KR19990080492A - Novel thiazoleoxyiminoacetamide derivatives - Google Patents

Abstract

The present invention relates to a novel thiazole oxyiminoacetamide derivative useful as an agricultural horticultural fungicide, wherein the thiazole oxyiminoacetamide derivative of the general formula (I) has a wide range of bactericidal effects against plant pathogens including resistant bacteria. It is excellent in preventing and treating as well as penetrating effect, and the fungicide composition containing an effective amount of the compound of the present invention as an active ingredient can be used against a wide range of plant pathogens with other ingredients.

Where

R ₁ is a C ₁ -C ₃ alkyl group, 1 to 3 chloro or fluoro-, or C _1-3 alkyl or alkoxy-substituted or unsubstituted phenyl groups, R ₄ NH or R ₅ CONH, wherein R ₄ is Hydrogen, allyl, or 1 to 3 chloro or fluoro-, or C _1-3 alkyl or alkoxy-substituted or unsubstituted phenyl groups, R ₅ is a C ₁ -C ₃ alkyl group, or 1 to 3 chloro or fluoro _Rho- , or C _1-3 alkyl or alkoxy-substituted or unsubstituted phenyl group;

R ₂ is hydrogen, a C ₁ -C ₃ alkyl group, a C ₁ -C ₃ alkylthio- or alkylsulphone-substituted alkyl group, or a benzyl group;

R ₃ is a C ₁ -C ₅ alkyl group.

Description

Novel thiazoleoxyiminoacetamide derivatives

The present invention relates to a novel thiazole oxyiminoacetamide derivative, which is useful as an agricultural horticultural fungicide, and specifically has a new framework structure different from existing acetimide derivatives, and has a wide range of bactericidal effects against plant pathogens including resistant bacteria. It relates to a thiazole oxyiminoacetamide derivative having.

Looking at the recent development of pesticides in the world, the development of low dose, high selectivity, low toxicity and low pollution pesticides is mainstream due to concerns about toxicity to the human body or organism and pollution to the environment. Metals, organophosphorus compounds and the like show stagnation and reduction, while penetrant transition fungicides such as azoles and benzenoids continue to grow. However, with the use of a large amount of these fungicides, resistant bacteria which are resistant to them are also rapidly expressed. Therefore, in order to reduce the expression of resistant bacteria, prevention and treatment as well as the penetration effect due to the derivation of a fungicide having a new mechanism of action are required. There is an urgent need for the development of effective drugs.

As a result, the present inventors conducted a thorough study and found a novel compound having a new skeletal structure having a wide range of bactericidal effects against plant pathogens including resistant bacteria and completing the present invention.

It is an object of the present invention to provide novel thiazoleoxyiminoacetamide derivatives having a wide range of bactericidal effects against plant pathogens including resistant bacteria.

In order to achieve the above object, the present invention provides a novel thiazoleoxyiminoacetamide derivative of the general formula (I):

Formula 1

Where

R ₁ is a C ₁ -C ₃ alkyl group, 1 to 3 chloro or fluoro-, or C _1-3 alkyl or alkoxy-substituted or unsubstituted phenyl groups, R ₄ NH or R ₅ CONH, wherein R ₄ is Hydrogen, allyl, or 1 to 3 chloro or fluoro-, or C _1-3 alkyl or alkoxy-substituted or unsubstituted phenyl groups, R ₅ is a C ₁ -C ₃ alkyl group, or 1 to 3 chloro or fluoro _Rho- , or C _1-3 alkyl or alkoxy-substituted or unsubstituted phenyl group;

R ₂ is hydrogen, a C ₁ -C ₃ alkyl group, a C ₁ -C ₃ alkylthio- or alkylsulphone-substituted alkyl group, or a benzyl group;

R ₃ is a C ₁ -C ₅ alkyl group.

Hereinafter, the present invention will be described in more detail.

The thiazole oxyiminoacetamide derivatives of the general formula (I) of the present invention are thiazole oxyiminoacetic acid chloride of the general formula (II) and the amino acid ester of the general formula (III) It can be prepared by the reaction of:

Wherein R ₁ , R ₂ and R ₃ are as defined above.

In the above reaction, the compound of the general formula (III) is used in the amount of 1 to 1.2 equivalents based on the compound of the general formula (II), and includes trialkylamines such as triethylamine as the acid remover; And 1 to 2 equivalents of inorganic salts such as sodium hydrogen carbonate, potassium carbonate and caustic soda, based on the compound of formula (II), and 2 to 4 when the amino acid ester of formula (III) is an acid addition salt. It can be reacted by adding an equivalent.

In addition, examples of the solvent used in the reaction include ethers such as diethyl ether, diisopropyl ether, tetrahydrofuran, dioxane and diphenyl ether; And halogenated hydrocarbons such as dichloroethane, chloroform and carbon tetrachloride. These may be used alone or in combination of one or more.

In addition, the reaction temperature is -30 to 50 ℃, the reaction time depends on the reaction temperature, but usually 1 to 24 hours is preferred.

Immediately after completion of the reaction, the solvent is distilled off or water is added to the reaction mixture, followed by extraction with an organic solvent insoluble in water such as dichloroethane, dichloromethane, chloroform and ethyl acetate. A crude product of oxyiminoacetamide derivative is obtained. This crude product is an alcohol solvent such as methanol and ethanol; Esters of organic acids such as ethyl acetate and methyl acetate; Hydrocarbons such as pentane and hexane; Ethers such as ethyl ether and tetrahydrofuran; And recrystallized from a solvent selected from the mixtures thereof, or can be easily separated and purified by column chromatography.

Meanwhile, according to the present invention, the thiazoleoxyiminoacetic acid chloride of the general formula (II) is 4-halo-2-methoxyimino-3 prepared by a known method (see European Patent Nos. 246603 and 416657). The oxobutanoic acid ester derivative (compound of formula (IV)) as a starting material can be prepared as in Scheme 2 below.

Where

X is Cl or Br;

R ₁ ′ is a C ₁ -C ₃ alkyl group, allyl, 1 to 3 chloro or fluoro-, or C _1-3 alkyl or alkoxy-substituted or unsubstituted phenyl group or R ₄ NH, wherein R ₄ is hydrogen Except as defined above);

R ₁ and R ₅ are as defined above.

