KR100212637B1 - Novel amino acid amide derivatieve and process for preparation thereof - Google Patents

Abstract

The present invention relates to a novel amino acid amide derivative represented by the following general formula (I), a stereoisomer thereof, a method for producing the compound, and a composition for inhibiting the onset by phytopathogens containing the compound as an active ingredient.

Wherein X ₁ and X ₂ each independently represent hydrogen, halogen, methyl or methoxy, R ₁ represents hydrogen, phenyl or —CHR ₃ R ₄ where R ₃ represents hydrogen or methyl and R ₄ is Hydrogen, C ₁ -C ₃ alkyl, hydroxy, thiol, alkylthiomethyl, phenyl or hydroxyphenyl), and R ₂ represents hydrogen or propylene together with R ₁ .

Description

Novel amino acid amide derivatives and preparation method thereof

The present invention relates to novel amino acid amide derivatives represented by the following general formula (I), geometric isomers and stereoisomers thereof, and methods for producing the compounds.

Wherein X ₁ and X ₂ each independently represent hydrogen, halogen, methyl or methoxy, R ₁ represents hydrogen, phenyl or —CHR ₃ R ₄ where R ₃ represents hydrogen or methyl and R ₄ is Hydrogen, C ₁ -C ₃ alkyl, hydroxy, thiol, alkylthiomethyl, phenyl or hydroxyphenyl), and R ₂ represents hydrogen or propylene together with R ₁ .

The compound of the general formula (I) according to the present invention is effective in inhibiting the onset by pathogens as a novel compound, and particularly exhibits an excellent effect on inhibiting the onset by phytopathogens and fungi. Plant diseases in which the compounds of the present invention are effective include Pyricularia grisea, Rhizoctonia solani, Phytophthora infestans, Plasmopara viticola, Cucumber gray fungus (Botrytis cinerea) , Puccinia recondita, Erysiphe graminis, Venturia inequalis, and others; powdery mildew or rust against other species of plants, or incomplete fungus (Deuteromycete), Plant diseases caused by Ascomycete or Basidio-mycete may be mentioned. Therefore, the present invention also relates to a composition for inhibiting the onset by phytopathogens, which comprises the compound of the general formula (I) as an active ingredient.

Late blight, Downy mildew and Asymptomatic fungi have a rapid onset of resistance, and resistance to existing drugs is currently a problem. Therefore, development of inhibitors of pathogenesis by a new plant phytopathogen having high activity and low toxicity is required. . In this regard, it has already been reported that derivatives containing amino acids in the molecule have an effect on the control of late blight, Downy mildew (DE 4203084 Al, DE 3936296 Al, EP 0398072 A2, EP 0493683 Al). However, these existing amino acid derivatives showed excellent bactericidal activity against late blight and downy mildew, whereas gray mold disease could not be controlled.

The present inventors have developed and filed an amino acid amide derivative of the following general formula (A) having excellent bactericidal activity and having a methoxy group substituted in the benzyl position.

을 나타내며, 여기서 R₄는 사이클로프로필, 2-클로로메틸, C₁-C₄알킬, C₁-C₄알콕시, C₁-C₃할로알콕시, 알릴옥시, 아릴옥시 또는 벤질옥시를 나타낸다.Wherein X ₁ and X ₂ each independently represent hydrogen, methoxy, methyl or halogen, or when X ₁ and X ₂ are attached to adjacent carbon atoms on a benzene ring, they are bonded to each other to form a methylenedioxy group And R ₁ represents hydrogen, methyl, 2-propyl, 2-methylpropyl, 2-butyl, phenyl or benzyl, R ₂ represents propylene with hydrogen or R ₁ and R ₃ represents hydrogen or

Wherein R ₄ represents cyclopropyl, 2-chloromethyl, C ₁ -C ₄ alkyl, C ₁ -C ₄ alkoxy, C ₁ -C ₃ haloalkoxy, allyloxy, aryloxy or benzyloxy.

The present invention has been made as a result of continuing research from this prior invention, the inventors of the formula (I) is a late blight, Bacillus disease, gray mold, as well as blast (Pyricularia grisea), rice leaf blight (Rhizoctonia) solani) and the like have been shown to show good efficacy to complete the present invention.

Hereinafter, the configuration of the present invention will be described in detail.

An object of the present invention is to provide a novel amino acid amide derivative represented by the following general formula (I).

Wherein X ₁ and X ₂ each independently represent hydrogen, halogen, methyl or methoxy, R ₁ represents hydrogen, phenyl or —CHR ₃ R ₄ where R ₃ represents hydrogen or methyl and R ₄ is Hydrogen, C ₁ -C ₃ alkyl, hydroxy, thiol, alkylthiomethyl, phenyl or hydroxyphenyl), and R ₂ represents hydrogen or propylene together with R ₁ .

Among the compounds of the general formula (I) which show excellent effects in inhibiting the onset by phytopathogens, the preferred compounds are X ₁ and X ₂ each independently represent hydrogen or halogen, R ₁ represents hydrogen, phenyl or -CHR ₃ R ₄ , where R ₃ represents hydrogen or methyl, R ₄ represents hydrogen, methyl, ethyl, isopropyl, hydroxy, thiol, alkylthiomethyl, phenyl or hydroxyphenyl, and R ₂ represents hydrogen Or a propylene with R ₁ .

The compound of general formula (I) may exist as two geometric isomers, namely (E) and (Z) -isomers produced by a double bond between carbon and nitrogen. In addition, when R ₁ is not a hydrogen atom, four pure stereoisomers of (E, L), (E, D), (Z, D) and (Z, L) are carbon atoms in which R ₁ is substituted. Or mixtures thereof.

