JPS63264478A - Pyridylpyrimidine derivative, production thereof and plant blight controller comprising said derivative as active ingredient - Google Patents

Abstract

NEW MATERIAL:A pyridylpyrimidine derivative shown by formula I (R1 is lower alkyl R2 and R3 are H or methyl; n is 0-5; R4 is lower alkyl, lower alkoxy, lower haloalkyl or halogen; R5 is H or lower alkyl; R6 is H, lower alkyl, lower alkoxy, lower alkenyloxy or lower alkylthio) or a salt thereof. EXAMPLE:2-(6-Methyl-2-pyridyl)-6-O-tolylpyrimidine. USE:Useful as a plant blight controller showing excellent effects on plant blights such as blast, helminthosporium leaf spot and sheath blight of rice plant. PREPARATION:A halopyrimidine derivative shown by formula II (X is halogen) is reacted with a compound shown by formula III (R6'' is lower alkoxy or lower alkenyloxy; Y is alkali metal) to give a compound shown by formula I.

Description

DETAILED DESCRIPTION OF THE INVENTION <Industrial Application Field> The present invention relates to a novel pyridylpyrimidine derivative, a method for producing the same, and a plant disease control agent containing the same as an active ingredient.

<Prior art> As pyridylpyrimidine derivatives, examples of synthesis of 4-methyl-2-(2-pyridyl)pyrimidine and 4-phenyl-2-(2-pyridyl)pyrimidine have been reported in J.
*Orga Cherna, 82.

1591 (1967), N.

Au5L J that N-dimethyl-2-(6-methyl-2-pyridyl-pyrimidin-4-ylthio)ethylamine is used as a potentiator for phleomycin (medicine).
, Chem, , 85, 1208 (1982
)It is described in.

However, it is not known that the above derivatives exhibit bactericidal activity.

<Problems to be solved by the invention> The purpose of the present invention is to develop compounds that have prophylactic or therapeutic effects on many plant diseases. Means> In order to achieve the above object, the present inventors have made intensive studies and found that the general formula [wherein the tortoise represents a lower alkyl group, R2 and R3
are the same or different and represent a hydrogen atom or a methyl group, n represents an integer of 0 to 5, R4 is the same or different and represents a lower alkyl group, a lower alkoxy group, a low haloalkyl group, or a halogen atom; represents a hydrogen atom or a lower alkyl group, and represents a hydrogen atom, a lower alkyl group, a lower alkoxy group, a lower alkenyloxy group, or a lower alkylthio group.] Pyrzylpyrimidine derivatives (hereinafter referred to as compounds of the present invention). ) was found to have excellent bactericidal activity, leading to the present invention.

Plant diseases that can be controlled by the compounds of the present invention include rice blast (Pyricularia oryzae).
), sesame leaf blight (Cochliobolus m1ya
beanus), sheath blight (Rhizoctonia 5)
olani), powdery mildew of wheat (Puccinia
striiformis, P. graminis XP
*rJ (1-ita P, hordei), eye spot (Pseudocercos-porella he
rpotrichoides), Rhynch
osporium 5ecalis), leaf blight (Sep.
toria tritici)% Blight (Leptos
phaeria nodorum), citrus black spot (Diaporthe citri), scab disease (E
lsinoefawcetti), apple powdery mildew (Podosphaeraleucotricha),
Leaf spot disease (Alternaria mali)
, Venturia 1naequalis
, Venturia nashicol
a), Al ternariakikuchi
ana), peach gray layer disease (Sllerotinia c
i-nerea), grape blackhead (Elsino
e ampelina), late rot disease (Glomorell)
a cingulata), powdery mildew (Uncinv
la necator), cucurbit anthracnose (Coll-
etotrichum lagenarium), powdery mildew (Spha-erotheca fuligin)
ea), ) vt Alter-nari
a 5olani＼plague (Phytophthora
1nfestans), eggplant brown spot disease (Phomops
i s vexans), black spot of cruciferous vegetables (Alternbria japonica), white spot (Gercosporella brassicae)
, green onion rust (Puccinia allii), soybean purpura (Cercosporakikuchi)
i), Elsinoe glycines
), kidney bean anthracnose (Colletotrichum
lindemu-thianum), groundnut black astringent disease (Mycosphaere-11a perso
natum), Cercospora ara
chi-dicola), powdery mildew of pea (E.
rys 1phepis i), summer blight of potato (Alternaria 5olani), brown spot of sugar beet (Cercospora beticola)
), Diplocarpon rosa
e), powdery mildew (Sphaerotheca pan)
nosa), botrytis (Botryti) of various crops
S cinerea), Sclerotinia
ia sclerotiorum).

Next, the method for producing the compound of the present invention will be explained in detail.
□ Among the compounds of the present invention, pyridylpyrimidine derivatives represented by the general formula [wherein R,, R2, Rs, IL4, R5 and n represent the same meanings as above, and λi represents a hydrogen atom] are represented by the general formula [In the formula, K1, R2, R3, R4, R5 and n represent the same meanings as above, and X represents a halogen atom. ] The halopyrimidine derivative represented by is reduced in a solvent in the presence of a catalyst with hydrogen gas at normal pressure under pressure at room temperature to 50'C! .

By contacting for 0.5 to 8 hours, the above general formula [sulfur]
A pyridylpyrimidine derivative represented by can be obtained.

Examples of the solvent that can be used in the above reaction include lower alcohols such as methanol and ethanol, esters such as dioxane and ethyl acetate, aromatic hydrocarbons such as toluene, water, and mixtures thereof. Examples of the catalyst include palladium on carbon, and the hydrogen pressure is preferably 1 to 8 atmospheres.

