2-phenylbicyclo<2.2.2>oct-2-en-5-one

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 2-phenylbicyclo<2.2.2>oct-2-en-5-one
• 英文别名: 5-phenylbicyclo[2.2.2]oct-5-en-2-one；rac-(1R*,4R*)-5-phenyl-bicyclo[2.2.2]oct-5-en-2-one
• 化学式: C₁₄H₁₄O
• 分子量: 198.265
• InChiKey: NGFMXHCCPBGFRE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  15
• 可旋转键数：
  1
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  17.1
• 氢给体数：
  0
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  2-phenylbicyclo<2.2.2>oct-2-en-5-one 在 甲基磺酰氯 、 三乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 生成 2-phenyl-5-(o-tolyl)bicyclo[2.2.2]octa-2,5-diene
  参考文献：
  名称：

  Scalable Synthesis of Enantiomerically Pure Bicyclo[2.2.2]octadiene Ligands

  摘要：

  An operationally simple and scalable synthesis of enantiomerically pure bicyclo[2.2.2]octadiene (bod*) ligands relying on an organocatalytic one-pot Michael addition-aldol reaction with cheap 2-cyclohexenone and phenylacetaldehyde is presented. The crystalline bicyclic product 4a (6-hydroxy-5-phenylbicyclo[2.2.2]octan-2-one) is transformed into phenylbicyclo[2.2.2]oct-5-en-2-one 2, a versatile starting material for the 2-step synthesis of both symmetrical, such as Hayashi's Ph-bod* ligand, as well as novel unsymmetrical chiral dienes.

  DOI：

  10.1021/jo3005638
• 作为产物：
  描述：

  5-(ethylenedioxy)bicyclo<2.2.2>octan-2-one 在 盐酸 、 硫酸 作用下， 以 乙醚 、 二氯甲烷 、 环己烷 为溶剂， 反应 4.58h， 生成 2-phenylbicyclo<2.2.2>oct-2-en-5-one
  参考文献：
  名称：

  Stereomutation of 7-tropylionorbornane, 2-tropyliobicyclo[2.2.2]octane, and 2-tropylioadamantane: evidence for the intermediacy of heptafulvenes

  摘要：

  The perchlorates of 7-tropylionorbornane (3), 2-tropyliobicyclo[2.2.2]octane (4), and 2-tropylioadamantane (5) were found to undergo stereomutation in acetonitrile at 25-85-degrees-C, as evidenced by following the change in the C-13 NMR spectra of their deuterium-labeled compounds in acetonitrile-d3. Addition of tetracyanoethylene to their solutions in acetonitrile gave the [8 + 2] cycloaddition products of the corresponding heptafulvenes, indicating the intermediacy of the heptafulvenes. This stereomutation was too slow to detect in dichloromethane at the same temperature. Therefore, it is concluded that the stereomutation proceeds through the abstraction of the alpha-hydrogen by acetonitrile as a base followed by the protonation of the heptafulvene intermediate from the rear side. The entropies of activation which are significantly negative and large indicate abstraction of the alpha-hydrogen is the rate-determining step. The enthalpy of activation for the norbornane system (22.1 +/- 1.1 kcal/mol) is about 8 kcal/mol greater than that for the bicyclo[2.2.2]octane system (15.4 +/- 1.1 kcal/mol) and that for the adamantane system (13.1 +/- 1.3 kcal/mol). Molecular mechanics calculations (MMPI, MM2') for the three heptafulvenes and the corresponding phenyl derivatives (instead of the tropylium ions) indicated that the angle strain at the 8-position of the heptafulvenes controls the rate of the steremutation.

  DOI：

  10.1021/jo00003a028

文献信息

• [EN] SALTS OF ISOBUTYRIC ACID (1 R*, 2R*, 4R* ) -2- (2-{ [3- (4, 7-DIMETH0XY-1 H-BENZOIMIDAZOL-2-YL) -PROPYL] -METHYL-AMINO } -ETHYL) -5-PHENYL-BICYCLO [2.2.2] OCT-5- EN- 2 -YL<br/>[FR] SELS DE L'ESTER DU (1R*,2R*,4R*)-2-(2-{[3-(4,7-DIMÉTHOXY-1H-BENZOIMIDAZOL-2-YL)-PROPYL]-MÉTHYL-AMINO}-ÉTHYL)-5-PHÉNYL-BICYCLO[2.2.2]OCT-5-ÈN-2-YLE DE L'ACIDE ISOBUTYRIQUE
  申请人：ACTELION PHARMACEUTICALS LTD

  公开号：WO2010046857A1

  公开（公告）日：2010-04-29

  The invention relates to crystalline salts of isobutyric acid (1R*,2R*,4R*)-2-(2-[3-(4,7-dimethoxy-1H-benzoimidazol-2-yl)-propyl]-methyl-amino}-ethyl)-5-phenyl-bicyclo[2.2.2]oct-5-en-2-yl ester, processes for the preparation thereof, pharmaceutical compositions containing said crystalline salts, and their use as medicaments, especially as calcium channel blockers.

