KR950005734B1 - 4h, oh-furo[3,4-c]isoxazole derivatives and process for preparing them - Google Patents

Abstract

The preparation method of isooxazol (I) dervatives which has antifungal activity consists of 1) reacting nitro-olefin and alcohol with basic catalyst to form nitro compounds, 2) dehydrating nitro compounds with triethylamine and phenylisocyanate to form cycles as (I) in benzene or dichlromethane. Derivatives of (I) are R1 = propyl or isopropyl, R2 = H or methyl, R3 = H, methyl, ethyl, phenyl, phenyl chloride, aldehyde, or oxime.

Description

[발명의 명칭][Name of invention]

4H, 6H-푸로[3,4-c]이소옥사졸 유도체와 그 제조방법4H, 6H-furo [3,4-c] isoxazole derivatives and preparation method thereof

[발명의 상세한 명칭]Detailed Name of the Invention

본 발명은 식물병원균에 대하여 살균활성을 갖는 다음 일반식(I)로 표시되는 신규한 4H, 6H-푸로[3, 4-c]이소옥사졸 유도체와 그를 제조하는 방법에 관한 것이다.The present invention relates to a novel 4H, 6H-furo [3,4-c] isoxazole derivative represented by the following general formula (I) having bactericidal activity against phytopathogens and a method for producing the same.

상기식에서, R¹은 C₁~C₆의 알킬기 또는 치환된 페닐기이고, R²는 수소원자 또는 C₁~C₃알킬기이며, R³는 수소원자, C₁~C₄의 알킬기, 페닐기, 할로겐 원자로 치환된 페닐기, 알데히드기, -CH₂-R⁴의 치환된 메틸기 또는 -CH=N=OR⁵의 옥심기이며, 여기서, R⁴는 히드록시기, 알콕시기, 2-피라닐옥시기, 알킬카르보닐옥시기, 할로겐원자 또는 아민기이며, R⁵는 수소원자, 저급알킬기 또는 저급알켄기이다.Wherein R ¹ is a C ₁ to C ₆ alkyl group or a substituted phenyl group, R ² is a hydrogen atom or a C ₁ to C ₃ alkyl group, R ³ is a hydrogen atom, a C ₁ to C ₄ alkyl group, a phenyl group, a halogen An phenyl group substituted with an atom, an aldehyde group, a substituted methyl group of -CH ₂ -R ⁴ or an oxime group of -CH = N = OR ⁵ , wherein R ⁴ is a hydroxy group, an alkoxy group, 2-pyranyloxy group, alkylcarbonyl jade It is a time period, a halogen atom, or an amine group, R <^5> is a hydrogen atom, a lower alkyl group, or a lower alkene group.

일반직으로 기존에 알련진 살균활성을 갖는 이소옥사졸린 유도체는 다음 일반식(가)로 표시되는 화합물이 있다.Ixoxazoline derivatives having conventionally known bactericidal activity as a general job include compounds represented by the following general formula (A).

상기 일반식(가)의 화합물은 잎집마른병, 마름병, 모썩음병, 등 일부 병원균에 대해 살균활성이 있는 것으로 알려져 있으나, 그 효과가 그다지 크지 못하거나 일부 병원균에서는 효과가 미미하여 새로운 살균제의 개발이 요구되고 있는 실정이었다.The compound of the general formula (A) is known to have bactericidal activity against some pathogens, such as dry leaf disease, blight disease, mole disease, etc., but the effect is not so great or the effect is insignificant in some pathogens is required to develop a new fungicide It was happening.

따라서, 본 발명은 이제까지 살균제로 알려진바 없는 새로운 구조를 가지며 각종 식물병원균에 대해 예방 효과를 나타내고, 특히 일부 병균에 대해 선택적으로 우수한 살균력을 나타내는 신규한 이소옥사졸린 화합물을 제공하는데 그 목적이 있다.Accordingly, an object of the present invention is to provide a novel isoxazoline compound which has a novel structure which has not been known as a fungicide and exhibits a prophylactic effect against various phytopathogens, and particularly shows an excellent bactericidal power selectively against some pathogens.

또한 본 발명은 상기와 같은 신규 화합물을 유효성분으로 함유하는 살균제를 제공하는데 또다른 목적이 있다.It is another object of the present invention to provide a fungicide containing the novel compound as an active ingredient.

이하, 본 발명을 상세히 설명하면 다음과 같다.Hereinafter, the present invention will be described in detail.

본 발명은 다음 일반식(I)로 표시되는 4H, 6H-푸로[3, 4-c]이소옥사졸린 유도체에 관한 것이다.The present invention relates to 4H, 6H-furo [3, 4-c] isooxazoline derivatives represented by the following general formula (I).

상기식에서, R¹, R²및 R³는 각각 상기 정의한 바와 같다.Wherein R ¹ , R ² and R ³ are each as defined above.

