KR100285280B1 - Isothiazolone derivatives containing beta-methoxyacrylate - Google Patents

Isothiazolone derivatives containing beta-methoxyacrylate Download PDF

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KR100285280B1
KR100285280B1 KR1019950053414A KR19950053414A KR100285280B1 KR 100285280 B1 KR100285280 B1 KR 100285280B1 KR 1019950053414 A KR1019950053414 A KR 1019950053414A KR 19950053414 A KR19950053414 A KR 19950053414A KR 100285280 B1 KR100285280 B1 KR 100285280B1
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methoxyacrylate
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KR970042528A (en
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조창묵
박기만
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조민호
에스케이케미칼주식회사
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D275/00—Heterocyclic compounds containing 1,2-thiazole or hydrogenated 1,2-thiazole rings
    • C07D275/02—Heterocyclic compounds containing 1,2-thiazole or hydrogenated 1,2-thiazole rings not condensed with other rings
    • C07D275/03—Heterocyclic compounds containing 1,2-thiazole or hydrogenated 1,2-thiazole rings not condensed with other rings with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
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    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
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    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/72—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms
    • A01N43/80—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms five-membered rings with one nitrogen atom and either one oxygen atom or one sulfur atom in positions 1,2

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Abstract

PURPOSE: Isothiazolone derivatives containing beta-methoxyacrylate and a producing method thereof are provided. The derivatives have improved germicidal and antimicrobial activity. CONSTITUTION: The isothiazolone derivatives containing beta-methoxyacrylate are represented by formula(I), in which R and R1 are the same or different, C1 to C4 linear or branched alkyl; R2 and R3 are the same or different, hydrogen, halogen, C1 to C4 haloalkyl, C1 to C9 linear or branched alkyl, cyano or phenyl; and X is oxygen or sulfur. The method for producing the isothiazolone derivatives containing beta-methoxyacrylate comprises the steps of: N-alkylation of substituted isothiazolone derivatives of formula(II) to produce compounds of formula(III); formylation of the compounds of formula(III) to produce compounds of formula(IV); and alkylation of the compounds of formula(IV).

Description

β -메톡시아크릴레이트기를 함유하는 이소티아졸론 유도체Isothiazolone derivative containing β-methoxyacrylate group

본 발명은 살균 및 항균력이 우수한 다음 구조식(I)로 표시되는 β -메톡시아크릴레이트기를 함유하는 이소티아졸론 유도체에 관한 것이다.The present invention relates to an isothiazolone derivative containing a β-methoxyacrylate group represented by the following structural formula (I) which is excellent in bactericidal and antibacterial activity.

상기식에서, R 및 R1은 서로 같거나 다른 것으로서 각각 C1∼C4의 직쇄상 또는 분쇄상 알킬기이고; R2및 R3은 서로 같거나 다른 것으로서 각각 수소원자, 할로겐원자, C1∼C4의 할로알킬기, C1~C9의 직쇄상 또는 분쇄상 알킬기, 시아노기 또는 페닐기이고; X는 산소원자 또는 황원자이다.Wherein R and R 1 are the same as or different from each other and are a C 1 to C 4 straight or crushed alkyl group; R 2 and R 3 are each the same or different as each is a hydrogen atom, a halogen atom, a C 1 ~C 4 haloalkyl group of, C 1 ~ C 9 linear or branched alkyl group having a cyano group or phenyl group; X is an oxygen atom or a sulfur atom.

β -메톡시아크릴레이트 유도체는 살균제 및 살충제로서 이미 잘 알려져 있다[유럽특허 제422,597호; 유럽특허 제178,826호; 독일특허 제3,836,581호 등]. 또한 2-알킬-4-이소티아졸린-3-온 유도체는 항균력이 탁월하여 공업용 냉각수계, 페인트, 사진 감광제, 계면활성제, 화장품, 및 제지공업 분야의 방부제로서 특히 방곰팡이 방부제로서 유응하다고 이미 잘 알려져있다[유럽특허 제95,907호].β-methoxyacrylate derivatives are well known as fungicides and insecticides [European Patent No. 422,597; European Patent No. 178,826; German Patent No. 3,836,581 and the like]. In addition, 2-alkyl-4-isothiazolin-3-one derivatives are already well known to be excellent antibacterial agents, and are well suited as preservatives in industrial cooling water systems, paints, photo sensitizers, surfactants, cosmetics, and paper industry. Known [European Patent No. 95,907].