  该发明涉及异丁酸晶体盐（1R*，2R*，4R*）-2-（2-[3-（4,7-二甲氧基-1H-苯并咪唑-2-基）-丙基]-甲基氨基}-乙基）-5-苯基-双环[2.2.2]辛-5-烯-2-基酯，其制备方法，含有所述晶体盐的药物组合物，以及其作为药物的用途，特别是作为钙通道阻滞剂。
• [EN] BENZIMIDAZOLE DERIVATIVES AS CALCIUM CHANNEL BLOCKERS<br/>[FR] DÉRIVÉS DE BENZIMIDAZOLE EN TANT QUE BLOQUEURS DES CANAUX CALCIQUES
  申请人：ACTELION PHARMACEUTICALS LTD

  公开号：WO2009130679A1

  公开（公告）日：2009-10-29

  The invention relates to compounds of formula (I) wherein R1 represents aryl, which is unsubstituted, or mono-, di-, or tri-substituted wherein the substituents are independently selected from the group consisting of (C1-4alkyl, (C1-4)alkoxy, halogen, and trifluoromethyl; R2 represents hydrogen, or -CO-R21; R21 represents (C1-5)alkyl, (C1-3)fluoroalkyl, or (C3-6)cycloalkyl; m represents the integer 2, or 3; p represents the integer 2 or 3; and R3 represents hydrogen, or (C1-5)alkyl; and pharmaceutically acceptable salts of such compounds. These compounds are useful as calcium channel blockers.

  该发明涉及具有以下结构的化合物（I），其中R1代表芳基，该芳基未经取代，或者经过单取代、双取代或三取代，其中取代基可独立地选择自（C1-4烷基）、（C1-4）烷氧基、卤素和三氟甲基的组成部分；R2代表氢，或-CO-R21；R21代表（C1-5）烷基、（C1-3）氟烷基或（C3-6）环烷基；m代表整数2或3；p代表整数2或3；R3代表氢，或（C1-5）烷基；以及这些化合物的药用盐。这些化合物可用作钙通道阻滞剂。
• PREPARATION OF BICYCLO[2.2.2]OCTAN-2-ONE COMPOUNDS
  申请人：Abele Stefan

  公开号：US20130211104A1

  公开（公告）日：2013-08-15

  The present invention relates to a new process for the preparation of 6-hydroxy-5-arylbicyclo[2.2.2]octan-2-one compounds of the formula (II); which may subsequently be further transformed to compounds of the formula (I): The present invention further relates to novel compounds as such, which compounds are useful intermediates in the above process.

  本发明涉及一种制备公式（II）的6-羟基-5-芳基双环[2.2.2]辛烷-2-酮化合物的新工艺，该化合物随后可进一步转化为公式（I）的化合物： 本发明还涉及上述过程中有用的新化合物作为中间体。
• [EN] DIASTEREOSELECTIVE PREPARATION OF BICYCLO[2.2.2]OCTAN-2-ONE COMPOUNDS<br/>[FR] PRÉPARATION DIASTÉRÉOSÉLECTIVE DE COMPOSÉS BICYCLO[2.2.2]OCTAN-2-ONES
  申请人：ACTELION PHARMACEUTICALS LTD

  公开号：WO2012052943A1

  公开（公告）日：2012-04-26

  The present invention relates to a new process for the diastereoselective preparation of (1R*,4R*,5S*,6S*)-6-hydroxy-5-arylbicyclo[2.2.2]octan-2-one compounds, the compounds of the formula (II), which may subsequently be further transformed to 5-aryl-bicyclo[2.2.2]oct-5-en-2-one compounds of the formula (I): Formula (I), Formula (II). The present invention further relates to novel (1R*,2S*,3S*,4R*)-6-oxo-3-arylbicyclo[2.2.2]octan-2-yl methanesulfonate compounds as such, which compounds are useful intermediates in the preparation of 5-aryl-bicyclo[2.2.2]oct-5-en-2-one compounds of the formula (I).

  本发明涉及一种新的过程，用于对(1R*，4R*，5S*，6S*)-6-羟基-5-芳基双环[2.2.2]辛烷-2-酮化合物进行对映选择性制备，该化合物为公式(II)的化合物，该化合物随后可以进一步转化为公式(I)的5-芳基双环[2.2.2]辛-5-烯-2-酮化合物。本发明还涉及新的(1R*，2S*，3S*，4R*)-6-氧代-3-芳基双环[2.2.2]辛烷-2-甲磺酸酯化合物，这些化合物本身就是有用的中间体，用于制备公式(I)的5-芳基双环[2.2.2]辛-5-烯-2-酮化合物。
• BRIDGED SIX-MEMBERED RING COMPOUNDS
  申请人：Hilpert Kurt

  公开号：US20100130545A1

  公开（公告）日：2010-05-27

  The invention relates to compounds of formula (I), wherein R 1 , R 2 , R 1a , R 2a , R 3 , R 4 , A, B, X, W and n are as defined in the description, and pharmaceutically acceptable salts of such compounds. These compounds are useful as calcium channel blockers.

  本发明涉及式(I)的化合物，其中R1、R2、R1a、R2a、R3、R4、A、B、X、W和n如描述中所定义，并且这些化合物的药学上可接受的盐。这些化合物可用作钙通道阻滞剂。