JP4534452B2 - 3-methylisothiazole-5-methanol derivative, process for producing the same, and agricultural and horticultural disease control - Google Patents

Description

  The present invention relates to a novel 3-methylisothiazole-5-methanol derivative derivative, a process for producing the derivative, and an agrochemical containing the compound as an active ingredient, particularly a plant disease control agent.

With respect to 3-methylisothiazole-5-methanol derivatives, its use is known as an insecticide.
JP-A-64-63568

It is also known for use as a tranquilizer.
British Patent No. 1395360

It is known that a 3-methylisothiazolecarboxylic acid derivative having a specific structure has an effect of protecting crops from pathogenic microorganisms.
Japanese Patent No. 2514823 JP-A-1-283270

On the other hand, 3-methylisothiazole-5-methanol according to the present invention can be synthesized, for example, by carrying out a reduction reaction using 3-methyl-5-isothiazolecarboxylic acid or its ester as a starting material. However, the use of 3-methylisothiazole-5-methanol derivatives of the present invention and 3-methylisothiazole-5-methanol and 3-methylisothiazole-5-methanol derivatives as agricultural fungicides is completely known. It wasn't.
J. Chem. Soc., 3061 1959 Heterocycles., 29 (1) 97 1989

  An object of the present invention is to provide a novel compound having an excellent effect for controlling various plant diseases, a method for synthesizing the compound, and an agrochemical, particularly a plant disease control agent, containing 3-methylisothiazole-5-methanol derivative as an active ingredient. It is to provide.

  The present inventors have eagerly created a novel agricultural and horticultural disease control agent that has low toxicity to human livestock, is highly safe in handling, and exhibits an excellent control effect on a wide range of plant diseases. As a result of repeated research, the 3-methylisothiazole-5-methanol derivative represented by the general formula (I) of the present invention is a novel compound not described in any literature, and is useful as an agricultural and horticultural disease control agent. The present invention has been found and completed.

  The present invention has been completed based on the above findings, and the first gist of the present invention resides in a 3-methylisothiazole-5-methanol derivative represented by the following formula (I).

In the formula, R represents a hydrogen atom; a C ₁ -C ₄ alkyl group; a C ₃ -C ₆ alkenyl group; a (cyano) C ₁ -C ₄ alkyl group; (unsubstituted or a C ₁ -C ₄ alkyl group, C ₁ -C ₄ alkoxy and _C 3 -C ₆ cycloalkyl substituted with same or different may be 1-4 groups selected from the group consisting of halogen _atom) C 1 -C ₄ alkyl group; (unsubstituted or _C 1 -C ₄ alkyl _group, C 1 -C ₄ alkoxy and _C 3 -C ₆ cycloalkyl same or different are selected from the group of halogen atoms are substituted with also good 1-4 groups) carbonyl group; (unsubstituted or C ₁ -C ₄ alkyl group, C ₁ -C ₄ alkoxy and phenyl substituted with same or different may be one to five groups selected from the group of halogen atom) C ₁ ~C ₄ Alkyl group; (unsubstituted or C ₁ -C ₄ alkyl group, C ₁ -C ₄ alkoxy and the same or different are selected from the group of halogen atoms is substituted with may also be 1 to 3 groups) pyrimidinyl group; (unsubstituted or C ₁ -C ₄ alkyl group, C ₁ -C ₄ alkoxy group and the same or different substituted with also good 1-4 groups pyridyl selected from the group of halogen atoms) carbonyl group; (unsubstituted or C ₁ -C ₄ alkyl group, C ₁ -C ₄ alkoxy group and the same or different substituted with also good 1-4 groups pyridyl selected from the group of halogen atom) C in (unsubstituted or _C 1 -C ₄ alkyl _group, C 1 -C ₄ same or different may be one or two groups selected from the group of alkoxy group and a halogen atom; ₁ -C ₄ alkyl group Conversion has been and _thiazolyl) C 1 -C ₄ alkyl group; (unsubstituted or _C 1 -C ₄ alkyl _group, C 1 -C ₄ same or different and may 1 is selected from the group of alkoxy group and a halogen atom A phenyl group (substituted with 5 groups); (unsubstituted or C ₁ -C ₄ alkyl group, C ₁ -C ₄ alkoxy group and may be the same or different selected from the group of halogen atoms 1-2 Isothiazolyl substituted with ₁ group) C ₁ -C ₄ alkyl group; (unsubstituted or identical or different selected from the group of C ₁ -C ₄ alkyl group, C ₁ -C ₄ alkoxy group and halogen atom) isothiazolyl) carbonyl group substituted with may also be one to two groups; or (unsubstituted or _C 1 -C ₄ alkyl _group, or a group of C 1 -C ₄ alkoxy group and a halogen atom A thiazolidinyl) C ₁ -C ₄ alkyl group substituted with 1 to 4 groups which may be the same or different.

