KR970011303B1 - Substituted carboxylic acid derivatives, process for preparing the same and agricultural or horiticultural fungicides containing the same - Google Patents

Abstract

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Description

Substituted carboxylic acid derivatives, their preparation and agricultural or horticultural fungicides containing the same

The present invention relates to a substituted carboxylic acid derivative, a method for preparing the same, and an agricultural or horticultural fungicide containing the same as an active ingredient.

The bactericidal activity of some carboxylic acid derivatives is described, for example, in Japanese Patent Laid-Open Nos. 52-87168, 56-96069 and 60-34949, US Pat. No. 4134967, GAWhites. Pesticide Biochemistry and Physiology 14,26 (1960), JL Huppatz, Aust. J. Chem. 36, 135 (1983), B. Janks, Pestic. Sci., 2, 43, 1971, DEOS 2611601, Chem. Abst. 70, 8779j (S. African 67 06, 681 Uniroyal Inc.), g. a. GA White et al., Pesticide Biochemistry and Physiology 5, 380-395, 1975, and M. Shell et al., Phyto-pathology 60, 1164-1169, 1970. ]. However, known compounds are not satisfactory in activity, and chemicals having high bactericidal activity have been required.

As a result of an in-depth study on compounds having high bactericidal activity, the inventors found a substituted carboxylic acid derivative of the formula (I) below (hereinafter referred to as the compound of the present invention).

In the formula, R ₁ represents a methyl or ethyl group;

또는

R₆을 나타내고 ; R₂는 메틸, 에틸 또는 트리플루오로메틸기를 나타내고 ; R₃은 메틸기 또는 할로겐 또는 수소원자를 나타내고 ; R₄는 불소 또는 수소원자를 나타내고 ; R₅는 메틸, 니트로 또는 트리플루오로메틸기 또는 할로겐원자를 나타내고 ; Z는 =CH…기 또는 N원자를 나타내고 ; R₆는 메틸, 에틸, 또는 트리플루오토메틸기를 나타내고 ; R₇은 아미노, 메틸기 또는 염소원자를 나타낸다.A is

or

R ₆ is represented; R ₂ represents a methyl, ethyl or trifluoromethyl group; R ₃ represents a methyl group or a halogen or a hydrogen atom; R ₄ represents fluorine or a hydrogen atom; R ₅ represents methyl, nitro or trifluoromethyl group or halogen atom; Z is = CH... Group or N atom; R ₆ represents a methyl, ethyl or trifluorotomethyl group; R ₇ represents an amino, methyl group or chlorine atom.

According to the invention, there is also provided a method for preparing a compound of the invention and an agricultural or horticultural fungicide containing the compound of the invention as an active ingredient.

The compounds of the present invention have the effect of preventing, treating and systematically combating plant diseases caused by various plant bacteria, in particular, bacteria belonging to Basidiomycetes, and hardly adversely affect the environment.

The following are plant diseases in which the compounds of the present invention have an excellent eradication effect: Rhizoctonia solani and Rhizoctonia oryzae, R. solani III B in rice; Puccinia striiformis, p. In wheat and barley. P. graminis, p. P. recondita, P.hordei, Typhula incarnata, T. T. ishikariensis, Ustilago tritici, and U. nuda; Rhizoctonia solani and Corticium rolfsii in various crops; Rhizoctonia solani on tomatoes and beet; Cymnosporangium haraeanum on the ship; Venturia inaequalis in apples; Rhizoctonia solani, Corticium rolfsii, Uromyces trifolii and Typhula incarnata, T. in pasture and grass. Preferred among the compounds of the present invention in terms of T. ishikariensis bactericidal activity are substituted carboxylic acid derivatives of the following formula (I '),

[Wherein, R ₁ , R ₂ and R ₃ are the same as defined above] More preferred are those of the following formula,

[Wherein R ₈ represents methyl or trifluoromethyl group and R ₉ represents halogen atom]

Most desirable

to be.

Compounds of the present invention include their optically active isomers due to inherent subtitle carbon atoms. One of the isomers is a substituted carboxylic acid derivative of formula (II) below.

[Wherein R ₁ , R ₂ and R ₃ are the same as defined above]

The preparation of the compounds of the invention is described in detail below.

[Method (A)]

Among the compounds of the present invention, the substituted carboxylic acid derivative of the following formula (I) reacts the substituted carboxylic acid of the following formula (III) or a reactive derivative thereof with the substituted 4-amino-2-oxane group of the following formula (IV) Are manufactured.

A-COOH... (III)

Wherein A and R ₁ are the same as defined above.