본 발명에 따른 상기 일반식(I)의 신규화합물은 상기 일반식(I)의 치환기중에서, R¹이 푸르필기 또는 이소프로필기이거나, 염소원자, 불소원자, 메틸기 또는 트리플루오로메틸기 등으로 치환된 페닐기이고, R²가 수소원자나 메틸기이고, R³가 수소원자, 메틸기, 에틸기, 페닐기, 염소원자로 치환된 페닐기, 알데히드기, -CH₂R⁴의 치환된 메틸기 또는 -CH=N=OR⁵의 옥심기이며, 이때 R⁴가 히드록시기, 메톡시기, 2-피리딜옥시기, 메틸카르보닐옥시기, 연소원자, 브롬원자 또는 모르폴린기이며, R⁵가 수소원자, 메틸기, 에틸기, 알릴기일때 바람직하다.The novel compound of the general formula (I) according to the present invention may be substituted with a chlorine atom, a fluorine atom, a methyl group, a trifluoromethyl group, or the like, in a substituent group of the general formula (I), wherein R ¹ is a furpil group or an isopropyl group. Is a phenyl group, R ² is a hydrogen atom or a methyl group, R ³ is a hydrogen atom, a methyl group, an ethyl group, a phenyl group, a phenyl group substituted with a chlorine atom, an aldehyde group, a substituted methyl group of -CH ₂ R ⁴ , or -CH = N = OR ⁵ Wherein R ⁴ is a hydroxy group, methoxy group, 2-pyridyloxy group, methylcarbonyloxy group, combustion atom, bromine atom or morpholine group, and R ⁵ is hydrogen atom, methyl group, ethyl group, allyl group desirable.

또한 상기 일반식(I)의 화합물의 대표적 예를들면 다음 표 1에 열거한 바와 같다.In addition, representative examples of the compound of the general formula (I) are as listed in Table 1 below.

[표 1a]TABLE 1a

[표 1b]TABLE 1b

[표 1c]TABLE 1c

[표 1d]TABLE 1d

[표 1e]TABLE 1e

상기 일반식(I)의 대표적인 화합물인 명칭을 열거하면 다음과 같다.If the name which is a typical compound of the said General formula (I) is listed, it is as follows.

1 6-(4-클로로페닐)-3-메틸-4H, 6H-푸로[3, 4-c]이소옥사졸 (6)1 6- (4-chlorophenyl) -3-methyl-4H, 6H-furo [3, 4-c] isoxazole (6)

2 6-(2, 4-디클로로페닐)-3-메틸-4H, 6H-푸로[3, 4-c]이소옥사졸 (10)2 6- (2,4-dichlorophenyl) -3-methyl-4H, 6H-furo [3, 4-c] isoxazole (10)

3 6-(4-플루오로페닐)-3-메틸-4H, 6H-푸로[3, 4-c]이소옥사졸 (18)3 6- (4-fluorophenyl) -3-methyl-4H, 6H-furo [3, 4-c] isoxazole (18)

4 6-(4-플루오로페닐)-3-메틸-4H, 6H-푸로[3, 4-c]이소옥사졸 (19)4 6- (4-fluorophenyl) -3-methyl-4H, 6H-furo [3, 4-c] isoxazole (19)

5 6-(2-클로로페닐)-3-히드록시메틸-4H, 6H-푸로[3, 4-c]이소옥사졸 (32)5 6- (2-chlorophenyl) -3-hydroxymethyl-4H, 6H-furo [3, 4-c] isoxazole (32)

6 6-(2-클로로페닐)-3-알데히도-4H, 6H-푸로[3, 4-c]이소옥사졸 (34)6 6- (2-chlorophenyl) -3-aldehyde-4H, 6H-furo [3, 4-c] isoxazole (34)

7 6-(2-클로로페닐)-3-에톡시이미노메틸-4H, 6H-푸로[3, 4-c]이소옥사졸 (35)7 6- (2-chlorophenyl) -3-ethoxyiminomethyl-4H, 6H-furo [3, 4-c] isoxazole (35)

8 6-(2-클로로페닐)-3-브로모메틸-4H, 6H-푸로[3, 4-c]이소옥사졸 (37)8 6- (2-chlorophenyl) -3-bromomethyl-4H, 6H-furo [3, 4-c] isoxazole (37)

9 6-(2-클로로페닐)-3-히드록시이미노메틸-4H, 6H-푸로[3, 4-c]이소옥사졸 (40)9 6- (2-chlorophenyl) -3-hydroxyiminomethyl-4H, 6H-furo [3, 4-c] isoxazole (40)

10 6-(4-클로로페닐)-3-(2-피라닐옥시)메틸-4H, 6H-푸로[3, 4-c]이소옥사졸 (42)10 6- (4-chlorophenyl) -3- (2-pyranyloxy) methyl-4H, 6H-furo [3, 4-c] isoxazole (42)

11 6-(2-클로로페닐)-3-(2-피라닐옥시)메틸-4H, 6H-푸로[3, 4-c]이소옥사졸 (43)11 6- (2-chlorophenyl) -3- (2-pyranyloxy) methyl-4H, 6H-furo [3, 4-c] isoxazole (43)

12 6-(4-클로로페닐)-3-히드록시메틸-4H, 6H-푸로[3, 4-c]이소옥사졸 (44)12 6- (4-chlorophenyl) -3-hydroxymethyl-4H, 6H-furo [3, 4-c] isoxazole (44)

13 6-(4-클로로페닐)-3-브로모메틸-4H, 6H-푸로[3, 4-c]이소옥사졸 (48)13 6- (4-chlorophenyl) -3-bromomethyl-4H, 6H-furo [3, 4-c] isoxazole (48)

