ethyl 4-(benzo[d][1,3]dioxol-5-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 - 苯并间二氧杂环戊烯类
• 英文名称: ethyl 4-(benzo[d][1,3]dioxol-5-yl)-6-methyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate
• 英文别名: ethyl 4-(benzo[d][1,3]dioxol-6-yl)-1,2,3,4-tetrahydro-6-methyl-2-oxopyrimidine-5-carboxylate；ethyl 6-methyl-4-(3,4-methylenedioxophenyl)-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate；ethyl 4-(benzo[d][1,3]dixol-5-yl)-1,2,3,4-tetrahydro-6-methyl-2-oxopyrimidine-5-carboxylate；ethyl 4-(1,3-benzodioxol-5-yl)-6-methyl-2-oxo-1,2,3,4-tetrahydro-pyrimidine-5-carboxylate；ethyl 4-(1,3-benzodioxol-5-yl)-6-methyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate；5-(ethoxycarbonyl)-4-(3,4-methylenedioxyphenyl)-6-methyl-3,4-dihydropyrimidin-2(1H)-one；4-(1,3-benzodioxol-5-yl)-6-methyl-2-oxo-3,4-dihydro-1H-pyrimidine-5-carboxylic acid ethyl ester；ethyl 4-(1,3-benzodioxol-5-yl)-6-methyl-2-oxo-3,4-dihydro-1H-pyrimidine-5-carboxylate
• 化学式: C₁₅H₁₆N₂O₅
• 分子量: 304.302
• InChiKey: SFJUFKUJXZOETL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  22
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  85.9
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  ethyl 4-(benzo[d][1,3]dioxol-5-yl)-6-methyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate 在 五氯化磷 、 三氯氧磷 作用下， 反应 10.0h， 以66%的产率得到ethyl 6-(benzo[d][1,3]dioxol-5-yl)-2-chloro-4-methyl-1,6-dihydropyrimidine-5-carboxylate
  参考文献：
  名称：

  One-pot Synthesis of 1,2,3,4-Tetrahydropyrimidin-2(1H)-thione Derivatives and their Biological Activity

  摘要：

  2‐Thioxo/oxo‐1,2,3,4‐tetrahydropyrimidine‐5‐carboxylate derivatives 2a, 2b, 2c, 2d were prepared by the reaction of ethyl acetoacetate and thiourea or urea with aldehydes using NH4Cl as a catalyst. Compounds 2a and 2c reacted with mono and bihalogenated compounds such as ethyl iodide, chloroacetonitrile, epichlorohydrin, acetyl chloride, ethyl bromoacetate, chloroacetic acid, chloroacetylchloride, and/or oxalyl chloride to afford compounds 3, 4a, 4b, 5, 6a, 6b, 7, 8, 9 and 10, respectively. Compounds 2a, 2c, and 7 were allowed to react with p‐fluorobenzaldehyde to yield the corresponding products 11a, 11b, and 12, respectively. Oxidation of 2a and 2c gave 2b, 13a, 13b, 14, 15, 16 dependent on the oxidizing agent used. Vilsmeiere‐Haack formylation of 2a and 2b with POCl3/DMF afforded 17a and 17b. Chlorination of 2b and 2d gave the chlorinated derivative 18a and 18b, which reacted with thiourea to give thioureidopyrimidine 19a and 19b. Reactions of 2a with hydrazine monohydrate, semicarbazide hydrochloride, and sodium hydroxide gave compounds 20, 21, 22, respectively. The cytotoxicity and in vitro anticancer evaluation of some prepared compounds have been assessed against two different human tumor cell lines including breast adenocarcinoma MCF‐7 and human hepatocellular carcinoma HepG2. Antimicrobial and antioxidant activities of some compounds were investigated. The newly synthesized compounds were characterized by IR, 1H‐NMR, 13C‐NMR, and mass spectral data.

