KR940000239B1 - Process for preparing 2-methyl-4-isothiazoline-3-one - Google Patents
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Description
본발명은 2-메틸-4-이소티아졸린-3-온 염의 제조방법에 관한 것으로서, 더욱 상세하게는 공업용냉각수계, 공업용금속가공유, 페인트, 화장품, 계면활성제, 감광제 및 제지공업분야등에 방부제나 살균제등으로 유용한 다음 구조식(I)로 표시되는 2-메틸-4-이소티아졸린-3-온 염만을 선택적으로 제조하는 개선된 방법에 관한 것이다.The present invention relates to a method for preparing 2-methyl-4-isothiazolin-3-one salt, and more particularly, to preservatives, such as industrial cooling water system, industrial metal processing, paint, cosmetics, surfactant, photosensitizer and paper industry. An improved method for selectively preparing only the 2-methyl-4-isothiazolin-3-one salt represented by the following structural formula (I) useful as a bactericide, and the like.
상기 구조식(I)로 표시되는 2-메틸-4-이소티아졸린-3-온 염의 합성방법은 유럽 특허공고 제0095907호에 공지되어 있는바, 그 합성방법을 요약하면 다음 반응식(가)의 아미드화(Amidation) 반응과 다음 반응식(나)의 클로로화 및 고리화 반응이 일어나 2종의 혼합물질로서 제조되며 살균제로 유용하다고 알려져 있다.The synthesis method of the 2-methyl-4-isothiazolin-3-one salt represented by the above formula (I) is known from European Patent Publication No. 0095907. In summary, the amide of the following reaction formula (A) The amidation reaction and the chlorolation and cyclization reactions of the following reactions (b) occur, which are prepared as a mixture of the two and are known to be useful as fungicides.
[반응식 1]Scheme 1
[반응식 2]Scheme 2
그러나, 상기 유럽특허에 기재된 방법에 의하면 필연적으로 2종의 혼합물 즉, 상기 구조식(I)의 2-메틸-4-이소티아졸린-3-온 염과 상기 구조식(Ia)의 5-클로로-2-메틸-4-이소티아졸린-3-온 염의 혼합물 상태로 제조되는데, 이중에서 구조식(Ia)의 5-클로로-2-메틸-4-이소티아졸린-3-온 염은 상기 구조식 (I)의 화합물에 비해 독성이 높아 인체적용이 곤란하고 상온에서 안정성이 떨어지므로 장기간 즉, 수주일 사용시 유효성이 없게 되어서 응용범위가 상당히 제한될 뿐아니라 그 제조수율도 15∼22.6%에 불과하여 제조방법상으로 개선의 여지가 많았다.However, according to the method described in the above European patent, inevitably two mixtures, namely, 2-methyl-4-isothiazolin-3-one salt of formula (I) and 5-chloro-2 of formula (Ia) Prepared as a mixture of -methyl-4-isothiazolin-3-one salts, of which 5-chloro-2-methyl-4-isothiazolin-3-one salts of formula (Ia) It is difficult to apply to human body due to its high toxicity compared to the compound, and its stability is low at room temperature. Therefore, it is not effective when used for a long time, that is, for several weeks. Therefore, the application range is limited considerably, and the production yield is only 15 to 22.6%. There was a lot of room for improvement.
그렇다고 하여 상기 혼합물중에서 구조식(I)의 화합물만을 별도로 분리하거나 선택적으로 제조할 수 있는 방법이 개발되어 있지도 않으며, 설사 분리한다 하더라도 분리공정이 복잡할 뿐아니라 경제적인 면에서 불리하므로 혼합물 상태 그대로 이용되고 있는 실정이었다.However, no method has been developed to separate or selectively prepare only the compound of formula (I) in the mixture, and even if separated, the separation process is complicated and economically disadvantageous, and thus the mixture is used as it is. It was a situation.
따라서, 본 발명은 종래와는 달리 상기 구조식(I)의 화합물을 제조함에 있어 고수율로 상기 구조식(I)의 화합물만을 선택적으로 제조할 수 있는 새로운 방법을 제공하는데 그 목적이 있다.Accordingly, an object of the present invention is to provide a new method capable of selectively preparing only the compound of formula (I) in high yield in preparing the compound of formula (I), unlike the prior art.
이하, 본발명을 상세히 설명하면 다음과 같다.Hereinafter, the present invention will be described in detail.
본발명은 3,3'-디티오디프로피온산과 티오닐클로라이드를 반응시켜서 다음 구조식(II)로 표시되는 3,3'-디티오디프로피오닐디클로라이드를 제조하고, 이를 메틸아민과 반응시켜 다음 구조식(III)으로 표시되는 N,N'-디메틸-3,3'-디티오디프로피온아미드를 제조한 다음, 이로부터 상기 구조식 (I)의 2-메틸-4-이소티아졸린-3-온 염을 제조함에 있어서, 다음 구조식(III)의 화합물에 다음 구조식(IV)로 표시되는 설프릴할라이드를 첨가하여 유기용매중에서 반응시키되 -20℃∼10℃의 반응온도에서 구조식(III)의 화합물과 구조식(IV) 화합물을 1:2 내지 1:3.7의 몰비로 첨가하여 고리화시켜서 선택적으로 상기 구조식(I)의 2-메틸-4-이소티아졸린-3-온 염만을 제조하는 방법을 그 특징으로 한다.The present invention reacts 3,3'-dithiodipropionic acid and thionyl chloride to prepare 3,3'-dithiodipropionyldichloride represented by the following structural formula (II), and reacts with methylamine to give the following structural formula ( N, N'-dimethyl-3,3'-dithiodipropionamide represented by III) was prepared, and 2-methyl-4-isothiazolin-3-one salt of the above formula (I) was prepared therefrom. To the compound of the following formula (III), the sulfyl halide represented by the following formula (IV) is added to react in an organic solvent, but the compound of formula (III) and the formula (IV) at a reaction temperature of -20 ℃ to 10 ℃ ) Is optionally cyclized by adding a compound in a molar ratio of 1: 2 to 1: 3.7 to optionally prepare only the 2-methyl-4-isothiazolin-3-one salt of formula (I).
상기식에서, X는 할로겐원소를 나타낸다.Wherein X represents a halogen element.
이와같은 본발명을 더욱 상세히 설명하면 다음과 같다.The present invention will be described in more detail as follows.
본발명은 3,3'-디티오디프로피온산과 티오닐클로라이드, 메틸아민 및 상기 구조식(IV)의 설프릴할라이드를 이용하여 상기 구조식(I)의 2-메틸-4-이소티아졸린-3-온 염을 선택적으로 제조하는 방법인 바, 상기 3,3'-디티오디프로피온산과 티오닐클로라이드를 1 : 2 내지 1 : 4의 몰비로 반응시키되 10∼30℃에서 반응시켜서 상기 구조식(II)로 표시되는 3,3'-디티오디프로피오닐디클로라이드를 제조한다.The present invention relates to 2-methyl-4-isothiazolin-3-one of formula (I) using 3,3'-dithiodipropionic acid, thionyl chloride, methylamine and sulfyl halide of formula (IV). As a method for selectively preparing a salt, the 3,3′-dithiodipropionic acid and thionyl chloride are reacted at a molar ratio of 1: 2 to 1: 4, and are reacted at 10 to 30 ° C. to represent the structural formula (II). To prepare 3,3'-dithiodipropionyldichloride.
이때 반응온도가 10℃보다 낮으면 반응시간이 너무 길어져서 경제성이 없게 되고, 30℃ 이상인 경우에는 독성이 있는 티오닐클로라이드의 증기가 심하게 발생되어 작업상 위험이 있으므로 좋지 않게 된다.At this time, if the reaction temperature is lower than 10 ℃, the reaction time is too long to become economical, and if it is 30 ℃ or more, the toxic thionyl chloride vapor is severely generated, which is not good because there is an operational risk.