Specifically, when R ₁ is R ₁ ′, 4-halo-2-methoxyimino-3-oxobutanoic acid t-butyl ester derivative of the general formula (IV) and thioamide of the general formula (V) Or reacting a thiourea derivative to produce 2- (2-substitutedthiazol-4-yl) -2-methoxyiminoacetic acid t-butyl ester of the general formula (VI-1) (step a), R ₁ When R ₅ CONH (wherein R ₅ is as defined above), R ₁ is NH ₂ (ie when R ₄ is hydrogen), i.e. 2- (2- Aminothiazol-4-yl) -2-methoxyiminoacetic acid t-butyl ester is reacted with an acyl chloride of general formula (VII) to form 2- (2-substituted thiazole-4- of general formula (VI-3) 2-) 2- (2-substituted thiazole) of formula (VIII) prepared by preparing 2-methoxyiminoacetic acid t-butyl ester (step b), followed by acid hydrolysis of this product (step c). Chloroylation of -4-yl) -2-methoxyiminoacetic acid d) it is possible to obtain the 2- (2-substituted thiazol-4-yl) -2-methoxy toksiyi diamino acid chloride of the general formula (II) by.

In Scheme 2, examples of the solvent used in step a include ethers such as diethyl ether, diisopropyl ether, tetrahydrofuran, dioxane and diphenyl ether; Halogenated hydrocarbons such as dichloroethane, chloroform and carbon tetrachloride; Aprotic polar solvents such as N, N-dimethylformamide, N, N-dimethylformacetamide, N-methylpyrrolidone and dimethyl sulfoxide; And alcohols such as methanol, ethanol, isopropanol and butanol. Examples of the solvent used in step b include ethers such as diethyl ether, diisopropyl ether, tetrahydrofuran, dioxane and diphenyl ether; And halogenated hydrocarbons such as dichloroethane, chloroform and carbon tetrachloride. These may be used alone or in combination of one or more.

In addition, the reaction temperature of steps a and b is -30 to 50 ℃, the reaction time depends on the reaction temperature, but usually 1 to 24 hours is preferred. Also, for the compound of formula (IV), the compound of formula (V) is 1 to 1.5 equivalents when the compound of formula (VI-1) is prepared, and 1 to 1.5 equivalents when the compound of formula (VI-2) is prepared. 3 equivalents are used, and in the preparation of the compound of formula (VI-3), 1 to 1.5 equivalents of the compound of formula (VII) are used relative to the compound of formula (VI-2). When R ₁ is R ₄ NH or R ₅ CONH, the compounds of the general formulas (VI-1) and (VI-2) become acid addition salts. As the acid is produced, trialkylamines such as triethylamine; And inorganic salts such as sodium hydrogen carbonate, potassium carbonate and caustic soda, for the compounds of the general formula (VI-1) and (VI-2), based on the compound of the general formula (IV), In the case of the compound of 3), it is added and reacted as 1-2 equivalent acid scavenger based on the compound of the general formula (VI-2).

After distilling the solvent of step a or b and purifying the crude product in the same manner as in Scheme 1 to obtain the compound of formula (VI-1), (VI-2) or (VI-3) Inorganic acids such as hydrochloric acid and sulfuric acid; And acid hydrolysis with organic acids such as acetic acid and trifluoroacetic acid to prepare the compound of formula (VIII) (step c), followed by inorganic chlorinating agents such as thionyl chloride and phosphorus pentachloride; And chlorolation with an organic chlorinating agent such as oxalyl chloride to prepare the compound of formula (II) (step d).

As a solvent used in steps c and d, ethers such as diethyl ether, diisopropyl ether, tetrahydrofuran, dioxane and diphenyl ether; And halogenated hydrocarbons such as dichloroethane, chloroform and carbon tetrachloride. These may be used alone or in combination of one or more.

In addition, the reaction temperature of steps c and d is -30 to 30 ℃, the reaction time depends on the reaction temperature, but usually 1 to 24 hours is preferred.

The thiazoleoxyiminoacetamide derivatives of the general formula (I) according to the present invention, prepared by the above method, exhibit high therapeutic and prophylactic antibacterial properties against a broad spectrum of plant pathogens. Examples of these bacteria include Piricularia oryzae of rice, Rhizoctonia solani of rice, Botrytis cinerea of cucumber, Sphaerotheca fuliginea of cucumber, and Pseudoperonospora cube of cucumber. ), downy mildew of grape fungus (Plasmopora viticola), Station pathogens of tomato (Phytophthora infestans), kkaessi pattern germs (Cochliobolus miyabeanus), brown pattern germs of peanut (Cercopora arachidicola), powdery mildew fungus of barley (Erysiphe graminis), wheat red rust Puccinia recondita and Puccinis graminis of wheat, which show excellent bactericidal effects against rice blast and barley powdery mildew.

According to the present invention, the compound of the general formula (I) of the present invention is used as an active ingredient in an amount of about 0.01 to 90% by weight based on the weight of the composition, so that the solid or liquid carrier, surfactant, diluent, electrodeposition agent, synergist, adhesive And mixed with a suitable adjuvant such as a dispersant to formulate agricultural fungicide compositions.

Solid carriers usable in formulating compositions in the present invention include talc, clay, bentonite, pyrophyllite, kaolin, diatomaceous earth, silica and the like, and liquid carriers include water, methanol, ethanol, acetone, dimethylformamide, ether , Benzene, xylene, toluene and naphthalene, and the like, and nonionic surfactants such as polyoxyethylene alkylphenylether and polyoxyethylene fatty acid esters and anionic surfactants such as alkylbenzenesulfonates, Lignin sulfonate, dinaphthyl methanesulfonate), and the like. Moreover, polyvinyl alcohol, CMC, gum arabic, etc. can be used as an adhesive agent.

According to the present invention, the disinfectant composition containing the compound of formula (I) of the present invention may be prepared as a powder or a hydrate powder, granules, emulsion concentrate, suspension, fumigant, gas and paste, etc. It is used to sterilize seedlings and seeds. For example, the compound of formula (I) may be uniformly dissolved in a hydrocarbon, acetone or alcohol with a suitable surfactant to prepare an emulsion concentrate or solution, or mixed with an inorganic powder and a suitable surfactant, Hydrated powder can be prepared by pulverizing and homogenizing to make a fine powder. The composition thus prepared may be diluted with water to a desired concentration, or mixed with inorganic powder, crushed and mixed homogeneously, and used as dust.

