3-hydroxy-2-methylene-3-(4-pyridinyl)propanenitrile

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: 3-hydroxy-2-methylene-3-(4-pyridinyl)propanenitrile
• 英文别名: 3-hydroxy-2-methylene-3-(4-pyridyl)propanenitrile；2-[hydroxy(pyridin-4-yl)methyl]acrylonitrile；2-[Hydroxy(pyridin-4-yl)methyl]prop-2-enenitrile
• 化学式: C₉H₈N₂O
• mdl: MFCD10657354
• 分子量: 160.175
• InChiKey: QRCHXUGMUUWFOK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.3
• 重原子数：
  12
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.111
• 拓扑面积：
  56.9
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3-hydroxy-2-methylene-3-(4-pyridinyl)propanenitrile 在 乙醛肟 、 palladium diacetate 、 三苯基膦 作用下， 以 乙醇 、 水 为溶剂， 反应 4.0h， 以84%的产率得到3-hydroxy-2-methylene-3-(pyridin-4-yl)propionamide
  参考文献：
  名称：

  丙烯酰胺Baylis-Hillman加合物的有效合成：Pd催化的丙烯腈Baylis-Hillman加合物的水合

  摘要：

  开发了一种有效的钯催化两步法合成丙烯酰胺的Baylis-Hillman加合物。该方法涉及丙烯腈Baylis-Hillman加合物的制备以及乙二醛与乙醛肟的Pd催化水合反应。

  DOI：

  10.1016/j.tetlet.2009.08.127
• 作为产物：
  描述：

  4-吡啶甲醛 、 丙烯腈 在 三乙烯二胺 作用下， 反应 0.3h， 以99%的产率得到3-hydroxy-2-methylene-3-(4-pyridinyl)propanenitrile
  参考文献：
  名称：

  Baylis–Hillman reaction under solvent-free conditions — Remarkable rate acceleration and yield enhancement

  摘要：

  为了在无溶剂的 "纯净条件 "下显著加快 Baylis-Hillman 反应的速率并提高产率，以及在无溶剂条件下分离产物，我们开发了一种简单而高效的方法。在 20 摩尔 DABCO 的存在下，等摩尔量的醛和烯烃在纯净条件下进行反应，在大多数情况下都能在最短的反应时间内获得最高的产率，为质子和非质子溶剂中的质子转移机制提供了支持。研究发现，在无溶剂条件下，芳香醛的反应尤其快速、选择性强且产率高。

  DOI：

  10.1139/v10-133

文献信息

• Synthesis of 1,3-Dialkyl-1,2,3-triazolium Ionic Liquids and Their Applications to the Baylis−Hillman Reaction
  作者：Yunkyung Jeong、Jae-Sang Ryu

  DOI：10.1021/jo100618d

  日期：2010.6.18

  Novel 1,3-dialkyl-1,2,3-triazolium ionic liquids were synthesized via click reactions using 1-trimethylsilylacetylene and alkyl azides and were efficient reaction media for the Baylis−Hillman reaction. The problems associated with deprotonation of the C-2 hydrogen of [bmim][PF6] could be suppressed in the reaction of [bmTr][PF6] or [bmTr][NTf2]. 1,3-Dialkyl-1,2,3-triazolium ionic liquids are chemically

  新型的1,3-二烷基-1,2,3-三唑鎓离子液体是通过使用1-三甲基甲硅烷基乙炔和叠氮化物的点击反应合成的，是Baylis - Hillman反应的有效反应介质。在[bmTr] [PF 6 ]或[bmTr] [NTf 2 ]的反应中，可以抑制与[bmim] [PF 6 ]的C-2氢的去质子化有关的问题。1，3-二烷基-1，2，3-三唑鎓离子液体在碱性条件下是化学惰性的，并且比普通的1，3-二烷基咪唑鎓离子液体更适合于涉及碱的反应介质。
• Antimitotic Activity on Sea Urchin Embryonic Cells of Seven Antiparasitic Morita-Baylis-Hillman Adducts: A Potential New Class of Anticancer Drugs
  作者：Jocelmo C. A. Leite、Claudio G. L. Junior、Fabio P. L. Silva、Suervy C.O. Sousa、Mario L. A. A. Vasconcellos、Luis F. Marques-Santos

  DOI：10.2174/1573406411208061003

  日期：2012.9.1

  In the present work we described improvements in the 1-7 antiparasitic Morita-Baylis-Hillman Adducts synthesis and their antimitotic activity on sea urchin embryonic cells. The 2-[Hydroxy(2-nitrophenyl)methyl]acrylonitrile (1) and 2-[Hydroxy(4-bromophenyl) methyl]acrylonitrile (4) were the most effective compounds to block the progression to embryonic morula stage (EC50 = 75.8 M and 72.6 M, respectively)

