KR100616098B1 - Process for preparing 1,2-benzisothiazolin-3-ones - Google Patents
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- 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
본 발명은 1,2-벤즈이소티아졸린-3-온의 제조방법에 관한 것으로서, 더욱 상세하기로는 다음 화학식 2로 표시되는 2,2'-디티오디벤조일 할라이드를 출발물질로 사용하고 이를 산화제 존재하에서 아민과 반응시킴으로써 별도의 분리공정없이 한 단계로 반응을 수행함과 동시에 산화제에 의한 과잉반응을 최소한으로하는 각종 살균제 및 방부제로 널리 이용되고 있는 다음 화학식 1로 표시되는 1,2-벤즈이소티아졸린-3-온을 대량생산하는데 유용한 제조방법에 관한 것이다.The present invention relates to a method for preparing 1,2-benzisothiazolin-3-one, and more particularly, using 2,2'-dithiodibenzoyl halide represented by the following Chemical Formula 2 as a starting material and presenting an oxidant 1,2-benzisothiazoline represented by the following general formula (1) which is widely used as various fungicides and preservatives to perform the reaction in one step without any separate process by minimizing the excessive reaction by the oxidizing agent by reacting with an amine under It relates to a production method useful for mass production of 3-ones.
상기 화학식에서 : R은 수소원자 또는 탄소원자수 1 ∼ 8의 저급알킬기를 나타내고; X는 할로겐원자를 나타낸다.In the formula: R represents a hydrogen atom or a lower alkyl group of 1 to 8 carbon atoms; X represents a halogen atom.
1,2-벤즈이소티아졸린-3-온1,2-benzisothiazolin-3-one
Description
본 발명은 1,2-벤즈이소티아졸린-3-온의 제조방법에 관한 것으로서, 더욱 상세하기로는 다음 화학식 2로 표시되는 2,2'-디티오디벤조일 할라이드를 출발물질로 사용하고 이를 산화제 존재하에서 아민과 반응시킴으로써 별도의 분리공정없이 한 단계로 반응을 수행함과 동시에 산화제에 의한 과잉반응을 최소한으로하는 각종 살균제 및 방부제로 널리 이용되고 있는 다음 화학식 1로 표시되는 1,2-벤즈이소티아졸린-3-온을 대량생산하는데 유용한 제조방법에 관한 것이다.The present invention relates to a method for preparing 1,2-benzisothiazolin-3-one, and more particularly, using 2,2'-dithiodibenzoyl halide represented by the following Chemical Formula 2 as a starting material and presenting an oxidant 1,2-benzisothiazoline represented by the following general formula (1) which is widely used as various fungicides and preservatives to perform the reaction in one step without any separate process by minimizing the excessive reaction by the oxidizing agent by reacting with an amine under It relates to a production method useful for mass production of 3-ones.
화학식 1Formula 1
화학식 2Formula 2
상기 화학식에서 : R은 수소원자 또는 탄소원자수 1 ∼ 8의 저급알킬기를 나타내고; X는 할로겐원자를 나타낸다.In the formula: R represents a hydrogen atom or a lower alkyl group of 1 to 8 carbon atoms; X represents a halogen atom.
상기 화학식 1로 표시되는 1,2-벤즈이소티아졸린-3-온은 안정성 및 지속성이 있는 방부제 및 살균제로서 잘 알려져 있는 바, 특히 pH 8 이상의 강염기성 영역에서 안정한 특성이 있어 pH가 높은 제품에 사용되어 살균력 및 방부력을 장기간 지속시켜 제품을 안정화 시키는 장점이 있다.1,2-benzisothiazolin-3-one represented by Chemical Formula 1 is well known as a preservative and a disinfectant and a fungicide, and especially in a strong pH region of pH 8 or higher, so that the product has a high pH. It has the advantage of stabilizing the product by long-lasting sterilization and antiseptic.