The reaction is usually carried out in the presence of a solvent but does not always require a solvent. The solvent is, for example, hydrocarbons such as benzene, toluene and xylene, halogenated hydrocarbons such as chlorobenzene, methylene chloride, chloroform and carbon tetrachloride, ethers such as diisopropylether, tetrahydrofuran and dioxane, acetone and methylethyl Ketones such as ketones, esters such as ethyl acetate, nitriles such as acetonitrile, dimethyl sulfoxide, dimethylformamide, water and the like, preferably tetrahydrofuran.

The amount of the reagent used in the reaction is 0.4-1.5 equivalents, preferably 0.5-substituted carboxylic acids or reactive derivatives thereof represented by formula (III) per substituted 4-amino-2-oxane dan equivalents represented by formula (IV). It is ~ 1.1 equivalency.

The reaction is carried out at an optional temperature from the freezing point of the solvent to the boiling point, preferably from 0 ° C. to the boiling point of the solvent.

Substituted carboxylic acids or reactive derivatives thereof represented by formula (III) include the corresponding carboxylic acids, acid anhydrides, acid chlorides, acidbutronides, carboxylic acid esters and the like.

The reaction can be carried out in the presence of a reaction aid depending on the substituted carboxylic acid or reactive derivative thereof represented by formula (III). Reaction aids are, for example, 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide methoxide and dicyclohexyl carbodiimide when carboxylic acid is used, sodium hydride, sodium methyl when carboxylic acid ester is used. It is the rate, sodium ethylate, etc., and when using an acid halide or an acid anhydride, it is sodium hydroxide, potassium hydroxide, triethylamine, N-methylmorpholine, pyridine, etc. The reaction aid is usually used in an amount of catalyst to 2 equivalents, preferably 0.95 to 1.1 equivalents.

After the reaction is completed, the reaction aid or its reaction product is filtered off and washed with water. The solvent is distilled off to give the desired substituted carboxylic acid derivative of formula (I). If necessary, the product is further purified by chromatography, recrystallization or the like.

[Method (B)]

Among the compounds of the present invention, the substituted carboxylic acid derivative of formula (II) is reacted with a substituted 4-amino-2-oxane group of the following formula (VI) Obtained.

[Wherein R ₁ , R ₂ and R ₃ are the same as defined above]

The reaction is usually carried out in the presence of a solvent but a solvent is not always necessary. Examples of the solvent include hydrocarbons such as benzene, toluene and xylene, halogens and hydrocarbons such as chlorobenzene, methylene chloride, chloroform and carbon tetrachloride, ethers such as diisopropylether, tetrahydrofuran and dioxane, acetone and methyl ethyl ketone Ketones, such as ethyl acetate, nitriles such as acetonitrile, dimethyl sulfoxide, dimethylformamide and water, preferably tetrahydrofuran.

The amount of the reagent is 0.4 to 1.5 equivalents, preferably 0.5 to 1.1 equivalents, of the substituted carboxylic acid represented by the formula (VI) or the reactive derivative thereof represented by the formula (V).

The reaction is carried out at a temperature from the coagulation to the boiling point of the solvent, preferably from 0 ° C. to the boiling point of the solvent.

Substituted carboxylic acids or reactive derivatives thereof of formula (V) are the corresponding carboxylic acids, acid anhydrides, acid chlorides, acid bromide and carboxylic acid esters.

The reaction can be carried out in the presence of a reaction aid depending on the substituted carboxylic acid of formula (V) or a reactive derivative thereof. As a reaction adjuvant, for example, when carboxylic acid is used, 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide merodide and dicyclohexyl carbodiimide are used; When carboxylic acid esters are used, they are sodium hydride, sodium methylate and sodium ethylate; When acid halides or acid anhydrides are used they are sodium hydroxide, potassium hydroxide, triethylamine, N-methylmorpholine and pyridine. The reaction aid is usually used in an amount of from 2 to 2 equivalents, preferably 0.95 to 1.1 equivalents.

After the reaction is completed, the reaction aid or its reaction product is filtered off and washed with water. The solvent is distilled off to give the desired substituted carboxylic acid derivative of formula (II). If necessary, the product is further purified by chromatography, recrystallization or the like.

[Method (C)]

Substituted carboxylic acid derivatives of the following formula (VII) among the compounds of the present invention are prepared by reacting substituted 4-amino-2-oxanedan derivatives of the following formula (VIII) with thioamide derivatives of the following formula (IX).

[Wherein, R ₁ and R ₆ are the same as defined above and R ₁₀ represents an amino or methyl group]

The reaction is usually carried out in the presence of a solvent, but a solvent is not always necessary. Examples of solvents include hydrocarbons such as benzene, toluene and xylene, halogenated hydrocarbons such as chlorobenzene, ethers such as diisopropylether, tetrahydrofuran and dioxane, esters such as ethyl acetate, alcohols such as methanol and ethanol, dimethyl sulfoxide Seeds, dimethylformamide and water.

