Benzyliden-cyanacetanilid | 25695-87-8

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 肉桂酸及其衍生物
• 英文名称: Benzyliden-cyanacetanilid
• 英文别名: (2E)-2-cyano-N,3-diphenylprop-2-enamide；(E)-2-cyano-N,3-diphenylprop-2-enamide
• CAS: 25695-87-8
• 化学式: C₁₆H₁₂N₂O
• 分子量: 248.284
• InChiKey: OIKLEXHAFRNQHO-SDNWHVSQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  19
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  52.9
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  二溴丙二酸二乙酯 、 Benzyliden-cyanacetanilid 在 锌 、 六甲基磷酰三胺 作用下， 以 四氢呋喃 、 乙醚 为溶剂， 以64%的产率得到ethyl 5-cyano-2,4-dioxo-3,6-diphenyl-3-azabicyclo[3.1.0]hexene-1-carboxylate
  参考文献：
  名称：

  Reactions of organozinc reagents derived from dialkyl 2,2-dibromomalonates with 3-aryl-2-cyanoprop-2-enamides

  摘要：

  Organozinc compounds obtained by treatment of dialkyl 2,2-dibromomalonates with metallic zinc reacted with N-substituted 3-aryl-2-cyanoprop-2-enoic acid amides to give alkyl 3-R-6-aryl-5-cyano-2,4-dioxo-3-azabicyclo[3.1.0]hexane-1-carboxamides as a single stereoisomer.

  DOI：

  10.1134/s1070363206060156
• 作为产物：
  描述：

  (E)-α-cyanocinnamic acid 在 氯化亚砜 、 三乙胺 作用下， 反应 5.0h， 生成 Benzyliden-cyanacetanilid
  参考文献：
  名称：

  Ganushchak; Lesyuk; Fedorovich, Russian Journal of Organic Chemistry, 2000, vol. 36, # 11, p. 1677 - 1682

  摘要：

  DOI：

文献信息

• Stereoselective control in the Staudinger reactions involving monosubstituted ketenes with electron acceptor substituents: experimental investigation and theoretical rationalization
  作者：Hengzhen Qi、Xinyao Li、Jiaxi Xu

  DOI：10.1039/c0ob00783h

  日期：——

  The stereoselectivity of the Staudinger reactions involving monosubstituted ketenes with electron acceptor substituents was investigated experimentally by determination of the product stereochemistry and theoretically via DFT calculations. The results indicate that imines preferentially attack the less sterically hindered exo-side of the ketenes to generate zwitterionic intermediates. Subsequently, for cyclic imines, the intermediates undergo a conrotatory ring closure directly to produce β-lactams, while for linear imines, the imine moiety of the intermediates isomerizes to more stable intermediates, which further undergo a conrotatory ring closure to afford trans-β-lactams. The steric hindrance and the isomerization, rather than the torquoelectronic effect, play crucial roles in controlling the stereoselectivity in the practical Staudinger reactions involving monosubstituted ketenes with electron acceptor substituents, although the unaccessible borylketene with a powerful electron acceptor group controls the stereoselectivity torquoelectronically, in theory.

  通过确定产物立体化学和基于密度泛函理论（DFT）的计算，实验上研究了涉及带有电子受体取代基的单取代乙烯酮的斯陶丁格反应的立体选择性。结果表明，亚胺优先攻击乙烯酮上立体障碍较小的外侧，生成内鎓离子中间体。随后，对于环状亚胺，中间体直接进行协同环合反应生成β-内酰胺；而对于线性亚胺，中间体的亚胺部分异构化为更稳定的中间体，后者进一步进行协同环合反应，产生反式β-内酰胺。在实际涉及带有电子受体取代基的单取代乙烯酮的斯陶丁格反应中，立体障碍和异构化而不是扭曲电子效应在控制立体选择性中起着关键作用，尽管在理论上，具有强电子受体基团的不可获得的硼乙烯酮通过扭曲电子效应控制立体选择性。
• Tandem halogenation/Michael-initiated ring-closing reaction of α,β-unsaturated nitriles and activated methylene compounds: one-pot diastereoselective synthesis of functionalized cyclopropanes
  作者：Xiaoqing Xin、Qian Zhang、Yongjiu Liang、Rui Zhang、Dewen Dong

  DOI：10.1039/c4ob00087k

  日期：——

  An efficient one-pot synthetic route to highly substituted cyclopropanes has been developed from readily available α,β-unsaturated nitriles and doubly activated methylene compounds under very mild conditions in a highly diastereoselective manner, which involves halogenation, Michael addition and intramolecular ring-closing reaction sequences.

