N-乙基1,1-二氧代-异噻唑烷 | 73343-04-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑烷类
• 中文名称: N-乙基1,1-二氧代-异噻唑烷
• 英文名称: N-ethyl-1,2-isothiazolidine-1,1-dioxide
• 英文别名: N-ethyl-γ-sultam；2-ethylisothiazolidine-1,1-dioxide；2-Ethylisothiazolidine 1,1-dioxide；2-ethyl-1,2-thiazolidine 1,1-dioxide
• CAS: 73343-04-1
• 化学式: C₅H₁₁NO₂S
• 分子量: 149.214
• InChiKey: OPDWKYYREJZWQH-UHFFFAOYSA-N

物化性质

• 沸点：
  235.0±23.0 °C(Predicted)
• 密度：
  1.204±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0
• 重原子数：
  9
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  45.8
• 氢给体数：
  0
• 氢受体数：
  3

安全信息

• 海关编码：
  2934100090

SDS

Material Safety Data Sheet

---

Section 1. Identification of the substance
Product Name: N-Ethyl-1,3-propanesultam
Synonyms: N-Ethyl 1,1-dioxo-isothiazolidine

---

Section 2. Hazards identification
Harmful by inhalation, in contact with skin, and if swallowed.

---

Section 3. Composition/information on ingredients.
Ingredient name: N-Ethyl-1,3-propanesultam
CAS number: 73343-04-1

---

Section 4. First aid measures
Skin contact: Immediately wash skin with copious amounts of water for at least 15 minutes while removing
contaminated clothing and shoes. If irritation persists, seek medical attention.
Eye contact: Immediately wash skin with copious amounts of water for at least 15 minutes. Assure adequate
flushing of the eyes by separating the eyelids with fingers. If irritation persists, seek medical
attention.
Inhalation: Remove to fresh air. In severe cases or if symptoms persist, seek medical attention.
Ingestion: Wash out mouth with copious amounts of water for at least 15 minutes. Seek medical attention.

---

Section 5. Fire fighting measures
In the event of a fire involving this material, alone or in combination with other materials, use dry
powder or carbon dioxide extinguishers. Protective clothing and self-contained breathing apparatus
should be worn.

---

Section 6. Accidental release measures
Personal precautions: Wear suitable personal protective equipment which performs satisfactorily and meets local/state/national
standards.
Respiratory precaution: Wear approved mask/respirator
Hand precaution: Wear suitable gloves/gauntlets
Skin protection: Wear suitable protective clothing
Eye protection: Wear suitable eye protection
Methods for cleaning up: Mix with sand or similar inert absorbent material, sweep up and keep in a tightly closed container
for disposal. See section 12.
Environmental precautions: Do not allow material to enter drains or water courses.

---

Section 7. Handling and storage
Handling: This product should be handled only by, or under the close supervision of, those properly qualified
in the handling and use of potentially hazardous chemicals, who should take into account the fire,
health and chemical hazard data given on this sheet.
Store in closed vessels.
Storage:

---

Section 8. Exposure Controls / Personal protection
Engineering Controls: Use only in a chemical fume hood.
Personal protective equipment: Wear laboratory clothing, chemical-resistant gloves and safety goggles.
General hydiene measures: Wash thoroughly after handling. Wash contaminated clothing before reuse.

---

Section 9. Physical and chemical properties
Appearance: Not specified
Boiling point: No data
No data
Melting point:
Flash point: No data
Density: No data
Molecular formula: C5H11NO2S
Molecular weight: 149.2

---

Section 10. Stability and reactivity
Conditions to avoid: Heat, flames and sparks.
Materials to avoid: Oxidizing agents.
Possible hazardous combustion products: Carbon monoxide, nitrogen oxides, sulfur oxides.

---

Section 11. Toxicological information
No data.

---

Section 12. Ecological information
No data.

---

Section 13. Disposal consideration
Arrange disposal as special waste, by licensed disposal company, in consultation with local waste
disposal authority, in accordance with national and regional regulations.

---

Section 14. Transportation information
Non-harzardous for air and ground transportation.

---

Section 15. Regulatory information
No chemicals in this material are subject to the reporting requirements of SARA Title III, Section
302, or have known CAS numbers that exceed the threshold reporting levels established by SARA
Title III, Section 313.

