JP4655932B2 - Salicylic acid derivative, its production method and agricultural and horticultural disease control agent - Google Patents

Description

  The present invention relates to a salicylic acid derivative, a method for producing the same, and an agricultural and horticultural disease control agent containing the salicylic acid derivative as an active ingredient.

  Conventionally, the use of salicylic acid derivatives as agricultural and horticultural fungicides has been proposed (Patent Documents 1 and 2).

In addition, the use of 2,6-dichloro-4-pyridinemethanol and its benzoate derivative as an agricultural chemical has been proposed (Patent Document 3).
JP-A-8-291110 JP-A-10-29961 Japanese Patent Laid-Open No. 11-171864

  In view of the above circumstances, the present inventors have developed an agricultural and horticultural disease control agent that is low in toxicity to human livestock, has high safety in handling, and exhibits an excellent control effect against a wide range of plant diseases. In order to achieve this, salicylic acid derivatives of the following formulas (I and II) and salts thereof were synthesized, and their disease control effects were examined. Accordingly, an object of the present invention is to provide an agricultural and horticultural disease control agent comprising a salicylic acid derivative, a production method thereof, and a salicylic acid derivative or a salt thereof as an active ingredient.

  As a result of intensive studies to solve such problems, the present inventors have found that the salicylic acid derivative represented by the formula (I · II) is a novel compound and is excellent as an agricultural and horticultural disease control agent, The present invention has been completed.

  The present invention has been completed on the basis of the above findings, and the first gist of the present invention is the control of agricultural and horticultural diseases containing, as an active ingredient, a salicylic acid derivative of the following formula (I · II) or a salt thereof: Lies in the drug.

In the formula, X represents a lower alkyl group, a lower alkoxy group, a lower haloalkyl group or a halogen atom, and m represents an integer of 0 to 3. When m is 2 or more, Xs may be the same or different. R ¹ represents a hydrogen atom or a lower alkyl group, and R ² represents a hydrogen atom, a hydroxyl group, a halogen atom, a dimethylamino group, a lower alkyl group or a lower haloalkyl group.

  The second gist of the present invention is the production of a salicylic acid ester of the formula (II) characterized by reacting a 2-hydroxybenzoic acid derivative of the following formula (III) with a substituted benzyl halide of the formula (IV) And a method for producing a substituted salicylic acid of formula (I), characterized in that the ester moiety is hydrolyzed.

In the formula, X represents a lower alkyl group, a lower alkoxy group, a lower haloalkyl group or a halogen atom, and m represents an integer of 0 to 3. When m is 2 or more, Xs may be the same or different. R represents a lower alkyl group. R ² represents a hydrogen atom, a hydroxyl group, a halogen atom, a dimethylamino group, a lower alkyl group or a lower haloalkyl group, and Y represents a halogen atom.

  The third gist of the present invention resides in the salicylic acid derivative of the above formula (I · II) or a salt thereof.

  According to the present invention, the salicylic acid derivative of formula (I / II) and a salt thereof can be used as an active ingredient of an agricultural and horticultural disease control agent, and the agricultural and horticultural disease control agent exhibits an excellent disease control effect.

Hereinafter, the present invention will be described in detail. Of the definitions of the substituents of the salicylic acid derivative (I / II) of the present invention (hereinafter sometimes abbreviated as “the compound of the present invention”), the substituents shown in the general concept include the following preferred substituents. Has been. Examples of the lower alkyl group for X include a methyl group, an ethyl group, a 1-methylethyl group, a 1,1-dimethylethyl group, and a propyl group. Examples of the lower alkoxy include methoxy, ethoxy, 1-methylethyloxy, 1 , 1-dimethylethyloxy and propyloxy, the halogen atom includes a fluorine atom, a chlorine atom, a bromine atom and an iodine atom, and the lower haloalkyl group includes a trifluoromethyl group. Preferred integers m are 0 and 1. Examples of the lower alkyl group for R ¹ and R include a methyl group, an ethyl group, and a 1-methylethyl group. Examples of the halogen atom for R ² include a fluorine atom, a chlorine atom, a bromine atom, and an iodine atom. Examples of the lower alkyl group include a methyl group, an ethyl group, a 1-methylethyl group, a propyl group, and a 2-methylpropyl group. Examples of the lower haloalkyl group include a trifluoromethyl group. Examples of the salt of the salicylic acid derivative (I · II) include salts containing sodium, potassium, copper or 1-methylethylamine. In the definition of the substituent, in the lower alkyl group, the lower alkoxy group and the lower haloalkyl group, a group containing a carbon chain having 1 to 4 carbon atoms including the exemplified groups is preferable. The lower haloalkyl group means a group in which one or more hydrogen atoms of the lower alkyl group are substituted with a halogen atom, preferably a fluorine atom.

