3-(4-chlorophenyl)-4,5-dihydroisoxazole-5-carboxylic acid ethyl ester | 109888-57-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 3-(4-chlorophenyl)-4,5-dihydroisoxazole-5-carboxylic acid ethyl ester
• 英文别名: ethyl 3-(4-chlorophenyl)-4,5-dihydroisoxazole-5-carboxylate；5-Isoxazolecarboxylic acid, 3-(4-chlorophenyl)-4,5-dihydro-, ethyl ester；ethyl 3-(4-chlorophenyl)-4,5-dihydro-1,2-oxazole-5-carboxylate
• CAS: 109888-57-5
• 化学式: C₁₂H₁₂ClNO₃
• 分子量: 253.685
• InChiKey: ZLFGTBHVMQMAHK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  17
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  47.9
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3-(4-chlorophenyl)-4,5-dihydroisoxazole-5-carboxylic acid ethyl ester 在 盐酸羟胺 、 potassium hydroxide 作用下， 以 甲醇 为溶剂， 反应 24.0h， 以40%的产率得到3-(4-chlorophenyl)-N-hydroxy-4,5-dihydroisoxazole-5-carboxamide
  参考文献：
  名称：

  Design, Synthesis, and Evaluation of Hydroxamic Acid Derivatives as Promising Agents for the Management of Chagas Disease

  摘要：

  Today, there are approximately 8 million cases of Chagas disease in the southern cone of South America alone, and about 100 million people are living with the risk of becoming infected. The present pharmacotherapy is sometimes ineffective and has serious side effects. Here, we report a series of 4,5 ''. -dihydroisoxazoles incorporating hydroxamate moieties, which act as effective inhibitors of the carbonic anhydrase (CA) from Trypanosoma cruzi (TcCA). One compound (5g)was evaluated in detail and shows promising features as an antitrypanosomal agent. Excellent values for the inhibition of growth for all three developmental forms of the parasite were observed at low concentrations of 5g (IC50 values from 7.0 to <1 mu M). The compound has a selectivity index (SI) of 6.7 and no cytotoxicity to macrophage cells. Preliminary in vivo data showed that 5g reduces bloodstream parasites and that all treated mice survived; it was also more effective than the standard drug benznidazole.

  DOI：

  10.1021/jm400902y
• 作为产物：
  描述：

  4-chlorobenzaldoxime 在 三氯异氰尿酸 、 三乙胺 作用下， 反应 24.0h， 生成 3-(4-chlorophenyl)-4,5-dihydroisoxazole-5-carboxylic acid ethyl ester
  参考文献：
  名称：

  Design, Synthesis, and Evaluation of Hydroxamic Acid Derivatives as Promising Agents for the Management of Chagas Disease

  摘要：

  Today, there are approximately 8 million cases of Chagas disease in the southern cone of South America alone, and about 100 million people are living with the risk of becoming infected. The present pharmacotherapy is sometimes ineffective and has serious side effects. Here, we report a series of 4,5 ''. -dihydroisoxazoles incorporating hydroxamate moieties, which act as effective inhibitors of the carbonic anhydrase (CA) from Trypanosoma cruzi (TcCA). One compound (5g)was evaluated in detail and shows promising features as an antitrypanosomal agent. Excellent values for the inhibition of growth for all three developmental forms of the parasite were observed at low concentrations of 5g (IC50 values from 7.0 to <1 mu M). The compound has a selectivity index (SI) of 6.7 and no cytotoxicity to macrophage cells. Preliminary in vivo data showed that 5g reduces bloodstream parasites and that all treated mice survived; it was also more effective than the standard drug benznidazole.

  DOI：

  10.1021/jm400902y

文献信息

• [2 + 2 + 1] Cycloaddition of <i>N</i>-tosylhydrazones, <i>tert</i>-butyl nitrite and alkenes: a general and practical access to isoxazolines
  作者：Liang Ma、Feng Jin、Xionglve Cheng、Suyan Tao、Gangzhong Jiang、Xingxing Li、Jinwei Yang、Xiaoguang Bao、Xiaobing Wan

  DOI：10.1039/d1sc02352g

  日期：——

  N-tosylhydrazones has not been examined. Herein, we report the first demonstrations of [2 + 2 + 1] cycloaddition reactions that allow the facile synthesis of isoxazolines, employing N-tosylhydrazones, tert-butyl nitrite (TBN) and alkenes as reactants. This process represents a new type of cycloaddition reaction with a distinct mechanism that does not involve the participation of nitrile oxides. This

  在过去的几十年里， N-甲苯磺酰腙已被证明是多功能的合成子。然而，据我们所知，基于N-甲苯磺酰腙的异恶唑啉的构建尚未得到研究。在此，我们报告了[2 + 2 + 1]环加成反应的首次演示，该反应可以使用N-甲苯磺酰腙、亚硝酸叔丁酯（TBN）和烯烃作为反应物轻松合成异恶唑啉。该过程代表了一种新型的环加成反应，具有独特的机制，不涉及氧化腈的参与。这种方法既通用又实用，具有广泛的底物范围、几乎通用的官能团兼容性、对水分和空气的耐受性、复杂生物活性分子功能化的潜力，并且易于扩大规模。对照实验和理论计算都表明，这种转化是通过N-甲苯磺酰腙和 TBN 的偶联原位生成硝基化合物，然后与烯烃进行环加成，然后消除叔丁氧基，得到所需的异恶唑啉。
• Efficient synthesis of isoxazoles and isoxazolines from aldoximes using Magtrieve™ (CrO2)
  作者：Sandeep Bhosale、Santosh Kurhade、Uppuleti Viplava Prasad、Venkata P. Palle、Debnath Bhuniya

