tetraethyl 2-(2-chlorophenyl)propane-1,1,3,3-tetracarboxylate | 6768-17-8

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: tetraethyl 2-(2-chlorophenyl)propane-1,1,3,3-tetracarboxylate
• 英文别名: α,α'-Bis-aethoxycarbonyl-β-<2-chlor-phenyl>-glutarsaeure-diaethylester；α,α'-Bis-aethoxycarbonyl-β-(2-chlor-phenyl)-glutarsaeure-diaethylester
• CAS: 6768-17-8
• 化学式: C₂₁H₂₇ClO₈
• 分子量: 442.894
• InChiKey: FMGVJSDSDXPQNN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  30
• 可旋转键数：
  15
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.52
• 拓扑面积：
  105
• 氢给体数：
  0
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  tetraethyl 2-(2-chlorophenyl)propane-1,1,3,3-tetracarboxylate 在 氢溴酸 作用下， 反应 48.0h， 生成 巴氯芬杂质8
  参考文献：
  名称：

  Synthesis, Screening, and Molecular Modeling of New Potent and Selective Antagonists at the α_1d Adrenergic Receptor

  摘要：

  In the present study, more than 75 compounds structurally related to BMY 7378 have been designed and synthesized. Structural variations of each part of the reference molecule have been introduced, obtaining highly selective ligands for the aid adrenergic receptor. The molecular determinants for selectivity at this receptor are essentially, held by the phenyl substituent in the phenylpiperazine moiety. The integration of an extensive SAR analysis with docking simulations using the rhodopsin-based models of the three alpha(1)-AR subtypes and of the 5-HT1A receptor provides significant insights into the characterization of the receptor binding sites as well as into the molecular determinants of ligand selectivity at the alpha(1d)-AR and the 5-HT1A receptors. The results of multiple copies simultaneous search (MCSS) on the substituted phenylpiperazines together with those of manual docking of compounds BAN 7378 and 69 into the putative binding sites of the alpha(1a)-AR, alpha(1b)-AR, alpha(1d)-AR, and the 5-HT1A receptors suggest that the phenylpiperazine moiety would dock into a site formed by amino acids in helices 3, 4, 5, 6 and extracellular loop 2, (E2), whereas the spirocyclic ring of the ligand docks into a site formed by amino acids of helices 1, 2, 3, and 7. This docking mode is consistent with the SAR data produced in this work. Furthermore, the binding site of the imide moiety does not allow for the simultaneous involvement of the two carbonyl oxygen atoms in H-bonding, interactions, consistent with the SAR data, in particular with the results obtained with the lactam derivative 128. The results of docking simulations also suggest that the second and third extracellular loops may act as selectivity filters for the substituted phenylpiperazines. The most potent and selective compounds for alpha(1d) adrenergic receptor, i.e., 69 (Rec 26D/038) and 128 (Rec 26D/073), are characterized by the presence of the 2,5-dichlorophenylpiperazine moiety.

  DOI：

  10.1021/jm030944+
• 作为产物：
  描述：

  o-chloro-N-tosylbenzaldimine 、 丙二酸二乙酯 在 potassium tert-butylate 作用下， 以 叔丁醇 为溶剂， 反应 4.0h， 以93%的产率得到tetraethyl 2-(2-chlorophenyl)propane-1,1,3,3-tetracarboxylate
  参考文献：
  名称：

  Tandem Knoevenagel−Michael Addition of Aryl Sulfonimines with Diethyl Malonate for Synthesis of Arylidene Dimalonates

  摘要：

  A highly efficient, one-flask tandem Knoevenagel-Michael addition reaction of sulfonimines with diethyl malonate in the presence of a catalytic amount of base affords the corresponding arylidene dimalonates in good to excellent yields.