이에 상기 화학식 1로 표시되는 1,2-벤즈이소티아졸린-3-온의 제조방법에 대해서는 많은 연구가 진행되어 왔다. 예컨대, 영국특허 제848,130호(1960)에는 다음 반응식 1에 나타낸 바와 같은 고전적인 세 가지 방법이 제시되어 있다.Accordingly, many studies have been conducted on the method for preparing 1,2-benzisothiazolin-3-one represented by Chemical Formula 1. For example, British Patent 848,130 (1960) suggests three classical methods, as shown in Scheme 1 below.
상기 반응식 1에서 : R1은 탄소원자수 4 이상의 고급알킬기를 나타내고; X 및 Y는 각각 할로겐원자를 나타낸다.In Reaction Scheme 1, R 1 represents a higher alkyl group having 4 or more carbon atoms; X and Y each represent a halogen atom.
상기 반응식 1에 따른 고전적인 제조방법은 유기용매에 섞이는 고급알킬아민을 사용하여 R1 치환기로서 탄소원자수 4 이상의 고급알킬기를 도입하고 있을뿐 탄소원자수 3 이하의 저급알킬기 도입에 대한 언급이 전혀없다. 이는 아마도 저급알킬아민이 기체상이나 보통 수용액상으로 이용 가능하기 때문인 것으로 추측된다. 즉, 저급알킬아민을 기체상으로 이용하는 경우 혐수성 용매에의 용해도가 낮으므로 반응속도가 느리며 기체의 손실이 클 수밖에 없고, 수용액상으로 이용하는 경우 전술한 바와 같은 문제를 갖을뿐더러 ii) 반응의 경우 용매인 물이 반응성이 좋은 설피닐 할라이드와 심한 부반응을 일으키는 단점이 있다. 더구나, i) 및 ⅱ) 반응은 다단계 공정으로 구성되어 있고 유기용매를 사용하는 등 조작이 번거로운 문제가 있고, ⅲ) 반응은 최고 수율이 50% 정도로 제한되어 있어 상업화하기에는 많은 어려움이 있다.The classical preparation method according to Scheme 1 introduces a higher alkyl group having 4 or more carbon atoms as R 1 substituent using a higher alkylamine mixed in an organic solvent, and there is no mention of introducing a lower alkyl group having 3 or less carbon atoms. This is probably because lower alkylamines are available in gaseous or ordinary aqueous phase. That is, when lower alkylamine is used in the gas phase, the solubility in the hydrophobic solvent is low, so the reaction rate is low and the loss of gas is large, and in the case of the aqueous solution, it has the problems described above. Water as a solvent has the disadvantage of causing severe side reactions with the reactive sulfinyl halides. In addition, i) and ii) the reaction is composed of a multi-step process, there is a problem that the operation is cumbersome, such as using an organic solvent, iii) the reaction is limited to a maximum yield of about 50%, there are many difficulties in commercialization.
다른 제조방법으로서, 미국특허 제4,736,040호(1986)에서는 2,2'-디티오디벤즈아미드를 출발물질로 하고 알칼리금속 수산화염과 산화제를 사용하여 1,2-벤즈이소티아졸린-3-온을 합성하였다. 이에 대해서는 다음 반응식 2에 나타내었으며, 이는 상기한 영국특허의 ⅲ) 반응을 개선한 것이다.As another manufacturing method, US Pat. No. 4,736,040 (1986) discloses 1,2-benzisothiazolin-3-one using 2,2'-dithiodibenzamide as a starting material and an alkali metal hydroxide and an oxidizing agent. Synthesized. This is shown in the following Scheme 2, which is an improvement of the iii) reaction of the British patent.
상기 반응식 2에서 : R2는 수소원자, 할로겐원자, 저급알킬기 또는 저급알콕시기를 나타낸다.In Reaction Formula 2, R 2 represents a hydrogen atom, a halogen atom, a lower alkyl group or a lower alkoxy group.
