JPS58198472A - 2,4-dimethoxy-5-methylthiopyrimidine derivative, its preparation, and agricultural and gardening fungicide - Google Patents

Abstract

NEW MATERIAL:A compound shown by the formula [X is -NR<1>R<2> (R<1> and R<2> are H, 1-3C alkyl, alkenyl, phenyl, alkoxycarbonylalkyl, carboxyalkyl, aminoalkyl, or amino), aziridino, or (substituted) morpholino]. EXAMPLE:2,4-Dimethoxy-6-(N-methylamino)-5-methylthiopyrimidine. USE:An agricultural and gardening fungicide. Having no phytotoxicity to cultivated plants, extremely low toxicity to warm-blooded animals, having improved fungicidal action and propagation inhibitory action on pathogenic fungi, capable of controlling plant blight caused by wide range of fungi, such as alternaria blotch of apples, blight of potatoes, gray mold, etc. PROCESS:5-Methylthio-2,4,6-trichloropyrimidine is reacted with sodium methylate and an amine shown by the formula XH in a solvent in the presence of a deoxidizer such as K2CO3, an amine shown by the formula XH, to give a compound shown by the formula I .

Description

[Detailed description of the invention]

The present invention is based on the general formula [wherein,
Each represents an alkoxycarbonylalkyl group, a carboxyalkyl group, an aminoalkyl group, or an amino group. ), each represents an aziridino group, a morpholino group, or a substituted morpholino group. 5-Methylthiopyrimidine derivatives and their production methods, as well as the use of these compounds as active ingredients, have been shown in the past.
A huge number of compounds have been synthesized, and many compounds that exhibit distinctive physiological activities have been discovered in the field of agricultural medicine. However, most of them have a pyrimidine skeleton that is easy to produce.
゜The substituents at the 4th and 6th positions are exchanged, and the 5th position has low reactivity, so there are a few methods known to directly introduce substituents such as nitration or halogenation under limited conditions. It's just being told. Among the substituents at the 5-position, there are few synthesis examples of compounds having a methylthio group and an amino group at the 2.4- or 6-position of the pyrimidine skeleton. Chemical abstract (
The following are the only related compounds described in CJLt□caJ AAAla, αc, L). Mu, 15896&Wataru1.16212χ'', 137181渥NIIM. 1, 156364a 1(3 Ie, 2C1, OM, 013..3-Pyridylmethoxy, 101721d Herbicide plate, 54968.y) The present inventors have a methylthio group at the 5-position, and 2. 4
Focusing on the fact that compounds with a methoxy group at the 6-position and an amino group at the 6-position have never been synthesized,
As a result of synthesizing various derivatives and testing their physiological activities, we discovered that these compounds of the present invention have extremely excellent control effects against many plant pathogenic bacteria, which could not be expected from known compounds. The invention has been completed. The compounds of the present invention have excellent bactericidal and growth inhibiting properties against plant pathogens, and can be applied to control plant diseases caused by a wide variety of fungi. For example, the compounds of the present invention can be used by spraying. as a soil treatment agent or as a soil treatment agent.
