KR0163291B1 - Preparation method of 2-sulfonyl thiazole carboxylic acid derivatives by h2o2 in the presence of h2wo4 - Google Patents
Preparation method of 2-sulfonyl thiazole carboxylic acid derivatives by h2o2 in the presence of h2wo4 Download PDFInfo
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- KR0163291B1 KR0163291B1 KR1019960004701A KR19960004701A KR0163291B1 KR 0163291 B1 KR0163291 B1 KR 0163291B1 KR 1019960004701 A KR1019960004701 A KR 1019960004701A KR 19960004701 A KR19960004701 A KR 19960004701A KR 0163291 B1 KR0163291 B1 KR 0163291B1
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- C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
- C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
- C07D277/20—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D277/32—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members 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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Abstract
하기 일반식(3)로 표시되는 2-술파닐티아졸 카르복실산 유도체를 과산화수소와 H2WO4를 사용하여 산화시킴을 특징으로 하는 하기 일반식(1)로 표시되는 2-술포닐티아졸 카르복실산 유도체의 제조방법을 제공하는 것이다.2-sulfonylthiazole represented by the following general formula (1), characterized by oxidizing a 2 -sulfanylthiazole carboxylic acid derivative represented by the following general formula (3) with hydrogen peroxide and H 2 WO 4 It is to provide a method for producing a carboxylic acid derivative.
Description
본 발명은 하기 일반식(Ⅰ)로 표시되는 2-술포닐티아졸 카르복실산 유도체의 제조방법에 관한 것이다.The present invention relates to a method for producing a 2-sulfonylthiazole carboxylic acid derivative represented by the following general formula (I).
상기식에서 R1은 C1-3직쇄알킬기를 나타내고, R2는 C1-3알킬 또는 C1-3할로알킬기를 나타내고, X는 -OH, -OR3또는 하기구조식(2)의 시아노-티오펜-2-일-메틸-아미노기이며,Wherein R 1 represents a C 1-3 linear alkyl group, R 2 represents a C 1-3 alkyl or C 1-3 haloalkyl group, X represents -OH, -OR 3 or cyano- of formula (2) Thiophen-2-yl-methyl-amino group,
R3는 메틸 또는 에틸기이다.R 3 is a methyl or ethyl group.
더욱 구체적으로, 본 발명은 하기 일반식(3)로 표시되는 2-술파닐-티아졸 카르복실산 유도체를 과산화수소수와 텅스텐산(H2WO4)을 사용하여 산화반응시킴을 특징으로하는 상기 일반식(1)로 표시되는 2-술포닐티아졸 카르복실산 유도의 제조방법을 제공하는 것이다.More specifically, the present invention is characterized in that the oxidation of 2 -sulfanyl-thiazole carboxylic acid derivative represented by the following general formula (3) using hydrogen peroxide and tungstic acid (H 2 WO 4 ) It is to provide a method for producing 2-sulfonylthiazole carboxylic acid derivative represented by the general formula (1).
상기식에서, R1, R2및 X는 각각 전술한 바와 같다.Wherein R 1 , R 2 and X are as described above, respectively.
상기 일반식(1)과 일반식(3)의 화합물은 역병균과 노균병균이 일으키는 식물병의 퇴치에 사용되는 살균물질의 제조에 있어서 중간체로서 유용하다. 상기 일반식(1)의 화합물의 제조방법은 본 발명자들에 의해 이미 대한민국 특허출원 95-41293호, 95-41294 호 및 95-41295호로 출원되었으며 여기에서는 다음의 반응도식Ⅰ에서와 같이 일반식(3)의 화합물을 용매의 존재하에 옥손(oxone) 또는 과산화수소를 사용하는 술폰으로의 산화방법을 제시하였다.The compounds of the general formulas (1) and (3) are useful as intermediates in the preparation of bactericidal substances used for combating plant diseases caused by late blight and fungal pathogens. The preparation method of the compound of Formula (1) has already been filed by the present inventors in Korean Patent Application Nos. 95-41293, 95-41294 and 95-41295, where the general formula (I) A method of oxidizing the compound of 3) to sulfone using oxone or hydrogen peroxide in the presence of a solvent is proposed.
상기식에서, R1, R2및 X는 각각 전술한 바와 같다.Wherein R 1 , R 2 and X are as described above, respectively.
