JP3385264B2 - Substituted thiophene derivatives and fungicides for agricultural and horticultural use containing the same as active ingredients - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION [0001] The present invention relates to a novel substituted thiol.
Gene derivatives, agricultural and horticultural killings containing the same as an active ingredient
The present invention relates to a fungicide and a method for controlling plant diseases using the same. [0002] 2. Description of the Related Art Fungicides with selective action developed in recent years
Differs from non-selective fungicides that have been used
Shows stable effect at low dose, but when used repeatedly
Have the problem that drug resistance appears in
You. For example, benzimidazole bactericides are widely used
It has a spectrum and excellent effect against gray mold
However, resistant bacteria emerged in the 1970s,
Caused a significant decrease in potency. An alternative to this
Carboximide bactericides attracted attention, but 198
In the 0s, even for dicarboximide drugs
With the emergence of resistant bacteria, measures to control gray mold resistant bacteria have been implemented in Japan
Not only in the world but also in the world. on the other hand,
Azole-based germicides have a broad germicidal spectrum,
Seed powdery mildew, rust, apple and pear scab
It is an excellent drug that is effective at a lower dose than ever before.
However, recently the emergence of resistant bacteria has greatly reduced the efficacy.
The bottom is the problem. Such drug-resistant bacteria are selective
This is an inevitable problem for fungicides,
Therefore, the development of new drugs is urgently needed. By the way, conventionally, aromatic aniline derivatives
Are known to exhibit bactericidal activity.
For example, JP-A-5-221994 and JP-A-6-1994.
Japanese Patent Application Laid-Open No. 1998003 discloses various aniline derivatives as gray
It is described as having an effect on rust. The present inventors
Is a variety of plants for the compounds specifically disclosed therein.
The bactericidal activity against pathogenic bacteria was tested, and the control effect was
Low even for gray mold, powdery mildew, red rust, etc.
Did not show any effect. [0004] SUMMARY OF THE INVENTION Therefore, the present invention
Has a broad disease spectrum against crop pathogens,
A new agriculture that solves the problem of resistant bacteria that is currently becoming more serious
It is an object to provide a horticultural fungicide. [0005] Means for Solving the Problems The present inventors have made various types of heads.
Research with interest in the biological activity of rocyclic amine derivatives
A derivative having a certain aminothiophene
Has a strong control effect on various plant diseases, and
Benzimidazole and dicarboximide drugs
Susceptible bacteria as well as resistant bacteria, and azoles
Excellent control effect against susceptible and resistant bacteria
Therefore, the safety of crops is high, and
And completed this research. Sand
The present invention relates to a compound represented by the general formula (1): [0006] Embedded image [Wherein Q represents a hydrogen atom, a methyl group, trifluoromethyl
Group, fluorine atom, chlorine atom, bromine atom, iodine atom,
Toxyl group, methylthio group, methylsulfoxy group, methyl
R represents a sulfonyl group, a nitro group or an amino group;
A linear or branched alkyl group of 1 to 12 carbon atoms, 1 carbon atom
~ 12 straight-chain or branched halogenoalkyl groups, carbon number
2 to 10 linear or branched alkenyl groups, 2 to 2 carbon atoms
10 straight-chain or branched halogenoalkenyl groups, carbon number
2 to 10 alkylthioalkyl groups, 2 to 10 carbon atoms
Alkyloxyalkyl group, cycloalkyl having 3 to 10 carbon atoms
Alkyl group, halogeno-substituted cycloalkyl having 3 to 10 carbon atoms
Or a group substituted by 1 to 3 substituents
A good phenyl group, and the substituent of the phenyl group is a hydrogen atom.
, An alkyl group having 1 to 4 carbon atoms, an alkene having 2 to 4 carbon atoms
Nyl group, alkynyl group having 2 to 4 carbon atoms, 3 to 6 carbon atoms
Cycloalkyl group, alkoxy group having 1 to 4 carbon atoms, carbon
A halogenoalkoxy group having 1 to 4 carbon atoms, an alkyl having 1 to 4 carbon atoms
Kirthio group, alkylsulfoxy group having 1 to 4 carbon atoms, charcoal
An alkylsulfonyl group having a prime number of 1 to 4, a halogen atom,
Ano group, acyl group having 2 to 4 carbon atoms, alkyl group having 2 to 4 carbon atoms
A oxycarbonyl group, an amino group, or a group having 1 to 3 carbon atoms
An amino group substituted with an alkyl group, wherein R and -NHC
The OArs are adjacent to each other, and Ar is the following (A1)
To (A8) [0007] Embedded image (Where R¹Is a trifluoromethyl group, difluoromethyl
Group, methyl group, ethyl group, chlorine atom, bromine atom or
An iodine atom;^TwoIs hydrogen atom, methyl group, trif
A fluoromethyl group or an amino group,^ThreeIs 1 carbon
And n is an integer of 0 to 2)
A substituted thiophene derivative represented by the formula:
General formula (2) which is an intermediate [0008] Embedded image (Wherein Q is a hydrogen atom, a methyl group, trifluoromethyl
Group, fluorine atom, chlorine atom, bromine atom, iodine atom,
Toxyl group, methylthio group, methylsulfoxy group, methyl
Sulfonyl group, cyano group, acetyl group, nitro group,
A oxycarbonyl group or an amino group, and Ym is hydrogen
Atom, alkyl group having 1 to 4 carbon atoms, alkyl group having 2 to 4 carbon atoms
Kenyl group, alkynyl group having 2 to 4 carbon atoms, 3 to 6 carbon atoms
A cycloalkyl group, an alkoxy group having 1 to 4 carbon atoms,
A halogenoalkoxy group having 1 to 4 carbon atoms, an alkoxy group having 1 to 4 carbon atoms
Alkylthio group, alkylsulfoxy group having 1 to 4 carbon atoms,
An alkylsulfonyl group having 1 to 4 carbon atoms, a halogen atom,
A cyano group, an acyl group having 2 to 4 carbon atoms, an acyl group having 2 to 4 carbon atoms,
Alkoxycarbonyl group, amino group, or carbon number 1-3
An amino group substituted with an alkyl group of the formula:
Where the phenyl and amino groups are adjacent to each other
The aminothiophene derivative represented by
General formula (3) [0009] Embedded image (Wherein Q is a hydrogen atom, a methyl group, trifluoromethyl
Group, fluorine atom, chlorine atom, bromine atom, iodine atom,
Toxyl group, methylthio group, methylsulfoxy group, methyl
Sulfonyl group, cyano group, acetyl group, nitro group,
A oxycarbonyl group or an amino group, and Ym is hydrogen
Atom, alkyl group having 1 to 4 carbon atoms, alkyl group having 2 to 4 carbon atoms
Kenyl group, alkynyl group having 2 to 4 carbon atoms, 3 to 6 carbon atoms
A cycloalkyl group, an alkoxy group having 1 to 4 carbon atoms,
A halogenoalkoxy group having 1 to 4 carbon atoms, an alkoxy group having 1 to 4 carbon atoms
Alkylthio group, alkylsulfoxy group having 1 to 4 carbon atoms,
An alkylsulfonyl group having 1 to 4 carbon atoms, a halogen atom,
A cyano group, an acyl group having 2 to 4 carbon atoms, an acyl group having 2 to 4 carbon atoms,
Alkoxycarbonyl group, amino group, or carbon number 1-3
An amino group substituted with an alkyl group of the formula:
Where the phenyl and nitro groups are adjacent to each other
Nitrothiophene derivative represented by the formula
8 (chemical formula 8) [0010] Embedded image (Wherein Q is a hydrogen atom, R is a 1-methylbutyl group, 3-
Methylbutyl group, 1,3-dimethylbutyl group or 1,3
-A dimethylpentyl group).
-Aminothiophene derivatives. The thiophene represented by the general formula (1) of the present invention
Specific examples of the substituent R of the sulfonic acid derivative include isopropyl, s
ec-butyl, tert-butyl, 1-methylbutyl,
1-methylhexyl, 1-ethylpropyl, 1,2-di
Methylbutyl, 1,3-dimethylbutyl, 1-ethyl-
3-methylbutyl, 1,2-dimethylhexyl, 1,3
-Dimethyloctyl, 3-methylbutyl, 3-methylpe
Methyl, 4-methyloctyl, 1,2,2,3-tetra
Methylbutyl, 1,3,3-trimethylbutyl, 1,
2,3-trimethylbutyl, 1,3-dimethyl pliers
1,3-dimethylhexyl, 5-methyl-3-hexyl
Sil, 2-methyl-4-heptyl, 2,6-dimethyl-
4-heptyl, 1-methyl-2-cyclopropylethyl
, N-butyl, n-hexyl group etc.