It is highly effective against potato late blight, tomato late blight, green pepper late blight, cucumber leaf blight, etc. caused by algal fungi, as well as gray mold, apple spot leaf blight caused by Deuteromycetes, and powdery mildew of various crops caused by Ascoli fungi. In addition, the compound of the present invention does not show any practical toxicity to cultivated plants1, has very weak toxicity to warm-blooded animals such as mice, rats, dogs, chickens, etc., does not show any toxicity to fish, and is used for agricultural purposes. It has extremely excellent properties as a bactericidal agent. The compounds of the present invention can be used in the following reaction scheme (breath) or -(8
) S'
Amount 3 (X in general formulas (1) to (III) is the same as above) The starting material 5-methylthio-2,4,6-dolichloropyrimidine is a chemical abstract (Ck tm=ca
It can be produced according to the method described in 1-A4J Mu-c4) 72, 3499s. Below, the manufacturing method of the present invention will be explained in detail for each step based on the above reaction formula. Route (α) Step (i): As a solvent, use something inert to metallic sodium such as tetrahydrofuran, dioxane, N,N-dimethylformamide, dimethylsulfoxide, hexamethylphosphoramide, benzene, toluene or ether, or methanol itself. Can be used. The reaction is initially carried out by diluting 2 equivalents or a slight excess of methanol into the solvent, and when using methanol as a solvent, use the required volume. ), 2 equivalent or slightly excess metallic sodium, or hydrogen 1
Add sodium chloride and stir well to adjust sodium methylate. After sodium methylate is formed, 5
-Methylthio-2,4,6-)lichloropyrimidine is added in portions as a solid or dissolved in a solvent. In this case, the reaction temperature is from -10°C to the boiling point of the solvent, but if added below room temperature, 6-chloro-2,4
-dimethoxy-5=methylthiopyrimidine is produced. The product can be easily isolated, but it can also be continued to the next step without isolation. Step (ii): The same solvent as in step ('l) is used as the solvent. Furthermore, water can also be used for amines with a low boiling point. As a deoxidizing agent, a tertiary amine such as sodium carbonate, sodium hydrogen carbonate, potassium carbonate, potassium hydrogen carbonate, triethylamine, or XII itself represented by the general formula (11) can be used. In the presence of the above deoxidizing agent, 6-chloro-2,4-
Add the above X to a solution of dimethoxy-5-methylthiopyrimidine.
H<II) Add tc to the serving size or slightly in excess. The reaction temperature can range from O'C to the boiling point of the solvent, but when heated, the reaction is often completed in 2 to 1 hour. An amine with a low boiling point? , (In the case of i, an autoclave may be used (.) To purify the target compound represented by the general formula (I) produced by recrystallization or column chromatography. Route (6) Step (iii) ): Same as step (ii). In the presence of a deoxidizing agent, 1 equivalent or slightly excess of general formula (11) is added to a solution of 5-methylthio-2,4,6-)lichloropyrimidine.
Add XHQ indicated by . The reaction temperature can range from 0°C to the boiling point of the solvent, but it is better to carry out the reaction below room temperature.
Side reactions such as polysubstituted products can be prevented. Reactions are 2-5
Many things can be completed in time. The compound represented by the general formula (III) can be easily isolated during recrystallization or column chromatography, but it can be directly isolated in the next step (iV) without being isolated.
) can also be continued. Step (iv): Same as step (jl). In a solution of 2 equivalents or a slight excess of sodium methylate, the general formula (II
The compound of I) may be added, or a previously prepared solution of sodium methylate may be added to the solution of the compound of general formula (1). The reaction temperature can range from room temperature to the boiling point of the solvent, but the reaction progresses more smoothly when heated.
Many can be completed in ~5 hours. The method for purifying the target compound is the same as in step (?I). The method for producing the compound of the present invention will be specifically explained below by giving synthesis examples. Synthesis Example 1 2.4-dimethoxy-6-(N-methylamino)-5-
Synthesis of methylthiopyrimidine (compound number 1)...
・Route (tl) ■Synthesis of 6-chloro-2,4-dimethoxy-5-methylthiopyri-sewing machine Add anhydrous methanol to a 50-meter flask equipped with a reflux condenser with a calcium chloride tube, a thermometer, and a stirrer: (Q
After charging 37 ml of sodium metal was added in small pieces. , 5 at 0°C after the metallic sodium has dissolved.
-Methylthio-2,4,6-)dichloropyrimidine 1.
8=1 was added little by little. 15 minutes at 0℃, 15 minutes at room temperature
After stirring for several minutes, the reaction solution was poured into ice water. The precipitated solid was collected by filtration to obtain inpropidimethoxy-5-methylthiopyrimidine (mp 58.5-59.5°C). Yield 1
．． 40g (yield 79.1%) NMR (CC14) δ2.
