2,6-dimethyl-3,5-dimethoxycarbonyl-4-(m-chlorophenyl)pyridine | 103026-82-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: 2,6-dimethyl-3,5-dimethoxycarbonyl-4-(m-chlorophenyl)pyridine
• 英文别名: (+/-)-dimethyl 4-(3-chlorophenyl)-2,6-dimethylpyridine-3,5-dicarboxylate；dimethyl 4-(3-chlorophenyl)-2,6-dimethyl-3,5-pyridinedicarboxylate；Dimethyl 4-(3-chlorophenyl)-2,6-dimethylpyridine-3,5-dicarboxylate
• CAS: 103026-82-0
• 化学式: C₁₇H₁₆ClNO₄
• 分子量: 333.771
• InChiKey: GFBKPZYODOUUQE-UHFFFAOYSA-N

物化性质

• 熔点：
  112.5-114.0 °C(Solv: isopropyl ether (108-20-3))
• 沸点：
  419.3±45.0 °C(Predicted)
• 密度：
  1.244±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  23
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  65.5
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2,6-dimethyl-3,5-dimethoxycarbonyl-4-(m-chlorophenyl)pyridine 生成 dimethyl 6-(3-chlorophenyl)-3,4-dimethyl-2,5-pyridinedicarboxylate 、 dimethyl 2-(3-chlorophenyl)-5,6-dimethyl-3,4-pyridinedicarboxylate
  参考文献：
  名称：

  Hantzsch 1,4-二氢吡啶和吡啶的光化学

  摘要：

  研究了一些在苯环上带有取代基的汉茨（Hantzsch）4-苯基-1,4-二氢吡啶（三个异构的氯衍生物和4'-硝基衍生物）的光化学性质。所有这些化合物均未有效芳香化为相应的吡啶（在366 nm处量子产率<10 -4，在254 nm处量子产率<10 -2）。此过程几乎不受分子氧的影响，并由质子转移引发（来自C 4–H），可能是从激发的单重态到溶剂。继而，如此形成的吡啶以相当或更高的效率是光反应性的。因此，对4-（3'-氯苯基）和4-（4'-氯苯基）汉茨吡啶进行位置重排以分别形成两个异构体。该反应通过杜瓦瓶苯-pr烷路径发生。如果是次要异构体，则在杜瓦瓶中还会发生1,3位移位。对4-（2'-氯苯基）衍生物进行C–Cl键均溶，这导致苯基环化到形成吡喃环的酯基之一上。

  DOI：

  10.1016/j.tet.2008.01.104
• 作为产物：
  描述：

  1,4-dihydro-2,6-dimethyl-4-(3-chlorophenyl)-3,5-pyridinedicarboxylic acid dimethyl ester 在 硝酸 作用下， 反应 1.0h， 以66%的产率得到2,6-dimethyl-3,5-dimethoxycarbonyl-4-(m-chlorophenyl)pyridine
  参考文献：
  名称：

  人肝微粒体对4-芳基和4-烷基取代的2,6-二甲基-3,5-双（烷氧基羰基）-1,4-二氢吡啶的氧化作用和涉及细胞色素P-450形式的免疫化学证据。

  摘要：

  4-取代的2,6-二甲基-3,5-双（烷氧基羰基）-1,4-二氢吡啶很重要，因为它们作为钙通道阻滞剂。检查了人肝微粒体对14个4-芳基和四个4-烷基取代的衍生物的混合功能氧化。所有4-芳基化合物的酶促氧化的主要产物是含有4-芳基的吡啶衍生物。相反，4-烷基化合物形成吡啶衍生物，其中在4-位存在氢原子并且烷基丢失；这些化合物还使细胞色素P-450失活，并在酶促氧化后导致硝苯地平氧化酶活性丧失。所有这些反应均受到针对纯化的人肝硝苯地平氧化酶细胞色素P-450（P-450NF）的抗体的抑制，表明该酶在这些化合物的氧化中起主要作用。4-烷基化合物的氧化不仅导致P-450NF的损失，而且还导致细胞色素P-450同工酶催化其他反应（非那西丁O-去乙基化和己糖3'-羟基化）的催化活性降低。结果表明，P-450NF（或密切相关的酶形式）负责人肝微粒体中这些硝苯地平相关化合物的氧化，并且代谢高度依赖于4-取

  DOI：

  10.1021/jm00159a007

文献信息

• Oxidation of 4-aryl- and 4-alkyl-substituted 2,6-dimethyl-3,5-bis(alkoxycarbonyl)-1,4-dihydropyridines by human liver microsomes and immunochemical evidence for the involvement of a form of cytochrome P-450
  作者：Ronald H. Boecker、F. Peter Guengerich

  DOI：10.1021/jm00159a007

  日期：1986.9

  lost; these compounds also inactivated cytochrome P-450 and caused the loss of nifedipine oxidase activity after enzymatic oxidation. All of these reactions were extensively inhibited by an antibody raised to purified human liver nifedipine oxidase cytochrome P-450 (P-450NF), indicating a major role for this enzyme in the oxidation of these compounds. Oxidation of the 4-alkyl compounds led not only