Accordingly, the scope of the present invention includes such geometric isomers, stereoisomers and mixtures thereof.

Compounds of the general formula (I) according to the present invention are prepared according to the following Scheme 1 to form a 2- (N-methoxyimino) -2-phenyl-ethylamine derivative of the general formula (II) It can be prepared by reacting with an amino acid derivative of the following general formula (III) in the presence.

Scheme 1:

In the above scheme, X ₁ , X ₂ , R ₁ and R ₂ are as defined above.

온도, 바람직하게는 -10 내지 30

의 온도에서 10분 내지 24 시간동안 진행시킨다.In the reaction, examples of the solvent include aromatic hydrocarbons such as benzene, toluene and xylene, halogenated hydrocarbons such as dichloromethane, 1,2-dichloroethane and chloroform, diethyl ether, dioxane, 1,2-dimethoxyethane, Ethers such as tetrahydrofuran, acetone, methyl ethyl ketone, ketones such as cyclohexanone, nitriles such as acetonitrile, propionitrile, esters such as methyl acetate, ethyl acetate, N, N-dimethylformamide, N One or more selected from polar solvents such as, N-dimethylacetamide and dimethyl sulfoxide may be used, and the base may be pyridine, 4-dimethylaminopyridine, triethylamine, N, N-dimethylaniline, tributylamine And one or more selected from organic bases such as N-methylmorpholine can be used, and as a coupling agent, dicyclohexylcarbodiimide (DCC), 1-ethyl-3- (3-dimethyla No Profile) may be used carbodiimide (EDC), such as a carboxylic body polyimides with silicon tetrachloride, such as at least one selected from an inorganic dehydrating agent in a state of being mixed with 1-hydroxybenzotriazole. In particular, 1-hydroxybenzotriazole is necessary to maintain the chirality of amino acid derivatives used as starting materials. The reaction is -30 to 70

Temperature, preferably -10 to 30

At a temperature of 10 minutes to 24 hours.

On the other hand, amino acid derivatives of the general formula (III) used as starting materials in the reaction can be prepared and used according to the method described in the literature (see JACS Vol. In addition, 2- (N-methoxyimino) -2-phenyl-ethylamine derivative of the general formula (II) used as the reactant may be prepared and used according to the method shown in Scheme 2 below.

Scheme 2:

In the above scheme, X ₁ and X ₂ are as defined above.

Compound (5) is obtained by carrying out an oxime etherification reaction with respect to starting compound (6). In this case, inorganic bases such as sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, sodium hydrogen carbonate, potassium hydrogen carbonate, sodium hydride and potassium hydride may be used. Particularly, metal hydrides such as sodium hydride and potassium hydride are preferable. Examples of the solvent include ethers such as diethyl ether, dioxane, 1,2-dimethoxyethane and tetrahydrofuran, ketones such as acetone, methyl ethyl ketone and cyclohexanone, and nitriles such as acetonitrile and propionitrile. Alcohols such as methanol, ethanol or polar solvents such as N, N-dimethylformamide, N, N-dimethylacetamide, and dimethyl sulfoxide may be used, but preferably, polar solvents of alcohols or amides are used.

의 온도에서 반응을 진행시킨다.Compound (4) can be prepared by carrying out the bromination reaction with respect to compound (5) obtained above. As bromination reagent, bromine, hydrobromic acid, N-bromosuccinimide, copper bromide (II) can be used, and as a solvent, aromatic hydrocarbons such as benzene, toluene, xylene, dichloromethane, 1,2-dichloroethane , Halogenated hydrocarbons such as chloroform, and one or more selected from esters such as methyl acetate and ethyl acetate may be used, and 0 to 100 depending on the type of brominated reagent selected.

The reaction proceeds at a temperature of.

에서 수행한다. 또한, 카르보닐의 환원반응은 환원제로 붕수소화나트륨, 수소화알루미늄리튬, 수소화붕소 등을 사용하거나 촉매 수소화반응을 수행함으로써 이루어지며, 용매로는 디에틸에테르, 디옥산, 1,2-디메톡시에탄, 테트라하이드로푸란과 같은 에테르류를 바람직하게 사용하고, 반응은 0 내지 80

의 온도범위에서 수행할 수 있다.Imino azido compound (3) is obtained by performing an azido reaction on compound (4). The azidation reaction is carried out using 0 to 30 equivalents of sodium azide in an excess of 5 equivalents or more in polar solvents such as N, N-dimethylformamide, N, N-dimethylacetamide, and dimethyl sulfoxide.

Perform on In addition, the reduction reaction of carbonyl is carried out by using sodium borohydride, lithium aluminum hydride, boron hydride, or the like as a reducing agent, or carrying out catalytic hydrogenation, and as a solvent, diethyl ether, dioxane, 1,2-dimethoxyethane. Ethers such as tetrahydrofuran are preferably used, and the reaction is from 0 to 80.

It can be carried out in the temperature range of.

In the reduction reaction of the imino azido compound (3) to the primary amine compound (IIa) or (IIb), the reaction is carried out using lithium aluminum hydride, triphenylphosphine, hydrogen sulfide, or the like as a reducing agent, or catalytic hydrogenation, zinc, Reduction reaction using a metal is used. At this time, the solvent may be one or more selected from halogenated hydrocarbons such as dichloromethane, 1,2-dichloroethane, chloroform, diethyl ether, dioxane, 1,2-dimethoxyethane, and tetrahydrofuran. It can be used and water can be added as needed. Hydrolysis of the resulting phosphonium addition product in the presence of a base in a solvent yields a mixture of compounds of formula (IIa) and (IIb), which is separated by silica gel column chromatography to obtain 2- (N It is possible to separate into (E) and (Z) -isomers of -methoxyimino) -2-phenyl-ethylamine.