The amount of the reagent is not limited, but is usually 0.5 to 10 equivalents, preferably 1 to 3 equivalents, of the thioamide derivative of the formula (IX) per equivalent of the substituted 4-amino-2-oxanedan derivative of the formula (VIII).

The reaction is carried out at a temperature from the condensation point to the boiling point of the solvent, preferably from 0 ° C. to the dew point of the solvent.

The reaction can be carried out in the presence of a base as a reaction aid. Bases are, for example, aqueous ammonia, amines such as triethylamine and N-methylmorpholin, and inorganic bases such as potassium carbonate and sodium carbonate.

After the reaction is completed, the reaction aid or its reaction product is filtered off, washed with water and the filtrate is distilled off to remove the solvent until the desired carboxylic acid derivative of formula (VII) is obtained. If necessary, the product can be purified, for example by chromatography.

[Method (D)]

Substituted carboxylic acid derivatives of the formula (II) of the compounds of the invention include formula (I ') a substituted carboxylic acid derivative, for the optically active column, for example, in "Sumi pack Oei ^{era" R 4100 ( "Sumipack OA"} R 4100 Obtained by separation into Sumike Chemical Analysis Service Ltd.

Substituted 4-amino-2-oxane groups represented by formula (IV), which is one of the starting materials for preparing a compound of the present invention, are described, for example, in literature; Jean Vene and Jean Tirouflet Compt rend 231, 911-12 (1950).

[Wherein, R ₁ is the same as defined above.]

That is, 4-acetaminophthalide may be reacted with a methylgrignard reagent (4-12 equivalents) such as methylmagnesium iodide at a temperature of -10 ° C to room temperature in an ether solvent such as diethyl ether and tetrahydrofuran. React until a) is obtained. Diol (a) is reacted with activated manganese dioxide (5-20 equivalents) under reflux in an ether solvent such as further acid and tetrahydrofuran or a halogenated hydrocarbon such as chloroform and dichloroethane to give lactone (b). Lactone (b) is then halved in an ether solvent such as diethyl ether and tetrahydrofuran at -30 ° C. to room temperature until methyllithium or ethyltitanium (24 equivalents) and acetal (c) are obtained.

The acetal (c) is hydrogenated in alcohol solvents such as methanol and ethanol at room temperature until an anilide (d) is obtained in the presence of a catalyst of palladium carbon and concentrated hydrochloric acid. Subsequently, the anhydride (d) is reacted with alkali metal hydroxides (5-20 equivalents) such as sodium hydroxide and calcium hydroxide until a substituted 4-amino-2-oxane group (IV) is obtained in ethylene glycol and water solvent under reflux. Let's do it.

Substituted 4-amino-2-oxane groups represented by formula (IV) can be used, for example, to photodegrade substituted 4-amino-2-oxane groups (IV) into (I) optically active carboxylic acids or (2) optically active columns. Can be obtained.

When the compound of the present invention is used as an active ingredient of a bactericide, it can be used without adding other ingredients, but is usually mixed with a solid or liquid carrier, a surface active agent, and other auxiliaries to prepare an emulsion, a wet powder, a suspension, a granule, and a dust It is formulated with liquid.

The content of the compound of the present invention as the active ingredient in this formulation is 0.1 to 99.9% by weight, preferably 0.2 to 80% by weight.

Solid carriers include, for example, clay clay, ether filite clay, bentonite, acid clay, pyrophylllifera, talc, diatomaceous earth, calcitic sheet, coon starch powder, rhodium shell powder urea, sulfuric ammonium, synthetic hydrous silicon dioxide, and the like. Fine powder or granules. Examples of the liquid carrier include aromatic hydrocarbons such as xylene and methylnaphthalene, alcohols such as isopropanol, ethylene glycol and cellosolve, acetone and cyclohexa, ketones such as isophorone, vegetable oils such as soybean oil and cottonseed oil, dimethylsulfoxide and the like. , Acetonitrile, water and the like.

Surfactants used in emulsification, dispersion, wetness, etc. include, for example, alkyl sulfates, alkyl (aryl) sulfonates, salts of dialkyl-sulfosuccinates, polyoxyethylene alkylaryl ether phosphate esters, naphthalenesulfonic acid / formalin concentrates. Anionic surfactants such as salts, and nonionic surfactants such as polyoxyethylene alkyl ethers, polyoxyethylene polyoxypropylene block copolymers, sorbitan fatty acid esters, polyoxyethylene sorbitan fatty acid esters and the like. Examples of the additive for the preparation include lignosulfonates, alginates, polyvinyl alcohols, arivia gums, CMC (carboxymethyl cellulose), PAP (acidic isopropyl phosphate), and the like.