Linear alkyl group or branched alkyl group; 3-chloro-1
-Methylbutyl, 2-chloro-1-methylbutyl, 1-
Chlorobutyl, 3,3-dichloro-1-methylbutyl,
3-chloro-1-methylbutyl, 1-methyl-3-tri
Fluoromethylbutyl, 3-methyl-1-trifluoro
A linear or branched C1-C12 group such as a methylbutyl group
Halogenoalkyl group; propenyl, 1-methyl-1-p
Lopenyl, 1-ethyl-1-butenyl, 2,4-dimethyl
1-pentenyl, 2,4-dimethyl-2-pentenyl
Linear or branched alkenyl having 2 to 10 carbon atoms such as
Group; carbon number of 2-chloro-1-methyl-1-butenyl and the like
2-10 straight-chain or branched halogenoalkenyl groups;
Clopropyl, cyclohexyl, 2-ethylcyclohexyl
3 carbon atoms such as sil and 2-isopropylcyclohexyl groups
1 to 10 cycloalkyl groups; 1-methylthiomethyl, 1
-Methylthioethyl, 1-ethylthioethyl, 1-methyl
Charcoal such as luthiopropyl and 1-isopropylthioethyl groups
An alkylthioalkyl group having a prime number of 2 to 10;
Alkyloxy having 2 to 10 carbon atoms such as a pyroxyethyl group
Cycloalkyl group; 2-chlorocyclohexyl, 3-chloro
Halogeno-substituted cycloalkyl having 3 to 10 carbon atoms such as cyclohexyl
A cycloalkyl group; or substituted by 1 to 3 substituents.
A phenyl group which may be substituted,
Specifically, a hydrogen atom; a methyl group, an ethyl group,
Propyl group, isopropyl group, sec-butyl group, ter
C1-C4 alkyl group such as t-butyl group; vinyl
Group, isopropenyl group, 1-methylpropenyl group, etc.
Alkenyl group having a prime number of 2 to 4; ethynyl group, 1-propynyl
Alkynyl group having 2 to 4 carbon atoms, such as
3 carbon atoms such as a group, cyclopentyl group and cyclohexyl group
To 6 cycloalkyl groups; methoxy group, ethoxy group,
An alkoxy group having 1 to 4 carbon atoms such as a toxic group;
Romethoxy group, 1,1,2,2,2-pentafluoroe
A halogenoalkoxy group having 1 to 4 carbon atoms such as a toxic group;
C1-C4 alkyl such as tylthio and ethylthio
Thio group; methylsulfoxy group, butylsulfoxy group, etc.
Alkylsulfoxy group having 1 to 4 carbon atoms; methylsulfoni
C1 to C4 alkyl groups such as
Rukylsulfonyl group; fluorine atom, chlorine atom, bromine atom
Halogen atom such as iodine atom, cyano group; acetyl
An acyl group having 2 to 4 carbon atoms, such as a group or a propionyl group;
2 carbon atoms such as xycarbonyl group and ethoxycarbonyl group
4 to 4 alkoxycarbonyl groups; an amino group;
Methylamino group, diethylamino group, propylamino group
Amino substituted with an alkyl group having 1 to 3 carbon atoms, such as
And the like. In particular, R is a branched alkyl having 3 to 12 carbon atoms.
Kill groups are preferred. Specifically, Ar is trifluoro at position 4.
Romethyl group, difluoromethyl group, methyl group, ethyl
Group, fluorine atom, chlorine atom, bromine atom or iodine atom
Is substituted, the 2-position is a methyl group, a trifluoromethyl group or
Is a 5-thiazolyl group optionally substituted with an amino group, e.g.
For example, 2-methyl-4-trifluoromethyl-5-thiazo
Ryl, 2-methyl-4-difluoromethyl-5-thiazo
Ryl, 2-methyl-4-chloro-5-thiazolyl, 2-
Methyl-4-iodo-5-thiazolyl, 4-trifluoro
Romethyl-5-thiazolyl group, 2,4-dimethyl-5-
Thiazolyl group, etc .; trifluoromethyl group at the 3-position, difur
Oromethyl group, methyl group, ethyl group, fluorine atom, chlorine
Atom, bromine atom or iodine atom,
4-pyrazolyl group substituted with a phenyl group; for example, 1-methyl-
3-trifluoromethyl-4-pyrazolyl, 1-methyl
-3-Difluoromethyl-4-pyrazolyl, 1,3 di
Methyl-4-pyrazolyl group, 1-methyl-3-chloro-
4-pyrazolyl, 1-methyl-3-bromo-4-pyrazo
A ril, 1-methyl-3-iodo-4-pyrazolyl group and the like;
The trifluoromethyl group, difluoromethyl group,
Chill, ethyl, chlorine, bromine or iodine
Substituted with a methyl group or trifluoromethyl at the 5-position
An optionally substituted 3-furyl group, for example, 2-methyl
3-furyl group, 2,5-dimethyl-3-furyl group;
The trifluoromethyl group, difluoromethyl group,
Chill, ethyl, chlorine, bromine or iodine
Is substituted with a methyl group at the 4- or 5-position
2-thienyl groups such as 3-methyl-2-thienyl
Group, 3-chloro-2-thienyl group, 3-iodo-2-
Thienyl group, 3,4-dimethyl-2-thienyl group and the like; 2
Trifluoromethyl group, difluoromethyl group, methyl
Group, ethyl group, fluorine atom, chlorine atom, bromine atom
Is a phenyl group substituted by an iodine atom; 2-chloronicotine
A 3-chloro-2-pyrazinyl group; a trif at the 4-position
Fluoromethyl group, difluoromethyl group, methyl group, ethyl
Group, chlorine atom, bromine atom or iodine atom
3-thienyl group, for example 4-methyl-3-thienyl group,
4-chloro-3-thienyl group and the like. In particular, A
r is preferably an A2 group. The substituted thio represented by the general formula (1) of the present invention
The phen derivative is a novel compound and has the following reaction formula
By a method similar to the known method shown in 9), the general formula
A substituted aminothiophene represented by (4) and a general formula (5)
A carboxylic acid halide represented by a molten state or a solvent
It can be produced by reacting in a solution. [0014] Embedded image (Wherein, Q, R and Ar represent the above-mentioned meanings, and X is a salt
Represents an atom, bromine or iodine. ) The solvent used in this reaction is inert to the reaction.
Anything, for example, fats such as hexane and petroleum ether
Aromatic hydrocarbons: benzene, toluene, chlorobenzene, a
Aromatics such as nisol; dioxane, tetrahydrofura
And ethers such as diethyl ether; acetonitrile
, Nitriles such as propionitrile; ethyl acetate
Esters such as dichloromethane, chloroform, 1,
Halogenated hydrocarbons such as 2-dichloroethane; dimethyl
Aprotic such as formamide and dimethyl sulfoxide
Solvents and the like, and a mixed solvent thereof are also used. This reaction may be carried out in the presence of a base.
Bases such as sodium hydroxide and potassium hydroxide
Metals and alkali metals such as calcium and calcium hydroxide
Lithium metal hydroxides; calcium oxide, magnesium oxide
Oxides of alkali metals and alkaline earth metals such as aluminum; water
Alkali metals such as sodium iodide and calcium hydride
And hydrides of alkaline earth metals; lithium amide, na
Amides of alkali metals such as thorium amide; sodium carbonate
Um, potassium carbonate, calcium carbonate, magnesium carbonate
Carbonates of metals such as metals and alkaline earth metals; hydrogen carbonate
Alkali metals such as sodium and potassium bicarbonate and
Alkaline earth metal bicarbonate; methyllithium, spot
Lithium, phenyllithium, methylmagnesium
Alkali metal alkyls such as chloride; sodium methoxide
Sid, sodium ethoxide, potassium-t-butoxy
Alkali metals such as
Alkoxides of alkaline earth metals; triethylamine, pi
Lysine, N, N-dimethylaniline, N-methylpiper
Various types such as gin, lutidine, 4-dimethylaminopyridine
Organic bases, particularly preferably triethyl alcohol.
Min, pyridine. The amount of these bases used is particularly limited.
Although not limited, preferably represented by the general formula (5)
5 to 20 mol% based on the carboxylic acid halide to be used.
Used in molar% excess. In the above reaction, the compound represented by the general formula (4)
Substituted aminothiophenes and a compound represented by the general formula (5)
Rubonic acid halides are generally used in equimolar amounts
However, to improve the yield, one is 1 mol% to 2
It may be used in an excess of 0 mol%. The reaction temperature is usually
The temperature is 20 to 150 ° C, preferably 0 to 40 ° C.
The reaction time is not particularly limited, but is usually 30 minutes to 5 hours.
You. Next, in the general formula (4) which is an intermediate of the present invention,
A method for synthesizing the represented compound will be described. 1) Synthesis of 2-substituted-3-aminothiophene (substituent is
Other than phenyl) These compounds are shown, for example, in the following reaction formula (Formula 10).
Can be synthesized by methods such as
Not something. (Method A): 2-substituted-3-O represented by the general formula (11)
Oxotetrahydrothiophene (wherein R^ThreeIs linear alk
Or branched alkyl group, halogenoalkyl group, alk
Luthioalkyl group, alkyloxyalkyl group, cyclo
Means alkyl group, halogeno-substituted cycloalkyl group
) In ethanol in the presence of barium hydroxide
After oximation with xylamine hydrochloride, ethyl acetate
By treating with hydrogen chloride in a
A method for obtaining min (US Pat. No. 4,317,915;
J. Org. Chem. ,52, 2611 (198
7)) (B-1 and B-2 methods): Formula (13)
Mercaptoacetones represented by the formula (wherein R^FourIs linear al
A killed or branched alkyl group, an alkylthioalkyl group,
Cycloalkyl group) and α-chloroacrylonitrile
Condensation with tolyl (Method B-1, Synth. Commu)
n. ,9, 731 (1979)), or 3-acetyl
Aminothiophene is added in the presence of anhydrous aluminum chloride.
After acylation with silk chloride, hydrolysis (Method B-2,
Bull. soc. chim. Fr. ,1976, 15
1) 2-acyl-3-amino of the formula (14) obtained by
Thiophene was added to di-t-butyl in the presence of triethylamine.