---

SECTION 16 - ADDITIONAL INFORMATION
N/A

反应信息

• 作为反应物：
  描述：

  N-乙基1,1-二氧代-异噻唑烷 在 六甲基磷酰三胺 、 正丁基锂 、 对甲苯磺酸 、 二异丙胺 作用下， 以 四氢呋喃 、 正己烷 、 甲苯 为溶剂， 反应 1.0h， 生成 (Z)-(5)-(3,5-di-tert-butyl-4-hydroxybenzylidene)-2-ethyl-1,2-isothiazolidine-1,1-dioxide
  参考文献：
  名称：

  Novel Antiarthritic Agents with 1,2-Isothiazolidine-1,1-dioxide (γ-Sultam) Skeleton: Cytokine Suppressive Dual Inhibitors of Cyclooxygenase-2 and 5-Lipoxygenase

  摘要：

  Various 1,2-isotkiazolidine-1,1-dioxide (gamma-sultam) derivatives containing an antioxidant moiety, 2i6-di-tert-butylphenol substituent, were prepared. Some compounds, which have a lower alkyl group at the 2-position of the gamma-sultam skeleton, showed potent inhibitory effects on both cyclooxygenase (COX)-2 and 5-lipoxygenase (5-LO), as well as production of interleukin (IL)-1 in in vitro assays. They also proved to be effective in several animal arthritic models without any ulcerogenic activities. Among these compounds, (E)-(5)-(3,5-di-tert-butyl-4-hydroxybenzyliclene)-2-ethyl-1,2-isothiazolidine-1, (S-2474) was selected as an antiarthritic drug candidate and is now under clinical trials. The structure-activity relationships (SAR) examined and some pharmacological evaluations are described.

  DOI：

  10.1021/jm9906015
• 作为产物：
  描述：

  N1-ethyl-3-chloro-1-propanesulfonamide 在 sodium hydride 作用下， 以 四氢呋喃 为溶剂， 反应 0.5h， 以93%的产率得到N-乙基1,1-二氧代-异噻唑烷
  参考文献：
  名称：

  Novel Antiarthritic Agents with 1,2-Isothiazolidine-1,1-dioxide (γ-Sultam) Skeleton: Cytokine Suppressive Dual Inhibitors of Cyclooxygenase-2 and 5-Lipoxygenase

  摘要：

  Various 1,2-isotkiazolidine-1,1-dioxide (gamma-sultam) derivatives containing an antioxidant moiety, 2i6-di-tert-butylphenol substituent, were prepared. Some compounds, which have a lower alkyl group at the 2-position of the gamma-sultam skeleton, showed potent inhibitory effects on both cyclooxygenase (COX)-2 and 5-lipoxygenase (5-LO), as well as production of interleukin (IL)-1 in in vitro assays. They also proved to be effective in several animal arthritic models without any ulcerogenic activities. Among these compounds, (E)-(5)-(3,5-di-tert-butyl-4-hydroxybenzyliclene)-2-ethyl-1,2-isothiazolidine-1, (S-2474) was selected as an antiarthritic drug candidate and is now under clinical trials. The structure-activity relationships (SAR) examined and some pharmacological evaluations are described.

  DOI：

  10.1021/jm9906015

文献信息

• Development of One-Pot Synthesis of New Antiarthritic Drug Candidate S-2474 with High <i>E</i>-Selectivity
  作者：Katsuo Oda、Takemasa Hida、Teruo Sakata、Masahiko Nagai、Yoshihide Sugata、Toshiaki Masui、Hideo Nogusa

  DOI：10.1021/op800008w

  日期：2008.5.1

  A one-pot synthesis of S-2474 was developed to overcome the problems of a large number of steps, low stereoselectivity, low yield, a large amount of waste, and severe reaction conditions. Aldol-type condensation of 3,5-di-tert-butyl-4-hydroxybenzaldehyde and N-ethyl-γ-sultam was carried out with LDA and then quenched with water. Dehydration proceeded under basic conditions, providing S-2474 directly

  为了解决步骤多，立体选择性低，收率低，浪费大量，反应条件苛刻的问题，开发了S-2474的一锅法合成方法。用LDA进行3，5-二叔丁基-4-羟基苯甲醛和N-乙基-γ-杜马的醛醇缩合，然后用水淬灭。脱水在碱性条件下进行，直接在亚苄基双键上以单一异构体形式提供S-2474。该反应机理似乎涉及醌甲基化物中间体。本文还讨论了该化合物开发的环境评估。
• Highly <i>E</i>-Selective and Effective Synthesis of Antiarthritic Drug Candidate S-2474 Using Quinone Methide Derivatives
  作者：Masanao Inagaki、Nobuhiro Haga、Makoto Kobayashi、Naoki Ohta、Susumu Kamata、Tatsuo Tsuri