This agent is administered directly to the soil or plant, either by itself or diluted, for example with water. More specifically, they are administered in various forms, for example, by spraying or dusting on plants, spraying on soil surfaces, dust or granule-sprinkleing or, if necessary, secondary soiling. In addition, when using this formulation as a seed treatment, the seed is covered or submerged in this formulation. The formulations may also be used in admixture with other fungicides, pesticides, mites, pesticides, herbicides, plant growth regulators, fertilizers, soil improvers and the like.

The compounds of the present invention are used as active ingredients of fungicides used in rice fields, arable land, orchards, grasslands, grasses and the like. When the compound of the present invention is used as an active ingredient of a fungicide, the dosage is usually 0.5 to 100 g per ar, depending on weather conditions, preparation type, time, method and place of administration, disease to be suppressed and processed grains, preferably 1 to 50 g. The concentration at the time of dilution with water in order to use an emulsion concentrate, a wet powder suspension preparation, a pharmaceutical preparation, etc., is 0.0001%-1%, Preferably it is 0.0005%-0.5%. Granules and dusts are used without dilution.

The compounds of the present invention are particularly effective against various plant diseases, particularly those caused by bacteria belonging to bacidiomycetes, so that the compounds of the present invention can be used as active ingredients of fungicides for various administrations.

The present invention is explained in more detail by reference examples, formulation examples and test examples in the following synthesis.

Synthesis Example 1 [Synthesis of Compound (2) by Method (A)]

5 mg of 1,1,3-trimethyl-2-oxa-4-aminoindane dissolved in 5 ml of tetrahydrofuran and 50 mg of triethylamine were dissolved in 2 ml of tetrahydrofuran at 5 ° C. or lower under ice-cooling with stirring. 89 mg of chloro-1,3-dimethylpyrazole-4-carbonyl chloride is added dropwise, followed by stirring at room temperature overnight. The reaction mixture is extracted with water and chloroform.

The organic layer is washed with water, dried and concentrated. The residue was purified by silica gel thin layer chromatography to give 119 mg of N- (1,1,3-trimethyl-2-oxa-4-indanyl) -5-chloro-1,3-dimethylpyrazole-4-carboxamide. To obtain.

Synthesis Example 2 [Synthesis of Compound (13) by Method (A)]

2-mg of 1,1,3-trimethyl-3-oxa-4-aminoindane dissolved in 5 ml of tetrahydrofuran and 44 mg of triethylamine were dissolved in 2 ml of tetrahydrofuron under stirring at a temperature of 5 ° C. under ice cooling. A solution of 83 mg of (triflu automethyl) benzoyl chloride is added dropwise, followed by stirring at room temperature overnight. The reaction mixture is then extracted with water and chloroform. The organic layer is washed with 5% hydrochloric acid and water, dried and biaxially. The residue is purified by silica gel thin layer chromatography to give 102 mg of N- (1,1,3-trimethyl-2-oxa-4-indanyl) -2- (tripolotomethyl) benzamide.

Synthesis Example 3 [Synthesis of Compound (19) by Method (A)]

A solution of 155 mg of 2-methylnicotinic acid and 335 mg of 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide matiodide dissolved in 10 ml of methylene chloride is stirred at room temperature for 1 hour.

200 mg of 1,1,3-trimethyl-2-oxa-4-aminoindane was added to the solution, and the reaction proceeded under reflux for 6 hours. Methylene chloride and water are added to the reaction mixture to extract the organic layer. The organic layer was concentrated and purified by silica gel thin layer chromatography to give N- (1,1,3-trimethyl-2-oxa-4-indanyl) -2-methylnicotinamide.

Synthesis Example 4 Synthesis by Method (A)

100 mg of 1,1,3-premethyl-2-oxa-4-amine indane dissolved in 5 ml of tetrahydrofuran and 63 mg of triethylamine in 2-methyl-4-trifluuromethyl dissolved in 2 ml of tralahydrofuran 130 mg of this Joule-5-carbonyl chloride solution is added to the mixture with stirring at an internal temperature of 5 ° C. or less under ice cooling. The dropwise addition, the reaction mixture is stirred overnight at room temperature and extracted with water and chloroform. The organic layer is washed with 5% hydrochloric acid and water, dried and concentrated.