Preferably, the reaction is carried out in the presence of a dehydrohalogenating agent, such as a base such as ammonia, sodium hydroxide, sodium carbonate, sodium acetate, etc., or Dowex 1 (registered trademark of The Dow Chemical Company). ) and other basic ion exchange resins.

After the reaction is completed, the catalyst is removed from the reaction solution by filtration, and the reaction solution is concentrated under reduced pressure. Next, when a dehydrohalogenating agent is not used, an aqueous base solution such as sodium carbonate is added, followed by extraction with an organic solvent, and when a dehydrohalogenating agent is used, water is added and then an organic solvent is extracted. After the extraction, the target compound can be obtained by performing usual post-treatments such as concentration under reduced pressure and, if necessary, subjecting it to operations such as chromatography.

Furthermore, among the compounds of the present invention, compounds of the general formula [wherein R1, R2, Rs, R4, R, and n represent the same meanings as above, and R6'' represents a lower alkoxy group, a lower alkenyloxy group, or a lower alkylthio group] ] The pyridylpyrimidine derivative represented by the general formula [厘]
By reacting a halopyrimidine derivative represented by the general formula % with an alkali metal derivative represented by the general formula % [[wherein 9-6'' represents the same meaning as above and Y represents an alkali metal atom]] can get.

Examples of the alkali metal atom of the alkali metal derivative include sodium and potassium.

In the above reaction, the reaction temperature is typically 10 to 120
"Q. The reaction time is 10 minutes to 48 hours. Also, the amount of the reagent used in the above reaction is usually one equivalent of the haloparimidine derivative represented by the general formula [v] The alkali metal derivative represented by is 1 to 1
．． It is 5 equivalents.

In the above reaction, a reaction solvent is not necessarily required, but it is generally carried out in the presence of a solvent. Examples of solvents that can be used include those in which R6 is a lower alkoxy group or a lower alkenyloxy group in the general formula [''V]. In the case of certain alkali metal compounds, examples include corresponding alcohols such as methanol, ethanol, allyl alcohol, ethers such as diethyl ether, dioxane, and tetrahydrofuran, aromatic hydrocarbons such as toluene, or mixtures thereof.

In the case of an alkali metal compound in which R6'' is a lower alkylthio group, examples include ethers such as diethyl ether, dioxane, and tetrahydrofuran, nitrites such as acetonitrile, aromatic hydrocarbons such as toluene, water, etc., or mixtures thereof. It will be done.

After completion of the reaction, the reaction solution is subjected to usual post-treatment operations such as concentration under reduced pressure, and optionally subjected to operations such as chromatography and recrystallization to obtain the target compound.

Furthermore, among the compounds of the present invention, pyridylpyrimidine derivatives represented by the general formula [wherein R1, R2, R3, k4, λ, and n represent the same meanings as above, and the symbol "' represents a lower alkyl group]" The halopyrimidine derivative represented by the general formula [side] and the general formula R, CH(CO
OR8)2C■] [In the formula, λ7 represents a hydrogen atom or a lower alkyl group, and - represents a lower alkyl group] is reacted with a malonic acid diester derivative in the presence of a base, and then hydrolyzed. , further decarboxylated.

In the reaction of the herobyrimidine derivative represented by the above general formula [melon] with the malonic acid diester derivative represented by the general formula CVM''J, the base used in the reaction may include, for example, an alkali metal hydride such as sodium hydride. kind, n
Examples include alkyllithiums such as -butyllithium, lithium dialkylamides such as lithium diisopropylamide (LDA), alkali metal alkoxides such as sodium methoxide, and alkali metal hydroxides such as sodium hydroxide.

In the above reaction, the reaction temperature is typically 0 to 150°.
C1 reaction time is 80 minutes to 24 hours, and the reagents used for the reaction are usually expressed by the general formula αI] per equivalent of the halopyrimidine derivative represented by the above general formula [I]. Malonic acid diester derivative and base are each 1
~2 equivalents.

In the above reaction, although a reaction solvent is not necessarily required, it is generally carried out in the presence of a solvent. Usable solvents include lower alcohols such as methanol and ethanol, nitriles such as acetonitrile, ethers such as diethyl ether and tetrahydrofuran, halohydrocarbons such as chloroform, aromatic hydrocarbons such as benzene and toluene, octoday aromatic hydrocarbons such as chlorobenzene,
Examples include ketones such as acetone and methyl isobutyl ketone, esters such as ethyl acetate, sulfur compounds such as dimethyl sulfoxide and sulfolane, and mixtures thereof.

Next, after the completion of the above reaction, the target compound can be obtained by hydrolysis and decarboxylation. 2.1 to 5 bases For example, an aqueous solution of an alkali metal hydroxide such as sodium hydroxide, or an alkali metal carbonate such as sodium carbonate, or a mixed solution of an aqueous solution of the base and a lower alcohol such as methanol or ethanol. is added to carry out an alkali hydrolysis reaction at a reaction temperature of 10 to 100'C and a reaction time of 10 minutes to 24 hours. Next, 2.5 to 6 equivalents of acid per equivalent of the halopyrimidine derivative represented by the above general formula [intestinal] are added to the reaction solution,
For example, by adding an inorganic acid such as sulfuric acid or an organic acid such as acetic acid,
Reaction temperature 20-150"C!, reaction time 10 minutes-24
The decarboxylation reaction takes place over a period of time.

After the reaction is complete, alkali metal hydroxides such as sodium hydroxide, alkaline earth metal hydroxides such as calcium hydroxide, alkali metal carbonates such as sodium carbonate, alkali metal hydrogen carbonates such as baking soda, triethylamine, etc. After neutralizing the reaction solution with an organic base, etc., the desired compound can be obtained by performing usual post-treatments such as concentration under reduced pressure and extraction, and if necessary, subjecting it to operations such as recrystallization and column chromatography. .