상기 반응식 2에서 출발물질로 사용하고 있는 2,2'-디티오디벤즈아미드의 경우, R2가 고급알킬기인 경우 상기한 영국특허 i)의 제법에 따라 제조하여 사용하고, R2가 수소원자인 경우 미국특허 제4,736,040호에 제시된 방법에 의해 안트라닐아미드로부터 합성하여 사용하도록 하고 있으나 실제로 합성하기 어려운 안트라닐아미도의 합성에 대해서는 특별한 언급이 없다. 또한, R2가 수소원자인 경우 최종 생성물로 생성되는 상기 반응식 2의 화합물(3)이 알칼리금속염에 완전히 용해되므로 반응중의 산화제 또는 여분의 산화제에 의한 과잉 산화반응을 막을 수 없는 문제가 있다. In the case of 2,2'-dithiodibenzamide used as a starting material in Scheme 2, when R 2 is a higher alkyl group, it is prepared according to the preparation method of British Patent i) described above, and R 2 is a hydrogen atom. In the case of using the method described in US Pat. In addition, when R 2 is a hydrogen atom, compound (3) of Scheme 2, which is produced as a final product, is completely dissolved in an alkali metal salt, and thus there is a problem in that an excessive oxidation reaction by an oxidizing agent or an extra oxidant during the reaction cannot be prevented.
상기에서 설명한 바와 같이, 종래의 제조방법에서는 상업적 이용 및 합성이 어려운 출발물질을 사용하여 비교적 낮은 제조수율로 1,2-벤즈이소티아졸린-3-온을 합성하기 때문에 산업에 적용하기에는 한계가 있다.As described above, in the conventional manufacturing method, since 1,2-benzisothiazolin-3-one is synthesized at a relatively low production yield using a starting material that is difficult to commercially use and synthesized, there is a limitation in applying it to industry. .
이에, 본 발명자들은 상업적으로 이용 가능하고 합성이 간편한 출발물질을 사용하고, 부반응을 최소화하여 반응수율 95 % 이상과 최종 목적물의 순도를 99 % 이상으로 유지할 수 있는 1,2-벤즈이소티아졸린-3-온의 개선된 제조방법을 개발함 으로써 본 발명을 완성하였다.Accordingly, the present inventors use commercially available starting materials, which are easy to synthesize, and minimize the side reactions to maintain the reaction yield of 95% or more and the purity of the final object to 99% or more, 1,2-benzisothiazoline- The present invention has been completed by developing an improved process for producing 3-ones.
따라서, 본 발명은 각종 살균제 또는 방부제로 널리 사용되고 있는 상기 화학식 1로 표시되는 1,2-벤즈이소티아졸린-3-온의 상업적인 대량생산에 유용한 제조방법을 제공하는 데 그 목적이 있다.
Accordingly, an object of the present invention is to provide a production method useful for commercial mass production of 1,2-benzisothiazolin-3-one represented by Chemical Formula 1, which is widely used as various fungicides or preservatives.
본 발명은 2,2'-디티오디벤조일 할라이드로부터 1,2-벤즈이소티아졸린-3-온을 제조하는 방법에 있어서, The present invention provides a method for preparing 1,2-benzisothiazolin-3-one from 2,2'-dithiodibenzoyl halide,
다음 화학식 2로 표시되는 2,2'-디티오디벤조일 할라이드를 아민 수용액과 과산화수소 존재하에서 반응시키며, 반응도중에 생성되는 중간체의 분리공정없이 한 단계로 반응을 수행시켜 제조하는 다음 화학식 1로 표시되는 1,2-벤즈이소티아졸린-3-온의 제조방법을 그 특징으로 한다.1, which is prepared by reacting 2,2'-dithiodibenzoyl halide represented by the following Chemical Formula 2 in the presence of an aqueous amine solution with hydrogen peroxide and carrying out the reaction in one step without separating the intermediate produced during the reaction; It is characterized by the manufacturing method of, 2-benzisothiazolin-3-one.
화학식 1Formula 1
화학식 2Formula 2
상기 화학식에서 : R은 수소원자 또는 탄소원자수 1 ∼ 8의 저급알킬기를 나타내 고; X는 할로겐원자를 나타낸다.In the formula: R represents a hydrogen atom or a lower alkyl group of 1 to 8 carbon atoms; X represents a halogen atom.
본 발명에 따른 상기 화학식 1로 표시되는 1,2-벤즈이소티아졸린-3-온의 제조방법은 다음 반응식 3과 같다.Method for preparing 1,2-benzisothiazolin-3-one represented by Formula 1 according to the present invention is shown in the following Scheme 3.