A represents an oxygen atom, a sulfur atom or -NB-, B represents a hydrogen atom or a _C 1 -C ₄ alkyl group. R is as defined above.

  A second gist of the present invention is a compound represented by the formula (I), characterized by reacting a compound represented by the following formula (II) with a compound represented by the following formula (III): -It exists in the manufacturing method of a methylisothiazole-5-methanol derivative.

In the formula, X and Y each represent a leaving group, a hydroxyl group, a mercapto group, or -NBH. B represents a hydrogen atom or a _C 1 -C ₄ alkyl group.

  The third gist of the present invention resides in an agricultural and horticultural plant disease control agent characterized by containing the 3-methylisothiazole-5-methanol derivative described in the first gist as an active ingredient.

Hereinafter, the present invention will be described in detail. Of the definitions of substituents of the 3-methylisothiazole-5-methanol derivative (hereinafter sometimes abbreviated as “the compound of the present invention”) represented by the above formula (I), the substituents represented by the general concept Includes the following preferred substituents. C ₁ -C ₄ alkyl includes methyl, ethyl, 1-methylethyl, 1,1-dimethylethyl, propyl and 2-methylpropyl. The C ₁ -C ₄ alkoxy, methoxy, ethoxy, 1-methylethyl-oxy, 1,1-dimethylethyl oxy, propyloxy and 2-methyl-propyloxy and the like. And as a halogen atom, a fluorine atom, a chlorine atom, a bromine atom, or an iodine atom is mentioned.

  In preferred combinations of substituents, the compounds of the following Tables 1 to 3 can be exemplified as the compounds of the present invention represented by the formula (I).

  The following can be illustrated as a diluent used with the manufacturing method of this invention. Water, organic acids such as formic acid, acetic acid and propionic acid, hydrocarbons such as benzene, toluene, xylene, petroleum ether, pentane, hexane and heptane, halogenated hydrocarbons such as methylene chloride, chloroform and carbon tetrachloride, methanol , Ethanol, isopropanol, alcohols such as t-butanol, diethyl ether, dimethoxyethane, diisopropyl ether, ethers such as tetrahydrofuran, diglyme, dioxane, carbon disulfide, acetonitrile, acetone, ethyl acetate, acetic anhydride, pyridine, dimethylformamide Dimethylacetamide, 1-methyl-2-pyrrolidinone, dimethyl sulfoxide, hexamethylphosphoric amide and the like.

  The following can be illustrated as a base. Alkaline metal carbonates such as sodium carbonate, sodium hydrogen carbonate, potassium carbonate, potassium hydrogen carbonate, alkaline earth metal carbonates such as calcium carbonate, barium carbonate, alkali metal such as sodium acetate, potassium acetate, sodium propionate Alkali metal hydroxides such as carboxylates, sodium hydroxide and potassium hydroxide, alkaline earth metal oxides such as magnesium oxide and calcium oxide, alkali metals such as lithium, sodium and potassium, and alkaline earths such as magnesium Alkali metals, sodium methoxide, sodium ethoxide, alkali metal alkoxides such as potassium t-butoxide, alkali metal hydrides such as sodium hydride and potassium hydride, methyllithium, ethyllithium, n-butyllithium, phenyllithium, etc. of Organic metal compound of Lucari metal, organic Grignard reagent such as methylmagnesium iodide, ethylmagnesium bromide, n-butylmagnesium bromide, organometallic compound of alkali metal, organic copper compound that can be prepared from Grignard reagent and copper (I) salt, Alkali metal amides such as lithium diisopropylamide, aqueous ammonia, ammonium hydroxides such as benzyltrimethylammonium hydroxide, tetramethylammonium hydroxide, methylamine, ethylamine, n-propylamine, benzylamine, ethanolamine, dimethylamine, benzyl And organic amines such as methylamine, dibenzylamine, triethylamine, triethanolamine, and pyridine.

