5,6-benzoquinoline N-oxide | 17104-69-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: 5,6-benzoquinoline N-oxide
• 英文别名: benzo[f]quinoline N-oxide；benzo[f]quinoline 4-oxide；Benzo(f)quinoline, 4-oxide；4-oxidobenzo[f]quinolin-4-ium
• CAS: 17104-69-7
• 化学式: C₁₃H₉NO
• 分子量: 195.221
• InChiKey: DKQBDZRIEMVCDX-UHFFFAOYSA-N

物化性质

• 熔点：
  132 °C
• 沸点：
  408.9±28.0 °C(Predicted)
• 密度：
  1.18±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  15
• 可旋转键数：
  0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  25.5
• 氢给体数：
  0
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  5,6-benzoquinoline N-oxide 在 N-溴代丁二酰亚胺(NBS) 、 silver hexafluoroantimonate 、 dichloro(pentamethylcyclopentadienyl)rhodium (III) dimer 、 sodium acetate 作用下， 以 2,2,2-三氟乙醇 为溶剂， 反应 12.0h， 以84%的产率得到8-bromo-benzo[f]quinoline N-oxide
  参考文献：
  名称：

  Rh(III)-Catalyzed C(8)–H Activation of Quinoline N-Oxides: Regioselective C–Br and C–N Bond Formation

  摘要：

  A highly efficient and regioselective Rh(III)-catalyzed protocol for C8-bromination and amidation of quinoline N-oxide was developed. The transformation was found to be successful up to gram scale with excellent functional group tolerance and wide substrate scope. The mechanistic study revealed five-membered rhodacycle with quinoline N-oxide as a key intermediate for regioselective C8-functionalization. In addition, NFSI (N-fluorobis-(phenylsulfonyl)-imide) was explored as an amidating reagent for C8-amidation of quinoline N-oxide for the first time.

  DOI：

  10.1021/acs.joc.9b01538
• 作为产物：
  描述：

  5.6-苯并喹啉 在 间氯过氧苯甲酸 作用下， 以 二氯甲烷 为溶剂， 生成 5,6-benzoquinoline N-oxide
  参考文献：
  名称：

  六元杂芳族化合物的2-位置选择性三氟甲基硫醇化

  摘要：

  通过CF 3 S源在亲电子活化的六元杂芳族环上的亲核攻击，开发了六元杂芳族化合物的区域选择性C–H三氟甲基硫醇化反应。即使以克为单位，反应也以良好的收率和良好的官能团耐受性进行。成功的区域选择性转化的关键是添加剂（2,4-二硝基苯磺酰氯）的存在。还证明了奎尼丁衍生物的区域选择性三氟甲基硫醇化。三氟甲基硫醇化，然后进行S-氧化，得到相应的砜。

  DOI：

  10.1021/acs.orglett.9b01474

文献信息

• Rh/O₂-Catalyzed C8 Olefination of Quinoline <i>N</i>-Oxides with Activated and Unactivated Olefins
  作者：Ritika Sharma、Rakesh Kumar、Upendra Sharma

  DOI：10.1021/acs.joc.8b03176

  日期：2019.3.1

  Molecular oxygen has been explored as an economic and clean oxidant, an alternative to inorganic oxidants. A wide substrate scope with respect to quinoline N-oxides and olefins (activated acrylates and styrenes; unactivated aliphatic olefins) demonstrates the robustness of the developed catalytic method. Interestingly, 2-substituted quinoline N-oxides also afforded good yields of the corresponding C8-olefinated

  开发了铑/ O 2系统催化的喹啉N-氧化物的远端C（sp 2）-H烯烃化反应。分子氧已被视为一种经济，清洁的氧化剂，可以替代无机氧化剂。关于喹啉N-氧化物和烯烃（活化的丙烯酸酯和苯乙烯；未活化的脂族烯烃）的广泛的底物范围证明了所开发的催化方法的鲁棒性。有趣的是，2-取代的喹啉N氧化物还提供了相应的C 8烯烃化产物的良好产率。已经进行了动力学同位素研究和氘标记实验以了解初步的机理途径。通过利用天然产物衍生的底物，以及通过将C8-烯化的喹啉N-氧化物转化成各种其他有用的分子，证明了所开发方法的适用性。
• Co(III)-Catalyzed C–H Amidation of Nitrogen-Containing Heterocycles with Dioxazolones under Mild Conditions
  作者：Ankit Kumar Dhiman、Ankita Thakur、Inder Kumar、Rakesh Kumar、Upendra Sharma

  DOI：10.1021/acs.joc.0c01237

  日期：2020.7.17

  A cobalt(III)-catalyzed C-8 selective C–H amidation of quinoline N-oxide using dioxazolone as an amidating reagent under mild conditions is disclosed. The reaction proceeds efficiently with excellent functional group compatibility. The utility of the current method is demonstrated by gram scale synthesis of C-8 amide quinoline N-oxide and by converting this amidated product into functionalized quinolines

  公开了在温和条件下使用重氮唑啉作为酰胺化试剂的钴（III）催化的喹啉N-氧化物的C-8选择性C–H酰胺化。该反应以优异的官能团相容性有效地进行。通过克规模合成C-8酰胺喹啉N-氧化物并将该酰胺化产物转化为官能化喹啉，证明了本方法的实用性。此外，开发的催化方法也适用于N-嘧啶二氢吲哚的C-7酰胺化和苯甲酰胺的正酰胺化。
• Regioselective Introduction of Heteroatoms at the C-8 Position of Quinoline <i>N</i>-Oxides: Remote C–H Activation Using <i>N</i>-Oxide as a Stepping Stone
  作者：Heejun Hwang、Jinwoo Kim、Jisu Jeong、Sukbok Chang