상기 반응식 3에서 : R은 수소원자 또는 탄소원자수 1 ∼ 8의 저급알킬기를 나타내고; X는 할로겐원자를 나타낸다.In Reaction Scheme 3: R represents a hydrogen atom or a lower alkyl group having 1 to 8 carbon atoms; X represents a halogen atom.
출발물질로서 사용되는 상기 화학식 2로 표시되는 2,2'-디티오디벤조일 할라이드는 상업적으로 이용 가능한 2,2'-디티오벤조산(Aldrich cat. No. 38,928-5)을 원료로하고 티오닐 할라이드를 할로겐화제로 사용하는 일반적인 방법으로 준비하여 사용할 수 있다.The 2,2'-dithiodibenzoyl halide represented by Formula 2 used as a starting material is based on commercially available 2,2'-dithiobenzoic acid (Aldrich cat. No. 38,928-5), and is thionyl halide. It can be prepared and used by the general method using a halogenating agent.
4 ∼ 50 당량의 아민 화합물이 함유된 1 ∼ 50 중량% 농도의 아민 수용액, 바람직하게는 10 ∼ 20 당량의 아민 화합물을 함유하는 20 ∼ 40 중량% 농도의 아민 수용액에 상기 화학식 2로 표시되는 2,2'-디티오디벤조일 할라이드를 분산시킨 후 1시간 이상 교반한다. 상기 반응용액에 1 ∼ 5 당량의 과산화수소(H2O2), 바람직하게는 1 ∼ 2 당량의 과산화수소(H2O2)를 첨가하고 0 ∼ 50℃, 바람직하게는 10 ∼ 30℃에서 0.5 ∼ 5시간, 바람직하게는 1 ∼ 2시간 반응시키다. 이때, 아 민 화합물으로는 RNH2(이때, R은 수소원자 또는 탄소원자수 1 ∼ 8의 저급알킬기)로 표시되는 화합물을 선택하여 사용하는 것이 바람직하다.2 represented by the formula (2) in an aqueous amine solution at a concentration of 1 to 50% by weight containing 4 to 50 equivalents of an amine compound, preferably at an aqueous amine solution at a concentration of 20 to 40% by weight containing 10 to 20 equivalents of the amine compound. The 2'-dithiodibenzoyl halide is dispersed and stirred for at least 1 hour. 1 to 5 equivalents of hydrogen peroxide (H 2 O 2 ), preferably 1 to 2 equivalents of hydrogen peroxide (H 2 O 2 ), are added to the reaction solution, and 0 to 50 ° C, preferably 10 to 30 ° C. It is made to react for 5 hours, Preferably it is 1-2 hours. At this time, it is preferable to select and use a compound represented by RNH 2 (wherein R is a hydrogen atom or a lower alkyl group having 1 to 8 carbon atoms) as the amine compound.
상기 반응에 있어서, 아민 화합물의 농도 및 사용량이 저조하게 되면 고리화 반응이 완결되지 못하여 순도가 떨어지며 따라서 별도의 분리 및 정제공정이 필요하여 생산비용이 높아지고, 그 농도 및 사용량이 과다하면 반응후 잔류하는 아민 화합물을 제거하기 위해 다량의 산이 사용되는 문제가 있다. 또한, 산화제로서 사용되는 과산화수소의 사용량이 상기 범위 미만이거나 과다하면 전체적인 제조수율이 저하되는 문제가 있다. 또한, 반응온도가 0℃ 미만이면 온도가 너무 낮아 반응진행 속도가 느리고, 50℃를 초과하면 반응조건이 격렬하여 산화제에 의한 과잉반응(Over-reaction)이 일어나 부산물이 생성되어 목적물의 순도와 수율이 감소된다. In the above reaction, when the concentration and the amount of the amine compound are low, the cyclization reaction is not completed and the purity is lowered. Therefore, a separate separation and purification process is required, and thus the production cost is high. There is a problem that a large amount of acid is used to remove the amine compound. In addition, when the amount of hydrogen peroxide used as the oxidant is less than or in the above range, there is a problem that the overall production yield is lowered. In addition, if the reaction temperature is less than 0 ℃, the temperature is too low, the reaction progress rate is slow, if it exceeds 50 ℃ reaction conditions are violent and over-reaction by oxidizing agent occurs to produce by-products of the desired purity and yield Is reduced.