이렇게 제조된 상기 구조식(II)의 화합물에다 메틸아민을 반응시키는데, 이때 구조식(II)와 메틸아민이 1 : 2∼1 : 6의 몰비가 되도록 반응시키는 것이 좋으며, 반응온도는 -10℃∼35℃, 바람직하게는 -10℃∼30℃, 더욱 바람직하기로는 15℃ 내지 상온으로 유지하는 것이 바람직하다.The methylamine is reacted with the compound of the above formula (II), wherein the reaction of the formula (II) and methylamine in a molar ratio of 1: 2 to 1: 6 is preferred, and the reaction temperature is -10 ° C to 35 ° C. It is preferable to keep it at -10 degreeC-preferably 30 degreeC-More preferably, 15 degreeC-normal temperature.
만일, 반응온도가 -10℃ 보다 낮으면 경제적으로 불리하고 35℃ 이상에서는 발열반응으로 인한 폭발의 위험이 있다. 또한, 이때의 반응몰비가 1 : 2 이하로 메틸아민을 적게 사용하면 미반응물질이 생성되고 1 : 6이상으로 과량 사용하면 화학반응상 불필요한 과량사용에 불과하므로 경제적으로 불리하다. 이러한 반응에서 반응용매로서는 톨루엔이나 벤젠을 사용하는 것이 좋다.If the reaction temperature is lower than -10 ° C economically disadvantageous and there is a risk of explosion due to exothermic reaction above 35 ° C. In addition, when the reaction molar ratio of less than 1: 2 is less methylamine is produced unreacted material, when used in excess of 1: 6 it is economically disadvantageous because only unnecessary excess use in the chemical reaction. In this reaction, toluene or benzene is preferably used as the reaction solvent.
상기와 같이 반응시키면 상기 구조식(III)의 N,N'-디메틸-3,3'-디티오디프로피온아미드가 생성되며, 여기에 상기 구조식(IV)의 설프릴할라이드를 첨가하여 유기용매중에서 고리화 반응시키면 목적하는 상기 구조식(I)의 2-메틸-4-이소티아졸린-3-온 염이 선택적으로 제조된다.The reaction as described above yields N, N'-dimethyl-3,3'-dithiodipropionamide of formula (III), which is added to the sulfyl halide of formula (IV) and cyclized in an organic solvent. The reaction optionally yields the desired 2-methyl-4-isothiazolin-3-one salt of formula (I).
이때, 상기 구조식(III)의 화합물과 설프릴할라이드는 1 : 2 내지 1 : 3.7의 몰비로 반응시키는 것이 좋은데, 만일 1 : 2 몰비보다 적은량으로 설프릴할라이드를 사용하면 미반응불순물이 생성되며, 1 : 3.7을 초과하여 사용하면 얻어지는 수율에 비하여 순도 및 경제성이 떨어진다. 이때 설프릴할라이드는 설프릴클로하이드가 바람직하게 사용될 수 있다.At this time, the compound of formula (III) and the sulfyl halide is preferably reacted in a molar ratio of 1: 2 to 1: 3.7, if the sulfyl halide is used in an amount less than 1: 2 molar ratio, unreacted impurities are produced, 1: When used exceeding 3.7, purity and economy are inferior to the yield obtained. In this case, the sulfyl halide may be preferably sulfyl chloride.
또한, 이때의 반응온도는 -20℃∼10℃로 반응시키는 것이 좋은바, 10℃ 보다 높은 온도에서는 최종생성물의 혼합물로 제조되기 때문에 안정성이 현저하게 떨어져서 수율이 현격하게 저하되는 문제가 있다.In addition, the reaction temperature at this time is good to react at -20 ℃ to 10 ℃, since the preparation of the mixture of the final product at a temperature higher than 10 ℃ there is a problem that the stability is significantly reduced and the yield is significantly reduced.
이러한 최종 반응에는 반응용매로서 유기용매, 즉 유기할로겐 화합물을 사용해야 하는데, 예컨대 CH2X2, CHX3, CX3CH3, CHX2CHX2등(여기서, X는 할로겐원소이다)을 사용하는 것이 바람직하다.In this final reaction, an organic solvent, i.e., an organic halogen compound, should be used as a reaction solvent. For example, the use of CH 2 X 2 , CHX 3 , CX 3 CH 3 , CHX 2 CHX 2, etc. (where X is a halogen element) desirable.
상기와 같이 본발명에 따라 합성된 상기 구조식(I)의 2-메틸-4-이소티아졸린-3-온 염은 종래에 필수적으로 함유되었던 5-클로로-2-메틸-4-이소티아졸린-3-온 염이 전혀 생성되지 않은 순수화합물로만 선택적으로 생성되며, 그 수율은 80몰% 이상으로 얻어진다.As described above, the 2-methyl-4-isothiazolin-3-one salt of formula (I) synthesized according to the present invention is 5-chloro-2-methyl-4-isothiazoline- It is selectively produced only with pure compounds in which no 3-one salt is produced, and the yield is obtained at 80 mol% or more.
이러한 상기 구조식(I)의 목적화합물은 안정성 및 지속성이 있는 바이오사이드로서 냉각탑내의 조류방지제, 도료방부제, 공업용금속가공용방부제, 화장품 및 샴푸첨가제, 제지용방부제, 계면활성제용방부제 등 일반공업용방부제로 매우 유용하고, 방곰팡이제 및 살균제로도 매우 유용하다.The target compound of the above formula (I) is a bioside having stability and durability as a general industrial preservative such as algae inhibitor, paint preservative, industrial metal processing preservative, cosmetic and shampoo additive, paper preservative, surfactant preservative, etc. It is useful and also very useful as an antifungal and fungicide.
상술한 바와같이 본발명에 따르면 2-메틸-4-이소티아졸린-3-온 염의 화합물만 선택적으로 제조되고, 공기중에서 부식성물질이며 용액중에서나 공기중에서 안정성이 현저하게 떨어져서 수주일만에 분해가 일어나는 5-클로로-2-메틸-4-이소티아졸린-3-온 염이 전혀 생성되지 않기 때문에, 상기와 같은 여러가지 분야의 용도에서 제한없이 모두 유용하게 사용될 수 있고, 특히 독성이 현저히 저하되어 인체에 직접 적용하는 화장품이나 샴푸등에도 사용할 수가 있으며, 안정성이 있어서 장기간 사용시에도 본래의 효과를 그대로 유지할 수가 있는 것이다As described above, according to the present invention, only a compound of 2-methyl-4-isothiazolin-3-one salt is selectively prepared, and it is corrosive in the air, and its stability in the solution or in the air is markedly degraded so that decomposition occurs in a few weeks. Since 5-chloro-2-methyl-4-isothiazolin-3-one salt is not produced at all, it can be usefully used without any limitation in the above various fields of application, and in particular, the toxicity is markedly lowered to the human body. It can be used for cosmetics and shampoos that are applied directly, and it is stable and can maintain its original effect even after long-term use.
또한, 그 제조방법이 종래에 비해 간단하여 경제적이며 고수율로 목적화합물을 제조할 수가 있는 장점이있다.In addition, the production method is simpler than the conventional method, there is an advantage that it is economical and can produce the target compound in high yield.
이하, 본발명을 실시예에 의거 상세히 설명한다.Hereinafter, the present invention will be described in detail with reference to Examples.
[실시예 1]Example 1
1ℓ 3구 플라스크에 온도계와 드롭핑펀텔을 장착시키고 N,N'-디메틸-3,3'-디티오디프로피온아미드 23.6g(0.1몰)을 메틸렌클로라이드 350ml에 녹인후 얼음 중탕에서 5℃ 이하로 유지시킨 후 드롭핑펀넬들 통하여 설프릴클로라이드 40.5g(0.3몰)을 3시간 동안 천천히 교반하면서 첨가시킨다.A 1 L three-neck flask was equipped with a thermometer and a dropping funtel, and 23.6 g (0.1 mol) of N, N'-dimethyl-3,3'-dithiodipropionamide was dissolved in 350 ml of methylene chloride and kept below 5 ° C in an ice bath. After the addition of 40.5 g (0.3 mol) of sulfyl chloride through the dropping funnels with slow stirring for 3 hours.
