1-methyl-3,5-bis-(2-methyl-benzylidene)-piperidin-4-one | 920030-39-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: 1-methyl-3,5-bis-(2-methyl-benzylidene)-piperidin-4-one
• 英文别名: 1-Methyl-3,5-bis-(2-methyl-benzyliden)-piperidin-4-on；(3E,5E)-1-methyl-3,5-bis[(2-methylphenyl)methylidene]piperidin-4-one
• CAS: 920030-39-3
• 化学式: C₂₂H₂₃NO
• 分子量: 317.431
• InChiKey: UIVIGAYSWQMFGB-ZIOPAAQOSA-N

物化性质

• 沸点：
  498.6±45.0 °C(Predicted)
• 密度：
  1.125±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  24
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.23
• 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-(2-methyl-benzylidene)-piperidin-4-one 在 溶剂黄146 、 三乙胺 作用下， 以 苯 为溶剂， 反应 0.13h， 生成 6-methyl-8-(2-methylphenyl)-4-[(E)-(2-methylphenyl)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-甲基-4-哌啶酮 、 2-甲基苯甲醛 在 sodium hydroxide 作用下， 以 乙醇 为溶剂， 反应 0.25h， 生成 1-methyl-3,5-bis-(2-methyl-benzylidene)-piperidin-4-one
  参考文献：
  名称：

  一种高度原子经济，化学，区域和立体选择性的合成方法以及螺吡咯并噻唑类抗结核药的评估

  摘要：

  源自取代的靛红和1,3-噻唑烷-4-羧酸的偶氮甲亚胺的1,3-偶极环加成反应生成一系列1-甲基-3,5-双[（E）-芳基亚甲基]-四氢-4（ 1 H）-吡啶酮以定量产率提供了化学，区域和立体选择性的新型螺-吡咯并噻唑。使用琼脂稀释法筛选这些化合物的抗结核分枝杆菌H37Rv（MTB）和耐多药结核分枝杆菌（MDR-TB）的体外活性。在合成的化合物中，螺[5.3''-5''-硝基氧吲哚-螺-[6.3']-1'-甲基-5'-（2,4-二氯苯基亚甲基）四氢-4'（1 H）吡啶酮-7-（2,4-二氯苯基）四氢-1 H-吡咯并[1,2-发现c ] [1,3]噻唑（9k）最具活性，对MTB和MDR-TB的最低抑菌浓度（MIC）为0.6μM。

  DOI：

  10.1016/j.bmcl.2009.10.107

文献信息

• γ-Pyridones by Isomerization. Substituted 1-Methyl-3,5-dibenzyl-4-pyridones
  作者：Nelson J. Leonard、David M. Locke

  DOI：10.1021/ja01612a042

  日期：1955.4
• An atom efficient, solvent-free, green synthesis and antimycobacterial evaluation of 2-amino-6-methyl-4-aryl-8-[(E)-arylmethylidene]-5,6,7,8-tetrahydro-4H-pyrano[3,2-c]pyridine-3-carbonitriles
  作者：Raju Ranjith Kumar、Subbu Perumal、Palaniappan Senthilkumar、Perumal Yogeeswari、Dharmarajan Sriram

  DOI：10.1016/j.bmcl.2007.09.095

  日期：2007.12

  An atom efficient, green protocol for the synthesis of fifteen 2-amino-6-methyl-4-aryl-8-[(E)-arylmethylidene]-5,6,7,8-tetrahydro4H-pyrano[3,2-c] pyridine-3-carbonitriles in quantitative yields from the reaction of 1-methyl-3,5-bis[(E)-arylmethylidene]tetrahydro-4(1H)-pyridinones with malononitrile in presence of solid sodium ethoxide under solvent-free condition is described. The compounds were tested for their in vitro activity against Mycobacterium tuberculosis H37Rv (MTB), multi-drug resistant tuberculosis (MDR-TB), and Mycobacterium smegmatis using agar dilution method. 2-Amino-4-[4-(dimethylamino) phenyl]-8-(E)-[4(dimethylamino) phenyl] methylidene-6-methyl-5,6,7,8-tetrahydro-4H-pyrano[3,2-c]-pyridine-3-carbonitrile was found to be the most potent compound (MIC: 0.43 mu M) against MTB and MDR-TB, being 100 times more active than standard, isoniazid against MDRTB. (c) 2007 Elsevier Ltd. All rights reserved.
• 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.
• A highly atom economic, chemo-, regio- and stereoselective synthesis, and discovery of spiro-pyrido-pyrrolizines and pyrrolidines as antimycobacterial agents
  作者：Raju Ranjith Kumar、Subbu Perumal、Palaniappan Senthilkumar、Perumal Yogeeswari、Dharmarajan Sriram

  DOI：10.1016/j.tet.2008.01.072

  日期：2008.3

  The 1,3-dipolar cycloaddition of azomethine ylides derived from acenaphthenequinone and alpha-amino acids viz. proline, phenylglycine and sarcosine to a series of 1-methyl-3,5-bis[(E)-arylmethylidene]tetrahydro-4(1H)-pyridinones afforded novel spiro-pyrido-pyrrolizines and pyrrolidines chemo-, regio- and stereoselectively in quantitative yields. These compounds were screened for their in vitro activity against Mycobacterium tuberculosis H37Rv (MTB), multi-drug resistant Mycobacterium tuberculosis (MDR-TB) and Mycobacterium smegmatis using agar dilution method. Among the synthesized compounds, spiro-[2.2 '']acenaphthene-1 ''-one-spiro [3.3']-5'-(2-chlorophenylmethylidene)-1'-methyltetrahydro-4'(1H)-pyridinone-4-(2-chlorophenyl)hexahydro-1H-pyrrolizine (3e) was found to be the most active with a minimum inhibitory concentration (MIC) of 0.4 mu g/mL against MTB and MDR-TB. (C) 2008 Elsevier Ltd. All rights reserved.
• 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.