1-chloro-4-(4-iodobenzyloxy)benzene

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 1-chloro-4-(4-iodobenzyloxy)benzene
• 英文别名: 1-Chloro-4-((4-iodobenzyl)oxy)benzene；1-chloro-4-[(4-iodophenyl)methoxy]benzene
• 化学式: C₁₃H₁₀ClIO
• 分子量: 344.579
• InChiKey: AKWYXXPBRXGLJT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  16
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  9.2
• 氢给体数：
  0
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  1-chloro-4-(4-iodobenzyloxy)benzene 在 三氟乙酸酐 、 sodium t-butanolate 作用下， 以 1,4-二氧六环 、 乙腈 为溶剂， 反应 4.0h， 生成
  参考文献：
  名称：

  芳烃形式脱氢合成芳烃

  摘要：

  芳烃为苯环化合物的多样化提供了巨大的潜力，苯环化合物存在于药物、农用化学品和液晶中。然而，获取这些高能中间体需要合成前体，这涉及苛刻的条件或多步合成。开发使用更简单的底物和更温和的条件获取芳烃的替代方法对于更简化的方法是必要的。在这里，我们描述了简单芳烃的两步正式脱氢，以在相对于传统反应性基团（例如卤化物）较远的位置生成芳烃。这种方法是通过区域选择性安装和弹出“鎓”离去基团实现的，我们证明了简单芳烃（20 个示例）和亲吻分子（8 个示例）的相容性。此外，通过直接比较，我们表明，与目前最先进的芳烃前体相比，我们的正式脱氢方法在生成芳烃方面更具官能团耐受性和效率。最后，我们证明芳炔中间体提供了不同于其他方法的区域选择性 C-H 胺化的机会。

  DOI：

  10.1021/jacs.2c13007
• 作为产物：
  描述：

  4-碘苄基溴 、 对氯苯酚 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 2.0h， 以79%的产率得到1-chloro-4-(4-iodobenzyloxy)benzene
  参考文献：
  名称：

  Radioiodinated Benzyloxybenzene Derivatives: A Class of Flexible Ligands Target to β-Amyloid Plaques in Alzheimer’s Brains

  摘要：

  Benzyloxybenzene, as a novel flexible scaffold without rigid planarity, was synthesized and evaluated as ligand toward A beta plaques. The binding site calculated for these flexible ligands was the hydrophobic Val18_Phe20 channel on the flat surface of A beta fiber. Structure activity relationship analysis generated a common trend that binding affinities declined significantly from para-substituted ligands to ortho-substituted ones, which was also quantitatively illustrated by 3D-QSAR modeling. Autoradiography in vitro further confirmed the high affinities of radioiodinated ligands [I-125]4, [I-125]24, and [I-125]22 (K-i = 24.3, 49.4, and 17.6 nM, respectively). In biodistribution, [I-125]4 exhibited high initial uptake and rapid washout property in the brain with brain(2 min)/brain(60 min) ratio of 16.3. The excellent in vitro and in vivo biostability of [I-125]4 enhanced its potential for clinical application in SPECT imaging of A beta plaques. This approach could also allow the design of a new generation of A beta targeting ligands without rigid and planar framework.

  DOI：

  10.1021/jm5004396

文献信息

• PHENYL BENZYL ETHER DERIVATIVE AND PREPARATION METHOD AND APPLICATION THEREOF
  申请人：ZHANG Zhiyong

  公开号：US20170037008A1

  公开（公告）日：2017-02-09

  Parts of compounds, after being labeled by radionuclide, of the phenyl benzyl ether derivative, are used as Aβ plaque imaging agent. The structural formula of the phenyl benzyl ether derivative is shown by formula (I). The present invention develops a kind of brand new phenyl benzyl ether derivative which has high affinity with Aβ plaques in brains of AD patients. The chemical structure of the phenyl benzyl ether derivative is different from that of compounds disclosed in the prior art and the phenyl benzyl ether derivative belongs to a brand new compound for diagnosing and treating AD. The obtained Aβ plaque imaging agent has the advantages that the in-vivo stability is good, the fat solubility is low, the removal speed for the brain is fast, the problem of removing the radionuclide in vivo does not exist, and the application prospect and the market value are great.