The preparation methods described above will be explained in more detail based on the following examples, and typical examples of the compound of general formula (I) synthesized according to these methods are shown in Table 1 below.

The compound of general formula (I) finally obtained according to the preparation method according to the present invention exhibits excellent efficacy in suppressing the onset by various phytopathogens as mentioned above. Therefore, according to the present invention, there is provided a composition for inhibiting the onset by phytopathogens, which comprises a compound of formula (I) as an active ingredient together with a carrier commonly used in the pesticide field.

In the preparation of the composition of the present invention, as a carrier usable, one or more selected from kaolin, bentonite, talc and xylene may be mentioned, and the formulation of the composition prepared with such a carrier includes a hydrating agent, an emulsion and a powder. Mention may be made of weakening or granulating agents.

In addition, in suppressing the onset by phytopathogens, the composition according to the present invention is preferably applied in the range of 250 to 500 g / ha based on the active compound.

Hereinafter, the present invention will be described in more detail based on the following Preparation Examples and Examples. However, this is only for better understanding of the present invention, and the scope of the present invention is not limited to these examples in any sense.

[Production Example 1]

[Synthesis of 2-amino-1- (2,4-dichloro-phenyl) -ethanone O-methyloxime]

[Step 1]

[Preparation of 1- (2,4-Dichloro-phenyl) -ethanone O-methyloxime]

가하고 12 시간동안 환류시키면서 교반한 후, 식히고 감압하에 메탄올을 증발시켰다. 반응액에 물을 붓고 에틸아세테이트로 추출한 다음, 무수 황산마그네슘으로 건조시키고 증발시켜 흰색 고체의 표제화합물 18.6g (수율 86%)을 수득하였다.18.7 g of 2,4-dichloroacetophenone, 9.07 g of methoxyamine hydrochloride and 68.2 g of potassium carbonate were added to methanol 250

After stirring and refluxing for 12 hours, the mixture was cooled and the methanol was evaporated under reduced pressure. Water was added to the reaction mixture, followed by extraction with ethyl acetate, followed by drying over anhydrous magnesium sulfate and evaporation to give 18.6 g (yield 86%) of the title compound as a white solid.

[Step 2]

[Preparation of 2-bromo-1- (2,4-dichloro-phenyl) -ethanone O-methyloxime]

에 가하고 10 시간동안 환류시키면서 교반한 후 식히고 감압하에 사염화탄소를 증발시켰다. 반응액에 물을 붓고 에틸아세테이트로 추출한 다음, 무수 황산마그네슘으로 건조시키고 증발시켜 노란색 액상의 표제화합물 15.0g (수율 70%)을 수득하였다.15.7 g of 1- (2,4-dichloro-phenyl) -ethanone O-methyloxime and 12.8 g of N-bromosuccinimide obtained in step 1 were added to carbon tetrachloride.

After stirring, the mixture was stirred with reflux for 10 hours, cooled, and carbon tetrachloride was evaporated under reduced pressure. Water was added to the reaction mixture, followed by extraction with ethyl acetate. The reaction solution was dried over anhydrous magnesium sulfate and evaporated to give 15.0 g (yield 70%) of the title compound as a yellow liquid.

[Step 3]

[Production of 2-azido-1- (2,4-dichloro-phenyl) -ethanone O-methyloxime]

에 용해시킨 후, 여기에 아지도화나트륨 9.86g을 0

에서 가하고 동온도에서 1시간동안 교반하였다. 반응액에 다량의 물을 붓고 에틸아세테이트로 추출한 다음, 무수 황산마그네슘으로 건조시키고 증발시켜 노란색 액상의 표제화합물 7.8g (수율 99%)을 수득하였다.9.01 g of 2-bromo-1- (2,4-dichloro-phenyl) -ethanone O-methyloxime obtained in step 2 was dissolved in dimethylformamide 100.

After dissolving in, add 9.86 g of sodium azizide to it

It was added at and stirred at the same temperature for 1 hour. Poured a large amount of water into the reaction solution, extracted with ethyl acetate, dried over anhydrous magnesium sulfate and evaporated to give 7.8g (yield 99%) of the title compound in a yellow liquid.

[Step 4]

[Preparation of 2-amino-1- (2,4-dichloro-phenyl) -ethanone O-methyloxime]

에 용해시킨 후 물을 1 내지 2 방울 가하였다. 여기에 트리페닐포스핀 6.80g을 가하고 8 시간정도 교반한 후 2N 수산화나트륨 수용액 30

를 가하고 환류시키면서 2 시간동안 교반하였다. 반응액을 냉각시키고 감압하에 테트라하이드로푸란을 제거한 다음, 디에틸에테르를 붓고 2N 염산수용액으로 추출하였다. 수산화나트륨을 사용하여 수층을 pH 11 까지 염기화시키고 디에틸에테르로 다시 추출한 다음, 무수 황산마그네슘으로 건조시키고 증발시켰다. 잔류물을 실리카겔 칼럼 크로마토그래피(용출액: 헥산/에틸아세테이트/트리에틸아민=5/2/0.5, v/v/v)에 적용하여 E, Z 이성체로 각각 분리하였다. 용매를 감압하에 증발시켜 노란 액상의 Z-형태 표제화합물 2.48g (수율 45%) 및 E-형태 표제화합물 2.03g (수율 37%)을 각각 수득하였다.6.11 g of 2-azido-1- (2,4-dichloro-phenyl) -ethanone O-methyloxime obtained in step 3 was converted to tetrahydrofuran 100.