  在本工作中，我们描述了1-7种抗寄生虫的森田-贝利斯-希尔曼加合物合成的改进及其对海胆胚胎细胞的抗有丝分裂活性。2- [羟基（2-硝基苯基）甲基]丙烯腈（1）和2- [羟基（4-溴苯基）甲基]丙烯腈（4）是阻止胚胎桑ula期发展的最有效化合物（EC50 = 75.8？ M和72.6？M分别）。化合物1和4在阻断第一细胞分裂方面也有效，但程度较小。2- [羟基（吡啶-4-基）甲基]丙烯腈（7）表现出强烈的细胞分裂抑制作用，并发展到第一个分裂和桑ula期。荧光染料挤出试验表明，这些加合物不是ABC蛋白的底物，这使这些新型的潜在抗癌药物引起了更多关注。
• Regio- and Diastereoselectivity in the Thiomethylation of α-(1-Hydroxyalkyl)acrylate Derivatives
  作者：Philip O. Deane、Jeffry J. Guthrie-Strachan、Perry T. Kaye、Ruth E. Whittaker

  DOI：10.1080/00397919808004829

  日期：1998.7

  Abstract The regio-and diastereoselectivity of reactions of selected α-(1-hydroxyalkyl)acrylate derivatives with sodium methanethiolate have been investigated. The hydroxy compounds typically undergo conjugate addition with up to 66% d.e., while the acetoxy and bromo analogues favour SN' and SN reactions, respectively.

  摘要 研究了选定的 α-（1-羟烷基）丙烯酸酯衍生物与甲硫醇钠反应的区域选择性和非对映选择性。羟基化合物通常以高达 66% 的 de 进行共轭加成，而乙酰氧基和溴类似物分别有利于 SN' 和 SN 反应。
• Hydroxyl ionic liquid (HIL)-immobilized quinuclidine for Baylis–Hillman catalysis: synergistic effect of ionic liquids as organocatalyst supports
  作者：Xueling Mi、Sanzhong Luo、Hui Xu、Long Zhang、Jin-Pei Cheng

  DOI：10.1016/j.tet.2005.12.045

  日期：2006.3

  Hydroxyl ionic liquid (HIL) has been explored as a novel support for Baylis-Hillman catalyst. The HIL-supported catalyst showed a better catalytic activity compared to other IL-immobilized catalyst that has no hydroxyl group attached to the IL scaffold. The hydroxyl group linked on IL played an important role in facilitating efficient catalysis under solvent-free conditions. The corresponding Baylis-Hillman and aza-Baylis-Hillman adducts were obtained in good to excellent yields in all cases examined. The HIL-supported quinuclidine can be readily recovered and reused for six times without significant loss of catalytic activity. (c) 2005 Elsevier Ltd. All rights reserved.
• Efficient synthesis of 16 aromatic Morita–Baylis–Hillman adducts: Biological evaluation on Leishmania amazonensis and Leishmania chagasi
  作者：Cláudio G.L. Junior、Priscila A.C. de Assis、Fábio P.L. Silva、Suervy C.O. Sousa、Natália G. de Andrade、Ticiano P. Barbosa、Patrícia L.N. Nerís、Luiz V.G. Segundo、Ítalo C. Anjos、Gabriel A.U. Carvalho、Gerd B. Rocha、Márcia R. Oliveira、Mário L.A.A. Vasconcellos

  DOI：10.1016/j.bioorg.2010.08.002

  日期：2010.12

  Sixteen aromatic Morita-Baylis-Hillman adducts (MBHA) 1-16 were efficiently synthesized in a one step Morita-Baylis-Hillman reaction (MBHR) involving commercial aldehydes with methyl acrylate or acrylonitrile (81-100% yields) without the formation of side products on DABCO catalysis and at low temperature (0 degrees C). The toxicities of these compounds were assessed against promastigote form of Leishmania amazonensis and Leishmania chagasi. The low synthetic cost of these MBHA, green synthetic protocols, easy one-step synthesis from commercially available and cheap reagents as well as the very good antileishmanial activity obtained for 14 and 16 (IC50 values of 6.88 mu g mL(-1) and 11.06 mu g mL(-1) respectively on L. amazonensis; 9.58 mu g mL(-1) and 14.34 mu g mL(-1) respectively on L. chagasi) indicates that these MBHA can be a novel and promising class of anti-parasitic compounds. (C) 2010 Elsevier Inc. All rights reserved.