(Z)-3-methoxycarbonylmethylene-6-chloro-3,4-dihydro-2H-1,4-benzoxazin-2-one | 70917-44-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并恶嗪类
• 英文名称: (Z)-3-methoxycarbonylmethylene-6-chloro-3,4-dihydro-2H-1,4-benzoxazin-2-one
• 英文别名: methyl 2,3-dihydro-6-chloro-2-oxo-4H-1,4-benzoxazine-3-methylenecarboxylate；(Z)-methyl 2-(6-chloro-2-oxo-2H-benzo[b][1,4]oxazin-3(4H)-ylidene)acetate；methyl (2Z)-(6-chloro-2-oxo-2H-1,4-benzoxazin-3(4H)-ylidene)ethanoate；methyl (2Z)-2-(6-chloro-2-oxo-4H-1,4-benzoxazin-3-ylidene)acetate
• CAS: 70917-44-1
• 化学式: C₁₁H₈ClNO₄
• 分子量: 253.642
• InChiKey: ZTENAAHURFCLOO-YVMONPNESA-N

物化性质

• 熔点：
  169-170 °C(Solv: ethanol (64-17-5))
• 沸点：
  393.6±42.0 °C(Predicted)
• 密度：
  1.500±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  17
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  64.6
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (Z)-3-methoxycarbonylmethylene-6-chloro-3,4-dihydro-2H-1,4-benzoxazin-2-one 在 platinum(IV) oxide 亚硝酸正戊酯 、 氢气 、 三乙胺 、 三氯乙酸 作用下， 以 四氢呋喃 、 溶剂黄146 、 N,N-二甲基甲酰胺 为溶剂， 25.0 ℃ 、405.3 kPa 条件下， 反应 14.5h， 生成 8-Chloro-4H-5-oxa-3,9b-diaza-cyclopenta[a]naphthalene-1,2-dicarboxylic acid 1-ethyl ester 2-methyl ester
  参考文献：
  名称：

  Danswan, Geoff W.; Hairsine, Peter W.; Rowlands, David A., Journal of the Chemical Society. Perkin transactions I, 1982, p. 1049 - 1058

  摘要：

  DOI：
• 作为产物：
  描述：

  丁炔二酸二甲酯 、 4-氯-2-氨基苯酚 反应 0.08h， 生成 (Z)-3-methoxycarbonylmethylene-6-chloro-3,4-dihydro-2H-1,4-benzoxazin-2-one
  参考文献：
  名称：

  球磨机中炔烃与邻位取代苯胺的加氢胺化反应：级联反应合成苯甲醚化的N-杂环

  摘要：

  结果表明，在行星式球磨机中，邻位取代的苯胺易于与乙炔二羧酸二乙酯发生加氢胺化反应。分子间加氢反应与分子内闭环的顺序偶联被用于由易得的结构单元即邻位具有OH，NH或SH基团的亲电炔烃和苯胺合成苯并恶嗪，喹喔啉和苯并噻嗪位置。对于杂环的形成，已表明几种应力条件能够以固态引发反应。就过程控制而言，在球磨机中进行处理似乎比用研钵和研杵粉碎更为有利。在后一种情况下，固态分析期间发生了显着的反应后修饰。低温研磨证明对试剂的分子转化有不利影响。

  DOI：

  10.1002/chem.201406306

文献信息

• Introduction of a clean and promising protocol for the synthesis of β-amino-acrylates and 1,4-benzoheterocycles: an emerging innovation
  作者：Garima Choudhary、Rama Krishna Peddinti

  DOI：10.1039/c1gc15701a

  日期：——

  A highly efficient, elegant and simple procedure with exceptionally mild conditions has been proposed for the synthesis of β-amino-acrylate derivatives and an array of biologically and pharmaceutically active benzoheterocycles. The protocol offers a valuable alternative to known methods and will find applications in the field of green synthesis. The regio- and stereo-chemistry of the products were established by IR, NMR and single crystal X-ray analysis.