이에 본 발명에서는 기존의 살균제보다 강력한 살균·팡균 활성력을 갖으면서 독성이 낮아 환경오염 문제를 야기시키지 않는 새로운 화합물을 제조하기 위해 연구노력한 결과 β -메톡시아크릴레이트기와 이소티아졸론기를 동시에 보유하는 새로운 화합물을 합성하므로써 본 발명을 완성하였다.Therefore, the present invention has a strong bactericidal and fungal activity than conventional fungicides and research results to produce a new compound that does not cause environmental pollution problems due to low toxicity, which simultaneously possesses β-methoxyacrylate group and isothiazolone group The present invention was completed by synthesizing new compounds.

따라서, 본 발명은 종래와는 달리 β -메톡시아크릴레이트기와 이소티아졸론기를 동시에 보유하는 새로운 구조를 나타내며, 제조공정이 간단하고 살균·항균력이 탁월할 뿐만아니라 살균·항균 스펙트럼이 넓어 여러 종류의 균류를 동시에 규제할 수 있는 신규 화합물과 이의 제조방법을 제공하는데 그 목적이 있다.Therefore, the present invention shows a new structure which simultaneously holds β-methoxyacrylate group and isothiazolone group unlike the conventional ones, and the manufacturing process is simple, excellent sterilization and antibacterial power, and wide sterilization and antibacterial spectrum. It is an object of the present invention to provide novel compounds and methods for their preparation that can simultaneously regulate fungi.

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

본 발명은 다음 구조식(I)로 표시되는 β -메톡시아크릴레이트기를 함유하는 이소티아졸론 유도체에 관한 것이다.The present invention relates to an isothiazolone derivative containing a β-methoxyacrylate group represented by the following structural formula (I).

상기식에서, R, R1, R2, R3및 X는 각각 상기에서 정의한 바와 같다.Wherein R, R 1 , R 2 , R 3 and X are as defined above, respectively.

이와 같은 본 발명을 더욱 상세히 설명하면 다음과 같다.Referring to the present invention in more detail as follows.

본 발명은 살균 및 항균력이 우수한 상기 구조식(I)로 표시되는 β -메톡시아크릴레이트기를 함유하는 이소티아졸론 유도체에 관한 것이다.The present invention relates to an isothiazolone derivative containing β-methoxyacrylate group represented by the above structural formula (I), which is excellent in bactericidal and antibacterial activity.

본 발명에 따른 상기 구조식(I)로 표시되는 화합물에 있어서, 보다 바람직한 치환기를 구체적으로 예시하면 다음과 같다.In the compound represented by the above structural formula (I) according to the present invention, more preferred substituents are specifically illustrated as follows.

R 및 R1은 C1~C4의 직쇄상 또는 분쇄상 알킬 라디칼로서 메틸기, 에틸기, n-프로필기, i-프로필기, n-부틸기, i-부틸기 또는 t-부틸기이다. R2및 R3은 수소원자, 염소원자, 브롬원자, 요오드원자 등의 할로겐원자, 클로로메틸기, 디클로로메틸기, 트리클로로메틸기, 브로모메틸기, 2-클로로메틸기, 트리플루오로메틸기, 2,3-디클로로프로필기 등의 C1∼C4의 할로알킬기, C1∼C9의 직쇄상 또는 분쇄상 알킬기, 시아노기, 또는 페닐기이다. X는 산소원자 또는 황원자이다.R and R 1 are C 1 to C 4 linear or pulverized alkyl radicals, which are methyl, ethyl, n-propyl, i-propyl, n-butyl, i-butyl or t-butyl groups. R 2 and R 3 are halogen atoms such as hydrogen atom, chlorine atom, bromine atom and iodine atom, chloromethyl group, dichloromethyl group, trichloromethyl group, bromomethyl group, 2-chloromethyl group, trifluoromethyl group, 2,3- straight-chain or branched alkyl group of a dichloropropyl group, and the like of the C 1 ~C 4 haloalkyl group, C 1 ~C 9 of, a cyano group, or a phenyl group. X is an oxygen atom or a sulfur atom.

