1-methyl-3,5-bis-[1]naphthylmethylene-piperidin-4-one | 2167-01-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: 1-methyl-3,5-bis-[1]naphthylmethylene-piperidin-4-one
• 英文别名: 1-Methyl-3,5-bis-[1]naphthylmethylen-piperidin-4-on；1-Methyl-3,5-bis-(1-naphthylmethylen)-4-piperidon；(3E,5E)-1-methyl-3,5-bis(naphthalen-1-ylmethylidene)piperidin-4-one
• CAS: 2167-01-3
• 化学式: C₂₈H₂₃NO
• 分子量: 389.497
• InChiKey: OEDJFAJIJMSAON-MUPYBJATSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.1
• 重原子数：
  30
• 可旋转键数：
  2
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  20.3
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  1-methyl-3,5-bis-[1]naphthylmethylene-piperidin-4-one 在 溶剂黄146 、 三乙胺 作用下， 以 苯 为溶剂， 反应 0.1h， 生成 6-methyl-8-(1-naphthyl)-4-[(E)-(1-naphthyl)methylidene]-1-phenyl-4,5,6,7,7a,8-hexahydro-[1,2,4]oxadiazolo[5,4-d]pyrido[3,4-c][1,5]benzothiazepine
  参考文献：
  名称：

  六氢吡啶并[3,4- c ] [1,5]苯并硫氮杂s与一氧化氮的简便合成及高度原子经济的1,3-偶极环加成反应：六氢[1,2,4]恶二唑[5,4- d ]的立体选择性形成] pyrido [3,4- c ] [1,5]苯并噻氮平

  摘要：

  获得了一系列新的2-甲基-11-芳基-4-[（E）-芳基亚甲基] -1,2,3,4,11,11a-六氢吡啶并[3,4- c ] [1,5]苯并噻氮平在无溶剂微波辐射下，在催化量的乙酸存在下，邻氨基苯硫酚与（E）-1-甲基-3,5-双（亚芳基）-4-哌啶酮的反应。这些双亲性化合物与一氧化二氮进行高度原子经济的1,3-偶极环加成反应，得到一系列新颖的6-甲基-1-苯基-8-芳基-4-[[（E）-芳基亚甲基] -4,5,6， 7,7a，8-六氢[1,2,4]恶二唑并[ 5,4- d ]吡啶并[3,4- c ] [1,5]苯并硫氮杂s类化合物。

  DOI：

  10.1016/j.tet.2007.05.097
• 作为产物：
  描述：

  N,N-二-(beta-羰基乙氧基乙基)甲胺 在 盐酸 、 氢氧化钾 、 乙醇 、 水 、 sodium hydride 、 苯 作用下， 生成 1-methyl-3,5-bis-[1]naphthylmethylene-piperidin-4-one
  参考文献：
  名称：

  Piperidine Derivatives. XIX. Esters of Substituted 4-Piperidinols

  摘要：

  DOI：

  10.1021/ja01185a052

文献信息

• Sacrificial azomethine ylide cycloaddition controlled chemoselective nitrile oxide cycloaddition to 1-methyl-3,5-bis[(E)-arylmethylidene]tetrahydro-4(1H)-pyridinones: formation of mono-spiro-isoxazolines
  作者：Raju Ranjith Kumar、Subbu Perumal

  DOI：10.1016/j.tet.2007.09.033

  日期：2007.12

  The 1,3-dipolar cycloaddition of an azomethine ylide to 1-methyl-3,5-bis[(E)-arylmethylidene]tetrahydro-4(1H)-pyridinones afforded novel spiro-pyrrolidines in good yields. Further cycloaddition of these spiro-pyrrolidines with nitrile oxide afforded mono-spiro-isoxazolines in moderate yields (45–56%), presumably via a di-spiro intermediate, which undergoes a spontaneous cycloreversion of the spiro-pyrrolidine

  偶氮甲碱内酯的1，3-偶极环加成反应成1-甲基-3,5-双[（E）-芳亚甲叉基]四氢-4（1 H）-吡啶酮，以良好的收率提供了新型螺吡咯烷。这些螺吡咯烷与一氧化二氮的进一步环加成，以中等收率（45-56％）提供了单螺-异恶唑啉，大概是通过双螺中间体，螺中间体经历了螺-吡咯烷单元的自发环还原。相反，将一氧化氮直接环加成到1-甲基-3,5-双[（E）-芳亚甲叉基]四氢-4（1 H）-吡啶酮中得到单螺-异恶唑啉作为次要产物，而二主要形成-螺-异恶唑啉。
• Discovery of Antimycobacterial Spiro-piperidin-4-ones: An Atom Economic, Stereoselective Synthesis, and Biological Intervention
  作者：Raju Ranjith Kumar、Subbu Perumal、Palaniappan Senthilkumar、Perumal Yogeeswari、Dharmarajan Sriram