Furthermore, among the compounds of the present invention, pyridylpyridhizine derivatives represented by the general formula [wherein R,, R2, "4s R4 and n represent the same meanings as above, and R5' and R61 represent hydrogen atoms] , the general formula [where ζ and n represent the same meanings as above], a picolinamidine derivative or a salt thereof represented by the general formula [where ζ and n represent the same meanings as above, It can be obtained by reacting enamine derivatives represented by 〇 representing a lower alkyl group in the presence of a base.

In the above reaction, the reaction temperature is typically 50 to 150℃.
C1 reaction time is 1-6 hours.

In addition, the amount of the reagent used in the above reaction is usually 1 to 1 equivalent of the enamine derivative represented by the general formula [X] per 1 equivalent of the picolinamidine derivative represented by the above general formula [■] or its salt. .5 equivalents, and the base is 2.5 equivalents from the catalytic amount.
It is equivalent.

Examples of bases that can be used include alkali metal alkoxides such as sodium methoxide, or organic bases such as triethylamine. Examples of solvents that can be used include lower alcohols such as methanol, cyclic ethers such as tetrahydrofuran, pyridine, N, N, etc. - Dimethylformamide, etc. and mixtures thereof, etc., but it is usually preferable to use sodium ethoxide in methanol, sodium methoxide or ethanol. The target compound can be obtained by post-treatment and, if necessary, subjecting it to chromatography or the like.

The compound of the present invention represented by the above general formula [I] can be converted into the respective salt by reacting it with a feared acid such as hydrogen chloride, hydrogen bromide, sulfuric acid, or nitric acid according to a conventional method. When producing these salts, for example, the compound of the present invention represented by the general formula [■] is dissolved in a solvent, and 1 equivalent of acid in gas or aqueous solution is added under water cooling or at room temperature for 10 minutes or more. 1
After standing for a period of time, post-treatment such as concentration under reduced pressure is performed, and if necessary, treatment is performed by recrystallization.

Reaction solvents include lower alcohols such as methanol and ethanol, aromatic hydrocarbons such as toluene and benzene, ethers such as ethyl ether, tetrahydrofuran and dioxane, halogenated hydrocarbons such as chloroform, ketones such as acetone, and ethyl acetate. , hydrocarbons such as hexane, water or mixtures thereof, etc. Halopyrimidine derivatives represented by the general formula [■] which are raw materials for producing the compounds of the present invention, and the general formula [
The picolinamidine derivative represented by [2] can be synthesized, for example, by the following synthetic route. R4, R5 and n represent the same meanings as above, K. and to.

represents a lower alkyl group, and M represents an alkali metal atom.] That is, J, Org, Chem, 48. 18
75-1877 (198B), etc., and an alkoxide represented by the general formula [][1]. An imidate derivative represented by the formula (2) is obtained, and by reacting the imidate derivative with an ammonium group, a picolinamidine derivative represented by the general formula [DD] is obtained.

Next, by reacting the thus obtained picorinia, midine derivative or salt thereof with a β-oxocarboxylic acid ester represented by the general formula CM in the presence of a base, a hydroxypyrimidine represented by the general formula J] is obtained. A derivative is obtained, and by reacting the hydroxypyrimidine derivative with a halogenating agent, a halopyrimidine derivative represented by the general formula [1lll] is obtained.

The above manufacturing method will be explained in detail below.

In the reaction between the cyanopyridine derivative represented by the general formula [■] and the alkoxide represented by the general formula [■], examples of the alkali gold oxide of the alkoxide used include sodium atoms, potassium atoms, etc.

In addition, in this reaction, the reaction temperature is typically 10 to 50°C.
The reaction time at °C1 is 1 to 48 hours, and the amount of reagent used for the reaction is 0.1 equivalent of the alkoxide represented by the general formula [xII] per equivalent of the cyanopyridine derivative represented by the general formula [(]). ~1 equivalent.

In the above reaction, although a reaction solvent is not necessarily required, it is generally carried out in the presence of a solvent.

As solvents that can be used, lower alcohols corresponding to Rqo of the alkoxide represented by the general formula [Xl], such as
Methanol, ethanol, n-propyl alcohol, isopropyl alcohol, n-butyl alcohol, etc. are preferred, and methanol and ethanol are preferred.The reaction solution after the reaction is neutralized with an acid, concentrated under reduced pressure, and then mixed with an organic solvent. The desired imidate derivative represented by the general formula 1 can be obtained by dissolving the insoluble alkali metal salt in the solution, removing the insoluble alkali metal salt, concentrating the solution under reduced pressure, and subjecting it to operations such as distillation, if necessary. .

Next, in the reaction of the imidate derivative represented by the general formula [" .

In addition, in this reaction, the reaction temperature is typically 30 to 10
0''C, the reaction time is 30 minutes to 5 hours, and the amount of reagent used in the reaction is usually 1 to 1.1 equivalents of ammonium salt per 1 equivalent of the imidate derivative represented by the general formula 1]. It is.

Although a solvent is not necessarily required in the reaction 1, it is generally carried out in the presence of a solvent.

Examples of solvents that can be used include lower alcohols, preferably a mixed solvent of ethanol and water.

After completion of the reaction, the reaction solution is subjected to usual post-treatments such as concentration under reduced pressure, and if necessary, recrystallization and other operations are performed to prepare the picolinamidine derivative represented by the general formula (DO) with hydrochloric acid, hydrobromic acid,
Salts of acetic acid, formic acid, etc. can be obtained.

