1-tert-butyl-4-(4-iodobenzyloxy)benzene

• 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: 1-tert-butyl-4-(4-iodobenzyloxy)benzene
• 英文别名: 1-Tert-butyl-4-[(4-iodophenyl)methoxy]benzene
• 化学式: C₁₇H₁₉IO
• 分子量: 366.242
• InChiKey: YNJGUSLLXWUGBF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.7
• 重原子数：
  19
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.29
• 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-tert-butyl-4-(4-iodobenzyloxy)benzene 、 在 bis-triphenylphosphine-palladium(II) chloride 、 copper(l) iodide 、 三乙胺 作用下， 以 四氢呋喃 为溶剂， 以67 %的产率得到dibutyl 5,5'-((((2,5-bis((4-((4-(tert-butyl)phenoxy)methyl)phenyl)ethynyl)-1,4-phenylene)bis(ethyne-2,1-diyl))bis(5-(tert-butyl)-3-(pyridin-3-ylethynyl)-2,1-phenylene))bis(ethyne-2,1-diyl))dinicotinate
  参考文献：
  名称：

  Rapid Access to Encapsulated Molecular Rotors via Coordination‐Driven Macrocycle Formation

  摘要：

  摘要大环的形成依赖于芳基乙炔结构中适当位置的吡啶配体的反式金属配位，这为获得封装在大环定子中的分子旋转体提供了快速可靠的途径。AgI 配位大环的 X 射线晶体学显示，中心旋转体没有明显的密切接触，这为旋转体在中心空腔内的无障碍旋转或摆动提供了可能性。PdII 配位大环化合物的固态 13C NMR 支持简单烷在晶格中无障碍运动的观点。溶液 1H NMR 研究表明，在室温下将 PdII 引入吡啶基配体后，大环立即完全形成。此外，所形成的大环在溶液中是稳定的；在冷却到 -50 °C 时，1H NMR 光谱没有明显变化，这与没有动态行为是一致的。这些大环的合成路线既简便又模块化，只需简单的四个步骤（包括 Sonogashira 偶联反应和脱保护反应）就能获得相当复杂的结构。

  DOI：

  10.1002/chem.202301745
• 作为产物：
  描述：

  4-叔丁基苯酚 、 4-碘苄基溴 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 2.0h， 以87.4%的产率得到1-tert-butyl-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.
• Rapid Access to Encapsulated Molecular Rotors via Coordination‐Driven Macrocycle Formation
  作者：Noah A. Grinde、Zachary R. Kehoe、Herh G. Vang、Lucas J. Mancheski、Eric Bosch、Scott A. Southern、David L. Bryce、Nathan P. Bowling

  DOI：10.1002/chem.202301745

  日期：2023.9.6

  Macrocycle formation that relies upon trans metal coordination of appropriately placed pyridine ligands within an arylene ethynylene construct provides rapid and reliable access to molecular rotators encapsulated within macrocyclic stators. Showing no significant close contacts to the central rotators, X‐ray crystallography of Ag^I‐coordinated macrocycles provides plausibility for unobstructed rotation or wobbling of rotators within the central cavity. Solid‐state ¹³C NMR of Pd^II‐coordinated macrocycles supports the notion of unobstructed movement of simple arenes in the crystal lattice. Solution ¹H NMR studies indicate complete and immediate macrocycle formation upon the introduction of Pd^II to the pyridyl‐based ligand at room temperature. Moreover, the formed macrocycle is stable in solution; a lack of significant changes in the ¹H NMR spectrum upon cooling to −50 °C is consistent with the absence of dynamic behavior. The synthetic route to these macrocycles is expedient and modular, providing access to rather complex constructs in four simple steps involving Sonogashira coupling and deprotection reactions.

  摘要大环的形成依赖于芳基乙炔结构中适当位置的吡啶配体的反式金属配位，这为获得封装在大环定子中的分子旋转体提供了快速可靠的途径。AgI 配位大环的 X 射线晶体学显示，中心旋转体没有明显的密切接触，这为旋转体在中心空腔内的无障碍旋转或摆动提供了可能性。PdII 配位大环化合物的固态 13C NMR 支持简单烷在晶格中无障碍运动的观点。溶液 1H NMR 研究表明，在室温下将 PdII 引入吡啶基配体后，大环立即完全形成。此外，所形成的大环在溶液中是稳定的；在冷却到 -50 °C 时，1H NMR 光谱没有明显变化，这与没有动态行为是一致的。这些大环的合成路线既简便又模块化，只需简单的四个步骤（包括 Sonogashira 偶联反应和脱保护反应）就能获得相当复杂的结构。