본 발명에 따른 상기 구조식(I)로 표시되는 화합물에 있어서 R 과 R1이 동시에 메틸기인 일때 가장 바람직한 살균·항균 활성을 나타낸다.In the compound represented by the above formula (I) according to the present invention, when R and R 1 are methyl groups at the same time, most preferable bactericidal and antibacterial activity is exhibited.

또한, 본 발명에 따른 상기 구조식(I)로 표시되는 β -메톡시아크릴레이트기를 함유하는 이소티아졸론 유도체는 XR1가 이중결합에 대하여 어떠한 배치를 갖느냐에 따라 다음과 같은 (E)-이성질체 또는 (Z)-이성질체가 존재한다.In addition, the isothiazolone derivative containing a β-methoxyacrylate group represented by the above structural formula (I) according to the present invention has the following (E) -isomer according to the arrangement of XR1 with respect to the double bond or ( Z) -isomers are present.

본 발명에서는 상기 입체이성질체 화합물중 분리가 가능한 화합물은 각각의 이성질체를 분리하여 각각에 대한 살균활성 및 항균활성을 평가하였으며, 분리가 어려운 경우는 이성질체 혼합물 상태로 활성을 평가하였다. 활성평가 결과에 의하면, E-이성질체에 비교하여 Z-이성질체가 월등히 우수한 살균·항균 활성력을 갖는 것으로 밝혀졌으며, 이러한 현상은 β -메톡시아크릴레이트기를 함유하는 모든 화합물에서도 동일한 결과를 나타낸바 있다[Liebigs Ann. Chem., 1984, 1616; Biochemistry, 1986, 25, 775 ; Pestic. Sci., 1991, 31 499].In the present invention, the compounds that can be separated among the stereoisomer compounds were evaluated for bactericidal activity and antimicrobial activity by separating the individual isomers, and when the separation was difficult, the activity was evaluated in the isomer mixture state. According to the results of the activity evaluation, it was found that the Z-isomer had a superior bactericidal and antibacterial activity as compared to the E-isomer, and this phenomenon showed the same result in all compounds containing β-methoxyacrylate group. Liebigs Ann. Chem., 1984, 1616; Biochemistry, 1986, 25, 775; Pestic. Sci., 1991, 31 499].

본 발명에 따른 상기 구조식(I)로 표시되는 β -메톡시아크릴레이트기를 함유하는 이소티아졸론 유도체의 대표적인 예를 들어보면 다음 표 1과 같다.Representative examples of isothiazolone derivatives containing β-methoxyacrylate groups represented by the above structural formula (I) according to the present invention are shown in Table 1 below.

[표 1]TABLE 1

본 발명에 따른 상기 구조식(I)로 표시되는 β -메톡시아크릴레이트기를 함유하는 이소티아졸론 유도체의 제조방법은 다음과 같다.The preparation method of the isothiazolone derivative containing (beta) -methoxyacrylate group represented by the said structural formula (I) which concerns on this invention is as follows.

[반응식][Scheme]

상기식에서, R, R1, R2, R3및 X는 각각 상기에서 정의한 바와 같고, L은 할로겐원자이다.Wherein R, R 1 , R 2 , R 3 and X are as defined above and L is a halogen atom.

