2,6-dichloro-4,4’-bipyridine | 116273-61-1

• 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
• 英文名称: 2,6-dichloro-4,4’-bipyridine
• 英文别名: 2,6-dichloro-4,4′-bipyridine；2,6-dichloro-4,4'-bipyridine；2,6-Dichloro-4,4'-bipyridine；2,6-dichloro-4-pyridin-4-ylpyridine
• CAS: 116273-61-1
• 化学式: C₁₀H₆Cl₂N₂
• 分子量: 225.077
• InChiKey: FLZJZVAEYWUCET-UHFFFAOYSA-N

物化性质

• 沸点：
  346.2±37.0 °C(Predicted)
• 密度：
  1.363±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  14
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  25.8
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  2,6-dichloro-4,4’-bipyridine 在 potassium tert-butylate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 0.33h， 生成 [Fe(4-pyridyl(2,6-bis(3-methylimidazol)pyridine))₂]*2PF₆
  参考文献：
  名称：

  Water‐Soluble Fe(II) Complexes for Theranostic Application: Synthesis, Photoacoustic Imaging, and Photothermal Conversion

  摘要：

  摘要 人们一直在努力开发可光激活的治疗剂，用于通过热消融对癌症进行局部图像引导治疗。在此背景下，铁复合物最近被确定为具有适当生物相容性和体内清除率的光激活治疗剂。本文报告了一系列含有多吡啶或 N-杂环碳化物的 FeII 复合物，这些复合物依靠合理的复合物工程，通过直接的方法实现了基于 MLCT 的激发态失活的红移。通过将光声学成像（PA）和光热疗法（PTT）中的跟踪结合起来，利用其 MLCT 在照射时的非辐射衰减达到治疗目的。本文讨论了结构修饰对复合物在生物相关水介质中的溶解度和稳定性的影响。探讨了复合物的设计、光声学对比度的产生和光热效率之间的关系，以开发定制的 PA/PTT 治疗剂。

  DOI：

  10.1002/ejic.202300138
• 作为产物：
  描述：

  4-碘吡啶 、 2,6-二氯吡啶-4-硼酸频哪醇酯 在 2-双环己基膦-2',6'-二甲氧基联苯 、 palladium diacetate 、 potassium carbonate 作用下， 以 四氢呋喃 、 水 为溶剂， 以58%的产率得到2,6-dichloro-4,4’-bipyridine
  参考文献：
  名称：

  贱金属铁(II)-钴(III)二元体的基本表征、光物理学和光催化

  摘要：

  通过杂配四 NHC 铁 (II) 光敏剂与 2,6-双[3-(2,6-二异丙基苯基)咪唑-2-亚基]吡啶的连接，获得了一种新的贱金属铁-钴二元体。 ,6-双(3-甲基-咪唑-2-亚基)-4,4'-联吡啶配体和钴肟催化剂。这种新型铁 (II)-钴 (III) 组装体已通过基态和激发态方法进行了广泛的表征，例如 X 射线晶体学、X 射线吸收光谱、（光谱）电化学以及稳态和时间分辨光学吸收光谱，特别关注溶液中分子组装的稳定性和激发态景观的测定。NMR 和 UV/Vis 光谱揭示了乙腈中浓度低于 1 mM 时二元体的解离和高光稳定性。激发到金属到配体电荷转移吸收带后的瞬态吸收光谱表明，弛豫级联源自热单线态和三线态 MLCT 态，导致3 MLCT 态的总体表现出最长的寿命。最后，衰变到基态涉及3 MC 态。将钴肟附着在铁光敏剂上可延长铁中心的3 MLCT 寿命。与连接体的定向效应一起，这可能使二元体在光催化质子还原实验中比由铁光敏剂和

  DOI：

  10.1002/chem.202100766
• 作为试剂：
  描述：

  1,3-dioxoisoindolin-2-yl 2,2-diphenylacetate 在 2,6-dichloro-4,4’-bipyridine 、 联硼酸频那醇酯 作用下， 以 甲基叔丁基醚 为溶剂， 反应 24.0h， 生成 1,1,2,2-四苯基乙烷
  参考文献：
  名称：

