2-(3,5-bistrifluoromethylphenyl)-benzooxazole

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 2-(3,5-bistrifluoromethylphenyl)-benzooxazole
• 英文别名: 2-(3,5-bis(trifluoromethyl)phenyl)benzoxazole；2-(3,5-Bis(trifluoromethyl)phenyl)benzo[d]oxazole；2-[3,5-bis(trifluoromethyl)phenyl]-1,3-benzoxazole
• 化学式: C₁₅H₇F₆NO
• 分子量: 331.217
• InChiKey: ZMOKBCBOFJKYGK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.2
• 重原子数：
  23
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.13
• 拓扑面积：
  26
• 氢给体数：
  0
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  N-(2-hydroxyphenyl)-3,5-bistrifluoromethylbenzamide 在 对甲苯磺酸 作用下， 以 xylene 为溶剂， 反应 4.0h， 以201 mg的产率得到2-(3,5-bistrifluoromethylphenyl)-benzooxazole
  参考文献：
  名称：

  Biochemical and Structural Evaluation of Highly Selective 2-Arylbenzoxazole-Based Transthyretin Amyloidogenesis Inhibitors

  摘要：

  To develop potent transthyretin (TTR) amyloidogenesis inhibitors that also display high binding selectivity in blood, it proves useful to systematically optimize each of the three substructural elements that comprise a typical inhibitor: the two aryl rings and the linker joining them. In the first study, described herein, structural modifications to one aryl ring were evaluated by screening a library of 2-arylbenzoxazoles bearing thyroid hormone-like aryl substituents on the 2-aryl ring. Several potent and highly selective amyloidogenesis inhibitors were identified that exhibit minimal thyroid hormone nuclear receptor and COX-1 binding. High resolution crystal structures (1.3-1.5 angstrom) of three inhibitors (2f, 4f, and 4d) in complex with TTR were obtained to characterize their binding orientation. Collectively, the results demonstrate that thyroid hormone-like substitution patterns on one aryl ring lead to potent and highly selective TTR amyloidogenesis inhibitors that lack undesirable thyroid hormone receptor or COX-1 binding.

  DOI：

  10.1021/jm0708735

文献信息

• Carbonates: eco-friendly solvents for palladium-catalysed direct arylation of heteroaromatics
  作者：Jia Jia Dong、Julien Roger、Cécile Verrier、Thibaut Martin、Ronan Le Goff、Christophe Hoarau、Henri Doucet

  DOI：10.1039/c0gc00229a

  日期：——

  The palladium-catalysed direct 2-, 4- or 5-arylation of a wide range of heteroaromatics with aryl halides proceed in moderate to good yields using the eco-friendly solvents carbonates. The best yields were obtained using benzoxazole or thiazole derivatives. The arylation of furan, thiophene, pyrrole, imidazole or isoxazole derivatives was found to require a more elevated reaction temperature.

  这 钯环保型芳烃卤化物催化的各种杂芳族化合物与芳基卤化物的直接2-，4-或5-芳基化反应均能以中等至良好的收率进行 溶剂碳酸盐。使用以下方法可获得最佳产量苯并恶唑 或者 噻唑衍生品。这芳基化 的 呋喃， 噻吩， 吡咯， 咪唑 或者 异恶唑 发现衍生物需要更高的反应温度。
• Unsymmetrical Pincer <i>N</i>-Heterocyclic Carbene–Nitrogen–Phosphine Chelated Palladium(II) Complexes: Synthesis, Structure, and Reactivity in Direct Csp²–H Arylation of Benzoxazoles
  作者：Yaqiu Li、Xiaojun Yu、Yangdiandian Wang、Haiyan Fu、Xueli Zheng、Hua Chen、Ruixiang Li

  DOI：10.1021/acs.organomet.8b00005

  日期：2018.3.26

  unsymmetrical pincer N-heterocyclic carbene–nitrogen–phosphine (CNP) and its palladium complexes PdCl2(κ2-CP) (4) and [PdCl(κ3-CNP)]PF6 (5·PF6) were synthesized. NMR spectra disclosed that the transformation of complex 4 structure occurred in the solution. Further NMR experimental and single crystal structure analysis of complex 4 provided unequivocal and structural evidence for the formation of complex [PdCl(κ3-CNP)]Cl

  不对称钳形ñ -杂环卡宾-氮-膦（CNP）和它的钯络合物的PdCl 2（κ 2 -CP）（4）和[的PdCl（κ 3 -CNP）] PF 6（5·PF 6）的合成。NMR光谱揭示在溶液中发生了复合物4结构的转变。此外NMR实验和复杂的单晶结构分析4为复合物的形成提供明确和结构证据[的PdCl（κ 3 -CNP）] Cl（上5·氯）在复杂的解决方案4。钯配合物的催化性能通过苯并恶唑与芳基溴化物的直接Csp 2 -H芳基化研究了4和5·PF 6。值得注意的是，在0.5％的络合物4的存在下，芳基溴化物最多可提供97％的芳基化产物。对于邻位取代的底物，位阻具有显着影响，但可通过延长反应时间显着提高产物收率。该结果表明该体系中的催化活性物质是稳定的，并保持较长的寿命。灵活的主干和N侧面的不对称钳形结构-杂环卡宾应该是实现有效催化转化的可行策略。这种简单的催化剂系统首先实现了芳基溴化物的直接芳基化，其催化剂负载量低至0
• Investigation of Pd‐PEPPSI catalysts and coupling partners towards direct C2‐arylation/heteroarylation of benzoxazole
  作者：Anusha Gokanapalli、Venkata Krishna Reddy Motakatla、Vasu Govardhana Reddy Peddiahgari