30 (3H, s), 3.97 (3H, s) 4.04 (3
1-1,s) 1'p2.4-dimethoxy-6-(N-methylamine)
-Synthesis of 5-methylthiopyrimidine In an autoclave, 1.769 of 6-chloro-2,4-dimethoxy-5-methylthiopyrimidine, 1.499 of a 40% aqueous methylamine solution and 25-
and heated at 110'C for 2 hours. The reaction solution was poured into water and extracted with ethyl acetate. After washing with water and dehydration, the crude product obtained by removing the solvent was recrystallized from isopropyl ether.
．． 4-dimethoxy-6-(N-methylamino)-5-methylthiopyrimidine (mp 57.5-59°C) was obtained. Yield: 1.37 mm (yield: 80%). NMR (CCe4) δ2.08 (3H, s), 4.99
(3H, d, J= 4.8l-1z), 3.86
(3H,s) , 3.92 (3H,s) , 5.94
(IH. 64etad) Synthesis Example 2 Synthesis of 2, 1-dimethoxy-5-methylthio-6-(N-phenylamino)pyrimidine (Compound No. 2)...
...Route (A) (T) 2.4-dichloro-5-methylthio-6-(N
-Synthesis of phenylamino)pyrimidine In a 100 ml four 11 flask equipped with a reflux condenser, a thermometer and a stirrer, 2°309 of 5-methylthio-2,,1,6-drichloropyrimidine and 2.76 g of potassium carbonate were added.
, and dimethyl sulfoxide 30- were charged and suspended. Aniline l. 12 was added and stirred at room temperature for 3 hours.
The reaction solution was poured into dilute hydrochloric acid and extracted with ethyl acetate. After washing with water and dehydration, the crude product obtained by removing the solvent was recrystallized from isopropyl ether to obtain 2,4-dichloro-5-methylthio-5-(N-phenylamino)pyrimidine (m91
30-131°C). Yield l. 63g (yield 57
%). NMR (CI) (“C3) δ2.39 (311, s),
7.1-7.7 (5H, m), 8a44 (III, (3
+,-=Jd) ■2. Synthesis of 4-dimethoxy5-methylthio-6-(N-phenylamino)pyrimidine Add anhydrous water to a 100-four-eye flask equipped with a reflux condenser with a calcium chloride tube, a thermometer, and a stirrer. methanol 30a
/ was charged. Next, add 0.559% of sodium metal in small pieces and, after completely dissolving, 2.4-cyclo-5-
1.149 ml of MeF-ruthio-6-(N-phenylamino)pyrimidine was added at room temperature. After heating under reflux for 2 hours, the reaction solution was poured into dilute hydrochloric acid and extracted with 15-ethyl acetate. After washing with water and dehydration, the crude product obtained by removing the solvent was recrystallized from n-hexane to obtain 2,4-dimethoxy-5-methylthio-6-(N-phenylamino)pyrimidine (mp-65-68 °C) was obtained. Yield 0.7
39 (yield 66%). NMR (CC4) δ2.20 (3H, s), 3°92 (
3H, s), 3°99 (311, s), 6.99 (IH
, d , J = 8.0 Hz), 7.24 (2H, dd,
J=8.0.8,011z), 7.62(2H,d,J
=8. QHz), 8.08 (11 (bow sheettd)) The compounds of the present invention represented by the general formula (I) are synthesized according to the above synthesis examples. The compounds of the present invention produced by the above method and The physical property values are shown in Table 1 below.
