JPS6253974A - 2-alkyl-6-thiocyanopyrimidine derivative, production thereof and agricultural and horticultural germicide - Google Patents

Abstract

NEW MATERIAL:A 2-alkyl-6-thiocyanopyrimidine derivative expressed by formula I (R is 1-3C alkyl; X is halogen). EXAMPLE:4-Chloro-2-methyl-5-methylthio-6-thiocyanopyrimidine. USE:An agricultural and horticultural germicide capable of exhibiting improved controlling effect on the wide range of plant blights, e.g. late blight, downy mildew, powdery mildew, gray mold, etc., of various crops and safe to crops with low toxicity to animals. PREPARATION:A pyrimidine derivative expressed by formula II is reacted with a thiocyanate expressed by formula III (M is alkali metal or ammonium) in an organic acid, e.g. formic acid, acetic acid or propionic acid, particularly formic acid to afford the aimed compound expressed by formula I.

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention is based on the general formula (1) [wherein R represents an alkyl group having 1 to 3 carbon atoms and X represents a halogen atom]. The present invention relates to a 2-alkyl-6-thiocyanopyrimidine derivative represented by the following, a method for producing the same, and an agricultural and horticultural fungicide containing the derivative as an active ingredient.

BACKGROUND OF THE INVENTION A great deal of research has been carried out on pyrimidine derivatives, a huge number of compounds have been synthesized, and many compounds with characteristic physiological activities have been discovered in the field of agricultural medicine. However, there are still no known examples of practical use of agricultural and horticultural fungicides in which a teocyano group is introduced into the pyrimidine nucleus. There are very few examples of synthesis of pyrimidine derivatives having a thiocyano group, and little is known about their biological activities. Slightly, Pharmaceutical Journal, Pay 10
86 (1963) describes thiocyanopyrimidine derivatives and their in vitro antibacterial activity. This document describes 15 types of thiocyanopyrimidine derivatives and their antibacterial activity.
The most active compound Fi2-(or 4-)chloro-6
-Methyl-4-(or 2-)thiocyanopyrimidine, which has a substituent at the 5-position, is described as having a generally low antibacterial activity. Nothing is known about compounds with a methylthio group at the 5th position.

In addition, plant pathogenic bacteria have an extremely large impact on agricultural and horticultural production, and in recent years, various fungicides have been used to treat various plant diseases, and there are still a number of fungicides that can be used to achieve somewhat stable production. Many deficiencies remain.

For example, existing fungicides require extremely large amounts of chemicals to control the late blight of various crops caused by algal fungi or downy mildew, and their effectiveness depends on the timing of application, weather, etc., and it is difficult to say that they are stable. hard. Furthermore, the emergence of drug-resistant bacteria in gray mold, sclerotium, etc. of various crops has made it almost impossible to expect the control effects of benzimidazole-based or dicarboxylic acid imide-based fungicides.

Problems to be Solved by the Invention The present invention is useful as a fungicide for agriculture and horticulture, and is effective against economically devastating late blight, downy mildew, gray mold, etc., and is also effective against bacteria resistant to existing chemicals. The purpose of the present invention is to provide compounds and compositions with new active structures that may have the following properties and methods for their production.

Means and Action for Solving the Problems In order to solve the above problems, the present inventors focused on the pyrimidine nucleus, which is thought to play a special role in interaction with living organisms, and conducted intensive studies on pyrimidine bamboo conductors. did.

The present inventors discovered that 2-alkyl-6-thiocyanopyrimidines having a methylthio group at the 5-position, despite the literature stating that the bactericidal activity of thiocyanopyrimidines with a substituent introduced at the 5-position is reduced. We have completed the present invention by discovering that pyrimidines have very excellent effects against many plant pathogens including Phytophthora blight, and that the methylthio group at the 5-position enhances the effect.

That is, the present invention is directed to the general formula (1) [wherein R represents an alkyl group having 1 to 3 carbon atoms and/or a halogen atom]. ] The present invention provides a 2-alkyl-6-thiocyanopyrimidine derivative represented by the following.