After dissolving in 1 to 2 drops of water were added. 6.80 g of triphenylphosphine was added thereto, followed by stirring for 8 hours, followed by 2N aqueous sodium hydroxide solution 30

Was added and stirred for 2 hours while refluxing. The reaction solution was cooled, tetrahydrofuran was removed under reduced pressure, diethyl ether was poured out, and extracted with 2N hydrochloric acid solution. The aqueous layer was basified to pH 11 with sodium hydroxide and extracted again with diethyl ether, dried over anhydrous magnesium sulfate and evaporated. The residue was subjected to silica gel column chromatography (eluent: hexane / ethyl acetate / triethylamine = 5/2 / 0.5, v / v / v) to separate the E and Z isomers, respectively. The solvent was evaporated under reduced pressure to give 2.48 g (yield 45%) of the yellow liquid Z-form title compound and 2.03 g (37% yield) of the E-form title compound, respectively.

[Production Example 2]

[Synthesis of 2-amino-1-phenyl-ethanone O-methyloxime]

3.28 g (total yield: 12%) of Z-form title compound was carried out in the same manner as in Preparation Example 1, except that 20 g of acetophenone was used instead of 2,4-dichloroacetophenone as a starting material. 3.61 g (13% total yield) of the E-form title compound were obtained.

Example 1

[Synthesis of (E, L) -2-t-butoxycarbonylamino-N- [2-methoxyimino-2-phenyl-ethyl] -3-methyl-butyramide (1)]

를 디메틸포름아미드 5

에 가하고 0

에서 10분간 교반한 다음, 여기에 (E)-2-아미노-1-페닐-에탄온 O-메틸-옥심 0.063g을 가하고 2 시간동안 교반하였다. 반응액을 다량의 물과 에틸아세테이트로 추출하고 무수 황산마그네슘으로 건조, 증발시켜 표제화합물 0.12g(수율 82%)을 수득하였다.0.088 g of Nt-butoxycarbonyl L-valine, 0.08 g of 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride, 0.057 g of 1-hydroxybenzotriazole hydrate and 0.060 of triethylamine

Dimethylformamide 5

Putting on 0

After stirring for 10 minutes, 0.063 g of (E) -2-amino-1-phenyl-ethanone O-methyl-oxime was added thereto and stirred for 2 hours. The reaction solution was extracted with a large amount of water and ethyl acetate, dried over anhydrous magnesium sulfate, and evaporated to yield 0.12 g (yield 82%) of the title compound.

Example 2

[(E, L) -2-t-butoxycarbonylamino-N- [2- (2,4-dichloro-phenyl) -2-methoxyimino-ethyl] -3-methyl-butyramide (2 Synthesis of)

를 디메틸포름아미드 5

에 가하고 0

에서 10분간 교반한 다음, 여기에 (E)-2-아미노-1-(2,4-디클로로-페닐)-에탄온 O-메틸-옥심 0.090g을 가하고 2 시간동안 교반하였다. 반응액을 다량의 물과 에틸아세테이트로 추출하고 무수 황산마그네슘으로 건조, 증발시켜 표제화합물 0.13g (수율 78%)을 수득하였다.0.088 g of Nt-butoxycarbonyl L-valine, 0.081 g of 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride, 0.057 g of 1-hydroxybenzotriazole hydrate and 0.060 of triethylamine

Dimethylformamide 5

Putting on 0

After stirring for 10 minutes, 0.090 g of (E) -2-amino-1- (2,4-dichloro-phenyl) -ethanone O-methyl-oxime was added thereto and stirred for 2 hours. The reaction solution was extracted with a large amount of water and ethyl acetate, dried over anhydrous magnesium sulfate, and evaporated to yield 0.13 g (yield 78%) of the title compound.

Example 3

[(E, L) -2-t-butoxycarbonylamino-4-methyl-pentanoic acid [2- (2,4-dichloro-phenyl) -2-methoxyimino-ethyl] -amide (3) synthesis]

0.13 g (yield 75%) of the title compound were obtained in the same manner as in Example 2, except that 0.094 g of Nt-butoxycarbonyl L-leucine was used instead of Nt-butoxycarbonyl L-valine. Obtained.

Example 4

[(E, L) -2-t-butoxycarbonylamino-3-methyl-pentanoic acid [2- (2,4-dichloro-phenyl) -2-methoxyimino-ethyl] -amide (4) synthesis]

0.14 g (82% yield) of the title compound by the same method as in Example 2, except that 0.094 g of Nt-butoxycarbonyl L-isoleucine was used instead of Nt-butoxycarbonyl L-valine. Obtained.

Example 5

[(E, L) -2-t-butoxycarbonylamino-N- [2- (2,4-dichloro-phenyl) -2-methoxyimino-ethyl] -3-phenyl-propionamide (5) Synthesis of

0.14 g (yield 75%) of the title compound were obtained in the same manner as in Example 2, except that 0.11 g of Nt-butoxycarbonyl L-phenylalanine was used instead of Nt-butoxycarbonyl L-valine. Obtained.

