ethyl 4-(4-methoxyphenyl)-1,6-dimethyl-2-oxo-1,2,3,4-tetrahydropyrimidin-5-carboxylate

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: ethyl 4-(4-methoxyphenyl)-1,6-dimethyl-2-oxo-1,2,3,4-tetrahydropyrimidin-5-carboxylate
• 英文别名: 5-ethoxycarbonyl-1,6-dimethyl-4-(4-methoxyphenyl)-3,4-dihydropyrimidin-2(1H)-one；Ethyl 4-(4-methoxyphenyl)-1,6-dimethyl-2-oxo-1,2,3,4-tetrahydro-5-pyrimidinecarboxylate；ethyl 6-(4-methoxyphenyl)-3,4-dimethyl-2-oxo-1,6-dihydropyrimidine-5-carboxylate
• 化学式: C₁₆H₂₀N₂O₄
• 分子量: 304.346
• InChiKey: NERCEXSWOAFAFC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  22
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  67.9
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  ethyl 4-(4-methoxyphenyl)-1,6-dimethyl-2-oxo-1,2,3,4-tetrahydropyrimidin-5-carboxylate 在 溴 作用下， 以 乙醇 、 氯仿 为溶剂， 生成 ethyl 6-{[3-cyano-4-(2-ethoxyphenyl)-6-oxo-1,4,5,6-tetra-hydropyridin-2-ylthio]methyl}-4-(4-meth-oxyphenyl)-1-methyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate
  参考文献：
  名称：

  Reaction of ethyl 4-aryl-6-bromomethyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylates with N-methylmorpholinium 3-cyano-1,4-dihydro- and 3-cyano-1,4,5,6-tetrahydropyridine-2-thiolates

  摘要：

  Alkylation of N-methylmorpholinium 4-Ar-1-3-cyano-6-oxo-1,4,5,6-tetrahydropyridine-2-thiolates using ethyl 4-Ar-6-bromomethyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylates (10 % KOH, DMF) gives mixtures of diastereomers of ethyl 4-Ar-6-[(4-Ar-1-3-cyano-1,4,5,6-tetrahydropyridin-2-ylthio)methyl]-1-methyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylates in overall 30-58 % yield. Under these conditions the N-methylmorpholinium 4-Ar1-5-(N-Ar-2-carbamoyl)-3-cyano-6-methyl-1,4-dihydropyridine-2-thiolates undergo aromatization of the dihydropyridine ring to give ethyl 4-Ar-6-[4-Ar-1-5-(N-Ar-2-carbamoyl)-3-cyano-6-methylpyridin-2-ylthio)methyl]-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylates (37-51 %). In the absence of KOH, only the substituted pyridine-2(1 H)-thione is formed as a product of oxidation of the dihydropyridine ring in the starting substrate. Some of the alkylation products obtained possess weak or moderate antibacterial activity towards the specific strains of Escherichia coli and Bacillus subtilis but are inactive towards Candida albicans and Staphylococcus aureus.

  DOI：

  10.1007/s10593-012-1016-0
• 作为产物：
  描述：

  乙酰乙酸乙酯 、 4-甲氧基苯甲醛 、 N-甲基脲 在 yttrium(III) acetate tetrahydrate 、 溶剂黄146 作用下， 反应 4.0h， 以82%的产率得到ethyl 4-(4-methoxyphenyl)-1,6-dimethyl-2-oxo-1,2,3,4-tetrahydropyrimidin-5-carboxylate
  参考文献：
  名称：

  Y(OAc)3 催化的便捷一锅 Biginelli 反应：一种改进的合成 3,4-二氢嘧啶-2(1H)-酮及其硫类似物的方案

  摘要：

  醋酸钇(III)水合物催化合成3,4-二氢嘧啶-2(1H)-(硫代)酮衍生物是通过多种醛、β-酮酯和尿素或N-甲基脲的一锅三组分缩合实现的或摩尔比为1:1:1.4的硫脲。与经典的 Biginelli 方法相比，这种催化方法具有反应时间短和产品收率提高的优点。

  DOI：

  10.5012/bkcs.2010.31.04.863

文献信息

• The Thorpe–Ziegler-type reaction of 3-cyanopyridine-2(1H)-thiones with Biginelli 6-bromomethyl-3,4-dihydropyrimidin-2(1H)-ones: cascade assembling of tetra- and pentacyclic heterocyclic scaffolds
  作者：Iryna O. Lebedyeva、Victor V. Dotsenko、Vladimir V. Turovtsev、Sergey G. Krivokolysko、V'yacheslav M. Povstyanoy、Mikhaylo V. Povstyanoy

  DOI：10.1016/j.tet.2012.09.041

  日期：2012.11

  3-Cyanopyridine-2(1H)-thiones have been shown to react with Biginelli-type ethyl 4-aryl-6-(bromomethyl)-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylates upon heating in DMF giving rise to ethyl 4-aryl-6-[(3-cyanopyridin-2-yl)thio]methyl}-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylates. The latter upon treatment with an excess of NaH or t-BuOK in boiling DMF undergo a tandem Thorpe–Ziegler-type

  已经显示3-氰基吡啶-2（1 H）-硫酮在加热时与Biginelli型4-芳基-6-（溴甲基）-2-氧-1,2,3,4-四氢嘧啶-5-羧酸乙酯反应在DMF中，生成4-芳基-6-[（（3-氰基吡啶-2-基）硫基]甲基] -2-氧代-1,2,3,4-四氢嘧啶-5-羧酸乙酯。后者在沸腾的DMF中用过量的NaH或t- BuOK处理后，进行串联的Thorpe–Ziegler型杂环化反应，得到吡啶并[3″，2″：4'，5'] thieno [2'，3'：5 ，6]吡啶[4,3- d ]嘧啶衍生物，收率高。测试所选化合物的抗菌和抗真菌活性。
• Synthesis of Biginelli Compounds Using Cobalt Hydrogen Sulfate
  作者：Hamid Reza Memarian、Mahnaz Ranjbar