먼저, 상기 구조식(II)로 표시되는 치환된 이소티아졸론 유도체를 출발물질로 하고, 이를 α -할로아세테이트와 N-알킬화반응시켜 상기 구조식(III)으로 표시되는 화합물을 제조한다. 상기 구조식(III)으로 표시되는 화합물을 포르밀화반응시켜 상기 구조식(IV)로 표시되는 화합물을 제조하는바, 이때 구조식(IV)로 표시되는 화합물은 (E)-와 (Z)-의 입체이성질체가 존재한다. 그리고 상기 구조식(IV)로 표시되는 화합물을 알킬화반응시켜 본 발명의 목적 화합물인 상기 구조식(I)로 표시되는 화합물을 얻는다.First, a substituted isothiazolone derivative represented by the above formula (II) is used as a starting material, and the compound represented by the above formula (III) is prepared by N-alkylation reaction with α-haloacetate. Formylation of the compound represented by the formula (III) to produce a compound represented by the formula (IV), wherein the compound represented by the formula (IV) is a stereoisomer of (E)-and (Z)- Is present. The compound represented by the above formula (I), which is the target compound of the present invention, is obtained by alkylating the compound represented by the above formula (IV).

본 발명에서 출발물질로 사용된 상기 구조식(II)로 표시되는 치환된 이소티아졸론 유도체는 이미 잘 알려진 공지의 화합물이며, 이는 디메틸포름아마이드, 테트라하이드로퓨란, 디에틸에테르 또는 디클로로메탄 등의 유기용매, 그리고 염기(base) 존재하에 알킬화제(LCH2C02R)에 의해 N-알킬화(alkylation)한다. 이때 N-알킬화는 -30 ∼ 100℃, 보다 바람직하기로는 0 ~ 40℃의 온도범위에서 진행되며, 염기(base)로는 소듐 하이드라이드, 소듐 메톡사이드, 소듐 에톡사이드, 포타시움 t-부톡사이드, 피리딘 또는 트리에틸아민 등을 사용한다. 그 사용량에 있어서, 상기 구조식(II)으로 표시되는 화합물에 대하여 알킬화제(LCH2CO2R)는 1 ∼ 3 당량 사용하고, 염기는 1 ∼ 3 당량 사용한다.Substituted isothiazolone derivatives represented by the above formula (II) used as starting materials in the present invention are well known compounds, which are organic solvents such as dimethylformamide, tetrahydrofuran, diethyl ether or dichloromethane. And N-alkylation with an alkylating agent (LCH 2 CO 2 R) in the presence of a base. At this time, the N-alkylation proceeds at a temperature range of -30 to 100 ° C., more preferably 0 to 40 ° C., and as a base, sodium hydride, sodium methoxide, sodium ethoxide, potassium t-butoxide, pyridine Or triethylamine or the like. In the amount used, the alkylating agent (LCH 2 CO 2 R) is used in the amount of 1 to 3 equivalents and the base in the amount of 1 to 3 equivalents based on the compound represented by the structural formula (II).

상기 포르밀화(formylation)는 디메틸포름아마이드, 테트라하이드로퓨란, 메탄을 또는 벤젠 등의 유기용매에서 상기 N-알킬화에서 예시한 동일 염기 존재하에 포르밀화제와 반응한다. 포르밀화는 -20 ∼ 120℃, 보다 바람직하기로는 0 ∼ 50℃의 온도범위에서 진행되며, 포르밀화제로는 메틸 포메이트, 에틸 포메이트 또는 1-포밀피페리딘이 사용된다. 그 사용량에 있어서, 상기 구조식(III)으로 표시되는 화합물에 대하여 포르밀화제는 2 ∼ 10당량 사용하고, 염기는 1 ∼ 3 당량 사용한다.The formylation is reacted with a formylating agent in the presence of the same base as exemplified in the N-alkylation in an organic solvent such as dimethylformamide, tetrahydrofuran, methane or benzene. Formylation proceeds in a temperature range of -20 to 120 ° C, more preferably 0 to 50 ° C, and methyl formate, ethyl formate or 1-formylpiperidine is used as the formylating agent. In the used amount, formylating agent is used in the amount of 2 to 10 equivalents and base is used in the amount of 1 to 3 equivalents based on the compound represented by the structural formula (III).

