4-tetradecylbenzonitrile | 479412-23-2

• 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: 4-tetradecylbenzonitrile
• 英文别名: 4-Tetradecylbenzonitrile
• CAS: 479412-23-2
• 化学式: C₂₁H₃₃N
• 分子量: 299.5
• InChiKey: YGSFYXAKKASFAL-UHFFFAOYSA-N

物化性质

• 沸点：
  417.4±24.0 °C(Predicted)
• 密度：
  0.91±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  8.7
• 重原子数：
  22
• 可旋转键数：
  13
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  23.8
• 氢给体数：
  0
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  4-tetradecylbenzonitrile 在 盐酸 、 6-chloro-3-((dimethylamino)(dimethyliminio)methyl)-1H-benzo[d][1,2,3]triazol-3-ium-1-olatehexafluorophosphate(V) 、 盐酸羟胺 、 三乙胺 、 N,N-二异丙基乙胺 作用下， 以 甲醇 、 乙醇 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 96.0h， 生成 (S)-tert-butyl (((tert-butoxycarbonyl)amino)(2-(3-(4-tetradecylphenyl)-1,2,4-oxadiazol-5-yl)pyrrolidin-1-yl)methylene)carbamate
  参考文献：
  名称：

  Structure–activity relationship studies of the lipophilic tail region of sphingosine kinase 2 inhibitors

  摘要：

  Sphingosine-1-phosphate (S1P) is a ubiquitous, endogenous small molecule that is synthesized by two isoforms of sphingosine kinase (SphK1 and 2). Intervention of the S1P signaling pathway has attracted significant attention because alteration of S1P levels is linked to several disease states including cancer, fibrosis, and sickle cell disease. While intense investigations have focused on developing SphK1 inhibitors, only a limited number of SphK2-selective agents have been reported. Herein, we report our investigations on the structure-activity relationship studies of the lipophilic tail region of SLR080811, a SphK2-selective inhibitor. Our studies demonstrate that the internal phenyl ring is a key structural feature that is essential in the SLR080811 scaffold. Further, we show the dependence of SphK2 activity and selectivity on alkyl tail length, suggesting a larger lipid binding pocket in SphK2 compared to SphK1. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2015.03.041
• 作为产物：
  描述：

  1-十四烯 在 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride 、 caesium carbonate 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 30.0h， 生成 4-tetradecylbenzonitrile
  参考文献：
  名称：

  Structure–activity relationship studies of the lipophilic tail region of sphingosine kinase 2 inhibitors

  摘要：

  Sphingosine-1-phosphate (S1P) is a ubiquitous, endogenous small molecule that is synthesized by two isoforms of sphingosine kinase (SphK1 and 2). Intervention of the S1P signaling pathway has attracted significant attention because alteration of S1P levels is linked to several disease states including cancer, fibrosis, and sickle cell disease. While intense investigations have focused on developing SphK1 inhibitors, only a limited number of SphK2-selective agents have been reported. Herein, we report our investigations on the structure-activity relationship studies of the lipophilic tail region of SLR080811, a SphK2-selective inhibitor. Our studies demonstrate that the internal phenyl ring is a key structural feature that is essential in the SLR080811 scaffold. Further, we show the dependence of SphK2 activity and selectivity on alkyl tail length, suggesting a larger lipid binding pocket in SphK2 compared to SphK1. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2015.03.041

文献信息

• Iron-Catalyzed Cross-Coupling Reactions
  作者：Alois Fürstner、Andreas Leitner、María Méndez、Helga Krause

  DOI：10.1021/ja027190t

  日期：2002.11.1

  and -CF(3) groups are compatible. The method also allows for consecutive cross-coupling processes in one pot, as exemplified by the efficient preparation of compound 12, and has been applied to the first synthesis of the cytotoxic marine natural product montipyridine 8. In contrast to the clean reaction of (hetero)aryl chlorides, the corresponding bromides and iodides are prone to a reduction of their

  简单的铁盐，如 FeCl(n)、Fe(acac)(n) (n = 2,3) 或 salen 络合物 4 被证明是高效、廉价、毒理学无害且环境友好的预催化剂，可用于许多交叉- 烷基或芳基格氏试剂、锌酸盐或有机锰物质与芳基和杂芳基氯化物、三氟甲磺酸盐甚至甲苯磺酸盐的偶联反应。原位制备的正式成分 [Fe(MgX)(2)] 的“无机格氏试剂”可能构成负责催化周转的传播物种，在许多情况下，即使在室温或室温以下，这种转化率也以前所未有的速度发生。由于反应条件异常温和，一系列官能团如酯、醚、腈、磺酸盐、磺酰胺、硫醚、缩醛、炔烃和 -CF(3) 基团是相容的。
• Cyclic ureas (DMI, DMPU) as efficient, sustainable ligands in iron-catalyzed C(sp²)–C(sp³) coupling of aryl chlorides and tosylates
  作者：Elwira Bisz、Michal Szostak

  DOI：10.1039/c7gc02690k

  日期：——

  Iron-catalyzed cross-coupling has emerged as a powerful tool for sustainable catalysis. However, by far the most common ligand in iron-catalyzed cross-couplings for preparative and industrial applications is reprotoxic NMP. Herein, we report that cyclic ureas (DMI, DMPU) are efficient and sustainable alternatives to NMP in iron-catalyzed alkylations of aryl chlorides and tosylates with alkyl Grignard

