methyl 4-(furan-2-yl)-6-methyl-2-oxo-1,2,3,4-tetrahydropyrimidine-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: methyl 4-(furan-2-yl)-6-methyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate
• 英文别名: (±)-methyl 4-(furan-2-yl)-6-methyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate；Methyl 4-(2-furyl)-6-methyl-2-oxo-1,2,3,4-tetrahydro-5-pyrimidinecarboxylate；methyl 4-(furan-2-yl)-6-methyl-2-oxo-3,4-dihydro-1H-pyrimidine-5-carboxylate
• 化学式: C₁₁H₁₂N₂O₄
• 分子量: 236.227
• InChiKey: KWOUPVFFEMXNRB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.1
• 重原子数：
  17
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  80.6
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  methyl 4-(furan-2-yl)-6-methyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate 在 lithium aluminium tetrahydride 作用下， 以 乙醚 为溶剂， 反应 3.0h， 生成
  参考文献：
  名称：

  LiAlH 4还原Biginelli化合物：快速获得分子多样性†

  摘要：

  在此，首次研究了LiAlH 4还原Biginelli化合物。还原尿素衍生的二氢嘧啶酮可产生80-95％的氢解产物（4-芳基-5-（m）乙基-6-甲基-3,4-二氢嘧啶-2（1 H）-ones； 11个实例），而N -1-甲基化的Biginelli化合物的还原得到相应的醇（4-芳基-5-（（1-）羟基（间）乙基）-6-甲基-3,4-二氢嘧啶-2（1 H）- ； 4个示例），产率为70-80％。获得的醇可以很容易地脱水成邻位的双（exo-亚甲基）衍生物（4-芳基-1-甲基-5-（间）亚乙基-6-亚甲基-四氢嘧啶-2（1 H）-那些; 4个实例）或在弱酸性条件下异构化为无环化合物（1-甲基-3-（1-芳基-2-亚甲基-3-氧代丁基）脲； 2个实例）。还原的结果还取决于其他结构特征和反应条件，例如：尿素/硫脲和1,3-二羰基化合物的类型，试剂的添加顺序等。LiAlH 4- Biginelli化合物

  DOI：

  10.1039/c6ra24535h
• 作为产物：
  描述：

  D-木糖 在 Fe₃O₄/SiO₂-SO₃H 作用下， 以 水 为溶剂， 反应 5.5h， 生成 methyl 4-(furan-2-yl)-6-methyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate
  参考文献：
  名称：

  Dehydration of Xylose to Furfural and Its Valorization via Different Multicomponent Reactions Using Sulfonated Silica with Magnetic Properties as Recyclable Catalyst

  摘要：

  Sulfonated silica with magnetic properties was studied for dehydration of xylose to furfural and posteriorly for furfural valorization through the Biginelli and Hantzsch multicomponent reactions. Eleven polysubstituted heterocycles were obtained in excellent yields and without any side-product (81-91 %), using a multicomponent green methodology. The presence of Fe3O4 particles allows an easy separation from the reaction medium giving a high yield in the reusability studies.

  DOI：

  10.1007/s10562-014-1267-8

文献信息

• First application of hexaaquaaluminium(III) tetrafluoroborate as a mild, recyclable, non-hygroscopic acid catalyst in organic synthesis: a simple and efficient protocol for the multigram scale synthesis of 3,4-dihydropyrimidinones by Biginelli reaction
  作者：Mladen Litvić、Ivana Večenaj、Zrinka Mikuldaš Ladišić、Marija Lovrić、Vladimir Vinković、Mirela Filipan-Litvić

  DOI：10.1016/j.tet.2010.03.024

  日期：2010.5

  used as a mild acid catalyst in organic synthesis. A simple method of its preparation based on the reaction of aluminium triisopropoxide and tetrafluoroboric acid in isopropanol afforded catalyst of high purity and activity. The three-component Biginelli condensation of acetoacetate esters, urea and aldehydes catalyzed by 10 mol % of [Al(H2O)6](BF4)3 in refluxing acetonitrile afforded 3,4-dihydropyrimidonones