상기 구조식(IV)로 표시되는 화합물의 알킬화(alkylation)에 의해 구조식(I)로 표시되는 최종 목적 화합물을 제조함에 있어서, 유기용매로는 디메틸포름아마이드, 테트라하이드로퓨란, 디에틸에테르, 아세토니트릴, 디클로로메탄 또는 디클로로에탄 등을 사용하고, 염기(base)는 상기에서 예시한 것과 동일하며, 알킬화제로는 C1∼C4의 직쇄상 또는 분쇄상의 할로알킬 또는 디메틸 설페이트를 사용한다. 그 사용량에 있어서, 상기 구조식(IV)으로 표시되는 화합물에 대하여 알킬화제는 1 ∼ 3 당량 사용하고, 염기는 1 ∼ 3 당량 사용한다.In preparing the final target compound represented by the formula (I) by alkylation of the compound represented by the formula (IV), the organic solvent is dimethylformamide, tetrahydrofuran, diethyl ether, acetonitrile, Dichloromethane or dichloroethane and the like are used, and the base is the same as exemplified above. As the alkylating agent, C 1 to C 4 linear or pulverized haloalkyl or dimethyl sulfate is used. In the usage amount, the alkylating agent is used in the amount of 1 to 3 equivalents and the base in the amount of 1 to 3 equivalents based on the compound represented by the above formula (IV).

고성능 액체크로마토그래피(HPLC)로 분석한 결과에 의하면, 상기와 같은 본 발명의 제조방법에 의한 경우 구조식(I)로 표시되는 이소티아졸론 유도체는 95% 이상이 (Z)-이성질체로 존재하였으며, 또한 매우 온화한 반응조건하에서 저가(低價)의 시약을 사용하여 손쉽게 목적화합물을 얻을 수 있다. 또한 본 발명의 목적 화합물인 상기 구조식(I)로 표시되는 화합물은 살균·항균력이 탁월하고 살균 스펙트럼이 넓어 공업용 냉각수계, 공업용금속가공유, 페인트, 화장품, 계면활성제, 수지(resin), 사진 감광제 및 제지공업 분야의 방부제로 유용하며, 특히 곰팡이성 방부제 등으로 사용시 탁월한 활성을 나타낸다.As a result of analysis by high performance liquid chromatography (HPLC), 95% or more of the isothiazolone derivative represented by Structural Formula (I) was present as the (Z) -isomer according to the preparation method of the present invention as described above. In addition, the target compound can be easily obtained by using a low-cost reagent under very mild reaction conditions. In addition, the compound represented by the structural formula (I), which is the target compound of the present invention, has excellent sterilization and antibacterial activity, and has a wide sterilization spectrum, so that the industrial cooling water system, industrial metal covalent, paint, cosmetics, surfactant, resin, photo sensitizer and It is useful as a preservative in the paper industry, and especially when used as a fungicide or preservative.

이와같은 본 발명을 실시예에 의거하여 더욱 상세히 설명하면 다음과 같은 바, 본 발명이 이에 한정되는 것은 아니다.When the present invention is described in more detail based on the embodiments as follows, the present invention is not limited thereto.

[실시예 1]Example 1

[메틸-2-(5-클로로-4-이소티아졸린-3-온일)-아세테이트 [구조식(111)]의 제조][Methyl-2- (5-chloro-4-isothiazolin-3-onyl) -acetate [Preparation of Structural Formula (111)]]

5-클로로-4-이소티아졸린-3-온(13.6g, 100 mmol)을 테트라하이드로퓨란(100ml)에 녹인 후, 여기에 트리에틸아민(15.3ml, 110 mmol)을 첨가하고, 반응용액의 온도를 0℃로 냉각한 다음, 메틸 클로로아세테이트(9.6ml, 110 mmol)을 첨가하였다. 0℃에서 1시간 교반한 다음, 반응온도를 상온(25℃)으로 상승시켜 6시간 교반하였다. 반응이 완료되면 물(200ml)을 넣고 에틸 아세테이트로 추출하였다. 유기층은 물(3×100ml)로 씻고 무수 황산 마그네슘으로 건조한 후, 여과하고 감압농축한 결과 액체 상태의 목적화합물(18.9g, 수율 91%)을 얻었다.5-chloro-4-isothiazolin-3-one (13.6 g, 100 mmol) was dissolved in tetrahydrofuran (100 ml), and triethylamine (15.3 ml, 110 mmol) was added thereto, followed by reaction of the reaction solution. The temperature was cooled to 0 ° C. and then methyl chloroacetate (9.6 ml, 110 mmol) was added. After 1 hour of stirring at 0 ° C., the reaction temperature was raised to room temperature (25 ° C.) and stirred for 6 hours. When the reaction was completed, water (200ml) was added and extracted with ethyl acetate. The organic layer was washed with water (3 × 100 ml), dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure to obtain a target compound (18.9 g, 91% yield) in the liquid state.

