KR850000785B1 - Process for preparing pyrimidine derivatives - Google Patents

Abstract

Pyrimidine derivatives(I), used as plant bactericides, are prepared from amidino hydrazine which has a chemical formula of Ar-CR1=N-NR2- C(NH)-NH2, through a reaction with β-diketone, which has a chemical formula of R3'-CO(CR4')-HCO-R5'. In the process, Ar = phenyl or naphthyl; R1 = lower alkyl, lower cycloalkyl, trifluoromethyl, lower alkoxycarbonyl, phenyl, or benzyl; R2 = H or lower alkyl; R3', R4', and R5' = H, lower alkyl, or lower alkenyl; or R4' = lower alkoxyl; or R3', R4', and R4', R5' = trimethylene or tetramethylene gp.

Description

Method for preparing pyrimidine derivative

It relates to a process for the preparation of the novel pyrimidine derivatives of the present invention. In more detail

Amidinohydrazone, represented by [the symbol in the diet means the same as the latter one]

[Wherein R ³ ′, R ⁴ ′, R ⁵ ′ are hydrogen atoms, lower alkyl or lower alkenyl groups, or R ⁴ ′ is a lower alkoxyl group, or R ³ ′, R ⁴ ′, R ⁴ ′ and R ⁵ 'is combined with each other to represent trimethylene or tetramethylene group]

[In the formula, Ar is a phenyl or naphthyl group, and may be substituted with lower alkyl, lower alkoxyl, lower alkylthio, lower alkylsulfinyl, lower alkylsulfonyl, halogen, nitro, triluolmethyl, dilower alkylamino group, R ¹ is lower alkyl, lower cycloalkyl, triruolmethyl, lower alkoxycarbonyl, phenyl or benzyl group, where the phenyl group may be substituted with halogen, and R ² represents a hydrogen atom or a lower alkyl group. R ³ ′, R ⁴ ′ and R ⁵ ′ refer to the same method as described above for the preparation of pyrimidine derivative (VI). With the urgent need for food production, a large number of organometallic crab fungicides, mainly organic mercury, have been produced in large quantities and have been frequently used for many years because of their excellent effect. As a result, in addition to its utility, various unfavorable negative effects on the human beings and the environment have been combined, resulting in social problems.

In place of these organometallic compounds, antibiotics, organophosphorus compounds, and organochlorine compounds have emerged and have reached the present. In general, however, in the cultivation of crops, despite the fact that a plurality of diseases concurrently coexist, all of the above nonmetallic fungicides that currently dominate the mainstream have high selectivity and narrow sterilization spectrum. Many are only valid for single diseases. Therefore, of course, in view of simultaneous control to save time and effort, it relies on the use of a mixed agent by mixing a plurality of active principal components, which can be considered to be preferable in view of the environment, resource efficiency, and cost. none.

In addition, according to these alternative medicines, a disease that has not yet been sufficiently overcome remains. For example, in the cultivation of water, the main diseases that cause this in our country include blast disease, paperback disease, cocci, neutrophil disease, and white leaf disease. Currently, there are drugs that control this to a certain extent for blast disease and paperback disease, but others remain unresolved, and in particular, bacteriococcal disease and horsetail leaf disease are beginning to be remarkably noticeable. At the same time, there is an urgent need for the emergence of a drug capable of exerting an excellent morbidity effect against minor mycobacterium nucleus and horseshoe lobe.

Also, in the fields, orchards, horticultural cultivation, etc., there are some differences in the types of the pests, but basically the situation is the same.

In order to meet these demands, the present inventors devote themselves to intensive whole-hearted research and, as a result, a group of compounds represented by the formula (VI) having a hydrazone bond in the molecule with a slightly different category of the compound than a conventional fungicide. It has been found that the novel pyrimidine derivatives have suitable properties to solve these problems at once, thus completing the present invention based on this new finding.

Ar in formulas (IV) and (VI) represents a phenyl group or a naphthal group. In the case of a naphthal group, the bonding position may be α-up or β-up. None of these bidirectional ring groups may be unsubstituted, and may have 1 to 5 substitutions in the phenyl group, and may have 1 to 7 substituents in the naphthal group.

