1-ethynyl-2-(2-(4-methoxyphenyl)-ethynyl)-1H-imidazole | 874399-42-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 1-ethynyl-2-(2-(4-methoxyphenyl)-ethynyl)-1H-imidazole
• 英文别名: 1-Ethynyl-2-[2-(4-methoxyphenyl)ethynyl]imidazole
• CAS: 874399-42-5
• 化学式: C₁₄H₁₀N₂O
• 分子量: 222.246
• InChiKey: SVDZZVRRGGSVCR-UHFFFAOYSA-N

物化性质

• 沸点：
  402.8±47.0 °C(Predicted)
• 密度：
  1.00±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  17
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  27
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  1-ethynyl-2-(2-(4-methoxyphenyl)-ethynyl)-1H-imidazole 、 苯硫酚 以 四氢呋喃 为溶剂， 反应 120.0h， 以43%的产率得到(Z)-2-(4-methoxyphenyl)ethynyl-1-(2-(phenylthiol)vinyl)-1H-imidazole
  参考文献：
  名称：

  基于细胞毒性1,2-二炔基咪唑的氮杂-烯二炔：氮杂-伯格曼重排速率不能预测细胞毒性

  摘要：

  由烯二炔抗肿瘤抗生素启发而来的一类新的潜在抗肿瘤药已被合成：1,2-二烷基炔基咪唑。从理论上在B3LYP / 6-31G（d，p）水平研究了这些1,2-二炔基咪唑的aza-Bergman重排，并通过测量1,4-环己二烯的重排动力学进行了实验研究。理论和实验结果之间有很好的相关性；实验证实了理论上预测的对初始氮杂-伯格曼环化屏障的微妙取代基作用。然而，尽管这些1，2-二酮基咪唑在相对温和的条件下能够发生Bergman重排成双自由基/卡宾中间体的能力，但Bergman环化速率与对A459细胞的细胞毒性之间没有相关性。此外，细胞毒素1 2-二炔基咪唑不会引起超螺旋质粒DNA的切口或牛血清白蛋白的裂解。细胞毒性的另一种机制涉及意外的选择性硫醇添加到提出了某些1，2-二乙炔基咪唑的N-乙炔基。

  DOI：

  10.1021/jm200289j
• 作为产物：
  描述：

  N-(2-trimethylsilyl)ethynyl-2-iodoimidazole 在 四(三苯基膦)钯 copper(l) iodide 、 四丁基氟化铵 、 三乙胺 作用下， 以 四氢呋喃 为溶剂， 反应 0.08h， 生成 1-ethynyl-2-(2-(4-methoxyphenyl)-ethynyl)-1H-imidazole
  参考文献：
  名称：

  Intra- and intermolecular trapping of cyclopentapyrazine carbenes derived from 1,2-dialkynylimidazoles

  摘要：

  The thermolysis of 1,2-dialkynylimidazoles in benzene solution affords high yields of 7-pheiiyl-5H-cyclopentapyrazines, which presumably form by solvent trapping of cyclopentapyrazine carbene intermediates. In cases where dialkynylimidazole contains side chains that can participate in intramolecular carbene C-H insertion or olefin addition, these processes compete with solvent addition to afford novel tri- and tetracyclic pyrazines, which can be obtained in good yield when the thermolysis is carried out in hexafluoro benzene. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetlet.2005.11.010

文献信息

• Cyclization kinetics and biological evaluation of an anticancer 1,2-dialkynylimidazole
  作者：Christophe Laroche、Jing Li、Cristina Gonzales、Wendi M. David、Sean M. Kerwin

  DOI：10.1039/b925261d

  日期：——

  1,2-Dialkynylimidazoles have been reported to undergo thermal cyclization/rearrangement to diradical and carbene intermediates. Optimization of the synthesis of the 1,2-dialkynylimidazole 3 has provided sufficient material for kinetic and biological studies. The 1,2-dialkynylimidazole 3 is cytotoxic against a wide range of cancer cells and induces apoptosis in A549 cells. Experimentally-determined kinetics of the thermolysis of 3 (Ea = 30.0 kcal mol−1) are in excellent agreement with DFT calculations of the cyclization/rearrangement to diradical and cyclopentapyrazine carbene intermediates (Ea = 29.7 kcal mol−1). Commensurate with the relatively high barrier for cyclization of 3, no evidence for cleavage of supercoiled DNA under physiological conditions was found; however, under aqueous conditions at 70 °C 3 formed a covalent adduct with a model peptide. These studies indicate that if cyclization of 3 is involved in its anticancer activity, the cyclization must be facilitated, perhaps through initial protein binding, which could lead to covalent protein modification.