설프릴클로라이드 첨가가 끝반후 반응온도를 0℃로 내린후 1시간 동안 교반을 시켜준 후 온도를 서서히 실온까지 올린후 물 중탕에서 온도를 25±5℃로 유지시킨 후 3시간 동안 교반해준다.After the addition of the sulfyl chloride, the reaction temperature was lowered to 0 ° C. and stirred for 1 hour. Then, the temperature was gradually raised to room temperature and the temperature was maintained at 25 ± 5 ° C. in a water bath, followed by stirring for 3 hours.
반응이 진행되면서 흰색 침전물이 생성되고 이 온도조건에서 반응이 완전히 끝난후 침전물을 석션으로 여과시켜 반응침전물을 수거한 후 남아있는 메틸렌클로라이드를 진공오븐에 3시간 동안 50℃로 유지시켜 완전히 제거하고 나면 2-메틸-4-이소티아졸린-3-온· HCI 27.1g(90몰%)을 얻는다.As the reaction proceeds, a white precipitate is formed. After the reaction is completed at this temperature condition, the precipitate is filtered through suction to collect the reaction precipitate, and then the remaining methylene chloride is kept at 50 ° C. in a vacuum oven for 3 hours and completely removed. 2-7.1 g (90 mol%) of 2-methyl-4-isothiazolin-3-one HCI is obtained.
1H-NMR 스펙트럼(100MHz, D2O) : δppm ; 8.52(d,5H), 6.35(d,4H), 3.41(s,CH3). 1 H-NMR spectrum (100 MHz, D 2 O): δ ppm; 8.52 (d, 5H), 6.35 (d, 4H), 3.41 (s, CH 3 ).
[실시예 2]Example 2
1ℓ 3구 플라스크에 온도계와 드롭핑펀넬을 장착시키고 N,N'-디메틸-3.3'-디티오디프로피온아미드 23.6g(0.1몰)을 메틸렌클로라이드 350m1에 녹인후 얼음 중탕에서 5℃ 이하로 유지시킨 후 드롭핑펀넬을 통하여 설프릴클로라이드 33.75g(0.25몰)을 3시간 동안 천천히 교반하면서 첨가시킨다.A 1 L three-necked flask was equipped with a thermometer and a dropping funnel, and 23.6 g (0.1 mol) of N, N'-dimethyl-3.3'-dithiodipropionamide was dissolved in 350 m1 of methylene chloride, and kept at 5 ° C in an ice bath. 33.75 g (0.25 mol) of sulfyl chloride are added via a dropping funnel with gentle stirring for 3 hours.
설프릴클로라이드 첨가가 끝난후 반응온도를 0℃로 내린후 1시간 동안 교반을 시켜준 후 온도를 서서히 실온까지 올린후 물 중탕에서 온도를 30±5℃로 유지시킨 후 3시간 동안 교반해준다.After the addition of the sulfyl chloride, the reaction temperature was lowered to 0 ° C. and stirred for 1 hour. Then, the temperature was gradually raised to room temperature and the temperature was maintained at 30 ± 5 ° C. in a water bath, followed by stirring for 3 hours.
반응이 진행되면서 횐색 침전물이 생성되고 30℃에서 반응이 완전히 끝난 후 침전물을 석션으로 여과시켜 반응침전물을 수거한 후 남아있는 메틸렌클로라이드를 진공오븐에 3시간 동안 50℃로 유지시켜 완전히 제거하고 나면 2-메틸-4-이소티아졸린-3-온·HCI 27.4g(90몰%)을 얻는다.As the reaction proceeds, a white precipitate is formed, and after completion of the reaction at 30 ° C, the precipitate is filtered by suction, and the reaction precipitate is collected. After that, the remaining methylene chloride is kept at 50 ° C in a vacuum oven for 3 hours and completely removed. 27.4 g (90 mol%) of methyl-4-isothiazolin-3-one and HCI are obtained.
1H-NMR 스펙트럼(100MHz, D2O) : δppm ; 8.53(d,5H), 6.34(d,4H), 3.41(s,CH3). 1 H-NMR spectrum (100 MHz, D 2 O): δ ppm; 8.53 (d, 5H), 6.34 (d, 4H), 3.41 (s, CH 3 ).
[실시예 3]Example 3
1ℓ 3구 플라스크에 온도계와 드롭핑펀넬을 장착시키고 N,N'-디메틸-3,3'-디티오디프로피온아미드 23.6g(0.1몰)을 메틸렌클로라이드 350ml에 녹인후 저온반응기내에 -5℃ 이하로 유지시킨 후 드롭핑펀넬을 통하여 설프릴클로라이드 28.35g(0.21몰)을 3시간 동안 천천히 교반하면서 첨가시킨다.A 1 L three-necked flask was equipped with a thermometer and a dropping funnel, and 23.6 g (0.1 mol) of N, N'-dimethyl-3,3'-dithiodipropionamide was dissolved in 350 ml of methylene chloride and then cooled to -5 ° C in a low temperature reactor. After holding, 28.35 g (0.21 mol) of sulfyl chloride was added through a dropping funnel with gentle stirring for 3 hours.
설프릴클로라이드 첨가가 끝난후 반응온도를 -5℃로 내린후 1시간 동안 교반을 시켜준 후 온도를 서서히 실온까지 올린후 물 중탕에서 온도를 35℃로 유지시킨 후 3시간 동안 교반해준다.After the addition of the sulfyl chloride, the reaction temperature was lowered to -5 ° C. and stirred for 1 hour. Then, the temperature was gradually raised to room temperature and the temperature was maintained at 35 ° C. in a water bath, followed by stirring for 3 hours.
반응이 진행되면서 흰색 침전물이 생성되고 35℃에서 반응이 완전히 끝난 후 침전물을 석션으로 여과시켜 반응침전물을 수거한 후 남아있는 메틸렌클로라이드를 진공오븐에 3시간 동안 50℃로 유지시켜 완전허 제거하고 나면 2-메틸-4-이소티아졸린-3-온·HCI 27.8g(91.7몰%)을 얻는다.As the reaction proceeds, white precipitate is formed. After completion of the reaction at 35 ° C, the precipitate is filtered by suction, and the reaction precipitate is collected. After that, the remaining methylene chloride is kept at 50 ° C in a vacuum oven for 3 hours and completely removed. 27.8 g (91.7 mol%) of 2-methyl-4-isothiazolin-3-one HCI are obtained.
1H-NMR 스펙트럼(100MHz, D2O) : δppm ; 8.53(d,5H), 6.33(d,4H), 3.41(s,CH3). 1 H-NMR spectrum (100 MHz, D 2 O): δ ppm; 8.53 (d, 5H), 6.33 (d, 4H), 3.41 (s, CH 3 ).
[실시예 4]Example 4
1ℓ 3구 플라스크에 온도계와 드롭핑펀넬을 장착시키고 N,N'-디메틸-3,3'-디티오디프로피온아미드 23.6g(0.1몰)을 메틸렌클로라이드 350ml에 녹인후 저온반응기를 이용 -5℃ 이하로 유지시킨 후 드롭핑펀넬을 통하여 설프릴클로라이드 27.0g(0.2몰)을 3시간 동안 천천히 교반하면서 첨가시킨다.A 1 L three-necked flask was equipped with a thermometer and a dropping funnel, and 23.6 g (0.1 mol) of N, N'-dimethyl-3,3'-dithiodipropionamide was dissolved in 350 ml of methylene chloride and then cooled to -5 ° C using a low temperature reactor. After maintaining the solution, 27.0 g (0.2 mol) of sulfyl chloride was added through a dropping funnel with gentle stirring for 3 hours.
설프릴클로라이드 첨가가 끝난후 반응온도를 0℃로 올린후 1시간 동안 교반을 시켜준 후 온도를 서서히 실온까지 올린후 물 중탕에서 온도를 40℃로 유지시킨 후 3시간 동안 교반해준다.After the addition of the sulfyl chloride, the reaction temperature was raised to 0 ° C. and stirred for 1 hour. Then, the temperature was gradually raised to room temperature and the temperature was maintained at 40 ° C. in a water bath, followed by stirring for 3 hours.