  Next, specific examples of salicylic acid derivatives (I and II) are shown in Table 1.

In the table, 5-Cl in compound (II-11) represents a chlorine atom bonded to the 5-position. 3,5-Cl ₂ in compound (II-20) indicates that a chlorine atom is bonded to the 3-position and the 5-position. That is, the number before the hyphen (-) indicates the bonding position, and the number after the hyphen (-) indicates the number when there are two or more substituents and the same kind of substituent. H in compound (II-1) indicates unsubstituted. This rule is also used for the substituent Xm.

  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, potassium hydride, methyl lithium, ethyl lithium, n-butyl lithium, phenyl lithium, etc. Organometallic compounds of alkali metals, organic magnesium compounds such as methylmagnesium iodide, ethylmagnesium bromide, n-butylmagnesium bromide, organometallic compounds of alkali metals, organocopper compounds that can be prepared from Grignard reagents and copper (I) salts, 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 Organic amines such as methylamine, dibenzylamine, triethylamine, triethanolamine and pyridine.

  As the salt of the first transition element used in the production of the metal complex salt of the salicylic acid derivative (I / II), three kinds of salts of acetate, hydrochloride, nitrate and sulfate (hydrochloride, nitrate or sulfate) are used. Sometimes it is advantageous to use alkali metal acetates, carbonates or hydroxides at the same time). Examples of the acid may include inorganic acids such as hydrochloric acid, hydrobromic acid, hydroiodic acid, perchloric acid, nitric acid and sulfuric acid, and organic acids such as formic acid, acetic acid, butyric acid and p-toluenesulfonic acid. .

  Salicylic acid ester (II) which is a precursor of substituted salicylic acid (I) is prepared by diluting 2-hydroxybenzoic acid derivative (III) and 2,6-dichloro-4-halogenomethylpyridine (IV) in the presence of a base. It can be advantageously manufactured in. In order to carry out the production method of the present invention, for example, a 2-hydroxybenzoic acid derivative (III) dissolved in the above-mentioned diluent is added, if necessary, in the presence of the above-mentioned base with 2,6- Dichloro-4-halogenomethylpyridine (IV) is usually added in an amount of 0.5 to 1.5 equivalents, or conversely, 2,6-dichloro-4-halogenomethylpyridine (IV) dissolved in a diluent, The 2-hydroxybenzoic acid derivative (III) and a base may be added and reacted. 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 usually 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 salicylic acid ester (II) can be obtained by evaporating the solvent under reduced pressure and purifying the resulting residue. The purification treatment can be performed by recrystallization or silica gel column chromatography.

  Hydrolysis of the ester moiety of salicylic acid ester (II) can be carried out as follows. Salicylic acid ester (II) and an alkali metal hydroxide are added to hydrous alcohol, and it is normally refluxed at 20-100 degreeC or 20 degreeC-the reflux point of a solvent normally for 1 to 20 hours. After the reaction, the reaction mixture is acidified, and the precipitate is collected by filtration, or the solvent is distilled off. Water is added to the residue and stirred well, and then the insoluble matter is collected by filtration. Then, the filtrate can be recrystallized to obtain the substituted salicylic acid (I).

  Since the substituted salicylic acid (I) thus obtained has an acidic proton, it can form a salt in which a hydrogen atom is substituted with an appropriate cation. These salts are generally metal salts, in particular alkali metal salts, alkaline earth metal salts or complex salts with first transition elements including copper, or in some cases ammonium salts, alkylated ammonium salts or organic amine salts. And preferably can be prepared in a solvent such as water, methanol or acetone, usually at a temperature of 20-100 ° C.

