4-methoxy-N-(3,4,5-trimethoxybenzylidene)aniline | 58896-43-8

• 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: 4-methoxy-N-(3,4,5-trimethoxybenzylidene)aniline
• 英文别名: N-(3,4,5-trimethoxybenzylidene)-4-methoxybenzenamine；N-(3,4,5-trimethoxybenzylidene)-4-methoxyphenylamine；(4-methoxyphenyl)(3,4,5-trimethoxybenzylidene)amine；N-(4-methoxyphenyl)-1-(3,4,5-trimethoxyphenyl)methanimine
• CAS: 58896-43-8
• 化学式: C₁₇H₁₉NO₄
• 分子量: 301.342
• InChiKey: OLLQPFXQODPYCB-UHFFFAOYSA-N

物化性质

• 熔点：
  108 °C(Solv: ethanol (64-17-5))
• 沸点：
  447.7±45.0 °C(Predicted)
• 密度：
  1.08±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  22
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  49.3
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  4-methoxy-N-(3,4,5-trimethoxybenzylidene)aniline 在 苯硅烷 、 C₄₃H₄₄FeN₂O₄ 作用下， 以 二甲基亚砜 为溶剂， 反应 12.0h， 以145 mg的产率得到4-methoxy-N-(3,4,5-trimethoxybenzyl)aniline
  参考文献：
  名称：

  一种高效的基础金属催化剂：使用异常的NHC–Fe（0）配合物将胺化学选择性还原成胺

  摘要：

  A base-metal, Fe(0)-catalyzed hydrosilylation of imines to obtain amines is reported here which outperforms its noble-metal congeners with the highest TON of 17000. The catalyst, (aNHC)Fe(CO)(4), works under very mild conditions, with extremely low catalyst loading (down to 0.005 mol %), and exhibits excellent chemoselectivity. The facile nature of the imine reduction under mild conditions has been further demonstrated by reducing imines towards expensive commercial amines and biologically important N-alkylated sugars, which are difficult to achieve otherwise. A mechanistic pathway and the source of chemoselectivity for imine hydrosilylation have been proposed on the basis of the well-defined catalyst and isolable intermediates along the catalytic cycle.

  DOI：

  10.1021/acs.organomet.6b00478
• 作为产物：
  描述：

  3,4,5-三甲氧基苯甲醛 、 甲氧苯胺 在 溶剂黄146 作用下， 以 乙醇 为溶剂， 生成 4-methoxy-N-(3,4,5-trimethoxybenzylidene)aniline
  参考文献：
  名称：

  某些三取代氮杂环丁烷-2-one 衍生物作为顺式限制性考布他汀 A-4 类似物的合成和细胞毒活性

  摘要：

  合成了一系列新的 1,3,4-三取代氮杂环丁烷-2-one 衍生物 8a-p，并提出作为细胞毒剂，通过抑制秋水仙碱结合位点的微管蛋白起作用。目标化合物的设计基于对血管靶向剂考布他汀 A-4 (CA-4) 结构的修改。CA-4 中的顺式双键接头被 azetidin-2-one 环取代，旨在防止抑制 CA-4 活性的顺/反异构化，从而增强其抗增殖活性。所有新化合物均针对 MCF-7 和 HCT-116 细胞系进行了体外研究。还评估了四种最有效的化合物 8g、8j、8n 和 8o 对微管蛋白聚合的抑制作用。最终目标的合成采用施陶丁格反应实现。

  DOI：

  10.1007/s12272-016-0849-y

文献信息

• 3-Vinylazetidin-2-Ones: Synthesis, Antiproliferative and Tubulin Destabilizing Activity in MCF-7 and MDA-MB-231 Breast Cancer Cells
  作者：Wang、Malebari、Greene、O’Boyle、Fayne、Nathwani、Twamley、McCabe、Keely、Zisterer、Meegan

  DOI：10.3390/ph12020056

  日期：——

  Microtubule-targeted drugs are essential chemotherapeutic agents for various types of cancer. A series of 3-vinyl-β-lactams (2-azetidinones) were designed, synthesized and evaluated as potential tubulin polymerization inhibitors, and for their antiproliferative effects in breast cancer cells. These compounds showed potent activity in MCF-7 breast cancer cells with an IC50 value of 8 nM for compound 7s 4-[3-Hydroxy-4-methoxyphenyl]-1-(3,4,5-trimethoxyphenyl)-3-vinylazetidin-2-one) which was comparable to the activity of Combretastatin A-4. Compound 7s had minimal cytotoxicity against both non-tumorigenic HEK-293T cells and murine mammary epithelial cells. The compounds inhibited the polymerisation of tubulin in vitro with an 8.7-fold reduction in tubulin polymerization at 10 M for compound 7s and were shown to interact at the colchicine-binding site on tubulin, resulting in significant G2/M phase cell cycle arrest. Immunofluorescence staining of MCF-7 cells confirmed that β-lactam 7s is targeting tubulin and resulted in mitotic catastrophe. A docking simulation indicated potential binding conformations for the 3-vinyl-β-lactam 7s in the colchicine domain of tubulin. These compounds are promising candidates for development as antiproiferative microtubule-disrupting agents.