1H NMR(CDCl3) δ : 3.52(s, 2H), 4.02(s, 3H), 6.8(s, 1H) 1 H NMR (CDCl 3 ) δ: 3.52 (s, 2H), 4.02 (s, 3H), 6.8 (s, 1H)

C6H6NO3SCl : FW. 207.60C 6 H 6 NO 3 SCl: FW. 207.60

[실시예 2]Example 2

[메틸-포밀-2-(5-클로로-4-이소티아졸린-3-온일)-아세테이트 [구조식(IV)]의 제조][Methyl-formyl-2- (5-chloro-4-isothiazolin-3-onyl) -acetate [Preparation of Structural Formula (IV)]]

소듐 하이드라이드(2.6g, 110 mmol)를 디메틸포름아미드(50 ml)에 녹인 후, 0℃에서 메틸-2-(5-클로로-4-이소티아졸린-3-온일)-아세테이트(10.4g, 50 mmol)가 디메틸포름아미드(50 ml)에 녹아 있는 용액과 메틸 포메이트(15.4ml, 250 mmol)을 서서히 첨가하였다. 0℃에서 1시간 교반한 후, 반응온도를 상온(25℃)으로 상승시켜 12시간 교반한 다음, 반응용액에 1% 염산 수용액을 서서히 첨가하여 pH 3으로 적정하였다. 디에틸에테르로 추출하고 물(3×100 ml)로 씻은 다음, 유기층을 무수 황산 마그네슘으로 건조, 여과 및 감압농축한 결과 액체 상태의 목적화합물(10.4g, 수율 88%)을 얻었다.Sodium hydride (2.6 g, 110 mmol) was dissolved in dimethylformamide (50 ml) and then methyl-2- (5-chloro-4-isothiazolin-3-onyl) -acetate (10.4 g, 50 mmol) and methyl formate (15.4 ml, 250 mmol) dissolved in dimethylformamide (50 ml) were added slowly. After stirring at 0 ° C. for 1 hour, the reaction temperature was raised to room temperature (25 ° C.), followed by stirring for 12 hours, and then a 1% aqueous hydrochloric acid solution was slowly added to the reaction solution to titrate to pH 3. The mixture was extracted with diethyl ether and washed with water (3 × 100 ml), and the organic layer was dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure to obtain a target compound (10.4 g, yield 88%) in a liquid state.

[실시예 3]Example 3

[메틸-2-(5-클로로-4-이소티아졸린-3-온일)-3-메톡시프로페노에이트[화합물번호 5]의 제조][Preparation of Methyl-2- (5-chloro-4-isothiazolin-3-onyl) -3-methoxypropenoate [Compound No. 5]]

메틸-포밀-2-(5-클로로-4-이소티아졸린-3-온일)-아세테이트(4.7g, 20 mmol)을 디메틸포름아미드(40 ml)에 녹인 후, 상온에서 탄산칼륨(4.1g, 30 mmol)과 디메틸 설페이트(3.0g, 24 mmol)을 서서히 차례로 첨가하였다. 상온에서 6시간 교반한 다음, 반응용액에 물(40ml)을 가하고 디에틸에테르(3×50 ml)로 추출한 후, 유기층은 물(3×50 ml)로 씻었다. 유기층을 무수 황산 마그네슘으로 건조, 여과 및 감압농축한 결과 액체 상태의 목적화합물(4.0g, 수율 81%)을 얻었다.Methyl-formyl-2- (5-chloro-4-isothiazolin-3-onyl) -acetate (4.7 g, 20 mmol) was dissolved in dimethylformamide (40 ml), and then potassium carbonate (4.1 g, 30 mmol) and dimethyl sulfate (3.0 g, 24 mmol) were added slowly. After stirring for 6 hours at room temperature, water (40 ml) was added to the reaction solution, extracted with diethyl ether (3 x 50 ml), and the organic layer was washed with water (3 x 50 ml). The organic layer was dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure to obtain a target compound in a liquid state (4.0 g, 81% yield).