반응이 진행되면서 흰색 침전물이 생성되고 40℃에서 반응이 완전히 끝난 후 침전물을 석션으로 여과시켜 반응침전물을 수거한 후 남아있는 메틸렌클로라이드를 진공오븐에 3시간 동안 50℃로 유지시켜 완전히 제거하고 나면 2-메틸-4-이소티아졸린-3-온·HCI 28.1g(92.7몰%)을 얻는다.As the reaction proceeds, a white precipitate is formed. After completion of the reaction at 40 ° C, the precipitate is filtered by suction, and the reaction precipitate is collected. After that, the remaining methylene chloride is kept at 50 ° C in a vacuum oven for 3 hours to completely remove it. 28.1 g (92.7 mol%) of methyl-4-isothiazolin-3-one HCI are obtained.
1H-NMR 스펙트럼(100MHz, D2O) : δppm ; 8.54(d,5H), 6.36(d,4H), 3.42(s,CH3). 1 H-NMR spectrum (100 MHz, D 2 O): δ ppm; 8.54 (d, 5H), 6.36 (d, 4H), 3.42 (s, CH 3 ).
[실시예 5]Example 5
1ℓ 3구 플라스크에 온도계와 드롭핑펀넬을 장착시키고 N,N'-디메틸-3,3'-디티오디프로피온아미드 23.6g(0.1몰)을 메틸렌클로라이드 350ml에 녹인후 저온반응기를 이용 -15℃ 이하로 유지시킨 후 드롭핑펀넬을 통하여 설프릴클로라이드 28.35g(0.21몰)을 3시간 동안 천천히 교반하면서 첨가시킨다.A 1 L three-neck flask was equipped with a thermometer and a dropping funnel, and 23.6 g (0.1 mol) of N, N'-dimethyl-3,3'-dithiodipropionamide was dissolved in 350 ml of methylene chloride and then cooled to -15 ° C or lower. After holding, 28.35 g (0.21 mol) of sulfyl chloride was added through a dropping funnel with gentle stirring for 3 hours.
설프릴클로라이드 첨가가 끝난후 -5℃에서 1시간 동안 교반을 시켜준 후 온도를 서서히 실온까지 올린후 물 중탕에서 온도를 40℃로 유지시킨 후 3시간 동안 교반해준다.After the addition of the sulfyl chloride, the mixture was stirred at -5 ° C for 1 hour, and then the temperature was gradually raised to room temperature. The temperature was maintained at 40 ° C in a water bath, followed by stirring for 3 hours.
반응이 진행되면서 흰색 침전물이 생성되고 40℃에서 반응이 완전히 끝난 후 침전물을 석션으로 여과시켜 반응침전물을 수거한 후 남아있는 메틸렌클로라이드를 진공오븐에 3시간 동안 50℃로 유지시켜 완전히 제거하고 나면 2-메틸-4-이소티아졸린-3-온·HCI 27 5g(90.7몰%)을 얻는다.As the reaction proceeds, a white precipitate is formed. After completion of the reaction at 40 ° C, the precipitate is filtered by suction, and the reaction precipitate is collected. After that, the remaining methylene chloride is kept at 50 ° C in a vacuum oven for 3 hours to completely remove it. 5 g (90.7 mol%) of methyl-4-isothiazolin-3-one-HCI 27 are obtained.
1H-NMR 스펙트럼(100MHz, D2O) : δppm ; 8.54(d,5H), 6.33(d,4H), 3.41(s,CH3). 1 H-NMR spectrum (100 MHz, D 2 O): δ ppm; 8.54 (d, 5H), 6.33 (d, 4H), 3.41 (s, CH 3 ).
[실시예 6]Example 6
1ℓ 3구 플라스크에 온도계와 드롭핑펀넬을 장착시키고 N,N'-디메틸-3,3'-디티오디프로퍼온아미드 23.6g(0.1몰)을 메틸렌클로라이드 350ml에 녹인후 저온반응기를 이용 -15℃ 이하로 유지시킨 후 드롭핑펀넬을 통하여 설프릴클로라이드 27.0g(0.2몰)을 3시간 동안 천천히 교반하면서 첨가시킨다.A 1 L three-necked flask was equipped with a thermometer and a dropping funnel, and 23.6 g (0.1 mol) of N, N'-dimethyl-3,3'-dithiodipropionamide was dissolved in 350 ml of methylene chloride and then cooled using a low temperature reactor. After keeping below, 27.0 g (0.2 mol) of sulfyl chloride was added through a dropping funnel with slow stirring for 3 hours.
설프릴클로라이드 첨가가 끝난후 -5℃에서 1시간 동안 교반을 시켜준 후 온도를 서서히 실온까지 올린후 물 중탕에서 온도를 40℃로 유지시킨 후 3시간 동안 교반해준다.After the addition of the sulfyl chloride, the mixture was stirred at -5 ° C for 1 hour, and then the temperature was gradually raised to room temperature. The temperature was maintained at 40 ° C in a water bath, followed by stirring for 3 hours.
반응이 진행되면서 흰색 침전물이 생성되고 40℃에서 반응이 완전히 끝난 후 침전물을 석션으로 여과시켜 반응침전물을 수거한 후 남아있는 메틸렌클로라이드를 진공오븐에 3시간 동안 50℃로 유지시켜 완전히 제거하고 나면 2-메틸-4-이소티아졸린-3-온·HCI 27.9g(92몰%)을 얻는다.As the reaction proceeds, a white precipitate is formed. After completion of the reaction at 40 ° C, the precipitate is filtered by suction, and the reaction precipitate is collected. After that, the remaining methylene chloride is kept at 50 ° C in a vacuum oven for 3 hours to completely remove it. 27.9 g (92 mol%) of methyl-4-isothiazolin-3-one HCI are obtained.
1H-NMR 스펙트럼(100MHz, D2O) : δppm ; 8.56(d,5H), 6.37(d,4H), 3.41(s,CH3). 1 H-NMR spectrum (100 MHz, D 2 O): δ ppm; 8.56 (d, 5H), 6.37 (d, 4H), 3.41 (s, CH 3 ).
[실시예 7]Example 7
1ℓ 3구 플라스크에 온도계와 드롭핑펀넬을 장착시키고 N,N'-디메틸-3,3'-디티오디프로피온아미드 23.6g(0.1몰)을 클로로포름 350ml에 녹인후 저온반응기를 이용 -15℃ 이하로 유지시킨 후 드롭핑펀넬을 통하여 설프릴클로라이드 40.5g(0.3몰)을 3시간 동안 천천히 교반하면서 첨가시킨다.A 1 L three-necked flask was equipped with a thermometer and a dropping funnel, and 23.6 g (0.1 mol) of N, N'-dimethyl-3,3'-dithiodipropionamide was dissolved in 350 ml of chloroform and then cooled to -15 ° C using a low temperature reactor. After holding, 40.5 g (0.3 mol) of sulfyl chloride was added through a dropping funnel with gentle stirring for 3 hours.
설프릴클로라이드 첨가가 끝난후 0℃에서 1시간 동안 교반을 시켜준 후 온도를 서서히 실온까지 올린후 물 중탕에서 온도를 25℃로 유지시킨 후 3시간 동안 교반해준다.After the addition of the sulfyl chloride, the mixture was stirred at 0 ° C. for 1 hour, and the temperature was gradually raised to room temperature. The temperature was maintained at 25 ° C. in a water bath, followed by stirring for 3 hours.