  吡嗪脱芳香二氢化的机理见解：自由基过程或非自由基过程？

  摘要：

  通过结合密度泛函理论（DFT）的计算和实验研究，研究了吡嗪脱芳香基二氢基化反应的机理。DFT计算表明，涉及两个连续的[3,3]-σ-重排型过程的非自由基机理是吡嗪与双（频哪醇）双硼（B 2 pin 2）的二氢甲酰化作用的原因。但是，这种非自由基方法对于空间受阻的吡嗪（2，3-二甲基吡嗪）的二硼基化反应非常不利。用于2,3-二甲基吡嗪与B 2销2的硼酸酯化反应在存在2,6-二氯-4,4'-联吡啶作为催化剂的情况下，优选通过B–B均质裂解/添加硼烷基进行4,4'-联吡啶介导的自由基途径。对照实验与动力学研究相结合，为拟议的机理提供了支持性证据。

  DOI：

  10.1039/d1dt00921d

文献信息

• [EN] AMINO-HETEROCYCLES AS VR-1 ANTAGONISTS FOR TREATING PAIN<br/>[FR] HETEROCYCLES AMINES EN TANT QU'ANTAGONISTES DU RECEPTEUR VANILLOIDE (VR-1) POUR LE TRAITEMENT DE LA DOULEUR
  申请人：MERCK SHARP & DOHME

  公开号：WO2004046133A1

  公开（公告）日：2004-06-03

  the present invention provides a compound of formula (I): wherein V represents NR5, O, S, SO or S(O)2; W and X each independently represent CH or N; Y represents N, CH or C-Ar2, with the proviso that at least one, but no more than two, of W, X and Y are N; Z represents CH or C-Ar2, with the proviso that when Y is N or CH then Z is C-Ar2, and with the further proviso that when Y is C-Ar2 then Z is CH; Ar1 represents a fused 9 or 10 membered heterobicyclic ring system containing one, two, three or four heteroatoms selected from nitrogen, oxygen and sulfur, wherein at least one of the rings in said ring system is aromatic; Ar2 represents an aromatic ring selected from phenyl, pyridyl, pyrimidinyl and pyridazinyl which is optionally fused and substituted; R1 represents halogen, hydroxy, oxo, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, haloC1-6alkyl, hydroxyC1-6alkyl, C1-6alkoxy, haloC1-6alkoxy, hydroxyC1-6alkoxy, C3-7cycloalkyl, C3-7cycloalkoxy, C3-5cycloalkylC1-4alkyl, cyano, nitro, SR6, SOR6, SO2R6, COR6, NR3COR6, CONR3R4, NR3SO2R6, SO2NR3R4, -(CH2)mcarboxy, esterified -(CH2)mcarboxy or -(CH2)mNR3R4; R2 represents hydrogen, halogen, hydroxy, C1-6alkyl, haloC1-6alkyl, C3-7cycloalkyl, C1-6alkoxy, haloC1-6alkoxy, unsubstituted phenyl or phenyl substituted with one or two groups selected from halogen, C1-6alkyl, haloC1-6alkyl, C3-7cycloalkyl, C1-6alkoxy or haloC1-6alkoxy; R3 and R4 are each independently hydrogen, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-7cycloalkyl or fluoroC1-6alkyl; or R3 and R4 and the nitrogen atom to which they are attached together form a heteroaliphatic ring of 4 to 7 ring atoms, optionally substituted by one or two groups selected from hydroxy or C1-4alkoxy, which ring may optionally contain as one of the said ring atoms an oxygen or a sulfur atom, S(O), S(O)2, or NR5; R5 represents hydrogen, C1-4alkyl, hydroxyC1-4alkyl or C1-4alkoxyC1-4alkyl; R6 represents hydrogen, C1-6alkyl, fluoroC1-6alkyl, C3-7cycloalkyl, unsubstituted phenyl, or phenyl substituted with one or two groups selected from halogen, C1-6alkyl, haloC1-6alkyl, C3-7cycloalkyl, C1-6alkoxy or haloC1-6alkoxy; m is either zero or an integer from 1 to 4; n is either zero or an integer from 1 to 3; or a pharmaceutically acceptable salt, N-oxide or a prodrug thereof; a pharmaceutical composition comprising it; its use in methods of treatment; use of it for the manufacture of a medicament for treating VR-1 related conditions such as those in which pain and/or inflammation predominate; and methods of treatment using it.