As the substituent, for example, lower (preferably C _1-4 ) alkyl groups such as methyl, ethyl, n-propyl, i-propyl, n-butyl, i-butyl, sec-butyl, t-butyl groups, etc. Lower (preferably C _1-4 ) alkoxy groups such as ethoxy, n-propoxy, i-propoxy, n-butoxy, i-butoxy, sec-butoxy, methylthio, ethylthio, n Lower (preferably C _1-4 ) alcoholyl groups such as -propylthio, i-propylthio, n-butylthio, i-butylthio, sec-butylthio groups: methylthio, ethylthio, n-propylthio, lower (preferably C _1-4 ) alkylthio groups such as i-propylthio, n-butylthio, i-butylthio, sec-butylthio groups: methylspinyl, ethylsulfinyl, n-propylspinyl, lower (preferably C _1-4 ) alkylsulfinyl groups such as i-propylsulfinyl, n-butylsulfinyl, i-butylsulfinyl and sec-butylsulfinyl groups: methylsulfonyl, ethylsulfonyl, n-propyl Sulfonyl, i-propylsulfonyl, n-butylsulfonyl, i-butylsulfonyl, sec-butylsulphyl Lower (preferably C _1-4) alkyl group such as seulpo group: fluorine, chlorine, bromine, iodine, a halogen atom: a nitro group, a trifluoro methyl group, dimethylamino, diethylamino, methyl-ethylamino, methyl -i- Dibasic (preferably C _1-4 ) alkylamino groups such as propylamino, di-n-propylamino, di-i-propylamino, di-n-butylamino and di-i-butylamino groups, and these substituents When two or more substituents are substituted, two or more hetero substituents may be substituted and mixed at the same time.

Among these substituents, lower alkyl groups such as methyl and ethyl and halogen atoms such as chlorine and bromine are particularly preferable.

Moreover, as a substitution position, although any substituent may be substituted in any position within five and some in a phenyl group, it is especially preferable that a substitution value exists in at least one 0-position (2-position), and in this case As the substituent, lower alkyl groups such as methyl and ethyl groups and halogen atoms such as chlorine and bromine are particularly preferable. As a substituent from 2nd to 4th, it may be substituted by what kind of remainder in any said substituent, and does not need to be carried out. However, the number of substituents is preferably one to four, and if any of the above substituents enter both 0-positions (2,6-positions) at the same time, the hydrazone bonds are generally less likely to be formed. In view of this, the number of substituents is particularly preferably 4 or less. The same can be said for the α- and β-naphthyl groups. For example, in the case of the α-naphthal group, a substituent is preferably present in the 1st or 3rd position in the case of the β-naphthyl group, and a lower alkyl group or a halogen atom as described in the phenyl group is used as the preferred substituent. The other substituent may be substituted at any remaining position, but the substituent is preferably substituted at the 4th and 6th positions. However, the number of substituents is particularly preferably one to two.

R ¹ in formulas (IV) and (VI) is lower (preferably, for example, methyl, ethyl, n-propyl, i-propyl, n-butyl, i-butyl, sec-butyl, t-butyl groups). Is a C _1-4 ) alkyl group: lower (preferably C _1-4 ) cycloalkyl group, such as cyclopropyl, cyclopentyl group, trifluoromethyl group: lower (preferably C, such as methoxycarbonyl, ethoxycarbonyl group) _1-4 ) Alkoxycarbonyl group: It represents a phenyl group and a benzyl group, The phenyl group may be substituted by the halogen as demonstrated above, For example, it is called a chlorophenyl group. Among these substituents, lower alkyl groups such as methyl and ethyl groups are particularly preferable.

R ² in formulas (IV) and (VI) is a hydrogen atom and lower (preferably C, for example methyl, ethyl, n-propyl, i-propyl, n-butyl, i-butyl, sec-butyl) _1-4 ) alkyl group. Among these substituents, hydrogen atoms are particularly preferable.

R ³ ′, R ⁴ ′, R ⁵ ′ in formulas (V) and (VI) are hydrogen atoms, for example methyl, ethyl, n-propyl, i-propyl, n-butyl, i-butyl, sec- Lower (preferably C _1-4 ) alkyl groups such as butyl and t-butyl groups, lower (preferably C _1-4 ) alkenyl groups such as vinyl, allyl, clotyl and metalallyl, methoxy, ethoxy, and lower alkoxyl groups such as n-propoxy, i-propoxy, n-butoxy, i-butoxy and sec-butoxy.

At least one of R ³ ′, R ⁴ ′, and R ⁵ ′ is preferably a lower (preferably C _1-4 ) alkyl group such as methyl or ethyl group.

Among these substituents, R ³ ′ is particularly preferably a lower alkyl group of methyl or ethyl group, R ⁴ ′ is particularly preferably a lower alkyl group such as a hydrogen atom, methyl or ethyl group, and R ⁵ ′ is methyl, It is especially preferable when it is lower alkyl groups, such as an ethyl group. When R <^3>', R <^4>' and R <^5>'is a lower alkyl group, these may mutually be equal and may differ, respectively.

