ethyl α-cyano-3-(2-naphthalenyl)propionate | 773084-85-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: ethyl α-cyano-3-(2-naphthalenyl)propionate
• 英文别名: ethyl 2-cyano-3-(naphthalen-2-yl)propanoate；Ethyl 2-cyano-3-naphthalen-2-ylpropanoate
• CAS: 773084-85-8
• 化学式: C₁₆H₁₅NO₂
• 分子量: 253.301
• InChiKey: UYHATDZXYTUJCI-UHFFFAOYSA-N

物化性质

• 沸点：
  440.0±25.0 °C(Predicted)
• 密度：
  1.153±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  19
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  50.1
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  ethyl α-cyano-3-(2-naphthalenyl)propionate 在 肼 作用下， 以6%的产率得到4-Naphthalen-2-ylmethyl-1,2-dihydro-pyrazol-3-one
  参考文献：
  名称：

  Studies on New Acidic Azoles as Glucose-Lowering Agents in Obese, Diabetic db/db Mice

  摘要：

  Bioisosteric substitution was used as a tool to generate several new structural alternatives to the thiazolidine-2,4-dione and tetrazole heterocycles as potential antidiabetic agents. Among the initial leads that emerged from this strategy, a family of acidic azoles isoxazol-3- and -5-ones and a pyrazol-3-one, showed significant plasma glucose-lowering activity (17-42% reduction) in genetically obese, diabetic db/db mice at a dose of 100 mg/kg/day x 4. Structure-activity relationship studies determined that 5-alkyl-4-(arylmethyl)pyrazol-3-ones, which exist in solution as aromatic enol/iminol tautomers, were the most promising new class of potential antidiabetic agent (32-45% reduction at 20 mg/kg/d x 4). Included in this work are convenient syntheses for several types of acidic azoles that may find use as new acidic bioisosteres in medicinal chemistry such as the antidiabetic lead 5-(trifluoromethyl)pyrazol-3-one (hydroxy tautomer) and aza homologs of the pyrazolones, 1,2,3-triazol-5-ones (hydroxy tautomer) and 1,2,3,4-tetrazol-5-one heterocycles. log P and pK(a) data for 15 potential acidic bioisosteres, all appended to a 2-naphthalenylmethyl residue so as to maintain a similar distance between the acidic hydrogen and arene nucleus, are presented. This new data set allows comparison of a wide variety of potential acid mimetics (pK(a) 3.78-10.66; log P -0.21 to 2.76) for future drug design.

  DOI：

  10.1021/jm00004a008
• 作为产物：
  描述：

  ethyl 2-cyano-3-(naphth-2-yl)acrylate 在 3,5-diethyl 1,4-dihydropyridine-3,5-dicarboxylate 作用下， 以 水 为溶剂， 反应 24.0h， 以96%的产率得到ethyl α-cyano-3-(2-naphthalenyl)propionate
  参考文献：
  名称：

  水中的Hantzsch酯无催化化学还原共轭烯烃中的碳-碳双键†

  摘要：

  描述了一种简单，有效和绿色的方案，用于通过Hantzsch酯化学共轭还原烯烃中的碳-碳双键。在没有任何其他催化剂的情况下，一系列具有强吸电子基团的共轭烯烃在水中被还原，收率极佳。所用的反应条件均能耐受诸如腈，酯，硝基，氟，氯，溴，呋喃基和苄基之类的官能团。

  DOI：

  10.1039/c3ra48072k

文献信息

• Base-Promoted Cascade Approach for the Preparation of Reduced Knoevenagel Adducts Using Hantzsch Esters as Reducing Agent in Water
  作者：Zhouyu Wang、Tao He、Ronghua Shi、Yimou Gong、Guangyou Jiang、Ming Liu、Shan Qian

  DOI：10.1055/s-0035-1562099

  日期：——

  condensation–reduction approach, which was carried out in water, has been reported. Using Hantzsch esters as reducing agent, under the promotion of base, a variety of reduced Knoevenagel adducts could be easily prepared by direct alkyl­ation of malononitrile, ethyl 2-cyanoacetate, and 2-(4-nitrophenyl)acetonitrile, respectively. Meanwhile, a gram-scale synthesis of the protocol was also realized with excellent

  已经报道了在水中进行的级联 Knoevenagel 缩合还原方法。以Hantzsch酯为还原剂，在碱的促进下，丙二腈、2-氰基乙酸乙酯和2-(4-硝基苯基)乙腈分别直接烷基化反应，可以很容易地制备出多种还原的Knoevenagel加合物。同时，该协议的克级合成也以优异的分离产率实现。
• Room Temperature, Reductive Alkylation of Activated Methylene Compounds: Carbon–Carbon Bond Formation Driven by the Rhodium-Catalyzed Water–Gas Shift Reaction
  作者：Scott E. Denmark、Malek Y. S. Ibrahim、Andrea Ambrosi