  DOI：10.1021/jo0106795

  日期：2002.1.1

  We have developed an efficient and E-selective synthesis of an antiarthritic drug candidate (E)-(5)-(3,5-di-tert-butyl-4-hydroxybenzylidene)-2-ethyl-1,2-isothiazolidine-1,1-dioxide (S-2474; 1), in which alpha-methoxy-p-quinone methide is used as a key intermediate. alpha-Methoxy-p-quinone methide was revealed to be an equivalent to a p-hydroxy protected benzaldehyde. It reacts smoothly with alpha-sulfonyl

  我们已经开发了一种抗关节炎候选药物（E）-（5）-（3,5-二叔丁基-4-羟基亚苄基）-2-乙基-1,2-异噻唑烷-1的有效且E选择性的合成，1-二氧化物（S-2474； 1），其中使用α-甲氧基-对-醌甲基化物作为关键中间体。据揭示，α-甲氧基-对醌甲基化物等同于对羟基保护的苯甲醛。它与α-磺酰基碳负离子平稳反应，生成1,6-加成中间体，可在存在碱的情况下将其进一步加工成S-2474。该步骤以优异的收率得到了亚苄基双键上几乎为单一异构体的S-2474，因此是适用于大规模合成的非常实用的方法。详细的机械方面进行了研究和讨论。
• Short Synthesis of <i>tert</i>-Butyl-Hydroxylated 3,5-Di-<i>tert</i>-butyl-4-hydroxybenzaldehyde:  Synthesis of <i>tert</i>-Butyl-Hydroxylated S-2474
  作者：Masanao Inagaki、Saichi Matsumoto、Tatsuo Tsuri

  DOI：10.1021/jo020587v

  日期：2003.2.1

  We have developed a very short synthesis of tert-butyl-hydroxylated di-tert-butyl-4-hydroxybenzaldehyde in which the HBr-DMSO system is used as an effective oxidant (overall yield of 45% for the entire four-step process from 2-tert-butyl-p-cresol). We also accomplished the synthesis of a major metabolite of the antiarthritic drug candidate S-2474.

  我们开发了一种非常短的叔丁基羟基化二叔丁基-4-羟基苯甲醛合成方法，其中将HBr-DMSO系统用作有效氧化剂（整个四步法的总收率为45％，从2 -叔丁基对甲酚）。我们还完成了抗关节炎药物候选药物S-2474的主要代谢产物的合成。
• Process for the separation of dienic or aromatic hydrocarbons from
  申请人：Compagnie Francaise de Raffinage

  公开号：US04170547A1

  公开（公告）日：1979-10-09

  Process for the extraction of diene or aromatic hydrocarbons from petroleum hydrocarbon fractions employing sulfonamides as solvents. Also described are new sulfonamides useful as solvents for the extraction process.

  使用磺酰胺作为溶剂从石油烃分离二烯或芳香族烃的提取过程。还描述了新的磺酰胺，可用作提取过程的溶剂。
• Synthesis and In Vitro Biological Evaluation of p-Carborane-Based Di-tert-butylphenol Analogs
  作者：Sebastian Braun、Sanja Jelača、Markus Laube、Sven George、Bettina Hofmann、Peter Lönnecke、Dieter Steinhilber、Jens Pietzsch、Sanja Mijatović、Danijela Maksimović-Ivanić、Evamarie Hey-Hawkins

  DOI：10.3390/molecules28114547

  日期：——

  p-carborane and further substitution of the p-position resulted in four carborane-based di-tert-butylphenol analogs that showed no or weak COX inhibition but high 5-LO inhibitory activities in vitro. Cell viability studies on five human cancer cell lines revealed that the p-carborane analogs R-830-Cb, S-2474-Cb, KME-4-Cb, and E-5110-Cb exhibited lower anticancer activity compared to the related di-tert-butylphenols

  靶向炎症介质和相关信号通路可能为癌症治疗提供合理的策略。在作为类花生酸生物合成关键酶的双重环加氧酶-2 (COX-2)/5-脂氧合酶 (5-LO) 抑制剂中加入代谢稳定、空间要求高和疏水的碳硼烷是一种很有前途的方法。二叔丁基苯酚衍生物 R-830​​、S-2474、KME-4 和 E-5110 是有效的双重 COX-2/5-LO 抑制剂。对碳硼烷的掺入和对位的进一步取代产生了四种基于碳硼烷的二叔丁基苯酚类似物，它们在体外没有显示出 COX 抑制作用或表现出较弱的 COX 抑制活性，但在体外具有高 5-LO 抑制活性。对五种人类癌细胞系的细胞活力研究表明，对碳硼烷类似物 R-830​​-Cb、S-2474-Cb、KME-4-Cb、与相关的二叔丁基苯酚相比，E-5110-Cb 表现出较低的抗癌活性。有趣的是，R-830​​-Cb 不影响原代细胞的活力，并且比其碳基 R-830​​ 对应物更有效地抑制