Moreover, R <^3>'and R <^4>', R <^4>'and R <^5>' combine, and represent a trimethylene or tetramethylene group. That is, R ³ ′ and R ⁴ ′, R ⁴ ′ or R ⁴ ′ and R ⁵ ′ combine with each other to form a crosslinking bond, and together with two carbons of the pyrimidine ring, a 5-6 membered saturated or unsaturated member ) Condensed carbocyclic ring is formed. Therefore, the combination of R ³ ′, R ⁴ ′, R ⁴ ′, and R ⁵ ′ to form a tetramethylene group means forming a tetrahydrobenzopyrimidine, that is, a tetrahydrokinazolin ring.

The pyrimidine derivative (VI) can also be produced by reacting amidinohydrazone (IV) with β-diketone (V).

In the reaction between the amidinohydrazone represented by the formula (IV) and the β-diketone represented by the formula (V), the former may be liberated and may be used in the reaction in the form of an organic or inorganic acid salt. do. That is, you may provide for reaction in the form of salt with inorganic acids, such as hydrochloric acid, a sulfuric acid, and phosphoric acid, for example, acid, acetic acid, a propionic acid. The present reaction is carried out by mixing the same molar amounts of both, but in some cases, a little more may be added. For example, when (beta) -diketone (V) is a liquid form, you may use it in excess and also serve as a solvent. Moreover, when both are solid, you may melt and liquefy by heating.

However, in order to advance this reaction smoothly, it is generally good to carry out in an organic solvent, and in this case, any organic solvent may be used as long as it does not interfere with the reaction. For example, alcohols, ethers, aromatic hydrocarbons and the like are particularly preferable. Namely, for example, alcohols such as methanol, ethanol, propanol, butanol, methyl cellosolve, ethylene cellosolve, ethers such as diethyl ether, terahydrofuran, dioxane, dimethoxyethane, Aromatic hydrocarbons, such as benzene, toluene, and xylene, are especially preferable. These solvents may be used alone or in various mixing ratios as two or more kinds of mixed solvents.

Since the present reaction proceeds smoothly in general, heating is not necessarily required when accompanied with sufficient stirring and mixing. However, when the reaction is desired to be completed within a short time, heating is sometimes required. Although reaction temperature is normally preferable from 40 degreeC to 200 degreeC, it is preferable to maintain at 60 degreeC to 150 degreeC among these.

In general, the reaction is carried out under normal pressure, but in some cases, the reaction can be carried out under pressure using a sealed container. The reaction time depends on the type of raw material, the solvent, and the reaction temperature. Usually, the reaction time is completed within several tens to several hours, but in some cases, it may take several tens of hours.

This reaction is essentially a pyrimidine ring formation reaction by dehydration condensation reaction between aminedine and β-diketone, and under normal conditions, it is not necessary to pay particular attention to dehumidification and dehydration of the reaction system. However, especially when it is desired to accelerate the reaction and improve the yield, it is of course used dry and dehydrated as well as the raw material and the solvent. Pay attention to moisture dampening during the reaction, and take out of the system because the water produced in the reaction system is boiled with the solvent. Or a dehydrating agent such as a molecular sieve, for example, may produce good results.

Although the presence of a solvent is not essential for this reaction, the reaction may be remarkably accelerated by adding a trace amount of an acid or a base. For example, an acid may be an organic acid or an inorganic acid, and as the organic acid, for example, acid, acetic acid, propionic acid, or the like may be used, and these may also serve as a solvent. As the inorganic acid, for example, Lewis acids such as hydrochloric acid, sulfuric acid, phosphoric acid or polyphosphoric acid (PPA), polyphosphoric ester (PPE), titanium tetrachloride, boron trifluoride, and the like can be used. PPA) and the like can also serve as a solvent and a dehydrating agent.

As a base, inorganic bases, such as potassium hydroxide, organic bases, such as a pyridine and a triethylamine, can be used, for example, and the latter can also serve as a solvent. As the solid catalyst, an acidic or basic ion exchange resin can also be used. In addition, neither the end point of reaction of (IV) and (V) can be confirmed easily by thin layer chromatography, for example. That is, the reaction may be completed on the thin layer of silica gel at a point where it can be detected by ultraviolet irradiation (2536 kPa) or Dragendorf reagent spray as a spot different from the raw material compound.