1H NMR(CDCl3) δ : 3.80(s, 3H), 4.04(s, 3H), 6.81(s, IH), 7.60(s, 1H) 1 H NMR (CDCl 3 ) δ: 3.80 (s, 3H), 4.04 (s, 3H), 6.81 (s, IH), 7.60 (s, 1H)

C8H8NO4SCl : FW. 249.66C 8 H 8 NO 4 SCl: FW. 249.66

Claims (5)

다음 구조식(I)로 표시되는 β -메톡시아크릴레이트기를 함유하는 이소티아졸론 유도체.Isothiazolone derivative containing the (beta) -methoxyacrylate group represented by following structural formula (I). 상기식에서, R 및 R1은 서로 같거나 다른 것으로서 각각 C1~C4의 직쇄상 또는 분쇄상 알킬기이고; R2및 R3은 서로 같거나 다른 것으로서 각각 수소원자, 할로겐원자,C1~C4의 할로겐알킬기, C1~C9의 직쇄상 또는 분쇄상 알킬기, 시아노기 또는 페닐기이고; X는 산소원자 또는 황원자이다.Wherein R and R 1 are the same as or different from each other and are a C 1 to C 4 straight or crushed alkyl group; R 2 and R 3 are each the same or different as each is a hydrogen atom, a halogen atom, C 1 ~ C 4 halogen alkyl, C 1 ~ linear or branched alkyl group of a C 9 of, a cyano group or a phenyl group; X is an oxygen atom or a sulfur atom. 제1항에 있어서, 상기 R 및 R1이 메틸기이고 X가 산소원자인 것을 특징으로 하는 β-메톡시아크릴레이트기를 함유하는 이소티아졸론 유도체.The isothiazolone derivative containing a beta -methoxyacrylate group according to claim 1, wherein R and R 1 are methyl groups and X is an oxygen atom. 상기 구조식(I)로 표시되는 화합물 제조에 유용한 다음 구조식(III)으로 표시되는 중간체 화합물Intermediate compound represented by the following structural formula (III) useful for the preparation of the compound represented by the structural formula (I) 상기식에서, R, R1, R2및 R3은 각각 상기 청구범위 제1항에서 정의한 바와 같다.Wherein R, R 1 , R 2 and R 3 are each as defined in claim 1 above. 상기 구조식(I)로 표시되는 화합물 제조에 유용한 다음 구조식(IV)으로 표시되는 중간체 화합물.An intermediate compound represented by the following structural formula (IV) useful for the preparation of the compound represented by the structural formula (I). 상기식에서, R, R1, R2및 R3은 각각 상기 청구범위 제1항에서 정의한 바와 같다.Wherein R, R 1 , R 2 and R 3 are each as defined in claim 1 above. 다음 구조식(II)로 표시되는 치환된 이소티아졸론 유도체를 N-알킬화반응시켜 다음 구조식(III)으로 표시되는 화합물을 제조하고; 구조식(III)으로 표시되는 화합물을 포르밀화반응시켜 다음 구조식(IV)로 표시되는 화합물을 제조하고; 그리고 나서 구조식(IV)로 표시되는 화합물을 알킬화반응시키는 것을 특징으로 하는 β-메톡시아크릴레이트기를 함유하는 이소티아졸론 유도체의 제조방법.N-alkylation of the substituted isothiazolone derivative represented by the following formula (II) to prepare a compound represented by the following formula (III); Formylation of the compound represented by formula (III) to prepare a compound represented by the following formula (IV); And a method for producing an isothiazolone derivative containing β-methoxyacrylate group, which is then subjected to alkylation of the compound represented by formula (IV). 상기식에서, R, R1, R2, R3및 X는 각각 상기 청구범위 제1항에서 정의한 바와 같다.Wherein R, R 1 , R 2 , R 3 and X are each as defined in claim 1 above.
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