°14 However, in practice, it is mixed with a carrier and other adjuvants as necessary to form a formulation that is used as a fungicide for agriculture and horticulture, such as powder, coarse powder, fine granules, granules, and hydrated It is prepared and used as a formulation, emulsion, aqueous solution, aqueous solution, oil suspension, etc. The term "carrier" as used herein refers to a synthetic or synthetic compound that is added to an artistic fungicide to help the active ingredient reach the area to be treated, and to facilitate the storage, transportation, and handling of the active ingredient compound. means a natural inorganic or organic substance. Appropriate t

[Solid carriers include clays such as montmorizonite and carolinite, diatomite, white clay, talc,
Inorganic substances such as vermiculite, gypsum, calcium carbonate, silica gel, and ammonium sulfate, vegetable organic substances such as soybean flour, sawdust, and wheat flour, and urea are produced. Suitable liquid carriers include aromatic hydrocarbons such as benzene, xylene, cumene, kerosene, paraffinic hydrocarbons such as mineral oil, halogenated hydrocarbons such as carbon tetrachloride, chloroform, dichloroethane, and acetone. , ketones such as methyl ethyl ketone, ethers such as dioxane and tetrahydrofuran, alcohols such as methanol, propatool, and ethylene glycol, dimethylformamide, dimethyl sulfoxide, and water. . Furthermore, in order to enhance the efficacy of the compound of the present invention, the following adjuvants may be used alone or in combination depending on the purpose, taking into account the dosage form of the preparation, the application situation, etc. For the purposes of emulsification, dispersion, spreading, wetting, bonding, and nitriding, water-soluble salts such as pyrogenine sulfonates, anionic surfactants such as alkylbenzene sulfonates, alkyl sulfate esters, and polyoxyethylene esters are used. Nonionic surfactants such as calcium stearate, lubricants such as wax, stabilizers such as isopropylhydrodiene phosphate, and others such as methyl cellulose, calhodic methyl cellulose, casein, and gum arabic. However, these components are not limited to those on μ. When the compound of the present invention is applied as a fungicide, other agricultural chemicals may also be used, such as insecticides, 1v1 agents, acaricides, nematicides, antiviral agents, weed control, and plant growth regulation. agents, attractants, such as organic phosphate compounds, carbamate compounds, dioxicarhamete compounds, thiol carbamate compounds, active ingredient compounds, dinitro compounds, antibiotic substances,
It can also be used in combination with urea compounds, triazine compounds, fertilizers, etc., or as a mixture. Various formulations or preparations containing the active ingredient of the present invention can be applied by application methods commonly used in the agricultural chemical manufacturing field, such as spraying, spraying (e.g., spraying, misting, atomizing, It can be carried out by dusting, dusting, water surface application), fumigation, soil application (mixing in one row, fumigation, irrigation), surface application (for example, painting, dusting, covering), dipping, etc. Next, the formulation method of the agricultural and horticultural fungicide of the present invention will be explained with reference to Examples. The active ingredient compounds are indicated by compound numbers in Table 1 above. "Parts" means "parts by weight." Example 1 Wettable powder compound 3: 300 parts, diatomaceous earth: 440 =+
<, White clay: 20 (1, Sodium ligninsulfonate:
25 parts, sodium alkylbenzenesulfonate: 15
and polyoxyethylene nonylphenyl ether: 20 parts were uniformly ground and mixed to obtain a wettable powder containing 30% of Compound 3 as an active ingredient. Example 2 Emulsion compound 15: 400 parts, cyclohexanone: 100 parts,
300 parts of xylene and 200 parts of Tsurpol (a surfactant manufactured by Toho Chemical Co., Ltd.) were uniformly dissolved and mixed to obtain an emulsion containing 40% of Compound 15 as an active ingredient. Example 3 Granule compound 2: 10 parts, bentonite: 62 parts, talc: 20 parts, sodium dodecylbenzenesulfonate = 2 parts, and sodium ligninsulfonate = 1 part were mixed, and an appropriate amount of water was added and kneaded. After, press 1. Granules containing 10% of Compound 2 as an active ingredient were obtained by a conventional method using a granulator. Example 4 Powder compound 8: 20 parts, calcium stearate = 5 parts,
Powdered silica gel: 5 parts, diatomaceous earth: 200 parts, Yamakami: 300 parts, and Merck: 470 parts were uniformly ground and mixed to obtain a powder containing 2% of Compound 8 as an active ingredient. Example 5 Oil compound 17: 0 parts, and ethyl cellosolve: 9
Mix and dissolve 0 parts of Compound 17 as an active ingredient to 10 parts.