The pyrimidine derivative (VI) thus prepared is a novel compound, which is not described in any of the literatures, and is usually a colorless to slightly colored crystalline solid or viscous oily substance at room temperature. It is a state or glass semi-solid. These are generally insoluble in water, and in addition to many organic solvents such as alcohols, ethers and aromatic hydrocarbons used in the reaction, for example, aliphatic halogenated hydrocarbons such as chloroform and methylene chloride, ethyl acetate And esters such as butyl acetate, acid amides such as dimethylformamide and acetonitrile, and nitriles. Therefore, in the case of a crystalline solid, the reaction product is cooled as it is after completion of the reaction, or in the case of a reaction solvent which can be mixed with water, water is added or the preparation obtained by distilling the reaction solvent is recrystallized from a suitable solvent. In addition, in the case of an oily substance, the preparation obtained by similar process is refine | purified using a column chromatography. When an acidic or basic catalyst is added or when an acidic or basic solvent is used, it is necessary to perform neutralization treatment depending on the liquidity. However, in the case of an acidic catalyst or an acidic solvent, the above treatment is carried out as it is and the reactive body is removed. It can also be isolated as an acid salt.

If desired, after isolation as a free base, it may be newly introduced into salts of various organic and inorganic acids as described above, and the obtained acid salt is a structure of a reactive body contained in the target product (VI) together with the free base. Can be confirmed by elemental analysis, infrared absorption spectrum, ultraviolet absorption spectrum, mass spectrometry and nuclear magnetic resonance spectrum.

The pyrimidine derivative (VI), which is a reactive substance of the reaction, is a kind of hydrazone compound, and has a C = N double bond in its molecule, and therefore, of course, there is an isomer of Z-type and E-type with respect to this bond. . For example, formation of both isomers is often confirmed as two adjacent spots on the thin layer chromatogram for the reaction product. However, the mixing ratio varies depending on the type of raw material and the solvent, the acidity of the reaction conditions (temperature and time) liquid, the type and presence of the catalyst, and the like. In some cases, only a single isomer may be given. In the case of a mixture, it can isolate | separate, for example by performing careful purification by column chromatography. For example, in the case of chromoform eluting, in many cases, Z forms first, and in the case of ethyl acetate, E forms first. In addition, each identification can be discriminated by chemical shift of the proton signal of NH in a molecule in a nuclear magnetic resonance spectrum. That is, the E side is usually located in the magnetic field lower than the Z body. Therefore, in the case of the mixture, the mixing ratio can be determined by the integral intensity ratio of each peak. However, these isomers are thixotropic and can be isomerized by heating or light irradiation. Therefore, when it is difficult to separate them, there is no meaning even if they are separated by separation, and even if they are used in the present invention in an unseparated state, there is no problem.

In the raw materials commonly used in the above reaction, the amidinohydra represented by the formula (IV) is an unsubstituted body (Ar = C ₆ H ₅ : R ¹ = CH ₃ : R ² = H) described in the literature. It is a well-known compound, and others can be synthesize | combined according to the well-known method described in the literature, or the method according to it. For example, aromatic ketones (II)

ArCOR '(Ⅱ)

[Symbol in the food means the same as above]

The aminoguanidine bicarbonate or acetate can be easily synthesized by reacting in the presence of an organic or inorganic base. Thus, since the obtained amidinohydrazone has basicity, it can also be isolate | separated as an organic-inorganic acid salt as a free base. Edenate may be neutralized anew in the reaction of the present invention, may be used as a free base for the reaction, or may be used for the reaction even as an acid salt. [Analen der chemie, Vol. 307, 293. Cotton (1899)]. In addition, with respect to the C = N bond of the amidinohydrazone, the presence of Z- and E-type protonic isomers is expected, but in the present invention, the present invention is not particularly specified without particular identification of mixtures or isomers. To provide in the reaction.

Table I below shows some of the physical constants of the novel compounds in amidinohydrazone (IV).

Table-I

Many types of aromatic ketones represented by formula (II) are listed in domestic and foreign reagent makers, and can be easily obtained. Others can be easily synthesized by a common aromatic ketone synthesis method, for example, a general method such as Friedel-Crafts type acylation reaction using a carboxylic acid or a derivative thereof to an aromatic hydrocarbon or a method similar thereto. G.A. Olah (Friedel-Krafts and Related Reactions), (Frledel Crafts and Related Reactions), Volume Ⅲ (Part 1), p. 1 (1964): Japanese Chemical Society, Experimental Chemistry Lecture, 19, 316 Cotton (1957): East, New Experimental Chemistry, Vol. 14 (II), p. 751 (1977)], for example, Journal of Organic Chemistry, Vol. 11, p. 444 ( 1946), Vol. 12, p. 617 (1947), Vol. 31, p. 1655 (1966): Journal of the Chemical Society, 1952, p. 1123, p. 4162, p. 1955, p. 3417, p. 1968C, p. 2502, p. 1971C, 3347: Canadian Journal of Chemistry, vol. 41, p. 2103 (1963) or the like, or synthesized by the same method. have.