그러나, 상기방법에 의한 산화방법은 과량의 산화제가 필요하며 또한 반응시간도 상당히 길어야 하는 단점이 있었다. 이제 본 발명자들은 선행기술방법의 문제점을 해결하기 위하여 수많은 연구와 실험을 거듭하던중 텅스텐산을 촉매로 첨가함으로써 과산화수소수를 이용한 머캅토기의 알킬술폰으로의 산화반응에서 반응수율을 증가시키고 반응시간을 단축하며 산화제의 사용량을 크게 감소시킬 수 있음을 밝혀내고 본 발명을 완성하게 되었다.However, the oxidation method according to the above method has the disadvantage that an excessive amount of oxidant is required and the reaction time must be considerably long. The present inventors have increased the reaction yield and reaction time in the oxidation reaction of mercapto group to alkyl sulfone using hydrogen peroxide by adding tungstic acid as a catalyst during numerous studies and experiments to solve the problems of the prior art method. The present invention has been accomplished by finding that it can shorten and greatly reduce the amount of oxidant used.
이하 본 발명을 상세히 설명한다.Hereinafter, the present invention will be described in detail.
본 발명에 따른 산화방법은 다음의 반응도식Ⅱ에 따라 과산화수소수를 산화제로 이용하며 텅스텐산(H2WO4)을 촉매로 첨가하여 반응을 진행시킨다. 과산화수소수의 사용량은 부반응의 생성물을 최소한 억제하고 반응시간을 줄임과 동시에 반응효율 측면에서 볼때 출발물질인 2-술파닐-티아졸-5-카르복실산 유도체(3)에 대하여 2 내지 3 몰배의 범위에서 사용하는 것이 바람직하며, 텅스텐산의 사용량은 0.01 내지 0.05 몰배의 범위에서 사용하는 것이 바람직하다.In the oxidation method according to the present invention, hydrogen peroxide is used as an oxidizing agent according to the following Reaction Scheme II, and tungstic acid (H 2 WO 4 ) is added as a catalyst to proceed with the reaction. The amount of hydrogen peroxide used is 2 to 3 mole times with respect to the starting material 2-sulfanyl-thiazole-5-carboxylic acid derivative (3) in terms of reaction efficiency, while at least inhibiting the side reaction product and reducing the reaction time. It is preferable to use in the range, and it is preferable to use the tungstic acid in the range of 0.01-0.05 mole times.
상기식에서, R1, R2및 X는 각각 전술한 바와 같다.Wherein R 1 , R 2 and X are as described above, respectively.
본 발명의 반응에서 사용되는 용매로는 메틸알콜, 에틸알콜, 이소프로필알콜, t-부틸알콜과 같은 알콜류, 1,2-디클로로에탄, 클로로포름과 같은 할로겐화 탄화수소류, 초산과 같은 산류, 그리고 물을 들 수 있으며, 필요에 따라서는 상기 열거한 용매들 중에서 두가지 이상의 용매를 혼합하여 사용하는 경우도 가능하다. 혼합용매로는 예를 들어서 물과 알콜류의 혼합용액, 물과 할로겐화 탄화수소류의 혼합용액등에 초산을 적당량 첨가하여 사용할 수 있다.As a solvent used in the reaction of the present invention, alcohols such as methyl alcohol, ethyl alcohol, isopropyl alcohol, t-butyl alcohol, halogenated hydrocarbons such as 1,2-dichloroethane, chloroform, acids such as acetic acid, and water If necessary, it is also possible to use a mixture of two or more of the solvents listed above. As the mixed solvent, for example, an appropriate amount of acetic acid can be added to a mixed solution of water and alcohols, a mixed solution of water and halogenated hydrocarbons, and the like.
또한 본 발명에 따른 반응은 0℃에서 100℃ 범위에서는 큰 지장업시 진행되지만 바람직하게는 20℃ 내지 80℃가 적당하고 물과 유기용매의 혼합용매를 사용할 경우 산화반응속도를 촉진시키기 위해서 상-전달 촉매를 첨가할 수 있다. 예를 들어 크라운 에테르 또는 유기 암모늄 화합물이 여기에 속한다.In addition, the reaction according to the present invention proceeds during a large trouble in the range of 0 ° C to 100 ° C, but preferably 20 ° C to 80 ° C is suitable, and phase-transfer to promote the oxidation reaction rate when using a mixed solvent of water and an organic solvent. Catalyst can be added. Crown ethers or organic ammonium compounds, for example, belong here.
이하 본 발명을 실시예에 의거 보다 구체적으로 설명하지만, 이들로 본 발명의 기술적 범위가 저하되는 것은 아니다.Hereinafter, the present invention will be described in more detail with reference to Examples, but the technical scope of the present invention is not reduced by these examples.