T-butyloxycarbonyl group using dicarbonate
Protected with an alkylating agent such as Grignard reagent (formula
Medium, R^Five Means an alkyl group)
After the compound of (15), trifluoroacetic acid
Method for obtaining amine of formula (16) by reduction with ethylsilane (Method C): 3-aminothiophen-2-ca
Rubonic acid ester was added to di-t- in the presence of triethylamine.
T-butyloxycarbonate using butyl dicarbonate
Alkylating agents such as Grignard reagents
(Where R^Five Has the same meaning as above.)
To (17), and then triethyl acetate in trifluoroacetic acid.
Method for obtaining amine of formula (18) by reduction with silane (Method D): Compound represented by formula (20)
Dehydrate with acetic anhydride and potassium hydrogen sulfate in DMF
After (21), the Boc group is eliminated with trifluoroacetic acid
To obtain an amine of the formula (19)
Can be synthesized. [0021] Embedded imageThe thus obtained 2-substituted 3-a
From minothiophene to general formula (9)
The compound of the present invention represented by the formula (1) can be synthesized. Ma
3-acylamino-2-al represented by the formula (22)
Kenyl-substituted thiophene (where Ar is the above general formula (1)
Which has the same meaning as in formula (3)),
Synthesizing acylamino-2-alkylthiophenes
You can also. 2) 4-alkyl-3-aminothiophene
Synthesis of (Method E): These compounds are shown in the following (Formula 11)
Thus, the 3-oxotetrahydrothiophene of formula (24)
4-carboxylic acid esters (U.S. Pat.
No. 5 and J. J. Org. Chem. ,52, 261
1 (1987)) in the presence of potassium carbonate
After alkylation with an amide, it is obtained by hydrolysis and decarboxylation.
3-oxotetrahydrothiophene of the formula (25)
Medium, R⁶ Represents an alkyl group) in ethanol
Oxygen with hydroxylamine hydrochloride in the presence of barium
And then treated with hydrogen chloride in ethyl ether
To form a 4-alkyl-3-aminothio of the formula (26)
You can get Fen. The thus obtained 4-alkyl-3
-From aminothiophene by the method described above
The compound of the present invention represented by the general formula (1) can be synthesized. [0025] Embedded image The following Tables 1 to 7 (Tables 1 to 7) have the general formula (8).
2-Alkyl-3-aminothiophene represented by the following formula (12)
Table 8 (Table 8) shows examples of the ene derivatives in the general formula (9).
4-alkyl-3-aminothiophene represented by 13)
The example of the derivative was illustrated. [0026] Embedded image [0027] [Table 1]   ((1S) means that the 1st position is the (S) configuration.       Means Mi body. ) [0028] [Table 2][0029] [Table 3] [0030] [Table 4][0031] [Table 5] [0032] [Table 6] [0033] [Table 7] ((1S) means that the 1st position is the (S) configuration.     Means Mi body. ) [0034] Embedded image [0035] [Table 8] 3) R is a phenyl group which may be substituted
in the case of No compounds represented by the general formulas (2) and (3)
These are also novel compounds, for example, the following reaction formula (Formula 14)
Can be produced. [0037] Embedded image (Wherein Q is a hydrogen atom, a methyl group, trifluoromethyl
Group, fluorine atom, chlorine atom, bromine atom, iodine atom,
Toxic group, methylthio group, methylsulfonyl group, cyano
Group, acetyl group, nitro group, alkoxycarbonyl group
Or Z represents a chlorine atom, a bromine atom or
Represents an iodine atom, Y_mIs a hydrogen atom, an alkyl having 1 to 4 carbon atoms
Kill group, alkenyl group having 2 to 4 carbon atoms,
Alkynyl group, cycloalkyl group having 3 to 6 carbon atoms, carbon
An alkoxy group having 1 to 4 carbon atoms and a halogenoal having 1 to 4 carbon atoms
Coxy group, C1-C4 alkylthio group, C1-C1
4 alkylsulfoxy groups, alkyls having 1 to 4 carbon atoms
Ruphonyl group, halogen atom, cyano group, having 2 to 4 carbon atoms
An acyl group, an alkoxycarbonyl group having 2 to 4 carbon atoms,
Amino groups or alkyl groups having 1 to 3 carbon atoms
A mino group; m is an integer of 1 to 3;
A phenyl group and an amino group in formula (2).
Indicates that the phenyl and nitro groups are next to each other.
You. ) That is, a nitrothiophene derivative represented by the general formula (3)
Is described, for example, by the method of Suzuki et al. (Synth. Commu).
n. ,11, 513 (1981); Bull. Che
m. Soc. Jpn. ,61, 3008 (1988);
Chem. Lett. ,1989, 1405; Pe
ters et al. Heterocycl. Chem. ,
28, 1613 (1991)).
The halogenonitrothiophene represented by (6) is a Pd catalyst
And phenylboric acid represented by (7) in the presence of a base
It can be produced by reacting with a derivative.
However, the present invention is not limited to this. The solvent used in this reaction is not
Any active substance such as hexane and petroleum
Aliphatic hydrocarbons such as ter; benzene, toluene, xylene
And aromatics such as anisole; dioxane, tetrahydric
Ethers such as lofuran and diethyl ether; acetonitrile
Nitriles such as tolyl and propionitrile;
Esters such as chill; dichloromethane, chloroform,
Halogenated hydrocarbons such as 1,2-dichloroethane;
Non-prototypes such as tilformamide and dimethyl sulfoxide
Solvents, alcohols such as methanol and ethanol,
Water and the like are used, and a mixed solvent thereof is also used. As the base used, for example, sodium hydroxide
Alkaline such as lium, potassium hydroxide, calcium hydroxide
Hydroxides of lithium and alkaline earth metals; calcium oxide
Alkali metals such as aluminum and magnesium oxide, alkaline earth
Oxides of a class of metals; sodium hydride, calcium hydride
Hydrides of alkali metals and alkaline earth metals such as;
Of alkali metals such as lithium amide and sodium amide
Amide; sodium carbonate, potassium carbonate, calcium carbonate
Metals and alkaline earth metals
Carbonates such as sodium bicarbonate and potassium bicarbonate
Alkali metal and alkaline earth metal bicarbonates;
Chilled lithium, butyl lithium, phenyl lithium,
Alkali metal alkyls such as chill magnesium chloride
Sodium methoxide, sodium ethoxide,
Such as lithium-t-butoxide and dimethoxymagnesium;
Alkoxides of alkali metals and alkaline earth metals;
Triethylamine, pyridine, N, N-dimethylanily
, N-methylpiperidine, lutidine, 4-dimethylamine
Various organic bases such as minopyridine are particularly preferred.
Preferable are sodium carbonate and potassium carbonate. these
The amount of the base used is not particularly limited, but is preferably used.
Or a halogenonitrothiophene represented by the general formula (6)
1.05 to 10 moles, preferably 1.5
Used in 3-fold molar excess. As a Pd catalyst, for example, Pd (PP
h_Three)_Four, PdCl_Two, Pd (OAc)_TwoEtc. are used. Halogennonite represented by the above general formula (6)
Rothiophenes and phenylborough represented by the general formula (7)
Acid derivatives are generally used in equimolar amounts, but yield
Therefore, one may exceed 1 mol% by 100 mol% with respect to the other.
Sometimes used in excess. The reaction temperature is usually from room temperature to 1
It is 50 degreeC, Preferably it is 80-110 degreeC. reaction
The time is not particularly limited, but is usually 30 minutes to 7 hours. On the other hand, aminothio represented by the general formula (2)
For the phen derivative, (3) is represented by, for example, methanol or ethanol.
Catalytic reduction in the presence of Pd / carbon in alcohols such as
Or by reduction with Fe powder in a solvent such as acetic acid
Can be synthesized, but other than that, for example, [New Experimental Chemistry Course,
15. Oxidation and reduction II(Edited by The Chemical Society of Japan, Maruzen, 197
6)] to reduce in a general way as shown in
Therefore, they can be synthesized. The following Tables 9 to 11 (Tables 9 to 11)
A new nitrothiophene derivative of the general formula (3)
Examples of conductors are shown in Tables 12 to 19 (Tables 12 to 19).
