4-(2-羟乙基氨基)-3-硝基苯甲酸乙酯 | 91214-94-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 4-(2-羟乙基氨基)-3-硝基苯甲酸乙酯
• 英文名称: ethyl 4-(2-hydroxyethylamino)-3-nitrobenzoate
• 英文别名: Ethyl 4-(2-hydroxyethylamino)-3-nitrobenzoate
• CAS: 91214-94-7
• 化学式: C₁₁H₁₄N₂O₅
• 分子量: 254.243
• InChiKey: YYLUAXOOVFHCQG-UHFFFAOYSA-N

物化性质

• 熔点：
  137-140.5 °C
• 沸点：
  455.2±40.0 °C(Predicted)
• 密度：
  1.344±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  18
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  104
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  4-(2-羟乙基氨基)-3-硝基苯甲酸乙酯 在 10% Pd/C 、 甲酸铵 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 0.08h， 生成 ethyl 2-phenyl-1-(2-hydroxyethyl)-1H-benzimidazole-5-carboxylate
  参考文献：
  名称：

  新型 1-(2'-α-OD-吡喃葡萄糖基乙基)2-芳基苯并咪唑的直接合成。

  摘要：

  通过1-(2'-羟乙基)-2-芳基苯并咪唑-5-羧酸酯衍生物的一锅糖基化制备了一系列新型1-(2'-α-OD-吡喃葡萄糖基乙基)2-芳基苯并咪唑。由 4-氟-3-硝基苯甲酸合成 2-芳基苯并咪唑苷元通过四个高产步骤完成。糖苷配基合成的还原和环缩合步骤在微波辐射下有效进行，在 2-3 分钟内以优异的产率提供合适的苯并咪唑。用过苯甲基化 1-羟基-吡喃葡萄糖对羟乙基苷元进行糖基化，用 Appel-Lee 试剂进行预处理，然后进行催化氢解，以简单的方法得到所需的 1-(2'-α-OD-吡喃葡萄糖基乙基) 2-芳基-苯并咪唑和直接的方式。

  DOI：

  10.3390/molecules17089887
• 作为产物：
  描述：

  4-氟-3-硝基苯甲酸 在 硫酸 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 8.0h， 生成 4-(2-羟乙基氨基)-3-硝基苯甲酸乙酯
  参考文献：
  名称：

  新型 1-(2'-α-OD-吡喃葡萄糖基乙基)2-芳基苯并咪唑的直接合成。

  摘要：

  通过1-(2'-羟乙基)-2-芳基苯并咪唑-5-羧酸酯衍生物的一锅糖基化制备了一系列新型1-(2'-α-OD-吡喃葡萄糖基乙基)2-芳基苯并咪唑。由 4-氟-3-硝基苯甲酸合成 2-芳基苯并咪唑苷元通过四个高产步骤完成。糖苷配基合成的还原和环缩合步骤在微波辐射下有效进行，在 2-3 分钟内以优异的产率提供合适的苯并咪唑。用过苯甲基化 1-羟基-吡喃葡萄糖对羟乙基苷元进行糖基化，用 Appel-Lee 试剂进行预处理，然后进行催化氢解，以简单的方法得到所需的 1-(2'-α-OD-吡喃葡萄糖基乙基) 2-芳基-苯并咪唑和直接的方式。

  DOI：

  10.3390/molecules17089887

文献信息

• Total Synthesis of Diversified 1,2-disubstituted Benzimidazoles with Green Approach at Room Temperature
  作者：Yeong Yoon、Mohamed Ali、Ang Wei、Tan Choon、Lim Leng、Oo Wei

  DOI：10.2174/157017861110141117150010

  日期：2014.11.17

  A green and facile method to synthesize diversified 1,2-disubstituted benzimidazoles has been developed. The total synthesis was performed at room temperature utilizing water and ethanol as solvents. As aqueous media and ethanol have low toxicity and are easily recyclable, the method presented is very suitable for scale-up production. Furthermore, products were obtained in high yield and easily isolated making this method very practical and attractive.

  一种绿色、简单的方法已被开发用于合成多样化的1,2-双取代苯并咪唑。整个合成过程在室温下进行，使用水和乙醇作为溶剂。由于水相和乙醇的低毒性和易于回收，该方法非常适合大规模生产。此外，所获得的产品产率高且易于分离，使该方法非常实用和具有吸引力。
• Novel Fluorescent Benzimidazoles: Synthesis, Characterization, Crystal Structure and Evaluation of Their Anticancer Properties
  作者：Yeong Yoon、Tze Chia、Ching Quah、Wan Lim、Chuan Oo、Amir Shirazi、Keykavous Parang、Tan Choon