반응이 진행되면서 흰색 침전물이 생성되고 25℃에서 반응이 완전히 끝난 후 침전물을 석션으로 여과시켜 반응침전물을 수거한 후 남아있는 클로로포름을 진공오븐에 3시간 동안 50℃로 유지시켜 완전히 제거하고 나면 2-메 틸 -4-이소티아졸린-3-온·HCI 27.2g (89.7몰%)을 얻는다.As the reaction proceeds, white precipitate is formed. After completion of the reaction at 25 ° C, the precipitate is filtered by suction, and the reaction precipitate is collected. After that, the remaining chloroform is maintained at 50 ° C in a vacuum oven for 3 hours, and then completely removed. 27.2 g (89.7 mol%) of methyl-4-isothiazolin-3-one HCI are obtained.
1H-NMR 스펙트럼(100MHz, D2O) : δppm ; 8.50(d,5H), 6.32(d,4H), 3.43(s,CH3). 1 H-NMR spectrum (100 MHz, D 2 O): δ ppm; 8.50 (d, 5H), 6.32 (d, 4H), 3.43 (s, CH 3 ).
[실시예 8]Example 8
1ℓ 3구 플라스크에 온도계와 드롭핑펀넬을 장착시키고 N, N'-디메틸-3,3'-디티오디프로피온아미드 23.6g(0.1몰)을 클로로포름 350ml에 녹인후 저온반응기를 이용 -10℃ 이하로 유지시킨 후 드롭핑펀넬을 통하여 설프릴클로라이드 33.75g(0.25몰)을 3시간 동안 천천히 교반하면서 첨가시킨다.A 1 L three-necked flask was equipped with a thermometer and a dropping funnel, and 23.6 g (0.1 mol) of N, N'-dimethyl-3,3'-dithiodipropionamide was dissolved in 350 ml of chloroform and then cooled to -10 ° C using a low temperature reactor. After holding, 33.75 g (0.25 mole) of sulfyl chloride was added through a dropping funnel with gentle stirring for 3 hours.
설프릴클로라이드 첨가가 끝난후 0℃에서 1시간 동안 교반을 시켜준 후 온도를 서서히 실온까지 올린후 물 중탕에서 온도를 30℃로 유지시킨 후 3시간 동안 교반해준다.After the addition of the sulfyl chloride, the mixture was stirred at 0 ° C. for 1 hour, and the temperature was gradually raised to room temperature. The temperature was maintained at 30 ° C. in a water bath, followed by stirring for 3 hours.
반응이 진행되면서 흰색 침전물이 생성되고 30℃에서 반응이 완전히 끝난 후 침전물을 석션으로 여과시켜 반응침전물을 수거한 후 남아있는 클로로포름을 진공오븐에 3시간 동안 50℃로 유지시켜 완전히 제거하고 나면 2-메틸-4-이소티아졸린-3-온·HCI 27.5g(90.7몰%)을 얻는다.As the reaction proceeds, a white precipitate is formed. After completion of the reaction at 30 ° C, the precipitate is filtered by suction. After collecting the reaction precipitate, the remaining chloroform is kept at 50 ° C in a vacuum oven for 3 hours to completely remove the residue. 27.5 g (90.7 mol%) of methyl-4-isothiazolin-3-one and HCI are obtained.
1H-NMR 스펙트럼(100MHz, D2O) : δppm ; 8.51(d,5H), 6.33(d,4H), 3.40(s,CH3). 1 H-NMR spectrum (100 MHz, D 2 O): δ ppm; 8.51 (d, 5H), 6.33 (d, 4H), 3.40 (s, CH 3 ).
[실시예 9]Example 9
1ℓ 3구 플라스크에 온도계와 드롭핑펀넬을 장착시키고 N,N'-디메틸-3,3'-디티오디프로피온아미드 23.6g(0.1몰)을 클로로포름 350ml에 녹인후 저온반응기를 이용 -5℃ 이하로 유지시킨 후 드롭핑펀넬을 통하여 설프릴클로라이드 28.35g(0.21몰)을 3시간 동안 천천히 교반하면서 첨가시킨다.A 1 L three-necked flask was equipped with a thermometer and a dropping funnel, and 23.6 g (0.1 mol) of N, N'-dimethyl-3,3'-dithiodipropionamide was dissolved in 350 ml of chloroform and then cooled to -5 ° C using a low temperature reactor. After holding, 28.35 g (0.21 mol) of sulfyl chloride was added through a dropping funnel with gentle stirring for 3 hours.
설프릴클로라이드 첨가가 끝난후 0℃에서 1시간 동안 교반을 시켜준 후 온도를 서서히 실온까지 올린후 물 중탕에서 온도를 35℃로 유지시킨 후 3시간 동안 교반해준다.After the addition of the sulfyl chloride, the mixture was stirred at 0 ° C. for 1 hour, and the temperature was gradually raised to room temperature. The temperature was maintained at 35 ° C. in a water bath, followed by stirring for 3 hours.
반응이 진행되면서 흰색 침전물이 생성되고 35℃에서 반응이 완전히 끝난 후 침전물을 석션으로 여과시켜 반응침전물을 수거한 후 남아있는 클로로포름을 진공오븐에 3시간 동안 50℃로 유지시켜 완전히 제거하고 나면 2-메틸-4-이소티아졸린-3-온·HCI 27.7g(91.3몰%)을 얻는다.As the reaction proceeds, white precipitate is formed. After completion of the reaction at 35 ° C, the precipitate is filtered by suction. After collecting the reaction precipitate, the remaining chloroform is kept at 50 ° C for 3 hours in a vacuum oven to completely remove it. 27.7 g (91.3 mol%) of methyl-4-isothiazolin-3-one HCI are obtained.
1H-NMR 스펙트럼(100MHz, D2O) : δppm ; 8.55(d,5H), 6.32(d,4H), 3.40(s,CH3). 1 H-NMR spectrum (100 MHz, D 2 O): δ ppm; 8.55 (d, 5H), 6.32 (d, 4H), 3.40 (s, CH 3 ).
[실시예 10]Example 10
1ℓ 3구 플라스크에 온도계와 드롭핑펀넬을 장착시키고 N,N'-디메틸-3,3'-디티오디프로피온아미드 23.6g(0.1몰)을 클로로포름 350ml에 녹인후 저온반응기를 이용 5℃ 이하로 유지시킨 후 드롭핑펀넬을 통하여 설프릴클로라이드 27.0g(0.2몰)을 3시간 동안 천천히 교반하면서 첨가시킨다.A 1 L three-necked flask was equipped with a thermometer and a dropping funnel, and 23.6 g (0.1 mol) of N, N'-dimethyl-3,3'-dithiodipropionamide was dissolved in 350 ml of chloroform and maintained at 5 ° C or below using a low temperature reactor. After the addition of 27.0 g (0.2 mol) of sulfyl chloride through a dropping funnel with slow stirring for 3 hours.
설프릴클로라이드 첨가가 끝난후 0℃에서 1시간 동안 교반을 시켜준 후 온도를 서서히 실온까지 올린후 물 중탕에서 온도를 40℃로 유지시킨 후 3시간 동안 교반해준다.After the addition of the sulfyl chloride, the mixture was stirred at 0 ° C. for 1 hour, and the temperature was gradually raised to room temperature. The temperature was maintained at 40 ° C. in a water bath, followed by stirring for 3 hours.
반응이 진행되면서 횐색 침전물이 생성되고 40℃에서 반응이 완전히 끝난 후 침전물을 석션으로 여과시켜 반응침전물을 수거한 후 남아있는 클로로포름을 진공오븐에 3시간 동안 50℃로 유지시켜 완전히 제거하고 나면 2-메틸-4-이소티아졸린-3-온·HCI 28.0g(92.3몰%)을 얻는다.As the reaction proceeds, a white precipitate is formed. After completion of the reaction at 40 ° C, the precipitate is filtered by suction. After collecting the reaction precipitate, the remaining chloroform is kept at 50 ° C in a vacuum oven for 3 hours to completely remove the residue. 28.0 g (92.3 mol%) of methyl-4-isothiazolin-3-one HCI are obtained.
1H-NMR 스펙트럼(100MHz, D2O) : δppm ; 8.47(d,5H), 6.31(d,4H), 3.42(s,CH3). 1 H-NMR spectrum (100 MHz, D 2 O): δ ppm; 8.47 (d, 5H), 6.31 (d, 4H), 3.42 (s, CH 3 ).
