One-Pot Synthesis of 3,4-Dihydropyrimidin-2(1H)-ones and Their Sulfur Derivatives with H2SO4 Supported on Silica Gel or Alumina

The one-pot condensation of aromatic aldehydes, β-dicarbonyl compounds, and urea or thiourea in the presence of H₂SO₄ supported on silica gel or alumina (80% m/m) in refluxing n-hexane produces 3,4-dihydropyrimidin-2(1H)-ones and their sulfur derivatives in high to excellent yields.     

Biginelli 3,4-二氢嘧啶-2-酮衍生物的合成研究新进展

1893年, 意大利化学家Biginelli首次利用芳香醛、乙酰乙酸乙酯和尿素三组分“一锅煮法”合成了3,4-二氢嘧啶-2(1H)-酮. 此类化合物具有良好的生物活性和反应活性, 对近几年来有关Biginelli 3,4-二氢嘧啶-2(1H)-酮的衍生化反应、Biginelli不对称合成和Biginelli反应在天然产物合成中的应用研究进行了综述.     

Synthesis of 3,4-Dihydropyrimidin-2(1H)-ones Using Ce(SO4)2-SiO2 as a Heterogeneous and Recyclable Catalyst

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, and tolerance toward various functional groups.     

超声法合成3,4-二氢嘧啶-2(1H)-酮衍生物

以取代芳醛（1a~1h）,乙酰乙酸乙酯(2)和脲(3)为原料,MMT/CuCl₂为催化剂,乙醇为溶剂,在超声条件下经Beginelli反应合成了8个3,4-二氢嘧啶-2(1H)-酮衍生物（4a~4h）,其结构经¹H NMR和IR确证。以4a为例,分别采用单因素法和正交实验法研究了催化剂、溶剂、反应温度、超声时间和物料比r［n(1a): n(2) :n(3)］对4a产率的影响。结果表明：在最优反应条件(1a 2.4 mol, r=1.2 : 1.0 : 1.0, MMT/CuCl₂20 mol%, EtOH 1 mL,于90 ℃超声15 min)下,4a产率88.4%。 MMT/CuCl₂循环使用3次,产率基本不变。     

Xanthan Sulfuric Acid: A New and Efficient Biosupported Solid Acid Catalyst for the Synthesis of 3,4-Dihydropyrimidin-2(1H)-Ones

Xanthan sulfuric acid (XSA) is employed as a recyclable catalyst for the synthesis of 3,4-dihydropyrimidin-2(1H)-ones. These syntheses were performed via a one-pot, three-component condensation of aldehydes, amines, and urea/thiourea under solvent-free conditions.     

Environmentally Friendly Preparation of 3,4-Dihydropyrimidin-2(1H)-thiones Catalyzed by Al(H2PO4)3

An efficient, facile, simple, and green synthetic protocol for the Biginelli reaction has been developed for the preparation of 3,4-dihydropyrimidin-2(1H)-thione derivatives under thermal and microwave irradiation, solvent-free conditions, in the presence of aluminum hydrogen phosphate, Al(H₂PO₄)₃, as an environmentally friendly heterogeneous recyclable catalyst, in high to excellent yields and short reaction time. In addition, the catalyst could be easily recovered from the reaction mixture by simple filtration and reused several times without any loss of activity.     

氯化亚锡催化“一锅法”合成N1-取代的3,4-二氢嘧啶-2(1H)-酮

以芳香醛、乙酰乙酸乙酯(甲酯)、单取代脲为原料,氯化亚锡为催化剂,在无溶剂、80℃条件下,通过三组分"一锅法"合成了一系列N1-取代的3,4-二氢嘧啶-2(1H)-酮衍生物。考察了催化剂用量和反应温度对产品收率的影响。通过IR、~1H NMR、~(13)C NMR和元素分析对目标产物结构进行确证,提出了可能的催化作用机理。本文的合成方法具有催化剂活性高、廉价易得和反应时间短、条件温和、产率高、绿色环保等优点。     

微波辐射下FeCl3•6H2O催化绿色合成3,4-二氢嘧啶-2-酮

在微波辐射下, 仅以六水合三氯化铁为催化剂, 将芳香醛、β-二羰基化合物和脲(物质的量比为1∶1.5∶1.5)在无水乙醇中回流, 高效地合成了3,4-二氢嘧啶-2-酮, 反应时间4～6 min, 操作简便, 环境友好.     

An Efficient Synthesis of New 3,4-Dihydropyrimidin- 2(1H)-ones Incorporating a Phenyl Moiety at C-5 and C-6 Catalyzed by TMSCl and Co(OAc)2.4H2O

New 3,4-dihydropyrimidin-2-ones having a phenyl moiety at C-5 and C-6 have been prepared by a microwave-assisted Biginelli–like reaction by a three-component, one-pot condensation of an aromatic aldehyde, deoxybenzoin and urea, or thiourea using TMSCl and Co(OAc) ₂ .4H ₂ O as an efficient Lewis acid catalyst.     

An efficient synthesis of 3,4-dihydropyrimidin-2(1H)-ones catalyzed by molten [Et3NH][HSO4]

A simple ammonium salt of sulfuric acid in molten state was used as a cheap and mild acidic ionic liquid for efficient synthesis of 3,4-dihydropyrimidin-2(1H)-ones in good to excellent yields.     