2-alkyl-6 represented by general formula (1) according to the present invention
- Thioquanopyrimidine derivative #2: A new compound that exhibits excellent control effects against a wide range of plant diseases including late blight, downy mildew, powdery mildew, and gray mold on various crops. Moreover, it is completely safe for crops, and shows no phytotoxicity to tomatoes, chieri, potatoes, etc.

It also has low toxicity to animals.

Furthermore, the present invention also provides a method for producing a 2-alkyl-6-thiodiazupyrimidine derivative represented by the general formula (1). That is, the method for producing the 2-alkyl-6-thiocyano group+7 midine derivative represented by the general formula (1) according to the present invention is based on the general formula (I) 0H3 [wherein R is an alkyl group having 1 to 3 carbon atoms and X represents a halogen atom. [In the formula, M represents an alkali metal or ammonium.

It is characterized by reacting thiocyanates shown in ] in an organic acid.

2-alkyl-6 represented by general formula (I) according to the present invention
The method for producing the -thiodiazupyrimidine derivative will be explained below.

The starting material (IF) is prepared by reacting amidines (■) with diethyl methylthiomalonate (2) in the presence of flucorate.
The dichlor compound (4,x
=Ct), dibromine (4,X
=Br) When the 4-benzene dichloro form is treated with concentrated hydroiodic acid, the 7-yoshijod form (5, x=E) is obtained, and when it is treated with potassium fluoride, the difluoro form (5, x=IP) is obtained.

2-alkyl-6-thiodiatubirimidine according to the present invention can be produced according to the following formula.

This reaction consists of dihalogen compound (II) and thiocyanate (1)
It consists of reacting in a solvent. Examples of the thiocyanate include potassium thiocyanate, sodium thiocyanate, and ammonium thiocyanate, and good results can be obtained using any of them. The type of solvent that has the greatest influence on this reaction is the type of solvent used. When the reaction is carried out in an alcohol such as methanol or ethanol, the reaction progresses slowly even under reflux, and resin-like by-products are produced, resulting in a very low yield. In addition, when reacted in an aprotic polar solvent such as acetone, dimethyl sulfoxide, N,N-dimethylformamide, and t3-dimethyl-2-imidazolidinone, products with two thiocyano groups substituted or thiocyano groups transferred may be produced. An isothiocyanate is generated, and the target product (1
) yield is low. However, unlike in the case of these solvents, the yield is surprisingly dramatically improved when the reaction is carried out in organic acids such as formic acid, acetic acid and propionic acid. The reactivity is best in the order of formic acid, acetic acid, and propionic acid, with formic acid being particularly effective. For example, in acetic acid it takes 5 hours or more to complete the reaction at 50°C, whereas in formic acid it takes less than 1 hour at the same temperature. The reaction temperature is 10
℃ to the boiling point of the solvent, but from the viewpoint of suppressing the formation of by-products and ensuring an appropriate reaction time, it is preferable to conduct the treatment in the range of 20-60℃. In this way, from both the selectivity and ease of reaction, formic acid has very good compatibility in this reaction, which is very different from other organic solvents and other organic acids, which are relatively good among them. It can be said that it has.

After the reaction is completed, the reaction solution is discharged into a large amount of water, and if the precipitate is solid, it is collected and dried to obtain crude crystals of the target product in a yield of 90% or more. If the precipitate is oily, it can be extracted with an inert solvent such as ethyl acetate, benzene or toluene, washed with water, and dehydrated to obtain a crude oil. The purity of the crude product itself is quite good, and it can be used as a pesticide as is, but if necessary, isopropyl nee? A
A purified product can be obtained by recrystallization from commonly used solvents such as /, chloroform, carbon tetrachloride, ethyl acetate, ethanol and methanol, or by column chromatography.

Furthermore, the present invention provides an agricultural and horticultural fungicide characterized by containing the pyrimidine rust conductor represented by the general formula (1) according to the present invention as an active ingredient. The compounds of the present invention exhibit excellent control effects against a wide range of plant diseases such as late blight, downy mildew, powdery mildew, and gray mold on various crops.

Methods for applying the compound of the present invention include seed disinfection, foliage spraying,
Examples include soil treatment, but any application method commonly used by those skilled in the art will exhibit sufficient efficacy. The application amount and concentration will depend on the target crop, target disease, degree of disease occurrence,
It varies depending on the dosage form of the compound, application method, various environmental conditions, etc., but when spraying, the amount is 95 to 200 g per area.
is suitable, preferably 10 to 100 g per area.