The salt thus obtained is decomposed by a conventional method such as neutralization with an inorganic base such as sodium hydroxide or potassium hydroxide or an alkali metal alkoxide such as sodium methoxide or sodium ethoxide. By doing so, a picolinamidine derivative represented by the general formula [■] can be obtained.

Alternatively, the salt can be directly subjected to the reaction in the next step, and the salt can be decomposed within the reaction system.

Next, in the reaction between the picolinamidine derivative represented by the general formula CEX obtained by C.

The reaction time is 1 to 24 hours, and the amount of reagent used in the reaction is equivalent to 1 equivalent of the picolinamidine derivative or its salt represented by the general formula CTX'J.In the above reaction, the solvent is not necessarily used. Although not required, it is generally carried out in the presence of a solvent.

Examples of solvents that can be used include lower alcohols such as methanol and ethanol, cyclic ethers such as dioxane and tetrahydrofuran, pyridine, N,N-dimethylformamide, water, etc., or mixtures thereof.
Examples of the base include inorganic bases such as sodium hydroxide, potassium hydroxide, potassium charcoal, alkali metal alkoxides such as sodium methoxide, triethylamine, N
, N-diethylaniline, and other organic bases.

After the completion of the reaction, the reaction solution is subjected to normal post-treatments such as removal of salt by passing through, etc., and condensation under reduced pressure, as necessary.If necessary, chromatography and recrystallization are performed to obtain the desired general formula. A hydroxypyrimidine derivative represented by r″Xv] can be obtained.

Next, in the reaction of the hydroxypyrimidine derivative represented by the general formula c' , phosphorus oxybromide, phosphorus tribromide, etc.

In the above reaction, the reaction temperature is typically 50 to 150
The reaction time at °C1 is 1 to 10 hours, and the amount of the halogenating agent used for the reaction is usually 1 to 10 hours per equivalent of the hydroxypyrimidine derivative represented by the general formula [■].
It is equivalent.

Although a solvent is not necessarily required in the above reaction, it is generally carried out in the presence of a solvent.

Examples of solvents that can be used include aromatic hydrocarbons such as benzene and toluene, and halogenated hydrocarbons such as chlorobenzene.

After the reaction is completed, the reaction solution is concentrated under reduced pressure, neutralized with an inorganic base such as sodium hydroxide, and subjected to usual post-treatments such as organic solvent extraction and concentration.If necessary, chromatography, recrystallization, etc. By this operation, the desired halopyrimidine derivative represented by the general formula ("l") can be obtained.

When the compound of the present invention is used as an active ingredient in a plant disease control agent, it may be used as is without adding any other ingredients, but it is usually used in combination with solid carriers, liquid carriers, surfactants, and other formulation auxiliaries. It is used by mixing it with other ingredients and preparing it into emulsions, wettable powders, suspensions, granules, powder solutions, etc.

These preparations contain the compound of the present invention as an active ingredient in a weight ratio of 0.1 to 99%, preferably 0.2 to 95%.

Examples of solid carriers include fine powders such as kaolin clay, attabulgite clay, bentonite, acid clay, pyrophyllite, talc, diatomaceous earth, calcite, corn cob powder, walnut shell powder, urea, ammonium sulfate, and synthetic hydrous silicon oxide. Liquid carriers include aromatic hydrocarbons such as xylene and methylnaphthalene, alcohols such as isopropanol, ethylene glycol, and cellosolve, ketones such as acetone, cyclohexanone, and isophorone, soybean oil, cottonseed oil, etc. Examples include vegetable oil, dimethyl sulfoxide, acetonitrile, water, etc.

Surfactants used for emulsification, dispersion, wet layer, etc. include alkyl sulfate salts, alkyl (aryl)
Anionic surfactants such as sulfonates, dialkyl sulfosuccinates, polyoxyethylene alkylaryl ether phosphate ester salts, naphthalene sulfonic acid formalin condensates, polyoxyethylene alkyl ethers, polyoxyethylene polyoxypropylene block copolymers, Examples include nonionic surfactants such as sorbitan fatty acid ester and polyoxyethylene sorbitan fatty acid ester.

As formulation auxiliaries, lignin sulfone @ salt, alkyne [1, polyvinyl alcohol, gum arabic, CN (
Examples include C (carboxymethyl cellulose) and PAL' (acidic phosphorylated isopropyl).

These preparations can be taken as they are, or diluted with water and sprinkled on a stalk, sprinkled or granulated and mixed into the soil, or applied to the soil. In addition, by mixing it with a pond plant disease control agent, it can be expected to increase the control effect. Furthermore, it can be used in combination with insecticides, acaricides, nematicides, herbicides, plant growth regulators, fertilizers, and soil conditioners.

When the compound of the present invention is used as an active ingredient of a plant disease control agent, the amount to be treated depends on weather conditions, formulation form, treatment time,
Although it varies depending on the method, location, target disease, target crop, etc., it is usually 0.2 to 200 g per are, preferably 1
~100g, and when applying emulsions, wettable powders, suspensions, solutions, etc. diluted with water, the application concentration is 0.005g.
~0.5% Preferably 0.01~0.2%, and granules, powders, etc. are applied as they are without any dilution.<Example> The present invention will be described below with production examples, reference examples, This will be explained in more detail with formulation examples and test examples.

First, a manufacturing example will be shown.