14 6-(4-클로로페닐)-3-알데히도-4H, 6H-푸로[3, 4-c]이소옥사졸 (49)14 6- (4-chlorophenyl) -3-aldehyde-4H, 6H-furo [3, 4-c] isoxazole (49)

15 6-(4-클로로페닐)-3-히드록시이미노메틸-4H, 6H-푸로[3, 4-c]이소옥사졸 (55)15 6- (4-chlorophenyl) -3-hydroxyiminomethyl-4H, 6H-furo [3, 4-c] isoxazole (55)

상기와 같은 본 발명의 일반식(I)로 표시되는 화합물은 이제까지 알려진바 없는 신규한 구조의 화합물로서, 각종 식물병원균에 대하여 예방효화 및 우수한 살균효과를 나타내며, 특히, 도열병, 잿빛곰팡이병, 흰가루병 등에 대해서 매우 우수한 살균 효력을 나타내며, 그외에도 벼입집무늬마름병, 토마토역병, 밀묽은녹병 등에 대해서도 매우 우수한 살균효력을 나타내는 것이므로 이를 유효성분으로 하는 농원예용 살균제로서 매우 유용하다.The compound represented by the general formula (I) of the present invention as described above is a compound of a novel structure that has not been known so far, exhibits a prophylactic effect and excellent bactericidal effect against various phytopathogens, in particular, heat, gray mold, powdery mildew It is very useful as an agricultural horticultural fungicide with an effective bactericidal effect, since it shows very good bactericidal effect against rice bran blight, tomato late blight, wheat rust disease, and the like.

본 발명에 따라 상기 일반식(I)의 이소옥사졸 유도체 화합물을 제조하는 방법을 상세히 살펴보면 다음과 같다.Looking at the method for producing the isoxazole derivative compound of the general formula (I) according to the invention in detail as follows.

종래에도 이소옥사졸 화합물을 제조하는 방법은 여러가지가 알려져 있지만(A.Lang and Y.-i. Lin, "Comprehensive Heterocyclic Chemistry", Ed. A.R.Katritzky, Pergamon Press, Oxford, Vol 6, 1984, pp.61-88), 본 발명에서 상기 일반식(I)의 화합물을 제조하기 위해서는 다음 일반식(Ⅱ)로 표시되는 니트로 올레핀 화합물과 다음 일반식(Ⅲ)으로 표시되는 알콜 유도체를 염기존재하에 반응시켜서 다음 일반식(Ⅳ)로 표시되는 니트로 화합물을 제조한 다음, 이를 탄수반응시키고 고리화시켜서 제조하는 방법을 사용하였다.There are many known methods for preparing isoxazole compounds (A. Lang and Y.-i. Lin, "Comprehensive Heterocyclic Chemistry", Ed. ARKatritzky, Pergamon Press, Oxford, Vol 6, 1984, pp. 61-88), in order to prepare the compound of the general formula (I) in the present invention by reacting the nitro olefin compound represented by the following general formula (II) and the alcohol derivative represented by the following general formula (III) in the presence of a base To prepare a nitro compound represented by the following formula (IV), and then carbohydrate reaction and cyclization was used.

상기 식들중에서, R¹, R²및 R³는 각각 상기 일반식(I)에서 정의한 바와 같다.In the formulas, R ¹ , R ² and R ³ are as defined in the general formula (I), respectively.

일반식(Ⅳ)의 니트로화합물을 문헌(T.Mukaiyama and T.Hoshino, J.Am.chem.Soc., 1960, 82, 5339)에 알려진 방법으로 탈수반응시키면 다음 구조식으로 나타내는 중간체인 니트릴옥사이드 화합물이 생성되며, 같은 반응조건에서 생성된 니트릴 옥사이드가 같은 분자내에 존재하는 삼중결합에 첨가되어 상기 일반식(I)의 화합물이 제조되게 된다.When the nitro compound of the general formula (IV) is dehydrated by a method known from T. Mukaiyama and T. Hoshino, J. Am. Chem. Soc., 1960, 82, 5339, a nitrile oxide compound which is an intermediate represented by the following structural formula The nitrile oxide produced under the same reaction conditions is added to the triple bond present in the same molecule to prepare the compound of formula (I).

그러나 본 발명의 방법에서는 상기 탈수 반응에 사용되는 시약으로 소량의 트리에틸아민과 2,5~3배에 해당하는 과량의 페닐이소시아네이트 혹은 P-클로로 페닐이소시아네이트가 사용될 수 있고, 용매는 벤젠이나 디클로로메탄도 사용가능하다.However, in the method of the present invention, a small amount of triethylamine and an excess of 2,5 to 3 times the amount of phenyl isocyanate or P-chloro phenyl isocyanate may be used as the reagent used in the dehydration reaction, and the solvent is benzene or dichloromethane. Also available.