Novel aminothiophene derivative of general formula (2)
An example of the body was given. In the latter case, substitution of the amino group
Compounds at the 2-position are generally unstable, so
Was directly amidated. Tables 9 to 19
In the table, general formula (3) (formula 15) and general formula (2)
Q in (Formula 16) represents a hydrogen atom. [0044] Embedded image [0045] [Table 9] [0046] [Table 10][0047] [Table 11][0048] Embedded image [0049] [Table 12]     * Due to the instability, amidation was performed without isolation after catalytic reduction. [0050] [Table 13] [0051] [Table 14][0052] [Table 15][0053] [Table 16][0054] [Table 17][0055] [Table 18][0056] [Table 19] The compound represented by the general formula (1) of the present invention is
Agricultural and horticultural fungicides contained as active ingredients are
Chicken disease (Pyricularia oryzae), Sesame leaf blight (Cochliobolus
miyabeanus), Sheath blight (Rhizoctonia solani), Idiot disease
(Gibberella fujikuroi), Wheat powdery mildew (Erysiph
e graminis f.sp.hordei; f.sp.tritici), Leaf spot disease (Pyre
nophora graminea), Reticulum disease(Pyrenophora teres), Red or
Blight (Gibberella zeae), Rust (Puccinia striiformi
s;P.graminis;P.recondita;P.hordei, Snow rot (Typh
ula sp .;Micronectriella nivalis), Naked smut (Ustila
go tritici;U.nuda), Eye spot disease (Pseudocercosporella he
rpotrichoides), Cloud disease (Rhynchosporiumsecalis),leaf
Blight (Septoria tritici), Fusarium wilt (Leptosphaeria nodor
um), Grape powdery mildew (Uncinula necator), Black pepper
disease(Elsinoe ampelina), Late rot (Glomerella cingulat
a), Rust (Phakopsora ampelopsidis), Apple udon
Sickness (Podosphaera leucotricha), Scab (Venturia i
naequalis), Spotted leaf disease (Alternaria mali), Scab (Gy
mnosporangium yamadae), Monilia disease (Sclerotinia mal
i), Rot (Valsa mali), Black spot of pear (Alternaria
kikuchiana), Scab (Venturia nashicola), Scab (Gy
mnosporangium haraeanum), Peach ash disease (Sclerotinia
cinerea), Scab (Cladosporium carpophilum),
Mopsis rot (Phomopsis sp.), oyster anthracnose (Gloeos
porium kaki), Deciduous disease (Cercospora kaki;Mycosphaerel
la nawae), Powdery mildew of cucumber (Sphaerotheca fuligin
ea), Anthracnose (Colletotrichum lagenarium), Vine blight (M
ycosphaerella melonis), Tomato ring rot (Alternaria
solani), Leaf mold (Cladosporium fulvam), Eggplant udon
Sickness (Erysiphe cichoracoarum), Brassicaceae vegetable black
Leaf spot (Alternaria japonica), Vitiligo (Cerocosporella b
arassicae), Green onion rust (Puccinia allii), Soybean
Purpura (Cercospora kikuchii), Black rot (Elsinoe glyc
ines), Sunspot (Diaporthe phaseololum), Kidney charcoal
The disease (Colletotrichum lindemuthianum), Peanut
Black scab (Mycosphaerella personatum), Brown spot (Cercospo
ra arachidicola), Pea powdery mildew (Erysiphe pi
si), Potato summer blight (Alternaria solani), Cha's
Net blast (Exobasidium reticulatum), Scab (Elsinoe
leucospila), Tobacco scab (Alternaria longipes),
Powdery mildew (Erysiphe cichoracearum), Anthracnose (Colleto
trichum tabacum), Sugar beet brown spot (Cercospora beti
cola), Rose scab (Diplocarpon rosae), Powdery mildew
(Sphaerotheca pannosa), Chrysanthemum spot of chrysanthemum (Septoria chry
santhemi-indici), White rust (Puccinia horiana), Ichi
Powdery mildew (Sphaerotheca humuli), Cucumber, toma
Gray mold on tomatoes, strawberries, grapes, etc.Botrytis cinere
a), Sclerotium disease (Sclerotinia sclerotiorum)
Shows control effect. The compound represented by the general formula (1) of the present invention is
When used as an agricultural or horticultural fungicide,
The active ingredient may be used as it is, but it is generally inactive
Mixed with a liquid carrier or solid carrier
Formulation powders, wettable powders, flowables, emulsions, granules
And other commonly used forms of preparation
Used. If necessary, add supplements if necessary
Can also. The carrier as used herein refers to a substance to be treated
Helps deliver the active ingredient, and stores and transports the active ingredient compound
Synthetic or natural compounded to facilitate transport and handling
Natural or organic substances. As a carrier,
Solid or horticultural drugs
Can be used in any liquid and is limited to certain
Not something. For example, as a solid carrier, montmorillona
Clays such as lite and kaolinite; diatomaceous earth, clay, and tar
, Vermiculite, gypsum, calcium carbonate, silica
Inorganic substances such as kagel and ammonium sulfate; soy flour, sawdust, flour, etc.
Vegetable organic substances and urea. As liquid carriers, toluene, xylene,
Aromatic hydrocarbons such as cumene; kerosene, mineral oil, etc.
Raffinic hydrocarbons; acetone, methyl ethyl ketone
Ketones such as dioxane, diethylene glycol di
Ethers such as methyl ether; methanol, ethanol
Alcohol, propanol, ethylene glycol, etc.
, Dimethylformamide, dimethyl sulfoxide
And aprotic solvents such as water and the like. In order to further enhance the efficacy of the compound of the present invention
In addition, consider the dosage form of the drug product,
Use the following auxiliaries, alone or in combination:
Can also be used. Auxiliaries usually include agricultural and horticultural medicines
Surfactants, binders (eg, lignin
Sulfonic acid, alginic acid, polyvinyl alcohol, ara
Beer gum, sodium CMC, etc.), stabilizers (eg, acid
Phenol compounds, thiol compounds or
Use higher fatty acid esters, etc.
Using phosphates and sometimes using light stabilizers)
They can be used alone or in combination as appropriate. In addition
Therefore, it is an industrial bactericide and a bactericidal and fungicide for antibacterial
And the like can be added. The auxiliary agent will be described in more detail. Emulsification,
Lignin for dispersion, spreading, wetting, bonding, stabilization, etc.
Sulfonate, alkylbenzene sulfonate, alkyl
Sulfate, polyoxyalkylene alkyl sulfate
Salt, polyoxyalkylene alkyl phosphate salt, etc.
Anionic surfactant; polyoxyalkylene alkyl
Ether, polyoxyalkylene alkyl aryl ester
-Tel, polyoxyalkylene alkylamine, polio
Xyalkylene alkyl amide, polyoxyalkylene
Alkyl amide, polyoxyalkylene alkyl thioe
Ter, polyoxyalkylene fatty acid ester, glycer
Phosphoric acid fatty acid ester, sorbitan fatty acid ester, poly
Oxyalkylene sorbitan fatty acid ester, polyoxy
Such as propylene polyoxyethylene block polymer
Nonionic surfactants: calcium stearate, wax
Lubricant such as grease; isopropylhydrodiene phosphate
Stabilizers, etc., other methylcellulose, carboxymethyl
Cellulose, casein, gum arabic, etc.
You. However, these components are limited to the above.
Not. One of the agricultural and horticultural fungicides according to the present invention.
The content of the compound represented by the general formula (1) depends on the preparation form.
However, it is usually 0.05 to 20% by weight for powder,
0.1-80% by weight for wettable powders, 0.1-20% for granules
% By weight, 1 to 50% by weight in emulsion,
1 to 50% by weight, 1 to 80 weight for dry flowable formulation
%, Preferably 0.5 to 5% by weight for powders,
5 to 80% by weight for wettable powders, 0.5 to 8% for granules
%, 5-20% by weight for emulsions, 5-5% for flo
50% by weight and 5 to 50 weights for dry flowable preparations
%. The content of the auxiliary agent is 0 to 80% by weight,
The content of the carrier is from 100% by weight to the active ingredient compound and
This is the amount obtained by subtracting the content of the auxiliary agent. The method of applying the composition of the present invention includes
Poisons, foliage spraying, etc., are usually used by those skilled in the art.
It is effective enough for any application method. Application rate
And the applied concentration depends on the target crop, the target disease, the extent of the disease
Temperature, compound dosage form, application method and various environmental conditions
However, when sprayed, the amount of active ingredient
50 to 1,000 g per quart is suitable and desirable
Or 100-500 g per hectare. Also water
Dilute a Japanese preparation, Floatable or emulsion with water and spray
In this case, the dilution ratio is suitably 200 to 20,000 times.
Yes, preferably 1,000 to 5,000 times. The agricultural and horticultural fungicides of the present invention are not limited to other fungicides,
Pesticides such as insecticides, herbicides and plant growth regulators, soil improvement
Of course, mixed with chemicals or fertilizers,
A mixed preparation of is also possible. Examples of fungicides include birds
Azimefon, hexaconazole, prochloraz, torif
Azole fungicides such as lumizole; metalaxyl, oki
Acylalanine fungicides such as sadixyl; thiophane
Sterilization of benzimidazoles such as trimethyl and benomyl
Fungicides; dithiocarbamate fungicides such as manzeb
Trachloroisophthalonitrile, sulfur, etc.
As insecticides, for example, fenitrothion, diazino
, Pyridafenthion, chlorpyrifos, marathon,
Fentate, dimethoate, methylthiometon,
Rothiophos, DDVP, acephate, salicion, E
Phosphorus insecticides such as PN; NAC, MTMC, BPMC,
Covers such as pirimicarb, carbosurfan, mesomill, etc.
Mate insecticides and etofenprox, permeth
Pyrethroid insecticides such as phosphorus and fenvalerate
But not limited thereto. [0067] EXAMPLES The compounds of the present invention will be further described in the following examples.
Explain physically. Example 1 N- [2- {3- (4-tolyl)} thieni
3] -3-trifluoromethyl-1-methylpyrazole
Synthesis of 4-Carboxamide (Compound No. 3.9) 1) 2-nitro-3- (4-tolyl) thiophene 3-bromo-2-nitrothiophene (0.8 g), 4-
Tolyl boric acid (0.52g), 2M potassium carbonate aqueous solution
Solution (5 ml) and ethanol (2.5 ml) in toluene
(30 ml) and stirred at room temperature for 30 minutes under a nitrogen stream.
