2-氰基-2-(1-氰基环己基)乙酸乙酯 | 51939-79-8

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 中文名称: 2-氰基-2-(1-氰基环己基)乙酸乙酯
• 英文名称: ethyl cyano(1-cyanocyclohexyl)acetate
• 英文别名: ethyl 2-cyano-2-(1-cyanocyclohexyl)acetate；Ethyl-1-cyanocyclohexyl-cyanoacetat；2-Cyan-2-(1-cyan-cyclohexyl)-essigsaeure-aethylester；cyano-(1-cyano-cyclohexyl)-acetic acid ethyl ester；1-Cyan-cyclohexan-cyanessigsaeure-(1)-aethylester；(1-cyanocyclohexyl) cyanoacetic acid ethyl ester；Cyan-(1-cyan-cyclohexyl)-essigsaeure-aethylester
• CAS: 51939-79-8
• 化学式: C₁₂H₁₆N₂O₂
• 分子量: 220.271
• InChiKey: VXAPUDWUMVBMHO-UHFFFAOYSA-N

物化性质

• 熔点：
  54 °C
• 沸点：
  210-212 °C(Press: 22 Torr)
• 密度：
  1.10±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  16
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.75
• 拓扑面积：
  73.9
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-氰基-2-(1-氰基环己基)乙酸乙酯 在 镍 盐酸 、 乙醇 、 水 、 氢气 作用下， 以 盐酸 、 乙醇 为溶剂， 25.0~90.0 ℃ 、1000.0 kPa 条件下， 反应 102.0h， 生成 加巴喷丁
  参考文献：
  名称：

  通过加氢氰酸到环己二烯丙二酸酯或氰基（亚环己基）乙酸酯来合成加巴喷丁的新方法

  摘要：

  研究了抗惊厥加巴喷丁（1-（氨基甲基）环己烷乙酸）的几种合成途径。讨论了不同路线的优缺点，并指出了最经济和技术上最可行的综合方法。

  DOI：

  10.1002/hlca.19910740208
• 作为产物：
  描述：

  环己酮 在 ammonium acetate 、 溶剂黄146 作用下， 以 乙醇 、 甲苯 为溶剂， 反应 5.0h， 生成 2-氰基-2-(1-氰基环己基)乙酸乙酯
  参考文献：
  名称：

  高Fsp3特征的螺[环烷-吡啶并酮]的合成

  摘要：

  背景：如今，在药物设计和发现过程中，除其候选药物的生物活性外，还非常关注候选药物的理化参数。不利的理化参数会阻碍候选药物的成功。 目标：Lovering等。介绍了Fsp3特性作为碳键饱和度的量度，该特性与药物的理化副弹药有关。药物研究集中于合成具有高Fsp3特性的化合物。 方法：为了改善候选药物分子的物理化学性质（clogP，溶解度，更有利的ADME谱等），一种可能性是用生物等排杂芳族部分（例如用一个或两个含氮原子的系统）代替全碳芳族系统例如吡啶和哒嗪等。另一种选择是增加候选药物的Fsp3特性。设计新的螺环化合物时考虑了这两个方面，在本研究中描述了其合成方法。 结果：从2-氧杂螺[4.5]癸烷-1,3-二酮或2-氧杂螺[4.4]壬烷-1,3-二酮开始，通过与苯甲醚或四氢呋喃的Friedel-Crafts反应获得了相应的酮羧酸。用肼，甲基肼或苯肼处理酮羧酸，形成哒嗪酮环。哒嗪酮的N-烷基化反

  DOI：

  10.2174/1570180816666190710130119

文献信息

• 2-aza-4-(alkoxycarbonyl)spiro[4,5]decan-3-one
  申请人：Lonza Ltd.

  公开号：US04956473A1

  公开（公告）日：1990-09-11

  2-Aza-4-(alkoxycarbonyl)spiro[4,5]-decan-3-one and a process for the production of it, starting either from cyclohexylidene malonic acid esters or cyclohexylidene cyanoalkylates. The cyclohexylidene malonic acid ester is reacted with hydrocyanic acid in the presence of a catalytic amount of alkali cyanide or with a stoichiometric amount of alkali cyanide, in an alcohol, and subsequently treated with an acid. The resultant (1-cyanocyclohexyl) malonic acid dialkyl ester is converted by catalytic hydrogenation into the product. The cyclohexylidene cyanoalkylate is reacted with a stoichiometric amount of alkali cyanide, in an alcohol or with hydrocyanic acid in the presence of a catalytic amount of an alkali cyanide. The resultant (1-cyanocyclohexyl)-cyanoacetic acid alkyl ester is reacted in an alcohol in an acid to provide (1-cyanocyclohexyl) malonic acid dialkyl ester. The later ester is converted by catalytic hydrogenation into the product. Process of using the product for the production of 1-(aminomethyl)cyclohexane acetic acid by converting the product with HCl or sulfuric acid at an elevated temperature.