Example 6

[(E, L) -2- [N- {2- (2,4-Dichloro-phenyl) -2-methoxyimino-ethyl} carbamoyl] -pyrrolidine-1-carboxylic acid t-butyl Synthesis of Ester (6)]

0.12 g (yield 70%) of the title compound were obtained in the same manner as in Example 2, except that 0.087 g of Nt-butoxycarbonyl L-proline was used instead of Nt-butoxycarbonyl L-valine. Obtained.

Example 7

[(E, L) -2-t-butoxycarbonylamino-N- [2- (2,4-dichloro-phenyler) -2-methoxyimino-ethyl] -2-phenyl-acetamide (7 Synthesis of)

The title compound 0.14 was carried out in the same manner as in Example 2, except that 0.10 g of Nt-butoxycarbonyl (s)-(2) -phenylglycine was used instead of Nt-butoxycarbonyl L-valine. g (yield 78%) was obtained.

Example 8

[Synthesis of (Z, L) -2-t-butoxycarbonylamino-N- [2-methoxyimino-2-phenyl-ethyl] -3-methyl-butyramide (8)]

를 디메틸포름아미드 5

에 가하고 0

에서 10분간 교반한 다음, 여기에 (Z)-2-아미노-1-페닐-에탄온 O-메틸-옥심 0.068g을 가하고 2 시간동안 교반하였다. 반응액을 다량의 물과 에틸아세테이트로 추출하고 무수 황산마그네슘으로 건조, 증발시켜 표제화합물 0.13g(수율 85%)을 수득하였다.0.095 g of Nt-butoxycarbonyl L-valine, 0.088 g of 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride, 0.062 g of 1-hydroxybenzotriazole hydrate and 0.064 g of triethylamine

Dimethylformamide 5

Putting on 0

After stirring for 10 minutes, 0.068 g of (Z) -2-amino-1-phenyl-ethanone O-methyl-oxime was added thereto and stirred for 2 hours. The reaction solution was extracted with a large amount of water and ethyl acetate, dried over anhydrous magnesium sulfate, and evaporated to yield 0.13 g (yield 85%) of the title compound.

Example 9

[(Z, L) -2-t-butoxycarbonylamino-N- [2- (2,4-dichloro-phenyl) -2-methoxyimino-ethyl] -3-methyl-butyramide (9 Synthesis of)

를 디메틸포름아미드 5

에 가하고 0

에서 10분간 교반한 다음, 여기에 Z-2-아미노-1-(2,4-디클로로-페닐)-에탄온 O-메틸-옥심 0.097g을 가하고 2 시간동안 교반하였다. 반응액을 다량의 물과 에틸아세테이트로 추출하고 무수 황산마그네슘으로 건조, 증발시켜 표제화합물 0.14g (수율 77%)을 수득하였다.0.095 g of Nt-butoxycarbonyl L-valine, 0.088 g of 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride, 0.062 g of 1-hydroxybenzotriazole hydrate and 0.064 g of triethylamine

Dimethylformamide 5

Putting on 0

After stirring for 10 minutes, 0.097 g of Z-2-amino-1- (2,4-dichloro-phenyl) -ethanone O-methyl-oxime was added thereto and stirred for 2 hours. The reaction solution was extracted with a large amount of water and ethyl acetate, dried over anhydrous magnesium sulfate, and evaporated to yield 0.14 g (yield 77%) of the title compound.

Example 10

[(Z, L) -2-t-butoxycarbonylamino-4-methyl-pentanoic acid [2- (2,4-dichloro-phenyl) -2-methoxyimino-ethyl] -amide (10) synthesis]

를 디메틸포름아미드 5

에 가하고 0

에서 10분간 교반한 다음, 여기에 Z-2-아미노-1-(2,4-디클로로-페닐)-에탄온 O-메틸-옥심 0.090g을 가하고 2 시간동안 교반하였다. 반응액을 다량의 물과 에틸아세테이트로 추출하고 무수 황산마그네슘으로 건조, 증발시켜 표제화합물 0.13g (수율 75%)을 수득하였다.0.094 g of Nt-butoxycarbonyl L-leucine, 0.081 g of 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride, 0.057 g of 1-hydroxybenzotriazole hydrate and 0.060 of triethylamine

Dimethylformamide 5

Putting on 0

After stirring for 10 minutes, 0.090 g of Z-2-amino-1- (2,4-dichloro-phenyl) -ethanone O-methyl-oxime was added thereto and stirred for 2 hours. The reaction solution was extracted with a large amount of water and ethyl acetate, dried over anhydrous magnesium sulfate, and evaporated to yield 0.13 g (yield 75%) of the title compound.

Example 11

[(Z, L) -2-t-butoxycarbonylamino-3-methyl-pentanoic acid [2- (2,4-dichloro-phenyl) -2-methoxyimino-ethyl] -amide (11) synthesis]

0.12 g (70% yield) of the title compound by the same method as in Example 10, except that 0.094 g of Nt-butoxycarbonyl L-isoleucine was used instead of Nt-butoxycarbonyl L-leucine. Obtained.

Example 12

[(Z, L) -2-t-butoxycarbonylamino-N- [2- (2,4-dichloro-phenyl) -2-methoxyimino-ethyl] -3-phenyl-propionamide (12) Synthesis of

0.15 g (yield 81%) of the title compound were obtained in the same manner as in Example 10, except that 0.11 g of Nt-butoxycarbonyl L-phenylalanine was used instead of Nt-butoxycarbonyl L-leucine. Obtained.