The residue was purified by silica gel thin film chromatography to give N- (1,1,3-trimethyl-2-oxa-4-indanyl) -2-methyl-4-trifluoromerylthiazole-5-carboxamide 172 mg are obtained.

Synthesis Example 5 [Synthesis of Compound (26) by Method (A)]

49 mg of thioacetamide and 193 mg of N- (1,1,3-trimethyl-2-oxa-4-indanyl) -2-chloroacetoacetamide dissolved in 10 ml of tetrahydrofuran were reacted under reflux for 3 hours.

90 mg of anhydrous potassium carbonate is added to the reaction mixture, and the mixture is reacted under reflux for 4 hours. The organic layer was dried, concentrated and purified by silica gel thin layer chromatography to give 89 mg of N- (1,1,3-trimethyl-2-oxa-4-indanyl) -2,4-dimethylthiazole-5-carboxamide. To obtain.

Some representative compounds of the invention that can be obtained by this method are shown in Table 1.

TABLE 1

Compound represented by the following formula

Synthesis Example 6 Synthesis of Compound (29) by Method (B)

160 mg of (3S) -1,1,3-trimethyl-2-oxa-4-aminoindan and 79 mg of pyridine dissolved in 10 ml of tetrahydrophorfuran and 4-chloro-1,3-dimethyl dissolved in 4 ml of petrihirobutane. A 178 mg solution of pyrazole-4-carbonyl chloride is added dropwise with stirring at an internal temperature of 5 ° C. or lower under ice cooling, followed by overnight at room temperature. Extract with water and chloroform. The organic layer is washed with 1% hydrochloric acid, dried and concentrated. The residue was purified by silica gel thin layer chromatography to give N-[(3S) -1,1,3-trimethyl-2-oxa-4-indinyl) -5-chloro-1,3-dimethylpyrazole-4-car 262 mg (yield 67%) of copyamide are obtained.

Synthesis Example 7 Synthesis of Compound (29) by Method (D)

N- (1,1,3-trimethyl-2-oxa-4-indanyl) -5-chloro-1,3-dimethylpyrazole-4-carboxamide was added to "Sumipac OA" -4100 optically active column [ Eluent; Hexane: 1,2-dichloroethane: ethanol = 500: 150: 1.5]. Preferred ^N -[(3S) -1,1,3-trimethyl-2-oxa-4-indanyl] -5-chloro-1,3-dimethylpyrazole-4-carboxamide elutes as forward peak ( Yield: 38%)

Compound (29) of the present invention obtained by the above synthesis example exhibits the following properties:

Melting Point 169.1 ℃

t16 = -74.3 ° (CHCl ₃ , c 1.0)

The manufacturing method of substituted 4-amino- 2-oxane group represented by Formula (IV) is demonstrated below.

Reference Example 1

α, α-dimethyl-2-hydroxymethyl-3-acetaminobenzyl alcohol synthesis

To a mixture of 9.5 g of metal magnesium and 60 ml of diethyl ether, a 56 g solution of methyl iodide dissolved in 120 ml of diethyl ether was slowly added with stirring. The mixed solution is heated and cooled under reduced pressure for 15 minutes. The methyl magnesium iodide solution dissolved in the ether thus prepared was slowly added to 7.5 g of 4-acetaminophthalide dissolved in 120 ml of tetrahydrofuran by stirring at an internal temperature of 10 ° C. or lower, and then stirred overnight at room temperature. do. After the reaction was completed, the reaction mixture was poured into an aqueous ammonium chloride solution (saturated) under ice cooling and extracted twice with 400 ml of ethyl acetate. The combined extracts are dried and concentrated to yield an oily substance. The oily substance was purified by silica gel column chromatography to obtain 7.2 g of α, α-dimethyl-2-hydroxymethyl-3-acetaminobenzyl alcohol as a white crystalline form. Melting Point 137.9 ℃

¹ H-NHR (CDC1 ₃ ) δppm

1.6 (6H, s), 2.1 (3H, s), 3.7 (2H, br s), 5.0 (2H, s), 7.2-7.8 (3H, m), 8.7 (1H, br s)

Reference Example 2

3,3-dimethyl-7-acetaminophthalide synthesis

A solution of 7.2 g of α, α-dimethyl-2-hydroxymethyl-3-acetaminobenzyl alcohol dissolved in 300 ml of chloroform was added to 28 g of active manganese dioxide and the mixture was reacted for 6 meals under reflux. After the reaction is complete, the reaction mixture is left to cool and filtered in a glass filter with a celite bed. The residue is washed with 100 ml of chloroform. The filtrate and wash solution are combined and concentrated to yield an oily substance. The oily substance is purified by silica gel column chromatography to obtain 4,4 g of 3,3-dimethyl-7-acetaminophthalide as a white crystalline form. Melting Point 124.1 ℃