In addition, according to the present invention, the disinfectant composition diluted to contain an effective amount of the compound of the general formula (I) of the present invention may be used for other agricultural chemicals such as insecticides, fungicides, herbicides, plant growth regulators and mites, and nutritional substances. And the like can be used in combination.

Examples of thiazoleoxyiminoacetamide derivatives of general formula (I) according to the present invention are shown in Table 1 below:

Compound number R ₁ R ₂ R ₃ Melting Point (℃) 1-1 CH ₃ CH ₂ C ₆ H ₅ tC ₄ H ₉ Liquid 1-2 CH ₃ CH (CH ₃ ) ₂ tC ₄ H ₉ 79-81 1-3 CH ₃ CH ₂ CH ₂ SCH ₃ CH ₃ 90-91 1-4 CH ₃ CH ₂ CH ₂ SCH ₃ CH ₂ CH ₃ 62-63 1-5 CH ₃ CH (CH ₃ ) ₂ CH ₂ CH ₃ Liquid 1-6 4-CH ₃ OC ₆ H ₄ CONH CH ₃ tC ₄ H ₉ 178-180 (decomposition) 1-7 4-CH ₃ OC ₆ H ₄ CONH H tC ₄ H ₉ 173-174 (decomposition) 1-8 4-CH ₃ OC ₆ H ₄ CONH CH (CH ₃ ) ₂ tC ₄ H ₉ 145-146 1-9 4-CH ₃ OC ₆ H ₄ CONH CH ₂ CH ₂ SO ₂ CH ₃ tC ₄ H ₉ - 1-10 4-CH ₃ OC ₆ H ₄ CONH CH ₂ CH ₂ SCH ₃ CH ₃ 70-71 1-11 4-CH ₃ OC ₆ H ₄ CONH CH ₂ CH ₂ SCH ₃ CH ₂ CH ₃ Liquid 1-12 4-CH ₃ OC ₆ H ₄ CONH CH (CH ₃ ) ₂ CH ₂ CH ₃ Liquid 1-13 4-CH ₃ OC ₆ H ₄ CONH CH ₂ CH (CH ₃ ) ₂ tC ₄ H ₉ 168-170 1-14 C ₆ H ₅ H tC ₄ H ₉ Liquid 1-15 C ₆ H ₅ CH (CH ₃ ) ₂ tC ₄ H ₉ Liquid 1-16 C ₆ H ₅ CH ₂ CH ₂ SCH ₃ CH ₃ - 1-17 C ₆ H ₅ CH ₂ CH ₂ SCH ₃ CH ₂ CH ₃ - 1-18 C ₆ H ₅ CH ₂ C ₆ H ₅ tC ₄ H ₉ Liquid 1-19 C ₆ H ₅ CH ₂ CH (CH ₃ ) ₂ tC ₄ H ₉ Liquid 1-20 C ₆ H ₅ CH ₂ CH ₂ SO ₂ CH ₃ tC ₄ H ₉ Liquid 1-21 C ₆ H ₅ CH ₂ SO ₂ CH ₂ C ₆ H ₅ tC ₄ H ₉ 105-107 1-22 CH ₂ = CHCH ₂ NH CH ₃ tC ₄ H ₉ Liquid 1-23 CH ₂ = CHCH ₂ NH H tC ₄ H ₉ - 1-24 CH ₂ = CHCH ₂ NH CH (CH ₃ ) ₂ tC ₄ H ₉ Liquid 1-25 CH ₂ = CHCH ₂ NH CH ₂ C ₆ H ₅ tC ₄ H ₉ Liquid 1-26 2-ClC ₆ H ₄ NH CH (CH ₃ ) ₂ tC ₄ H ₉ Liquid 1-27 2-ClC ₆ H ₄ NH H tC ₄ H ₉ 120-121 1-28 C ₆ H ₅ NH CH ₃ tC ₄ H ₉ Liquid 1-29 C ₆ H ₅ NH CH ₂ CH ₂ SCH ₃ CH ₂ CH ₃ Liquid 1-30 3,5-Cl ₂ C ₆ H ₃ CONH CH ₂ CH ₂ SO ₂ CH ₃ tC ₄ H ₉ 184-186 1-31 3,5-Cl ₂ C ₆ H ₃ CONH CH ₂ CH (CH ₃ ) ₂ tC ₄ H ₉ 144-145 1-32 3,5-Cl ₂ C ₆ H ₃ CONH CH ₂ C ₆ H ₅ tC ₄ H ₉ 130-131 1-33 4-ClC ₆ H ₄ CONH H tC ₄ H ₉ 208-209 1-34 4-ClC ₆ H ₄ CONH CH (CH ₃ ) ₂ tC ₄ H ₉ 169-170 1-35 4-ClC ₆ H ₄ CONH CH (CH ₃ ) ₂ CH ₂ CH ₃ 142-143 1-36 CH ₃ CONH CH ₃ tC ₄ H ₉ 71-72 1-37 CH ₃ CONH CH ₂ CH ₂ SCH ₃ CH ₂ CH ₃ - 1-38 3-CF ₃ C ₆ H ₄ CONH CH (CH ₃ ) ₂ CH ₂ CH ₃ 130-132 1-39 3-CF ₃ C ₆ H ₄ CONH CH ₂ C ₆ H ₅ tC ₄ H ₉ Liquid 1-40 3-CF ₃ C ₆ H ₄ CONH H tC ₄ H ₉ 129-131 (Disassembly)

Hereinafter, the present invention will be described in more detail based on the following Preparation Examples and Examples. However, the following examples are not intended to limit the invention only.

Preparation Example 1

2- (2-aminothiazol-4-yl) -2-methoxyiminoacetic acid t-butyl ester (compound of formula (VI-2))

4-bromo-2-methoxyimino-3-oxobutanoic acid t-butyl ester (compound of formula (IV)) (42.9 g, 0.153 mol) followed by sodium hydrogencarbonate (12.9 g, 0.153 mol) After dissolving in 190 ml of water and 110 ml of tetrahydrofuran, thiourea (compound of formula (V)) (25.2 g, 0.332 mol) dissolved in 45 ml of water and 45 ml of tetrahydrofuran was added dropwise at room temperature for 1 hour, followed by 1 The reaction was carried out for a time. After completion of the reaction, 200 ml of water was added, extracted with 50 ml of ethyl acetate four times, dried over magnesium sulfate, and distilled under reduced pressure. The residue was purified by column chromatography to give 37.5 g of the desired product in 95.3% yield.