Example 13

[(Z, L) -2- [N- {2- (2,4-Dichloro-phenyl) -2-methoxyimino-ethyl} carbamoyl] -pyrrolidine-1-carboxylic acid t-butyl Synthesis of Ester (13)]

0.13 g (yield 80%) of the title compound were obtained in the same manner as in Example 10, except that 0.087 g of Nt-butoxycarbonyl L-proline was used instead of Nt-butoxycarbonyl L-leucine. Obtained.

Example 14

[(Z, L) -2-t-butoxycarbonylamino-N- [2- (2,4-dichloro-phenyl) -2-methoxyimino-ethyl] -2-phenyl-acetamide (14) Synthesis of

0.14 g of the title compound was carried out in the same manner as in Example 10, except that 0.10 g of Nt-butoxycarbonyl (s) -2-phenylglycine was used instead of Nt-butoxycarbonyl L-leucine. Yield 78%).

Example 15

[Synthesis of (E, L) -2-t-butoxycarbonylamino-N- [2-methoxyimino-2-phenyl-ethyl] -acetamide (15)]

0.11 g (yield 75%) of the title compound was obtained in the same manner as in Example 2, except that 0.074 g of Nt-butoxycarbonyl glycine was used instead of Nt-butoxycarbonyl L-valine. .

Example 16

[Synthesis of (E, L) -2-t-butoxycarbonylamino-N- [2- (2,4-dichloro-phenyl) -2-methoxyimino-ethyl] propionamide (16)]

0.12 g (yield 78%) of the title compound was obtained in the same manner as in Example 2, except that 0.080 g of Nt-butoxycarbonyl L-alanine was used instead of Nt-butoxycarbonyl L-valine. Obtained.

Example 17

[(E, L) -2-t-butoxycarbonylamino-N- [2- (2,4-dichloro-phenyl) -2-methoxyimino-ethyl] -3-hydroxy-propionamide (17 Synthesis of)

0.11 g (yield 70%) of the title compound was obtained in the same manner as in Example 2, except that 0.087 g of Nt-butoxycarbonyl L-serine was used instead of Nt-butoxycarbonyl L-valine. Obtained.

Example 18

[(E, L) -2-t-butoxycarbonylamino-N- [2- (2,4-dichloro-phenyl) -2-methoxyimino-ethyl] -3-hydroxy-butyramide ( 18) Synthesis]

0.12 g (yield 69%) of the title compound were obtained in the same manner as in Example 2, except that 0.093 g of Nt-butoxycarbonyl L-threonine was used instead of Nt-butoxycarbonyl L-valine. Obtained.

Example 19

[(E, L) -2-t-butoxycarbonylamino-N- [2- (2,4-dichloro-phenyl) -2-methoxyimino-ethyl] -4-methylthio-butyramide ( Synthesis of 19]

0.15 g (85% yield) of the title compound were obtained in the same manner as in Example 2, except that 0.106 g of Nt-butoxycarbonyl L-methionine was used instead of Nt-butoxycarbonyl L-valine. Obtained.

Example 20

[(E, L) -2-t-butoxycarbonylamino-N- [2- (2,4-dichloro-phenyl) -2-methoxyimino-ethyl] -3- (4-hydroxyphenyl) Synthesis of Propionamide (20)]

0.16 g (yield 84%) of the title compound were obtained in the same manner as in Example 2, except that 0.119 g of Nt-butoxycarbonyl L-tyrosine was used instead of Nt-butoxycarbonyl L-valine. Obtained.

Example 21

[Synthesis of (Z, L) -2-t-butoxycarbonylamino-N- [2- (2,4-dichloro-phenyl) -2-methoxyimino-ethyl] -acetamide (21)]

0.12 g (yield 77%) of the title compound were obtained in the same manner as in Example 10, except that 0.074 g of Nt-butoxycarbonyl glycine was used instead of Nt-butoxycarbonyl L-leucine. .

Example 22

[Synthesis of (Z, L) -2-t-butoxycarbonylamino-N- [2-methoxyimino-2-phenyl-ethyl] -propionamide (22)]

0.12 g (yield 76%) of the title compound were obtained in the same manner as in Example 10, except that 0.080 g of Nt-butoxycarbonyl L-alanine was used instead of Nt-butoxycarbonyl L-leucine. Obtained.

Example 23

[(Z, L) -2-t-butoxycarbonylamino-N- [2- (2,4-dichloro-phenyl) -2-methoxyimino-ethyl] -3-hydroxy-propionamide (23 Synthesis of)

0.12 g (yield 72%) of the title compound were obtained in the same manner as in Example 10, except that 0.087 g of Nt-butoxycarbonyl L-serine was used instead of Nt-butoxycarbonyl L-leucine. Obtained.

Example 24

[(Z, L) -2-t-butoxycarbonylamino-N- [2- (2,4-dichloro-phenyl) -2-methoxyimino-ethyl] -3-hydroxy-butyramide ( Synthesis of 24]

0.11 g (yield 67%) of the title compound were obtained in the same manner as in Example 10, except that 0.093 g of Nt-butoxycarbonyl L-threonine was used instead of Nt-butoxycarbonyl L-leucine. Obtained.

Example 25

[(Z, L) -2-t-butoxycarbonylamino-N- [2- (2,4-dichloro-phenyl) -2-methoxyimino-ethyl] -4-methylthio-butyramide ( Synthesis of 25]

0.15 g (yield 84%) of the title compound were obtained in the same manner as in Example 10, except that 0.11 g of Nt-butoxycarbonyl L-methionine was used instead of Nt-butoxycarbonyl L-leucine. Obtained.