¹ H-NMRδppm

1.6 (6H, s), 2.2 (3H, s), 7.0 (1H, d, J = 8.0 Hz), 7.6 (1H, t, J = 8.0 Hz), 8.5 (1H, d, J = 8.0 Hz), 9.7 (1H, broad singlet)

Reference Example 3

1,1,3-trimethyl-3-hydroxy-2-oxa-4-acetaminoindan synthesis

To a 4.4 g solution of 3,3-dimethyl-7-acetaminophthalide dissolved in 80 ml of tetrahydrobutane, 43 ml of a methyllithium solution (1.4M) dissolved in ether was added dropwise at -20 ° C, followed by stirring for 20 minutes at the same temperature. do. After the reaction was completed, the reaction mixture was poured into an aqueous ammonium chloride solution (saturated) under ice cooling and extracted twice with 200 ml of ethyl acetate. The combined extracts were dried and concentrated to give 4.7 g of 1,1,3-trimethyl-3-hydroxy-2-oxa-4-acetaminoindan as an oily substance.

¹ H-NMRδppm

1.5 (6H, s), 1.7 (3H, s), 2.1 (3H, br s), 4.7 (1H, s), 6.85 (1H, d, J = 8.0 Hz), 7.3 (1H, t, J = 8.0 Hz), 7.9 (1H, d, J = 8.0 Hz), 8.0 (1H, s)

Reference Example 4

1,1,3-trimethyl-2-oxa-4-acetaminoindane synthesis

To a 4.7 g solution of 1,13-trimethyl-3-hydroxy-2-oxa-4-acetaminoinane dissolved in 120 ml of ethanol was added the amount of concentrated hydrochloric acid and 10% palladium carbon, and vigorously stirred for 6 hours under hydrogen atmosphere at room temperature. Stir. After the reaction is completed, the reaction mixture is filtered through a glass filter with a celite bed and the residue is washed with 60 ml of ethanol. The filtrate and washing solution are combined and 4.3 g of 1,1,3-trimethyl-2-oxa-4-acetaminoindane is obtained in the form of an oily substance.

¹ H-NMRδppm

1.4 (3H, s), 1.4 (3H, d, J = 6.0 Hz), 1.5 (3H, s), 2.1 (3H, s), 5.4 (1H, q, J = 6.0 Hz), 6.8-7.4 (3H , m), 8.1 (1H, s)

Synthesis Example 8

Synthesis of 1,1,3-trimethyl-2-oxa-4-aminophosphate

To a 4.3 g solution of 1,1,3-trimethyl-2-oxa-4-acetaminoindan dissolved in 60 ml of ethylene glycol and 30 ml of water, 11 g of potassium hydroxide was added and the mixture was heated under reflux for 6 hours under nitrogen atmosphere. After the reaction was completed, the reaction mixture was left to cool, diluted with 60 ml of water, and extracted four times with 60 ml of chloroform. The combined extracts are washed three times with water, dried and concentrated. The obtained oily substance was purified by silica gel thin layer chromatography to obtain 2.0 g of 1,1,3-trimethyl-2-oxa-4-aminoindan as a white crystalline form. Melting Point 75.5 ℃

¹ H-NMRδppm

1.4 (3H, s), 1.5 (3H, d, J-6.0 Hz), 1.5 (3H, s), 3.6 (2H, br s), 5.25 (1H, q, J = 6.0 Hz), 6.2-6.7 ( 2H, m), 7.1 (1H, dd, J = 6.0 Hz each)

Synthesis Example 9

1,1-dimethyl-3-ethyl-2-oxa-4-aminoindane is obtained by a method similar to Synthesis Example 6.

¹ H-NMRδppm

1.0 (3H, t, J = 6.0 Hz), 1.45 (3H, s), 1.55 (3H, s), 1.4-2.1 (2H, m), 3.5 (2H, br s,), 5.15 (1H, dd, J = 6.0 Hz, 4.0 Hz), 6.45 (2H, br d), 7.0 (1H, dd, J = 8.0 Hz, J = 6.0 Hz)

The semester is a formulation example, and the compounds of the present invention used herein are based on the weight given and indicated by the numbers given in Table 1 and the synthesis examples.

Formulation Example 1

50 parts of each of the compounds (1) to (29) of the present invention, 3 parts of calcium lignosulfonate, 2 parts of sodium lauryl sulfate and 45 parts of synthetic hydrated silicon dioxide were thoroughly ground and mixed to obtain 50% of the active ingredient concentration. Obtaining wet powder containing

Formulation Example 2

Emulsion concentrate having 10% of active ingredient concentration by thoroughly mixing 10 parts of compounds (1) to (29) of the present invention, 14 parts of polyoxyethylene styrylphenyl ether, 6 parts of calcium dodecylbenzenesulfonate and 70 parts of xylene To obtain.