  本发明提供了一种具有以下结构的化合物（I）：其中V代表NR5、O、S、SO或S(O)2；W和X分别独立地代表CH或N；Y代表N、CH或C-Ar2，但至少有一个但不超过两个W、X和Y为N；Z代表CH或C-Ar2，但当Y为N或CH时，则Z为C-Ar2，并进一步规定当Y为C-Ar2时，Z为CH；Ar1代表包含一个、两个、三个或四个从氮、氧和硫中选择的杂原子的融合的9或10成员杂双环系统，其中所述环系中的至少一个环是芳香的；Ar2代表选择自苯基、吡啶基、嘧啶基和吡啶嗪基的芳香环，可以是可选地融合和取代的；R1代表卤素、羟基、氧、C1-6烷基、C2-6烯基、C2-6炔基、卤代C1-6烷基、羟基C1-6烷基、C1-6烷氧基、卤代C1-6烷氧基、羟基C1-6烷氧基、C3-7环烷基、C3-7环烷氧基、C3-5环烷基C1-4烷基、氰基、硝基、SR6、SOR6、SO2R6、COR6、NR3COR6、CONR3R4、NR3SO2R6、SO2NR3R4、-(CH2)m羧基、酯化的-(CH2)m羧基或-(CH2)mNR3R4；R2代表氢、卤素、羟基、C1-6烷基、卤代C1-6烷基、C3-7环烷基、C1-6烷氧基、卤代C1-6烷氧基、未取代的苯基或苯基，其上取代有一个或两个从卤素、C1-6烷基、卤代C1-6烷基、C3-7环烷基、C1-6烷氧基或卤代C1-6烷氧基中选择的基团；R3和R4各自独立地代表氢、C1-6烷基、C2-6烯基、C2-6炔基、C3-7环烷基或氟代C1-6烷基；或R3和R4和它们连接的氮原子共同形成一个由4到7个环原子组成的杂原烷环，可选地取代为一个或两个从羟基或C1-4烷氧基中选择的基团，该环可能可选地包含作为所述环原子之一的氧或硫原子、S(O)、S(O)2或NR5；R5代表氢、C1-4烷基、羟基C1-4烷基或C1-4烷氧基C1-4烷基；R6代表氢、C1-6烷基、氟代C1-6烷基、C3-7环烷基、未取代的苯基或苯基，其上取代有一个或两个从卤素、C1-6烷基、卤代C1-6烷基、C3-7环烷基、C1-6烷氧基或卤代C1-6烷氧基中选择的基团；m为零或从1到4的整数；n为零或从1到3的整数；或其药学上可接受的盐、N-氧化物或前药；包含它的药物组合物；其在治疗方法中的用途；用于制造用于治疗VR-1相关病症的药物，例如疼痛和/或炎症占优势的病症的用途；以及使用它的治疗方法。
• Organocatalytic Diboration Involving “Reductive Addition” of a Boron–Boron σ-Bond to 4,4′-Bipyridine
  作者：Toshimichi Ohmura、Yohei Morimasa、Michinori Suginome

  DOI：10.1021/jacs.5b00546

  日期：2015.3.4

  A 4,4'-bipyridine-based catalyst system for diboration of pyrazine derivatives was established. The catalyst cycle consists of the following two steps: (1) reductive addition of the boron-boron bond of bis(pinacolato)diboron to 4,4'-bipyridine to form N,N'-diboryl-4,4'-bipyridinylidene and (2) oxidative boryl transfer from the intermediate to pyrazine to give N,N'-diboryl-1,4-dihydropyrazine with regeneration

  建立了用于吡嗪衍生物二硼化的4,4'-联吡啶基催化剂体系。催化剂循环包括以下两个步骤：（1）双（频哪醇）二硼的硼-硼键还原加成到 4,4'-联吡啶形成 N,N'-二硼基-4,4'-联吡啶亚基和(2) 从中间体氧化硼基转移到吡嗪，得到 N,N'-二硼基-1,4-二氢吡嗪，再生 4,4'-联吡啶。
• Mechanism of 2,6-Dichloro-4,4′-bipyridine-Catalyzed Diboration of Pyrazines Involving a Bipyridine-Stabilized Boryl Radical
  作者：Toshimichi Ohmura、Yohei Morimasa、Tomoya Ichino、Yusuke Miyake、Yasujiro Murata、Michinori Suginome、Kunihiko Tajima、Tetsuya Taketsugu、Satoshi Maeda

