4-(phenylethynyl)-6-methyl-2-pyrone | 186032-77-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡喃
• 英文名称: 4-(phenylethynyl)-6-methyl-2-pyrone
• 英文别名: 6-Methyl-4-(2-phenylethynyl)pyran-2-one
• CAS: 186032-77-9
• 化学式: C₁₄H₁₀O₂
• 分子量: 210.232
• InChiKey: NWTHBCFWDMBJDA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  26.3
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  4-(phenylethynyl)-6-methyl-2-pyrone 在 palladium on activated charcoal 喹啉 、 氢气 作用下， 以 苯 为溶剂， 反应 1.0h， 以87.2%的产率得到(Z)-4-phenylethenyl-6-merthyl-2-pyrone
  参考文献：
  名称：

  2-Pyrones possessing antimicrobial and cytotoxic activities

  摘要：

  The 2-pyrone sub-unit is found in a number of natural products possessing broad spectrum biological activity. Such compounds are validated as being capable of binding to specific protein domains and able to exert a remarkable range of biological effects. In an effort to identify synthetic 2-pyrones with interesting biological effects, herein we report the synthesis and biological evaluation of 4-substituted-6-methyl-2-pyrones. Synthetic routes to 4-alkyl/alkenyl/aryl/alkynyl-6-methyl-2-pyrones have been developed utilising Sonogashira, Suzuki and Negishi cross-coupling starting from readily available 4-bromo-6-methyl-2-pyrone. Specific conditions for each organometallic protocol were required for successful cross-coupling. In particular, a triethylamine/acetonitrile-base/solvent mixture was crucial to Sonogashira alkynylation of 4-bromo-6-methyl-2-pyrone, whereas thallium carbonate was a mandatory base for the Suzuki cross-coupling of trialkylboranes. The 2-pyrones demonstrate potent inhibitory activity against Bacillus subtilis, Escherichia coli, Staphylococcus aureus, Schizosaccharomyces pombe and Botrytis cinerea. The growth inhibitory activities of selected 2-pyrones were determined in A2780 human ovarian carcinoma and K562 human chronic myelogenous leukaemia cell lines using an in vitro cell culture system (MTT assay). These studies demonstrate that 4-phenylethynyl-, 4-tetrahydropyranylpropargyl ether- and 4-ethynyl-6-methyl-2-pyrones have excellent potential as a new class of anticancer agents. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2004.01.051
• 作为产物：
  描述：

  4-羟基-6-甲基-2-吡喃酮 在 bis-triphenylphosphine-palladium(II) chloride copper(l) iodide 、 三乙胺 、 三氯氧磷 作用下， 以 乙腈 为溶剂， 反应 20.0h， 生成 4-(phenylethynyl)-6-methyl-2-pyrone
  参考文献：
  名称：

  Sonogashira交叉偶联中的卤代-2-吡喃酮：Pd介导反应的GC分析的局限性，优化和后果

  摘要：

  在CuI助催化剂的存在下，详细研究了Pd（PPh 3）2 Cl 2介导的4-溴-6-甲基-2-吡喃酮（5）与苯乙炔的Sonogashira偶联。Pd的浓度极大地影响了产品的产量，较低的Pd负载量有利于更高的转化率和更纯的交叉偶联产品。在仅用硅胶淬灭的样品（用CH 2 Cl 2洗脱）中观察到产物转化的后反应时间依赖性。在使用4-硝基溴苯（14）以及较小程度地（E）和（Z）-3-碘-2-丙酸乙酯（16）的反应中反映出了这种效果。）在相似的条件下。已经开发出了更有效的淬火系统（使用过量的dppe）以能够准确确定产品转化率。或者，在真空中除去溶剂和碱（Et 3 N），或用饱和氯化铵水溶液淬灭，可防止Sonogashira偶联剂进一步流失。对通过硅胶洗脱的样品进行了ESI-MS研究，以探讨可溶性Pd / Cu物质的性质。4-氯和6-氯-2-吡喃酮的Sonogashira交叉偶联（18和20，分别进行

  DOI：

  10.1016/j.tet.2005.07.102

文献信息

• Palladium-Catalysed Alkynylations of 2-Pyrone (Pyran-2-one) Halides
  作者：Ian J. Fairlamb、Feng Ju Lu、Jan Peter Schmidt

  DOI：10.1055/s-2003-42405

  日期：——

  The 2-pyrone sub-unit is found in a large number of natural products possessing broad-spectrum biological activity. As such, efficient synthetic methods are required to enable facile access to substituted 2-pyrone derivatives. Important conditions for the Sonogashira alkynylation of 4-bromo-6-methyl-2-pyrone (3a) have been developed, and compared against Negishi’s methodology. The best conditions for Sonogashira alkynylation was found to be the use of Pd/C with added Ph3P as the catalyst, in the presence of catalytic CuI, in a mixture of MeCN and Et3N at reflux. Using Negishi’s standard conditions, terminal alkynylzinc reagents, generated in situ from terminal alkynes with LDA or n-BuLi and subsequent reaction with anhydrous ZnBr2, were reacted with 3a at room temperature using Pd(PPh3)4 as the catalyst in THF.