  DOI：10.1002/aoc.6296

  日期：2021.8

  partners like aryl/heteroaryl halide/carboxylic acid/diazonium tetrafluoroborate/sulfonyl chloride/boronic acids in the presence of different symmetrical and unsymmetrical Pd-PEPPSI (pyridine-enhanced pre-catalyst preparation by stabilization initiation) catalysts via C (sp2)–C (sp2) bond formation. Compared with other coupling partners, boronic acids coupled with benzoxazole very efficiently in the presence

  2-芳基/杂芳基取代的苯并恶唑是重要的杂环基序，广泛存在于多种生物活性分子、药物和天然产物中。鉴于这些化合物的重要性，需要开发最简单、最简单的合成路线。目前这项工作的动机是在不同对称和不对称 Pd-存在下，对苯并恶唑与各种交叉偶联伙伴（如芳基/杂芳基卤化物/羧酸/四氟硼酸重氮/磺酰氯/硼酸）进行直接的 C2-芳基化反应。 PEPPSI（通过稳定引发的吡啶增强预催化剂制备）催化剂通过 C (sp 2 )–C (sp 2) 键的形成。与其他偶联伙伴相比，硼酸与苯并恶唑在露天和电子可调的大体积 1,3-双（N,N' -2,4,6-三异丙基苄基）苯并咪唑鎓-Pd-PEPPSI 络合物的存在下非常有效地偶联到提供相应的 C2-芳基/杂芳基苯并恶唑化合物。此外，值得一提的是，无需任何外部氧化剂/配体/添加剂即可将起始分子完全转化为产物。反应在广泛的底物范围内成功进行，并在乙醇/水 (1:1) 介质中的
• Direct arylation of oxazole and benzoxazole with aryl or heteroaryl halides using a palladium–diphosphine catalyst
  作者：Fazia Derridj、Safia Djebbar、Ouassini Benali-Baitich、Henri Doucet

  DOI：10.1016/j.jorganchem.2007.10.028

  日期：2008.1

  Through the use of PdCl(dppb)(C3H5) as a catalyst, a range of aryl bromides and chlorides undergoes coupling via C-H bond activation/flunctionalization reaction with oxazole or benzoxazole in good yields. This air-stable catalyst can be used at low loadings with several substrates. Surprisingly, better results in terms of substrate/catalyst ratio were obtained in several cases using electron-excessive aryl bromides than with the electron-deficient ones. This seems to be mainly due to the relatively low thermal stability of some of the 2-arylbenzoxazoles formed with electron -deficient aryl halides. With these substrates, in order to obtain higher yields of product, the reactions had to be performed at a lower temperature (100-120 degrees C) using a larger amount of catalyst. On the other hand, in the presence of the most stable products, the reactions were performed at 150 degrees C using as little as 0.2 mol% catalyst. Arylation of benzoxazole with heteroaryl bromides also gave the coupling products in moderate to high yields using 0.2-5 mol% catalyst. With this catalyst, electron-deficient aryl chloride such as 4-chlorobenzonitrile, 4-chloroacetophenone or 2-chloronitrobenzene have also been used successfully. (c) 2007 Elsevier B.V. All rights reserved.
• Biochemical and Structural Evaluation of Highly Selective 2-Arylbenzoxazole-Based Transthyretin Amyloidogenesis Inhibitors
  作者：Steven M. Johnson、Stephen Connelly、Ian A. Wilson、Jeffery W. Kelly

  DOI：10.1021/jm0708735

  日期：2008.1.1

  To develop potent transthyretin (TTR) amyloidogenesis inhibitors that also display high binding selectivity in blood, it proves useful to systematically optimize each of the three substructural elements that comprise a typical inhibitor: the two aryl rings and the linker joining them. In the first study, described herein, structural modifications to one aryl ring were evaluated by screening a library of 2-arylbenzoxazoles bearing thyroid hormone-like aryl substituents on the 2-aryl ring. Several potent and highly selective amyloidogenesis inhibitors were identified that exhibit minimal thyroid hormone nuclear receptor and COX-1 binding. High resolution crystal structures (1.3-1.5 angstrom) of three inhibitors (2f, 4f, and 4d) in complex with TTR were obtained to characterize their binding orientation. Collectively, the results demonstrate that thyroid hormone-like substitution patterns on one aryl ring lead to potent and highly selective TTR amyloidogenesis inhibitors that lack undesirable thyroid hormone receptor or COX-1 binding.