Production Example 1 (Compound (5)) 4-chloro-2-(6-methyl-2-pyridyl)-6-
o-1 Lylpyrimidine 1f was dissolved in toluene 10- and ethanol 5-, and to this was added a solution of sodium carbonate Q, 271 dissolved in water 5- and 5% palladium-carbon 0.11.
was added and melted with hydrogen gas at room temperature. After 80 minutes, remove the catalyst and water 207! and 80% of toluene were added for extraction. The organic layer was dried over anhydrous magnesium sulfate and concentrated under reduced pressure to give 2-(6-methyl-2-pyridyl")-6-
0-) Lylpyrimidine 0.829 was obtained rlllLp* 119.4°C PMR (CDC4M) δ ppm2 2.58 (8
, 8H, -CH5) 2.74 (8, 8H, -CHx) 9.00 (d, IH, pyrimidine-H', J=4.2
H2) Production Example 2 (Compound (14)) 4-chloro-6-(2,4-dimethylphenyl)-2-
Methanol 5- was added to (6-methyl-2-pyridyl)pyrimidine 1f, and 0.8 g of 28% sodium methoxide methanol solution was added thereto, followed by stirring at room temperature for 80 minutes.

To the reaction solution were added 80 mm of water and 100 fnt of chloroform to separate the layers, and the chloroform layer was washed with water and then dried over anhydrous magnesium sulfate. Concentration under reduced pressure yielded 0.9 g of 6-(2,4-dimethylphenyl)-4-methoxy-2-(6-mer-2-pyridyl)pyrimidine.

m, p* 97.7℃ PMR (CDC1,ri δppm 1.28 (S, 3H, CH,) 1.42 (3,8H, CHi) L, 62 (s, 80.CH,) 4.07 ( S,8H,QC)I,) 6.70(S,IH,pyrimidine-o5)7.52
(t, IH, pyridine-H', J=7.2Hz)8.
16(d,to,pyridine-Hs, J=7.2Hz
) Production Example 8 (Compound (19)) Sodium methoxide prepared from 4-chloro-6-o-fluorophenyl-2-(6-methylni-2-pyridyl)pyrimidine 1f, 0.1 g of sodium metal and 10-methanol The mixture was stirred at room temperature for 1 hour, and 80% of water and 100% of ethyl acetate were added thereto for extraction.

After drying the organic layer with anhydrous magnesium sulfate, m pressure ss
and 4-0-fluorophenyl-6-medoxy2-
(6-Methyl-2-pyridyl)pyrimidine 0.829 m1Ip 99.5℃ PMR (CDC1s) δppm 2.65 (8,8H, -CHl) 4.08 (8,8H, -QC tan- 3) 7.58 (t, IH, pyridine-H', J=7.2H
z) Production Example 4 (Compound (7)) 1.4 g of diethylmalonic acid and 60% oily sodium hydride Q, 851 were added to tetrahydrofuran 80-, and 4-chloro-2-(6-methyl-2-pyridyl )−
6-o-tolylpyrimidine 2f was added. After heating this under reflux for 80 minutes, add 0.81 sodium hydroxide to 10 ml of water.
Add a mixture of - and ethanol 10- and add 80
The mixture was heated to reflux for a minute.

Furthermore, 1.51 g of concentrated sulfuric acid was added to the reaction solution, and the mixture was heated under reflux for 30 minutes. After the reaction, the reaction solution was neutralized with sodium carbonate solution and concentrated under reduced pressure, and the residue was treated with silica gel column chromatography (hexane:acetone=2:1).
4-Methyl-2-(6-methyl-2-pyridyl)-6-
1.2 g of 0-tolylpyrimidine was obtained.

mepa 88.2°C PMR (CDCLM) δppm 2.47 (s, 8H, CH,) 2.69 (3, 6H, 2XCH,) 7.68 (t, IH, pyridine-H, J=7. 802)
Production Example 5 (Compound (84)) Diethylmalon! 1.5f and 0.41 of 60% oily sodium hydride were added to 80% of tetrahydrofuran, and 4-chloro-6-0-chlorophenyl-2-(6-methyl-2-pyridyl)pyrimidine 1f was added thereto. After addition,
After heating under reflux for 80 minutes, a solution prepared by dissolving 0.81 of sodium hydroxide in a mixture of 10 parts of water and 10 parts of methanol was added, and the mixture was further heated under reflux for 20 minutes. After cooling to room temperature, 1.5 l of concentrated sulfuric acid was carefully added, and the mixture was further heated under reflux for 80 minutes.

After cooling to room temperature, an aqueous IN sodium carbonate solution was added to neutralize the mixture, and the mixture was concentrated under reduced pressure.

The residue was treated with silica gel column chromatography (n-hexane:acetone=3:1) to obtain 1.42 g of 4-O-chlorophenyl-6-methyl-2-(6-methyl-2-pyridyl)pyrimidine.

m, p, 90.8°C PMR (CDCts) δppm: 170 (s
, 6H, -CHgx2) 8.31 (d, IH, pyridine-H3, J = 7.8Hz
) Production Example 6 (Compound (1)) 1.51 of 6-methyl-2-picolinamidine hydrochloride was dissolved in 50% of methanol, and 2.21% of a 28% sodium methoxide methanol solution and 8-dimethylamino-
Add 1.7 g of 1-phenyl-2-buten-1-one,
The mixture was heated under reflux for 2 hours.

After concentrating the reaction solution under reduced pressure, the residue was subjected to silica gel column chromatography (n-hexane: ethyl acetate = 2:
1), 2-(6-methyl-2-pyridyl)-
One ton (1.6 g) of 4-phenylpi was obtained.

nDt, 6829 PMR(CDCLg) δppm: 2.74
(8,8H, -CH 8.48 (d, IH, pyridine-Hl, J = 7.28
Z) 8.92 (d, IH, pyrimidine-H', J=5
．． 9H2) Next, Table 1 shows some of the compounds of the present invention that can be produced by such a production method.

Table 1 general formula Next, production examples of these raw material compounds will be shown as reference examples.