  2-吡喃酮亚基存在于许多具有广谱生物活性的天然产物中。因此，需要高效的合成方法以便于制备取代的2-吡喃酮衍生物。已经开发出重要的条件用于4-溴-6-甲基-2-吡喃酮（3a）的Sonogashira炔基化反应，并与其基于Negishi的方法进行了比较。最佳的Sonogashira炔基化条件是使用添加了Ph3P的Pd/C作为催化剂，在含有催化量CuI的MeCN和Et3N混合物中回流。按照Negishi的标准条件，由端炔与LDA或n-BuLi反应生成并随后与无水ZnBr2反应生成的端炔基锌试剂，在室温下以Pd(PPh3)4作为催化剂在THF中与3a反应。
• Sonogashira Cross-Coupling Reactions Catalysed by Copper-Free Palladium Zeolites
  作者：Laurent Djakovitch、Patrick Rollet

  DOI：10.1002/adsc.200404141

  日期：2004.12

  A heterogeneous copper-free [Pd(NH3)4]2+/(NH4)Y catalyst was employed to achieve the heterogeneous Sonogashira reaction of aryl halides with terminal alkynes. Several reaction parameters like solvent, base and temperature were evaluated. When optimised, the coupling reaction of bromobenzene with phenylacetylene gave a 45% yield of diphenylacetylene within 3 h using only 1 mol % Pd. This catalyst was

  使用非均相的无铜[Pd（NH 3）4 ] 2+ /（NH 4）Y催化剂实现芳基卤化物与末端炔的非均相Sonogashira反应。评价了一些反应参数，例如溶剂，碱和温度。当进行优化时，仅使用1 mol％的Pd，溴苯与苯乙炔的偶合反应在3小时内可得到45％的二苯乙炔收率。该催化剂已成功应用于一系列芳基碘化物和溴化物的偶合反应：芳基碘化物和活化的芳基溴化物几乎给出定量的产率，而未活化的芳基溴化物导致合理的产率（20％至45％）。该异质[Pd（NH 3）4 ] 2+对无铜Sonogashira反应而言，对（/ NH 4）Y催化剂显示出有效，稳定的浸出性和可回收性。
• A natural light induced regioselective 6π-electrocyclisation–oxidative aromatisation reaction: experimental and theoretical insights
  作者：Benjamin E. Moulton、Hao Dong、Ciara T. O'Brien、Simon B. Duckett、Zhenyang Lin、Ian J. S. Fairlamb

  DOI：10.1039/b811284c

  日期：——

  Stoichiometric intermolecular Pauson-Khand reactions of 4-(phenylethynyl)-6-methyl-2-pyrones with norbornene and dicobalt(0)octacarbonyl provide cyclopentenone products that undergo a facile 6pi-electrocyclisation-oxidative aromatisation transformation in the presence of natural light and oxygen, affording functionalised benzo[h]indeno[1,2-f]isochromene type products. The results are rationalised by

  4-（苯基乙炔基）-6-甲基-2-吡喃酮与降冰片烯和二甲双（0）八羰基的化学计量分子间Pauson-Khand反应提供了环戊烯酮产品，该产品在自然光和氧气存在下容易进行6pi-电环化-氧化芳构化转化，提供官能化的苯并[h]茚并[1,2-f]异戊二烯型产品。通过理论研究使结果合理化，这些研究证实了在2吡喃环系统中C3有利于电环化过程。“三烯基”取代基的身份和精确排列控制着电环化是否在自然光下发生。
• Kalinin; Shilova; Okladnoi, Doklady Chemistry, 1996, vol. 351, # 1-3, p. 276 - 278
  作者：Kalinin、Shilova、Okladnoi、Schmidhammer

  DOI：——

  日期：——
• An efficient synthesis of 4-alkenyl/alkynyl-6-methyl-2-pyrones via Pd-catalysed coupling on 4-bromo-6-methyl-2-pyrone
  作者：Lester R. Marrison、Julia M. Dickinson、Razwan Ahmed、Ian J.S. Fairlamb

  DOI：10.1016/s0040-4039(02)02207-4

  日期：2002.12

  We herein report the efficient syntheses of biologically active 4-alkenyl- and 4-alkynyl-6-methyl-2-pyrones using Pd-catalysed coupling procedures. A palladium on carbon/triphenylphosphine combination is shown to be the most effective catalyst for Sonogashira cross-coupling of several terminal acetylenes with 4-bromo-6-methyl-2-pyrone in yields of up to 95%. (C) 2002 Elsevier Science Ltd. All rights reserved.