또한, 상기 일반식(Ⅳ)의 화합물은 상기 일반식(Ⅱ)의 니트로올레핀류에다 적절히 치환된 상기 일반식(Ⅲ)의 알콜유도체를 부가시켜서 높은 수율로 얻을 수 있는바, 이때 사용되는 염기는 예컨대 노르말부틸리튬이 적당하고, 용매는 예컨대 테트라히드로푸란이나 에틸에테르가 바람직하다.In addition, the compound of the general formula (IV) can be obtained in high yield by adding the alcohol derivative of the general formula (III) appropriately substituted with the nitroolefins of the general formula (II). Normally, for example, normal butyllithium is preferable, and the solvent is preferably tetrahydrofuran or ethyl ether.

본 발명에 의한 일반식(I)의 화합물을 제조하는 방법을 다음의 실시예에 의해서 구체적으로 설명하겠는바, 본 발명이 실시예에 의해 한정되는 것은 아니다.The method for producing the compound of formula (I) according to the present invention will be specifically described by the following examples, but the present invention is not limited by the examples.

[실시예 1]Example 1

6-(2-클로로페닐)-3-메틸-4H, 6H-푸로[3, 4-c]이소옥사졸(7)의 제조Preparation of 6- (2-chlorophenyl) -3-methyl-4H, 6H-furo [3, 4-c] isoxazole (7)

[단계 1][Step 1]

1-(2-클로로페닐)-2-니트로에틸 2-부티닐에테르(A)의 합성Synthesis of 1- (2-chlorophenyl) -2-nitroethyl 2-butynyl ether (A)

2-부틴-1-올 2.10g (0.03몰)을 테트라히드로푸란 20㎖에 녹인 용액을 -78℃로 냉각하고, n-부틸리튬용액(1.6M) 18.8㎖를 천천히 가한다. 반응온도를 0℃까지 천천히 올린후 20분간 교반하고, 여기에 α-(2-클로로페닐)-β-니트로에틸렌 1.84g(0.01몰)을 5㎖의 테트라히드로푸란에 녹인 용액을 가한다.A solution of 2.10 g (0.03 mol) of 2-butyn-1-ol in 20 ml of tetrahydrofuran is cooled to -78 ° C, and 18.8 ml of n-butyllithium solution (1.6 M) is slowly added. After slowly raising the reaction temperature to 0 ° C., the mixture was stirred for 20 minutes, and a solution of 1.84 g (0.01 mol) of α- (2-chlorophenyl) -β-nitroethylene was added to 5 ml of tetrahydrofuran.

반응혼합물을 실온에서 4시간 교반시킨후, 다시 얼음물로 냉각한다. 묽은 초산(0.03몰)을 천천히 가하면서 교반시킨다. 층을 분리한후 물층을 에틸에테르로 추출하고 유기층을 모아서 소금물로 세척한후 건조시키고 농축하여 크로마토그라피로 정제하여 순수한 표제화합물 A를 2.22g (수율 87.6%) 얻는다.The reaction mixture is stirred at room temperature for 4 hours and then cooled with ice water. Dilute acetic acid (0.03 mol) is slowly added while stirring. After separating the layers, the water layer was extracted with ethyl ether, the organic layers were collected, washed with brine, dried, concentrated and purified by chromatography to obtain 2.22 g (yield 87.6%) of pure title compound A.

[단계 2][Step 2]

단계 1에서 제조한 화합물 A 2.15g(8.5밀리몰)과 페닐이소시아네이트 2.52g (21.2밀리몰)을 벤젠 60㎖에 녹인후 몇 방울의 트리에틸아민을 넣고 질소기류하에서 상온에서 교반시킨다. 반응완료후 생긴 고체를 여과하고 여과액에 물 2㎖를 넣고 다시 상온에서 3시간 동안 교반시킨다. 반응물을 감압여과후 층을 분리하여 유기층을 취하여 건조시킨 후 농축하여 크로마토그라피로 정제하여 순수한 목적화합물 1.72g (수율 86.2%)를 얻는다.2.15 g (8.5 mmol) of Compound A prepared in Step 1 and 2.52 g (21.2 mmol) of phenyl isocyanate were dissolved in 60 mL of benzene, followed by adding a few drops of triethylamine, followed by stirring at room temperature under a nitrogen stream. After the reaction was completed, the resulting solid was filtered, and 2 ml of water was added to the filtrate, and the mixture was stirred at room temperature for 3 hours. The reaction product was filtered under reduced pressure, the layers were separated, the organic layer was taken, dried, concentrated and purified by chromatography to obtain 1.72 g (yield 86.2%) of pure target compound.

융점 : 88.7-89.2℃Melting Point: 88.7-89.2 ℃

[실시예 2]Example 2

6-(2-클로로페닐)-3-알데히도-4H, 6H-푸로[3, 4-c]이소옥사졸(34)의 제조Preparation of 6- (2-chlorophenyl) -3-aldehyde-4H, 6H-furo [3, 4-c] isoxazole (34)

6-(2-클로로페닐)-3-히드록시메틸-4H, 6H-푸로[3, 4-c]이소옥사졸 1.77g (7밀리몰)을 디클로로메탄 10㎖에 녹이고, 여기에 피리디늄 디크로메이트 3.98g(10밀리몰)을 넣고 실온에서 하룻동안 교반시킨다.Dissolve 1.77 g (7 mmol) of 6- (2-chlorophenyl) -3-hydroxymethyl-4H, 6H-furo [3,4-c] isoxazole in 10 ml of dichloromethane, and pyridinium dichromate Add 3.98 g (10 mmol) and stir at room temperature overnight.