[실시예 11]Example 11
1ℓ 3구 플라스크에 온도계와 드롭핑펀넬을 장착시키고 N,N'-디메틸-3,3'-디티오디프로피온아미드 23.6g(0.1몰)을 클로로포름 350ml에 녹인후 저온반응기를 이용 -10℃ 이하로 유지시킨 후 드롭핑펀넬을 통하여 설프릴클로라이드 28.35g(0.21몰)을 3시간 동안 천천히 교반하면서 첨가시킨다.A 1 L three-necked flask was equipped with a thermometer and a dropping funnel, and 23.6 g (0.1 mol) of N, N'-dimethyl-3,3'-dithiodipropionamide was dissolved in 350 ml of chloroform and then cooled to -10 ° C using a low temperature reactor. After holding, 28.35 g (0.21 mol) of sulfyl chloride was added through a dropping funnel with gentle stirring for 3 hours.
설프릴클로라이드 첨가가 끝난후 0℃에서 1시간 동안 교반을 시켜준 후 온도를 서서히 실온까지 올린후 물 중탕에서 온도를 40℃로 유지시킨 후 3시간 동안 교반해준다.After the addition of the sulfyl chloride, the mixture was stirred at 0 ° C. for 1 hour, and the temperature was gradually raised to room temperature. The temperature was maintained at 40 ° C. in a water bath, followed by stirring for 3 hours.
반응이 진행되면서 흰색 침전물이 생성되고 40℃에서 반응이 완전히 끝난 후 침전물을 석션으로 여과시켜 반응침전물을 수거한 후 남아있는 클로로포름을 진공오븐에 3시간 동안 50℃로 유지시켜 완전히 제거하고 나면 2-메틸-4-이소티아졸린-3-온·HCI 27.6g(91몰%)을 얻는다.As the reaction proceeds, a white precipitate is formed. After completion of the reaction at 40 ° C, the precipitate is filtered by suction. After collecting the reaction precipitate, the remaining chloroform is maintained at 50 ° C in a vacuum oven for 3 hours to completely remove the residue. 27.6 g (91 mol%) of methyl-4-isothiazolin-3-one and HCI are obtained.
1H-NMR 스펙트럼(100MHz, D2O) : δppm ; 8.49(d,5H), 6.33(d,4H), 3.41(s,CH3). 1 H-NMR spectrum (100 MHz, D 2 O): δ ppm; 8.49 (d, 5H), 6.33 (d, 4H), 3.41 (s, CH 3 ).
[실시예 12]Example 12
1ℓ 3구 플라스크에 온도계와 드롭핑펀넬을 장착시키고 N,N'-디메틸-3,3'-디티오디프로피온아미드 23.6g(0.1몰)을 클로로포름 350ml에 녹인후 저온반응기를 이용 -15℃ 이하로 유지시킨 후 드롭핑펀넬을 통하여 설프릴클로라이드 27.0g(0.2몰)을 3시간 동안 천천히 교반하면서 첨가시킨다.A 1 L three-necked flask was equipped with a thermometer and a dropping funnel, and 23.6 g (0.1 mol) of N, N'-dimethyl-3,3'-dithiodipropionamide was dissolved in 350 ml of chloroform and then cooled to -15 ° C using a low temperature reactor. After holding, 27.0 g (0.2 mol) of sulfyl chloride were added through a dropping funnel with gentle stirring for 3 hours.
설프릴클로라이드 첨가가 끝난후 -5℃에서 1시간 동안 교반을 시켜준 후 온도를 서서히 실온까지 올린후 물 중탕에서 온도를 40℃로 유지시킨 후 3시간 동안 교반해준다.After the addition of the sulfyl chloride, the mixture was stirred at -5 ° C for 1 hour, and then the temperature was gradually raised to room temperature. The temperature was maintained at 40 ° C in a water bath, followed by stirring for 3 hours.
반응이 진행되면서 흰색 침전물이 생성되고 40℃에서 반응이 완전히 끝난 후 침전물을 석션으로 여과시켜 반응침전물을 수거한 후 남아있는 클로로포름을 진공오븐에 3시간 동안 50℃로 유지시켜 완전히 제거하고 나면 2-메틸-4-이소티아졸린-3-온· HCI 28.0g(92. 3몰%)을 얻는다.As the reaction proceeds, a white precipitate is formed. After completion of the reaction at 40 ° C, the precipitate is filtered by suction. After collecting the reaction precipitate, the remaining chloroform is maintained at 50 ° C in a vacuum oven for 3 hours to completely remove the residue. Methyl-4-isothiazolin-3-one HCI 28.0g (92.3 mol%) is obtained.
1H-NMR 스펙트럼(100MHz, D2O) : δppm ; 8.52(d,5H), 6.34(d,4H), 3.42(s,CH3). 1 H-NMR spectrum (100 MHz, D 2 O): δ ppm; 8.52 (d, 5H), 6.34 (d, 4H), 3.42 (s, CH 3 ).
[실시예 13]Example 13
1ℓ 3구 플라스크에 온도계와 드롭핑펀넬을 장착시키고 N, N'-디메틸-3,3'-디티오디프로피온아미드 23.6g(0.1몰)을 1,1,1-트리클로로에탄 350ml에 녹인후 저온반응기를 이용 0℃ 이하로 유지시킨 후 드롭핑펀넬을 통하여 설프릴클로라이드 40.5g(0.3몰)을 3시간 동안 천천히 교반하면서 첨가시킨다.A 1 L three-necked flask was equipped with a thermometer and a dropping funnel, and 23.6 g (0.1 mol) of N, N'-dimethyl-3,3'-dithiodipropionamide was dissolved in 350 ml of 1,1,1-trichloroethane, followed by low temperature. After maintaining the reactor at 0 ° C. or lower, 40.5 g (0.3 mol) of sulfyl chloride was added through a dropping funnel while stirring slowly for 3 hours.
설프릴클로라이드 첨가가 끝난후 0℃에서 1시간 동안 교반을 시켜준 후 온도를 서서히 실온까지 올린후 물 중탕에서 온도를 25℃로 유지시킨 후 3시간 동안 교반해준다.After the addition of the sulfyl chloride, the mixture was stirred at 0 ° C. for 1 hour, and the temperature was gradually raised to room temperature. The temperature was maintained at 25 ° C. in a water bath, followed by stirring for 3 hours.
반응이 진행되면서 흰색 침전물이 생성되고 25℃에서 반응이 완전히 끝난 후 침전물을 석션으로 여과시켜 반응침전물을 수거한 후 남아있는 1,1,1-트리클로로에탄을 진공오븐에 3시간 동안 50℃로 유지시켜 완전히 제거하고 나면 2-메틸-4-이소티아졸린-3-온·HCI 27.3g(90몰%)을 얻는다.As the reaction proceeds, a white precipitate is formed. After completion of the reaction at 25 ° C., the precipitate is filtered by suction, and the remaining precipitate is collected. The remaining 1,1,1-trichloroethane is kept at 50 ° C. in a vacuum oven for 3 hours. After maintenance and complete removal, 27.3 g (90 mol%) of 2-methyl-4-isothiazolin-3-one-HCI were obtained.
1H-NMR 스펙트럼(100MHz, D2O) : δppm ; 8.47(d,5H), 6.34(d,4H), 3.41(s,CH3). 1 H-NMR spectrum (100 MHz, D 2 O): δ ppm; 8.47 (d, 5H), 6.34 (d, 4H), 3.41 (s, CH 3 ).