¹ H NMR (CDCl ₃ ): δ 7.9 (s, 1H) 5.1 (s, 5H) 4.1 (s, 3H) 1.5 (s, 9H)

Preparation Example 2

2- (2-allylaminothiazol-4-yl) -2-methoxyiminoacetic acid t-butyl ester (compound of formula (VI-1))

4-bromo-2-methoxyimino-3-oxobutanoic acid t-butyl ester (compound of formula (IV)) (19.6 g, 0.07 mol) and 1-allyl-2-thiourea (formula ( The same reaction as in Preparation Example 1 was carried out from the compound V) (8.12 g, 0.07 mol) to give 22.05 g of the desired product in 92% yield.

¹ H NMR (CDCl ₃ ): δ 6.7 (s, 1H) 6.2 (br.s, 1H) 5.9 (m, 1H) 5.2 (m, 2H) 4.0 (s, 3H) 3.9 (br.t, 3H) 1.5 (s, 9H)

Preparation Example 3

2- [2- (2-chlorophenylamino) thiazol-4-yl] -2-methoxyiminoacetic acid t-butyl ester (compound of formula (VI-1))

4-bromo-2-methoxyimino-3-oxobutanoic acid t-butyl ester (compound of formula (IV)) (16.0 g, 0.057 mol) and 1- (2-chlorophenyl) -2-thio The same reaction as in Preparation Example 1 was carried out from urea (compound of formula (V)) (10.6 g, 0.057 mol) to obtain 9.1 g of the desired product in 43% yield.

¹ H NMR (CDCl ₃ ): δ 8.1-6.9 (m, 6H) 4.1 (s, 3H) 3.87 (br.s, 3H) 1.6 (s, 9H)

Preparation Example 4

2- [2- (2-chlorophenyl) thiazol-4-yl] -2-methoxyiminoacetic acid t-butyl ester (compound of formula (VI-1))

4-bromo-2-methoxyimino-3-oxobutanoic acid t-butyl ester (compound of formula (IV)) (20.44 g, 0.073 mol) was dissolved in 90 ml of water and 110 ml of tetrahydrofuran, and then Thiobenzamide (compound of formula (V)) (10.01 g, 0.073 mol) dissolved in 15 ml and 15 ml of tetrahydrofuran was added dropwise at room temperature for 1 hour and reacted at the same temperature for 1.5 hours. After the same treatment as in Preparation Example 1 to give the desired product 22.1g in 95% yield.

¹ H NMR (CDCl ₃ ): δ 8.13-7.26 (m, 6H) 3.96 (s, 3H) 1.53 (s, 9H)

Preparation Example 5

2- [2- (4-chlorobenzoylamino) thiazol-4-yl] -2-methoxyiminoacetic acid t-butyl ester (compound of formula (VI-3))

To 2- (2-aminothiazol-4-yl) -2-methoxyiminoacetic acid t-butyl ester (compound of general formula (VI-2)) obtained in Preparation Example 1 (3.1 g, 0.012 mol) After adding 50 ml of dry dichloromethane and 2 ml (0.0144 mol) of triethylamine, 4-chlorobenzoyl chloride (compound of formula (VII)) (2.1 g, 0.012 mol) dissolved in 10 ml of dry dichloromethane was stirred at room temperature for 30 minutes. It dripped. The mixture was reacted at the same temperature for 1 hour, dichloromethane was distilled under reduced pressure, 50 ml of water was added, extraction was carried out three times with 30 ml of ethyl acetate, dried over magnesium sulfate, and the residue was obtained by distillation under reduced pressure in a mixed solvent of hexane-ethyl acetate. Recrystallization gave 3.1 g of the desired product in a yield of 64.7%.

Melting Point (° C): 181-186 (Decomposition)

¹ H NMR (CDCl ₃ ): δ 10.1 (br.s, 1H) 7.8 (d, J = 8.7Hz, 2H) 7.5 (d, J = 8.7Hz, 2H) 3.9 (s, 3H) 1.5 (s, 9H )

Preparation Example 6

2- (2-acetylaminothiazol-4-yl) -2-methoxyiminoacetic acid t-butyl ester (compound of formula (VI-3))

2- (2-aminothiazol-4-yl) -2-methoxyiminoacetic acid t-butyl ester (compound of formula (VI-2)) obtained in Preparation Example 1 (2.57 g, 0.01 mol) and The same reaction as in Preparation Example 5 was carried out from acetylchloride (compound of formula (VII)) (0.94 g, 0.012 mol) to obtain 1.80 g of the desired product in 60% yield.

Melting Point (℃): 175-176 (Decomposition)

¹ H NMR (CDCl ₃ ): δ 10.9 (br.s, 1H) 7.2 (s, 1H) 4.0 (s, 3H) 2.2 (s, 3H) 1.9 (s, 9H)

Preparation Example 7

2- [2- (4-methoxybenzoylamino) thiazol-4-yl] -2-methoxyiminoacetic acid t-butyl ester (compound of formula (VI-3))

2- (2-aminothiazol-4-yl) -2-methoxyiminoacetic acid t-butyl ester (compound of formula (VI-2)) obtained in Preparation Example 1 (2.57 g, 0.01 mol) and The same reaction as in Preparation Example 5 was carried out from 4-methoxybenzoyl chloride (compound of formula (VII)) (1.88 g, 0.011 mol) to obtain 2.58 g of the desired product in 66% yield.