  The compound represented by the general formula (I) of the present invention can be advantageously produced, for example, by formula (II) and formula (III) in a diluent in the presence of a base. In order to carry out the production method of the present invention, for example, the formula (III) is dissolved in the above-mentioned diluent, and, if necessary, the formula (III) Add 1.5 equivalents, or conversely, add Formula (II) and a base to a solution of Formula (III) dissolved in a diluent. As the reaction temperature at this time, any temperature from the freezing point to the boiling point of the diluent as the solvent can be applied, but in practice, the reaction is preferably performed at a temperature in the range of 0 to 100 ° C. The reaction time is in the range of 1 to 10 hours, and it is desirable to carry out the reaction with stirring. After completion of the above reaction, the reaction mixture obtained by the reaction is cooled, extracted with an organic solvent such as ethyl acetate, chloroform, benzene, etc. to separate the organic layer, and then the organic layer is washed with water and dried. The 3-methylisothiazole-5-methanol derivative (I) can be obtained by distilling off the solvent under reduced pressure and purifying the resulting residue. The purification treatment can be performed by recrystallization or silica gel column chromatography.

  Also, 3-methylisothiazole-5-methanol or its alcoholate is reacted with a halogenated alkyl derivative, a carboxylic acid derivative, a carboxylic acid chloride derivative, etc. in an appropriate solvent in the presence of a dehydrating agent, acid or base as necessary. By doing so, a 3-methylisothiazole-5-methanol derivative represented by the formula (I) can be obtained.

  Alternatively, after forming a leaving group by reacting 3-methylisothiazole-5-methanol with an appropriate halogenating agent, alkyl sulfonic acid chloride or aryl sulfonic acid chloride, etc., carboxylic acid derivatives, alcohol derivatives, amine derivatives, etc. To give a 3-methylisothiazole-5-methanol derivative represented by the formula (I). Alternatively, 3-methylisothiazole-5-methanol can be added to an olefin derivative or the like in the presence of a catalyst such as an acid or a base to obtain a compound represented by the general formula (I).

  Next, the usefulness of the 3-methylisothiazole-5-methanol derivative of the formula (I) according to the present invention as an active ingredient of an agricultural and horticultural disease control agent will be described. The 3-methylisothiazole-5-methanol derivative (I) of the present invention exhibits a controlling effect against the following extensive plant diseases. For example, rice blast (Pyricularia oryzae), rice sesame leaf blight fungus (Cochliobolus miyabeanus), rice seedling fungus (Gibberella fujikuroi), rice small black rot fungus (Helminthosporium sigmoideum), rice blight fungus (Rhizoctonia solani) Botrytis cinerea, Sclerotinia sclerotiorum, watermelon vine split fungus (Fusarium oxysporum f.sp.niveum), cucumber vine split fungus (Fusarium oxysporum f.sp.cucumerinum), cucurbits Colletotrichum lagenarium, sugar beet brown fungus (Cercospora beticola), soybean purpura fungus (Cercospora kikuchii), peach blight fungus (Sclerotinia cinerea), apple leaf spot fungus (Alternaria alternata (mali)), pear black spot fungus (Alternaria alternata (kikuchiana)), grape rot fungus (Glomerella cingulata), cucumber downy mildew (Pseudoperonosora cubensis), tomato plague (Phytophthra infestans), cucumber Color Phytophthora (Phytophthora capsici), rice seedling blight (Pythium aphanidermatum), and the like.