[실시예 14]Example 14
1ℓ 3구 플라스크에 온도계와 드롭핑펀넬을 장착시키고 N,N'-디메틸-3,3'-디티오디프로피온아미드 23.6g(0.1몰)을 1,1,1-트리클로로에탄 350ml에 녹인후 얼음 중탕에서 5℃ 이하로 유지시킨 후 드롭핑펀넬을 통하여 설프릴클로라이드 33.75g(0.25몰)을 3시간 동안 천천히 교반하면서 첨가시킨다.A 1 L three-necked flask was equipped with a thermometer and a dropping funnel, and 23.6 g (0.1 mol) of N, N'-dimethyl-3,3'-dithiodipropionamide was dissolved in 350 ml of 1,1,1-trichloroethane and iced. After maintaining at 5 ° C. or lower in a bath, 33.75 g (0.25 mole) of sulfyl chloride was added through a dropping funnel with gentle stirring for 3 hours.
설프릴클로라이드 첨가가 끝난후 0℃에서 1시간 동안 교반을 시켜준 후 온도를 서서히 실온까지 올린후 물 중탕에서 온도를 30℃로 유지시킨 후 3시간 동안 교반해준다.After the addition of the sulfyl chloride, the mixture was stirred at 0 ° C. for 1 hour, and the temperature was gradually raised to room temperature. The temperature was maintained at 30 ° C. in a water bath, followed by stirring for 3 hours.
반응이 진행되면서 흰색 침전물이 생성되고 30℃에서 반응이 완전히 끝난 후 침전물을 석션으로 여과시켜 반응침전물을 수거한 후 남아있는 1,1,1-트리클로로에탄을 진공오븐에 3시간 동안 50℃로 유지시켜 완전히 제거하고 나면 2-메틸-4-이소티아졸린-3-온·HCI 27.5g(90.7몰%)을 얻는다.As the reaction proceeds, a white precipitate is formed. After completion of the reaction at 30 ° C, the precipitate is filtered by suction, and the remaining precipitate is collected. The remaining 1,1,1-trichloroethane is kept at 50 ° C in a vacuum oven for 3 hours. After maintenance and complete removal, 27.5 g (90.7 mol%) of 2-methyl-4-isothiazolin-3-one-HCI were obtained.
1H-NMR 스펙트럼(100MHz, D2O) : δppm ; 8.50(d,5H), 6.34(d,4H), 3.43(s,CH3). 1 H-NMR spectrum (100 MHz, D 2 O): δ ppm; 8.50 (d, 5H), 6.34 (d, 4H), 3.43 (s, CH 3 ).
[실시예 15]Example 15
1ℓ 3구 플라스크에 온도계와 드롭핑펀넬을 장착시키고 N,N'-디메일-3,3'-디티오디프로피온아미드 23.6g(0.1몰)을 1,1,1-트리클로로에탄 350ml에 녹인후 저온반응기를 이용 -5℃ 이하로 유지시킨 후 드롭핑펀넬을 통하여 설프릴클로라이드 28.35g(0.21몰)을 3시간 동안 천천히 교반하면서 첨가시킨다.A 1 L three-neck flask was equipped with a thermometer and a dropping funnel, and 23.6 g (0.1 mol) of N, N'-dimail-3,3'-dithiodipropionamide was dissolved in 350 ml of 1,1,1-trichloroethane. After maintaining at −5 ° C. or lower using a low temperature reactor, 28.35 g (0.21 mol) of sulfyl chloride was added through a dropping funnel with slow stirring for 3 hours.
설프릴클로라이드 첨가가 끝난후 0℃에서 1시간 동안 교반을 시켜준 후 온도를 서서히 실온까지 올린후 물 중탕에서 온도를 35℃로 유지시킨 후 3시간 동안 교반해준다.After the addition of the sulfyl chloride, the mixture was stirred at 0 ° C. for 1 hour, and the temperature was gradually raised to room temperature. The temperature was maintained at 35 ° C. in a water bath, followed by stirring for 3 hours.
반응이 진행되면서 흰색 침전물이 생성되고 35℃에서 반응이 완전히 끝난 후 침전물을 석션으로 여과시켜 반응침전물을 수거한 후 남아있는 1,1,1-트리클로로에탄을 진공오븐에 3시간 동안 50℃로 유지시켜 완전히 제거하고 나면 2-메틸-4-이소티아졸린-3-온·HCI 27.3g(90몰%)을 얻는다.As the reaction proceeds, a white precipitate is formed. After completion of the reaction at 35 ° C, the precipitate is filtered by suction, and then the remaining 1,1,1-trichloroethane is collected in a vacuum oven at 50 ° C for 3 hours. After maintenance and complete removal, 27.3 g (90 mol%) of 2-methyl-4-isothiazolin-3-one-HCI were obtained.
1H-NMR 스펙트럼(100MHz, D2O) : δ ; 8.54(d,5H), 6.34(d,4H), 3.40(s,CH3). 1 H-NMR spectrum (100 MHz, D 2 O): δ; 8.54 (d, 5H), 6.34 (d, 4H), 3.40 (s, CH 3 ).
[실시예 16]Example 16
1ℓ 3구 플라스크에 온도계와 드롭핑펀넬을 장착시키고 N,N'-디메틸-3,3'-디티오디프로피온아미드 23.6g(0.1몰)을 1,1,1-트리클로로에탄 350m1에 녹인후 저온반응기를 이용 -5℃ 이하로 유지시킨 후 드롭핑펀넬을 통하여 설프릴클로라이드 27.0g(0.2몰)을 3시간 동안 천천히 교반하면서 첨가시킨다.A 1 L three-neck flask was equipped with a thermometer and a dropping funnel, and 23.6 g (0.1 mol) of N, N'-dimethyl-3,3'-dithiodipropionamide was dissolved in 350 m1 of 1,1,1-trichloroethane and then After the reactor was maintained at -5 ° C or lower, 27.0 g (0.2 mol) of sulfyl chloride was added through a dropping funnel with slow stirring for 3 hours.
설프릴클로라이드 첨가가 끝난후 0℃에서 1시간 동안 교반을 시켜준 후 온도를 서서히 실온까지 올린후 물 중탕에서 온도를 40℃로 유지시킨 후 3시간 동안 교반해준다.After the addition of the sulfyl chloride, the mixture was stirred at 0 ° C. for 1 hour, and the temperature was gradually raised to room temperature. The temperature was maintained at 40 ° C. in a water bath, followed by stirring for 3 hours.
반응이 진행되면서 흰색 침전물이 생성되고 40℃에서 반응이 완전히 끝난 후 침전물을 석션으로 여과시켜 반응침전물을 수거한 후 남아있는 1,1,1-트리클로로에탄을 진공오븐에 3시간 동안 50℃로 유지시켜 완전히 제거하고 나면 2-메틸-4-이소티아졸린-3-온·HCI 27.5g(90.7몰%)을 얻는다.As the reaction proceeds, a white precipitate is formed. After completion of the reaction at 40 ° C, the precipitate is filtered by suction, and the remaining precipitate is collected. The remaining 1,1,1-trichloroethane is kept at 50 ° C in a vacuum oven for 3 hours. After maintenance and complete removal, 27.5 g (90.7 mol%) of 2-methyl-4-isothiazolin-3-one-HCI were obtained.
1H-NMR 스펙트럼(100MHz, D2O) : δppm ; 8.54(d,5H), 6.33(d,4H), 3.41(s,CH3). 1 H-NMR spectrum (100 MHz, D 2 O): δ ppm; 8.54 (d, 5H), 6.33 (d, 4H), 3.41 (s, CH 3 ).
[실시예 17]Example 17
1ℓ 3구 플라스크에 온도계와 드롭핑펀넬을 장착시키고 N,N'-디메틸-3,3'-디티오디프로피온아미드 23.6g(0.1몰)을 1,1,1-트리클로로에탄 350ml에 녹인후 저온반응기를 이용 -10℃ 이하로 유지시킨 후 드롭핑펀넬을 통하여 설프릴클로라이드 28.35g(0.21몰)을 3시간 동안 천천히 교반하면서 첨가시킨다.A 1 L three-necked flask was equipped with a thermometer and a dropping funnel, and 23.6 g (0.1 mol) of N, N'-dimethyl-3,3'-dithiodipropionamide was dissolved in 350 ml of 1,1,1-trichloroethane, followed by low temperature. After the reactor was maintained at -10 ° C or lower, 28.35 g (0.21 mol) of sulfyl chloride was added through a dropping funnel with slow stirring for 3 hours.