  Next, the usefulness of the salicylic acid derivative of the above formula (I / II) according to the present invention as an active ingredient of an agricultural and horticultural disease control agent will be described. The salicylic acid derivative (I / II) of the present invention exhibits a controlling effect against the following extensive plant diseases. For example, rice blast disease (Piculararia oryzae), rice sesame leaf blight fungus (Cochliobolus miyabeaneus), rice shoot seedling fungus (Gibberella fuujikurii), rice small black rot fungus (Helminosporumii) Botrytis cinerea, sclerotia sclerotiorum, Fusarium oxysporum f. Sp. Numum, and Fusarium cucumber sp. Colletotrichum lag narium), sugar beet blight fungus (Cercospora beticola), soybean purpura fungus (Cercospora kikuchii), peach blight fungus (Sclerotinia cinerea), apple spotted fungus (Alternaria alternata) (Alternaria alternata) )), Grape late rot fungus (Glomerella cingula), cucumber downy mildew (Pseudoperonosora cubensis), tomato blight (Phytophthra infestans), cucumber gray blight fungus (Phytophthora capsici), rice seedling fungus, Phytophathora capsici, and rice seedling.

  In order to apply the salicylic acid derivative (I / II) as a disease control agent for agricultural and horticultural use as described above, the compound can be used as it is, but usually together with formulation adjuvants, powders, wettable powders, granules, emulsions It is used in various forms such as. At this time, one or more salicylic acid derivatives (I and II) are usually contained in the preparation in an amount of 0.1 to 95% by weight, preferably 0.5 to 90% by weight, more preferably 2 to 70% by weight. To be formulated. 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., and surfactants should be used properly depending on their effects. 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%. The amount of the compound of the present invention is usually 20 to 5000 g, preferably 50 to 1000 g, per 1 ha of agricultural or horticultural land such as fields, fields, orchards, and greenhouses. Since the concentration and amount of use 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. Incidentally, since this compound contains a carboxylic acid, it can be used in the form of inorganic salts, organic salts or metal complex salts.

  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, q: quadruple line, m: multiple line, b: broad line, dd: double double line, qq: quadruple line

Production Example 1:
<Production of 6-chloro-2- (2,6-dichloro-4-pyridylmethoxy) benzoic acid methyl ester (Compound No. II-4)>
0.93 g of 6-chlorosalicylic acid methyl ester was dissolved in 50 ml of acetone, 1.35 g of potassium carbonate and 1.1 g of 4-chloromethyl-2,6-dichloropyridine were added, and the mixture was heated to reflux for 8 hours. After completion of the reaction, water was poured into the reaction solution and extracted with ethyl acetate. The organic layer was washed successively with water and saturated brine, dried over anhydrous sodium sulfate, the solvent was distilled off, and the resulting residue was treated with column chromatography (Wakogel C-300 hexane / ethyl acetate = 8/1). As a result, 1.3 g of the target compound was obtained. The physical properties of this compound are shown in Table 2.

Production Example 2:
<Production of 2- (2,6-dichloro-4-pyridylmethoxy) -5-chlorobenzoic acid methyl ester (Compound No. II-11)>
0.186 g of 5-chlorosalicylic acid methyl ester was dissolved in 6 ml of anhydrous acetone, 1.1 g of potassium carbonate and 0.241 g of 4-bromomethyl-2,6-dichloropyridine were added, and the mixture was heated to reflux for 16 hours. After completion of the reaction, water was added to the reaction solution and extracted with ethyl acetate. The organic layer was washed successively with saturated brine and water, dried over anhydrous sodium sulfate, and then the solvent was distilled off under reduced pressure. The resulting residue was purified by silica gel column chromatography to obtain 0.294 g of the target compound. Table 3 shows the physical properties of this compound.

Production Example 3:
<Production of 2- (2,6-dichloro-4-pyridylmethoxy) -6-hydroxybenzoic acid (Compound No. I-2)>
Under a nitrogen stream, 0.4 g of 60% oily sodium hydride was washed with anhydrous hexane and then suspended in 100 ml of anhydrous dimethylformamide. 1.68 g of 2,6-dihydroxybenzoic acid methyl ester was added under ice cooling and stirring, and then a solution prepared by dissolving 2.65 g of 4-bromomethyl-2,6-dichloropyridine in 30 ml of dimethylformamide was added dropwise. After 1 hour, the reaction temperature was gradually raised, and the reaction was carried out for 6 hours while maintaining the temperature at about 30 ° C. After completion of the reaction, water was added to the reaction station, and extraction was performed using ethyl acetate. The organic layer was washed successively with water and saturated brine, and dried over anhydrous sodium sulfate. After distilling off the solvent, the resulting residue was purified by silica gel column chromatography to obtain 2.3 g of a salicylic acid ester (Compound No. II-3) corresponding to the methyl ester of the target compound. Table 4 shows the physical properties of this compound.