Later, Pd (PPh _Three)_Four(0.15 g) and add for 7 hours
Heated to reflux. After separating the two layers, wash with water and separate the organic layer with anhydrous sodium sulfate.
After drying with lithium, the solvent was distilled off under reduced pressure.
Purification by column chromatography, the desired product (0.5
6 g) were obtained as yellow crystals (yield: 70%).¹ H-NMR (CDCl_Three, δ value): 2.42 (s, 3H), 7.01 (d, J = 5.1, 1H), 7.2
5 (d, J = 8.1,2H), 7.37 (d, J = 8.1,2H), 7.47 (d, J = 5.1,1H) 2) 2-amino-3- (4-tolyl) thiophene 2-nitro-3- (4-tolyl) thiophene (0.5
g) is dissolved in dioxane (20 ml) and 5% Pd / C
(0.25 g) and subjected to catalytic reduction at room temperature for 5 hours.
Was. This solution was used for the next reaction as it was after filtration. 3) N- [2- {3- (4-tolyl)} H
Enyl] -3-trifluoromethyl-1-methylpyrazo
4-Carboxamide After filtering the reaction solution obtained in the above 2), pyridine (0.7
3g), 3-trifluoromethyl-1-methylpyrazo
Carboxylic acid chloride (0.45 g)
Stir for 1 hour. Extract with ethyl acetate, saturated sodium bicarbonate
After washing with a lithium solution, it was dried over anhydrous sodium sulfate.
The solvent was distilled off under reduced pressure, and the residue was subjected to silica gel column chromatography.
Purification by luffy gave the desired product (0.4 g) (yield:
47%: from nitro form). Example 2 N- [2- {3- (4-chloro)
Phenyl) thienyl] -3-trifluoromethyl-1
Synthesis of -methylpyrazole-4-carboxylic acid amide
Compound No. 3.2) 1) 2-Nitro-3- (4-chlorophenyl) thiophene
N In Example 1, instead of 4-tolyl boric acid, 4-chloro
Synthesize in exactly the same way except using rophenylboric acid.
(Yield: 91%). mp: 108 ~ 110 ℃¹ H-NMR (CDCl_Three, δ value): 7.00 (d, J = 5.1, 1H), 7.37 to 7.44 (m, 4
H), 7.50 (d, J = 5.1,1H) 2) 2-amino-3- (4-chlorophenyl) thiof
Even In Example 1, 2-nitro-3- (4-tolyl) thio
2-nitro-3- (4-chlorophenyl) instead of phen
B) Synthesized in exactly the same way except using thiophene
This was used for the next reaction as it was. 3) N- [2- {3- (4-chlorophenyl)} thienyl
3] -3-trifluoromethyl-1-methylpyrazole
-4-carboxylic acid amide In Example 1, 2-amino-3- (4-tolyl) thio
2-amino-3- (4-chlorophenyl)
B) Synthesized in exactly the same way except using thiophene
(Yield: 41%: from nitro form). Example 3 N- [3- {2- (4-chloro)
Phenyl) thienyl] -3-trifluoromethyl-1
Synthesis of -methylpyrazole-4-carboxylic acid amide
Compound No. 1.61) 1) 3-nitro-2- (4-chlorophenyl) thiophene
N 2-bromo-3-nitrothiophene in 50 ml of toluene
1 g, 4-chlorophenylboric acid 0.75 g, 2M-
5 ml of potassium carbonate aqueous solution and 2 ml of ethanol were added,
After stirring at room temperature for 30 minutes under a nitrogen stream, Pd (PPh_Three)
_Four0.28 g was added, and the mixture was heated under reflux for 2 hours. Two-layer separation
After washing with water, the organic layer was dried over anhydrous sodium sulfate and depressurized.
The solvent was distilled off under the residue, and the residue was subjected to silica gel column chromatography.
Purification by filtration yielded 1.1 g of the desired product as yellow crystals.
(Yield: 98%).¹ H-NMR (CDCl_Three, δ value): 7.29 (d, J = 5.9, 1H), 7.43 (s, 4H), 7.6
6 (d, J = 5.9,1H) 2) 3-Amino-2- (4-chlorophenyl) thiof
Even 3-nitro-2- (4-chlorophenyl) thiophene 1
g and iron powder (0.93 g) in acetic acid (20 ml).
Heated for hours. After the reaction solution was filtered through Celite,
Chill was added, and the mixture was extracted five times with a 5% aqueous hydrochloric acid solution. This water
Neutralize the layer with sodium bicarbonate and extract with ethyl acetate
And dried over anhydrous sodium sulfate. The solvent is distilled off under reduced pressure
Then, 0.54 g of the target product was obtained as tan crystals (yield:
62%).¹ H-NMR (CDCl_Three, δ value): 3.82 (brs, 2H), 6.64 (d, J = 5.1, 1H),
7.12 (d, J = 5.1,1H), 7.34-7.39 (m, 2H), 7.43-7.48 (m, 2H) 3) N- [3- {2- (4-chlorophenyl)} thieni
3] -3-trifluoromethyl-1-methylpyrazole
-4-carboxylic acid amide 3-amino-2- (4-chlorophenyl) thiophene
0.25 g, pyridine 0.38 g in methylene chloride 20m
3-trifluoromethyl-
1-methylpyrazole-4-carboxylic acid chloride
A solution of 3 g dissolved in 5 ml of methylene chloride was added dropwise.
After stirring at room temperature for 1 hour, 5% hydrochloric acid, saturated sodium bicarbonate
And then with saturated saline, and then dried over anhydrous sodium sulfate.
Dried. After distilling off the solvent under reduced pressure, the residue was
Purify by chromatography to obtain 0.37 g of the desired product colorless
This was obtained as crystals (yield: 81%). Example 4 N- [3- {2- (4-tri
Ru) {thienyl] -3-trifluoromethyl-1-methyl
Synthesis of lupyrazole-4-carboxylic acid amide (compound N
o. 1.68) 1) 3-nitro-2- (4-tolyl) thiophene Instead of 4-chlorophenylboric acid in Example 3
Synthesis was performed in exactly the same manner except that 4-tolyl boric acid was used.
(Yield: 78%).¹ H-NMR (CDCl_Three, δ value): 2.41 (s, 3H), 7.23 to 7.27 (m, 3H), 7.3
7 (dd, J = 2.2,8.1,2H)), 7.64 (d, J = 5.9,1H) 2) 3-amino-2- (4-tolyl) thiophene In Example 3, 3-nitro-2- (4-chlorophenyl)
L) Instead of thiophene, 3-nitro-2- (4-tri
B) Synthesized in exactly the same way except using thiophene
(Yield: 68%).¹ H-NMR (CDCl_Three, δ value): 2.37 (s, 3H), 3.79 (brs, 2H), 6.54 (d,
J = 5.1), 7.09 (d, J = 5.1,1H), 7.22 ((d, J = 8.1,2H), 7.41 (d, J
= 8.1,2H) 3) N- [3- {2- (4-tolyl)} thienyl] -3
-Trifluoromethyl-1-methylpyrazole-4-ca
Rubonamide In Example 3, 3-amino-2- (4-chlorophene
3-amino-2- (4-
Tolyl) In exactly the same way except using thiophene
It was synthesized (yield: 85%). Example 5 N- [3- {2- (4-methoxy)
Cyphenyl) {thienyl] -3-trifluoromethyl-
Synthesis of 1-methylpyrazole-4-carboxylic acid amide
(Compound No. 1.64) 1) 3-nitro-2- (4-methoxyphenyl) thiof
Even Instead of 4-chlorophenylboric acid in Example 3
Exactly the same except that 4-methoxyphenylboric acid was used
(Yield: 96%).¹ H-NMR (CDCl_Three, δ value): 3.86 (s, 3H), 6.96 (d, J = 7.3, 2H), 7.2
0 (d, J = 5.1,1H), 7.44 (d, J = 7.3,2H), 7.63 (d, J = 5.1,1H) 2) 3-amino-2- (4-methoxyphenyl) thio
Fen In Example 3, 3-nitro-2- (4-chlorophenyl)
3) Instead of thiophene, 3-nitro-2- (4-meth
Exactly the same except that (xyphenyl) thiophene was used.
(Yield: 79%).¹ H-NMR (CDCl_Three, δ value): 3.77 (brs, 2H), 3.83 ((s, 3H), 6.65
((d, J = 5.9,1H), 6.96 (d, J = 8.8,2H), 7.07 (d, J = 5.9,1H), 7.
43 (d, J = 8.8,2H) 3) N- [3- {2- (4-methoxyphenyl)} thiye
Nil] -3-trifluoromethyl-1-methylpyrazo
Le-4-carboxylic acid amide In Example 3, 3-amino-2- (4-chlorophene
3-amino-2- (4-
Methoxyphenyl) Except for using thiophene
(Yield: 75%). Example 6 N- (2-isopropenyl-3)
-Thienyl) -3-trifluoromethyl-1-methylpi
Synthesis of Razole-4-Carboxamide (Compound No.
1.71) 1) 3- (t-butoxycarbonylamino) thiophene
-2-Carboxylic acid methyl ester 3-aminothiophene-2-carboxylic acid methyl ester
10 g and 7.72 g of triethylamine in methylene chloride 5
Di-t-butyl dicarbonate was added to the solution dissolved in 0 ml.