  DOI：

  10.1002/jhet.2358
• 作为产物：
  描述：

  胡椒醛 在 potassium permanganate 、 氯化铵 作用下， 以 水 、 丙酮 为溶剂， 反应 8.0h， 生成 ethyl 4-(benzo[d][1,3]dioxol-5-yl)-6-methyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate
  参考文献：
  名称：

  One-pot Synthesis of 1,2,3,4-Tetrahydropyrimidin-2(1H)-thione Derivatives and their Biological Activity

  摘要：

  2‐Thioxo/oxo‐1,2,3,4‐tetrahydropyrimidine‐5‐carboxylate derivatives 2a, 2b, 2c, 2d were prepared by the reaction of ethyl acetoacetate and thiourea or urea with aldehydes using NH4Cl as a catalyst. Compounds 2a and 2c reacted with mono and bihalogenated compounds such as ethyl iodide, chloroacetonitrile, epichlorohydrin, acetyl chloride, ethyl bromoacetate, chloroacetic acid, chloroacetylchloride, and/or oxalyl chloride to afford compounds 3, 4a, 4b, 5, 6a, 6b, 7, 8, 9 and 10, respectively. Compounds 2a, 2c, and 7 were allowed to react with p‐fluorobenzaldehyde to yield the corresponding products 11a, 11b, and 12, respectively. Oxidation of 2a and 2c gave 2b, 13a, 13b, 14, 15, 16 dependent on the oxidizing agent used. Vilsmeiere‐Haack formylation of 2a and 2b with POCl3/DMF afforded 17a and 17b. Chlorination of 2b and 2d gave the chlorinated derivative 18a and 18b, which reacted with thiourea to give thioureidopyrimidine 19a and 19b. Reactions of 2a with hydrazine monohydrate, semicarbazide hydrochloride, and sodium hydroxide gave compounds 20, 21, 22, respectively. The cytotoxicity and in vitro anticancer evaluation of some prepared compounds have been assessed against two different human tumor cell lines including breast adenocarcinoma MCF‐7 and human hepatocellular carcinoma HepG2. Antimicrobial and antioxidant activities of some compounds were investigated. The newly synthesized compounds were characterized by IR, 1H‐NMR, 13C‐NMR, and mass spectral data.

  DOI：

  10.1002/jhet.2358

文献信息

• A New Biginelli Reaction Procedure Using Potassium Hydrogen Sulfate as the Promoter for an Efficient Synthesis of 3,4-Dihydropyrimidin-2(1<i>H</i>)-one
  作者：Shujiang Tu、Fang Fang、Songlei Zhu、Tuanjie Li、Xiaojing Zhang、Qiya Zhuang

  DOI：10.1055/s-2004-815419

  日期：——

  conditions have been found to carry out the Biginelli reaction for the synthesis of 3,4-dihydropyrimidin-2(1H)-one derivatives. This synthesis was performed using potassium hydrogen sulfate as the promoter in glycol solution. Compared with the classical Biginelli reaction conditions, this new method has the advantage of excellent yields (85-99%) and short reaction time (0.5-2 h).

  已经发现简单和改进的条件可以进行 Biginelli 反应以合成 3,4-二氢嘧啶-2(1H)-one 衍生物。该合成是在乙二醇溶液中使用硫酸氢钾作为促进剂进行的。与经典的 Biginelli 反应条件相比，这种新方法具有收率高（85-99%）和反应时间短（0.5-2 h）的优点。
• A One-Pot Synthesis of 3,4-Dihydropyrimidin-2-(1H)-ones from Primary Alcohols Promoted by Bi(NO3)3·5H2O in Two Different Media: Organic Solvent and Ionic Liquid
  作者：Ahmad Reza Khosropour、Ahmad R. Khosropour、Mohammd M. Khodaei、Mojtaba Beygzadeh、Mahbubeh Jokar

  DOI：10.3987/com-04-10257

  日期：——

  A new, simple and efficient procedure for the one-pot conversion of alcohols instead of aldehydes to the corresponding 3,4-dihydropyrimidin-2(1H)-ones (DHPMs) with Bi(NO 3 ) 3 .5H 2 O as a commercially available, inexpensive, stable and non-toxic reagent in two media, acetonitrile (as an organic solvent) and tetrabutylammonium bromide (as an ionic liquid) is described. This one-pot oxidation-cyclocondensation