  提出了一种高效、优雅且简单的过程，用于合成β-氨基丙烯酸酯衍生物和一系列具有生物学及药物活性的苯并杂环化合物，条件极为温和。该方案为已知方法提供了一种有价值的替代方案，并将应用于绿色合成领域。产品的区域和立体化学性质通过红外光谱、核磁共振和单晶X射线分析得以确定。
• Expedient synthesis of novel 1,4-benzoxazine and butenolide derivatives
  作者：Garima Choudhary、Ram Tilak Naganaboina、Rama Krishna Peddinti

  DOI：10.1039/c4ra01736f

  日期：——

  A rapid and efficient protocol for the synthesis of 2-hydroxy-1,4-benzoxazine derivatives has been developed. These intermediates served as precursors for the synthesis of a series of novel butenolide derivatives and 2-amino-1,4-benzoxazine derivatives.

  已开发出一种快速高效的合成2-羟基-1,4-苯并噁嗪衍生物的方案。这些中间体作为合成一系列新型丁烯内酯衍生物和2-氨基-1,4-苯并噁嗪衍生物的前体。
• Construction of Polyheterocyclic Compounds by Lewis Acid Mediated Intramolecular [3+2] Cycloaddition Reaction
  作者：Pooja Dahiya、Anoop Yadav、Rajnish Budhwan、Rama Krishna Peddinti

  DOI：10.1002/ejoc.202300251

  日期：2023.8.14

  A practical and efficient regioselective synthesis of pyrrolo-fused polyheterocyclic compounds from 2-substituted-2-hydroxy-indane-1,3-diones and 1,4-benzoxazinones via intramolecular [3+2] cycloaddition has been demonstrated. The protocol obviates column chromatography and products were isolated in good to excellent yields by simple filtration. Electronic effects of both electron-releasing and electron-withdrawing

  已经证明了通过分子内[3+2]环加成从2-取代-2-羟基-茚满-1,3-二酮和1,4-苯并恶嗪酮实际有效地区域选择性合成吡咯稠合多杂环化合物。该方案避免了柱色谱法，并且通过简单的过滤即可以良好至优异的产率分离产物。释放电子基团和吸电子基团的电子效应都具有良好的耐受性。
• Design, synthesis and antimycobacterial activity of benzoxazinone derivatives and open-ring analogues: Preliminary data and computational analysis
  作者：Daniele Zampieri、Maria Grazia Mamolo、Julia Filingeri、Sara Fortuna、Alessandro De Logu、Adriana Sanna、Davide Zanon

  DOI：10.1016/j.bmcl.2019.07.025

  日期：2019.9

  This study examines in depth benzoxazine nucleus for antimycobacterial property. We synthesized some benzoxazin-2-one and benzoxazin-3-one derivatives, which were tested for activity against a panel of Mycobacterium tuberculosis (Mtb) strains, including H37Ra, H37Rv and some resistant strains. Several compounds displayed a high antimycobacterial activity and the three isoniazid analogue derivatives 8a-c exhibited a MIC range of 0.125-0.250 mu g/mL (0.37-0.75 mu M) against strain H37Ra, therefore lower than the isoniazid reference drug. Two benzoxazin-2-one derivatives, 1c and 5j, together with isoniazid-analogue compound 8a, also revealed low MIC values against resistant strains and proved highly selective for mycobacterial cells, compared to mammalian Vero cells. To predict whether molecule 8a is able to interact with the active site of InhA, we docked it into the crystal structure; indeed, during the molecular dynamic simulation the compound never left the protein pocket. The more active compounds were predicted for ADME properties and all proved to be potentially orally active in humans.
• Kawahara, Norio; Nakajima, Takako; Itoh, Tsuneo, Chemical and pharmaceutical bulletin, 1984, vol. 32, # 3, p. 1163 - 1169
  作者：Kawahara, Norio、Nakajima, Takako、Itoh, Tsuneo、Takayanagi, Hiroaki、Ogura, Haruo

  DOI：——

  日期：——