반응혼합물을 여과하고 여과액을 크로마토그라피로 정제하여 순수한 목적화합물 849㎎(수율48.3%)을 얻는다.The reaction mixture was filtered and the filtrate was purified by chromatography to give 849 mg (48.3%) of pure target compound.

[실시예 3]Example 3

6-(2-클로로페닐)-3-(0-에틸옥시미노)-4H, 6H-푸로[3, 4-c]이소옥사졸(35)의 제조Preparation of 6- (2-chlorophenyl) -3- (0-ethyloxymino) -4H, 6H-furo [3, 4-c] isoxazole (35)

상기 실시예 2에서 제조한 알데히드 화합물 594㎎ (2.38밀리몰)와 에톡시 아민 염산염 278㎎ (2.85밀리몰)을 10㎖의 에탄올에 녹이고 여기에 초산 나트륨 234㎎을 넣고 1시간 동안 교반시킨다. 반응혼합물에 에틸에테르 20㎖를 가하고 물로 세척후, 건조 및 농축하여 크로마토그라피로 정제하여 순수한 목적화합물 347㎎ (수율 49.9%)을 얻는다.594 mg (2.38 mmol) of the aldehyde compound prepared in Example 2 and 278 mg (2.85 mmol) of ethoxy amine hydrochloride were dissolved in 10 ml of ethanol, and 234 mg of sodium acetate was added thereto and stirred for 1 hour. 20 ml of ethyl ether was added to the reaction mixture, washed with water, dried, concentrated and purified by chromatography to obtain 347 mg (yield 49.9%) of the title compound.

[실시예 4]Example 4

6-(4-클로로페닐)-3-브로모메틸-4H, 6H-푸로[3, 4-c]이소옥사졸의제조Preparation of 6- (4-chlorophenyl) -3-bromomethyl-4H, 6H-furo [3, 4-c] isoxazole

6-(4-클로로페닐-3-히드록시 메틸푸로[3, 4-c]이소옥사졸 1.50g (5.9밀리몰)과 사브롬화탄소 2.75g (17.8밀리몰)을 디클로로메탄 15㎖에 녹인 용액을 0℃로 냉각하고, 여기에 트리페닐포스틴 4.68g (4.7밀리몰)을 조금씩 가하면서 교반시킨다. 첨가완료후 반응혼합물을 상온에서 30분간 더 교반한후 에틸에테르 10㎖를 가한다. 생성된 고체물질을 여과하고 여과액을 농축하여 크로마토그라피로 정제하여 순수한 목적화합물 680㎎ (수율 36.4%)을 얻는다.1.50 g (5.9 mmol) of 6- (4-chlorophenyl-3-hydroxy methylfuro [3,4-c] isoxazole and 2.75 g (17.8 mmol) of carbon tetrabromide in 15 mL of dichloromethane were dissolved. After cooling, the mixture was stirred while adding 4.68 g (4.7 mmol) of triphenylphosphine in small portions, and after the addition was completed, the reaction mixture was further stirred at room temperature for 30 minutes, and 10 ml of ethyl ether was added thereto. The filtrate was concentrated and the filtrate was purified by chromatography to give 680 mg (yield 36.4%) of pure target compound.

융점 : 61-63℃Melting Point: 61-63 ℃

상기와 같이 하여 제조된 본 발명의 4H, 6H-푸로[3, 4-c]이소옥사졸 유도체(I)는 농원예용 살균제로서 그자체를 사용할 수도 있으나, 종래의 방법에 따라 통상의담체, 계면활성체, 분산제, 또는 보조제와 혼합하여 분말제제, 습윤성 분말, 유화성농축물, 과립형제제, 펠렛형 제제 등과 같은 제제형으로 조제하여 사용할 수 있다.The 4H, 6H-furo [3, 4-c] isoxazole derivative (I) of the present invention prepared as described above may be used as an agricultural horticultural fungicide itself, but according to conventional methods, conventional carriers, interfaces It can be used in admixture with active agents, dispersants, or auxiliaries in the form of powders, wettable powders, emulsifiable concentrates, granules, pellets and the like.

한편, 본 발명이 화합물들에 대하여 다음과 같은 시험방법으로 살균활성을 측정하였는바, 이때, 본 발명의 따른 일반식(I)의 신규화합물의 식물병원균에 대한 예방효과(protective effect)조사를 위하여 상기 일반식(I)의 화합물 25㎎을 10㎖의 아세톤에 용해시키고, 이 용액에 트위 20 250ppm 수용액 90㎖를 첨가하여 그 농도기 250ppm 또는 500ppm이 되게 조정한후 일정 크기의 기주식물에 50㎖씩 엽면 살포하였다.On the other hand, the present invention was measured the bactericidal activity of the compounds by the following test method, at this time, to investigate the protective effect (phytopathogenic effect) of the novel compounds of the general formula (I) according to the present invention 25 mg of the compound of formula (I) was dissolved in 10 ml of acetone, and 90 ml of a tween 20 250 ppm aqueous solution was added to the solution to adjust the concentration to 250 ppm or 500 ppm, and then 50 ml each of the host plants having a predetermined size. Foliar spray was applied.