  首次将四氟硼酸六铝铝（III）用作有机合成中的弱酸催化剂。基于三异丙醇铝和四氟硼酸在异丙醇中反应的简单制备方法提供了高纯度和活性的催化剂。10 mol％的[Al（H 2 O）6 ]（BF 4）3催化的乙酰乙酸酯，脲和醛的三组分Biginelli缩合反应在回流的乙腈中，以克数为单位，以高至高收率得到3，4-二氢嘧啶酮。对酸敏感性反应物（例如噻吩基和呋喃基甲醛）的耐受性，对位阻β-酮酸酯的适用性以及在不损失催化活性的情况下简单的可回收性，使得该催化剂成为文献方法的良好替代品。该反应的机理包括形成所谓的“脲基-巴豆酸酯”而不是布朗斯台德型催化剂中发现的相应的酰基亚胺基中间体。
• Double catalytic effect of (PhNH3)2CuCl4 in a novel, highly efficient synthesis of 2-oxo and thioxo-1,2,3,4-tetra-hydopyrimidines
  作者：Nenad Jankovic、Zorica Bugarcic、Svetlana Markovic

  DOI：10.2298/jsc141028011j

  日期：——

  An innovative route for the construction of 2-oxo and thioxo-1,2,3,4-tetrahydropyrimidines was delineated through a multicomponent reaction under Biginelli conditions, starting from different aromatic aldehydes, ?-ketoesters and urea or thiourea. Proper choice of copper complex (PhNH3)2CuCl4, as a novel homogeneous catalyst, enables facile, efficient, and inexpensive reaction under mild experimental conditions. Moreover, we present the first application of this complex salts in organic synthesis ever. The obtained products are of high purity, and can be easily isolated from the reaction mixture in good to excellent yields. Also, compared to the classical Biginelli reaction conditions, the present method has the advantages in higher yields and experimental and work-up simplicity. To illustrate the joint catalytic action of the Cu2+ and phenylammonium ions, two key steps of Biginelli reaction were examined using the M06 functional.

  通过多组分方法，为构建 2-氧代和硫代-1,2,3,4-四氢嘧啶的 和硫代-1,2,3,4-四氢嘧啶的创新路线。 在Biginelli条件下，通过多组分反应，从不同的芳香 醛、酮酯和脲或硫脲为起点，在 Biginelli 条件下通过多组分反应进行了研究。正确选择铜络合物 (PhNH3)2CuCl4 作为新型均相催化剂，可以在温和的实验条件下进行简便、高效和廉价的反应、 而且成本低廉。此外，我们 此外，我们还首次将这种复合盐应用于有机合成中。 我们还首次将这种复盐应用于有机合成。所得到的产物纯度很高，可以很容易地从反应混合物中分离出 从反应混合物中分离出来，而且产量极高。此外，与 比吉内利反应条件相比，本方法具有 而且，与传统的 Biginelli 反应条件相比，本方法具有产率高、实验和操作简单等优点。为了 Cu2+ 和苯基铵离子的联合催化作用、 使用 M06 功能对 Biginelli 反应的两个关键步骤进行了研究。
• Nanoparticles of Organosilane-based NaHSO4 Ionic Liquid Immobilized on Silica as Reusable Heterogeneous Catalyst for One-pot Synthesis of 2-oxo-and thioxo-4-phenyl-1,2,3,4-tetrahydropyrimidines
  作者：Abdolreza Abri、Mohsen Ghasemian khojasteh

