tert-butyl 2,3,4,5,6-pentafluorobenzoate | 98040-93-8

• 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: tert-butyl 2,3,4,5,6-pentafluorobenzoate
• 英文别名: Benzoic acid, pentafluoro-, 1,1-dimethylethyl ester
• CAS: 98040-93-8
• 化学式: C₁₁H₉F₅O₂
• mdl: MFCD05988135
• 分子量: 268.183
• InChiKey: MWMSVYICOCCEKL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  18
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.363
• 拓扑面积：
  26.3
• 氢给体数：
  0
• 氢受体数：
  7

安全信息

• 危险性防范说明：
  P261,P264,P270,P271,P280,P301+P312,P302+P352,P304+P340,P305+P351+P338,P330,P332+P313,P337+P313,P362,P403+P233,P405,P501
• 危险性描述：
  H302,H315,H319,H335

反应信息

• 作为反应物：
  描述：

  tert-butyl 2,3,4,5,6-pentafluorobenzoate 在 4-二甲氨基吡啶 、 三乙胺 、 三氟乙酸 、 sodium iodide 作用下， 以 二氯甲烷 、 N,N-二甲基乙酰胺 、 丙酮 为溶剂， 反应 84.67h， 生成 4-[Bis-(2-iodo-ethyl)-amino]-2,3,5,6-tetrafluoro-benzoic acid
  参考文献：
  名称：

  Novel Fluorinated Prodrugs for Activation by Carboxypeptidase G2 Showing Good in Vivo Antitumor Activity in Gene-Directed Enzyme Prodrug Therapy

  摘要：

  Sixteen novel polyfluorinated benzoic acid mustards have been synthesized for use in gene-directed enzyme prodrug therapy (GDEPT). Eight of these were benzoic acid L-glutamate mustards for evaluation as prodrugs and the other eight were the active drugs formed by the action of the bacterial enzyme carboxypeptidase G2 (CPG2). All of the di- and trifluorinated prodrugs were efficiently cleaved by the enzyme. In contrast, the tetrafluorinated prodrugs were found to be competitive inhibitors of CPG2, the first such inhibitors to have been described. The di- and trifluorinated prodrugs were differentially cytotoxic to human breast carcinoma cells (MDA MB 361) expressing CPG2, compared to control cells that did not express the enzyme. The difluorinated prodrug {4-[bis(2-bromoethyl)amino]-3,5-difluorobenzoyl}-L-glutamic acid and its iodoethylamino analogue were effective substrates for the enzyme and showed excellent therapeutic activity in CPG2-expressing MDA MB 361 xenografts, either curing or greatly inhibiting tumor growth and extending the life of the animals.

  DOI：

  10.1021/jm0502182
• 作为产物：
  描述：

  五氟苯甲酰氯 、 lithium tert-butoxide 以 四氢呋喃 为溶剂， 反应 1.75h， 以68%的产率得到tert-butyl 2,3,4,5,6-pentafluorobenzoate
  参考文献：
  名称：

  铜催化烯烃与多氟芳烃的加氢脱氢。

  摘要：

  开发了在dppbz连接的Cu催化剂和硅烷存在下，烯烃与多氟芳烃的催化脱氟加氢芳基化反应。该方法为合成重要的多氟代芳烃提供了一种简单易行的替代途径，该芳烃具有容易获得且稳定的烯烃作为潜在亲核试剂，因此避免了传统上对化学计量数量的有机金属试剂的依赖。该反应在非常温和的条件下进行，并且表现出良好的官能团相容性和高水平的区域选择性。这种方法的合成潜力通过克级合成得到了进一步证明，并且还进行了一系列实验研究以阐明可能的机理。

  DOI：

  10.1002/anie.202010492

文献信息

• Photocatalytic Hydrodefluorination: Facile Access to Partially Fluorinated Aromatics
  作者：Sameera M. Senaweera、Anuradha Singh、Jimmie D. Weaver

  DOI：10.1021/ja500031m

  日期：2014.2.26

  science as well as the pharmaceutical and agrochemical industries and yet are often difficult to access. This Communication describes a photocatalytic hydrodefluorination approach which begins with easily accessible perfluoroarenes and selectively reduces the C-F bonds. The method allows facile access to a number of partially fluorinated arenes and takes place with unprecedented catalytic activity

  多氟芳烃对于材料科学以及制药和农业化学工业至关重要，但通常很难获得。该通讯描述了一种光催化加氢脱氟方法，该方法从容易获得的全氟芳烃开始并选择性地减少 CF 键。该方法可以轻松获得许多部分氟化的芳烃，并且使用安全且廉价的胺作为还原剂以前所未有的催化活性发生。
• Catalyst-Free Hydrodefluorination of Perfluoroarenes with NaBH₄
  作者：Timothy D. Schoch、Mukulesh Mondal、Jimmie D. Weaver