The spray concentration is suitably 100 to 1.000 ppm, preferably 200 to 500 ppm.

The agricultural and horticultural fungicide of the present invention can be used not only in combination with other fungicides, insecticides, herbicides, agricultural chemicals such as plant growth regulators, soil conditioners, or fertilizing substances, but also in mixed formulations with these. is also possible.

The compounds of the present invention may be applied neat, but preferably they are mixed with a carrier, including a solid or liquid diluent, and applied in the form of a composition. As used herein, carrier means an inorganic or organic substance, synthetic or natural, which is incorporated to aid in the delivery of the active ingredient to the site to be treated and to facilitate storage, transport and handling of the active ingredient compound.

Suitable solid carriers include clays such as montmorillonite and kaolinite, inorganic materials such as chilium earth, china clay, talc, vermikeyite, gypsum, calcium carbonate, silica gel, and ammonium sulfate, and vegetable organic materials such as soybean flour, sawdust, and wheat flour. Examples include substances and urea.

Suitable liquid carriers include aromatic hydrocarbons such as toluene, xylene and cumene; paraffinic hydrocarbons such as kerosene and mineral oil; halogenated hydrocarbons such as carbon tetrachloride, chloroform and dichloroethane; ketones such as acetone and methyl ethyl ketone; Ethers such as dioxane and tetrahydrofuran, alcohols such as methanol, furopanol, and ethylene glycol, dimethylformamide, dimethyl sulfoxide, and water can be used.

Furthermore, in order to enhance the efficacy of the compound of the present invention, the following adjuvants may be used individually or in combination depending on the purpose, taking into account the dosage form of the preparation, the application situation, etc.

For the purpose of emulsification, dispersion, spreading, wetting, binding, stabilization, etc., water-soluble bases such as genin sulfonate, nonionic surfactants such as alkylbenzene sulfonate, alkyl sulfate, calcium stearate, wax, etc. lubricants, stabilizers such as inpropylhydrodiene phosphate, and other substances such as methylcellulose, carboxymethylcellulose, casein, and gum arabic. but,
These components are not limited to those mentioned above.

The amount of active ingredient in the composition of the compound of the present invention is usually (
L5 to 20% by weight, emulsion 5 to 30% by weight, water use agent 10 to 90% by weight, granule 0.1 to 20% by weight, 11% by weight,
For 70 wobble agents, it is 10 to 90% by weight.

Examples Next, specific examples of the 2-alkyl-6-thiodiazupyrimidine derivatives represented by the general formula (1) according to the present invention are 4-chloro-2-methyl-5-methylthio-6-thiocyanopyrimidine. , 4-chloro-2-ethyl-5-methylthio-6-thiocyanopyrimidine, 4-chloro-2-isopropyl-5-methylthio-6-thiocyanopyrimidine, 4-iodo-2-methyl-5-methylthio- Examples include 6-thiocyanopyrimidine.

Next, the method for producing the compound of the present invention will be specifically explained by giving a synthesis example.

Synthesis Example 1 0.95 y (4.5 mmol) of 4,6-dichloro-2-methyl-5-methylthiopyrimidine and 058 y (60 mmol) of potassium thiocyanate were placed in a four-way flask equipped with a thermometer, a reflux condenser, and a stirrer. ) and 8 d of formic acid were charged and stirred at room temperature for 30 minutes. Drain the reaction solution into water,
The precipitate was extracted with ethyl acetate. After washing with water and dehydration, the solvent was distilled off to obtain crude crystals.

Silica gel column chromatography (elution solvent; n-
Purify with hexane:ethyl acetate=8:2) to obtain the desired 4-
Chloro-2-methyl-5-methylthio-6-thiocyanopyrimidine ayly (yield: 689 g) was obtained. mp
108-fiO<0>C.

NMR; 67M8 s (ppm); 2-46 (!
IHIS) p 2.77 (3H, s) In addition, a small amount of 2-methyl-4,6-bis(thiocyano)-6-methylthiopyrimidine, mp185-6℃
I got it.