Reference Example 1 [Production of picolinamidine derivative [■] (hydrochloride)] 80 g of 2-cyano-6-methylpyridine was mixed with 80 g of methanol
14.7 jl of a 28% sodium methoxide methanol solution was added to the reaction solution, which was left at room temperature for 8 hours. Vinegar @4.61 was added to the reaction mixture, and the mixture was concentrated under reduced pressure. The resulting residue was diluted with ether 800- and water. After drying the ether layer with anhydrous magnesium sulfate, it was concentrated under reduced pressure to obtain methyl 6-methyl-2-picolinimidate.Next, to this was added 200 s of ethanol + 111 liters of ethanol, and further added 18.6 liters of ammonium chloride. A solution of 50% of water was added and heated under reflux for 80 minutes.The reaction solution was thoroughly concentrated under reduced pressure, and the resulting crystalline residue was washed with acetone to obtain 87N of 6-methyl-2-picolinamidine hydrochloride. Obtained.

maps 188.0'C Next, Table 2 shows some of the picolinamidine 3 conductors represented by the monochrome formula [■] and their salts produced by such a production method.

Table 2 Reference Example 2 [Hydroxypyrimidine derivative (manufacture of IVI)] 5 g of 6-methyl-2-picolinamidine hydrochloride was added to 50% methanol, and to this was added 28% sodium methoxide methanol solution 6.81 and 2.4%. 6.761 ml of ethyl dimethylbenzoylacetate was added, and the mixture was heated under reflux for 1 hour.

After cooling, acetic acid was added to the reaction solution to make it neutral, and the mixture was concentrated under reduced pressure.

The resulting residue was washed with water and then with hexane.
-(2,4-dimethylphenyl)-4-hydroxy-2
6.9 g of -(6-methyl-2-pyridyl)pyrimidine was obtained.

mop @ 145.6°C PMR (CDCLs) δppm 2.84 (s, 8H, CH,,) 2.48 (S, 8) 1. C1 (,) 2.58 (s, 8H, CHs) 6.49 (s, II (, Pi'J Z Shin-H5)
7.66 (t, IH, pyridine-〇', J-7.2
Hz)8.19 (d, U(, pyridine-H',
J = = 7.2 Hz.

Next, the general formula (XV) that can be produced by such a production method
Some of the hydroxypyrimidine gWK shown in Table 8 are shown in Table 8. Table 8 General Formula Reference Example 8 [Production of halopyrimidine derivative [m]] 6-
(2,4-dimethylphenyl)-4-hydroxy-2-
To 5 g of (6-methyl-2-pyridyl)pyridine, 100 toluene and 5 g of phosphorus oxychloride were added, and the mixture was heated under reflux for 1 hour. After cooling, neutralize with sodium carbonate aqueous solution,
The liquid was separated. The toluene layer was washed with water, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to give 4-chloro-6-(2,4
-dimethylphenyl)-2-(6-methyl-2-pyridyl)pyrimidine 4.81 was obtained.

m, p, 127.2°C PMR (CDC1s) δppm 2.85 (8,8H9CHs) 2.47 (8,8H,CHs) 2.69 (lB, af(,CHs) 7.66 (t, IH , pyridine-H', J=7.2
8Z) 8.26 (d, IH, pyridine-H”, J=
7.2) 1z) Next, Table 4 shows some halopyrimidine derivatives represented by the general formula [1] that can be produced by such a production method.

Table 4 General formulas Examples of formulations are shown below. The compounds of the present invention are indicated by compound numbers in Table 1, and parts are parts by weight.

Formulation Example 1 50 parts each of the compounds (1) to (50) of the present invention, 8 parts of calcium lignin sulfonate, 2 parts of sodium lauryl sulfate, and 45 parts of synthetic hydrous silicon oxide were thoroughly ground and mixed to form a hydrating agent for each of the compounds of the present invention. get.

Formulation Example 2 25 parts each of the compounds (1) to (50) of the present invention, 8 parts of polyoxyethylene sorbitan monooleate, 8 parts of CMC, and 69 parts of water were mixed and wet-pulverized until the particle size of the active ingredient became 5 microns or less. A suspension of each of the compounds of the present invention is obtained.

Formulation Example 8 2 parts each of the compounds (1) to (50) of the present invention, 88 parts of kaolin clay, and 10 parts of talc are thoroughly ground and mixed to obtain a powder of each of the compounds of the present invention.

Formulation Example 4 20 parts each of the compounds (1) to (50) of the present invention, 14 parts of polyoxyethylene styrylphenyl ether, 6 parts of calcium dodecylbenzenesulfonate, and 60 parts of xylene
The components are thoroughly mixed to obtain an emulsion of each compound of the present invention.

Formulation Example 5 2 parts each of the compounds (1) to (50) of the present invention, 1 part of synthetic hydrous silicon oxide, 2 parts of calcium lignin sulfonate, 80 parts of bentonite and 65 parts of kaolin clay are thoroughly ground and mixed, and water may be added. After kneading, the mixture is granulated and dried to obtain granules of each compound of the present invention.

Next, test examples will show that the compounds of the present invention are useful as fungicides. The compounds of the present invention are indicated by the compound numbers in Table 1, and the compounds used for comparison are indicated by the compound symbols in Table 5. , Visually observe the bacterial flora on the stems, etc., and the degree of 6 spots. If no bacterial flora or lesions are observed, rate it as ``5'', if around 10 parts are observed, rate it as ``4'', and if around 80 parts are observed, rate it as ``18''. If around 50 copies are approved, it will be ``2J'', and if around 70 copies are approved, it will be ``1J''.
'', and if there is no difference from the disease onset state when no compound is tested, it is evaluated as ``0'' and evaluated on a 6-level scale, with 5.4, 3.2, and 1.0, respectively.