설프릴클로라이드 첨가가 끝난후 -5℃에서 1시간 동안 교반을 시켜준 후 온도를 서서히 실온까지 올린후 물 중탕에서 온도를 40℃로 유지시킨 후 3시간 동안 교반해준다.After the addition of the sulfyl chloride, the mixture was stirred at -5 ° C for 1 hour, and then the temperature was gradually raised to room temperature. The temperature was maintained at 40 ° C in a water bath, followed by stirring for 3 hours.
반응이 진행되면서 흰색 침전물이 생성되고 40℃에서 반응이 완전히 끝난 후 침전물을 석션으로 여과시켜 반응침전물을 수거한 후 남아있는 1,1,1-트리클로로에탄을 진공오븐에 3시간 동안 50℃로 유지시켜 완전히 제거하고 나면 2-메틸-4-이소티아졸린-3-온·HCI 27.8g(91.7몰%)을 얻는다.As the reaction proceeds, a white precipitate is formed. After completion of the reaction at 40 ° C, the precipitate is filtered by suction, and the remaining precipitate is collected. The remaining 1,1,1-trichloroethane is kept at 50 ° C in a vacuum oven for 3 hours. After maintenance and complete removal, 27.8 g (91.7 mole%) of 2-methyl-4-isothiazolin-3-one HCI was obtained.
1H-NMR 스펙트럼(100MHz, D2O) : δppm ; 8.53(d,5H), 6.34(d,4H), 3.42(s,CH3). 1 H-NMR spectrum (100 MHz, D 2 O): δ ppm; 8.53 (d, 5H), 6.34 (d, 4H), 3.42 (s, CH 3 ).
[실시예 18]Example 18
1ℓ 3구 플라스크에 온도계와 드롭핑펀넬을 장착시키고 N,N'-디메틸-3.3'-디티오디프로피온아미드 23.6g(0.1몰)을 1,1,1-트리글로로에탄 350ml에 녹인후 얼음 중탕에서 5℃ 이하로 유지시킨 후 드롭핑펀넬을 통하여 설프릴클로라이드 27.0g(0.2몰)을 3시간 동안 천천허 교반하면서 첨가시킨다.A 1 liter three-necked flask was equipped with a thermometer and a dropping funnel, and 23.6 g (0.1 mol) of N, N'-dimethyl-3.3'-dithiodipropionamide was dissolved in 350 ml of 1,1,1-trigloethane, followed by ice. After maintaining at 5 ° C. or lower in a water bath, 27.0 g (0.2 mol) of sulfyl chloride was added through a dropping funnel with gentle stirring for 3 hours.
설프릴클로라이드 첨가가 끝난후 -5℃에서 1시간 동안 교반을 시켜준 후 온도를 서서히 실온까지 올린후 물 중탕에선 온도를 40℃로 유지시킨 후 3시간 동안 교반해준다.After the addition of the sulfyl chloride, the mixture was stirred at -5 ° C for 1 hour, and then the temperature was gradually raised to room temperature. In the water bath, the temperature was maintained at 40 ° C and stirred for 3 hours.
반응이 진행되면서 흰색 침전물이 생성되고 40℃에서 반응이 완전히 끝난 후 침전물을 석션으로 여과시켜 반응침전물을 수거한 후 남아있는 1,1,1-트리클로로에탄을 진공오븐에 3시간 동안 50℃로 유지시켜 완전히 제거하고 나면 2-메틸-4-이소티아졸린-3-온·HCI 27.6g(91몰%)을 얻는다.As the reaction proceeds, a white precipitate is formed. After completion of the reaction at 40 ° C, the precipitate is filtered by suction, and the remaining precipitate is collected. The remaining 1,1,1-trichloroethane is kept at 50 ° C in a vacuum oven for 3 hours. After maintenance and complete removal, 27.6 g (91 mol%) of 2-methyl-4-isothiazolin-3-one-HCI were obtained.
1H-NMR 스펙트럼(100MHz, D2O) : δppm ; 8.56(d,5H), 6.37(d,4H), 3.43(s,CH3). 1 H-NMR spectrum (100 MHz, D 2 O): δ ppm; 8.56 (d, 5H), 6.37 (d, 4H), 3.43 (s, CH 3 ).
[비교예 1]Comparative Example 1
1ℓ 3구 플라스크에 온도계와 드롭핑펀넬을 장착시키고 N,N'-디메틸-3,3'-디티오디프로피온아미드 23.6g(0.1몰)을 메틸렌클로라이드 350ml에 녹인후 물 중탕에서 70℃ 이상으로 유지시킨 후 드롭핑펀넬을 통하여 설프릴클로라이드 40.5g(0.3몰)을 3시간 동안 천천히 교반하면서 첨가시킨다. 이때 메틸렌클로라이드의 증기로 인하여 반응을 진행시킬 수 없었다.A 1 L three-necked flask was equipped with a thermometer and a dropping funnel, and 23.6 g (0.1 mol) of N, N'-dimethyl-3,3'-dithiodipropionamide was dissolved in 350 ml of methylene chloride and maintained at 70 ° C. or higher in a water bath. After adding 40.5 g (0.3 mol) of sulfyl chloride through a dropping funnel, the mixture was slowly stirred for 3 hours. At this time, the reaction could not proceed due to the vapor of methylene chloride.
[비교예 2]Comparative Example 2
1ℓ 3구 플라스크에 온도계와 드롭핑펀넬을 장착시키고 N,N'-디메틸-3,3'-디티오디프로피온아미드 23.6g(0.1몰)을 클로로포름 350ml에 녹인후 물 중탕에서 70℃ 이상으로 유지시킨 후 드롭핑펀넬을 통하여 설프릴클로라이드 40.5g(0.3몰)을 3시간 동안 천천히 교반하면서 첨가시킨다. 이때 클로로포름의 증기로 인하여 반응을 진행시킬 수 없었다.A 1 L three-necked flask was equipped with a thermometer and a dropping funnel, and 23.6 g (0.1 mol) of N, N'-dimethyl-3,3'-dithiodipropionamide was dissolved in 350 ml of chloroform and maintained at 70 ° C. or higher in a water bath. Then, 40.5 g (0.3 mol) of sulfyl chloride was added to the dropping funnel while stirring slowly for 3 hours. At this time, the reaction could not proceed due to the vapor of chloroform.
Claims (3)
Priority Applications (6)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| KR1019910007541A KR940000239B1 (en) | 1991-05-10 | 1991-05-10 | Process for preparing 2-methyl-4-isothiazoline-3-one |
| US08/146,172 US5453507A (en) | 1991-05-10 | 1992-05-11 | Process for preparing 4-isothiazolin-3-one |
| DE4291487T DE4291487T1 (en) | 1991-05-10 | 1992-05-11 | Process for the preparation of 4-isothiazolin-3-one |
| PCT/KR1992/000014 WO1992020664A1 (en) | 1991-05-10 | 1992-05-11 | A process for preparing 4-isothiazolin-3-one |
| GB9323198A GB2274283B (en) | 1991-05-10 | 1992-05-11 | A process for preparing 4-isothiazolin-3-one |
| JP4509538A JPH07119219B2 (en) | 1991-05-10 | 1992-05-11 | Method for producing 4-isothiazolin-3-one |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| KR1019910007541A KR940000239B1 (en) | 1991-05-10 | 1991-05-10 | Process for preparing 2-methyl-4-isothiazoline-3-one |
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| Publication Number | Publication Date |
|---|---|
| KR920021521A KR920021521A (en) | 1992-12-18 |
| KR940000239B1 true KR940000239B1 (en) | 1994-01-12 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| KR1019910007541A KR940000239B1 (en) | 1991-05-10 | 1991-05-10 | Process for preparing 2-methyl-4-isothiazoline-3-one |
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| Country | Link |
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| KR (1) | KR940000239B1 (en) |
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