Table-II below shows some of the physical constants or properties of the novel compounds in aromatic ketones (II).

TABLE-II

ArCOR '

Many types of β-diketones represented by the formula (V) are listed in lists of domestic and foreign reagent makers, and can be easily obtained. Others can be easily synthesized by a general β-diketone synthesis method, for example, a general method such as alkyl acetylation reaction of acetylacetone or the like. [H · O · House, Modern Cinderic Riaxon's ( Modern Synthetic Reactions 2nd Edition, p. 492, p. 734 (1972): Japanese Chemistry Part, Experimental Chemistry Lecture, Vol. 19, p. 316 (1957): Pyeong, New Experimental Chemistry Lecture, Volume 14 (II), 751 (1977)], for example, Organic Syntheses, Volume III, p. 291 (1955), East V, p. 785, p. 848 (1973), Japanese Chemical Magazine, vol. 88 , Page 1068 (1967): by the methods described in the Journal of the American Chemical Society, Volume 68, page 453 (1946), or the like.

The pyrimidine derivative (VI) prepared in the method of the present invention has a strong antibacterial activity against a wide range of phytopathogens, especially fungi, and, for example, when applied as a fungicide for answers, not only kills the germicidal pathogens. At the same time, it has a strong morbidity against morbidity bacteria, micrococcus pneumoniae bacteria, and spp. In addition, as well as pathogens of rice, it has a strong antimicrobial activity against pathogens causing diseases in many crops, such as vegetables and vegetables. For example, it has antimicrobial activity against cucumber gray blight, Kangnam cocci, and strawberry gray fungus.

In addition, the compound (VI) produced by the present invention not only has a therapeutic ability to inhibit the progress of the diseased plants, but also treats plants that are not yet diseased, thereby preventing the infection of pathogens. It also has the preventive ability to prevent and protect plants. In addition, as a treatment method, not only the conventional spraying treatment on plant stems and leaves, but also the treatment on the volume part of plants, due to its strong penetrating properties, it is absorbed in the plants and shifted in the body to be widely distributed, thereby increasing the concentration required for plant protection. Have the ability to maintain.

Although none of the compound group (VI) has strong bactericidal activity, it has low skin irritation and oral toxicity to warm-blooded animals, and has little effect on the environment such as fish toxicity. In addition, the various crops show no damage at all, or are extremely slight, and do not affect the growth and yield after death. It is speculated that these compound groups (VI) have strong affinity for plants and at the same time have moderate chemical stability. Therefore, it is estimated that the hydrolysis of the hydrazone bond according to the present invention gradually deactivates. That is, the pyrimidine derivative (VI) in the molecule can be said to be a new compound group having extremely excellent qualities as a multipurpose agricultural fungicide.

The agricultural fungicide of the present invention may contain not only one kind of the compound of the general formula (VI) but also two or more kinds thereof. The free base or organic-inorganic acid salt (hereinafter sometimes referred to as an active ingredient) of the compound of the present invention may be used alone, or various natural products, additives, solvents, or the like may be added again as necessary.

In more detail, the active ingredient may be used as it is as a solid agent and used for the purpose of sustaining the effect for a long time, and dissolved in or dispersed in a suitable liquid sample (for example, a solvent) or a suitable solid sample. (For example, a diluent, a weight agent) or adsorbed thereto, and furthermore, an emulsifier, a dispersant, a suspending agent, an electrodeposition agent, a penetrant, a humectant, a store agent, a stabilizer and the like are added thereto, and an oil agent, You may use it as infrared formulations, such as an emulsion, a hydrating agent, a water-soluble agent, a suspending agent, a powder, a granule, a granule, a tablet, and a spraying agent.

Next, as such a solvent, For example, water, alcohols (for example, methyl, alcohol, ethyl alcohol, ethylene glycol, propylene glycol, etc.), ketones (for example, acetone, methyl ethyl ketone etc.) , Ethers (e.g. dioxane, tetrahydrofuran, semorosorb, etc.), aliphatic hydrocarbons (e.g. gasoline, kerosene, kerosene, fuel oil, mechanical oil, etc.), aromatic hydrocarbons (e.g. , Benzene, toluene, xylene, solvent, naphtha, methylnaphthalene, etc., other organic bases (e.g., pyridine, aldehyde collidine, etc.), halogenated hydrocarbons (e.g., chlorophorium, carbon tetrachloride, etc.) Acid amides (e.g., dimethylformamide, etc.), esters (e.g., ethyl acetate, butyl acetate, aliphatic glyceline esters, etc.), and nitriles (e.g., acetonitrile), Sulfur-containing compounds (for example, dimeth It may be used seulpok seed, such as methylene la ted seulpon etc.).