Test Example 1 Rice blast control test (preventive effect) A plastic pot was filled with sandy loam, and rice (Kinki No. 33) was returned to Japan and grown in a greenhouse for 20 days. A test drug made into a suspension according to Formulation Example 2 was diluted with water to a specified concentration on young rice seedlings, and the solution was sprayed on the foliage to ensure sufficient adhesion to the leaf surface.After spraying, the plants were air-dried. , Spray and inoculate with a spore suspension of blast fungus.After inoculation, incubate at 28°C1 in darkness and humidity
After installing the equipment, we investigated its pesticidal efficacy. The results are shown in Table 6.

Table 6 Test Example 2 Rice blast control test (therapeutic effect) A plastic pot was filled with sandy loam, and rice (Kinki No. 88) was sown and grown in a greenhouse for 20 days. Rice seedlings were sprayed and inoculated with a spore suspension of the blast fungus. After vaccination, 28
℃, dark, and humid for 16 hours, the test drug made into a wettable powder according to Formulation Example 1 was diluted with water to a predetermined concentration.
It was sprayed on the foliage so that it adhered sufficiently to the leaf surface. After spraying, the plants were grown for 8 days at 28° C. in darkness and high humidity, and their control efficacy was investigated.

The results are shown in Table 7.

Test Example 8 Rice sheath blight control test (preventive effect) A plastic pot was filled with sandy loam, and rice (Kinki No. 88) was sown and grown in a greenhouse for 28 days. The test drug, made into an emulsion according to Formulation Example 4, was diluted with water to a specified concentration on young rice seedlings, and sprayed on the foliage so that it adhered sufficiently to the leaf surface.After spraying, the plants were air-dried and sheathed. A edible agar suspension of diseased bacteria was sprayed and covered. After being exposed to water, the plants were kept in the apparatus for 4 days at 28°C in darkness and high humidity, and then their pesticidal efficacy was investigated. The results are shown in Table 8.

Table 8 Test Example 4 Wheat Eye Spot Disease Control Test (Preventive Effect) Fill plastic pots with sandy loam and grow wheat (Norin No. 78)
To wheat seedlings, which were sown and grown in a greenhouse for 10 days, dilute the test drug prepared as a wettable powder with water according to Formulation Example 1 to a predetermined concentration, and thoroughly adhere it to the leaf surface. After spraying on the foliage as described above, the plants were air-dried and then sprayed and inoculated with a spore suspension of MBC-resistant eyelid fungus.

After inoculation, the seeds were grown for 4 days at 15° C. in the dark and humid, and then grown for another 4 days in light and humid to investigate the control efficacy.

The results are shown in Table 9.

Table 9 Test Examples ♂ Wheat leaf blight control test (therapeutic effect) Sand loam was packed into a plastic pot, and wheat (Norin No. 78) was sown and grown in a greenhouse for 8 days. Wheat seedlings were sprayed and inoculated with a spore suspension of the leaf blight fungus. After inoculation, 15°
C1 f for 8 days in darkness and high humidity! 1, then 4 under the lighting
After growing for one day, the test drug was made into an emulsion according to Formulation Example 4, diluted with water to a predetermined concentration, and sprayed on the foliage so that it would sufficiently adhere to the leaf surface. After spraying, 11 hours under 15°C lighting.
The control efficacy was investigated after growing for several days. The result is the first
Shown in table 0.

Table 10 Test Example 6 Apple scab control test (preventive effect) Apple seeds were sown in plastic pots filled with sandy loam soil and grown in a greenhouse for 20 days. Apple seedlings with 4th to 5th true leaves developed. Next, a test drug prepared as a suspension according to Formulation Example 2 was diluted with water to a predetermined concentration, and the solution was sprayed on the leaves so that it would adhere sufficiently to the leaves. After spraying 1. A spore suspension of apple scab fungus was sprayed and fenced.

After inoculation, the seeds were left at 15° C. under humid conditions for 4 days, and then grown under lighting for 15 days to investigate the pesticidal efficacy. The results are shown in Table 11. Table 11 Test Example 7 Cucumber anthracnose control test (preventive effect) Fill a plastic pot with sand J soil, sow cucumbers (Sumo Hanshiro), and grow them in a greenhouse for 14 days. did. After 1 spraying, the test drug, which had been made into a hydrating powder according to Formulation Example 1, was diluted with water to a predetermined concentration, and was sprayed on the foliage of cucumber seedlings with developed cotyledons so that it would sufficiently adhere to the leaf surface. A spore suspension of cucumber anthracnose was inoculated by spraying. After inoculation, the seeds were grown for 1 day at 28° C. under high humidity, and then grown for 4 days under lighting, and the pesticidal efficacy was investigated. The results are shown in Table 12.

Table 12 Test Example 8 Wheat powdery mildew control test (therapeutic effect)
Fill plastic pots with sandy loam and grow wheat (Agricultural and Forestry 78)
No.) was sown and grown in a greenhouse for 10 days. Young wheat seedlings were inoculated with powdery mildew. After inoculation and growing for 3 days at 28°C, the test drug was made into an emulsion according to Formulation Example 4, diluted with water to a predetermined concentration, and sprayed on the leaves so that it would adhere sufficiently to the leaf surface. After spraying, the seeds were grown for 7 days in a greenhouse at 28°C, and the control efficacy was investigated.

The results are shown in Table 18.

