2-氯-6-(4-甲氧基苯基)吡啶 | 851595-31-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 中文名称: 2-氯-6-(4-甲氧基苯基)吡啶
• 英文名称: 2-chloro-6-(4-methoxyphenyl)pyridine
• CAS: 851595-31-8
• 化学式: C₁₂H₁₀ClNO
• 分子量: 219.671
• InChiKey: KNPKFNDRHIKPPI-UHFFFAOYSA-N

物化性质

• 熔点：
  77-79 °C
• 沸点：
  344.9±32.0 °C(Predicted)
• 密度：
  1.194±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  15
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  22.1
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  2-氯-6-(4-甲氧基苯基)吡啶 在 吡啶 、 sodium tetrahydroborate 、 1,10-菲罗啉 、 nickel diacetate 作用下， 生成 2-(4-甲氧基苯基)吡啶
  参考文献：
  名称：

  A Micellar Catalysis Strategy for Suzuki–Miyaura Cross-Couplings of 2-Pyridyl MIDA Boronates: No Copper, in Water, Very Mild Conditions

  摘要：

  Suzuki-Miyaura (SM) cross-couplings of 2-pyridyl MIDA boronates can be successfully carried out in the complete absence of copper by attenuation of the Lewis basicity associated with the pyridyl nitrogen using selected substituents (e.g., fluorine or chlorine) on the ring. This strategy imparts additional synthetic options compared with existing approaches based on the use of Lewis acids or N-oxides. Thus, access to highly valued 2-substituted pyridyl rings via an initial Suzuki-Miyaura coupling can be followed by dehalogenation, SNAr reactions, or a second SM coupling to arrive at 2,6-disubstituted pyridyl arrays, all run in a single pot, enabled by micellar catalysis in water. Accessing targets within drug-like space is demonstrated in a four-step, one-pot sequence. Computational data suggest that the major role being played by electron-withdrawing substituents in promoting these cross-couplings without the need for copper is to slow the rates of protodeboronation of intermediate 2-pyridylboronic acids.

  DOI：

  10.1021/acscatal.7b03241
• 作为产物：
  描述：

  2-(4-甲氧基苯基)吡啶 在 正丁基锂 、 N,N-二甲基乙醇胺 、 六氯乙烷 作用下， 以 正己烷 、 四氢呋喃 为溶剂， 反应 1.5h， 以90%的产率得到2-氯-6-(4-甲氧基苯基)吡啶
  参考文献：
  名称：

  茴香醚的吡啶基定向锂化：功能性吡啶基酚的新途径

  摘要：

  已经研究了九种茴香基吡啶的锂化。尽管通常的试剂在吡啶环上不发生反应或未提供加成产物，但BuLi-LiDMAE（LiDMAE = Me 2 N（CH 2）2 OLi）超碱诱导了吡啶基定向金属化反应。该新反应的有用性允许有效地制备一系列α官能的吡啶基酚。随后还成功地将合适的异构体成功环化为相应的苯并呋喃基吡啶。

  DOI：

  10.1016/j.tet.2004.10.100

文献信息

• Direct Arylation of N-Heteroarenes with Aryldiazonium Salts by Photoredox Catalysis in Water
  作者：Dong Xue、Zhi-Hui Jia、Cong-Jun Zhao、Yan-Yan Zhang、Chao Wang、Jianliang Xiao

  DOI：10.1002/chem.201304120

  日期：2014.3.3

  solvent, an array of xanthenes, thiazole, pyrazine, and pyridazine are compatible with this new arylation approach. The broad substrate scope, mild reaction conditions, and use of water as reaction solvent make this procedure a practical and environmentally friendly method for the synthesis of compounds containing aryl‐heteroaryl motifs.

  已经开发出一种高效的可见光促进的N-杂芳烃与芳基重氮盐在水中的“自由基型”偶联。在室温下将反应继续进行的[Ru（联吡啶）3 ]氯2 ⋅ 6 H 2O作为光敏剂，商用灯泡作为光源。在这些反应条件下，吡啶和各种取代的吡啶是有效的底物，仅形成具有不同区域选择性的单取代产物。使用甲酸水溶液作为溶剂，一系列的黄嘌呤，噻唑，吡嗪和哒嗪与这种新的芳基化方法兼容。广泛的底物范围，温和的反应条件以及使用水作为反应溶剂，使得该程序成为合成具有芳基-杂芳基基序的化合物的实用且环境友好的方法。
• Pyridino-directed lithiation of anisylpyridines: new access to functional pyridylphenols
  作者：Michaël Parmentier、Philippe Gros、Yves Fort

