monoethyl benzylidenemalonate | 24302-12-3

• 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: monoethyl benzylidenemalonate
• 英文别名: (E)-2-(Ethoxycarbonyl)-3-phenylprop-2-enoic acid；E-ethyl hydrogen benzalmalonate；benzylidene-malonic acid monoethyl ester；Benzalmalonsaeure-monoaethylester；Benzyliden-malonsaeure-monoaethylester；Benzalmalonaethylestersaeure；2-(Ethoxycarbonyl)-3-phenylacrylic acid；(E)-2-ethoxycarbonyl-3-phenylprop-2-enoic acid
• CAS: 24302-12-3
• 化学式: C₁₂H₁₂O₄
• 分子量: 220.225
• InChiKey: BHKULYKFSYZBQR-CSKARUKUSA-N

物化性质

• 沸点：
  370.8±30.0 °C(Predicted)
• 密度：
  1.238±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  16
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  63.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  monoethyl benzylidenemalonate 在 monomethyl prenylidenemalonate 、 L-脯氨醇 作用下， 以 苯 为溶剂， 反应 48.0h， 以71%的产率得到反式-肉桂酸乙酯
  参考文献：
  名称：

  由α-支化α,β-烯醛催化不对称合成多取代环己-1,3-二烯

  摘要：

  摘要 3-甲基-和3-苯基丁-2-烯醛在苯或THF中（S）-脯氨醇（0.1当量）存在下与亚烯基、芳基亚甲基-和亚烷基丙二酸的酸性单酯在-10至+反应22 °C 以中等 (10–43%) 的产率得到 4,6-二取代的环六-1,3-二烯-1-羧酸的旋光酯。由棉绒两种类型的酸性亚亚丙二酸酯形成的产物的对映体纯度在 28% 至 68% 之间变化，并且高于在相关亚烷基丙二酸酯的情况下观察到的纯度。在类似的条件下，亚环己基乙醛得到 1,5,6,7,8,8a-六氢萘的旋光衍生物，为顺式和反式异构体的混合物。

  DOI：

  10.1007/bf01435793
• 作为产物：
  描述：

  亚苯甲基丙二酸二乙酯 在 lithium hydroxide 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 4.0h， 生成 monoethyl benzylidenemalonate
  参考文献：
  名称：

  Structure–Activity Relationships and Blood Distribution of Antiplasmodial Aminopeptidase-1 Inhibitors

  摘要：

  Malaria is a severe infectious disease that causes between 655 000 and 1.2 million deaths annually. To overcome the resistance to current drugs, new biological targets are needed for drug development. Aminopeptidase M1 (PfAM1), a zinc metalloprotease, has been proposed as a new drug target to fight malaria. Herein, we disclosed the structure-activity relationships of a selective family of hydroxamate PfAM1 inhibitors based on the malonic template. In particular, we performed a "fluoro-scanning" around hit 1 that enlightened the key positions of the halogen for activity. The docking of the best inhibitor 2 is consistent with in vitro results. The stability of 2 was evaluated in microsomes, in plasma, and toward glutathione. The in vivo distribution study performed with the nanomolar hydroxamate inhibitor 2 (BDM14471) revealed that it reaches its site of action. However, it fails to kill the parasite at concentrations relevant to the enzymatic inhibitory potency, suggesting that killing the parasite remains a challenge for potent and druglike catalytic-site binding PfAM1 inhibitors. In all, this study provides important insights for the design of inhibitors of PfAM1 and the validity of this target.

  DOI：

  10.1021/jm301506h

文献信息

• Synthesis of polysubstituted 1,3-cyclohexadienes from ?-branched ?,?-alkenals and monoesters of ylidenemalonic acids
  作者：A. G. Nigmatov、I. N. Kornilova、E. P. Serebryakov

  DOI：10.1007/bf01433750

  日期：1996.1

  configurations of which were determined by means of1H NMR spectroscopy. In some cases the formation of cyclic dienes is impeded by the competing process of decarboxylation of acidic ylidenemalonates. The derivatives of 4,6-diphenyl-1,3-cyclohexadienecarboxylic acid were shown to be convenient precursors for the preparation ofmeta-terphenyls.