Melting Point (℃): 175-176 (Decomposition)

¹ H NMR (CDCl ₃ ): δ 10.0 (br.s, 1H) 8.9 (d, J = 8.5 Hz, 2H) 7.0 (d, J = 8.5 Hz, 2H) 4.0 (s, 3H) 3.9 (s, 3H ) 1.5 (s, 9H)

Preparation Example 8

2- [2- (3,5-dichlorobenzoylamino) thiazol-4-yl] -2-methoxyiminoacetic acid t-butyl ester (compound of formula (VI-3))

2- (2-aminothiazol-4-yl) -2-methoxyiminoacetic acid t-butyl ester (compound of formula (VI-2)) obtained in Preparation Example 1 (2.57 g, 0.01 mol) and The same reaction as in Preparation Example 5 was carried out from 3,5-dichlorobenzoyl chloride (compound of formula (VII)) (2.30 g, 0.011 mol) to give 2.92 g of the desired product in 68% yield.

Melting Point (℃): 178-179 (Decomposition)

¹ H NMR (CDCl ₃ ): δ 11.3-10.9 (br.s, 1H) 7.7 (s, 2H) 7.6 (s, 1H) 7.2 (s, 1H) 3.8 (s, 3H) 1.6 (s, 9H)

Preparation Example 9

2- [2- (3-trifluoromethylbenzoylamino) thiazol-4-yl] -2-methoxyiminoacetic acid t-butyl ester (compound of formula (VI-3))

2- (2-aminothiazol-4-yl) -2-methoxyiminoacetic acid t-butyl ester (compound of formula (VI-2)) obtained in Preparation Example 1 (2.57 g, 0.01 mol) and The same reaction as in Preparation Example 5 was carried out from 3-trifluoromethylbenzoyl chloride (compound of formula (VII)) (2.29 g, 0.011 mol) to give 2.62 g of the desired product in 61% yield.

Melting Point (° C): 182-183 (Decomposition)

¹ H NMR (CDCl ₃ ): δ 10.8 (br.s, 1H) 8.2 (s, 1H) 8.1 (d, J = 7.6Hz, 1H) 7.9 (d, J = 7.6Hz, 1H) 7.7 (t, J = 7.6Hz, 1H) 7.0 (d, J = 8.3Hz, 2H) 7.2 (s, 1H) 3.8 (s, 3H) 1.6 (s, 9H)

Preparation Example 10 (General Experimental Example)

2- (2-substitutedthiazol-4-yl) -2-methoxyiminoacetic acid (compound of formula (VIII))

2- (2-substitutedthiazol-4-yl) -2-methoxyiminoacetic acid t-butyl ester (compound of formula (VI-1), (VI-2) or (VI-3)) (0.05 mol) ) Was added to 50 ml of dichloromethane and 50 ml of trifluoroacetic acid, stirred for 2 hours, acid hydrolyzed and distilled under reduced pressure at room temperature to obtain the desired crude product.

Preparation Example 11 (General Experimental Example)

2- (2-substitutedthiazol-4-yl) -2-methoxyiminoacetic acid chloride (compound of formula (II))

50 ml of ethyl ether was added to 2- (2-substituted thiazol-4-yl) -2-methoxyiminoacetic acid (compound of formula (VIII)) (0.05 mol), and oxalyl chloride (0.06 mol) was added to ethyl ether. It melt | dissolved in 20 ml and dripped. The mixture was stirred for 2 hours, subjected to chlorolation, and the solvent was evaporated under reduced pressure to obtain the desired crude product.

Example 1

2- [2- (2-methylthiazol-4-yl) -2-methoxyiminoacetylamino] -3-methylpropanoic acid t-butyl ester (Compound 1-2)

To a solution of valine t-butyl ester (compound of general formula (III)) (0.17 g, 1.0 mmol), triethylamine (0.17 ml, 1.2 mmol) and 20 ml of dry tetrahydrofuran-(2-methylthiazole- 4-yl) -2-methoxyiminoacetic acid chloride (compound of formula (II)) (0.22 g, 1.0 mmol) was dissolved in 5 ml of dry tetrahydrofuran and dripped for 30 minutes. Then, the reaction was carried out for 2 hours, and after the reaction was completed, 50 ml of water was added, extracted with 20 ml of ethyl acetate three times, dried over magnesium sulfate, and distilled under reduced pressure. After adding 50 ml of dry dichloromethane and 2 ml (0.0144 mol) of triethylamine, 4-chlorobenzoyl chloride (2.1 g, 0.012 mol) dissolved in 10 ml of dry dichloromethane was added dropwise at room temperature for 30 minutes. After reacting at the same temperature for 1 hour, dichloromethane was distilled under reduced pressure, 50 ml of water was added thereto, extracted with 30 ml of ethyl acetate three times, dried over magnesium sulfate, and the residue obtained by distillation under reduced pressure was purified by column chromatography. 0.26 g was obtained in 72% yield.

Melting Point (℃): 79-81

¹ H NMR (CDCl ₃ ): δ 7.6 (s, 1H) 6.7 (br.d, J = 9.0 Hz, 1H) 4.6 (dd, J = 9.0, 4.0 Hz, 1H) 4.1 (s, 3H) 2.7 (s , 3H) 2.3-2.2 (m, 1H) 1.4 (s, 9H) 1.1-0.8 (m, 6H)

Example 2

2- [2- (2-methylthiazol-4-yl) -2-methoxyiminoacetylamino] -4-methylthiobutanoic acid ethyl ester (Compound 1-4)

Methionine ethyl ester (compound of formula (III)) (0.17 g, 1.0 mmol) and 2- (2-methylthiazol-4-yl) -2-methoxyiminoacetic acid chloride (compound of formula (II)) (0.22 g, 1.0 mmol) was subjected to the same reaction as in Example 1 to obtain 0.27 g of the desired product in 77% yield.

Melting Point (℃): 62-63

¹ H NMR (CDCl ₃ ): δ 8.4 (br.d, J = 6.9, 1H) 8.0 (s, 1H) 4.9 (td, J = 8.9, 5.3 Hz, 1H) 4.2 (q, J = 7.5 Hz, 2H ) 4.1 (s, 3H) 2.8 (s, 3H) 2.6 (m, 2H) 2.4-2.2 (m, 2H) 2.1 (s, 3H) 1.3 (t, J = 7.5Hz, 3H)

Example 3

2- {2- [2- (4-methoxybenzoylamino) thiazol-4-yl] -2-methoxyiminoacetylamino} -4-methylpentanoic acid t-butyl ester (Compound 1-13)

Leucine t-butyl ester (compound of formula (III)) (0.19 g, 1.0 mmol) with 2- [2- (4-methoxybenzoylamino) thiazol-4-yl] -2-methoxyiminoacetic acid chloride (Compound (II)) (0.35 g, 1.0 mmol) was subjected to the same reaction as in Example 1 to obtain 0.36 g of the desired product in a yield of 65%.