An oil solution containing % was obtained. Next, the effect of the compound of the present invention as a fungicide will be explained in detail using test examples. The test compound is indicated by the above-mentioned 1k compound number. Test Example 1 Apple Spot Leaf Disease Test Apple videos (variety: Star King, 2-year-old seedlings) with approximately 8 newly developed leaves planted in a No. 3 clay pot were treated with a prescribed concentration of 1710 ointment (
The test compound was prepared as a hydrating agent by the method of Example 1 and diluted with water to a predetermined concentration).
-0'e9/JJ) was used to spray 100- per 3 pots. After air-drying, a conidial suspension of a pre-cultured apple leaf spot fungus (cultivated for 7 days in V-8 vegetable youth medium) was spray inoculated. The number of lesions was examined per ear on each of the eight leaves in each pot, the average number of lesions per leaf was determined, and the control value was calculated using the following formula. The results are shown in Table 2. 1,000 2nd table t (revised reference 1 to the proboscis: thiophanate methyl A' groan example 2
Gray mold control test section Specified / 1% chemical solution on common bean cotyledons (variety Nidotsubu crop) (the test compound was made into a wettable powder by the method of Example 1, and this was diluted with water to the specified concentration) )
Soaked in water for 1 minute. After air-drying, mycelial pieces (diameter 6 mm) of gray mold fungi (B, Mu μi...y (t Ha, 1, cultured for 5 days in PSA medium)) were placed on kidney bean soil at a temperature of 20°C and humidity. It was maintained at 95% or less for 4 days. The diameter of the lesion on each leaf was chewed and the control value was calculated from the following formula. The results are shown in Table 3. Control Compound A: Thiophanate methyl test example 4
Potato Phytophthora control test Potatoes grown in pots in a greenhouse (variety: Otoshiaku, length of about 25.1 cm) were treated with a prescribed # degree of drug (the test compound was used as a hydrating agent by the method of Example 1 above, This was diluted with water to a predetermined concentration) and was sprayed at 5 parts/m/m per 3 pots using a spray gun, and air-dried. A zoospore suspension was prepared from potato Phytophthora blight that had been previously cultured on potato sections for 7 days, and this suspension was further kept at 7° C. for 3 hours to prepare a zoospore suspension. This suspension was spray-inoculated onto potato plants sprayed with chemicals, and the temperature of the test plants was 17 to 1.
After being kept at 9° C. and humidity of 95% or higher for 5 hours, the degree of lesion formation was investigated. The evaluation criteria are as follows. Morbidity 0: Lesion area ratio 0% 1: 1-5% 2: 6-25% 3: 26-50% 4: 51% or more The results are shown in Table 4. Table 4:・χ・S Compound B: Zinc ethylene bis (dithiocarbamate) Patent applicant Mitsui Toatsu Chemical Co., Ltd. Continued from page 1 0 Inventor Hitoshi Shimotori 2882 Iijima-cho, Totsuka-ku, Yokohama-0 Inventor Iidakai 2084 Oiso, Oiso-cho, Naka-gun, Kanagawa 0 Inventor Akihiro-O 6104-3 Hino-cho, Konan-ku, Yokohama 0 Inventor Shuji Ozawa 4-10-8 Kuki, Zushi City

Claims (1)

[Scope of Claims] [In the formula, or an amine group, respectively), an aziridine group, a morpholino group, or a substituted morpholino group. ] A 5-methylthiopyrimidine derivative represented by: 2.5-Methylthio-2,,1,6-)lichloropyrimidine with sodium methylate and general formula XH (11
) [wherein, X is -Nlzerf(a", R" is a hydrogen atom,
Each represents an alkyl group having 1 to 3 carbon atoms, an alkenyl group, a phenyl group, an alkoxycarbonyl alkyl group, a carboxyl alkyl group, an aminoalkyl group, or an amino group. ), respectively representing an aziridino group, a morpholino group, or a substituted morpholino group. . 3. General formula [wherein, Each represents an amine group.) Each represents an aziridine group, a morpholino group, or a substituted morpholino group. ] An agricultural and horticultural fungicide characterized by containing a 5-methylthiopyrimidine derivative represented by the following as an active ingredient.