  一种新的、简单且有效的方法，用于将醇而不是醛一锅转化为相应的 3,4-二氢嘧啶-2(1H)-酮 (DHPM)，其中 Bi(NO 3 ) 3 .5H 2 O 作为商业应用描述了在乙腈（作为有机溶剂）和四丁基溴化铵（作为离子液体）这两种介质中可获得、廉价、稳定和无毒的试剂。这种一锅氧化-环缩合反应无需分离任何中间体（醛）即可进行，从而缩短了时间，节省了能源和原材料。另一方面，用这种新的一锅法处理伯醇产生的脱氢嘧啶酮的产率高于传统方法中的产率。
• Synthesis of 3,4-Dihydropyrimidin-2(1H)-ones Using Ce(SO₄)₂-SiO₂as a Heterogeneous and Recyclable Catalyst
  作者：Wen Pei、Qin Wang

  DOI：10.1080/00397910903061076

  日期：2010.3.19

  A simple and efficient synthesis of 3,4-dihydropyrimidinones or thiones is described, using silica-supported ceric sulfate [Ce(SO4)2-SiO2] as a heterogeneous catalyst from an aldehyde, 1,3-dicarbonyl compound, and urea or thiourea at 110 °C under solvent-free conditions. Compared with the classical Biginelli reaction, this new method consistently has better yields, short reaction time, easy separation

  描述了一种简单有效的 3,4-二氢嘧啶酮或硫酮合成方法，使用二氧化硅负载的硫酸铈 [Ce(SO4)2-SiO2] 作为来自醛、1,3-二羰基化合物和尿素或硫脲的非均相催化剂在 110 °C 无溶剂条件下。与经典的 Biginelli 反应相比，这种新方法始终具有更高的产率、更短的反应时间、易于分离以及对各种官能团的耐受性。
• Cu(OTf)2: a reusable catalyst for high-yield synthesis of 3,4-dihydropyrimidin-2(1H)-ones
  作者：A.S. Paraskar、G.K. Dewkar、A. Sudalai

  DOI：10.1016/s0040-4039(03)00619-1

  日期：2003.4

  Copper(II) triflate catalyzes efficiently the three-component condensation reaction of an aldehyde, β-ketoester and urea in acetonitrile to afford the corresponding 3,4-dihydropyrimidin-2(1H)-ones in high yields. The catalyst exhibited remarkable reusable activity.

  三氟甲磺酸铜（II）有效催化醛，β-酮酸酯和尿素在乙腈中的三组分缩合反应，从而以高收率提供相应的3,4-二氢嘧啶-2（1 H）-酮。该催化剂表现出显着的可重复使用的活性。
• The Biginelli Reaction with an Imidazolium-Tagged Recyclable Iron Catalyst: Kinetics, Mechanism, and Antitumoral Activity
  作者：Luciana M. Ramos、Bruna C. Guido、Catharine C. Nobrega、José R. Corrêa、Rafael G. Silva、Heibbe C. B. de Oliveira、Alexandre F. Gomes、Fábio C. Gozzo、Brenno A. D. Neto

  DOI：10.1002/chem.201204314

  日期：2013.3.25

  The present work describes the synthesis, characterization, and application of a new ion‐tagged iron catalyst. The catalyst was employed in the Biginelli reaction with impressive performance. High yields have been achieved when the reaction was carried out in imidazolium‐based ionic liquids (BMI⋅PF6, BMI⋅NTf2, and BMI⋅BF4), thus showing that the ionic‐liquid effects play a role in the reaction. Moreover

  本工作描述了新型离子标记铁催化剂的合成，表征和应用。该催化剂用于Biginelli反应中，具有令人印象深刻的性能。当反应在咪唑鎓基的离子液体进行（BMI高的产率已经达到⋅ PF 6，BMI ⋅ NTF 2，和BMI ⋅ BF 4），因此表明离子液体效应在反应中起作用。此外，离子标记的催化剂可以回收并重复使用多达八次，而活性没有任何明显的损失。通过使用高分辨率电喷雾电离四极杆飞行时间质谱（HR-EI-QTOF）光谱和动力学实验进行的机理研究表明，只有一种反应途径可以排除发展条件下的其他两种可能性。理论计算符合所提出的铁催化剂的作用机理。最后，Biginelli反应的产物37种二氢嘧啶酮衍生物在针对MCF-7癌细胞线的测定中评估了其细胞毒性，并获得了令人鼓舞的结果，其中某些衍生物对健康细胞线（成纤维细胞）几乎无毒。