4-azido-3-nitrobenzonitrile | 1027935-60-9

• 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: 4-azido-3-nitrobenzonitrile
• CAS: 1027935-60-9
• 化学式: C₇H₃N₅O₂
• 分子量: 189.133
• InChiKey: IAEMWVVQFVYDRR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  14
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  84
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  4-azido-3-nitrobenzonitrile 以 甲苯 为溶剂， 反应 2.0h， 生成 5-benzofuroxancarbonitrile
  参考文献：
  名称：

  Hypoxia-Selective Agents Derived from Quinoxaline 1,4-Di-N-oxides

  摘要：

  Hypoxic cells, which are a common feature of solid tumors, but not normal tissues, are resistant to both anticancer drugs and radiation therapy. Thus the identification of drugs with selective toxicity toward hypoxic cells is an important objective in anticancer chemotherapy. The benzotriazine di-N-oxide (SR 4233, Tirapazamine) has been shown to be an efficient and selective cytotoxin for hypoxic cells. Since the bioreductive activation of Tirapazamine is thought to be due to the presence of the 1,4-di-N-oxide moiety, a series of 3-aminoquinoxaline-2-carbonitrile 1,4-di-N-oxides with a range of electron-donating and -withdrawing substituents in the 6- and/or 7- positions has been synthesized and evaluated for toxicity to hypoxic cells. Electrochemical studies of the quinoxaline di-N-oxides and Tirapazamine showed that as the electron-withdrawing nature of the 6(7)-substituent increases, the reduction potential becomes more positive and the compound is more readily reduced. Apart from the unsubstituted 6a and the 6,7-dimethyl derivative 6c, the quinoxaline di-N-oxides have reduction potentials significantly more positive than Tirapazamine (E(pc)-0.90 V). The most potent cytotoxins to cells in culture were the 6,7,-dichloro and 6,7-difluoro derivatives 6i and 6l, which were 30-fold more potent than Tirapazamine. The 6(7)-fluoro and 6(7)-chloro compounds, 6e and 6h, showed the greatest hypoxia selectivity. Four of the compounds, 6e, 6f, 6h and 6i, killed the inner cells of multicellular tumor spheroids in vitro. In vivo Balb/c mice tolerated a dose of these four compounds twice the size of that of Tirapazamine. This study demonstrates that quinoxaline 1,4-di-N-oxides could provide useful hypoxia-selective therapeutic agents.

  DOI：

  10.1021/jm00010a023
• 作为产物：
  描述：

  4-氯-3-硝基苯甲腈 在 sodium azide 作用下， 以 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 0.08h， 以85%的产率得到4-azido-3-nitrobenzonitrile
  参考文献：
  名称：

  SNAr在相转移或微波辐射下合成硝基苯基和氟苯基叠氮化物和二叠氮化物：快速和温和的方法来制备光亲和标记，交联和点击化学试剂

  摘要：

  介绍了两种快速温和的方法来制备硝基苯基和氟苯基叠氮化物。这些芳基叠氮化物被广泛用作交联，光亲和标记和点击化学试剂。取代的芳基叠氮化物是通过用相转移催化剂（PTC）（例如四氟硼酸四乙铵）（TEATFB）在卤代苯上进行S N Ar取代而制备的，该反应在相当温和的温度（25°C至70°C）下进行了数小时）。此外，还在稍高的温度（50℃至70℃）下在微波辐射下在数分钟内制备芳基叠氮化物。这些程序可用于制备其他芳基叠氮化物。在取代的五氟苯（pF），每个反应中获得的产物类型取决于叠氮化钠的量以及吸电子取代基（COH，COR，COOR，CN，NO 2或F）的强度和位置。讨论了在这些S N Ar反应中的机理和所获得的产物。

  DOI：

  10.1002/poc.4171

文献信息

• SNAr azidation of phenolic functions utilizing diphenyl phosphorazidate
  作者：Kotaro Ishihara、Takayuki Shioiri、Masato Matsugi

  DOI：10.1016/j.tetlet.2019.151493

  日期：2020.2

  A useful method for the synthesis of aryl azides via SNAr reaction of phenol derivatives using diphenyl phosphorazidate (DPPA) as an azidation reagent was developed. Various phenol derivatives bearing electron-withdrawing groups were converted into the corresponding aryl azides in a single step. This method is easy to perform and enables the preparation of aryl azides without the use of explosive azide