  DOI：10.1021/acscatal.6b03183

  日期：2017.1.6

  The rhodium-catalyzed water–gas shift reaction has been demonstrated to drive the reductive alkylation of several classes of activated methylene compounds at room temperature. Under catalysis by rhodium trichloride (2–3 mol %), carbon monoxide (10 bar), water (2–50 equiv), and triethylamine (2.5–7 equiv), the scope has been successfully expanded to cover a wide range of alkylating agents, including

  铑催化的水煤气变换反应已被证明可在室温下驱动几类活化的亚甲基化合物的还原烷基化反应。在三氯化铑（2-3％摩尔），一氧化碳（10 bar），水（2-50当量）和三乙胺（2.5-7当量）的催化下，其范围已成功扩大，涵盖了广泛的烷基化反应中等至高产率的包括脂肪族和芳香族醛以及环状酮在内的助剂。在某些方面，该方法与现有的还原烷基化方案相当，并且在某些方面超过了该方法。
• Catalyst-Free [3 + 3] Annulation/Oxidation of Cyclic Amidines with Activated Olefins: When the Substrate Olefin Is Also an Oxidant
  作者：Wendan Han、Yuanhang Li、Kaki Raveendra Babu、Jing Li、Yuhai Tang、Yong Wu、Silong Xu

  DOI：10.1021/acs.joc.1c00717

  日期：2021.6.4

  DBN (1,5-diazabicyclo(4.3.0)non-5-ene) with activated olefins, i.e., 2-arylidenemalononitriles and 2-cyano-3-aryl acrylates, to afford tricyclic 2-pyridones and pyridin-2(1H)-imines, respectively. The mechanism has been proposed based on DFT calculations. In the reaction, the cyclic amidines serve as C,N-bisnucleophiles for the cyclization, while the olefins play a dual role by acting as both reactants

  在此，我们描述了环脒如 DBU（1,8-二氮杂双环（5.4.0）undec-7-ene）和 DBN（1,5-二氮杂双环（4.3 .0)non-5-ene)与活化的烯烃，即2-亚芳基丙二腈和2-氰基-3-芳基丙烯酸酯，分别提供三环2-吡啶酮和吡啶-2(1 H )-亚胺。该机制是基于 DFT 计算提出的。在反应中，环脒作为环化的C，N-双亲核试剂，而烯烃通过作为反应物和氧化剂发挥双重作用。
• Tandem catalytic condensation and hydrogenation processes in ionic liquids
  作者：Mubeen Baidossi、Asutosh V. Joshi、Sudip Mukhopadhyay、Yoel Sasson

  DOI：10.1016/j.tetlet.2005.01.092

  日期：2005.3

  A domino reaction composed of a Knoevenagel condensation combined with a simultaneous catalytic hydrogenation is reported in an ionic liquid solvent under mild conditions (298-363 K and 300 kPa). No interference between the catalysts (Pd/C and amine acetate salt) of the two diverse steps was monitored. The product could be neatly extracted by diethyl ether and the solvent containing the catalysts could be recycled and reused five times without any loss in activity or selectivity. The same methodology in a common organic solvent such as DMA resulted in significant competing parallel hydrogenation of the aidehyde to alcohol. (C) 2005 Elsevier Ltd. All rights reserved.
• Studies on New Acidic Azoles as Glucose-Lowering Agents in Obese, Diabetic db/db Mice
  作者：Kenneth L. Kees、Thomas J. Caggiano、Kurt E. Steiner、John J. Fitzgerald、Michael J. Kates、Thomas E. Christos、John M. Kulishoff、Robin D. Moore、Michael L. McCaleb

  DOI：10.1021/jm00004a008

  日期：1995.2

  Bioisosteric substitution was used as a tool to generate several new structural alternatives to the thiazolidine-2,4-dione and tetrazole heterocycles as potential antidiabetic agents. Among the initial leads that emerged from this strategy, a family of acidic azoles isoxazol-3- and -5-ones and a pyrazol-3-one, showed significant plasma glucose-lowering activity (17-42% reduction) in genetically obese, diabetic db/db mice at a dose of 100 mg/kg/day x 4. Structure-activity relationship studies determined that 5-alkyl-4-(arylmethyl)pyrazol-3-ones, which exist in solution as aromatic enol/iminol tautomers, were the most promising new class of potential antidiabetic agent (32-45% reduction at 20 mg/kg/d x 4). Included in this work are convenient syntheses for several types of acidic azoles that may find use as new acidic bioisosteres in medicinal chemistry such as the antidiabetic lead 5-(trifluoromethyl)pyrazol-3-one (hydroxy tautomer) and aza homologs of the pyrazolones, 1,2,3-triazol-5-ones (hydroxy tautomer) and 1,2,3,4-tetrazol-5-one heterocycles. log P and pK(a) data for 15 potential acidic bioisosteres, all appended to a 2-naphthalenylmethyl residue so as to maintain a similar distance between the acidic hydrogen and arene nucleus, are presented. This new data set allows comparison of a wide variety of potential acid mimetics (pK(a) 3.78-10.66; log P -0.21 to 2.76) for future drug design.