  DOI：10.1016/j.tetlet.2009.04.073

  日期：2009.7

  Treatment of aldoximes 1 with Magtrieve™ (CrO2) in presence of dipolarophile 3 or 4, furnished a variety of isoxazolines 5a–u and isoxazoles 6a–q as 1,3-dipolar cycloaddition (1,3-DC) products (38 examples; 63–90% isolated yields). In situ formation of a nitrile oxide intermediate was confirmed through isolation of the dimerization product furoxane 2a in absence of any dipolarophile. The methodology

  在存在偶极亲和剂3或4的情况下，用Magtrieve ™（CrO 2）处理醛肟1，提供了各种异恶唑啉5a–u和异恶唑6a–q作为1,3-偶极环加成（1,3-DC）产品（38个例子） ； 63–90％的独立收益率）。通过在不存在任何双亲性物质的情况下分离二聚产物呋喃烷2a来确认一氧化氮中间体的原位形成。该方法已扩展到分子内一氧化氮环加成（INOC）反应，以获得高度有用的7-8色烷衍生物（分离产率为75-80％）。Magtrieve ™作为用于1,3-DC反应的新试剂，它具有出色的底物通用性，同时还表现出对敏感保护基和富电子官能团的耐受性。
• 1,3-Dipolar cycloaddition reaction of aryl nitrile oxides with alkenes using imidazole and pyridine containing reusable polymeric base catalysts
  作者：Nilesh N. Korgavkar、Shriniwas D. Samant

  DOI：10.1080/00397911.2017.1399207

  日期：2018.2.16

  electron microscopy (FE-SEM), and Brunauer-Emmett-Teller (BET) surface area analysis. Their swelling behavior was also studied. They were used as base catalysts for 1,3-dipolar cycloaddition reaction of aryl nitrile oxides, generated in situ from N-hydroxyimidoyl chloride, with N-phenylmaleimide and ethyl acrylate, to obtain 3-arylisoxazolines. Both the bases gave excellent results. These polymers

  摘要 使用不同量的二乙烯基苯作为交联剂，通过自由基聚合由各自的乙烯基单体制备了交联聚-1-(4-乙烯基苄基)咪唑和交联聚-4-乙烯基吡啶。通过FT-IR、TGA、场发射扫描电子显微镜(FE-SEM)和Brunauer-Emmett-Teller (BET)表面积分析表征聚合物碱。还研究了它们的溶胀行为。它们被用作 1,3-偶极环加成反应的碱催化剂，芳基腈氧化物由 N-羟基亚氨酰氯原位生成，与 N-苯基马来酰亚胺和丙烯酸乙酯反应，得到 3-芳基异恶唑啉。两种碱基都得到了极好的结果。这些聚合物是可重复使用的、使用安全的，并且为吡啶和三乙胺等危险的有机不可重复使用的碱提供了良好的替代品。
• Cu(0) nanoparticle catalyzed efficient reductive cleavage of isoxazoline, carbonyl azide and domino cyclization in water medium
  作者：Krishnanka S. Gayen、Tista Sengupta、Yasmin Saima、Adita Das、Dilip K. Maiti、Atanu Mitra

  DOI：10.1039/c2gc35252d

  日期：——

  Small Cu(0)-nanoparticles (NPs) are fabricated utilizing CuSO4·5H2O, surfactant (SDS) and ascorbic acid in aqueous medium. Its outstanding catalytic activity under low catalyst loading is developed toward reductive cleavage of isoxazoline, carbonyl azide and domino cyclization to furnish valuable 2-hydroxy-4-keto esters, primary amides and a new class of heterocycle, 4-hydroxy-2-pyrroline-5-one.

  利用 CuSO4-5H2O、表面活性剂（SDS）和抗坏血酸在水介质中制造出了小型 Cu(0)- 纳米粒子（NPs）。在低催化剂负载条件下，该催化剂具有出色的催化活性，可还原裂解异噁唑啉、叠氮羰基和多米诺环化反应，生成有价值的 2-hydroxy-4-keto 酯、伯酰胺和一类新型杂环 4-hydroxy-2-pyrroline-5-one 。
• A New Route to Nitrile Oxides from Primary Alkylhalides for <i>in situ</i> Dipolar Cycloadditions
  作者：Dilipkumar Maiti、Pranab K. Bhattacharya

  DOI：10.1055/s-1998-1669

  日期：1998.4

  A new route to nitrile oxide preparation from primary alkylbromide, chloride, nitrite and their cycloadditions with olefins to form isoxazolines in a single pot are described.

  该论文描述了一条从伯烷基溴化物、氯化物和亚硝酸盐制备氧化腈的新路线，以及它们与烯烃发生环化反应生成异恶唑的过程。