In addition, as a solid solution such as a diluent or a weighting agent, for example, plant component powder (for example, rice bran, soybean powder, rice flour, wheat flour, wood powder, etc.), mineral powder (for example, kaolin, bentite, phosphoric acid) Clays such as calcium and acid clay, talc powders such as talc powder, feldspar powder, silicas such as diatomaceous earth and mica powders), and alumina, sulfur powder, activated carbon, and the like are also used. Can be used.

Moreover, as an emulsifier, an electrodeposition agent, a penetrant, a dispersing agent, a soap, a sulfuric acid ester of a higher alcohol, an alkylsulfonic acid, an alkylarylsulfonic acid, a quaternary ammonium salt, an oxyalkylamine, a fatty acid ester, a polyalkylene oxide type, anhydrous Surfactants, such as a sorbitol system, are widely used, and generally it is good to contain about 0.2 to 10% in reconstitution. Moreover, casein, gelatin, starch, alginic acid, agar, CMC, polyvinyl alcohol, pine root oil, steel oil, bentonite, cresol soap, etc. may be used as needed. If necessary, other types of fungicides (for example, organic chlorine fungicides, organophosphate fungicides, benzimidazole fungicides, copper fungicides, organic sulfur fungicides, phenolic fungicides, antibiotics, etc.) and insecticides (natural insecticides) , Carbamate-based fungicides, organophosphorus insecticides, etc.), other, acaricides, nematicides, herbicides, plant growth regulators, stabilizers, cooperative agents, attractants, repellents, fragrances, plant nutrients, fertilizers, various amino acids, low molecular weight Phosphates of the polymer and the like may be mixed as appropriate, and metal salts may be added for the purpose of enhancing the effect.

As for the content rate of the active ingredient in the control agent composition in this invention, about 10 to 90% of emulsions and emulsifiers, about 0.1 to 10% of emulsions, powders, etc. 5 to 50% is suitable. In addition, emulsion emulsions, etc., should be sprayed with red dilution (for example, 50 to 5000 times) with water or the like again when used.

The amount of the active ingredient or the combination of the mixture with other kinds of drugs, and the mixing ratio thereof may be determined depending on the conditions such as the growth stage, the growth situation, the type of disease, the condition of the disease, the time of use or the method of use of the target plant. Although different, generally, what is necessary is just to adjust so that it may become about 10-300g per 10 argon. As the use concentration, the effective ingredient may be in the range of 10 to 1000 ppm, and as a use method, if the amount of spraying, spraying or seeding is added to the crop, and the safety and effectiveness are effectively used, However, even if the concentration or method of use is not limited to the present invention.

The plant disease control agent of the present invention has extremely low side effects, and can have a simple and inexpensive effect with excellent effect, and thus is extremely useful in the art.

Next, Examples and Examples will be described.

Example 1

1- (2,4-dimethylphenyl) ethylidene-amino-guanidyl Dean (Ⅵ: Ar = 2,4- (CH 3) 2 · C 6 H 3: R 1 = CH 3: R 2 = H) 2.00g ( 10 mM) and 2.90 g (23 mM) of 3-ethyl acetylacetone (V: R ³ = R ⁵ = CH ₃ : R ⁴ = C ₂ H ₅ ) are stirred at about 130 to 140 ° C. on an oil bath for about 3 hours. After the reaction, excess β-diketone was distilled off under reduced pressure, and the remaining viscous oil was subjected to column chromatography (silica gel / ethyl acetate + n-hexane) to give 5-ethyl-4,6-dimethyl-2- [1- When both isomers of (2,4-dimethylphenyl) ethylidenehydrazino] pyrimidine are eluted with a mixed solvent of ethyl acetate and n-hexane, the E form elutes while the Z forms overlap with some Z forms first, followed by thin layer chromatography. When the eluents containing the same isomers are collected and concentrated while checking by chromatography, the Z forms as crystalline solids and the E forms as viscous oils.