Melting Point (℃): 168-170

¹ H NMR (CDCl ₃ ): δ 10.2 (br.s, 1H) 7.9 (d, J = 8.4Hz, 2H) 7.8 (s, 1H) 7.5 (d, J = 9.4Hz, 1H) 7.0 (d, J = 8.4 Hz, 2H) 4.6 (m, 1H) 4.1 (s, 3H) 3.9 (s, 3H) 1.8-1.6 (m, 3H) 1.5 (s, 9H) 1.0 (d, J = 4.4 Hz, 6H)

Example 4

2- [2- (2-phenylaminothiazol-4-yl) -2-methoxyiminoacetylamino] -3-methylpropanoic acid t-butyl ester (Compound 1-15)

Valine t-butyl ester (compound of formula (III)) (0.17 g, 1.0 mmol) with 2- (2-phenylaminothiazol-4-yl) -2-methoxyiminoacetic acid chloride (formula (II) Compound) (0.28 g, 1.0 mmol) in the same manner as in Example 1 to obtain 0.31 g of the desired product in a yield of 74%.

¹ H NMR (CDCl ₃ ): δ 8.6 (br.d, J = 7.7 Hz, 1H) 8.2 (s, 1H) 8.1-7.9 (m, 2H) 7.5-7.4 (m, 3H) 4.9-4.7 (m, 1H) 4.2 (s, 3H) 1.9-1.6 (m, 3H) 1.5 (s, 9H) 1.1-0.9 (m, 6H)

Example 5

2- [2- (2-phenylaminothiazol-4-yl) -2-methoxyiminoacetylamino] -4-methylthiobutanoic acid ethyl ester (Compound 1-17)

Methionine ethyl ester (compound of formula (III)) (0.17 g, 1.0 mmol) and 2- (2-phenylaminothiazol-4-yl) -2-methoxyiminoacetic acid chloride (compound of formula (II) (0.28 g, 1.0 mmol) in the same manner as in Example 1 to obtain 0.29 g of the desired product in 76% yield.

¹ H NMR (CDCl ₃ ): δ 8.8 (d, J = 8.4 Hz, 1H) 8.2 (s, 1H) 8.0-7.7 (m, 2H) 7.4-7.2 (m, 2H) 4.9 (m, 1H) 4.2 ( q, J = 7.4Hz, 2H) 4.1 (s, 3H) 2.6 (t, J = 7.4Hz, 2H) 2.4-2.1 (m, 2H) 2.0 (s, 3H) 1.2 (t, J = 7.4Hz, 3H )

Example 6

2- [2- (2-phenylaminothiazol-4-yl) -2-methoxyiminoacetylamino] -3-phenylpropanoic acid t-butyl ester (Compound 1-18)

Phenylalanine t-butyl ester (compound of formula (III)) (0.22 g, 1.0 mmol) with 2- (2-phenylaminothiazol-4-yl) -2-methoxyiminoacetic acid chloride (formula (II) Compound) (0.28 g, 1.0 mmol) in the same manner as in Example 1 to obtain 0.31 g of the desired product in a yield of 67%.

¹ H NMR (CDCl ₃ ): δ 8.0 (m, 2H) 7.6 (s, 1H) 7.4 (m, 3H) 7.3 (m, 5H) 7.0 (br.d, J = 8.5 Hz, 1H) 5.0 (td, J = 7.2, 8.5 Hz, 1H) 4.2 (s, 3H) 1.9-1.6 (m, 3H) 1.5 (s, 9H) 1.1-0.9 (m, 6H)

Example 7

2- [2- (2-phenylaminothiazol-4-yl) -2-methoxyiminoacetylamino] -4-methylsulfonylbutanoic acid t-butyl ester (Compound 1-20)

2-amino-4-methylsulfonyl butanoic acid t-butyl ester (compound of formula (III)) (0.23 g, 1.0 mmol) and 2- (2-phenylaminothiazol-4-yl) -2- The same reaction as in Example 1 was carried out from methoxyiminoacetic acid chloride (compound of formula (II)) (0.28 g, 1.0 mmol) to obtain 0.30 g of the desired product in 63% yield.

¹ H NMR (CDCl ₃ ): δ 7.9 (m, 2H) 7.4-7.2 (m, 2H) 7.4 (m, 3H) 7.1 (br.d, J = 6,6 Hz, 1H) 4.8 (m, 1H) 4.1 (s, 3H) 3.4-3.1 (m, 2H) 2.8 (s, 3H) 2.7-2.1 (m, 2H) 1.5 (s, 9H)

Example 8

2- [2- (2-allylaminothiazol-4-yl) -2-methoxyiminoacetylamino] -3-phenylpropanoic acid t-butyl ester (Compound 1-25)

Phenylalanine t-butyl ester (compound of formula (III)) (0.22 g, 10 mmol) and 2- (2-allylaminothiazol-4-yl) -2-methoxyiminoacetic acid chloride (formula (II) Compound) (0.26 g, 1.0 mmol) in the same manner as in Example 1 to obtain 0.33 g of the desired product in a yield of 74%.

¹ H NMR (CDCl ₃ ): δ 9.1 (d, J = 5.3, 1H) 7.5 (s, 1H) 7.2 (s, 5H) 5.9-5.7 (m, 1H) 5.6 (br.s, 1H) 5.3-5.1 (m, 2H) 4.9 (m, 1H) 4.1 (s, 3H) 3.8 (br.s, 2H) 3.3 (m, 2H) 1.4 (s, 9H)

Example 9

2- {2- [2- (2-chlorophenylamino) thiazol-4-yl] -2-methoxyiminoacetylamino} -3-methylpropanoic acid t-butyl ester (Compound 1-26)

Valine t-butyl ester (compound of formula (III)) (0.17 g, 1.0 mmol) with 2- [2- (2-chlorophenylamino) thiazol-4-yl] -2-methoxyiminoacetic acid chloride ( The same reaction as in Example 1 was carried out from the compound of formula (II)) (0.33 g, 1.0 mmol) to obtain 0.28 g of the desired product in a yield of 59%.