  DOI：10.1246/bcsj.20210145

  日期：2021.7.15

  pyrazines was studied by experimental observation of the intermediates and by theoretical calculations. Intermediary radical species were detected by ESR measurement of the reactions of 2,6-dichloro-4,4'-bipyridines with bis(pinacolato)diboron and identified by simulation. Based on these observations, radical processes involving 4,4’-bipyridine-stabilized boryl radicals were evaluated by DFT calculations

  通过中间体的实验观察和理论计算，研究了4,4'-联吡啶催化吡嗪二硼化反应的机理。通过 2,6-二氯-4,4'-联吡啶与双（频哪醇）二硼反应的 ESR 测量检测中间自由基物种，并通过模拟进行鉴定。基于这些观察结果，通过 DFT 计算结合单组分人工力诱导反应 (SC-AFIR) 评估了涉及 4,4'-联吡啶稳定的硼基自由基的自由基过程。计算结果表明，从 4,4'-联吡啶稳定的硼基自由基到吡嗪的自由基转移过程是催化反应的主要途径。2,6-二氯-4,4'催化效率高的由来N , N' -diboryl-4,4'-bipyridinylidene。
• Amino-heterocycles as vr-1 antagonists for treating pain
  申请人：Blurton Peter

  公开号：US20060040947A1

  公开（公告）日：2006-02-23

  the present invention provides a compound of formula (I): wherein V represents NR 5 , O, S, SO or S(O) 2 ; W and X each independently represent CH or N; Y represents N, CH or C—Ar 2 , with the proviso that at least one, but no more than two, of W, X and Y are N; Z represents CH or C—Ar 2 , with the proviso that when Y is N or CH then Z is C—Ar 2 , and with the further proviso that when Y is C—Ar 2 then Z is CH; Ar 1 represents a fused 9 or 10 membered heterobicyclic ring system containing one, two, three or four heteroatoms selected from nitrogen, oxygen and sulfur, wherein at least one of the rings in said ring system is aromatic; Ar 2 represents an aromatic ring selected from phenyl, pyridyl, pyrimidinyl and pyridazinyl which is optionally fused and substituted; R 1 represents halogen, hydroxy, oxo, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, haloC 1-6 alkyl, hydroxyC 1-6 alkyl, C 1-6 alkoxy, haloC 1-6 alkoxy, hydroxyC 1-6 alkoxy, C 3-7 cycloalkyl, C 3-7 cycloalkoxy, C 3-5 cycloalkylC 1-4 alkyl, cyano, nitro, SR 6 , SOR 6 , SO 2 R 6 , COR 6 , NR 3 COR 6 , CONR 3 R 4 , NR 3 SO 2 R 6 , SO 2 NR 3 R 4 , —(CH 2 ) m carboxy, esterified —(CH 2 ) m carboxy or —(CH 2 ) m NR 3 R 4 ; R 2 represents hydrogen, halogen, hydroxy, C 1-6 alkyl, haloC 1-6 alkyl, C 3-7 cycloalkyl, C 1-6 alkoxy, haloC 1-6 alkoxy, unsubstituted phenyl or phenyl substituted with one or two groups selected from halogen, C 1-6 alkyl, haloC 1-6 alkyl, C 3-7 cycloalkyl, C 1-6 alkoxy or haloC 1-6 alkoxy; R 3 and R 4 are each independently hydrogen, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-7 cycloalkyl or fluoroC 1-6 alkyl; or R 3 and R 4 and the nitrogen atom to which they are attached together form a heteroaliphatic ring of 4 to 7 ring atoms, optionally substituted by one or two groups selected from hydroxy or C 1-4 alkoxy, which ring may optionally contain as one of the said ring atoms an oxygen or a sulfur atom, S(O), S(O) 2 , or NR 5 ; R 5 represents hydrogen, C 1-4 alkyl, hydroxyC 1-4 alkyl or C 1-4 alkoxyC 1-4 alkyl; R 6 represents hydrogen, C 1-6 alkyl, fluoroC 1-6 alkyl, C 3-7 cycloalkyl, unsubstituted phenyl, or phenyl substituted with one or two groups selected from halogen, C 1-6 alkyl, haloC 1-6 alkyl, C 3-7 cycloalkyl, C 1-6 alkoxy or haloC 1-6 alkoxy; m is either zero or an integer from 1 to 4; n is either zero or an integer from 1 to 3; or a pharmaceutically acceptable salt, N-oxide or a prodrug thereof; a pharmaceutical composition comprising it; its use in methods of treatment; use of it for the manufacture of a medicament for treating VR-1 related conditions such as those in which pain and/or inflammation predominate; and methods of treatment using it.