약제가 살포된 식물을 실내온도에서 24시간 동안 방치하여 용매 및 물을 휘산시킨 뒤, 각기 아래와 같은 준비된 병원균을 접종하였다. 모든 실험은 2회 반복으로 실시하였다.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, respectively. All experiments were conducted in two replicates.

[시험예 1][Test Example 1]

벼도열병에 대한 살균효과Bactericidal Effect against Rice Fever

병원균(Pyricularia oryzae)의 균주를 쌀겨 한천배지(Rice Polish 20g, Dextrose 10g, Agar 15g, D.W. 1ℓ)에 접종하여 26℃ 배양기에서 2주간 배양하였다.Pathogens (Pyricularia oryzae) strains were inoculated in rice bran agar medium (Rice Polish 20g, Dextrose 10g, Agar 15g, D.W. 1L) and incubated for 2 weeks in a 26 ℃ incubator.

병원균이 자란 배지를 고무쓸개로 배지 표면을 긁어 기중균사를 제거하고 형광등이 켜진 선반(25~28℃)에서 48시간 동안 포자를 형성시켰다.The pathogen-grown medium was scraped off the surface of the medium with a rubber gallbladder to remove aerial hyphae, and spores were formed for 48 hours on a fluorescent lamp-turned shelf (25-28 ° C).

병균접종은 형성시킨 분생포자를 살균증류수를 이용하여 일정 농도의 포자현탁액(10⁶포자/㎖)을 만든 뒤, 벼 도열병에 감수성이 낙동벼(2엽기)에 흘러 내릴정도로 충분히 분무하였다.Bacterial inoculation was made of spore suspension (10 ⁶ spores / ml) at a certain concentration using sterilized distilled water, and then sprayed sufficiently so that susceptibility to rice blast was flowed to Nakdong rice (2 leaf phase).

접종된 벼는 습실상에서 암상태로 24시간 놓아둔뒤에, 상대습도 90%이상이며 온도 26±2℃인 항온항습실에서 5일간 둔뒤 발병 면적을 조사하였다. 병조사는 3-4엽기 벼의 최상위엽 바로 밑의 완전 전개된 잎에 형성된 병반 면적을 표준 이병면적을 대비표에 준하여 조사하였다.The inoculated rice was left in the dark for 24 hours, and then incubated for 5 days in a constant temperature and humidity room with a relative humidity of 90% or higher and a temperature of 26 ± 2 ° C. The disease was investigated by examining the lesion area formed on the fully developed leaf just below the top leaf of 3-4 leaf rice.

[시험예 2][Test Example 2]

벼잎집무늬 마름병에 대한 살균효과Bactericidal Effect on Rice Leaf House Blight

적당한 양의 밀기울을 1ℓ배양병에 넣고 멸균한 후 감자 한천배지에서 3일간 자란 병원균(Rhizpctonia solani)의 한천조각을 접종한후 배양된 균사 덩어리를 적당히 잘게 마쇄하여 2-3엽기의 낙동벼가 자란 포트(5㎝)에 고르게 접종하여 습실상(28±1℃)에서 배양후 상대습도 80% 이상이 항온항습실에서 5일간 둔뒤 병 발생을 조사하였다.Put a proper amount of bran into 1ℓ bottle and sterilize it, inoculate agar pieces of pathogen (Rhizpctonia solani) grown on potato agar medium for 3 days, and then cultivate the mycelial cultivated into small pieces. (5cm) and inoculated evenly in a humidified room (28 ± 1 ℃) after the relative humidity of more than 80% was placed in a constant temperature and humidity room for 5 days and the disease was investigated.

발병조사는 3엽기 유묘의 잎집에 발병된 병반의 면적율을 잎집면적에 대한 병반면적이 차지하는 비율을 기준으로 하여 작성한 이병면적을 대비표에 준하여 조사하였다.The incidence survey was conducted based on the comparison table of the diseased area, which was based on the ratio of the lesion area to the leaf area, of the lesions in the leaflets of the three-leaf seedlings.

[시험예 3][Test Example 3]

오이 잿빛곰팡이 병에 대한 살균효과Bactericidal Effect on Cucumber Gray Mold Disease

토마토로부터 분리한 균주(Botrytis cinerea)를 감자한천배지(PDA)에 접종하고 25℃의 배양기에 플레이트를 놓아 광암상태하에서 15일간 배양하여 포자를 형성시켰다. 배지에 형성된 포자를 플레이트당 10㎖의 증류수를 넣은 후, 붓으로 포자를 긁어 이를 가아제로 걸러서 포자를 수확한후 포자농도가 10⁶개/㎖가 되게 한뒤 1엽의 병반면적율을 조사하였다.Strains isolated from tomato (Botrytis cinerea) were inoculated in potato agar medium (PDA) and placed in a plate at 25 ℃ incubator for 15 days in the light dark state to form spores. The spores formed on the medium were put in 10 ml of distilled water per plate, the spores were scraped with a brush, and the spores were collected by gauze, and the spore concentration was 10 ⁶ / ml.