¹ H NMR (CDCl ₃ ): δ 8.1-8.0 (m, 1H) 7.9 (br.d, J = 9.3 Hz, 1H) 7.6 (s, 1H) 7.4-7.2 (m, 3H) 7.0-6.9 (m, 1H) 4.6 (dd, J = 9.3, 3.7 Hz, 1H) 4.1 (s, 3H) 2.4-2.2 (m, 1H) 1.5 (s, 9H) 1.1-0.9 (m, 6H)

Example 10

2- {2- [2- (2-chlorophenylamino) thiazol-4-yl] -2-methoxyiminoacetylamino} -acetic acid t-butyl ester (compound 1-27)

Glycine t-butyl ester (compound of formula (III)) (0.13 g, 1.0 mmol) with 2- [2- (2-chlorophenylamino) thiazol-4-yl] -2-methoxyiminoacetic acid chloride ( The reaction of Compound (II)) (0.33 g, 1.0 mmol) in the same manner as in Example 1 gave 0.24 g of the desired product in 57% yield.

Melting Point (℃): 120-121

¹ H NMR (CDCl ₃ ): δ 8.1-7.8 (m, 3H) 7.6 (s, 1H) 7.4-7.2 (m, 2H) 7.0 (m, 1H) 4.2-4.0 (m, 5H) 1.5 (s, 9H )

Example 11

2- {2- [2- (4-chlorobenzoylamino) thiazol-4-yl] -2-methoxyiminoacetylamino} -acetic acid t-butyl ester (compound 1-33)

Glycine t-butyl ester (compound of formula (III)) (0.13 g, 1.0 mmol) with 2- [2- (4-chlorobenzoylamino) thiazol-4-yl] -2-methoxyiminoacetic acid chloride ( The reaction was carried out in the same manner as in Example 1 from the compound of formula (II)) (0.33 g, 1.0 mmol) to give 0.26 g of the desired product in 62% yield.

Melting Point (℃): 208-209

¹ H NMR (CDCl ₃ ): δ 11.1 (br.s, 1H) 8.1 (t, J = 5.5 Hz, 1H) 7.9 (d, J = 6.8 Hz, 2H) 7.7 (s, 1H) 7.4 (d, J = 6.8Hz, 2H) 4.1 (d, J = 5.5Hz, 2H) 4.0 (s, 3H) 1.5 (s, 9H)

Example 12

2- {2- [2- (4-chlorobenzoylamino) thiazol-4-yl] -2-methoxyiminoacetylamino} -3-methylpropanoic acid t-butyl ester (Compound 1-34)

Valine t-butyl ester (compound of formula (II)) (0.17 g, 1.0 mmol) with 2- {2- [2- (4-chlorobenzoylamino) thiazol-4-yl] -2-methoxyimino The same reaction as in Example 1 was carried out from acetic chloride (compound of formula (II)) (0.33 g, 1.0 mmol) to obtain 0.31 g of the desired product in a yield of 66%.

Melting Point (℃): 169-170

¹ H NMR (CDCl ₃ ): δ 11.1 (br.s, 1H) 8.1 (t, 1H) 7.9 (d, J = 6.8Hz, 2H) 7.7 (s, 1H) 7.4 (d, J = 6.8Hz, 2H ) 4.1 (d, 2H) 4.0 (s, 3H) 1.5 (s, 9H)

Example 13

2- [2- (2-acetylaminothiazol-4-yl) -2-methoxyiminoacetylamino] -2-methylacetic acid t-butyl ester (compound 1-36)

Alanine t-butyl ester (compound of formula (III)) (0.15 g, 1.0 mmol) with 2- (2-acetylaminothiazol-4-yl) -2-methoxyiminoacetic acid chloride (formula (II) Compound) (0.26 g, 1.0 mmol) in the same manner as in Example 1 to obtain 0.26 g of the desired product in a yield of 69%.

Melting Point (℃): 71-72

¹ H NMR (CDCl ₃ ): δ 10.8 (br.s, 1H) 8.1 (d, J = 6.4, 1H) 7.6 (s, 1H) 4.3 (m, 1H) 4.0 (s, 3H) 2.0 (s, 3H ) 1.3 (m, 12H)

Example 14

2- {2- [2- (3-trifluorobenzoylamino) thiazol-4-yl] -2-methoxyiminoacetylamino} -acetic acid t-butyl ester (Compound 1-40)

Glycine t-butyl ester (compound of formula (III)) (0.13 g, 1.0 mmol) with 2- [2- (3-trifluorobenzoylamino) thiazol-4-yl] -2-methoxyiminoacetic acid The same reaction as in Example 1 was carried out from chloride (compound of formula (II)) (0.39 g, 1.0 mmol) to give 0.31 g of the desired product in 63% yield.

Melting Point (℃): 129-131 (Decomposition)

¹ H NMR (CDCl ₃ ): δ 11.2 (br.s, 1H) 8.3-8.1 (m, 3H) 7.9-7.5 (m, 3H) 4.1 (d, J = 6.7 Hz, 2H) 3.9 (s, 3H) 1.5 (s, 9H)

The bactericidal effect of the thiazole oxyiminoacetamide derivative of the general formula (I) of the present invention prepared as in Example was measured by the following test method.

Bactericidal effect test

To investigate the protective effect against plant pathogens, 25 mg of test compound was dissolved in 10 ml of acetone, 90 ml of a 250 ppm aqueous solution containing Tween 20 was added to the solution, and the concentration was adjusted to 250 ppm. 50 ml of foliar spray was applied to host plants. The sprayed plants were left at room temperature for 24 hours to volatilize the solvent and water. Thus, the plants (treatment) and the untreated plants (control) treated with the disinfectant composition were inoculated with specific plant pathogens as shown in the following test examples, and left under the same conditions (humidity and temperature) for the same period of time. The control area (Control Value,%) was calculated as shown in Equation 1 by obtaining the disease area ratio (obtained from the ratio of the disease area ratio prepared based on the ratio of the measured disease area to the leaf area). The higher the control value, the better the sterilization effect.