  铁催化的交叉偶联已经成为可持续催化的有力工具。然而，到目前为止，用于制备和工业应用的铁催化交叉偶联中最常见的配体是具有生殖毒性的NMP。在这里，我们报道在铁催化的芳基氯化物烷基化和甲苯磺酸与烷基格氏试剂的烷基化反应中，环状脲（DMI，DMPU）是NMP的有效和可持续替代品。这种对环境无害的方法可以完成传统上具有挑战性的C（sp2）–C（sp3）与具有β氢的有机金属的交叉偶联，其效率与NMP相当或更高。该反应与各种亲电功能手柄兼容。描述了双重和位点特异性烷基化的应用。双重NK1 / 5-羟色胺受体拮抗剂的合成中的关键偶联突出了该方法的潜力。考虑到可持续铁催化的关键重要性，我们认为该方法将在绿色化学中得到广泛应用。
• <i>N</i> -Methylcaprolactam as a Dipolar Aprotic Solvent for Iron-Catalyzed Cross-Coupling Reactions: Matching Efficiency with Safer Reaction Media
  作者：Elwira Bisz、Pamela Podchorodecka、Michal Szostak

  DOI：10.1002/cctc.201802032

  日期：2019.2.20

  to the more conventional palladium and nickel in the cross‐coupling arena, the major limitation is the necessity for carcinogenic N‐methylpyrrolidone as a co‐solvent in the vast majority of catalytic reactions. Herein, we introduce N‐methylcaprolactam as an efficient, non‐toxic and practical dipolar aprotic solvent for iron‐catalyzed C(sp2)−C(sp3) alkylative cross‐coupling of aryl chlorides and tosylates

  尽管在交叉偶联领域，铁催化提供了更常规的钯和镍的强大替代品，但主要的局限性是在大多数催化反应中必须使用致癌的N-甲基吡咯烷酮作为助溶剂。在此，我们介绍N-甲基己内酰胺作为一种有效，无毒且实用的偶极非质子溶剂，用于铁催化芳基氯和甲苯磺酸酯的C（sp 2）-C（sp 3）烷基化交叉偶联。该方法的实用性体现在其广泛的底物范围，高收率和能够交叉偶联易被b-氢化物消除和均偶联的具有挑战性的烷基有机金属的能力。考虑到铁催化交叉偶联的广泛用途，我们设想N-甲基己内酰胺将广泛用作致癌性NMP的替代品。
• Iron-catalyzed C(sp²)–C(sp³) cross-coupling at low catalyst loading
  作者：Elwira Bisz、Marlena Kardela、Aleksandra Piontek、Michal Szostak

  DOI：10.1039/c8cy02374c

  日期：——

  The iron-catalyzed C(sp2)–C(sp3) cross-coupling provides a highly economical route to exceedingly valuable alkylated arenes that are widespread in medicinal chemistry and materials science. Herein, we report an operationally-simple protocol for the selective C(sp2)–C(sp3) iron-catalyzed cross-coupling of aryl chlorides with Grignard reagents at low catalyst loading. A broad range of electronically-varied

  铁催化的C（sp 2）–C（sp 3）交叉偶联为在医药化学和材料科学中广泛使用的极有价值的烷基化芳烃提供了一种非常经济的途径。在这里，我们报告选择性C（sp 2）–C（sp 3）在低催化剂负载下铁催化的芳基氯化物与格氏试剂的交叉偶联。使用具有挑战性的具有β氢的烷基有机金属化合物，以高达2000 TON的高效率对多种电子可变的芳基氯化物和杂芳基氯化物进行交叉偶联。该方案的显着特征是使用了环境友好的环状脲配体。提供了一系列指导芳基亲电试剂的交叉偶联反应性的指南。
• 2-Methyltetrahydrofuran: A Green Solvent for Iron-Catalyzed Cross-Coupling Reactions
  作者：Elwira Bisz、Michal Szostak

  DOI：10.1002/cssc.201800142

  日期：2018.4.25

  conditions. Furthermore, large‐scale cross‐coupling, cross‐coupling of heteroaromatic substrates, and cross‐coupling of challenging aryl tosylates and carbamates mediated by Fe–N‐heterocyclic carbene catalytic systems in eco‐friendly 2‐MeTHF were also carried out. The developed method was applied to the key cross‐coupling in the synthesis of a fibrinolysis inhibitor, further highlighting the potential of 2‐MeTHF

  铁催化的交叉偶联反应可利用经济高效的，地球上富集的贱金属催化物，用于复杂的药物，天然产物和精细化学品的合成，以可持续方式形成C-C键。维持过程的完全可持续性的主要挑战是鉴定绿色和可再生溶剂，可利用这些溶剂替代传统溶剂以实现这一极具吸引力的反应。本文发现，以绿色，可持续且环保的2-甲基四氢呋喃（2-MeTHF）为溶剂，芳基氯化物和甲苯磺酸盐与具有挑战性的具有β-氢的有机金属试剂进行铁催化的交叉偶联，收率良好。 。该反应在非常温和的条件下以优异的官能团耐受性进行。此外，大规模的交叉耦合 还进行了杂芳族底物的交叉偶联以及Fe-N-杂环卡宾催化体系介导的具有挑战性的芳基甲苯磺酸盐和氨基甲酸酯在生态友好的2-MeTHF中的交叉偶联。该开发的方法已应用于纤维蛋白溶解抑制剂合成中的关键交叉偶联，进一步凸显了2-MeTHF作为可持续的铁催化交叉偶联反应的一般溶剂的潜力。