본 발명에 따른 제조방법의 경우, 아민 화합물을 염기로 사용함으로써 최종 생성물인 1,2-벤즈이소티아졸린-3-온이 산화제에 의해 과잉반응(Over-reaction)을 일으켜 수율이 저하되는 현상을 1/3 정도로 줄이는 효과를 얻을 수 있었다. 이러한 효과는 1,2-벤즈이소티아졸린-3-온의 아민 화합물에의 낮은 용해도에 의한 상분리 현상에 기인하기도 하지만 아민 화합물 자체의 산화제 순화기능에 기인하기도 한다. 실제로 아민 화합물의 산화제 순화기능에 의한 과잉반응 저지효과는 낮은 용해도에 의한 효과보다 더 큼을 확인할 수 있었다[실시예 1 ∼ 3 참조].In the case of the production method according to the present invention, by using an amine compound as a base, the final product 1,2-benzisothiazolin-3-one causes an over-reaction by the oxidizing agent to reduce the yield The effect was reduced to about one third. This effect may be due to the phase separation phenomenon due to the low solubility of 1,2-benzisothiazolin-3-one in the amine compound, but also due to the oxidizing agent purifying function of the amine compound itself. In fact, it was confirmed that the effect of inhibiting excessive reaction by the oxidizing agent purifying function of the amine compound was greater than the effect due to low solubility [see Examples 1 to 3].
상기 반응이 완료되면, 무기산 예를 들면 염산, 황산 또는 질산을 사용하여 반응용액의 pH를 대략 1 ∼ 7 범위로 산성화 또는 중화한 뒤 여과하여 본 발명이 목적으로 하는 1,2-벤즈이소티아졸-3-온을 얻는다. 한편, 아민 화합물으로서 탄소원자수 4 이상의 알킬아민을 사용한 경우, 무기산에 의한 산성화 또는 중화과정을 생략하고, 직접 유기용매로 추출한 후 용매를 증발시켜 2-알킬-1,2-벤즈이소티아졸린-3-온을 얻을 수도 있다. 이때 추출용매로는 디에틸에테르, 염화메틸렌, 클로로포름 및 톨루엔 중에서 선택하여 사용하는 것이 바람직하다.Upon completion of the reaction, the pH of the reaction solution is acidified or neutralized to approximately 1-7 range using inorganic acids such as hydrochloric acid, sulfuric acid, or nitric acid, followed by filtration to produce 1,2-benzisothiazole as an object of the present invention. Get 3-one. On the other hand, when an alkylamine having 4 or more carbon atoms is used as the amine compound, 2-acid-1,2-benzisothiazoline-3 is extracted by directly extracting with an organic solvent and then evaporating the solvent. You can also get -on. At this time, the extraction solvent is preferably selected from diethyl ether, methylene chloride, chloroform and toluene.
상기에서 설명한 바와 같이, 본 발명에서는 상업적으로 이용 가능한 물질로부터 쉽게 합성되는 상기 화학식 2로 표시되는 2,2'-디티오디벤조일 할라이드를 출발물질로 하여 별도의 중간체 분리공정없이 반응을 진행시키므로 사실상 한 단계로 1,2-벤즈이소티아졸린-3-온을 제조할 수 있었다.As described above, in the present invention, the reaction proceeds without a separate intermediate separation process using 2,2'-dithiodibenzoyl halide represented by Chemical Formula 2, which is easily synthesized from a commercially available material. A 1,2-benzisothiazolin-3-one can be prepared in a step.
이와 같은 본 발명을 다음의 비교예와 실시예에 의거하여 더욱 상세히 설명하겠는 바, 본 발명이 이에 한정되는 것은 아니다.The present invention will be described in more detail based on the following Comparative Examples and Examples, but the present invention is not limited thereto.