  DOI：10.2174/1570178614666170127163214

  日期：2017.4.13

  Background: In spite of the fact that there are numerous reagents and methods to synthesize the dihydropyrimidinones via Biginelli reaction, but excellent yields, shorter reaction time and easy work-up are important factors which are not usually found together in a chemical reaction. This work aims to introduce a new reagent with above-mentioned capabilities in mild reaction conditions. Methods: With the benefit of NaHSO4 ionic liquid immobilized on silica as reusable heterogeneous catalyst, prepared via sol-gel method and characterized by SEM and XRD techniques, we could synthesize dihydropyrimidinones derivatives in mild conditions. Results: Data obtained from different identifying techniques, such as SEM and XRD for characterization of the structure of catalyst, and also IR, NMR and Mass spectroscopic techniques for characterization of products obviously confirm the efficacy and integrity of the method. Conclusion: In conclusion, the present procedure provides an efficient reagent for the synthesis of Biginelli compounds. Mild reaction conditions, ease in work-up, high yields, stability and recyclability of the reagent are features of this new procedure.

  背景：尽管已有众多试剂和方法通过Biginelli反应合成二氢嘧啶酮，但优异的产率、较短的反应时间和简便的后处理通常在化学反应中难以同时实现。本研究旨在引入一种新试剂，具备上述优点并可在温和的反应条件下使用。 方法：利用固定在硅胶上的NaHSO4离子液体作为可重用的异相催化剂，通过溶胶-凝胶法制备，并通过SEM和XRD技术进行表征，我们能够在温和条件下合成二氢嘧啶酮衍生物。 结果：通过不同的表征技术获得的数据，如用于催化剂结构表征的SEM和XRD，以及用于产品表征的IR、NMR和质谱技术，明显确认了该方法的有效性和完整性。 结论：综上所述，当前的程序为Biginelli化合物的合成提供了一种高效的试剂。温和的反应条件、简便的后处理、高产率、试剂的稳定性和可回收性是该新程序的特点。
• Soluble polymer-supported synthesis of Biginelli compounds
  作者：Min Xia、Yan-Guang Wang

  DOI：10.1016/s0040-4039(02)01850-6

  日期：2002.10

  An efficient and general liquid-phase synthesis of Biginelli compounds has been developed. Polyethylene glycol (PEG) bound acetoacetate reacted with urea and aldehydes under reflux or solvent-free microwave irradiation conditions to afford PEG-supported 3,4-dihydropyrimidin-2(1H)-ones. The desired 3,4-dihydropyrimidin-2(1H)-ones were cleaved from the polymer support under mild conditions in high yields

  已经开发了一种高效且通用的Biginelli化合物液相合成方法。在回流或无溶剂微波辐射条件下，聚乙二醇（PEG）结合的乙酰乙酸酯与脲和醛反应，得到PEG负载的3,4-二氢嘧啶-2（1 H）-one。在温和的条件下以高收率和高纯度从聚合物载体上裂解出所需的3，4-二氢嘧啶-2（1 H）-1 。
• An Efficient Protocol for the Liquid-Phase Synthesis of Methyl 3,4-Dihydro­pyrimidin-2(1<i>H</i>)-one-5-carboxylate Derivatives
  作者：Min Xia、Yan-guang Wang

  DOI：10.1055/s-2003-36816

  日期：——

  or solvent-free microwave irradiation through the Biginelli three-component cyclocondensation. Compared with the classical solution-phase Biginelli reactions, the yields could he considerably improved and the reaction lime could he shortened dramatically under microwave promotion in a liquid-phase protocol. Moreover, the polymer-supported synthesis provided the target compounds in high purity.

  在聚乙二醇(PEG) 4000 的可溶性聚合物上，通过Biginelli 三组分环缩合反应，通过加热或无溶剂微波辐照，有效地合成了3,4-二氢嘧啶-2(1H)-one-5-carboxylate 甲酯衍生物7。与经典的液相 Biginelli 反应相比，在液相协议的微波促进下，产率可以显着提高，反应时间可以显着缩短。此外，聚合物支持的合成提供了高纯度的目标化合物。