[실시예 1]Example 1
4-에틸-2-메틸술폰닐-티아졸-5-카르복실산 메틸 에스테르의 제조Preparation of 4-ethyl-2-methylsulfonyl-thiazole-5-carboxylic acid methyl ester
[방법 A][Method A]
4-에틸-2-메틸술파닐-티아졸-5-카르복실산 메틸 에스테르의(72g, 0.33mol) 테트라부틸암모늄 브로마이드(0.72g, 1g%)를 1,2-디클로로에탄(216g)에 녹이고, 초산(3.6g)과 텅스텐산(0.82g, 1mol%), 물(72ml)을 가한다. 50℃에서 격렬하게 교반하면서 과산화수소수(30%, 94g, 2.5 당량)를 천천히 적가한다. 70℃에서 2시간동안 교반한후 유기층을 분리하여 무수망초로 건조시키고 감압증류시켜 표제화합물(82g, 0.33mol)를 얻는다(수율 99%).(72 g, 0.33 mol) tetrabutylammonium bromide (0.72 g, 1 g%) of 4-ethyl-2-methylsulfanyl-thiazole-5-carboxylic acid methyl ester was dissolved in 1,2-dichloroethane (216 g). Acetic acid (3.6 g), tungstic acid (0.82 g, 1 mol%) and water (72 ml) are added. Hydrogen peroxide solution (30%, 94 g, 2.5 equiv) was slowly added dropwise with vigorous stirring at 50 ° C. After stirring at 70 ° C. for 2 hours, the organic layer was separated, dried over anhydrous and distilled under reduced pressure to obtain the title compound (82 g, 0.33 mol) (yield 99%).
[방법 B][Method B]
4-에틸-2-메틸술파닐-티아졸-5-카르복실산 메틸 에스테르(72g,0.33mol), 텅스텐산(0.82g, 1mol%)을 초산(72g)에 녹이고 물 72g을 가한후 50℃에서 격렬하게 교반하면서 과산화수소수(30%, 82g, 2.2 당량)를 천천히 적가한다. 70℃ 에서 2시간동안 교반한후 얼음물(216ml)를 가하여 고체를 석출시킨 후 여과시키고 건조시켜서 표제화합물(68g, 0.27mol)을 얻는다(수율 82%).4-ethyl-2-methylsulfanyl-thiazole-5-carboxylic acid methyl ester (72 g, 0.33 mol) and tungstic acid (0.82 g, 1 mol%) were dissolved in acetic acid (72 g), and 72 g of water was added thereto, followed by 50 ° C. Hydrogen peroxide (30%, 82 g, 2.2 equiv) is slowly added dropwise with vigorous stirring at. After stirring at 70 ° C. for 2 hours, ice water (216 ml) was added to precipitate a solid, followed by filtration and drying to give the title compound (68 g, 0.27 mol) (yield 82%).
[실시예 2]Example 2
4-에틸-2-메틸술포닐-티아졸-5-카르복실산의 제조Preparation of 4-ethyl-2-methylsulfonyl-thiazole-5-carboxylic acid
[방법 A][Method A]
4-에틸-2-메틸술파닐-티아졸-5-카르복실산(20g, 0.098mol)을 메탄올(60g)에 녹이고, 초산(0.6g)과 텅스텐산(0.25g 1mol%)을 물(20ml)를 가한다. 80℃에서 격렬하게 교반하면서 과산화수소수(30%, 24.9g, 2.2 당량)를 2시간에 걸쳐 천천히 적가한다. 1시간동안 환류시키면서 10시간동안 교반한 뒤 감압증류하여 메탄올을 제거한 다음 남은 수용액을 여과한다. 분리한 고체를 티오황산나트륨수용액 상에서 30분동안 교반시키고 다시 여과하고 건조시켜 표제화합물(19.9g, 0.085mol)을 86%의 수율로 얻는다.4-ethyl-2-methylsulfanyl-thiazole-5-carboxylic acid (20 g, 0.098 mol) was dissolved in methanol (60 g), acetic acid (0.6 g) and tungstic acid (0.25 g 1 mol%) were dissolved in water (20 ml). ) Hydrogen peroxide (30%, 24.9 g, 2.2 equiv) was slowly added dropwise over 2 hours with vigorous stirring at 80 ° C. After stirring for 10 hours while refluxing for 1 hour, distilled under reduced pressure to remove methanol, and the remaining aqueous solution was filtered. The separated solid was stirred for 30 minutes on aqueous sodium thiosulfate solution, filtered again and dried to give the title compound (19.9 g, 0.085 mol) in 86% yield.