  微管靶向药物是各种癌症的重要化疗药物。一系列3-乙烯基-β-内酰胺（2-氮杂环丙酮）被设计、合成并评估为潜在的微管聚合抑制剂，以及它们在乳腺癌细胞中的抗增殖效应。这些化合物在MCF-7乳腺癌细胞中表现出强大的活性，其中化合物7s（4-[3-羟基-4-甲氧基苯基]-1-(3,4,5-三甲氧基苯基)-3-乙烯基氮杂环丙酮）的IC50值为8 nM，与康布雷他定A-4的活性相当。化合物7s对非肿瘤性HEK-293T细胞和小鼠乳腺上皮细胞均具有最小的细胞毒性。这些化合物在体外抑制了微管的聚合，在10 μM的浓度下，化合物7s使微管聚合减少了8.7倍，并且显示出它们与微管上的秋水仙碱结合位点相互作用，导致显著的G2/M期细胞周期阻滞。MCF-7细胞的免疫荧光染色证实了β-内酰胺7s靶向微管，并导致有丝分裂灾难。对于3-乙烯基-β-内酰胺7s在微管秋水仙碱结合区域的潜在结合构象进行的对接模拟表明了潜在的结合构象。这些化合物是作为抗增殖微管破坏剂的发展有前途的候选药物。
• Alkyl Transfer from CC Cleavage
  作者：Guangxun Li、Rong Chen、Lei Wu、Qingquan Fu、Xiaomei Zhang、Zhuo Tang

  DOI：10.1002/anie.201303696

  日期：2013.8.5

  Hydrogenation was only the beginning: Hantzsch esters have now been used to transfer alkyl groups to imines under mild catalytic conditions to provide a variety of amines (see scheme). Benzyl, secondary alkyl, and tertiary alkyl groups containing ether, ester, and hydroxy functionalities were transferred successfully. The use of Hantzsch esters as alkylation reagents offers a practical and complementary

  氢化仅仅是个开始：汉茨酯已被用于在温和的催化条件下将烷基转移到亚胺上，以提供多种胺（参见方案）。含有醚，酯和羟基官能团的苄基，仲烷基和叔烷基已成功转移。Hantzsch酯作为烷基化试剂的使用为有机金属工艺提供了一种实用且互补的替代方法。
• One Pot, Simple, and Efficient Synthesis of 2-Azetidinones Mediated by 3-(Diethoxyphosphoryloxy)-1,2,3-benzotriazin-4-(3H)-one
  作者：Mahnaz Saraei、Maaroof Zarei、Saleheh Zavar

  DOI：10.2174/1570180814666170612120845

  日期：2017.8.22

  (diethoxyphosphoryloxy)-1,2,3-benzotriazin-4-(3H)-one (DEPBT) for the synthesis of 2-azetidinones under mild reaction conditions at room temperature. Methods: The present methodology deals with one pot [2+2] ketene-imine cycloaddition reaction of imine and substituted ketene to synthesis of 2-azetidinones in mild condition at room temperature. In addition, detailed experimental procedures are provided. Results:

  背景：2-氮杂环丁酮（β-内酰胺类）在有机化学和药物中占有重要地位。β-内酰胺抗生素作为抗生素药物被广泛应用于对抗微生物。施陶丁格的乙烯酮-亚胺环加成法是2-氮杂环丁酮合成中最常用的方法之一。本文的目的是描述一种基于3-（二乙氧基磷酰氧基）-1,2,3-苯并三嗪-4-（3H）-一（DEPBT）在温和的反应条件下合成2-氮杂环丁酮的方法室内温度。 方法：本方法论是在温和的条件下于室温下进行亚胺和取代的烯酮的一锅[2 + 2]烯酮-亚胺环加成反应合成2-氮杂环丁酮。另外，提供了详细的实验程序。 结果：通过一锅[2 + 2]烯酮-亚胺环加成反应，合成了一系列2-氮杂环丁酮，收率良好至优异。通过简单的结晶以高收率纯化获得的产物。所有合成的化合物都通过光谱和物理数据很好地表征。 结论：已开发出一种简单的方法，可以使用3-（二乙氧基磷酰氧基）-1,2,3-苯并三嗪-4-（3H）-一（DEPBT）将各种
• Simple Brønsted acid catalyzed C–H functionalization: efficient access to poly-substituted pyridines
  作者：Shujun Lai、Xuwen Ren、Jinzhong Zhao、Zhuo Tang、Guangxun Li

  DOI：10.1016/j.tetlet.2016.05.061

  日期：2016.7

  An exceptionally simple and environmentally friendly methodology has been developed for directly functionalizing the benzylic C–H bond of the poly-substituted pyridines with aromatic imines. Simple Brønsted acid catalysts including salicylic acid and TsOH were successfully employed. Different types of poly-substituted pyridines could be efficiently obtained with moderate yields. Traditional ways to

  已经开发了一种非常简单且对环境友好的方法，用于将多取代吡啶的苄基CH键与芳族亚胺直接官能化。成功地使用了简单的布朗斯台德酸催化剂，包括水杨酸和TsOH。可以以中等收率有效地获得不同类型的多取代吡啶。制备这类吡啶的传统方法涉及相应的Hantzsch 1,4-二氢吡啶的芳构化，而该方法大大简化了合成步骤。
• Synthesis of β-lactams via Staudinger reaction using <i>N</i>-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline as a carboxylic acid activator
  作者：Saleheh Zavar、Maaroof Zarei、Mahnaz Saraei

  DOI：10.1080/00397911.2016.1244691

  日期：2016.12.16

  ABSTRACT N-Ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ) has been used as an efficient and convenient reagent for the one-pot synthesis of β-lactams by [2+2] ketene–imine cycloaddition (Staudinger reaction). Cleanliness, simplicity of method, and good to excellent yields of products are some advantages of this method. GRAPHICAL ABSTRACT

  摘要 N-Ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ) 已被用作一种有效且方便的试剂，用于通过 [2+2] 烯酮-亚胺环加成反应（Staudinger 反应）一锅法合成 β-内酰胺. 该方法的一些优点是清洁度、方法简单以及产品的收率非常好。图形概要