  DOI：10.2174/1570178614666161205123900

  日期：2017.2.13

  Background: The benzimidazole core structure is an interesting platform for drug discovery since it possess a wide spectrum of pharmacological activities such as antiviral, anti-inflammatory and anticancer. Previously the antiproliferative effect of novel substituted benzimidazole derivative was demonstrated based on the ethyl 1-(2-hydroxyethyl)-2-phenyl-1H-benzo[d]imidazole-5-carboxylate scaffold through the inhibition of sirtuin activity. This work aimed to further explore the previous work for identifying novel fluorescent benzimidazoles which possess anti proliferative activities based on the reported scaffold. Methods: Compounds were synthesized based on a multistep but facile protocol. Structure of the compounds was elucidated using NMR, FT-IR, LC-MS, elemental analysis and unambiguously confirmed through crystal X-ray diffraction. Molar extinction coefficient of the autofluorescence compounds were determined using UV spectroscopy while cancer cell growth inhibitory activity was carried out using MTS assay. Results: Four novel benzimidazole derivatives were successfully synthesized in this study. All four compounds were found to emit blue fluorescence when light-irradiated with molar extinction coefficient ranging from 21000 to 29000 (mol L-1)-1cm-1. Two of the synthesized compounds showed good anti proliferative activity against four cancer cell lines tested in this study. Conclusion: Four novel benzimidazole derivatives presented in this study were synthesized using multistep protocol starting from 4-fluoro-3-nitrobenzoic acid. Their structures have been elucidated using multiple techniques such as NMR, FT-IR, LC-MS, elemental analysis and X-ray crystallography where possible. They were found to have high autofluorescence and two of them were able to inhibit the growth of cancer cells tested in this study.

  背景：苯并咪唑核心结构是一个有趣的药物发现平台，因为它具有广泛的药理活性，如抗病毒、抗炎和抗癌。此前，基于 1-(2-羟乙基)-2-苯基-1H-苯并[d]咪唑-5-羧酸乙酯支架的新型取代苯并咪唑衍生物通过抑制 sirtuin 活性而被证实具有抗增殖作用。这项工作旨在进一步探索以前的工作，在已报道的支架基础上确定具有抗增殖活性的新型荧光苯并咪唑。 方法：化合物的合成基于一个多步骤但简便的方案。利用核磁共振、傅立叶变换红外光谱、液相色谱-质谱、元素分析等方法阐明了化合物的结构，并通过晶体 X 射线衍射得到了明确的证实。利用紫外光谱测定了自发荧光化合物的摩尔消光系数，并利用 MTS 法进行了癌细胞生长抑制活性测定。 结果：本研究成功合成了四种新型苯并咪唑衍生物。所有四种化合物在光照射下都会发出蓝色荧光，摩尔消光系数在 21000 至 29000（mol L-1）-1cm-1 之间。在本研究测试的四种癌细胞株中，有两种合成化合物显示出良好的抗增殖活性。 结论：本研究以 4-氟-3-硝基苯甲酸为起点，采用多步合成法合成了四种新型苯并咪唑衍生物。在可能的情况下，利用核磁共振、傅立叶变换红外光谱、液相色谱-质谱、元素分析和 X 射线晶体学等多种技术阐明了它们的结构。研究发现，它们具有较高的自发荧光，其中两种能够抑制本研究中测试的癌细胞的生长。
• Synthesis and evaluation of novel benzimidazole derivatives as sirtuin inhibitors with antitumor activities
  作者：Yeong Keng Yoon、Mohamed Ashraf Ali、Ang Chee Wei、Tan Soo Choon、Hasnah Osman、Keykavous Parang、Amir Nasrolahi Shirazi

  DOI：10.1016/j.bmc.2013.12.029

  日期：2014.1

  A total of 15 novel benzimidazole derivatives were designed, synthesized and evaluated for their SIRT1 and SIRT2 inhibitory activity. All compounds showed better inhibition on SIRT2 as compared to SIRT1. Among these, compound 5j displayed the best inhibitory activity for SIRT1 (IC50 = 58.43 mu M) as well as for SIRT2 (IC50 = 45.12 mu M). Cell cytotoxicity assays also showed that compound 5j possesses good antitumor activity against two different cancer cell lines derived frombreast cancer (MCF-7 and MDA-MB-468). A simple structure-activity-relationship (SAR) study of the newly synthesized benzimidazole derivatives was also discussed. (C) 2013 Elsevier Ltd. All rights reserved.
• Straightforward Synthesis of Novel 1-(2′-α-O-D-Glucopyranosyl ethyl) 2-Arylbenzimidazoles
  作者：Natarajan Arumugam、Aisyah Saad Abdul Rahim、Shafida Abd Hamid、Hasnah Osman

  DOI：10.3390/molecules17089887

  日期：——

  series of novel 1-(2'-α-O-D-glucopyranosyl ethyl) 2-arylbenzimidazoles has been prepared via one-pot glycosylation of ethyl-1-(2'-hydroxyethyl)-2-arylbenzimidazole-5-carboxylate derivatives. Synthesis of the 2-arylbenzimidazole aglycones from 4-fluoro-3-nitrobenzoic acid was accomplished in four high-yielding steps. The reduction and cyclocondensation steps for the aglycone synthesis proceeded efficiently

  通过1-(2'-羟乙基)-2-芳基苯并咪唑-5-羧酸酯衍生物的一锅糖基化制备了一系列新型1-(2'-α-OD-吡喃葡萄糖基乙基)2-芳基苯并咪唑。由 4-氟-3-硝基苯甲酸合成 2-芳基苯并咪唑苷元通过四个高产步骤完成。糖苷配基合成的还原和环缩合步骤在微波辐射下有效进行，在 2-3 分钟内以优异的产率提供合适的苯并咪唑。用过苯甲基化 1-羟基-吡喃葡萄糖对羟乙基苷元进行糖基化，用 Appel-Lee 试剂进行预处理，然后进行催化氢解，以简单的方法得到所需的 1-(2'-α-OD-吡喃葡萄糖基乙基) 2-芳基-苯并咪唑和直接的方式。