  DOI：10.1021/ja5053768

  日期：2014.7.30

  Reported herein is the metal-catalyzed regioselective C-H functionalization of quinoline N-oxides at the 8-position: direct iodination and amidation were developed using rhodium and iridium catalytic systems, respectively. Mechanistic study of the amidation revealed that the unique regioselectivity is achieved through the smooth formation of N-oxide-chelated iridacycle and that an acid additive plays

  本文报道了金属催化的 8 位喹啉 N-氧化物的区域选择性 CH 官能化：分别使用铑和铱催化系统开发了直接碘化和酰胺化。酰胺化的机理研究表明，独特的区域选择性是通过 N-氧化物螯合的铱环的顺利形成实现的，并且酸添加剂在决定原脱金属的速率步骤中起着关键作用。虽然这种使用 N-氧化物作为导向基团的远程 CH 活化方法可以在温和条件下很容易地应用于各种杂环底物，具有高官能团耐受性，但证明了锌喹酯（一种荧光锌指示剂）的有效合成。
• Evaluation of Antiplasmodial Potential of C2 and C8 Modified Quinolines: in vitro and in silico Study
  作者：Rakesh Kumar、Ritika Sharma、Inder Kumar、Pooja Upadhyay、Ankit Kumar Dhiman、Rohit Kumar、Rakesh Kumar、Rituraj Purohit、Dinkar Sahal、Upendra Sharma

  DOI：10.2174/1573406414666181015144413

  日期：2019.10.14

  Malaria remains a common life-threatening infectious disease across the globe due to the development of resistance by Plasmodium parasite against most antimalarial drugs. The situation demands new and effective drug candidates against Plasmodium.

  The objective of this study is to design, synthesize and test novel quinoline based molecules against the malaria parasite.

  C2 and C8 modified quinoline analogs obtained via C-H bond functionalization approach were synthesized and evaluated for inhibition of growth of P. falciparum grown in human red blood cells using SYBR Green microtiter plate based screening. Computational molecular docking studies were carried out with top fourteen molecules using Autodoc software.

  The biological evaluation results revealed good activity of quinoline-8-acrylate 3f (IC50 14.2 µM), and the 2-quinoline-α-hydroxypropionates 4b (IC50 6.5 µM), 4j (IC50 5.5 µM) and 4g (IC50 9.5 µM), against chloroquine sensitive Pf3D7 strain. Top fourteen molecules were screened also against chloroquine resistant Pf INDO strain and the observed resistant indices were found to lie between 1 and 7.58. Computational molecular docking studies indicated a unique mode of binding of these quinolines to Falcipain-2 and heme moiety, indicating these to be the probable targets of their antiplasmodial action.

  An important finding of our work is the fact that unlike Chloroquine which shows a resistance Index of 15, the resistance indices for the most promising molecules studied by us were about one indicating equal potency against drug sensitive and resistant strains of the malaria parasite.

  背景： 疟疾仍然是全球常见的危及生命的传染病，因为疟原虫对大多数抗疟药物产生了抗药性。情况要求寻找针对疟原虫的新型有效药物候选物。 目标： 本研究的目标是设计、合成和测试基于喹啉的新型分子来对抗疟原虫。 方法： 通过C-H键官能化方法获得的C2和C8修饰的喹啉类似物被合成并评估其对在人类红细胞中生长的疟原虫P. falciparum生长的抑制作用，使用SYBR Green微孔板筛选法。采用Autodoc软件对前十四种分子进行了计算分子对接研究。 结果： 生物评价结果显示，喹啉-8-丙烯酸酯3f（IC50为14.2 µM），以及2-喹啉-α-羟基丙酸酯4b（IC50为6.5 µM）、4j（IC50为5.5 µM）和4g（IC50为9.5 µM）对氯喹敏感的Pf3D7菌株表现出良好的活性。前十四种分子还对氯喹耐药的Pf INDO菌株进行了筛选，观察到的耐药指数在1和7.58之间。计算分子对接研究表明，这些喹啉类化合物与Falcipain-2和血红素部分有独特的结合方式，表明它们可能是抗疟作用的潜在靶点。 结论： 我们工作的一个重要发现是，与氯喹的抗性指数为15相比，我们研究的最有前途的分子的抗性指数约为1，表明它们对抗药敏和耐药菌株的疟原虫具有相同的效力。
• Rhodium-Catalyzed Remote C-8 Alkylation of Quinolines with Activated and Unactivated Olefins: Mechanistic Study and Total Synthesis of EP4 Agonist
  作者：Ritika Sharma、Inder Kumar、Rakesh Kumar、Upendra Sharma

  DOI：10.1002/adsc.201700542

  日期：2017.9.4

  rhodium(III)‐catalyzed regioselective distal C(sp2)‐H bond alkylation of quinoline N‐oxides using olefins as alkyl source and N‐oxide as the traceless directing group. The reaction exhibits broad substrate scope with excellent selectivity for C‐8 position and good yields of alkylated products. The usefulness of the developed catalytic protocol is established by synthesis of EP4 agonist. In mechanistic study, C‐8 olefinated

  本文报道的是铑（III）催化的区域选择性远侧C（SP 2）-H键的喹啉烷基化ñ -oxides使用烯烃作为烷基源和Ñ氧化物作为无痕引导组。该反应具有广泛的底物范围，对C-8位置具有出色的选择性，并且烷基化产物的收率高。通过合成EP4激动剂可以确定已开发的催化方案的实用性。在机理研究中，C-8烯烃化喹啉被确定为反应中间体，在存在铑（I）物种（反应过程中由铑（III）生成）和甲酸的情况下，该中间体还原为所需的C-8烷基化产物。在四氟硼酸银的存在下，由二甲基甲酰胺生产甲酸。