After dropwise adding a solution of 13.9 g of methylene chloride in 20 ml,
A catalytic amount of 4-dimethylaminopyridine was added. 5 at room temperature
After stirring for 2 hours, separate two layers, wash with water, and dry with anhydrous sodium sulfate.
Dried. After distilling off the solvent under reduced pressure, the precipitated crystals are filtered off.
Separately, the filtrate was purified by silica gel chromatography.
4.2 g of the target product were obtained as colorless crystals (yield: 75%).¹ H-NMR (CDCl_Three, δ value): 1.52 (s, 9H), 3.88 (s, 3H), 7.43 (d, J =
5.1,1H), 7.88 (d, J = 5.1,1H), 9.35 (brs, 1H) 2) 2- (1-hydroxy-1-methyl) ethyl-3-
(T-butoxycarbonylamino) thiophene 5. 3M solution of MeMgBr in ether under nitrogen atmosphere
5 ml was diluted with 5 ml of THF, cooled to 10 ° C.,
(T-butoxycarbonylamino) thiophen-2-ca
A solution of 1 g of rubonic acid methyl ester in 5 ml of THF is added dropwise.
did. After stirring at room temperature for 3 hours,
After discharging, extract with ethyl acetate, wash with saturated saline,
Dried over sodium hydrogen sulfate. After distilling off the solvent under reduced pressure,
The desired product was obtained as a yellow oil (yield: quantitative).¹ H-NMR (CDCl_Three, δ value): 1.50 (s, 9H), 1.65 (s, 6H), 7.02 (d, J =
5.1,1H), 7.27 (d, J = 5.1,1H), 8.09 (brs, 1H) 3) 3-t-butoxycarbonylamino-2-isopro
Penylthiophene 2- (1-hydroxy-1-methyl) ethyl-3- (t
-Butoxycarbonylamino) thiophene 1.8 g, no
1.4 g of aqueous acetic acid and 0.06 g of potassium hydrogen sulfate in DMF
Added to 10 ml and heated at 60 ° C. for 2 hours. Add water,
After extraction with ethyl acetate, the extract is washed with saturated saline and dried over anhydrous sodium sulfate.
Dried with thorium. After distilling off the solvent under reduced pressure, the residue
The product was purified by Ricagel chromatography.
g were obtained as an orange oil (yield: 60%).¹ H-NMR (CDCl_Three, δ value): 1.50 (s, 9H), 2.11 (s, 3H), 5.18 ((s, 1
H), 5.27 (m, 1H), 6.71 (brs, 1H), 7.13 (d, J = 5.9,1H), 7.56
(d, J = 5.9,1H) 4) 3-amino-2-isopropenylthiophene hydrochloride 3- (t-butoxycarbonylamino) -2-isopro
Dissolve 0.3 g of phenylthiophene in 7 ml of methylene chloride
The solution was cooled to 0 ° C. and dioxane of 4N-hydrogen chloride was
3 ml of the solution is gradually added, and this is directly used for the next reaction.
Using. 5) N- (2-isopropenyl-3-thienyl) -3-
Trifluoromethyl-1-methylpyrazole-4-cal
Bonamide The above solution was cooled to 0 ° C., and 5 ml of pyridine was added.
3-trifluoromethyl-1-methylpyrazole-
0.27 g of 4-carboxylic acid chloride was added to methylene chloride 5
The solution dissolved in ml was dropped. After stirring for 1 hour at room temperature,
5% hydrochloric acid, saturated sodium bicarbonate, and saturated saline sequentially
After washing, it was dried over anhydrous sodium sulfate. Solvent distillation under reduced pressure
After removal, the residue was purified by silica gel column chromatography.
To give 0.12 g of the desired product as crystals (yield: 30
%). Example 7 N- [3- {2- (4-trif)
Fluoromethylphenyl) thienyl] -3-trifluoro
Romethyl-1-methylpyrazole-4-carboxylic acid
Synthesis of Compound (Compound No. 1.77) 1) 3-nitro-2- (4-trifluoromethylphenyi)
Le) Thiophene Instead of 4-chlorophenylboric acid in Example 3
Other than using 4-trifluoromethylphenylboric acid
Was synthesized in exactly the same way (yield: quantitative).¹ H-NMR (CDCl_Three, δ value): 7.35 (d, J = 5.9, 1H), 7.61 (d, J = 8.1, 2
H), 7.69-7.76 (m, 3H) 2) 3-amino-2- (4-trifluoromethylphen)
Nil) thiophene In Example 3, 3-nitro-2- (4-chlorophenyl)
L) Instead of thiophene, 3-nitro-2- (4-tri
Other than using fluoromethylphenyl) thiophene
Synthesized by exactly the same method (yield: 70%)¹ H-NMR (CDCl_Three, δ value): 4.00 (brs, 2H), 6.67 (d, J = 5.1, 1H),
7.18 (d, J = 5.1,1H), 7.64 (s, 1H) 3) N- [3- {2- (4-trifluoromethylphenyi)
Ru) {thienyl] -3-trifluoromethyl-1-methyl
Lupyrazole-4-carboxylic acid amide In Example 3, 3-amino-2- (4-chlorophenyl)
L) 3-Amino-2- (4-tri) in place of thiophene
Other than using fluoromethylphenyl) thiophene
It was synthesized in exactly the same way (yield: 58%). Example 8 N- [3- {2- (3-chloro)
Phenyl) thienyl] -3-trifluoromethyl-1
Synthesis of -methylpyrazole-4-carboxylic acid amide
Compound No. 1.75) 1) 3-nitro-2- (3-chlorophenyl) thiophene
N Instead of 4-chlorophenylboric acid in Example 3
Exactly the same except that 3-chlorophenylboric acid was used
(Yield: 84%).¹ H-NMR (CDCl_,δ value): 7.31 (d, J = 5.9,1H), 7.36 ~ 7.46 (m, 3
H), 7.48 (s, 1H), 7.66 (d, J = 5.9,1H) 2) 3-amino-2- (3-chlorophenyl) thiof
Even In Example 3, 3-nitro-2- (4-chlorophenyl)
3) Instead of thiophene, 3-nitro-2- (3-chloro
Exactly the same except using (phenyl) thiophene
(Yield: 71%).¹ H-NMR (CDCl_Three, δ value): 3.84 (brs, 2H), 6.65 (d, J = 5.1, 1H),
7.14 (d, J = 5.1,1H), 7.21 (dd, J = 1.5,8.8,1H), 7.35 (dt, J =
1.5,8.8,1H), 7.41 (dd, J = 1.5,8.8,1H), 7.51-7.53 (m, 1H) 3) N- [3- {2- (3-chlorophenyl)} thieni
3] -3-trifluoromethyl-1-methylpyrazole
-4-carboxylic acid amide In Example 3, 3-amino-2- (4-chlorophenyl)
3) Instead of thiophene, 3-amino-2- (3-chloro
Exactly the same except using (phenyl) thiophene
(Yield: 79%). Example 9 N- {3- (2-phenyl) thio
Enyl} -4-trifluoromethyl-2-methylthiazo
Synthesis of Toluene-5-Carboxamide (Compound No. 1.
62) 1) 3-nitro-2-phenylthiophene Instead of 4-chlorophenylboric acid in Example 3
Synthesized in exactly the same way except using phenylboric acid
(Yield: 85%)¹ H-NMR (CDCl_Three, δ value): 7.27 (d, J = 5.1, 1H), 7.42 to 7.51 (m, 5
H), 7.65 (d, J = 5.1,1H) 2) 3-amino-2-phenylthiophene In Example 3, 3-nitro-2- (4-chlorophenyl)
L) 3-nitro-2-phenylthio instead of thiophene
Synthesized in exactly the same way except using offen
(Yield: 81%).¹ H-NMR (CDCl_Three, δ value): 3.82 (brs, 2H), 6.66 (d, J = 5.1, 1H),
7.12 (d, J = 5.1,1H), 7.22 ~ 7.29 (m, 1H), 7.42 ((dt, J = 1.5,
7.3,2H), 7.52 (dd, J = 1.5,7.3,2H) 3) N- {3- (2-phenyl) thienyl} -4-tri
Fluoromethyl-2-methylthiazole-5-carboxy
Acid amide 0.5 g of 3-amino-2-phenylthiophene, pyridi
0.70 g of methylene chloride in 30 ml of methylene chloride
Under stirring, 4-trifluoromethyl-2-methylthiazole
0.75 g of methyl 5-carboxylate chloride was dissolved in methyl chloride
A solution dissolved in 10 ml of solution was added dropwise. 1.5 hours at room temperature
After stirring, 5% hydrochloric acid, saturated sodium bicarbonate, saturated diet
After sequentially washing with brine, the extract was dried over anhydrous sodium sulfate. Dissolution
After distilling off the solvent under reduced pressure, the residue was subjected to silica gel column chromatography.
Purification by filtration yielded 0.59 g of the desired product as colorless crystals.
(Yield: 51%). Example 10 N- {3- (2-phenyl)
Thienyl} -3-trifluoromethyl-1-methylpyra
Synthesis of sol-4-carboxylic acid amide (Compound No.
1.60) 3-amino-2- (4-chlorophenyl) thiophene
0.2 g, pyridine 0.35 g in methylene chloride 20 ml
3-trifluoromethyl-1 was added to the solution dissolved in
-Methylpyrazole-4-carboxylic acid chloride 0.2
A solution of 9 g dissolved in 5 ml of methylene chloride was added dropwise.