Example 26

[(Z, L) -2-t-butoxycarbonylamino-N- [2- (2,4-dichloro-phenyl) -2-methoxyimino-ethyl] -3- (4-hydroxyphenyl) Synthesis of Propionamide (26)]

0.16 g (yield 84%) of the title compound were carried out in the same manner as in Example 10, except that 0.12 g of Nt-butoxycarbonyl L-tyrosine was used instead of Nt-butoxycarbonyl L-leucine. Obtained.

¹ H NMR data of the compounds of Formula (I) synthesized according to the above Examples are shown in Table 2 below.

Biological Experimental Example

In order to verify the control effect against the phytopathogens of the compound of general formula (I) according to the present invention, the following four plant diseases were selected and the antimicrobial activity of each compound was investigated according to the method as described below. The compound of was found to exhibit excellent control effect.

씩 엽면살포하였으며, 이때 각 화합물의 처리농도가 250ppm으로 되도록 하였다. 약제가 살포된 식물을 실내온도에서 24시간 동안 방치하여 용매 및 물을 휘산시킨 다음, 하기 실험예들에 기재된 바와 같이 준비된 병원균을 접종하고 무처리구와 비교하여 식물병 예방효과를 산출하였다. 모든 실험은 2회 반복하였으며, 표 3의 기준에 따라 등급을 나누어 평가하였다.That is, after dissolving the compound in 10% acetone aqueous solution containing 250 ppm of Tween-20,

Leaf spraying was carried out, and the concentration of each compound was adjusted to 250 ppm. The plants sprayed with the medicament were left at room temperature for 24 hours to volatilize the solvent and water, and then inoculated with the prepared pathogens as described in the following experimental examples, and the plant disease prevention effect was calculated in comparison with the non-treated group. All experiments were repeated twice, and the ratings were divided according to the criteria in Table 3.

Experimental Example 1

[Antibacterial Activity against Rice Fever]

)에 접종하여 26.2

배양기에서 2주간 배양하였다. 병원균이 자란 배지의 표면을 고무쓸개로 긁어 기중균사를 제거하고 형광등이 켜진 선반(26 내지 28

)위에 놓아둠으로써 48시간동안 포자를 형성시켰다. 형성된 분생포자로부터 살균증류수를 이용하여 일정농도의 포자현탁액 (10⁶포자/

)을 제조한 후 벼도열병에 감수성인 낙동벼(3 내지 4엽기)에 흘러내릴 정도로 충분히 분무함으로써 병원균을 접종하였다.Rice febrile pathogens (Pyricularia grisea) rice bran agar medium (Rice Ploish 20g, dextrose 10g, agar 15g, distilled water 1

) 26.2

The incubator was incubated for 2 weeks. A shelf on which the pathogen was grown was scraped with a rubber gallbladder to remove airborne hyphae and fluorescent lights were turned on (26 to 28).

Spores were formed for 48 hours by placing them on. Spore suspension of a certain concentration using sterilized distilled water from conidia formed (10 ⁶ spores /

) Was inoculated with pathogens by spraying enough to flow down to Nakdong rice (3-4 leaves) susceptible to rice fever.

의 항온항습실에서 5일간 놓아둔 다음 발병면적을 계산하였다. 이때, 발병조사는 3 내지 4엽기 벼의 최상위엽 바로 밑의 완전히 전개된 잎에 형성된 병반면적을 표준이병면적률 대비표(전체 잎면적에 대해 병반면적이 차지하는 비율을 기준으로 하여 작성한 이병면적률 대비표)에 준하여 조사하고 표 3의 기준에 따라 등급을 매긴 후 그 결과를 표 4 에 나타내었다.Inoculated rice is left in the dark for 24 hours in a humid state, relative humidity is above 90%, temperature 26.2

After 5 days in the constant temperature and humidity room of the area was calculated. At this time, the onset of disease was calculated by comparing the diseased area formed on the fully developed leaf just below the uppermost leaves of the 3-4 leafy rice to the standard disease area ratio table (compared to the diseased area rate based on the ratio of the diseased area to the total leaf area). Table 4) shows the results according to the criteria of Table 3 and grades them according to the criteria in Table 3.

Experimental Example 2

[Antibacterial Activity against Rice Leaf House Blight]

배양병에 넣고 멸균한 후 감자 한천배지에서 3일간 배양시킨 병원균(Rhizoctonia solani AG-1)의 한천조각을 접종하였다. 10일간 배양한 후 균사 덩어리를 잘게 마쇄하여 2 내지 3엽기의 낙동벼가 자란 포트에 10

씩 고르게 접종하여 습실상(28.1

)에서 3일동안 배양하였다. 상대습도 80%이상의 항온항습실에 5일간 놓아둔 뒤 병발생율을 조사하였다. 발병정도는 2 내지 3엽기 유묘의 잎집에 형성된 병반면적을 표준이병면적율 대비표에 준하여 조사하고 표 3의 기준에 따라 등급을 매긴 후 그 결과를 표 4 에 나타내었다.Take the right amount of bran 1

After the sterilization in a culture bottle was inoculated with agar pieces of the pathogen (Rhizoctonia solani AG-1) incubated for three days in potato agar medium. After incubation for 10 days, finely ground mycelial mass,

Evenly inoculate evenly (28.1)

Incubated for 3 days. The incidence rate was investigated after 5 days of relative humidity at 80% relative humidity. The extent of incidence was investigated by examining the lesion area formed in the leaflets of 2 to 3 leaf seedlings according to the standard bleeding area ratio comparison table, and graded according to the criteria of Table 3, and the results are shown in Table 4 below.