  In order to apply the compound of the present invention as an agricultural or horticultural disease control agent as described above, the compound can be used as it is, but usually various preparations such as powders, wettable powders, granules, emulsions and the like are prepared. It is formulated into a form and used. At this time, one or more 3-methylisothiazole-5-methanol derivatives (I) are usually 0.1 to 95% by weight, preferably 0.5 to 90% by weight, more preferably in the preparation. Formulated to contain 2-70% by weight. Examples of carriers, diluents and surfactants used as formulation aids include solid carriers such as talc, kaolin, bennite, diatomaceous earth, white carbon, clay, etc., and liquid diluents such as water, xylene , Toluene, chlorobenzene, cyclohexane, cyclohexanone, dimethyl sulfoxide, dimethylformamide, alcohol, etc., surfactants should be used properly depending on their effects, and as emulsifiers, polyoxyethylene alkyl aryl ether, polyoxyethylene sorbitan monolaurate Examples of the dispersant include lignin sulfonate and dibutyl naphthalene sulfonate, and examples of the wetting agent include alkyl sulfonate and alkylphenyl sulfonate. The above preparations include those used as they are and those diluted to a predetermined concentration with a diluent such as water. The concentration of the compound of the present invention when diluted is preferably in the range of 0.001 to 1.0%. Moreover, the usage-amount of this invention compound is 20-5000g normally, preferably 50-1000g per 1 ha of agricultural and horticultural lands such as a field, a rice field, an orchard, and a greenhouse. Since these use concentrations and amounts differ depending on the dosage form, use time, use method, use place, target crop, etc., it is of course possible to increase or decrease without sticking to the above range. Furthermore, the compound of the present invention can be used in combination with other active ingredients such as fungicides, insecticides, acaricides and herbicides.

  According to the present invention, the 3-methylisothiazole-5-methanol derivative of the formula (I) can be used as an active ingredient of agricultural and horticultural disease control agents.

  Hereinafter, the present invention will be described in more detail with reference to production examples, formulation examples, and test examples. However, the present invention is not limited to the following production examples as long as the gist thereof is not exceeded. The NMR spectrum was measured using TMS as an internal standard, and indicated by the following symbol or a combination thereof. s: single line, d: double line, t: triple line, m: multiple line, b: broad line, dd: double double line, qq: quadruple line

(Production Example 1)
<Production of (3-methylisothiazol-5-yl) methyl 2-chloropyridine-4-carboxylate (Compound No. 13)>
Under an argon atmosphere, 0.152 g of 2-chloroisonicotinic acid and 0.253 g of triphenylphosphine were dissolved in 2.7 ml of anhydrous tetrahydrofuran, and further 0.4 ml of a tetrahydrofuran solution of 0.104 g of 3-methylisothiazole-5-methanol. Was added. At room temperature, 0.152 ml of diethyl azodicarboxylate was added dropwise and stirred for 2 hours. After completion of the reaction, the solvent was distilled off under reduced pressure, and the resulting residue was subjected to silica gel column chromatography (“Wakogel C-300” (trade name) hexane / ethyl acetate = 3/1). 22 g was obtained. Table 4 shows the physical properties of this compound.

  The compounds shown in Tables 7 to 8 below were synthesized by the operation according to Production Example 1. The NMR data of these compounds are shown in Tables 5-6.

(Formulation example 1)
<Dust>
3 parts by weight of the compound of the present invention (Compound No. 3), 40 parts by weight of clay and 57 parts by weight of talc are pulverized and mixed and used as dust.

(Formulation example 2)
<Wettable powder>
50 parts by weight of the compound of the present invention (Compound No. 5), 5 parts by weight of lignin sulfonate, 3 parts by weight of alkyl sulfonate and 42 parts by weight of diatomaceous earth are pulverized and mixed to obtain a wettable powder and diluted with water for use. .

(Formulation example 3)
<Granule>
The compound of the present invention (Compound No. 8), 5 parts by weight, 43 parts by weight of bennite, 45 parts by weight of clay, and 7 parts by weight of lignin sulfonate are mixed uniformly and further kneaded with water, and granulated with an extrusion granulator. Process dry to form granules.

(Formulation example 4)
<Emulsion>
20 parts by weight of the compound of the present invention (Compound No. 15), 10 parts by weight of polyoxyethylene alkyl aryl ether, 3 parts by weight of polyoxyethylene sorbitan monolaurate and 67 parts by weight of xylene are uniformly mixed and dissolved to prepare an emulsion.