  DOI：

  10.1021/jo070726e

文献信息

• Lewis acidic ionic liquids for the synthesis of electrophilic alkenes via the Knoevenagel condensation
  作者：Jitendra R Harjani、Susheel J Nara、Manikrao M Salunkhe

  DOI：10.1016/s0040-4039(01)02341-3

  日期：2002.2

  [bpy]Cl·AlCl3, N=0.67 ionic liquids were found to work well as the Lewis acid catalyst and solvent in the Knoevenagel condensations of benzaldehyde and substituted benzaldehydes with diethyl malonate to give benzylidene malonates. The benzylidene malonates subsequently underwent Michael additions with diethyl malonate. The extent of Michael product formed during the reaction was found to vary with the Lewis acidity

  1-丁基-3-甲基咪唑鎓氯铝酸盐，[bmim] Cl·AlCl 3，N = 0.67和1-丁基吡啶鎓氯铝酸盐，[bpy] Cl·AlCl 3，N发现＝ 0.67离子液体在苯甲醛和取代的苯甲醛与丙二酸二乙酯的Knoevenagel缩合反应中作为路易斯酸催化剂和溶剂很好地工作，得到亚苄基丙二酸酯。亚苄基丙二酸酯随后与丙二酸二乙酯进行迈克尔加成。发现反应过程中迈克尔产物的形成程度随路易斯酸度和离子液体的摩尔比而变化。证明了离子液体的路易斯酸度对Knoevenagel和Michael产品的影响。在2-羟基芳基醛的情况下，该反应导致在环境条件下形成3-乙氧基羰基香豆素。
• Synthesis, Screening, and Molecular Modeling of New Potent and Selective Antagonists at the α_1d Adrenergic Receptor
  作者：Amedeo Leonardi、Daniela Barlocco、Federica Montesano、Giorgio Cignarella、Gianni Motta、Rodolfo Testa、Elena Poggesi、Michele Seeber、Pier G. De Benedetti、Francesca Fanelli

  DOI：10.1021/jm030944+

  日期：2004.4.1

  In the present study, more than 75 compounds structurally related to BMY 7378 have been designed and synthesized. Structural variations of each part of the reference molecule have been introduced, obtaining highly selective ligands for the aid adrenergic receptor. The molecular determinants for selectivity at this receptor are essentially, held by the phenyl substituent in the phenylpiperazine moiety. The integration of an extensive SAR analysis with docking simulations using the rhodopsin-based models of the three alpha(1)-AR subtypes and of the 5-HT1A receptor provides significant insights into the characterization of the receptor binding sites as well as into the molecular determinants of ligand selectivity at the alpha(1d)-AR and the 5-HT1A receptors. The results of multiple copies simultaneous search (MCSS) on the substituted phenylpiperazines together with those of manual docking of compounds BAN 7378 and 69 into the putative binding sites of the alpha(1a)-AR, alpha(1b)-AR, alpha(1d)-AR, and the 5-HT1A receptors suggest that the phenylpiperazine moiety would dock into a site formed by amino acids in helices 3, 4, 5, 6 and extracellular loop 2, (E2), whereas the spirocyclic ring of the ligand docks into a site formed by amino acids of helices 1, 2, 3, and 7. This docking mode is consistent with the SAR data produced in this work. Furthermore, the binding site of the imide moiety does not allow for the simultaneous involvement of the two carbonyl oxygen atoms in H-bonding, interactions, consistent with the SAR data, in particular with the results obtained with the lactam derivative 128. The results of docking simulations also suggest that the second and third extracellular loops may act as selectivity filters for the substituted phenylpiperazines. The most potent and selective compounds for alpha(1d) adrenergic receptor, i.e., 69 (Rec 26D/038) and 128 (Rec 26D/073), are characterized by the presence of the 2,5-dichlorophenylpiperazine moiety.
• Tandem Knoevenagel−Michael Addition of Aryl Sulfonimines with Diethyl Malonate for Synthesis of Arylidene Dimalonates
  作者：Renhua Fan、Weizi Wang、Dongming Pu、Jie Wu

  DOI：10.1021/jo070726e

  日期：2007.7.1

  A highly efficient, one-flask tandem Knoevenagel-Michael addition reaction of sulfonimines with diethyl malonate in the presence of a catalytic amount of base affords the corresponding arylidene dimalonates in good to excellent yields.