Experimental Example 3

[Antibacterial Activity against Tomato Blight]

)에 접종한 후, 20

의 16시간 광처리 및 8시간 암처리 배양기에서 14일간 배양하여 유주자낭의 생성을 유도하였다. 플레이트에 살균 증류수를 가하고 시약스푼을 이용하여 균층으로부터 생성된 유주자낭을 분리한 후 4겹의 가아제로 유주자낭을 걸러내었다. 수확한 유주자낭의 농도를 5×10⁴개/

로 조정하여 접종원으로 사용하였다. 이 접종원을 토마노 유묘 하나당 3

씩 분무접종하였다. 접종한 식물체를 20

습실에서 5일 동안 발병시킨 후 병반면적율(%)을 조사하고 표 3의 기준에 따라 등급을 매긴 후 그 결과를 표 4에 나타내었다.Phytophthora infestans were added to Rye B agar medium (Rye 60g, sucrose 20g, β-sitosterol 50mg, agar 15g, distilled water)

20) after inoculation

Incubation was carried out for 14 days in a 16-hour light treatment and 8-hour dark treatment incubator to induce the production of endosperm sacs. Sterile distilled water was added to the plate, and the spooned sachets were separated from the bacterial layer using a reagent spoon. The concentration of harvested fertilizer sacs is 5 × 10 ⁴ /

Was used as the inoculum. It is three per one seedlings of Tomano seedlings

It was sprayed vigorously. 20 inoculated plants

After 5 days of invasion in a wet room, the area ratio (%) was investigated and graded according to the criteria of Table 3, and the results are shown in Table 4.

Experimental Example 4

[Antimicrobial Activity against Cucumber Gray Mold]

배양기에서 16시간 광처리와 8시간 암처리를 반복하여 10일간 수행함으로써 분생포자를 형성시켰다. 감자액체배지(감자 200g, 덱스트로스 20g, 증류수를 가하여 1

)를 배지에 붓고 형성된 포자를 긁은 다음 이를 가아제로 걸러서 포자를 수확하였다. 포자농도를 1×10⁶개/

가 되도록 조정하고 이를 접종원으로 하여 1엽기 오이 유묘에 3

씩 분무접종하였다. 접종한 식물체를 20

습실에서 4일간 습실처리하고 본엽 1엽의 병반면적율(%)을 조사한 다음, 표 3의 기준에 따라 등급을 매긴 후 그 결과를 표 4에 나타내었다.Pathogens isolated from tomatoes (Botrytis cinerea KC1) were inoculated in rice bran agar medium (RPA), and then

Conidia were formed by repeating 16 hours light treatment and 8 hours dark treatment in the incubator for 10 days. Potato liquid medium (potato 200g, dextrose 20g, distilled water is added 1

) Was poured into the medium, the formed spores were scraped, and then filtered by gauze to harvest the spores. Spore Concentration 1 × 10 ⁶ /

To the seedling cucumber seedlings 3

It was sprayed vigorously. 20 inoculated plants

After 4 days of wet treatment in the wet room, the leaf area ratio (%) of the first leaf was investigated, and graded according to the criteria of Table 3, and the results are shown in Table 4.

Claims (8)

Amino acid amide derivatives of the general formula (I) below, their geometric and stereoisomers:

Wherein X ₁ and X ₂ each independently represent hydrogen, halogen, methyl or methoxy, R ₁ represents hydrogen, phenyl or —CHR ₃ R ₄ where R ₃ represents hydrogen or methyl and R ₄ is Hydrogen, C ₁ -C ₃ alkyl, hydroxy, thiol, alkylthiomethyl, phenyl or hydroxyphenyl), and R ₂ represents hydrogen or propylene together with R ₁ . The compound of claim 1, wherein X ₁ and X ₂ each independently represent hydrogen or halogen, R ₁ represents hydrogen, phenyl or —CHR ₃ R ₄ (wherein R ₃ represents hydrogen or methyl, R ₄ represents hydrogen, Methyl, ethyl, isopropyl, hydroxy, thiol, alkylthiomethyl, phenyl or hydroxyphenyl), and R ₂ represents hydrogen or propylene together with R ₁ . A process for preparing a compound of formula (I) characterized by condensing a compound of formula (III) with a compound of formula (II) in the presence of a base and a coupling agent in a solvent:

Wherein X ₁ , X ₂ , R ₁ and R ₂ are as defined in claim 1. The solvent of claim 3 wherein the solvent is benzene, toluene, xylene, dichloromethane, 1,2-dichloroethane, chloroform, diethyl ether, dioxane, 1,2-dimethoxyethane, tetrahydrofuran, acetone, methylethylketone , Cyclohexanone, acetonitrile, propionitrile, methyl acetate, ethyl acetate, N, N-dimethylformamide, N, N-dimethylacetamide and dimethyl sulfoxide. The method according to claim 3, wherein the base is at least one selected from pyridine, 4-dimethylaminopyridine, triethylamine, N, N-dimethylaniline, tributylamine and N-methylmorpholine. The method according to claim 3, wherein the coupling agent is selected from dicyclohexylcarbodiimide (DCC), 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide (EDC) and silicon tetrachloride. Process with hydroxybenzotriazole. The reaction of claim 3 wherein the reaction is -30 to 70

10 minutes to 24 hours in the temperature range of. A composition for inhibiting the onset by phytopathogens, comprising a compound of formula (I) as defined in claim 1 together with a carrier commonly used in the field of pesticides.