  化合物的部分，在被放射性核素标记后，苯基苄醚衍生物被用作Aβ斑块成像剂。苯基苄醚衍生物的结构式如公式（I）所示。本发明开发了一种全新的苯基苄醚衍生物，其与AD患者大脑中的Aβ斑块具有高亲和力。苯基苄醚衍生物的化学结构与先前公开的化合物不同，且该苯基苄醚衍生物属于一种全新的用于诊断和治疗AD的化合物。所得的Aβ斑块成像剂具有优点，即体内稳定性好，脂溶性低，对大脑的清除速度快，不存在体内去除放射性核素的问题，且应用前景和市场价值巨大。
• Radioiodinated Benzyloxybenzene Derivatives: A Class of Flexible Ligands Target to β-Amyloid Plaques in Alzheimer’s Brains
  作者：Yanping Yang、Mengchao Cui、Xiaoyang Zhang、Jiapei Dai、Zhiyong Zhang、Chunping Lin、Yuzhi Guo、Boli Liu

  DOI：10.1021/jm5004396

  日期：2014.7.24

  Benzyloxybenzene, as a novel flexible scaffold without rigid planarity, was synthesized and evaluated as ligand toward A beta plaques. The binding site calculated for these flexible ligands was the hydrophobic Val18_Phe20 channel on the flat surface of A beta fiber. Structure activity relationship analysis generated a common trend that binding affinities declined significantly from para-substituted ligands to ortho-substituted ones, which was also quantitatively illustrated by 3D-QSAR modeling. Autoradiography in vitro further confirmed the high affinities of radioiodinated ligands [I-125]4, [I-125]24, and [I-125]22 (K-i = 24.3, 49.4, and 17.6 nM, respectively). In biodistribution, [I-125]4 exhibited high initial uptake and rapid washout property in the brain with brain(2 min)/brain(60 min) ratio of 16.3. The excellent in vitro and in vivo biostability of [I-125]4 enhanced its potential for clinical application in SPECT imaging of A beta plaques. This approach could also allow the design of a new generation of A beta targeting ligands without rigid and planar framework.
• Synthesis of Arynes via Formal Dehydrogenation of Arenes
  作者：Riley A. Roberts、Bryan E. Metze、Aleksandra Nilova、David R. Stuart

  DOI：10.1021/jacs.2c13007

  日期：2023.2.15

  development of alternative methods to access arynes using simpler substrates and milder conditions is necessary for a more streamlined approach. Here, we describe a two-step formal dehydrogenation of simple arenes to generate arynes at a remote position relative to traditionally reactive groups, e.g., halides. This approach is enabled by regioselective installation and ejection of an “onium” leaving group, and

  芳烃为苯环化合物的多样化提供了巨大的潜力，苯环化合物存在于药物、农用化学品和液晶中。然而，获取这些高能中间体需要合成前体，这涉及苛刻的条件或多步合成。开发使用更简单的底物和更温和的条件获取芳烃的替代方法对于更简化的方法是必要的。在这里，我们描述了简单芳烃的两步正式脱氢，以在相对于传统反应性基团（例如卤化物）较远的位置生成芳烃。这种方法是通过区域选择性安装和弹出“鎓”离去基团实现的，我们证明了简单芳烃（20 个示例）和亲吻分子（8 个示例）的相容性。此外，通过直接比较，我们表明，与目前最先进的芳烃前体相比，我们的正式脱氢方法在生成芳烃方面更具官能团耐受性和效率。最后，我们证明芳炔中间体提供了不同于其他方法的区域选择性 C-H 胺化的机会。