After stirring at room temperature for 2 hours, 5% hydrochloric acid and saturated sodium bicarbonate
And then with saturated saline, and then dried over anhydrous sodium sulfate.
Dried. After distilling off the solvent under reduced pressure, the residue was
Purify by chromatography to obtain 0.28 g of the target product in colorless form.
This was obtained as crystals (yield: 66%). Example 11 N- {3- (2-phenyl)
Synthesis of Thienyl} -2-chlorobenzoic acid amide (compound
No. 1.96) 0.18 g of 3-amino-2-phenylthiophene, pyri
Solution of 0.35 g of gin dissolved in 20 ml of methylene chloride
Under stirring, 0.18 g of 2-chlorobenzoic acid chloride was added.
A solution dissolved in 5 ml of methylene chloride was added dropwise. At room temperature
After stirring for 1 hour, 5% hydrochloric acid, saturated sodium bicarbonate,
After washing sequentially with a saline solution, the extract is dried over anhydrous sodium sulfate.
Was. After evaporating the solvent under reduced pressure, the residue was subjected to silica gel column chromatography.
Purification by chromatography gave 0.14 g of the desired product as colorless crystals.
(Yield: 47%). Example 12 N- {3- (2-phenyl)
Synthesis of Thienyl I-2-chloronicotinamide (Compound
Object No. 1.97) 0.2 g of 3-amino-2-phenylthiophene, pyridi
0.35 g of methylene chloride in 20 ml of methylene chloride
Under stirring, 0.20 g of 2-chloronicotinic acid chloride was added.
A solution dissolved in 5 ml of methylene chloride was added dropwise. At room temperature
After stirring for 1 hour, 5% hydrochloric acid, saturated sodium bicarbonate,
After washing sequentially with a saline solution, the extract is dried over anhydrous sodium sulfate.
Was. After evaporating the solvent under reduced pressure, the residue was subjected to silica gel column chromatography.
Purification by chromatography gave 0.11 g of the desired product as colorless crystals.
(Yield: 39%). Example 13 N- [2-｛(1S) -1-
Methylpropyl) {-3-thienyl] -3-trifluoro
Romethyl-1-methylpyrazole-4-carboxylic acid
Synthesis of Compound (Compound No. 1.2, Method A) 1) 3-Amino-2-{(1S) -1-methylpropyl
Le)｝ thiophene 2-{(1S) -1-methylpropyl} tetrahydrothio
Offen-3-one (1.7 g) and hydroxylamine
Dissolve the hydrochloride (1.1 g) in ethanol (50 ml)
Then, barium hydroxide octahydrate (3.4 g) was added thereto.
The mixture was refluxed for 5 hours. After cooling and filtration, the solvent is distilled off under reduced pressure.
And add ethyl ether, wash with water, and dry with anhydrous sodium sulfate.
After drying, the solvent was distilled off under reduced pressure to obtain an oxime compound. to this
After adding ethyl ether (50 ml), 6.5N-salt was added.
A methanol solution of hydrogen hydride (1.7 ml) was added and the mixture was added at room temperature.
The mixture was stirred for 3 hours and then left at room temperature for 12 hours. Saturated charcoal
Neutralize with aqueous sodium hydrogen oxyoxide and extract with ethyl ether.
And washed with saturated saline. Dry with anhydrous sodium sulfate
After drying, the solvent is distilled off under reduced pressure.
Purify by chromatography and weigh 0.44 g of the desired product in yellow oil.
(Yield: 26%). 2) N- [2-{(1S) -1-methylpropyl)}-
3-thienyl] -3-trifluoromethyl-1-methyl
Pyrazole-4-carboxylic acid amide In Example 3, 3-amino-2- (4-chlorophenyl)
Ru) 3-Amino-2-｛(1S) instead of thiophene
Except for using -1-methylpropyl)｝ thiophene
It was synthesized in exactly the same way (yield: 75%). Example 14 N- {2- (1,3-dimethyl)
Rubutyl) -3-thienyl} -3-trifluoromethyl
Synthesis of -1-methylpyrazole-4-carboxylic acid amide
(Compound No. 1.13, Method B) 1) 2- (1-hydroxy-1,3-dimethylbutyl)
-3-tert-butoxycarbonylaminothiophene Tetramethyl 2-methylpropylmagnesium bromide
Lofuran solution (2.9 g of 2-methylpropyl bromide,
0.47 g of magnesium, 20 ml of tetrahydrofuran
Was cooled to 10 ° C., and 2-acetyl-3-t-
Butyloxycarbonylaminothiophene (1g)
Drop a tetrahydrofuran (10 ml) solution below 15 ° C
After stirring at room temperature for 2 hours,
Aqueous solution was added dropwise. Extract with ethyl acetate, saturated saline
And then dried over anhydrous sodium sulfate. Decompress the solvent
Evaporation gave 1.2 g of the desired product (yield: 98%). 2) 3-amino-2- (1,3-dimethylbutyl) thio
Fen 2- (1-hydroxy-1,3-dimethylbutyl) -3
1.2 g of t-butoxycarbonylaminothiophene
Dissolve in methylene chloride (10 ml) and add triethylsilane
(0.44 g) and trifluoroacetic acid (4.3 g).
After stirring at room temperature for 20 hours,
Neutralization, extraction (ethyl acetate), washing (saturated saline), drying
(Anhydrous magnesium sulfate). After distilling off the solvent under reduced pressure, the remaining
The gel was purified by silica gel column chromatography,
0.43 g of the target were obtained as crystals. 3) N- {2- (1,3-dimethylbutyl) -3-thier
Nil} -3-trifluoromethyl-1-methylpyrazo
Le-4-carboxylic acid amide In Example 3, 3-amino-2- (4-chlorophenyl)
L) 3-Amino-2- (1,3-
Exactly the same except that dimethylbutyl) thiophene was used
(Yield: 41%). Example 15 N- ｛2-isopropyl-3
-Thienyl} -3-trifluoromethyl-1-methylpi
Synthesis of Razole-4-Carboxamide (Compound No.
1.1, C method) 1) 3-amino-2-isopropylthiophene 2- (1-hydroxy-1-me) which is an intermediate of Example 6
Tyl) ethyl-3-t-butoxycarbonylaminothio
Dissolve phen (0.9 g) in methylene chloride (10 ml)
And triethylsilane (0.41 g), trifluorovinegar
An acid (4 g) was added, and the mixture was stirred at room temperature for 20 hours.
Neutralized with sodium bicarbonate, extracted with ethyl acetate, saturated saline
Washed and dried over anhydrous magnesium sulfate. Solvent distillation under reduced pressure
After removal, the residue was purified by silica gel column chromatography.
To give 0.29 g of the desired product as crystals (yield: 62
%). 2) N- {2-isopropyl-3-thienyl} -3-to
Trifluoromethyl-1-methylpyrazole-4-carbo
Acid amide In Example 3, 3-amino-2- (4-chlorophenyl)
3) Instead of thiophene, 3-amino-2-isopropyl
Synthesized in exactly the same way except using luthiophene.
(Yield: 53%). Example 16 N- ｛2-isopropyl-3
-Thienyl} -3-trifluoromethyl-1-methylpi
Synthesis of Razole-4-Carboxamide (Compound No.
1.1, Method D) 1 g of the compound of Example 6 (Compound No. 1.71) was
Dissolved in 5% Pd / carbon (0.2 ml).
g) and perform catalytic reduction under normal pressure at room temperature for 8 hours.
Was. After filtration and washing with methanol, the filtrate was concentrated under reduced pressure to obtain
Sludge the oily material with hexane
0.8 g of the product was obtained as crystals (yield: 79%). Others synthesized in the same manner as in the examples
Examples of the compound of the formula (1) are shown in Tables 20 to 62 below (Table 1).
20 to Table 62). Tables 20 to 62
In Tables 20 to 62, R in A2 of Ar^Three
Are all methyl groups. [0085] Embedded image [0086] [Table 20][0087] [Table 21] [0088] [Table 22][0089] [Table 23][0090] [Table 24][0091] [Table 25] [0092] [Table 26][0093] [Table 27] [0094] [Table 28][0095] [Table 29] [0096] [Table 30][0097] [Table 31][0098] [Table 32] [0099] [Table 33] [0100] [Table 34][0101] [Table 35][0102] [Table 36] [0103] [Table 37] [0104] [Table 38] [0105] [Table 39][0106] [Table 40][0107] [Table 41][0108] [Table 42][0109] [Table 43][0110] [Table 44][0111] [Table 45] [0112] [Table 46][0113] [Table 47] [0114] [Table 48] [0115] [Table 49][0116] [Table 50][0117] [Table 51] [0118] [Table 52] [0119] [Table 53][0120] [Table 54][0121] [Table 55][0122] Embedded image [0123] [Table 56][0124] [Table 57] [0125] Embedded image [0126] [Table 58][0127] [Table 59] [0128] [Table 60][0129] Embedded image [0130] [Table 61] [0131] [Table 62]Next, the preparation of the fungicide for agricultural and horticultural use according to the present invention.