[시험예 4][Test Example 4]

토마토역병 대한 살균효과Sterilization Effect against Tomato Blight

역병(Phytophthora infestans)균을 V-8쥬스한천(V-8 juice 200㎖, CaCo₃4.5g, agar 15g, distilled water 800㎖) 배지에 올려놓고 20℃에서 16시간 광처리와 8시간 암처리 하여 14일 배양한 후 포자를 수확하였다. 이때 플레이트에 살균 증류수를 넣고 흔들어서 유주자안을 균총으로부터 떼어낸 후 4겹 헝겊조각을 사용하여 유주자낭을 걸렀다. 수확한 유주자낭의 농도를 10⁵개/㎖로 조정하였고, 이 접종원을 토마토 유묘에 분무접종하여 20℃ 습실상에서 1일동안 습실 처리한 후 20℃ 상대습도 80% 이상의 항은 항습실로 옮겨 4일 동안 발병시킨 후 토마토 1엽과 2엽의 병반면적율(5)을 조사하였다.Phytophthora infestans were put on V-8 juice agar (V-8 juice 200ml, CaCo ₃ 4.5g, agar 15g, distilled water 800ml) medium, and light treatment at 20 ℃ for 16 hours and dark treatment for 14 hours. Spores were harvested after one incubation. At this time, sterile distilled water was added to the plate and shaken to remove the inside of the fungus from the fungus, and then, 4 pieces of cloth were used to filter the fungal porridge. The concentration of harvested saponiferous sac was adjusted to 10 ⁵ pcs / ml, and the inoculum was sprayed with tomato seedlings for 1 day in a 20 ° C. chamber. After the onset, the lesion area ratio (5) of one and two leaves of tomato was examined.

[시험예 5][Test Example 5]

밀 붉은녹병에 대한 살균효과Sterilization Effect against Wheat Red Rust

병원균(Puccinia recondita)은 실험실에서 식물체에 직접 계대배양하여 사용하였다. 균주의 계대배양 및 약효조사를 위해서 일회용 포트(직경 : 6.5㎝)에 15립씩의 밀종자(은파)를 파종하여 온실에서 7일간 재배한 1엽기의 밀에 포자를 털어서 접종하였다. 접종한 1엽기의 밀은 20℃의 습실상에서 1일간 습실 처리 한후에 상대습도가 70%인 20℃의 항온 항습실로 옮겨서 발병을 유도하고 접종 10일후에 발병을 조사하였다. 발병조사는 녹병포자를 접종한지 10일후에 병반면적율을 조사하였다.The pathogen (Puccinia recondita) was used for direct passage to plants in the laboratory. For subculture and pharmacological investigation of the strain, 15 seed grains (silver onions) were seeded in a disposable pot (diameter: 6.5 cm), and the spores were inoculated by shaking the one-leafed wheat grown for 7 days in a greenhouse. After inoculation of 1 leaf wheat inoculated at 20 ° C. for 1 day, it was transferred to a constant temperature and humidity room of 20 ° C. with a relative humidity of 70% to induce the onset, and 10 days after inoculation was investigated. The incidence was investigated 10 days after inoculation of rust spores.

[시험예 6][Test Example 6]

보리 흰가루병에 대한 살균효과Bactericidal Effect on Barley Powder Disease

병원균(Erysiphe graminis f.sp.hordei)은 실험실에서 계대 배양하여 사용하였다. 균주의 계대배양 및 약효조사를 위해서 일회용 포토(직경 : 6.5㎝)에 15립씩의 보리종자(동보리 1호)를 파종하여, 온실(25±5℃)에서 7일간 재배한 1엽기의 보리에 흰가루병 포자를 털러 접종하여 발병시켰다. 위와 같은 방법으로 접종된 식물을 상대습도 50%, 22-24℃ 정도의 항온항습실에 옮겨 7일간 발병을 유도한뒤 병반면적율을 조사하였다.The pathogen (Erysiphe graminis f.sp.hordei) was used by passage in the laboratory. For subculture and pharmacological investigation of strains, seeded barley seeds (East barley No. 1) of 15 grains were placed in a disposable photo (diameter: 6.5 cm), and then grown on a barley barley grown for 7 days in a greenhouse (25 ± 5 ℃). The powdery mildew spores were inoculated by the inoculation. The inoculated plants were inoculated in the same way as 50% relative humidity and 22-24 ℃ in a constant temperature and humidity room to induce the onset for 7 days and then the area ratio of the lesions was investigated.

상기 시험예 1에서 6까지의 시험결과에 대하여 다음식에 따라 방제가를 산출하고 그 결과는 다음 표 2에 나타내었다.For the test results of Test Examples 1 to 6, the control value was calculated according to the following equation, and the results are shown in Table 2 below.