  据报告，1,2-二炔基咪唑会经历热环化/重排，生成二自由基和炔烃中间体。1,2-二炔基咪唑3的合成优化为动力学和生物学研究提供了充足的原料。1,2-二炔基咪唑3对多种癌细胞具有细胞毒性，可诱导A549细胞凋亡。实验测定的3的热解动力学（Ea = 30.0 kcal mol-1）与DFT计算的环化/重排生成二自由基和环戊并吡嗪炔烃中间体（Ea = 29.7 kcal mol-1）非常吻合。与3相对较高的环化障碍相一致，没有发现超螺旋DNA在生理条件下发生断裂的证据；然而，在70°C的水溶液条件下，3与一种模型肽形成了共价加合物。这些研究表明，如果3的环化与其抗癌活性有关，则必须促进环化，这可能是通过最初的蛋白质结合，从而引起共价蛋白质修饰。
• Spirocyclic Products via Carbene Intermediates from Thermolysis of 1,2-Dialkynylpyrrole and 1,2-Diethynylimidazole
  作者：Sean M. Kerwin、Ashley L. Jewett、Joshua A. Bondoc、Bradford L. Gilbreath、Brandon J. Reinus

  DOI：10.1055/s-0041-1737937

  日期：2022.4

  cyclopenta[b]pyrazine carbene intermediates. Here we show that a similar rearrangement also occurs in the case of 1,2-diethynyl-1H-pyrrole, and that trapping the intermediate cyclopenta[b]pyridine carbene with solvent THF affords an ylide that undergoes a Stevens rearrangement to a spirocyclic product. An analogous rearrangement and trapping is observed for thermolysis of 1,2-dialkynylimidazoles in

  1,2-二炔基咪唑的热重排已被证明会导致捕获环戊二烯[ b ]吡嗪卡宾中间体的产物。在这里，我们表明在 1,2-二乙炔基-1 H-吡咯的情况下也发生了类似的重排，并且用溶剂 THF 捕获中间体环戊二烯[ b ]吡啶卡宾提供了一个叶立德，该叶立德经历了史蒂文斯重排成螺环产物. 对于 1,2-二炔基咪唑在 THF 或 1,4-二恶烷中的热解，观察到类似的重排和捕获。
• Cytotoxic 1,2-Dialkynylimidazole-Based Aza-Enediynes: Aza-Bergman Rearrangement Rates Do Not Predict Cytotoxicity
  作者：Christophe Laroche、Jing Li、Sean M. Kerwin

  DOI：10.1021/jm200289j

  日期：2011.7.28

  synthesized: the 1,2-dialkynylimidazoles. The aza-Bergman rearrangement of these 1,2-dialkynylimidazoles has been investigated theoretically at the B3LYP/6-31G(d,p) level and experimentally by measuring the kinetics of rearrangement in 1,4-cyclohexadiene. There is a good correlation between the theoretical and experimental results; subtle substituent effects on the initial aza-Bergman cyclization barrier predicted

  由烯二炔抗肿瘤抗生素启发而来的一类新的潜在抗肿瘤药已被合成：1,2-二烷基炔基咪唑。从理论上在B3LYP / 6-31G（d，p）水平研究了这些1,2-二炔基咪唑的aza-Bergman重排，并通过测量1,4-环己二烯的重排动力学进行了实验研究。理论和实验结果之间有很好的相关性；实验证实了理论上预测的对初始氮杂-伯格曼环化屏障的微妙取代基作用。然而，尽管这些1，2-二酮基咪唑在相对温和的条件下能够发生Bergman重排成双自由基/卡宾中间体的能力，但Bergman环化速率与对A459细胞的细胞毒性之间没有相关性。此外，细胞毒素1 2-二炔基咪唑不会引起超螺旋质粒DNA的切口或牛血清白蛋白的裂解。细胞毒性的另一种机制涉及意外的选择性硫醇添加到提出了某些1，2-二乙炔基咪唑的N-乙炔基。
• Intra- and intermolecular trapping of cyclopentapyrazine carbenes derived from 1,2-dialkynylimidazoles
  作者：Asha K. Nadipuram、Sean M. Kerwin

  DOI：10.1016/j.tetlet.2005.11.010

  日期：2006.1

  The thermolysis of 1,2-dialkynylimidazoles in benzene solution affords high yields of 7-pheiiyl-5H-cyclopentapyrazines, which presumably form by solvent trapping of cyclopentapyrazine carbene intermediates. In cases where dialkynylimidazole contains side chains that can participate in intramolecular carbene C-H insertion or olefin addition, these processes compete with solvent addition to afford novel tri- and tetracyclic pyrazines, which can be obtained in good yield when the thermolysis is carried out in hexafluoro benzene. (c) 2005 Elsevier Ltd. All rights reserved.