1-[(4-氯苯基)甲基]吡咯烷-2,5-二酮 | 91349-11-0

• 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: 1-[(4-氯苯基)甲基]吡咯烷-2,5-二酮
• 英文名称: 1-(4-chlorobenzyl)pyrrolidine-2,5-dione
• 英文别名: 1-[(4-chlorophenyl)methyl]pyrrolidine-2,5-dione
• CAS: 91349-11-0
• 化学式: C₁₁H₁₀ClNO₂
• mdl: MFCD00564067
• 分子量: 223.659
• InChiKey: UQMSJLNFASHBGZ-UHFFFAOYSA-N

物化性质

• 熔点：
  136.5 °C(Solv: water (7732-18-5); acetic acid (64-19-7))
• 沸点：
  423.1±28.0 °C(Predicted)
• 密度：
  1.371±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  15
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.272
• 拓扑面积：
  37.4
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  1-[(4-氯苯基)甲基]吡咯烷-2,5-二酮 、 吡嗪-2,3-二羧酸 二甲酯 在 甲醇 、 sodium hydride 作用下， 以 四氢呋喃 为溶剂， 反应 48.0h， 以48%的产率得到7-(4-chloro-benzyl)-5,9-dihydroxy-pyrrolo[3,4-g]quinoxaline-6,8-dione
  参考文献：
  名称：

  Design and Optimization of Tricyclic Phtalimide Analogues as Novel Inhibitors of HIV-1 Integrase

  摘要：

  Human immunodeficiency virus type-1 integrase is an essential enzyme for effective viral replication and hence a valid target for the design of inhibitors. We report here on the design and synthesis of a novel series of phthalimide analogues as integrase inhibitors. The short synthetic pathway enabled us to synthesize a series of analogues with a defined structure diversity. The presence of a single carbonyl-hydroxy-aromatic nitrogen motif was shown to be essential for the enzymatic activity and this was confirmed by molecular docking studies. The enzymatically most active compound from this series is 743,4-dichlorobenzyl)-5,9dihydroxypyrrolo[3,4-g]quinoxaline-6,8-dione (151) with an IC50 value of 112 nM on the HIV-1 integrase enzyme, while ((7-(4-chlorobenzyl)-5,9-dihydroxy-pyrrolo[3,4-g]quinoxaline-6,8-dione (15k)) showed an EC50 of 270 nM against HIV-1 in a cell-based assay.

  DOI：

  10.1021/jm049559q
• 作为产物：
  描述：

  对氯苯甲腈 、 1,4-丁二醇 在 [RuH2(PPh3)4] 、 sodium hydride 、 1,3-diisopropylimidazolium bromide 作用下， 以 苯 为溶剂， 反应 18.0h， 以67%的产率得到1-[(4-氯苯基)甲基]吡咯烷-2,5-二酮
  参考文献：
  名称：

  使用氢转移作为底物活化策略由腈和二醇合成环状酰亚胺

  摘要：

  开发了一种从腈和二醇合成环状酰亚胺的原子经济且用途广泛的方法。该方法利用Ru催化的转移氢化反应，其中以氧化还原中性的方式将底物，二醇和腈同时活化为内酯和胺，以提供相应的环酰亚胺，其中放出H 2气体作为唯一的副产物。这种操作简单且催化合成的方法为环状酰亚胺提供了一种可持续且容易获得的途径。

  DOI：

  10.1021/ol501835t

文献信息

• 一种N-(芳基/杂芳基)烷基-二酰胺的制备方 法
  申请人：中国科学院兰州化学物理研究所

  公开号：CN112047925B

  公开（公告）日：2021-06-25

  本发明涉及一种N‑(芳基/杂芳基)烷基‑二酰胺的制备方法，在氮气保护下，将过渡金属、膦或氮配体、助催化剂、碱、溶剂、N‑卤代环二酰胺、烷基‑芳环或烷基‑杂芳环化合物依次加入到反应容器中，于80~140℃发生氧化胺化反应，6~48小时后反应结束，经蒸干溶剂、柱层析分离即得N‑(芳基/杂芳基)烷基‑二酰胺类化合物。本发明合成工艺简单，反应条件温和，产率高，易于工业化。
• Direct Synthesis of Cyclic Imides from Carboxylic Anhydrides and Amines by Nb₂ O₅ as a Water-Tolerant Lewis Acid Catalyst
  作者：Md. A. Ali、Sondomoyee K. Moromi、Abeda S. Touchy、Ken-ichi Shimizu