  0.25 g of the obtained salicylic acid ester was dissolved in 30 ml of ethanol, 20 ml of water and 0.5 g of sodium hydroxide were added, and the mixture was heated at 50 ° C. for 3 hours. After completion of the reaction, the reaction solution was neutralized with dilute hydrochloric acid and extracted with chloroform. The organic layer was washed successively with water and saturated brine, and then dried over anhydrous sodium sulfate. The solvent was distilled off and recrystallization from chloroform-methanol gave 0.15 g of the target compound. Table 5 shows the physical properties of this compound.

  The compounds shown in Tables 6 to 7 below were synthesized by operations according to the above Production Examples 1 to 3. The melting points and NMR data of these compounds are shown in Tables 6-7.

Formulation Example 1:
<Dust>
3 parts by weight of the compound of the present invention (Compound No. II-2), 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. II-3), 5 parts by weight of lignin sulfonate, 3 parts by weight of alkyl sulfonate and 42 parts by weight of diatomaceous earth were mixed to obtain a wettable powder and diluted with water. use.

Formulation Example 3:
<Granule>
5 parts by weight of the compound of the present invention (Compound No. II-7), 43 parts by weight of bennite, 45 parts by weight of clay and 7 parts by weight of lignin sulfonate are further mixed and kneaded with water. Processed into granules and dried to form granules.

Formulation Example 4:
<Emulsion>
The present compound (Compound No. II-10) 20 parts by weight, polyoxyethylene alkylaryl ether 10 parts by weight, polyoxyethylene sorbitan monolaurate 3 parts by weight and xylene 67 parts by weight are mixed and dissolved uniformly to give an emulsion. .

Test Example 1:
<Rice blast control effect test (water surface application)>
Grain prepared in accordance with Formulation Example 3 at a predetermined concentration (500 g / 10a) after transplanting rice (variety: Koshihikari) at the 3-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. 10-20 days after inoculation, the disease incidence rate (%) was investigated objectively, and according to the survey criteria shown in Table 8 below (Chinese agricultural leaf potato survey criteria), the disease severity was investigated for all seedlings per test zone. The control value (%) was calculated from the average disease degree per pot by the following formula: control value = (1−treatment area disease degree / no treatment area disease degree) × 100. The results are shown in Table 9.

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. From 10 to 20 days after the inoculation, the disease area ratio (%) was investigated objectively, and calculated from the average disease severity per pot according to the survey criteria shown in Table 10 below: control value = (1−treatment disease severity / The control value (%) was calculated by (non-treated morbidity) × 100. The results are shown in Table 11.

Claims (3)

An agricultural and horticultural disease control agent comprising a salicylic acid derivative of the following formula (I · II) or a salt thereof as an active ingredient.

(In the formula, X represents a lower alkyl group, a lower alkoxy group, a lower haloalkyl group or a halogen atom, and m represents an integer of 0 to 3. When m is 2 or more, X may be the same or different. R ¹ represents a hydrogen atom or a lower alkyl group, and R ² represents a hydrogen atom, a hydroxyl group, a halogen atom, a dimethylamino group, a lower alkyl group or a lower haloalkyl group. A method for producing a salicylic acid ester of the formula (II), comprising reacting a 2-hydroxybenzoic acid derivative of the following formula (III) with a substituted benzyl halide of the formula (IV).

(In the formula, X represents a lower alkyl group, a lower alkoxy group, a lower haloalkyl group or a halogen atom, and m represents an integer of 0 to 3. When m is 2 or more, X may be the same or different. R represents a lower alkyl group, R ² represents a hydrogen atom, a hydroxyl group, a halogen atom, a dimethylamino group, a lower alkyl group or a lower haloalkyl group, and Y represents a halogen atom.) A salicylic acid derivative represented by the following formula (I · II) or a salt thereof.

(In the formula, X represents a lower alkyl group, a lower alkoxy group, a lower haloalkyl group or a halogen atom, and m represents an integer of 0 to 3. When m is 2 or more, X may be the same or different. R ¹ represents a hydrogen atom or a lower alkyl group, and R ² represents a hydrogen atom, a hydroxyl group, a halogen atom, a dimethylamino group, a lower alkyl group or a lower haloalkyl group.