Table 18 Test Example 9 Cucumber gray mold control test @ (preventive effect) A plastic pot was filled with sandy loam, and cucumbers (Sumo Hanshiro) were sown and grown in a greenhouse for 14 days. A test drug prepared as a hydrating powder according to Formulation Example 1 was diluted with water to a predetermined concentration on cucumber seedlings surrounded by cotyledons, and sprayed on the foliage of the cucumber seedlings so as to sufficiently adhere to the leaf surface. After spraying, the plants were air-dried and inoculated with mycelia of cucumber botrytis fungus resistant to benzimidazole-thiononel-methyl fungicides. After vaccination,
The plants were grown for 8 days at 15°C in darkness and high humidity, and their pesticidal efficacy was investigated. The results are shown in Table 14.

Table 14 Test Example 10 Wheat rust control test (therapeutic effect)
Fill plastic pots with sandy loam and grow wheat (Agricultural and Forestry 78)
No.) was sown and grown in a greenhouse for 8 days. Young wheat seedlings were sprinkled with spores of Fusarium rust and inoculated. After vaccination, 28
After being left in the dark and humid at 1°C for 1 day, the test drug made into a suspension according to Formulation Example 2 was diluted with water to a specified concentration, and then sprayed on the foliage to ensure sufficient adhesion to the leaf surface. . After spraying,
The plants were grown under illumination at 28°C for 7 days and their control efficacy was investigated. The results are shown in Table 15. <Effects of the Invention> The compounds of the present invention have excellent effects against plant diseases caused by various plant pathogens, and therefore can be used in various applications as active ingredients of plant disease control agents. Uruuu

Claims (6)

[Claims] (1) General formula ▲ There are mathematical formulas, chemical formulas, tables, etc. , R_4 is the same or different and represents a lower alkyl group, lower alkoxy group, lower haloalkyl group or halogen atom, R_5 represents a hydrogen atom or a lower alkyl group,
R_6 represents a hydrogen atom, a lower alkyl group, a lower alkoxy group, a lower alkenyloxy group or a lower alkylthio group. ] A pyridylpyrimidine derivative or a salt thereof. (2) General formula ▲ Numerical formula, chemical formula, table, etc. ▼ (In the formula, R_1 represents a lower alkyl group, R_2 and R_3 are the same or different and represent a hydrogen atom or a methyl group, and n is an integer from 0 to 5. , R_4 is the same or different and represents a lower alkyl group, lower alkoxy group, lower haloalkyl group or halogen atom, R_5 represents a hydrogen atom or a lower alkyl group,
X represents a halogen atom. ] General formula ▲ There are mathematical formulas, chemical formulas, tables, etc. that are characterized by reducing the halopyrimidine derivative represented by [In the formula, R_1, R_2, R_3, R_4, R_5 and n represent the same meanings as above, R_6' represents a hydrogen atom. ] A method for producing a pyridylpyrimidine derivative. (3) General formula ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ [In the formula, R_1 represents a lower alkyl group, R_2 and R_3 are the same or different and represent a hydrogen atom or a methyl group, and n is an integer from 0 to 5. , R_4 is the same or different and represents a lower alkyl group, lower alkoxy group, lower haloalkyl group or halogen atom, R_5 represents a hydrogen atom or a lower alkyl group,
X represents a halogen atom. ] A halopyrimidine derivative represented by the general formula R_6''Y [wherein R_6'' represents a lower alkoxy group, a lower alkenyloxy group or a lower alkylthio group, and Y represents an alkali metal. ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ [In the formula, R_1, R_2, R_3, R_4, R_5, R
_6'' and n represent the same meanings as above.] A method for producing a pyridylpyrimidine derivative represented by the following. (4) General formula▲There are mathematical formulas, chemical formulas, tables, etc.▼ [In the formula, R_1 represents a lower alkyl group, R_2 and R_3 are the same or different and represent a hydrogen atom or a methyl group, and n is an integer from 0 to 5. R_4 are the same or different and represent a lower alkyl group, a lower alkoxy group, a lower haloalkyl group or a halogen atom, R_5 represents a hydrogen atom or a lower alkyl group, and X represents a halogen atom. ] A halopyrimidine derivative represented by the general formula R_7CH(COOR_8)_2 [wherein R_7 represents a hydrogen atom or a lower alkyl group, and R_8 represents a lower alkyl group. ] The general formula is characterized by reacting a malonic acid diester derivative represented by the following in the presence of a base, followed by hydrolysis and further decarboxylation ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ (In the formula, R_1, R_2, R_3, R_4, R_5 and n represent the same meanings as above, and R_6'' represents a lower alkyl group.] A method for producing a pyridylpyrimidine derivative represented by the following. (5) General formula▲ Numerical formula, chemical formula, table, etc.▼ [In the formula, R_1 represents a lower alkyl group, and R_2 and R_3 are the same or different and represent a hydrogen atom or a methyl group. ] Picolinamidine derivatives or their salts represented by the general formula ▲ Numerical formulas, chemical formulas, tables, etc. or represents a halogen atom, and R_9 represents a lower alkyl group. ] A general formula characterized by reacting with an enamine derivative shown in the presence of a base ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ [In the formula, R_1, R_2, R_3, R_4 and n represent the same meanings as above. , R'_5 and R'_6 represent hydrogen atoms. ] A method for producing a pyridylpyrimidine derivative. (6) General formula ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ [In the formula, R_1 represents a lower alkyl group, R_2 and R_3 are the same or different and represent a hydrogen atom or a methyl group, and n is an integer from 0 to 5. R_4 is the same or different and represents a lower alkyl group, lower alkoxy group, lower haloalkyl group or halogen atom, R_5 represents a hydrogen atom or a lower alkyl group, R_
6 represents a hydrogen atom, a lower alkyl group, a lower alkoxy group, a lower alkenyloxy group or a lower alkylthio group. ] A plant disease control agent characterized by containing a pyridylpyrimidine derivative or a salt thereof as an active ingredient.