  DOI：10.1002/cctc.201501172

  日期：2016.3.7

  highest activity for the synthesis of N‐phenylsuccinimide by dehydrative condensation of succinic anhydride and aniline. Nb2O5 was used in the direct imidation of a wide range of carboxylic anhydrides with NH3 or amines with various functional groups and could be reused. Kinetic studies showed that the Lewis acid Nb2O5 catalyst was more water tolerant than both the Lewis acidic oxide TiO2 and the homogeneous

  在筛选的20种非均相和均相催化剂中，Nb 2 O 5通过琥珀酸酐和苯胺的脱水缩合合成N-苯基琥珀酰亚胺的活性最高。Nb 2 O 5用于直接将各种羧酸酐与NH 3或具有各种官能团的胺直接酰亚胺化，可以重复使用。动力学研究表明，路易斯酸Nb 2 O 5催化剂比路易斯酸性氧化物TiO 2和均相路易斯酸ZrCl 4具有更高的耐水性，这通过使用Nb可以提高酰亚胺的收率。2 O 5。
• Synthesis of Cyclic Imides by Acceptorless Dehydrogenative Coupling of Diols and Amines Catalyzed by a Manganese Pincer Complex
  作者：Noel Angel Espinosa-Jalapa、Amit Kumar、Gregory Leitus、Yael Diskin-Posner、David Milstein

  DOI：10.1021/jacs.7b08341

  日期：2017.8.30

  base-metal-catalyzed dehydrogenative coupling of diols and amines to form cyclic imides is reported. The reaction is catalyzed by a pincer complex of the earth abundant manganese and forms hydrogen gas as the sole byproduct, making the overall process atom economical and environmentally benign.

  报告了碱金属催化的二醇和胺脱氢偶联形成环状酰亚胺的第一个例子。该反应由地球上丰富的锰的钳形络合物催化，并形成氢气作为唯一的副产品，使整个过程原子经济且环保。
• Versatile and Sustainable Synthesis of Cyclic Imides from Dicarboxylic Acids and Amines by Nb₂O₅as a Base-Tolerant Heterogeneous Lewis Acid Catalyst
  作者：Md. Ayub Ali、S. M. A. Hakim Siddiki、Kenichi Kon、Junya Hasegawa、Ken-ichi Shimizu

  DOI：10.1002/chem.201404538

  日期：2014.10.27

  Catalytic condensation of dicarboxylics acid and amines without excess amount of activating reagents is the most atom‐efficient but unprecedented synthetic method of cyclic imides. Here we present the first general catalytic method, proceeding selectively and efficiently in the presence of a commercial Nb2O5 as a reusable and base‐tolerant heterogeneous Lewis acid catalyst. The method is effective for

  二羧酸和胺的催化缩合反应没有过量的活化剂是最高效，最空前的环状酰亚胺合成方法。在这里，我们介绍了第一种通用催化方法，该方法在作为可重用和耐碱多相路易斯酸催化剂的商业Nb 2 O 5的存在下选择性而有效地进行。该方法可有效地从二羧酸或酸酐与胺，羟胺或氨直接合成药学上或工业上重要的环状酰亚胺，例如苯甲酰亚胺，N-羟基邻苯二甲酰亚胺（NHPI）和未取代的环状酰亚胺。
• Design and Optimization of Tricyclic Phtalimide Analogues as Novel Inhibitors of HIV-1 Integrase
  作者：Wim G. Verschueren、Inge Dierynck、Katie I. E. Amssoms、Lili Hu、Paul M. J. G. Boonants、Geert M. E. Pille、Frits F. D. Daeyaert、Kurt Hertogs、Dominique L. N. G. Surleraux、Piet B. T. P. Wigerinck

  DOI：10.1021/jm049559q

  日期：2005.3.1

  Human immunodeficiency virus type-1 integrase is an essential enzyme for effective viral replication and hence a valid target for the design of inhibitors. We report here on the design and synthesis of a novel series of phthalimide analogues as integrase inhibitors. The short synthetic pathway enabled us to synthesize a series of analogues with a defined structure diversity. The presence of a single carbonyl-hydroxy-aromatic nitrogen motif was shown to be essential for the enzymatic activity and this was confirmed by molecular docking studies. The enzymatically most active compound from this series is 743,4-dichlorobenzyl)-5,9dihydroxypyrrolo[3,4-g]quinoxaline-6,8-dione (151) with an IC50 value of 112 nM on the HIV-1 integrase enzyme, while ((7-(4-chlorobenzyl)-5,9-dihydroxy-pyrrolo[3,4-g]quinoxaline-6,8-dione (15k)) showed an EC50 of 270 nM against HIV-1 in a cell-based assay.