  DOI：10.1002/jccs.201190016

  日期：2011.8

  Efficient synthesis of various 2‐oxo(thioxo)‐1,2,3,4‐tetrahydropyrimidines containing acetyl, carboethoxy, carbomethoxy and carboxamide groups on 5‐position of the N1‐substituted and N1‐unsubstituted heterocyclic ring was achieved using cobalt hydrogen sulfate Co(HSO4)2 under thermal conditions. Good to high yield, shorter reaction times, easy work up and simple preparation of Co(HSO4)2 are the advantages

  使用钴实现了在N 1-取代和N 1-未取代的杂环的5位上含有乙酰基，碳乙氧基，碳甲氧基和羧酰胺基团的各种2-氧代（thioxo）-1、2、3、4-四氢嘧啶的高效合成在热条件下产生硫酸氢Co（HSO 4）2。该合成方法的优点是产率高至高，反应时间短，易于后处理和制备Co（HSO 4）2简便。
• Phytic acid: a biogenic organocatalyst for one-pot Biginelli reactions to 3,4-dihydropyrimidin-2(1H)-ones/thiones
  作者：Qiguo Zhang、Xin Wang、Zhenjiang Li、Wenzhuo Wu、Jingjing Liu、Hao Wu、Saide Cui、Kai Guo

  DOI：10.1039/c4ra02084g

  日期：——

  The natural organocatalyst phytic acid catalyzed one-pot Biginelli reactions by coupling β-ketoesters, aldehydes, and (thio)ureas to afford 3,4-dihydropyrimidin-2(1H)-ones/thiones. This phytic acid catalysis featured good to excellent isolated yields, solvent-free conditions, a simple workup, environmental friendliness, and a short reaction time.

  天然有机催化剂植酸通过耦合β-酮酸酯，醛和（硫）脲催化一锅Biginelli反应，从而提供3,4-二氢嘧啶-2（1 H）-酮/硫酮。植酸催化具有良好的分离收率，无溶剂条件，简单的后处理，环境友好和反应时间短的特点。
• Cerous <i>p</i>-Toluenesulfonate as an Efficient and Recyclable Catalyst for the Synthesis of <i>N</i>1-Substituted-4-aryl-3,4-dihydropyrimidin-2(1<i>H</i>)-ones
  作者：Min Wang、Hongxu Jiang、Shun Zhang、He Pan

  DOI：10.1080/00304948.2018.1525672

  日期：2018.9.3

  agents and a1aantagonists. Since the first straightforward synthetic method for DHPMs was reported by Biginelli in 1893, many improved protocols were developed. Not only new catalysts and reaction conditions were explored but also some novel reactive species were formed. The scope of the Biginelli reaction extended to various building blocks, so a large number of multifunctional pyrimidine derivatives with

  由于杂环上的六个功能点，二氢嘧啶酮 (DHPM) 具有广泛的合成重要性。DHPMs 还具有多种生物和药物活性，如钙通道阻滞剂、抗高血压剂和 a1a 拮抗剂。自从 1893 年 Biginelli 报告了第一个直接的 DHPM 合成方法以来，开发了许多改进的协议。不仅探索了新的催化剂和反应条件，而且形成了一些新的反应物种。Biginelli 反应的范围扩展到各种构建模块，因此获得了大量具有重要生物学特性的多功能嘧啶衍生物。其中，N1 取代的 DHPMs 也具有重要的生物活性和区域选择性。然而，关于 DHPM 的 N1-烷基化的参考文献很少，而且它们在产率、有毒试剂和反应条件方面都有局限性。尿素上的取代基主要限于 Me 和 Et。这鼓励我们开发一种新颖有效的方法来合成更多 N1 取代的 DHPM。作为耐水路易斯酸催化剂，金属磺酸盐被认为在合成化学中具有广泛的应用前景。它们高效、无毒并可重复使用。作为我们在金属磺酸盐催化的
• Substituent effects on the voltammetric studies of 2-oxo-1,2,3,4-tetrahydropyrimidines
  作者：Hamid R. Memarian、Mahnaz Ranjbar、Hassan Sabzyan、Abolfazl Kiani

  DOI：10.1016/j.crci.2012.09.009

  日期：2012.11

  nature and steric hindrance of the substituents, their positions and their orientations towards the heterocyclic ring, determine their effects on the oxidation peak potential. The electron detachment process in this study is also affected by the nature of solvent, which explains the extent of solvation of both neutral THPM and THPṀ + . Analysis of the computational results obtained at the DFT-B3LYP/6-31++G**

  摘要 使用伏安法在玻碳电极上研究了各种取代的 2-oxo-1,2,3,4-四氢嘧啶 (THPM) 在乙腈中的电化学氧化，以研究取代基对 1- 、 4- 和 5- 位的杂环。对本研究中提出的结果的分析表明，取代基的电子性质和位阻、它们的位置和它们对杂环的取向，决定了它们对氧化峰电位的影响。本研究中的电子脱离过程也受溶剂性质的影响，这解释了中性 THPM 和 THPṀ + 的溶剂化程度。对在 DFT-B3LYP/6-31++G** 理论水平上获得的计算结果的分析表明了一种机制，其中第一次电子去除发生在 N1 原子上。此过程之后是快速去除质子，导致形成稳定的烯丙基和/或苄基自由基，然后进一步氧化成 2-氧代-1,2-二氢嘧啶 (DHPM)。