  2-Aza-4-(烷氧羰基)螺[4,5]-癸烷-3-酮及其生产方法，可以从环己烯基丙二酸酯或环己烯基氰烷酸酯出发。将环己烯基丙二酸酯与氢氰酸在碱性氰化物的催化剂存在下或与等量的碱性氰化物在醇中反应，然后用酸处理。所得的（1-氰基环己基）丙二酸二烷基酯经催化氢化转化为产物。环己烯基氰烷酸酯与等量的碱性氰化物在醇中反应，或者在碱性氰化物的催化剂存在下与氢氰酸反应。所得的（1-氰基环己基）-氰乙酸烷基酯在酸性条件下在醇中反应，形成（1-氰基环己基）丙二酸二烷基酯。后者经催化氢化转化为产物。使用该产物生产1-(氨甲基)环己烷乙酸的方法是将产物与HCl或硫酸在高温下反应。
• Eco-friendly conjugate hydrocyanation of α-cyanoacrylates using potassium hexacyanoferrate(II) as cyanating reagent
  作者：Yu-Peng Zhang、Xiao-Chun Hu、Zheng Li

  DOI：10.1515/chempap-2015-0055

  日期：2015.1.1

  The conjugate hydrocyanation of α-cyanoacrylates through chemoselective 1,4-addition to synthesise α,β-dicyanopropanoates by one-pot two-step procedure using potassium hexacyanoferrate(II) as an eco-friendly cyanide source, benzoyl chloride as a promoter and potassium carbonate as a catalyst is described. The advantages of this protocol are use of a non-toxic, non-volatile and inexpensive cyanating reagent

  使用六氰合铁酸钾（II）作为环境友好的氰化物源，苯甲酰氯作为促进剂和钾，通过一锅两步法通过化学选择的1,4-加成反应进行化学选择性的1,4-加成，使α-氰基丙烯酸酯共轭氢氰化描述了碳酸盐作为催化剂。该方案的优点是使用无毒，不挥发和廉价的氰化试剂，高产品收率和简单的操作程序。
• Synthesis of 4,4-Disubstituted 2,3-Dicyano-5-imino-2-pyrrolines. Reaction of Alkylidenemalononitriles with Trimethylsilyl Cyanide
  作者：Naoto Chatani、Terukiyo Hanafusa

  DOI：10.1246/bcsj.63.2134

  日期：1990.7

  The reaction of alkylidenemalononitriles with trimethylsilyl cyanide in the presence of KCN/18-crown-6 gave 4,4-disubstituted 2,3-dicyano-5-imino-2-pyrrolines in high yields.

  在 KCN/18-crown-6 存在下，亚烷基丙二腈与三甲基甲硅烷基氰化物的反应以高产率得到 4,4-二取代的 2,3-二氰基-5-亚氨基-2-吡咯啉。
• Antiarthritic and supressor cell inducing activity of azaspiranes: structure-function relationships of a novel class of immunomodulatory agents
  作者：Alison M. Badger、David A. Schwartz、Donald H. Picker、James W. Dorman、Fontaine C. Bradley、Elaine N. Cheeseman、Michael J. DiMartino、Nabil Hanna、Christopher K. Mirabelli

  DOI：10.1021/jm00173a010

  日期：1990.11

  Spirogermanium (1; 8,8-diethyl-N,N-dimethyl-2-aza-8- germaspiro[4.5]decane-2-propanamine dihydrochloride) is a potent cytotoxic agent in vitro which has demonstrated limited activity in experimental animal tumor models. Subsequently, it has been reported that spirogermanium has antiarthritic and suppressor cell-inducing activity. We have synthesized a series of substituted 8-hetero-2-azaspiro[4.5]decane and 9-hetero-3-azaspiro[5.5]undecane analogues of spirogermanium to identify the heteroatom requirements for in vivo antiarthritic and suppressor cell-inducing activity. This structure-activity relationship study has identified that appropriately substituted silicon and carbon analogues of spirogermanium retain both antiarthritic and immunosuppressive activity, with the 8,8-dipropyl (carbon) analogue being among the most active. Following the identification of N,N-dimethyl-8,8-dipropyl-2-azaspiro[4.5]decane-2-propanamine++ + dihydrochloride (9) as a more active analogue than spirogermanium, a series of 8,8-dipropyl analogues with various amine substituents were synthesized. A number of these analogues had activity similar to that of 9. A correlation between activity in the adjuvant arthritic rat and the ability to induce suppressor cells (r = 0.894, p less than 0.001) suggests an association between the two pharmacologic effects. While the precise biochemical mechanism(s) for the pharmacological activity is unclear, these data suggest that compounds within this series, e.g., N,N-dimethyl-8,8-dipropyl-2-azaspiro[4.5]decane-2-propanamine++ + dihydrochloride, may provide effective therapy in diseases of autoimmune origin and/or the prevention of rejection in tissue transplantation.
• Le Moal,H. et al., Bulletin de la Societe Chimique de France, 1964, p. 579 - 584
  作者：Le Moal,H. et al.

  DOI：——

  日期：——