Synthesis Example 2 4-chloro-2-inglovir-5-methylthio-6-
Synthesis of Thiocyanopyrimidine (Compound No. 2) Synthesis Example 1 Using 46-dichloro-2-isopropyl-5-methylthiopyrimidine (5,5 mmol), formic acid 9g and potassium thiocyanate OBOy (8,3 mmol) 4-chloro-2-isopropyl-
0.93 y (yield: 65 y) of 5-methylthio-6-thiocyanopyrimidine was obtained as an oil.

NMR,, (1! DCI3 *, M8 (ppm); t3a (6H1a, J=aaz
); z, a4 (3H, s); &20 (IH, q, J=
8Hz) Next, the method for producing the agricultural and horticultural fungicide according to the present invention will be explained using formulation examples. The active ingredient compounds are indicated by the compound numbers in the above synthesis examples. "Part" means "part by weight".

Formulation Example 1 Wettable powder compound (1): 30 parts, diatomaceous earth: 44 parts, white clay 22
0 parts, 21 parts of sodium ligninsulfonate, and 2 parts of sodium hyalkylbenzenesulfonate were uniformly ground and mixed to obtain 100 parts of an irrigation agent.

Formulation Example 2 Emulsion Compound (2): 20 parts, cyclohexanone: 10 parts, xylene: 50 parts and Nlupol (surfactant manufactured by Toho Chemical) 20 parts were uniformly dissolved and mixed to obtain 100 parts of an emulsion.

Formulation Example 3 Granules Compound (3) Near Part, Polyethylene Glycol Noni A/
1 part of phenyl ether, 3 parts of polyvinyl alcohol, and 289 parts of clay were uniformly mixed, granulated with water, and dried to obtain 100 parts of granules.

Formulation Example 4 Powder 2 parts of compound (1), 240 parts of calcium carbonate, and 258 parts of clay were uniformly mixed to obtain 100 parts of a powder.

Formulation Example 5 Wettable powder Compound (1): 50 parts, talc: 40 parts, sodium lauryl phosphate: 5 parts, and sodium alkylnaphthalene sulfonate = 5 parts were mixed to obtain 100 parts of an irrigation agent.

Formulation Example 6 Flowable agent Compound (3): 40 parts, carboxymethyl cellulose: 3 parts, sodium lignin sulfonate: 2 parts, dioctyl sulfosuccinate sodium salt: 1 part and 54 parts of water were wet-pulverized with a sand grinder to form a flowable agent. Got 100 copies.

Next, the efficacy of the compound of the present invention as a fungicide for agricultural and horticultural purposes will be explained using test examples. In addition, the following compounds were used as controls in the test examples.

A: 2-Chloa-6-mether-4-thiocyanopyrimidine B: Tetrachloroisophthalonitrile (Daconyl) C: 1-(phthylcarpamoyl)-2-benzimidazole methylcarbamate (benlate) Control compound A is The aforementioned 'Pharmaceutical Journal, Volume 183, Page 1086 (1965
), B is a commercially available drug as a control agent for potato late blight, chyurium blight, etc., and C is a commercially available drug as a control agent for botrytis blight, etc.

Test Example 1 Potato Phytophthora Control Test Potatoes (variety: Baron, about 25 cm tall) grown in pots in a greenhouse were injected with a prescribed concentration of the drug (a test compound was added to prepare an irrigation agent according to the method of Formulation Example 8 above, Dilute this with water to a specified degree) with a spray gun (tOK9/C
``) was used to spray 50 ml per 3 pots and air-dry it. After culturing on potato sections for 7 days, a zoospore suspension was prepared from the potato Phytophthora fungus. This suspension was applied to potato plants sprayed with the agent. After inoculating the test plants by spraying and keeping them at 17-19°C and a humidity of 95% or higher for 6 days, the degree of lesion formation was investigated.

The lesion area ratio was observed and evaluated for each famous confectionery to determine the lesion index, and the lesions were determined for each section using the following formula.

4n, +3n, +2n, -1-1n□+On0ri lesion = The evaluation criteria are as follows.