  已经从易于获得的α，β-不饱和腈和双活化的亚甲基化合物在非常温和的条件下以高度非对映选择性的方式开发了一种高效的一锅合成路线，该路线涉及卤化，迈克尔加成和分子内闭环反应序列。
• The Compound (E)-2-Cyano-N,3-diphenylacrylamide (JMPR-01): A Potential Drug for Treatment of Inflammatory Diseases
  作者：Pablo Rayff da Silva、Renan Fernandes do Espírito Santo、Camila de Oliveira Melo、Fábio Emanuel Pachú Cavalcante、Thássia Borges Costa、Yasmim Vilarim Barbosa、Yvnni M. S. de Medeiros e Silva、Natália Ferreira de Sousa、Cristiane Flora Villarreal、Ricardo Olímpio de Moura、Vanda Lucia dos Santos

  DOI：10.3390/pharmaceutics14010188

  日期：——

  The compound (E)-2-cyano-N,3-diphenylacrylamide (JMPR-01) was structurally developed using bioisosteric modifications of a hybrid prototype as formed from fragments of indomethacin and paracetamol. Initially, in vitro assays were performed to determine cell viability (in macrophage cultures), and its ability to modulate the synthesis of nitrite and cytokines (IL-1β and TNFα) in non-cytotoxic concentrations. In vivo, anti-inflammatory activity was explored using the CFA-induced paw edema and zymosan-induced peritonitis models. To investigate possible molecular targets, molecular docking was performed with the following crystallographic structures: LT-A4-H, PDE4B, COX-2, 5-LOX, and iNOS. As results, we observed a significant reduction in the production of nitrite and IL-1β at all concentrations used, and also for TNFα with JMPR-01 at 50 and 25 μM. The anti-edematogenic activity of JMPR-01 (100 mg/kg) was significant, reducing edema at 2–6 h, similar to the dexamethasone control. In induced peritonitis, JMPR-01 reduced leukocyte migration by 61.8, 68.5, and 90.5% at respective doses of 5, 10, and 50 mg/kg. In silico, JMPR-01 presented satisfactory coupling; mainly with LT-A4-H, PDE4B, and iNOS. These preliminary results demonstrate the strong potential of JMPR-01 to become a drug for the treatment of inflammatory diseases.

  化合物 (E)-2-氰基-N,3-二苯基丙烯酰胺（JMPR-01）是通过对吲哚美辛和扑热息痛片段形成的混合原型进行生物异构修饰而开发的。首先进行了体外试验，以确定细胞活力（在巨噬细胞培养物中）及其在无细胞毒性浓度下调节亚硝酸盐和细胞因子（IL-1β 和 TNFα）合成的能力。在体内，使用 CFA 诱导的爪水肿和齐莫散诱导的腹膜炎模型探索了抗炎活性。为了研究可能的分子靶标，与以下晶体结构进行了分子对接：LT-A4-H、PDE4B、COX-2、5-LOX 和 iNOS。结果发现，在所有使用浓度下，亚硝酸盐和 IL-1β 的产生均显著减少，JMPR-01 在 50 和 25 μM 浓度下，TNFα 的产生也显著减少。JMPR-01（100 毫克/千克）的抗致畸活性非常显著，可在 2-6 小时内减轻水肿，与地塞米松对照组相似。在诱导腹膜炎中，JMPR-01 的剂量分别为 5、10 和 50 毫克/千克时，白细胞迁移率分别降低了 61.8%、68.5% 和 90.5%。在硅学中，JMPR-01 与 LT-A4-H、PDE4B 和 iNOS 的耦合效果令人满意。这些初步结果表明，JMPR-01 极有可能成为一种治疗炎症性疾病的药物。
• Hassaneen, Hamdi M.; Shawali, Ahmad S.; Elwan, Nehal M., Heterocycles, 1990, vol. 31, # 2, p. 247 - 253
  作者：Hassaneen, Hamdi M.、Shawali, Ahmad S.、Elwan, Nehal M.

  DOI：——

  日期：——
• Reaction of organozinc reagents prepared from bromomalonic acid esters and zinc with 3-aryl-2-cyanopropenoic acid primary amides
  作者：V. V. Shchepin、P. S. Silaichev、Yu. G. Stepanyan、N. Yu. Russkikh、M. I. Vakhrin、M. A. Ezhikova、M. I. Kodess

  DOI：10.1134/s1070428006110054

  日期：2006.11

  Organozinc compounds prepared from bromomalonic acid esters and zinc react with 3-aryl-2-cyanopropenoic acid primary amides giving a single diastereomer of the corresponding 1-R'-4-aryl-2,6-dioxo-5-cyanopiperidine-3-carboxylic acid esters, or 3-R'-6-aryl-2,4-dioxo-5-cyano-3-azabicyclo[3.1.0]hexene-1-carboxylic acid esters.