  DOI：10.1021/acs.orglett.0c04305

  日期：2021.3.5

  Presented is an economical means of removing fluorine from various highly fluorinated arenes using NaBH4. The procedure was adapted for different classes of perfluoroarenes. A novel isomer of an emerging class of organic dyes based on the carbazole phthalonitrile motif was succinctly synthesized in two steps from tetrafluorophthalonitrile, demonstrating the utility of the hydrodefluorination procedure

  提出了一种使用 NaBH 4从各种高度氟化的芳烃中去除氟的经济方法。该程序适用于不同类别的全氟芳烃。一种基于咔唑邻苯二甲腈基序的新兴有机染料的新型异构体由四氟邻苯二甲腈分两步合成，证明了加氢脱氟过程的实用性。对该染料的初步探索表明它具有光活性，并且能够促进逆热力学苯乙烯类E / Z异构化。
• Dual C–F, C–H Functionalization via Photocatalysis: Access to Multifluorinated Biaryls
  作者：Sameera Senaweera、Jimmie D. Weaver

  DOI：10.1021/jacs.5b13450

  日期：2016.3.2

  An alternative approach to selective fluorination of biaryls is to couple an arene that already possesses C-F bonds in the desired location. This strategy has been regularly utilized and relies heavily on traditional cross-coupling strategies that employ organometallics and halides (or pseudohalides) in order to achieve the coupling. Herein we report conditions for the photocatalytic coupling via

  多氟化联芳基化合物的合成具有挑战性，但仍是一类重要的分子。由于与选择性氟化相关的困难，这类分子代表了一项艰巨的合成挑战。选择性氟化联芳基的另一种方法是在所需位置偶联已经具有 CF 键的芳烃。该策略已被经常使用，并且在很大程度上依赖于采用有机金属和卤化物（或伪卤化物）以实现耦合的传统交叉耦合策略。在此，我们报告了通过全氟芳烃的 CF 键和其他芳烃的 CH 键的直接官能化进行光催化偶联的条件，以提供获得多氟化联芳基化合物的便捷途径。温和的条件和良好的官能团耐受性使范围广泛，包括获得碱性杂环的反 Minisci 产物。最后，我们通过光催化和 SNAr 化学的协同使用，利用高氟含量系统地构建包含 2 到 5 个 Cyl-F 键的复杂联芳基，证明了 CF 功能化方法的价值。
• CF Activation in Perfluorinated Arenes with Isonitriles under UV-Light Irradiation
  作者：Abhishek Dewanji、Christian Mück-Lichtenfeld、Klaus Bergander、Constantin G. Daniliuc、Armido Studer

  DOI：10.1002/chem.201502298

  日期：2015.8.24

  materials science, development of methods for preparation of fluorinated arenes is of high importance. They can be either accessed by arene fluorination or by partial arene defluorination. However, the carbonfluorine bond belongs to the strongest σ‐bonds, which renders CF activation highly challenging. Here it is shown that aryl and alkyl isonitriles efficiently activate the strong CF bond in perfluoroarenes

  由于氟化芳烃在农业化学，药物化学和材料科学中的巨大价值，开发氟化芳烃的方法的开发非常重要。它们可以通过芳烃氟化或部分芳烃脱氟来获得。但是，碳氟键属于最强的σ键，这使CF活化极具挑战性。此处表明，在温和的条件下，通过简单的紫外线照射，芳基和烷基异腈可以有效地活化全氟芳烃中的强CF键。反应是通过将异腈正式直接插入CF键而没有任何过渡金属而进行的。活化发生在芳烃CF键上，而脂肪族CF债券仍未反应。对于选定的全氟芳烃，CF活化具有很高的区域选择性，所得的亚氨基酰氟被转化为其他有价值的化合物。理论研究为反应机理提供了见识。
• Transition-Metal-Free Catalytic Hydrodefluorination of Polyfluoroarenes by Concerted Nucleophilic Aromatic Substitution with a Hydrosilicate
  作者：Kotaro Kikushima、Mary Grellier、Masato Ohashi、Sensuke Ogoshi

  DOI：10.1002/anie.201708003

  日期：2017.12.18

  A transition‐metal‐free catalytic hydrodefluorination (HDF) reaction of polyfluoroarenes is described. The reaction involves direct hydride transfer from a hydrosilicate as the key intermediate, which is generated from a hydrosilane and a fluoride salt. The eliminated fluoride regenerates the hydrosilicate to complete the catalytic cycle. Dispersion‐corrected DFT calculations indicated that the HDF

  描述了多氟芳烃的无过渡金属催化加氢脱氟（HDF）反应。该反应涉及从氢硅酸盐作为主要中间体的氢化物直接转移，这是由氢硅烷和氟化物盐生成的。除去的氟化物使氢硅酸盐再生，从而完成催化循环。分散校正的DFT计算表明HDF反应通过协调的亲核芳族取代（CS N Ar）过程进行。