(Test Example 1)
<Rice blast control effect test (water surface application)>
Grains prepared in accordance with Formulation Example 3 to have a predetermined concentration (500 g / 10a) after transplanting rice (variety: Koshihikari) at the third leaf stage into a 1 / 10000a Wagner pot filled with paddy soil. Applied to the water surface. 10 to 20 days after the drug treatment, a spore suspension of rice blast fungus formed on rice disease was spray-inoculated and kept under high humidity in a vinyl tunnel in a glass greenhouse. 10 to 20 days after inoculation, the disease area ratio (%) was investigated objectively, and the disease incidence was investigated for all seedlings per test area according to the survey criteria shown in Table 7 below (Chinese agricultural leaf potato survey criteria). The control value (%) was calculated from the average disease degree per pot by the following formula: control value = (1−treatment disease degree / non-treatment disease occurrence degree) × 100. The results are shown in Table 8.

(Test Example 2)
<Wheat powdery mildew control effect (stem and leaf spray)>
Using a square-shaped pot (1.5 cm × 2.0 cm), a wet concentration prepared in accordance with Formulation Example 2 was added to wheat (cultivar: Norin 61) grown in a tillering greenhouse. 125 g / ha) was diluted with water and suspended at a rate of 1000 L / ha. 10 to 20 days after the drug treatment, spores were inoculated with spores of wheat powdery mildew. After that, she was sick in a glass greenhouse. On the 10th to 20th day after the inoculation, the disease incidence rate (%) was investigated objectively, and calculated from the average disease severity per pot according to the survey criteria shown in Table 9 below: control value = (1−treatment disease severity / The control value (%) was calculated by (non-treated morbidity) × 100. The results are shown in Table 10.

Claims (3)

3-methylisothiazole-5-methanol derivative represented by the following formula (I).

[Wherein, R represents a hydrogen _atom; C 1 -C ₄ alkyl _group; C 3 -C ₆ alkenyl group; _(cyano) C 1 -C ₄ alkyl group; (unsubstituted or _C 1 -C ₄ alkyl groups, C ₍ C ₃ -C ₆ cycloalkyl) substituted with 1 to 4 groups which may be the same or different and selected from the group of _{1 to} C ₄ alkoxy groups and halogen atoms; C _{1 to} C ₄ alkyl groups; C ₃ -C ₆ cycloalkyl substituted or substituted with ₁ to ₄ groups which may be the same or different and selected from the group consisting of C ₁ -C ₄ alkyl group, C ₁ -C ₄ alkoxy group and halogen atom ) carbonyl group, (unsubstituted or C ₁ -C ₄ alkyl groups, phenyl substituted with C ₁ -C ₄ alkoxy group and the same or different and may be 1 to 5 groups selected from the group of halogen atom ) _C 1 ~C Alkyl group; (unsubstituted or C ₁ -C ₄ alkyl group, C ₁ -C ₄ alkoxy and the same or different are selected from the group of halogen atoms is substituted with may also be 1 to 3 groups) pyrimidinyl group; (unsubstituted or C ₁ -C ₄ alkyl group, C ₁ -C ₄ alkoxy group and the same or different substituted with also good 1-4 groups pyridyl selected from the group of halogen atoms) carbonyl group; (unsubstituted or C ₁ -C ₄ alkyl group, C ₁ -C ₄ alkoxy group and the same or different substituted with also good 1-4 groups pyridyl selected from the group of halogen atom) C ₁ -C ₄ alkyl group; (unsubstituted or _C 1 -C ₄ alkyl _group, C 1 -C ₄ alkoxy group and the same or different and may be 1 to 2 groups selected from the group of halogen atom Is substituted _thiazolyl) C 1 -C ₄ alkyl group; (unsubstituted or _C 1 -C ₄ alkyl _group, C 1 -C ₄ same or different and may 1 is selected from the group of alkoxy group and a halogen atom A phenyl group (substituted with 5 groups); (unsubstituted or C ₁ -C ₄ alkyl group, C ₁ -C ₄ alkoxy group and may be the same or different selected from the group of halogen atoms 1-2 number of which is substituted by a group _{isothiazolyl)} C 1 -C ₄ alkyl group; (unsubstituted or _C 1 -C ₄ alkyl _group, the same or different and are selected from the group of C 1 -C ₄ alkoxy group and a halogen atom Or an isothiazolyl substituted by 1 to 2 groups) carbonyl group; or (unsubstituted or C ₁ -C ₄ alkyl group, C ₁ -C ₄ alkoxy group and a group of halogen atoms Represents a thiazolidinyl group substituted with 1 to 4 groups which may be the same or different, and C ₁ -C ₄ alkyl group, A represents an oxygen atom, a sulfur atom or —NB—, and B represents represents a hydrogen atom or a _C 1 -C ₄ alkyl group. However, 3-methylisothiazole-5-methanol and 3-methylisothiazole-5-methylamine are excluded from the compound of the chemical formula (I). ] A 3-methylisothiazole-5-methanol derivative represented by the formula (I), which comprises reacting a compound represented by the following formula (II) with a compound represented by the following formula (III): Manufacturing method.