제조예 : 2,2'-디티오벤조일 클로라이드의 제조 Preparation Example: Preparation of 2,2'-dithiobenzoyl chloride
2,2'-디티오벤조산(50.0 g, 0.163 mmol)을 톨루엔(180 ㎖)에 분산시킨 후, 티오닐 클로라이드(46 g, 0.39 mmol)와 촉매량의 N,N-디메틸술폰아마이드(1.0 g)를 넣고 1시간 동안 환류하였다. 완전히 투명한 용액이 되었을 때 감압을 걸어 용매와 여분의 티오닐 클로라이드를 증류해낸 뒤 진공으로 건조하여 2,2'-디티오벤조일 클로라이드(54.3 g, 0.158 mmol)를 얻었다.2,2'-dithiobenzoic acid (50.0 g, 0.163 mmol) was dispersed in toluene (180 mL), followed by thionyl chloride (46 g, 0.39 mmol) and a catalytic amount of N, N-dimethylsulfonamide (1.0 g) Was added and refluxed for 1 hour. When the solution became completely clear, the solvent was evaporated under reduced pressure, and the excess thionyl chloride was distilled off and dried in vacuo to give 2,2'-dithiobenzoyl chloride (54.3 g, 0.158 mmol).
실시예 1Example 1
물(50 g)과 29% 암모니아수(120 g, 2.0 mmol)를 섞은 용액에 2,2'-디티오디벤조일 클로라이드(54.3 g, 0.158 mmol)를 첨가하였다. 반응 혼합물은 1시간동안 교반한 후 내부온도를 10 ℃ 까지 냉각하였고, 반응기 내부온도를 25 ℃ 이하로 유지시키면서 35% 과산화수소(18 g, 0.185 mmol)를 천천히 첨가하였다. 과산화수소의 첨가가 끝나면 30분동안 추가로 교반한 후, 35% 염산수용액으로 반응용액의 pH를 1 ∼ 2로 조절하였다. 반응액을 냉각하여 10 ℃ 이하로 유지한 후 침전물을 감압 여과하여 얻고, 이를 진공건조하여 1,2-벤즈이소티아졸린-3-온(45.9 g, 0.304 mmol, 수율 96.2%)을 얻었다.To a solution of water (50 g) and 29% aqueous ammonia (120 g, 2.0 mmol) was added 2,2'-dithiodibenzoyl chloride (54.3 g, 0.158 mmol). After the reaction mixture was stirred for 1 hour, the internal temperature was cooled to 10 ° C, and 35% hydrogen peroxide (18 g, 0.185 mmol) was slowly added while maintaining the temperature inside the reactor at 25 ° C or lower. After the addition of hydrogen peroxide was further stirred for 30 minutes, the pH of the reaction solution was adjusted to 1-2 with 35% aqueous hydrochloric acid. The reaction solution was cooled and maintained at 10 ° C. or lower, and then the precipitate was obtained by filtration under reduced pressure, followed by vacuum drying to obtain 1,2-benzisothiazolin-3-one (45.9 g, 0.304 mmol, yield 96.2%).
실시예 2Example 2
2,2'-디티오디벤조일 클로라이드(34.3 g, 100 mmol)을 물(100 ㎖)에 분산시킨 후, n-부틸아민(73 g)을 첨가하였다. 반응 혼합물은 1시간동안 교반한 후, 반응기 내부온도를 25 ℃ 이하로 유지시키면서 35% 과산화수소(11.4 g, 117 mmol)를 천천히 첨가하였다. 과산화수소의 첨가가 끝나면 30분동안 추가로 교반한 후, 디에틸에테르(100 ㎖×3)로 추출하고, 추출액을 무수 황산마그네슘으로 건조하고 감압 증류하여 황갈색 액체의 2-n-부틸 1,2-벤즈이소티아졸린-3-온(40.3 g, 194 mmol, 수율 97.0 %)을 얻었다.2,2'-dithiodibenzoyl chloride (34.3 g, 100 mmol) was dispersed in water (100 mL) and then n-butylamine (73 g) was added. The reaction mixture was stirred for 1 hour and then 35% hydrogen peroxide (11.4 g, 117 mmol) was slowly added while maintaining the reactor internal temperature below 25 ° C. After the addition of hydrogen peroxide, the mixture was further stirred for 30 minutes, extracted with diethyl ether (100 mL × 3), the extract was dried over anhydrous magnesium sulfate, and distilled under reduced pressure to obtain a yellowish brown liquid, 2-n-butyl 1,2- Benzisothiazolin-3-one (40.3 g, 194 mmol, yield 97.0%) was obtained.