Disease severity index 0: Lesion area ratio 0%1:
1-5% 2: 6-25% 5: 26-50 inches 4: 51 inches or more n0: Number of leaves with disease severity index 0 n: 11 n,: 2y n3: 3# n,': 4 # N = rl 0-1-n, +n, -)-n 3-
)-n.

Table 1 Results of Potato Phytophthora control test Test Example 2 Potato blight control test Test of disease control with Tomo Kieuribe grown in pots in a greenhouse (variety: Sumo Hanshiro,
A spray gun (10~/Cm) was applied with a prescribed concentration of a drug (prepared as an aquarium using the test compound according to the method of Formulation Example 8 above, and diluted with water to a prescribed concentration) onto two leaves (spread).
't-Use 30 drops per 3 pots and air dry. The downy mildew fungus was collected from the diseased spot on a leaf of a downy mildew, and a spore suspension was made with demineralized water, which was then inoculated by spraying. The inoculated pots were immediately kept at 18-20°C and a humidity of 95% or higher for 24 hours, then transferred to a greenhouse (room temperature 18-27°C), and after 7 days, the degree of lesion formation was examined.

The evaluation criteria and lesion display method were as shown in Test Example 1.

The results are shown in Table-2.

Table 2 Cucumber and disease control test results Test example 3 Gray mold (bean leaf test) prescribed concentration (s
oo ppm) of the drug (each test compound was added to the above Formulation Example 1).
An irrigation agent was prepared according to the method and diluted with water.
was inoculated onto the leaves and placed in a greenhouse at 22°C in the dark.
Days later, the diameter of the lesions was examined, and the control rate was calculated using the following formula.

The results are shown in Table-3.

Table 3 Botrytis blight control test (green bean leaves) Test example 4 Botrytis blight (cucumber fruit test) Cucumber fruit (commercially available) was thoroughly washed, cut into 4-5 cm pieces, and treated with soo ppm of the chemical (each test compound in the above formulation). A wettable powder was prepared according to Example 1, diluted with water, immersed in water for about 50 seconds, and air-dried. Gray mold fungi (5 to 7
Stand the air-dried cucumber fruit on top of the fungus. Thereafter, the cucumbers were kept in a humid greenhouse for 4 days, and the growth and growth of fungus on the surface of the cucumbers was examined, and the control rate was calculated using the following formula. The results are shown in Table 4.

Table 4 Results of Botrytis blight control test (Botrytis fruit) From the results of Test Examples 1 to 4, the compounds of the present invention are used more widely than ever against completely different plant diseases such as potato late blight, Botrytis blight, and Botrytis blight. It is clear that this product has an extremely high pesticidal effect compared to commercially available fungicides.

In addition, the 2-
Chloro-6-methyl-4-thiocyanopyrimidine has almost no disease control effect, and the compound of the present invention has excellent properties that could not be predicted based on any previous knowledge.

it is obvious.

Effects of the Invention As is clear from the above explanation, the 2-alkyl-6-thiocyanopyrimidine derivatives of the present invention can be used as agricultural and horticultural fungicides to treat completely different types of potato late blight, cabbage rot, and gray mold. It is clear that it has superior control effects compared to commercially available drugs against a wide range of plant diseases.

Claims (3)

[Claims] (1) General formula (I) ▲Mathematical formulas, chemical formulas, tables, etc.▼(I) [In the formula, R represents an alkyl group having 1 to 3 carbon atoms and X represents a halogen atom. ] A 2-alkyl-6-thiocyanopyrimidine derivative. (2) General formula (II) ▲ Numerical formulas, chemical formulas, tables, etc. are available ▼ (II) [In the formula, R represents an alkyl group having 1 to 3 carbon atoms and X represents a halogen atom. The pyrimidine derivative represented by the general formula (III) MSCN (III) [wherein M represents an alkali metal or ammonium]. [In the formula, R and X represent the above meanings] . ] A method for producing a 2-alkyl-6-thiocyanopyrimidine derivative. (3) General formula (I) ▲ Numerical formulas, chemical formulas, tables, etc. are available ▼ (I) [In the formula, R represents an alkyl group having 1 to 3 carbon atoms and X represents a halogen atom. ] An agricultural and horticultural fungicide characterized by containing a 2-alkyl-6-thiocyanopyrimidine derivative represented by the following.