  4-取代的2,6-二甲基-3,5-双（烷氧基羰基）-1,4-二氢吡啶很重要，因为它们作为钙通道阻滞剂。检查了人肝微粒体对14个4-芳基和四个4-烷基取代的衍生物的混合功能氧化。所有4-芳基化合物的酶促氧化的主要产物是含有4-芳基的吡啶衍生物。相反，4-烷基化合物形成吡啶衍生物，其中在4-位存在氢原子并且烷基丢失；这些化合物还使细胞色素P-450失活，并在酶促氧化后导致硝苯地平氧化酶活性丧失。所有这些反应均受到针对纯化的人肝硝苯地平氧化酶细胞色素P-450（P-450NF）的抗体的抑制，表明该酶在这些化合物的氧化中起主要作用。4-烷基化合物的氧化不仅导致P-450NF的损失，而且还导致细胞色素P-450同工酶催化其他反应（非那西丁O-去乙基化和己糖3'-羟基化）的催化活性降低。结果表明，P-450NF（或密切相关的酶形式）负责人肝微粒体中这些硝苯地平相关化合物的氧化，并且代谢高度依赖于4-取
• Mild, Selective and High-Yield Oxidation of Hantzsch 1,4-Dihydropyridines with Lead(IV) Acetate
  作者：Mladen Litvić、Ivica Cepanec、Mirela Filipan、Karmen Kos、Anamarija Bartolinčić、Vinka Drušković、Mohamed Majed Tibi、Vladimir Vinković

  DOI：10.3987/com-04-10194

  日期：——

  Aromatization of 1, 4-dihydropyridines with lead(IV) acetate under mild reaction conditions is described. The method is very selective, mild and versatile in the synthesis of different substituted pyridines.

  描述了在温和的反应条件下用乙酸铅 (IV) 芳构化 1, 4-二氢吡啶。该方法在不同取代吡啶的合成中选择性强、温和且通用。
• Rapid, efficient, room temperature aromatization of Hantzsch-1,4-dihydropyridines with vanadium(V) salts: superiority of classical technique versus microwave promoted reaction
  作者：Mirela Filipan-Litvić、Mladen Litvić、Vladimir Vinković

  DOI：10.1016/j.tet.2008.08.103

  日期：2008.11

  The aromatization of 1,4-dihydropyridines (1,4-DHPs) employing group 4 (Zr and Hf) and 5 (V, Nb, Ta) elements of periodic system has been studied. The reaction with VOCl3 in dichloromethane at room temperature afforded products, substituted pyridines, in high-to-excellent yield. For the first time, the formation of charge-transfer complexes (CTCs) has been evidenced in preorganization step between

  研究了使用周期系统的第4组（Zr和Hf）和第5组（V，Nb，Ta）元素对1,4-二氢吡啶（1,4-DHPs）进行的芳构化。在室温下与VOCl 3在二氯甲烷中的反应以高至优异的产率提供了产物，取代的吡啶。首次在电子转移之前的1,4-DHP和氧化剂之间的预组织步骤中证明了电荷转移络合物（CTC）的形成。仅在中性溶剂（如二氯甲烷）中形成四氯化碳，其特征是强烈的着色。V 2 O 5将1,4-DHP芳构化在无溶剂介质中，乙酸在回流中的作用优于微波促进的反应。唯一合理的解释是在V 2 O 5的聚合物结构中发现的，该结构缓慢转移了活化反应物所需的微波能量。已发现4-正丙基-1，4-DHP的溶剂极性依赖性氧化脱烷基。出乎意料的是，与在相同反应条件下在二氯甲烷中获得的91％相比，在乙酸中的反应仅提供33％的脱烷基化产物。
• Oxidation of dihydropyridine calcium channel blockers and analogs by human liver cytochrome P-450 IIIA4
  作者：F. Peter Guengerich、William R. Brian、Masahiko Iwasaki、Marie Agnes Sari、Catharina Baeaernhielm、Peder Berntsson

  DOI：10.1021/jm00110a012

  日期：1991.6

  A series of 21 different 4-substituted 2,6-dimethyl-3-(alkoxycarbonyl)-1,4-dihydropyridines was considered with regard to oxidation to pyridine derivatives by human liver microsomal cytochrome P-450 (P-450). Antibodies raised against P-450 IIIA4 inhibited the microsomal oxidation of nifedipine and felodipine to the same extent, as did cimetidine and the mechanism-based inactivator gestodene. Gestodene was approximately 10(3) times more effective an inhibitor than cimetidine, on a molar basis. When rates of oxidation of the 1,4-dihydropyridines were compared to each other in different human liver microsomal preparations, all were highly correlated with each other with the exceptions of a derivative devoid of a substituent at the 4-position and an N1-CH3 derivative. A P-4.50 IIIA4 cDNA clone was expressed in yeast and the partially purified protein was used in reconstituted systems containing NADPH-cytochrome P-450 reductase and cytochrome b5. This system catalyzed the oxidation of all of the 1,4-dihydropyridines except the two for which poor correlation was seen in the liver microsomes. Principal component analysis supported the view that most of these reactions were catalyzed by the same enzyme in the yeast P-450 IIIA4 preparation and in the different human liver microsomal preparations, or by a closely related enzyme showing nearly identical properties of catalytic specificity and regulation. The results indicate that the enzyme P-450 IIIA4 is probably the major human catalyst involved in the formal dehydrogenation of most but not all 1,4-dihydropyridine drugs.
• A highly efficient biomimetic aromatization of Hantzsch-1,4-dihydropyridines with t-butylhydroperoxide, catalysed by iron(III) phthalocyanine chloride
  作者：Mirela Filipan-Litvić、Mladen Litvić、Vladimir Vinković

  DOI：10.1016/j.bmc.2008.09.004

  日期：2008.10

  Rapid aromatization of Hantzsch-1,4-DHPswith t-butylhydroperoxide catalysed by iron(III) phthalocyanine chloride is described. The reaction proceeds smoothly at room temperature within 1-35 min and the products of high purity were isolated in excellent yields. To explain the reactivity of this catalytical system plausible mechanism have been proposed to involve formation of high-valent oxoferryl species as in cytochrome P450 itself. (C) 2008 Elsevier Ltd. All rights reserved.