[방법 B][Method B]
4-에틸-2-메틸술파닐-티아졸-5-카르복실산(30g, 0.15mol), 텅스텐산(0.37g, 1mol%)을 초산(30g)에 녹이고 물 30g을 가한후 50℃에서 격렬하게 교반하면서 과산화수소수(30%, 37.4g, 2.2 당량)을 천천히 적가한다. 70℃에서 2시간동안 교반한 후 얼음물(90g)를 가하여 고체를 석출시킨다. 여과한 고체를 티오황산나트륨수용액상에서 30분동안 교반시키고 다시 여과하고 건조시켜 표제화합물(28.1g, 0.12mol)을 80%의 수율로 얻는다.4-Ethyl-2-methylsulfanyl-thiazole-5-carboxylic acid (30 g, 0.15 mol) and tungstic acid (0.37 g, 1 mol%) were dissolved in acetic acid (30 g), and 30 g of water was added thereto and then heated at 50 ° C. Hydrogen peroxide (30%, 37.4 g, 2.2 equiv) is slowly added dropwise with stirring. After stirring at 70 ° C. for 2 hours, ice water (90 g) was added to precipitate a solid. The filtered solid was stirred for 30 min in aqueous sodium thiosulfate solution, filtered again and dried to give the title compound (28.1 g, 0.12 mol) in 80% yield.
[실시예 3]Example 3
4-에틸-2-메틸술포닐-티아졸-5-카르복실산(시아노-티오펜-2-일-메틸)아미드의 제조Preparation of 4-ethyl-2-methylsulfonyl-thiazole-5-carboxylic acid (cyano-thiophen-2-yl-methyl) amide
[방법 A][Method A]
4-에틸-2-메틸술파닐-티아졸-5-카르복실산(시아노-티오펜-2-일-메틸)아미드(100g, 0.31mol), 테트라부틸암모늄 브로마이드(1g, 1g%)를 1,2-디클로로에탄(300g)에 녹이고, 초산(3g)과 텅스텐산(1.2g, 1.5mol%), 물(100ml)를 가한다. 50℃에서 격렬하게 교반하면서 과산화수소수(30%, 88g, 2.5 당량)을 천천히 적가한다. 70℃에서 6시간동안 교반한 후 유기층을 분리하여 무수망초로 건조시키고 감압증류시켜 표제화합물(93g, 0.26mol)를 얻는다(수율 84%).4-Ethyl-2-methylsulfanyl-thiazole-5-carboxylic acid (cyano-thiophen-2-yl-methyl) amide (100 g, 0.31 mol), tetrabutylammonium bromide (1 g, 1 g%) It is dissolved in 1,2-dichloroethane (300g), acetic acid (3g), tungstic acid (1.2g, 1.5mol%) and water (100ml) are added. Hydrogen peroxide solution (30%, 88 g, 2.5 equiv) was slowly added dropwise with vigorous stirring at 50 ° C. After stirring at 70 ° C. for 6 hours, the organic layer was separated, dried over anhydrous manganese, and distilled under reduced pressure to obtain the title compound (93 g, 0.26 mol) (yield 84%).
[방법 B][Method B]
4-에틸-2-메틸술파닐-티아졸-5-카르복실산(시아노-티오펜-2-일-메틸)아미드(100g, 0.31mol), 텅스텐산(0.77g, 1mol%)를 초산(100g)에 녹이고 50℃에서 격렬하게 교반하면서 과산화수소수(30%, 77g, 2.2 당량)를 천천히 적가한다. 70℃에서 4시간동안 교반한 후 얼음물(300ml)를 가하여 고체를 석출시킨후 이를 여과시키고 건조시켜서 표제화합물(82g, 0.23mol)을 얻는다(수율 74%).4-ethyl-2-methylsulfanyl-thiazole-5-carboxylic acid (cyano-thiophen-2-yl-methyl) amide (100 g, 0.31 mol), tungstic acid (0.77 g, 1 mol%) Dissolve in (100 g) and slowly add dropwise hydrogen peroxide solution (30%, 77 g, 2.2 equiv) with vigorous stirring at 50 ° C. After stirring for 4 hours at 70 ° C., ice water (300 ml) was added to precipitate a solid, which was then filtered and dried to obtain the title compound (82 g, 0.23 mol) (yield 74%).
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| KR1019960004701A KR0163291B1 (en) | 1996-02-26 | 1996-02-26 | Preparation method of 2-sulfonyl thiazole carboxylic acid derivatives by h2o2 in the presence of h2wo4 |
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| Country | Link |
|---|---|
| KR (1) | KR0163291B1 (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR20010026648A (en) * | 1999-09-08 | 2001-04-06 | 성재갑 | A novel process for preparing N-alkyloxycarbonyl-β-alkylsulfonylvaline |
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| Publication number | Publication date |
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| KR970061879A (en) | 1997-09-12 |
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