Control value (%) = (1- (Length of treatment area / Length of control area)) × 100

Activation Index +++: Control from 81 to 100%

++: Control is 61-80%

+: Control is 41 to 60%

-: Control is 40% or less

Test Example 1

Sterilization Effect on Rice Blast

Strains of pathogens ( Pyricularia oryzae ) were inoculated in rice bran agar medium (Rice Polish 20g, dextrose 10g, agar 15g, distilled water 1L) and incubated for 2 weeks in a 26 ℃ incubator. The surface of the medium in which the pathogen was grown was scraped off with a rubber gallbladder to remove aerial mycelium and spores were formed for 48 hours on a fluorescent lamp turned on at 25 to 28 ^° C.

Germ inoculation was sprayed sufficiently to flow into Nakdong rice (3-4 leaves) susceptible to rice blast bottle after making a spore suspension (106 pieces / ㎖) of a certain concentration using sterilized distilled water.

The inoculated rice was incubated for 24 hours in a dark state, and the incidence of leaf area was determined by induction for 5 days in a constant temperature and humidity chamber with a relative humidity of 90% or higher and 26 ± 2 ^o C. At this time, the lesion area formed on the fully developed leaf just below the top leaf of 3-4 leaf rice was measured.

Test Example 2

Bactericidal Effect on Rice Leaf House Blight

Put an appropriate amount of bran into a 1 liter culture bottle and sterilize it, inoculate agar pieces of pathogen ( Rhizoctonia solani ) grown on potato agar medium (PDA) for 3 days. Inoculated evenly in the pot (5cm) and induced the disease for 5 days in a constant temperature and humidity room with a temperature of 28 ± 1 ℃ and a relative humidity of 80% or more to determine the leaf area ratio of the leaves of 2-3 leaves seedlings.

Test Example 3

Bactericidal Effect on Cucumber Gray Mold Disease

Strains ( Botrytis cinerea ) isolated from tomatoes were inoculated in potato agar medium and plated in a 25 ° C. incubator to incubate for 15 days under light dark conditions to form spores. Spores formed on the medium were put in 10ml of distilled water per plate, scraped with a brush, and then spores were filtered with gauze to harvest spores, and the spore concentration was 106 / ml, and then sprayed on single-leaf cucumbers. This was induced for 3 days in a 20 ° C wet room, and the lesion area ratio of the first lobe was determined.

Test Example 4

Bactericidal Effect on Tomato Blight

Phytophthora infestans were placed on V-8 juice agar medium (V-8 juice 200ml, CaCO ₃ 4.5g, agar 15g, distilled water 800ml) and light treated at 20 ℃ for 16 hours and dark treated for 14 hours. Spores were harvested after incubation. At this time, sterile distilled water was added to the plate and shaken to separate the zygote sac from the flora, and then the stool sac was filtered using a 4-ply piece of cloth. The concentration of strained strains was adjusted to 105 / ml using sterile distilled water, and this inoculum was sprayed with tomato seedlings for 1 day in a 20 ° C. chamber, and then kept at a temperature of 20 ° C. and a relative humidity of 80% or higher. After 4 days of onset, the lesion area ratio of one and two leaves of tomato was investigated.

Test Example 5

Sterilization Effect against Wheat Red Rust

The pathogen ( Puccinia recondita ) was used for direct passage to plants in the laboratory. For subculture and pharmacological investigation of strains, 15 seed grains (silver onions) were seeded in a disposable pot (diameter: 6.5 cm), and spores were inoculated by sprinkling the wheat of one leaf grown for 7 days in a greenhouse. The inoculated one-leafed wheat was incubated at 20 ° C. for 1 day and then transferred to a constant temperature and humidity chamber of 70% and 20 ° C. for 10 days to induce onset, and then the leaf area ratio of the leaves was determined.

Test Example 6

Bactericidal Effect on Barley Powder Disease

The pathogen ( Erysiphe graminis f.sp.hordei ) was used by passage in the laboratory. For the subculture and pharmacological investigation of strains, seedlings of 15 barley seeds (East barley No. 1) were sown in a disposable pot (diameter: 6.5 cm), and barley was grown for 7 days in a greenhouse (25 ± 5 ^o C) for 7 days. Was inoculated with powdery mildew spores and transferred to a constant temperature and humidity room at a relative humidity of 50% and 22 to 24 ° C to induce the onset for 7 days, and then calculate the area ratio of the leaves.

The control value was calculated by substituting the lesion area ratios of the treated and control leaves measured in Test Examples 1 to 6, and the results are shown in Table 2 as the activity index.

Compound number Rice fever Rice leaf pattern Cucumber gray mold Tomato plague Wheat Red Rust Wheat flour 1-2 - - - - +++ +++ 1-4 +++ + - - - - 1-14 +++ + - - ++ +++ 1-15 +++ + - - ++ +++ 1-18 ++ + - - + + 1-19 +++ - + - + +++ 1-20 +++ + - - +++ +++ 1-26 +++ - - - - - +++: 81 to 100% ++: control 61 to 80% +: 41 to 60% CONTROL-: 40% or less

The thiazoleoxyiminoacetamide derivatives according to the present invention have a wide range of bactericidal effects against plant pathogens, as can be seen from Table 2 above, and in particular, against rice blast and barley powdery mildew. In addition, it is excellent in preventing and treating effects as well as penetration.

Claims (2)

Novel thiazoleoxyiminoacetamide derivatives of the general formula (I) Formula 1 Where R ₁ is a C ₁ -C ₃ alkyl group, 1 to 3 chloro or fluoro-, or C _1-3 alkyl or alkoxy-substituted or unsubstituted phenyl groups, R ₄ NH or R ₅ CONH, wherein R ₄ is Hydrogen, allyl, or 1 to 3 chloro or fluoro-, or C _1-3 alkyl or alkoxy-substituted or unsubstituted phenyl groups, R ₅ is a C ₁ -C ₃ alkyl group, or 1 to 3 chloro or fluoro _Rho- , or C _1-3 alkyl or alkoxy-substituted or unsubstituted phenyl group; R ₂ is hydrogen, a C ₁ -C ₃ alkyl group, a C ₁ -C ₃ alkylthio- or alkylsulphone-substituted alkyl group, or a benzyl group; R ₃ is a C ₁ -C ₅ alkyl group. An agricultural and horticultural fungicide composition containing an effective amount of the compound of formula (I) according to claim 1 as an active ingredient.