Z body

Yield 1.50 g (51%) Melting Point 127-129 ° C

Application Analysis (C ₁₈ H ₂₄ N ₄ )

Calculated Value: C, 72.93, H, 8.16, N, 18.90%

Found: C, 72.35, H, 8.09, N, 18.72%

NMR (CDCl ₃ , ppm) NH: 7.72 (1H, s)

E body (Z body is mixed)

Yield 0.70 g (24%) viscous oil

Elemental Analysis Value (C ₁₈ H ₂₄ N ₄ )

Calculated Value: C, 72.93, H, 8.16, N, 18.90%

Found: C, 72.78, H, 7.99, N, 18.48%

NMR (CDCl ₃ , ppm) NH: 7.75 & 8.08 (Z ratio: E ratio 1: 2)

Example 2

In the same manner as in Example 1, the following compound No. 1 to 126 were prepared, and their chemical structures (Ar, R ¹ , R ² , R ³ , R ⁴ , R ⁵ ) containing method and physical constants (properties) were also included in the following table including the compound of Example 1. In addition, in table (ratio of Z: E), E shows only E body, Z shows only Z body, and Z + E shows that the mixing ratio unidentified thing was obtained as a good mixture. Moreover, compound No. 115 is the same as Ar and R ¹ and does not have a structural isomer, it can be separated only by concentration after the reaction.

Example 3

Compound (3) 50%, sodium lignin sulfonate 2%, white carbon 3%, polyoxyethylene alkylaryl ether 5%, clay 40% mixed with a water hydrate, diluted from 1000 times to 3000 times with water 10 l per each Spray 20 liters from

Example 4

500 g is sprayed directly from 300 g per 1 ar of a bonsai obtained by mixing 3% of compound (9), 0.1% of aluminum stearate and 96.9% of clay.

Example 5

Granules obtained by mixing and assembling 5% of compound (18), 5% of gum arabic, 30% of bentonite, and 60% of talc. Directly use 500 g from 300 g per arear.

Example 6

An emulsion containing 20% of compound (20), 75% of xylene, and 5% of polyoxyethylene alkylaryl ether. Dilute 40 to 2000 times with water and directly spray 10 liters per each bottle.

Example 7

A hydrating agent obtained by mixing and grinding 30% of compound (38), 5% of lignin sulfonate, 5% of polyoxyethylene alkyl ether, and 60% of clay. Spray it 40 to 2000 times with water and spray it directly 10 liters per each are.

Example 8

Granules granulated by adding water to a mixture of 10% of compound (41), 5% of sodium lignin sulfonate and 85% of bentonite. Directly use 500 g from 300 g per arear.

[Test Example 1]

By the agar dilution method by agar medium, the anti-arm force test of the representative compound (represented by the compound No. described in Example 3) and the control compound was carried out as follows, and the results were summarized in the table below.

(1) Assay medium Glucosebuion agar medium or agar medium per potato stand (used only in test group No. 5)

(2) Pharmaceutical Preparation Dissolve 40 ml of the test compound in a mixture of 0.5 ml of N, N-dimethylformamide and 9.5 ml of acetone. Dilute to 1000 µg / ml with sterilized water (concentration in medium is 1/10).

(3) test group

1) Pyricularia oryzae IFO 5279, rice fever

2) Helminthosposrium sigmoideum IFO 4867, rice micrococci

3) Helminthosporium oryzae Rice Homolococci

4) Pellicularia sasakii IFO 6330, rice paddy bacteria

5) Phytohthora capsici IFO 8386, cucumber gray blight

6) Botryis cinerer strawberry gray fungus

7) Sclerotinis sclerotiorum IFO 4876, Mycobacterium tuberculosis

(4) control compound

Compound of Example 2 of Japanese Patent Laid-Open No. 53-12876:

(5) Inoculation bacteria No. 4,5,7 is inoculated with agar piece containing mycelium

(6) Cultured bacteria No. 1,2,6 is bacteria No. 3, 4, 7 is 28 ℃ 3 days, bacteria No. 5 is 28 ℃ 5-6 days

(7) Judgment minimum growth inhibition concentration (MIC µg / ml) was obtained.

[Test Example 2]

The effectiveness of rice fever control in the case of foliage application was investigated by the following test method, and the results are summarized in the table below. In addition, the test compound was represented by the compound No. of Example 3.