[표 2]TABLE 2

Claims (8)

다음 일반식(I)로 표시되는 4H, 6H-푸로[3, 4-c]이소옥사졸 유도체.4H, 6H-furo [3, 4-c] isoxazole derivatives represented by the following general formula (I). 상기식에서, R¹은 C₁~C₆의 알킬기 또는 치환된 페닐기이고, R²는 수소원자 또는 C₁~C₃알킬기이며, R³는 수소원자, C₁~C₄의 알킬기, 페닐기, 할로겐 원자로 치환된 페닐기, 알데히드기, -CH₂-R⁴의 치환된 메틸기 또는 -CH=N=OR⁵의 옥심기이며, 여기서, R⁴는 히드록시기, 알콕시기, 2-피라닐옥시기, 알킬카르보닐옥시기, 할로겐원자 또는 아민기이며, R⁵는 수소원자, 저급알킬기 또는 저급알켄기이다.Wherein R ¹ is a C ₁ to C ₆ alkyl group or a substituted phenyl group, R ² is a hydrogen atom or a C ₁ to C ₃ alkyl group, R ³ is a hydrogen atom, a C ₁ to C ₄ alkyl group, a phenyl group, a halogen An phenyl group substituted with an atom, an aldehyde group, a substituted methyl group of -CH ₂ -R ⁴ or an oxime group of -CH = N = OR ⁵ , wherein R ⁴ is a hydroxy group, an alkoxy group, 2-pyranyloxy group, alkylcarbonyl jade It is a time period, a halogen atom, or an amine group, R <^5> is a hydrogen atom, a lower alkyl group, or a lower alkene group. 제1항에 있어서, R¹은 푸로필기 또는 이소프로필기이거나, 염소원자, 불소원자, 메틸기 또는 트리플루오로메틸기로 치환된 페닐기인 것을 특징으로 하는 4H, 6H-푸로[3, 4-c]이소옥사졸 유도체.The 4H, 6H-furo [3, 4-c] according to claim 1, wherein R ¹ is a fluoro group or an isopropyl group, or a phenyl group substituted with a chlorine atom, a fluorine atom, a methyl group or a trifluoromethyl group. Ixoxazole derivatives. 제1항에 있어서, R²는 수소원자나 메틸기인 것을 특징으로 하는 4H, 6H-푸로[3, 4-c]이소옥사졸 유도체.The 4H, 6H-furo [3,4-c] isoxazole derivative according to claim 1, wherein R ² is a hydrogen atom or a methyl group. 제1항에 있어서, R³는 수소원자, 메틸기, 에틸기, 페닐기, 염소원자로 치환된 페닐기, 알데히드기, -CH₂R⁴의 치환된 메틸기 또는 -CH=N-OR⁵의 옥심기인 것을 특징으로 하는 4H, 6H-푸로[3, 4-c]이소옥사졸 유도체.R ³ is a hydrogen atom, a methyl group, an ethyl group, a phenyl group, a phenyl group substituted with a chlorine atom, an aldehyde group, a substituted methyl group of -CH ₂ R ⁴ , or an oxime group of -CH = N-OR ⁵ . 4H, 6H-furo [3, 4-c] isoxazole derivatives. 제4항에 있어서, R⁴는 히드록시기, 메톡시기, 2-피리딜옥시기, 메틸카르보닐옥시기, 염소원자, 브롬원자, 또는 모르폴린기인 것을 특징으로 하는 4H, 6H-푸로[3, 4-c]이소옥사졸 유도체.The 4H, 6H-furo [3,4-] according to claim 4, wherein R ⁴ is a hydroxy group, a methoxy group, a 2-pyridyloxy group, a methylcarbonyloxy group, a chlorine atom, a bromine atom, or a morpholine group. c] isoxazole derivatives. 제4항에 있어서, R⁵는 수소원자, 메틸기, 에틸기, 알릴기인 것을 특징으로 하는 4H, 6H-푸로[3, 4-c]이소옥사졸 유도체.The 4H, 6H-furo [3, 4-c] isoxazole derivative according to claim 4, wherein R ⁵ is a hydrogen atom, a methyl group, an ethyl group, or an allyl group. 다음 일반식(I)로 표시되는 4H, 6H-푸로[3, 4-c]이소옥사졸 유도체를 유효성분으로 함유하여 농원예용으로 사용가능한 고체 또는 액체 담체와 혼합하여 이루어진 농원예용 살균제조성물.A horticultural germicide composition comprising 4H, 6H-furo [3, 4-c] isoxazole derivatives represented by the following general formula (I) as an active ingredient and mixed with a solid or liquid carrier usable for farm horticulture. 상기식에서, R¹, R²및 R³는 각각 상기 청구번위 제1항의 일반식(I)에서 정의한 바와 같다.Wherein R ¹ , R ² and R ³ are each as defined in formula (I) of claim 1 above. 다음 일반식(Ⅱ)로 표시되는 니트로올레핀 화합물과 다음 일반식(Ⅲ)으로 표시되는 알콜유도체를 염기 존재하에 반응시켜서 다음 일반식(Ⅳ)로 표시되는 니트로화합물을 제조한 다음, 이를 탈수반응시키고 고리화시켜서 다음 일반식(I)로 표시되는 4H, 6H-푸로[3, 4-c]이소옥사졸 유도체를 제조하는 방법.The nitroolefin compound represented by the following general formula (II) and the alcohol derivative represented by the following general formula (III) are reacted in the presence of a base to prepare a nitro compound represented by the following general formula (IV), which is then dehydrated. A method for producing a 4H, 6H-furo [3, 4-c] isoxazole derivative represented by the following general formula (I) by cyclization. 상기식들 중에서, R¹, R²및 R³는 각각 상기 청구범위 제1항의 일반식(I)에서 정의한 바와 같다.Among the above formulas, R ¹ , R ² and R ³ are each as defined in formula (I) of claim 1 above.