[Wherein X and Y represent a leaving group, a hydroxyl group, a mercapto group, or -NBH. B represents a hydrogen atom or a _C 1 -C ₄ alkyl group. R is the same as defined in claim 1. However, 3-methylisothiazole-5-methanol and 3-methylisothiazole-5-methylamine are excluded from the compound of the chemical formula (I). ] A plant disease control agent for agricultural and horticultural use comprising 3-methylisothiazole-5-methanol derivative represented by the following formula (I) as an active ingredient.

[Wherein, R represents a hydrogen _atom; C 1 -C ₄ alkyl _group; C 3 -C ₆ alkenyl group; _(cyano) C 1 -C ₄ alkyl group; (unsubstituted or _C 1 -C ₄ alkyl groups, C ₍ C ₃ -C ₆ cycloalkyl) substituted with 1 to 4 groups which may be the same or different and selected from the group of _{1 to} C ₄ alkoxy groups and halogen atoms ; C _{1 to} C ₄ alkyl groups; C ₃ -C ₆ cycloalkyl substituted or substituted with ₁ to ₄ groups which may be the same or different and selected from the group consisting of C ₁ -C ₄ alkyl group, C ₁ -C ₄ alkoxy group and halogen atom ) carbonyl group, (unsubstituted or C ₁ -C ₄ alkyl groups, phenyl substituted with C ₁ -C ₄ alkoxy group and the same or different and may be 1 to 5 groups selected from the group of halogen atom ) _C 1 ~C Alkyl group; (unsubstituted or C ₁ -C ₄ alkyl group, C ₁ -C ₄ alkoxy and the same or different are selected from the group of halogen atoms is substituted with may also be 1 to 3 groups) pyrimidinyl group; (unsubstituted or C ₁ -C ₄ alkyl group, C ₁ -C ₄ alkoxy group and the same or different substituted with also good 1-4 groups pyridyl selected from the group of halogen atoms) carbonyl group; (unsubstituted or C ₁ -C ₄ alkyl group, C ₁ -C ₄ alkoxy group and the same or different substituted with also good 1-4 groups pyridyl selected from the group of halogen atom) C ₁ -C ₄ alkyl group; (unsubstituted or _C 1 -C ₄ alkyl _group, C 1 -C ₄ alkoxy group and the same or different and may be 1 to 2 groups selected from the group of halogen atom Is substituted _thiazolyl) C 1 -C ₄ alkyl group; (unsubstituted or _C 1 -C ₄ alkyl _group, C 1 -C ₄ same or different and may 1 is selected from the group of alkoxy group and a halogen atom A phenyl group (substituted with 5 groups); (unsubstituted or C ₁ -C ₄ alkyl group, C ₁ -C ₄ alkoxy group and may be the same or different selected from the group of halogen atoms 1-2 Isothiazolyl substituted with ₁ group ) C ₁ -C ₄ alkyl group; (unsubstituted or identical or different selected from the group of C ₁ -C ₄ alkyl group, C ₁ -C ₄ alkoxy group and halogen atom) Or isothiazolyl substituted with 1 to 2 groups) carbonyl group; or (unsubstituted or C ₁ -C ₄ alkyl group, C ₁ -C ₄ alkoxy group and a group of halogen atoms Represents a thiazolidinyl group substituted with 1 to 4 groups which may be the same or different from each other, and C _{1 to} C ₄ alkyl group, A represents an oxygen atom, a sulfur atom or —NB—, and B represents represents a hydrogen atom or a _C 1 -C ₄ alkyl group. ]