I. Test Method

1. Pathogens: pyricularis oryzae

2. Testimonials: Rice, varieties Asahi No. 4, 9cm pots, 10 plants, about 32 days

3. Inoculation: Natural Infections from Blight Damage Leaves

4. Pharmaceutical treatment: Combination of the disclosed compounds in accordance with Example 7 and diluting to a predetermined concentration and spraying, spreading electrodeposition agent (dyne, brand name, Dadak pharmaceutical agent (addition, 2 days after the start of inoculation)

5. Remedy: 1 port 2 ports

6. Investigation: 7 days after inoculation, published by the Japan Plant Protection Association (Digestion 49 (1974), 2.15), "Standards for the Area of Leaf Blight", "Standards for Investigating Pests" (Pages 4-7). .

II. Test result

[Test Example 3]

The effectiveness of rice fever control in the case of sleep was investigated by the following test method, and the results were summarized in the following table. In addition, the test compound was represented by the compound No. of Example 3.

I. Test Methods

1. Pathogen: According to Test Example 2

2. Testimonial plants: According to Test Example 2. However, grow with 1 / 10,000 Wagner pot

3. Inoculation: According to Test Example 2

4. Pharmaceutical treatment: The disclosed compounds were combined in accordance with Example 7, and treated directly or in a diluted solution to a predetermined concentration in water. Inoculation started 2 days after treatment

5. Remedy: According to Test Example 2

6. Investigation: According to Test Example 2.

II. Test result

[Test Example 4]

The effects of rice leaf lobe disease control on leaf spraying were examined by the following test method, and the results were summarized in the following table. In addition, the test compound was represented by the compound No. of Example 3.

I. Test Methods

Pathogens: Helminthosporium oryzae

2. Testimonial plants: According to Test Example 2.

3. Inoculation: A suspension of spores (spore concentration of 1 to 2 × 10 ⁵ / ml) formed by incubating at 28 ° C for 10 days on a single medium per potato was sprayed and inoculated at 28 ° C and 100% RH for 2 days after inoculation. Relative humidity) and then left in the greenhouse

4. Pharmaceutical treatment: According to Test Example 2, but inoculated after spraying air drying

5. Remedy: According to Test Example 2

6. Investigation: Japanese plant control group fire extinguishing 49 (1974) 7 days after inoculation. 2.15) Investigation by Method 2 (p. 27) of "Criteria according to the degree of incidence of barley micro, small and black rice disease"

II. Test result

[Test Example 5]

The effects of the control of rice follicles on sleep when applied to sleep were examined by the following test, and the results are summarized in the table below. In addition, the test compound was represented by the compound No. of Example 3.

I. Test Methods

1. Pathogen: According to Test Example 4.

2. Testimonial plants: According to Test Example 2.

3. Inoculation: According to Test Example 4.

4. Pharmaceutical treatment: According to Test Example 4.

5. Remedy: According to Test Example 2.

6. Investigation: According to Test Example 4.

II. Test result

[Test Example 6]

The effects of rice paddy disease control were investigated by the following test methods, and the results were summarized in the table below. In addition, the test compound is the compound No. Marked as.

I. Test Methods

1. Pathogens: Pelicuraria Sasakii (Resortonia Sorani Sasakii)

[Pellicularia sasakii (Rhizoctonia solani sasakii type)]

2. Testimonials: Rice, varieties of Longanghu, three 9cm pots, 80 ~ 90 days seedlings.

3. Inoculation: The periphery of the bacterial flora incubated for 28 days at 28 ° C on potato agar plates was punched out with a 10 mm diameter cork perforator. Maintained under% RH.

4. Pharmaceutical treatment: According to Test Example 2. However, inoculate after spraying air dry.

5. Rescue: 1 port 2 ports.

6. Investigation: 10 days after inoculation, the height from the base of the dorsum to the top of the lesion was calculated.

II. Test result

Claims (1)

[In the formula, Ar is a phenyl or naphthyl group, which may be substituted with a lower alkyl, lower alkoxyl, lower alkylthio, lower alkylspinyl, lower alkylsulfonyl, halogen, nitro, trifluoromethyl, dilower alkylamino group. , R ¹ is lower alkyl, lower haloalkyl, trifluoromethyl, lower alkoxycarbonyl, phenyl or benzyl group, where the phenyl group may be substituted with halogen, and R ² represents a hydrogen atom or a lower alkyl group. With amidino hydrazone to lose

[Wherein R ^{3 ′} , R ^{4 ′} , R ^{5 ′} is a hydrogen atom, a lower alkyl or lower alkenyl group or R ^{4 ′} is a lower alkoxyl group, or R ^{3 ′} and R ^{4 ′} , R ^{4 ′} and R ^{5 'is} characterized in that reacting a β- diketone represented by the sum haejyeoseo represents a trimethylene or tetramethylene; each other, formula

A method for producing a pyrimidine derivative represented by [symbols in the formula is the same as described above].