실험예Experimental Example
1,2-벤즈이소티아졸린-3-온(2.19 g, 14.5 mmol)을 물(20 g)에 분산시킨 후 다음 표 1에 나타낸 바와 같은 수산화나트륨, 암모니아 또는 이들의 혼합물을 선택 첨가하여 완전히 녹인 다음, 35% 과산화수소(0.14 g, 1.45 mmol)를 첨가한 후에 계속 교반하였다. 반응 혼합물은 1시간동안 교반한 후, 500배로 묽혀 반응을 종료시켰다. 반응 종류후의 1,2-벤즈이소티아졸린-3-온의 잔존량은 HPLC로 정량하여 다음 표 1에 나타내었다.1,2-benzisothiazolin-3-one (2.19 g, 14.5 mmol) was dispersed in water (20 g), and then dissolved completely by addition of sodium hydroxide, ammonia or a mixture thereof as shown in Table 1 below. Then, 35% hydrogen peroxide (0.14 g, 1.45 mmol) was added and stirring continued. The reaction mixture was stirred for 1 hour and then diluted 500 times to terminate the reaction. The residual amount of 1,2-benzisothiazolin-3-one after the reaction was quantified by HPLC and shown in Table 1 below.
상기 표 1의 결과에 의하면, 1,2-벤즈이소티아졸린-3-온의 과산화수소 산화제에 의한 과잉반응(Over-reaction)을 저지하는데 있어서는 아민 화합물이 탁월함을 알 수 있다.According to the results of Table 1, it can be seen that the amine compound is excellent in preventing the over-reaction of 1,2-benzisothiazolin-3-one by the hydrogen peroxide oxidizing agent.
본 발명에 따른 제조방법에서는 상업적으로 이용 가능한 출발물질을 사용하고 반응중에 생성되는 중간체를 간단히 분리하고 별도의 건조공정 없이 다음 반응을 진행시킴으로써 단위시간당 생산성이 높을 뿐만 아니라 99% 이상의 고순도 및 95% 이상의 제조수율로 1,2-벤즈이소티아졸린-3-온의 제조가 가능하였다. In the production method according to the present invention using commercially available starting materials and by simply separating the intermediates produced during the reaction and proceeding the next reaction without a separate drying process, not only is the productivity per unit time high, but also high purity of 99% or more and 95% or more Production of 1,2-benzisothiazolin-3-one was possible in the production yield.
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| US4736040A (en) * | 1985-01-10 | 1988-04-05 | Basf Aktiengesellschaft | Preparation of 1,2-benzisothiazolones |
| US5936094A (en) * | 1995-03-17 | 1999-08-10 | Zeneca Limited | Process for the preparation of 1,2-benzisothiazolin-3-ones |
| KR20000018793A (en) * | 1998-09-04 | 2000-04-06 | 조민호 | Method for manufacturing 1,2-benzisothiazolones-3-one |
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| US4736040A (en) * | 1985-01-10 | 1988-04-05 | Basf Aktiengesellschaft | Preparation of 1,2-benzisothiazolones |
| US5936094A (en) * | 1995-03-17 | 1999-08-10 | Zeneca Limited | Process for the preparation of 1,2-benzisothiazolin-3-ones |
| KR100429082B1 (en) * | 1995-03-17 | 2004-08-25 | 아베시아 리미티드 | Process for the preparation of 1,2-benzisothiazolin-3-ones |
| KR20000018793A (en) * | 1998-09-04 | 2000-04-06 | 조민호 | Method for manufacturing 1,2-benzisothiazolones-3-one |
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