  DOI：10.1021/jm800545k

  日期：2008.9.25

  An atom economic and stereoselective synthesis of several spiro-piperidin-4-ones through 1,3-dipolar cycloaddition of azomethine ylides generated in situ from isatin and (alpha-amino acids viz. proline, phenylglycine, and sarcosine to a series of 1-methyl- 3,5-bis [(E)-arylmethylidene]tetrahydro-4(1H)-pyridinones is described. These compounds were evaluated for their in vitro and in vivo activity against Mycobacterium tuberculosis H37Rv (MTB), multidrug resistant Mycobacterium tuberculosis (MDR-TB), and Mycobacterium smegmatis (MC2). Compound 4-(4-fluorophenyl)-5-phenylpyrrolo(spiro[2.3"]oxindole)spiro[3.3']-1'-methyl-5'-(4-fluorophenylmethylideiie)piperidin-4'-one (4e) was found to be the most active in vitro with a MIC value of 0.07 mu M against MTB and was 5.1 and 67.2 times more potent than isoniazid and ciprofloxacin, respectively. In vivo, compound 4e decreased the bacterial load in lung and spleen tissues with 1.30 and 3.73-log 1.0 protections respectively and was considered to be promising in reducing bacterial count in lung and spleen tissues.
• Multi-component, 1,3-dipolar cycloaddition reactions for the chemo-, regio- and stereoselective synthesis of novel hybrid spiroheterocycles in ionic liquid
  作者：Stephen Michael Rajesh、Balasubramainan Devi Bala、Subbu Perumal

  DOI：10.1016/j.tetlet.2012.07.078

  日期：2012.10

  A library of novel 1-methyl-4-arylpyrrolo-(spiro(2.2']indan-1',3'-dione)-spiro[3.3 '']-1 ''-methyl/benzyl-5 ''-(arylmethylidene)piperidin-4 ''-ones and 1-methyl-4-arylpyrrolo-(spiro[2.11']-11H-indeno(1,2-b]quinoxaline)-spiro[3.3 '']-1 ''-methyl/benzyl-5 ''-(arylmethylidene)piperidin-4 ''-ones have been synthesized via 1,3-dipolar azomethine ylide cycloaddition in the ionic liquid, 1-butyl-3-methylimidazolium bromide ([BMIm]Br), in excellent yields. (C) 2012 Elsevier Ltd. All rights reserved.
• Chemo-, regio- and stereoselective 1,3-dipolar cycloaddition of C-aryl-N-phenylnitrones over 3,5-bis(arylidene)-1-methylpiperidin-4-ones: synthesis of highly substituted novel spiro-isoxazolidines
  作者：Raju Ranjith Kumar、Subbu Perumal、Henri B. Kagan、Regis Guillot

  DOI：10.1016/j.tet.2006.09.106

  日期：2006.12

  1,3-Dipolar cycloaddition of C-aryl-N-phenylnitrones to 3,5-bis-(arylidene)-1-methylpiperidin-4-ones affords novel mono- and bis-spiroisoxazolidines in moderate yields. In general, this reaction predominantly yields mono-spiroisoxazolidine, wherein the oxygen of the nitrone is linked to the beta-carbon of the benzylidene moiety, while 3,5-bis-(2-chloro- and 3-nitro-benzylidene)-1-methylpiperidin-4-ones afford predominantly bis-spiroisoxazolidines. The cycloaddition of mono-spiroisoxazolidines occurs with facial diastereoselectivity to furnish bis-spiroisoxazolidines. The nitrogen in the heterocyclic ring of the 3,5-bis-(arylidene)-1-methylpiperidin-4-ones facilitates the cycloaddition through transannular ((NC)-C-...=O) and/or homoconjugative ((NC)-C-...=C) interactions. (c) 2006 Elsevier Ltd. All rights reserved.
• An atom economic synthesis and AChE inhibitory activity of novel dispiro 7-aryltetrahydro-1H-pyrrolo[1,2-c][1,3]thiazole and 4-aryloctahydroindolizine N-methylpiperidin-4-one hybrid heterocycles
  作者：Sathiyamoorthi Sivakumar、Raju Ranjith Kumar、Mohamed Ashraf Ali、Tan Soo Choon

  DOI：10.1016/j.ejmech.2013.04.050

  日期：2013.7

  The 1,3-dipolar cycloaddition of azomethine ylides generated in situ from acenaphthenequinone and alpha-amino acids viz. 1,3-thiazolone-4-carboxylic acid and piperidine-2-carboxylic acid to a series of 1-methyl-3,5-bis[(E)-arylmethylidene]tetrahydro-4(1H)-pyridinones afforded novel spiro[5.2 '']acenaphthene-1 ''-onespiro[6.3']-5'-arylmethylidene-1'-methylpiperidin-4'-one-7-aryltetrahydro-1H-pyrrolo[12-c][1,3]thiazoles and spiro[2.2 '']acenaphthene-1 ''-onespiro[3.3']-5'-arylmethylidene-1'-methylpiperidin-4'-one-4-aryloctahydroindolizines respectively in quantitative yields. These compounds were evaluated for their AChE inhibitory activity and compound 3c was found to be the most potent with IC50 1.86 mu mol/L. (C) 2013 Elsevier Masson SAS. All rights reserved.