微波辐射下FeCl3·6H2O催化绿色合成3,4-二氢嘧啶-2-酮

在微波辐射下,仅以六水合三氯化铁为催化剂,将芳香醛、β-二羰基化合物和脲(物质的量比为1:1.5:1.5)在无水乙醇中回流,高效地合成了3,4-二氢嘧啶-2-酮,反应时间4～6min,操作简便,环境友好.     

新型无毒离子液体催化“一锅煮”合成3,4-二氢嘧啶-2(1H)-酮

利用新型无毒离子液体(BMImSac)作催化剂, 芳香醛、1, 3-二羰基化合物和尿素或硫脲三组分“一锅煮”合成了3,4-二氢嘧啶-2(1H)-酮. 与传统方法相比, 该法是一种操作简单、产率高、用时少的环境友好方法.     

可膨胀石墨催化的一锅法合成3,4-二氢嘧啶-2-酮衍生物

在可膨胀石墨催化下, 由芳香醛、β-酮酸酯和尿素(摩尔比1∶1∶1.5)三组分缩合制备3,4-二氢嘧啶-2-酮衍生物, 反应时间1.5～2 h, 产率可达72%～93%, 且催化剂可回收重复利用. 产物的结构经¹H NMR, IR确证.     

Synthesis of 4-Alkynyl-substituted 3,4-Dihydropyrimidin-2(1H)-ones

4-Alkynyl-3,4-dihydropyrimidin-2-(1H)-ones were synthesized by a one-pot reaction of propynals, ethyl acetoacetate, and urea. The yields of acetylenic dihydropyrimidinones depend significantly upon the propynal structure and catalyst type. A comparative study of the catalysts revealed an important advantage of polyphosphate ester in tetrahydrofuran in comparison with hydrochloric acid in methanol or trimethylchlorosilane in dimethylformamide, allowing the preparation of target compounds in good or moderate yields.     

以磷酸二氢铵为催化剂一锅法合成 3,4-二氢嘧啶-2-酮(英文)

A one-pot three component Biginelli condensation of different substituted aromatic and aliphatic aldehydes with ethyl acetoacetate and urea to the respective 3,4-dihydropyrimidin-2-( 1H)-ones under sol...     

微波催化固相法合成3,4-二氢嘧啶-2(1H)-酮

在固相无溶剂条件下,使用微波辐射技术,由β－酮酸酯、芳香醛、脲合成了一系列3,4－二氢嘧啶－2（1H）－酮,实验简单方便,产率高,纯度高。     

(英)硫酸氢钾高效催化一锅法合成5-未取代的3,4-二氢嘧啶-2(1H)-酮

无溶剂条件下,硫酸氢钾可有效催化芳香醛、苯乙酮衍生物和脲的三组分"一锅法"Biginelli反应来合成5-未取代的3,4-二氢嘧啶-2(1H)-酮。确定了优化反应条件。产品结构经IR、1H NMR、MS和元素分析进行表征。     

Cytoprotective Activity of Newly Synthesized 3-(Arylmethylamino)-6-Methyl-4-Phenylpyridin-2(1H)-Ones Derivatives

Currently, studies are being conducted on the possible role of the cytoprotective effect of biologically active substances in conditions of cerebral hypoxia or cardiomyopathies. At the same time, oxidative stress is considered one of the important mechanisms of cellular cytotoxicity and a target for the action of cytoprotectors. The aim of this study is to search for derivatives of 3-(arylmethylamino)-6-methyl-4-phenylpyridin-2(1H)-ones. The probability of cytoprotective action was assessed by measuring cell viability using two tests (with neutral red dye and MTT test). It was found that some derivatives of 3-(arylmethylamino)-6-methyl-4-phenylpyridin-2(1H)-ones under the conditions of our experiment had a pronounced cytoprotective activity, providing better cell survival in vitro, including the MTT test and conditions of blood hyperviscosity. To correlate the obtained results in vitro, molecular docking of the synthesized derivatives was also carried out. The standard drug omeprazole (co-crystallized with the enzyme) was used as a standard. It was shown that all synthesized derivatives of 3-(arylmethylamino)-6-methyl-4-phenylpyridin-2(1H)-ones had higher affinity for the selected protein than the standard gastro-cytoprotector omeprazole. The studied derivatives of 3-(arylmethylamino)-6-methyl-4-phenylpyridin-2(1H)-ones also fully satisfy Lipinski’s rule of five (RO5), which increases their chances for possible use as orally active drugs with good absorption ability and moderate lipophilicity. Thus, the results obtained make it possible to evaluate derivatives of 3-(arylmethylamino)-6-methyl-4-phenylpyridin-2(1H)-ones as having a relatively high cytoprotective potential.     

3,4-二氢-1-(4-哌啶基)-2(1H)-喹啉酮的合成

以苄胺为原料,经6步反应得到新型抗高血压药OPC-21268的中间体3,4-二氢-1-(4-哌啶基)-2(1H)-喹啉酮,总收率13．9％．     

Al(HSO4)3 and Al2O3-SO3H as Efficient Catalysts for Modified Preparation of 3,4-Dihydropyrimidin-2 (1H)-ones/thiones

An environmentally friendly procedure for the preparation of dihydropyrimidinone derivatives or their sulfur analogues under thermal solvent-free conditions in the presence of aluminium hydrogen sulfate [Al(HSO₄)₃] and alumina sulfuric acid (Al₂O₃-SO₃H) as heterogeneous catalysts was developed.