Formulation Example 3

2 parts of the compounds (1) to (29) of the present invention, 1 part of synthetic hydrated silicon dioxide, 2 parts of calcium lignosulfonate, 30 parts of bentonite, and 65 parts of kaolin clay were thoroughly pulverized and kneaded well with water and then granulated. And dry to obtain granules having an active ingredient concentration of 2%.

Formulation Example 4

25 parts of compounds (1) to (29) of the present invention, 3 parts of polyoxyethylene sorbitan monooleate, 3 parts of CMC, and 69 parts of water were mixed and wet-pulverized to obtain a particle size of 5 microns or less, and an active ingredient concentration of 25 A suspension with% is obtained.

Formulation Example 5

In the present invention, 2 parts of compounds (1) to (29), 66 parts of kaolin clay and 10 parts of talc are completely ground and mixed to obtain a powder having an active ingredient concentration of 2%.

Formulation Example 6

10 parts of compounds (1) to (29) of the present invention, 1 part of polyoxy ethylene styryl phenyl ether, and 89 parts of water are mixed to obtain an aggregate having 10% of the active ingredient concentration.

The compound of the present invention shows the effect of the fungicide as an active ingredient in the following test example. The compound of the present invention used is indicated by the compound number given in Table 1 and Synthesis Example, and the compound used as a control indicates the compound given in Table 2.

TABLE 2

Determine the disease state of the test plant, ie the degree of fungus and the area of infection of the stem and stem, and the state of the disease by measuring the following six indexes 0,1,2,3,4 and 5 do.

5... No area of infection and fungus.

4… Areas of infection and fungi are observed in about 10% of the leaves and stems.

3... Infection areas and fungi are observed in approximately 30% of the leaves and stems.

2… Infection areas and fungi are observed in approximately 50% of the leaves and stems.

One… Areas of infection and fungi are observed in approximately 70% of the leaves and stems.

0… Over 70% of areas of infection and fungi are observed, and changes in disease status are not recognized when the compounds are used.

The measurements apply to all of the following tests.

Test Example 1 Effect of preventing eradication against the foliar plaque of rice plant (Lytononia solani)

Fill a plastic pot with sandy loam, plant rice (variety: Gingki No. 33), and cultivate in a greenhouse for 20 days for 20 days to grow into plants of 4-5 days. The test compound is prepared in emulsion concentrate according to Formulation Example 2, diluted with water to a given concentration.

The plant is leaf-sprayed so that it is completely deposited on one surface. After 4 hours from spraying, the plants are inoculated with agar pieces containing liqanthoniasolani. After inoculation, the plants are grown at 28 ° C. for 4 days under very humid conditions and the inhibitory effect is observed. The results are shown in Table 3.

TABLE 3

Test Example 2 Systematic Fighting Effect Test of Rice Leaf Death Disease (Lygitonia solani)

Fill a 130 ml plastic pot with sandy loam, sow rice (variety: Gingki 33), and cultivate in a greenhouse for 3 weeks to grow into plants of 4-5 days. The test compound is formulated in wet powder according to 1 into the formulation, diluted with water and sprayed in the soil in a given amount. After spraying, the plants were grown in greenhouses for 7 days and inoculated with agar pieces containing lizartonia solani. After inoculation, plants are grown at 28 ° C. for 4 days under very humid conditions and the inhibitory effect is measured. The results are shown in Table 4.

TABLE 4

Test Example 3 Test for eradication effect of southern coriander (Cortisium Rolfsey)

Fill a 250 ml plastic pot with well-mixed sandy loam with a pre-cultivated Cortium Rolf Seed in a bran batch and seed the Gangnam beans. Test compounds are formulated into wet powders according to Formulation Example 1 and diluted with water. A given amount of test compound is sprayed onto the soil. After spraying, cultivate in the greenhouse for 3 weeks and test the inhibitory effect by observing the degree of disease of the stem near the soil surface. The results are shown in Table 5.

TABLE 5

Test Example 4 Effect of Treatment Eradication on Brown Rust Disease (Puccinia Recondita)

Fill the sandy loam with a plastic pot, sow wheat (variety: Norin 73), grow in a greenhouse for 10 days, become a 2-3-day plant, and inoculate it with spuccinia of Puccinia recondita. After inoculation, the plants are grown at 23 ° C. for 1 day under very humid conditions, and the plants are prepared as emulsified concentrates according to Formula 2 and diluted with water to leaf-inject the test compound made at a given concentration to completely dissolve the compound on the leaf surface. To be deposited. After spraying, the plants were grown at 23 ° C. for 7 days under illumination and the inhibitory effect was observed. The results are shown in Table 6.