  开发了一种有用的方法，该方法通过使用叠氮磷酸二苯酯（DPPA）作为叠氮化试剂通过苯酚衍生物的SNAr反应进行芳基叠氮化物的合成。带有吸电子基团的各种酚衍生物可在一个步骤中转化为相应的芳基叠氮化物。该方法易于实施，并且能够在不使用爆炸性叠氮化物源的情况下制备芳基叠氮化物。
• Hypoxia-Selective Agents Derived from Quinoxaline 1,4-Di-N-oxides
  作者：Antonio Monge、Juan A. Palop、Adela Lopez de Cerain、Virginia Senador、Francisco J. Martinez、Yolanda Sainz、Susana Narro、Estrella Garcia、Carlos de Miguel

  DOI：10.1021/jm00010a023

  日期：1995.5

  Hypoxic cells, which are a common feature of solid tumors, but not normal tissues, are resistant to both anticancer drugs and radiation therapy. Thus the identification of drugs with selective toxicity toward hypoxic cells is an important objective in anticancer chemotherapy. The benzotriazine di-N-oxide (SR 4233, Tirapazamine) has been shown to be an efficient and selective cytotoxin for hypoxic cells. Since the bioreductive activation of Tirapazamine is thought to be due to the presence of the 1,4-di-N-oxide moiety, a series of 3-aminoquinoxaline-2-carbonitrile 1,4-di-N-oxides with a range of electron-donating and -withdrawing substituents in the 6- and/or 7- positions has been synthesized and evaluated for toxicity to hypoxic cells. Electrochemical studies of the quinoxaline di-N-oxides and Tirapazamine showed that as the electron-withdrawing nature of the 6(7)-substituent increases, the reduction potential becomes more positive and the compound is more readily reduced. Apart from the unsubstituted 6a and the 6,7-dimethyl derivative 6c, the quinoxaline di-N-oxides have reduction potentials significantly more positive than Tirapazamine (E(pc)-0.90 V). The most potent cytotoxins to cells in culture were the 6,7,-dichloro and 6,7-difluoro derivatives 6i and 6l, which were 30-fold more potent than Tirapazamine. The 6(7)-fluoro and 6(7)-chloro compounds, 6e and 6h, showed the greatest hypoxia selectivity. Four of the compounds, 6e, 6f, 6h and 6i, killed the inner cells of multicellular tumor spheroids in vitro. In vivo Balb/c mice tolerated a dose of these four compounds twice the size of that of Tirapazamine. This study demonstrates that quinoxaline 1,4-di-N-oxides could provide useful hypoxia-selective therapeutic agents.
• Synthesis of nitrophenyl and fluorophenyl azides and diazides by S _N Ar under phase‐transfer or microwave irradiation: Fast and mild methodologies to prepare photoaffinity labeling, crosslinking, and click chemistry reagents
  作者：Elisa Leyva、Johana Aguilar、Regina M. González‐Balderas、Sarai Vega‐Rodríguez、Silvia E. Loredo‐Carrillo

  DOI：10.1002/poc.4171

  日期：2021.5

  (50°C to 70°C). These procedures could be applied in the preparation of other aryl azides. In the case of substituted pentafluoro benzene (pF), the type of products obtained in each reaction depends on the amount of sodium azide and the strength and position of electron‐withdrawing substituents (COH, COR, COOR, CN, NO2, or F). A discussion on the mechanisms and the products obtained in these SNAr reactions

  介绍了两种快速温和的方法来制备硝基苯基和氟苯基叠氮化物。这些芳基叠氮化物被广泛用作交联，光亲和标记和点击化学试剂。取代的芳基叠氮化物是通过用相转移催化剂（PTC）（例如四氟硼酸四乙铵）（TEATFB）在卤代苯上进行S N Ar取代而制备的，该反应在相当温和的温度（25°C至70°C）下进行了数小时）。此外，还在稍高的温度（50℃至70℃）下在微波辐射下在数分钟内制备芳基叠氮化物。这些程序可用于制备其他芳基叠氮化物。在取代的五氟苯（pF），每个反应中获得的产物类型取决于叠氮化钠的量以及吸电子取代基（COH，COR，COOR，CN，NO 2或F）的强度和位置。讨论了在这些S N Ar反应中的机理和所获得的产物。