  摘要 3-甲基-和3-苯基-2-丁烯醛与亚烷基-、亚链烯基-和芳基亚甲基丙二酸的单酯在哌啶作为催化剂的存在下反应得到4,6-二取代的1,3-环己二烯羧酸在23 –96% 的产量。在相同条件下，亚环己基乙醛与异戊二烯-和亚苄基丙二酸的单酯反应，得到 1,5,6,7,8,8a 1-取代烷基的 1,8a-反式和 1,8a-顺式异构体的混合物-六氢化萘-2-羧酸盐，其比例和构型通过 1 H NMR光谱测定。在某些情况下，环状二烯的形成受到酸性亚亚基丙二酸酯脱羧的竞争过程的阻碍。4,6-二苯基-1的衍生物，
• Steric and electronic requirements of amide and ester groups in benzylidenemalonates
  作者：John M. Brown、Patrick J. Guiry、J. Christopher、P. Laing、Michael B. Hursthouse、K.M. Abdul Malik

  DOI：10.1016/0040-4020(95)00368-i

  日期：1995.7

  isolated stereoisomerically pure and is the only product of other synthetic routes. The configuration of benzylidinemalonates was established in two cases by X-ray crystallography, and the relative stability of the isomeric forms correctly simulated by MM2 calculations. In both the amide and oxazolidinone series, asymmetric hydrogenation catalysed by cationic Rh complexes gave a configurationally stable

  已经合成了立体异构的苄基丙二酸酯。在N-（2-乙氧基羰基-3-苯基丙烯酰基）-2-恶唑烷酮的情况下，可以同时获得E-和Z-异构体，但在存在下Z-异构体异构化（> 95％）为E-异构体催化量的Rh（I）络合催化剂。对于叔丁基酰胺基苯二丙二酸乙酯，Z-异构体最初在Knoevenagel条件下占主导地位，但很容易转变成更稳定的E-异构体，在此是分离的立体异构纯，是其他合成途径的唯一产物。在两种情况下，通过X射线晶体学确定了苄基丙二酸酯的构型，并通过MM2计算正确地模拟了异构体的相对稳定性。在酰胺和恶唑烷酮系列中，
• A process for the synthesis of β-ketoesters using in-situ generated (trimethylsilyl)malonates
  作者：Xui Wang、William T. Monte、James J. Napier、Ameen Ghannam

  DOI：10.1016/s0040-4039(00)78532-7

  日期：1994.12

  (TMS)ethyl malonate can be generated in-situ by treating potassium ethyl malonate with trimethylsilyl chloride and acylated with aliphatic or aromatic acyl imidazoles or chlorides in the presence of DBU to prepare a variety of β-ketoesters. This constitutes a high yield method for preparing β-ketoesters, which also can be extended to the formation of alkylidene malonates.

  （TMS）丙二酸乙酯可以通过用三甲基甲硅烷基氯处理丙二酸钾钾并在DBU的存在下用脂族或芳族酰基咪唑或氯化物酰化以制备各种β-酮酸酯来原位产生。这构成了制备β-酮酸酯的高产率方法，其也可以扩展到亚烷基丙二酸酯的形成。
• Copper-Catalyzed Carboxylation of C–F Bonds with CO₂
  作者：Si-Shun Yan、Dong-Shan Wu、Jian-Heng Ye、Li Gong、Xin Zeng、Chuan-Kun Ran、Yong-Yuan Gui、Jing Li、Da-Gang Yu

  DOI：10.1021/acscatal.9b02351

  日期：2019.8.2

  An effective Cu-catalyzed selective formal carboxylation of C-F bonds with an atmospheric pressure of CO2 is reported. A variety of gem-difluoroalkenes, gem-difluorodienes, and alpha-trifluoro-methyl alkenes show high reactivity and selectivity for this ipso monocarboxylation. Under mild conditions, diverse important alpha-fluoroacrylic acids and alpha,alpha-difluorocarboxylates are obtained in good-to-high yields. Moreover, this operationally simple protocol features good functional group tolerance, is readily scalable, and the resulting products are readily converted into bioactive alpha-fluorinated carbonyl compounds, indicating potential application in biochemistry and drug discovery. Mechanistic studies reveal that fluorinated boronate esters might be vital intermediates in this transformation.
• Enzyme-catalyzed hydrolyses of E/Z-diastereotopic and E/Z-diastereomeric esters. Effect on selectivity by reaction media
  作者：Tanja Schirmeister、Hans Hartwig Otto

  DOI：10.1021/jo00070a015

  日期：1993.8

  PLE-catalyzed hydrolyses of different types of E/Z-diastereotopic diesters and E/Z-diastereomeric monoesters have been studied. Arylidenepropanedioic diesters are specifically hydrolyzed to the Z-half esters, whereas the de values for dialkylated methylene propanedioic diesters range between 33 and 79% (Z). D values for the hydrolyses of the 3-methyleneazetidin-2-ones in detergent-buffer systems depend on the size of the substituent in the alpha-position. Diastereoselectivity of these substrates is affected by addition of the cosolvents acetonitrile and methanol.