TABLE 6

Claims (14)

Substituted carboxylic acid derivatives of the following formula (I)

In the formula, R ₁ represents methyl or ethyl group, A is

R ₂ represents a methyl, ethyl or trifluoromethyl group, R ₃ represents a methyl group or a halogen or a hydrogen atom, R ₄ represents a fluorine or a hydrogen atom, R ⁵ represents a methyl, nitro or trifluoromethyl group or A halogen atom, Z represents a = CH- group or an N atom, R ₆ represents a methyl, ethyl or trifluoromethyl group, and R ₇ represents an amino or methyl group or a chlorine atom. Substituted carboxylic acid derivatives of the following formula (I ')

In the formula, R ₁ represents a methyl or ethyl group, R ₂ represents a methyl, ethyl or trifluoromethyl group, and R ₃ represents a methyl group or a halogen or hydrogen atom. Substituted carboxylic acid derivatives of the following formula

In the formula, R ₈ represents a methyl or trifluoromethyl group, and R ₉ represents a halogen atom. The substituted carboxylic acid derivative of claim 3 wherein

The substituted carboxylic acid derivative of claim 3 wherein

The substituted carboxylic acid derivative of claim 3 wherein

Substituted carboxylic acid derivatives of the following formula (II)

In the formula, R ₁ represents a methyl or ethyl group, R ₂ represents a methyl, ethyl or trifluoromethyl group, and R ₃ represents a methyl group or a halogen or hydrogen atom. Substituted 4-amino-2-oxane groups of formula (IV)

In the formula, R ₁ represents methyl or ethyl group. Preparation of the substituted carboxylic acid derivative of the following formula (I) characterized by reacting the substituted carboxylic acid of the following formula (III) or its reactive derivative with the substituted 4-amino-2-oxane group of the following formula (IV) Way.

A-COOH... (III)

In the formula, R ₁ represents methyl or ethyl group, A is

R ₂ represents methyl, ethyl or trifluoromethyl group, R ₃ represents methyl group or halogen or hydrogen atom, R ₄ represents fluorine or hydrogen atom, R ₅ represents methyl, nitro or trifluoromethyl group Or a halogen atom, Z represents a = CH- group or an N atom, R ₆ represents a methyl, ethyl or trifluoromethyl group, and R ₇ represents an amino or methyl group or a chlorine atom. Preparation of the substituted carboxylic acid derivative of the following formula (II) characterized by reacting the substituted carboxylic acid of the following formula (V) or a reactive derivative thereof with the substituted 4-amino-2-hexanesine group of the following formula (VI) Way.

In the formula, R ₁ represents methyl or ethyl group, R ₂ represents methyl, ethyl or trifluoromethyl group, and R ₃ represents methyl group or halogen or hydrogen atom. A method for producing a substituted carboxylic acid derivative of formula (VII), wherein the substituted 4-amino-2-oxadan derivative of formula (VIII) is reacted with a thioamide derivative of formula (IX).

In the formula, R ₁ represents a methyl or ethyl group, R ₆ represents a methyl, ethyl or trifluoromethyl group, and R ₁₀ represents an amino or methyl group. A process for producing a substituted carboxylic acid derivative of formula (II), wherein the substituted carboxylic acid derivative of formula (I ′) is transferred to an optically active column.

In the formula, R ₁ represents methyl or ethyl group, R ₂ represents methyl, ethyl or trifluoromethyl group, and R ₃ represents methyl group or halogen or hydrogen atom. An agricultural or horticultural fungicide comprising as an active ingredient a substituted carboxylic acid derivative of formula (I) together with an inert carrier.

In the formula, R ₁ represents methyl or ethyl group, A is

R ₂ represents methyl, ethyl or trifluoromethyl group, R ₃ represents methyl group or halogen or hydrogen atom, R ₄ represents fluorine or hydrogen atom, R ₅ represents methyl, nitro or trifluoromethyl group or A halogen atom, Z represents a = CH- group or an N atom, R ₆ represents a methyl, ethyl or trifluoromethyl group, and R ₇ represents an amino or methyl group or a chlorine atom. Agricultural or horticultural fungicides containing a substituted carboxylic acid derivative of formula (II)

In the formula, R ₁ represents methyl or ethyl group, R ₂ represents methyl or trifluoromethyl group, and R ₃ represents methyl group or halogen or hydrogen atom.