  本发明提供了一种化合物，其化学式为（I）：其中V代表NR5、O、S、SO或S（O）2；W和X各自独立地代表CH或N；Y代表N、CH或C-Ar2，但至少有一个，但不超过两个，W、X和Y是N；Z代表CH或C-Ar2，但当Y为N或CH时，Z为C-Ar2，且进一步规定当Y为C-Ar2时，Z为CH；Ar1代表一个融合的9或10个成员的杂双环环系统，其中包含从氮、氧和硫中选择的一个、两个、三个或四个杂原子，其中至少一个环为芳香环；Ar2代表一种芳香环，选择自苯基、吡啶基、嘧啶基和吡啶嗪基，可选地融合和取代；R1代表卤素、羟基、氧代、C1-6烷基、C2-6烯基、C2-6炔基、卤代C1-6烷基、羟基C1-6烷基、C1-6烷氧基、卤代C1-6烷氧基、羟基C1-6烷氧基、C3-7环烷基、C3-7环烷氧基、C3-5环烷基C1-4烷基、氰基、硝基、SR6、SOR6、SO2R6、COR6、NR3COR6、CONR3R4、NR3SO2R6、SO2NR3R4、-(CH2)m羧基、酯化的-(CH2)m羧基或-(CH2)mNR3R4；R2代表氢、卤素、羟基、C1-6烷基、卤代C1-6烷基、C3-7环烷基、C1-6烷氧基、卤代C1-6烷氧基、未取代苯基或取代一个或两个群的苯基，所述群从卤素、C1-6烷基、卤代C1-6烷基、C3-7环烷基、C1-6烷氧基或卤代C1-6烷氧基中选择；R3和R4各自独立地代表氢、C1-6烷基、C2-6烯基、C2-6炔基、C3-7环烷基或氟代C1-6烷基；或R3和R4及它们所连接的氮原子一起形成4至7个环原子的杂脂环，可选地取代一个或两个群，所述群从羟基或C1-4烷氧基中选择，该环可以选择地包含一个氧原子或硫原子、S（O）、S（O）2或NR5作为其中一个所述环原子；R5代表氢、C1-4烷基、羟基C1-4烷基或C1-4烷氧基C1-4烷基；R6代表氢、C1-6烷基、氟代C1-6烷基、C3-7环烷基、未取代苯基或取代一个或两个群的苯基，所述群从卤素、C1-6烷基、卤代C1-6烷基、C3-7环烷基、C1-6烷氧基或卤代C1-6烷氧基中选择；m为零或1至4的整数；n为零或1至3的整数；或其药学上可接受的盐、N-氧化物或前药；包含它的制药组合物；它在治疗方法中的用途；用于制造治疗VR-1相关疾病的药物，例如疼痛和/或炎症占主导地位的疾病；以及使用它的治疗方法。
• Synthesis of Non‐centrosymmetric Dipolar 4,4′‐Bipyridines: Potential Molecular Tectons for Programmed Assembly of Supramolecular Systems
  作者：Hannes Kühner、Louis Leyen、Zahid Hassan、Christof Wöll、Stefan Bräse

  DOI：10.1002/cplu.202200425

  日期：2023.1

  Non-centrosymmetric Molecular Tectons: Modular synthesis of a new series of non-centrosymmetric dipolar 4,4′-bipyridines bearing 2,6- and 3,5-functionalized pyridyl moieties at the peripheries is described. Selective substitution on one pyridyl motif that could contain electron-donating or electron-withdrawing groups causes electronic/steric effects on the nitrogen atoms in 4,4′-bipyridines, paving

  非中心对称分子构造：描述了在外围带有 2,6- 和 3,5- 功能化吡啶基部分的一系列新的非中心对称偶极 4,4'-联吡啶的模块化合成。对一个可能包含给电子或吸电子基团的吡啶基基序的选择性取代对 4,4'-联吡啶中的氮原子产生电子/空间效应，为实现非中心对称超分子组装铺平了道路