing heterocycle;
R ¹ and R ² are each independently a halogen atom, optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted alkoxy, optionally substituted alkylthio, nitro, or optionally substituted. Good amino, optionally substituted alkylsulfinyl, or optionally substituted alkylsulfonyl;
l and m are each independently an integer of 0 to 4]
The plant disease control agent containing the compound or its salt represented by these. Formula (I):

[Where:
A ¹ and A ² are each independently amidino which may be protected;
X ¹ and X ² are each independently alkylene which may be substituted with a halogen atom (methylene in the alkylene may be replaced with an oxygen atom or a sulfur atom);
Z is an optionally substituted imino or an optionally substituted nitrogen-containing heterocycle;
R ¹ and R ² are each independently a halogen atom, optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted alkoxy, optionally substituted alkylthio, nitro, or optionally substituted. Good amino, optionally substituted alkylsulfinyl, or optionally substituted alkylsulfonyl;
l and m are each independently an integer of 0 to 4]
A method for controlling plant diseases, which comprises applying a compound represented by the formula or a salt thereof to a plant. Formula (I):

[Where:
A ¹ and A ² are each independently amidino which may be protected;
X ¹ and X ² are each independently alkylene which may be substituted with a halogen atom (methylene in the alkylene may be replaced with an oxygen atom or a sulfur atom);
Z is an optionally substituted imino or an optionally substituted nitrogen-containing heterocycle;
R ¹ and R ² are each independently a halogen atom, optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted alkoxy, optionally substituted alkylthio, nitro, or optionally substituted. Good amino, optionally substituted alkylsulfinyl, or optionally substituted alkylsulfonyl;
l and m are each independently an integer of 0 to 4;
(1) (i) both A ¹ and A ² are bonded in the para position to X ¹ and X ² and
(a) when both X ¹ and X ² are alkylenes replaced by oxygen atoms and the oxygen atoms are both bonded to a benzene ring, or (b) ^one of X ¹ and X ² is replaced by a sulfur atom Alkylene, the other is an alkylene substituted with an oxygen atom or a sulfur atom, the sulfur atom and the oxygen atom are both bonded to a benzene ring, and Z is an optionally substituted imino;
(ii) A ¹ is bonded to X ¹ in the para position, and ^one of X ¹ and X ² is an alkylene substituted with a sulfur atom, and the other is an alkylene substituted with an oxygen atom or a sulfur atom, and the sulfur atom and when the oxygen atom both bonded to the benzene ring, and the nitrogen atom to which Z constitutes the a and said heterocyclic and nitrogen-containing heterocyclic ring which may be substituted is bound to X ^1, or
(iii) A ² is bonded to X ² at the para position, ^one of X ¹ and X ² is an alkylene substituted with a sulfur atom, and the other is an alkylene substituted with an oxygen atom or a sulfur atom, the sulfur atom And the oxygen atom is bonded to the benzene ring, and Z is a nitrogen-containing heterocyclic ring which may be substituted, and the nitrogen atom constituting the heterocyclic ring is bonded to X ² ,
At least one of R ¹ and R ² is selected from the group consisting of optionally substituted alkylthio, nitro, optionally substituted amino, optionally substituted alkylsulfinyl, and optionally substituted alkylsulfonyl;
(2) A nitrogen-containing complex in which A ² is bonded to X ² in the para position, X ¹ is alkylene, the alkylene is bonded to the benzene ring through a carbon atom, and Z may be substituted. In the case of a ring, the carbon atom constituting the heterocyclic ring is bonded to X ² ;
(3) A nitrogen-containing complex in which A ¹ is bonded to X ¹ in the para position, X ² is alkylene, the alkylene is bonded to the benzene ring through a carbon atom, and Z may be substituted. When it is a ring, the carbon atom constituting the heterocyclic ring is bonded to X ¹ ]
Or a salt thereof.