  DOI：10.1016/j.tet.2004.10.100

  日期：2005.3

  The lithiation of nine anisylpyridines has been studied. While usual reagents did not react or gave addition products on pyridine ring, the BuLi-LiDMAE (LiDMAE=Me2N(CH2)2OLi) superbase induced exclusive pyridino directed metallation. The usefulness of this new reaction allowed the efficient preparation of a range of alpha functional pyridylphenols. A successful subsequent cyclisation of an appropriate

  已经研究了九种茴香基吡啶的锂化。尽管通常的试剂在吡啶环上不发生反应或未提供加成产物，但BuLi-LiDMAE（LiDMAE = Me 2 N（CH 2）2 OLi）超碱诱导了吡啶基定向金属化反应。该新反应的有用性允许有效地制备一系列α官能的吡啶基酚。随后还成功地将合适的异构体成功环化为相应的苯并呋喃基吡啶。
• STUDIES IN THE PREPARATION OF ANTIMALARIALS FROM PYRIDINE
  作者：Henry Gilman、John T. Edward

  DOI：10.1139/v53-061

  日期：1953.4.1

  The addition of aryllithium compounds to pyridine followed by air oxidation gives satisfactory yields of several 2-arylpyridines. These are readily oxidized by perbenzoic acid to 2-arylpyridine-N-oxides, from which 2-aryl-4- and 6-chloropyridines may be obtained. 2-Arylpyridines and aryllithiums give low yields of 2,6-diarylpyridines. From three different 2-arylpyridines three antimalarials modelled after the plasmoquin type have been prepared.

  芳基锂化合物加入吡啶，随后进行空气氧化可得到几种2-芳基吡啶的满意产率。这些化合物可被过苯甲酸氧化成2-芳基吡啶-N-氧化物，从中可以获得2-芳基-4-和6-氯吡啶。2-芳基吡啶和芳基锂化合物产率较低的2,6-二芳基吡啶。从三种不同的2-芳基吡啶中合成了三种类似于贫血原虫喹诺酮类的抗疟疾药物模型。
• Cross-coupling study of iodo/chloropyridines and 2-chloroquinoline with atom-economic triarylbismuth reagents under Pd-catalysis
  作者：Maddali L.N. Rao、Ritesh J. Dhanorkar

  DOI：10.1016/j.tet.2014.11.036

  日期：2015.1

  This study describes the palladium-catalyzed couplings of iodopyridines, chloropyridines, and chloroquinoline with atom-economic BiAr3 reagents in sub-stoichiometric loadings. Mono-arylations of iodo and chloropyridines produced arylpyridines in high yields. The couplings addressed with dihalopyridines have afforded chemo- and regio-selective coupling products. Arylations of 2-chloroquinoline with different triarylbismuth reagents demonstrated fruitful coupling reactivity under the established conditions. This sumptuous study demonstrates the remarkable cross-coupling reactivity of iodo/chloropyridines and chloroquinoline with triarylbismuth reagents. (C) 2014 Elsevier Ltd. All rights reserved.
• Practical Routes to 2,6-Disubstituted Pyridine Derivatives
  作者：Lucie Vandromme、Hans-Ulrich Reißig、Susie Gröper、Jürgen P. Rabe

  DOI：10.1002/ejoc.200701200

  日期：2008.4

  starting from readily available 2-substituted pyridines. The main sequence involves a selective α-lithiation reaction with halogen functionalization followed by a Grignard reaction catalyzed by Fe(acac)3. After demonstration of the easy feasibility of this strategy by synthesizing 2,6-disubstituted pyridines 1, the route was applied to obtain pyridine derivatives bearing electron-donating or electron-withdrawing

  我们报告了从容易获得的 2-取代吡啶开始以直接方式合成一系列 2,6-二取代吡啶。主要序列涉及具有卤素官能化的选择性α-锂化反应，然后是由 Fe(acac)3 催化的格氏反应。在通过合成 2,6-二取代吡啶 1 证明了该策略的简单可行性后，该路线被应用于获得带有给电子或吸电子基团的吡啶衍生物。因此，获得了一系列在 6 位带有芳基部分和在 2 位带有烷基链的吡啶。研究了吡啶在有机溶液和石墨基面之间的界面处的自组装能力。报告了一种化合物的初步 STM 结果。