Examples and test examples are shown. Formulation Example 1 Powder 3 parts of compound No. 1.2, 20 parts of diatomaceous earth,
77 parts of Leh were uniformly ground and mixed to obtain 100 parts of powder. Formulation Example 2 wettable powder 25 parts of compound No. 1.13, diatomaceous earth 72
Part, sodium lignin sulfonate 1 part and alkyl
Evenly pulverize and mix 2 parts of sodium benzenesulfonate
Thus, 100 parts of wettable powder was obtained. Formulation Example 3 wettable powder 50 parts of compound No. 1.24, 30 parts of clay, e
10 parts of wite carbon, 5 parts of sodium lauryl phosphate
And 5 parts of sodium alkylnaphthalenesulfonate
The mixture was mixed to obtain 100 parts of a wettable powder. Formulation Example 4 wettable powder Compound No. 1.61, 50 parts of compound, lignin sulfone
Sodium naphthalene sulfonate 10 parts
5 parts of thorium, 10 parts of white carbon and diatom
25 parts of soil was mixed and pulverized to obtain 100 parts of wettable powder. Formulation Example 5 Emulsion 10 parts of compound No. 1.77, cyclohexane 1
0 parts, xylene 60 parts and Solpol (Toho Chemical Industry)
(Surfactant) 20 parts were uniformly dissolved and mixed, and 100 parts of the emulsion was mixed
Obtained. Formulation Example 6 Flowable 40 parts of compound of compound number 1.13, carboxymethyl
3 parts of cellulose, 2 parts of sodium ligninsulfonate,
1 part of dioctyl sulfosuccinate sodium salt and
Wet pulverize 54 parts of water with a sand grinder,
To obtain 100 parts of a pharmaceutical preparation. Next, the compound of the present invention is used as a fungicide for agricultural and horticultural use.
Will be described by test examples. Test Example 1 Test for controlling bean gray mold (1) Cotyledon in 7.5cm diameter plastic pot in greenhouse
Beans grown two by two until development (varieties: without vine
Top crop), wettable powder prepared according to Formulation Example 3
Is diluted to a predetermined concentration (active ingredient concentration 200 ppm),
50 ml was sprayed per 4 pots. After the chemical has dried
Gray mold fungus cultured on PDA medium (MBC resistant, RS
Conidia suspension (1 × 10^FivePieces / m
l) is spray-inoculated on cotyledons, and the temperature is 20 to 23 ° C and the humidity is 95%.
It was kept in the above greenhouse for 7 days. 7 days after inoculation, 1 bean leaf
The area occupied by gray mold spots per area according to the following indicators
Was investigated. The results are shown in Tables 63 to 72 (Tables 63 to 72).
72). The average value of each treated section and the untreated section was defined as the disease severity. Control value (%) = (1-degree of disease in treated area / incidence in untreated area)
Degree) x 100 [0139] Test Example 2 Bean gray mold control test (2) Cotyledon in 7.5cm diameter plastic pot in greenhouse
Beans grown two by two until development (varieties: without vine
Top crop), wettable powder prepared according to Formulation Example 3
Is diluted to a predetermined concentration (active ingredient concentration 200 ppm),
50 ml was sprayed per 4 pots. After the chemical has dried
Gray mold fungus grown on PDA medium (MBC resistant, Zika)
Separation prepared from ruboximide drug resistant, RR bacteria)
Spore suspension (1 × 10^Five/ Ml) on the cotyledon
And kept in a greenhouse at 20 to 23 ° C and a humidity of 95% or more for 7 days.
Was. 7 days after inoculation, gray mold disease per kidney bean leaf
The area occupied by the spots was investigated according to the following indices. The result
The results are shown in Tables 63 to 72 (Tables 63 to 72).The average value of each treated section and the untreated section was defined as the disease severity. Control value (%) = (1-degree of disease in treated area / incidence in untreated area)
Degree) x 100 Test Example 3 Cucumber Powdery Mildew Control Test 1.5cm in a 7.5cm diameter plastic pot in the greenhouse
Cucumbers grown two by two until the leaf stage (cultivar: Sagamihan
White), the wettable powder prepared according to Formulation Example 3 at a predetermined concentration
(Active ingredient concentration 200ppm)
50 ml each. After the chemical has dried, a small amount of
Suspend the conidia of powdery mildew of cucumber in water
Conidia suspension (1 × 10⁶Pcs / ml)
They were inoculated by fog and kept in a greenhouse for 7 days. 7 days after inoculation, cucumber 1
The area occupied by powdery mildew spots per leaf as the next index
Therefore investigated. The results are shown in Tables 63 to 72 (Tables 63 to 63).
It is shown in Table 72). The average value of each treated section and the untreated section was defined as the disease severity. Control value (%) = (1-degree of disease in treated area / incidence in untreated area)
Degree) x 100 Test Example 4 Wheat powdery mildew (resistant to EBI agent)
Test) 1.5 leaf stage in 6cm diameter plastic pot in greenhouse
Wheat (cultivar: Chiho)
H), the wettable powder prepared according to Formulation Example 3 at a predetermined concentration
(Active ingredient concentration 200ppm)
50 ml each. After the chemical dries, wheat
After spraying the conidia of powdery mildew (EBI drug resistant bacteria), 18
It left in the room of ° C. 7 days after inoculation, udon on the first leaf of wheat
The area occupied by the lesions of sickness was surveyed according to the following indicators.
Was. The results are shown in Tables 63 to 72 (Tables 63 to 72).
You. The average value of each treated section and the untreated section was defined as the disease severity. Control value (%) = (1-degree of disease in treated area / incidence in untreated area)
Degree) x 100 Test Example 5 Wheat Leaf Rust Control Test 1.5 leaf stage in 6cm diameter plastic pot in greenhouse
Up to 15 to 20 plants (cultivar: Norin 6)
No. 4), a wettable powder prepared according to Formulation Example 3 at a predetermined concentration
(Active ingredient concentration 200ppm)
50 ml each. After the chemical dries, wheat red
After spraying rust spores and placing them in a humidified state for 2 days, 18
Transferred to room temperature. 10 days after inoculation, the first leaf of the wheat has redness
The area occupied by the lesions of rust was investigated according to the following indices.
The results are shown in Tables 63 to 72 (Tables 63 to 72). The average value of each treated section and the untreated section was defined as the disease severity. Control value (%) = (1-degree of disease in treated area / incidence in untreated area)
Degree) x 100 [0143] [Table 63]The numerical values in the table represent the control value. --- represents an untested sample. [0144] [Table 64] [0145] [Table 65][0146] [Table 66][0147] [Table 67][0148] [Table 68][0149] [Table 69][0150] [Table 70][0151] [Table 71][0152] [Table 72]Control Compound 1: Procymidone, trade name = Sumirex,
Chemical name = N- (3,5-dichlorophenyl) -1,2-
Dimethylcyclopropane-1,2-dicarboximide Control Compound 2: Triadimefon, trade name = bileton,
Chemical name = 1- (4-chlorophenoxy) -3,3-dim
Tyl-1- (1,2,4-triazol-1-yl)-
2-butanone Control compound 3: described in JP-A-5-221994
(Compound of No. 10.1), chemical name = N- (2-iso
Propylphenyl) -5-chloro-1,3-dimethylpi
Lazole-4-carboxylic acid amide Control compound 4: described in JP-A-5-221994
(Compound of No. 9.2), Chemical Name = N- (2-Propylene)
Ruphenyl) -2-methyl-4-trifluoromethylthio
Azole-5-carboxamide [0153] The compound of the present invention represented by the general formula (1)
Is a variety of crops such as gray mold, powdery mildew, rust, etc.
Has excellent control effects on the disease of rice, and is now becoming more serious
It is also effective against drug-resistant bacteria,
Useful as a fungicide.

──────────────────────────────────────────────────続 き Continued on the front page (72) Inventor Kan Takahashi 1144 Togo, Mobara-shi, Chiba Mitsui Chemicals, Inc. (72) Inventor Shunichi Inami 1144 Togo, Togo, Mobara-shi, Chiba Mitsui Chemicals (72) Inventor Yuji Yanase 1144 Togo, Mobara-shi, Chiba Prefecture Mitsui Chemicals Co., Ltd. (72) Inventor Junro Kishi 1144 Togo, Mobara-shi, Chiba Mitsui Chemicals Co., Ltd. (72) Inventor Hitoshi Shimotori Togo, Mobara-shi, Chiba Pref. 1144 Mitsui Chemicals, Inc. (72) Inventor Naofumi Tomura 1144, Togo, Mobara-shi, Chiba Mitsui Chemicals, Inc. (56) References JP-A-56-97282 (JP, A) JP-A-53-40755 (JP, A) Table 11-11501616 (JP, A) US Patent 4,451,660 (US, A) Chemical Abstracts, vol. 64, 3451a-h J.P. Org. Chem. , (1971), 36 (16), p. 2236-2244 J.P. Chem. Soc. , Perkin Trans. 2, (1972), (11), p. 1594-7 Acta Chemical Scan. , (1972) 25 (5), p. 1581-9 Acta Chemical Scan. , (1970), 24 (7), p. 2629-33 Acta Chemical Scan. , (1967), 21 (10), p. 2823-33J. Heterocycl. Chem. , (1982), 19 (2), p. 443-5 J.P. Heterocycl. Chem. , (1994), 31 (2), p. 305-12 Bull. Chem. Soc. Jpn. , (1994), 67 (8), p. 2187-94 (58) Field surveyed (Int. Cl. ⁷ , DB name) C07D 333/36 CA (STN) REGISTRY (STN)

Claims (1)

(57) [Claim 1] Formula 8 (Formula 3) (Wherein Q is a hydrogen atom, R is a 1-methylbutyl group, 1,
A 3-dimethylbutyl group or a 1,3-dimethylpentyl group).