2-Acylmethyl-1H-benzimidazoles in the Biginelli Reaction

By cyclocondensation of 2-acylmethyl-1H-benzimidazoles with aromatic aldehydes and urea according to the Biginelli reaction, we have obtained previously unknown 6-substituted 4-aryl-5-(2-benzimidazolyl)-2-oxo-1,2,3,4-tetrahydropyrimidines. We have developed an efficient procedure for conducting the three-component reaction at fairly low temperatures. We have analyzed the structural features of the synthesized compounds based on ¹H NMR spectra and IR spectroscopy.     

Dichloroacetylaroylmethanes as two-carbon synthons in the Biginelli reaction

Acid-catalyzed cyclocondensation in a three component system of dichloromethylacetylbenzoylmethanes, urea, and aromatic aldehydes occurred regio-and stereoselectively to give polyfunctional derivatives of perhydropyrimidine. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 9, 1414–1417, September, 2006.     

不对称Biginelli反应的研究进展

综述了金属配合物、有机小分子(手性磷酸、手性硫脲)、金属Lewis酸与有机小分子共催化及纳米材料催化不对称Biginelli反应的研究进展。详述了反应机理,分析了催化剂、底物及反应条件对产物收率和对映选择性的影响。参考文献52篇。     

Vulnerability of substituted aromatic hydroxy aldehydes to undergo Biginelli reaction in water

Abstract

Aromatic aldehydes having hydroxyl substituent(s) react with urea (or thiourea), and ethyl acetoacetate (or acetylacetone) in the presence of p-toluenesulfonic acid as catalyst and water as solvent to give substituted dihydropyrimidinones (Biginelli compounds) in good to excellent yields.     

Synthesis of 4—Aryl—3,4—dihydropyrimidinones Using Microwaveassisted Solventless Biginelli Reaction

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A Different Role of Meldrum's Acid in the Biginelli Reaction

A Biginelli‐type condensation using Meldrum's acid has been accomplished in refluxing AcOH to give 6‐substituted dihydropyrimidine‐2,4‐(1H,3H)‐diones. In contrast to other aldehydes, the three‐component reaction with salicylaldehyde led to an oxygen‐bridged pyridine. A reaction mechanism is proposed.     

I2负载蒙脱土超声法催化Biginelli反应

以芳香醛、乙酰乙酸乙酯及脲为原料,I2负载蒙脱土为催化剂,对超声条件下Biginelli反应进行研究。用单因素法考察溶剂及催化剂对产率的影响,通过正交试验优化温度、超声时间及原料摩尔比。优化反应条件为:反应温度80℃,超声时间5min,芳香醛、乙酰乙酸乙酯和脲的摩尔比为1∶1∶1,催化剂用量为10(mol)%,产率最高可达86.9%。合成的7种3,4-二氢嘧啶-2(1H)-酮衍生物的结构通过红外光谱、核磁共振氢谱和熔点进行表征。     

Stepping Further from Coupling Tools: Development of Functional Polymers via the Biginelli Reaction

Multicomponent reactions (MCRs) have been used to prepare polymers with appealing functions. The Biginelli reaction, one of the oldest and most famous MCRs, has sparked new scientific discoveries in polymer chemistry since 2013. Recent years have seen the Biginelli reaction stepping further from simple coupling tools; for example, the functions of the Biginelli product 3,4-dihydropyrimidin-2(1H)-(thi)ones (DHPM(T)) have been gradually exploited to develop new functional polymers. In this mini-review, we mainly summarize the recent progress of using the Biginelli reaction to identify polymers for biomedical applications. These polymers have been documented as antioxidants, anticancer agents, and bio-imaging probes. Moreover, we also provide a brief introduction to some emerging applications of the Biginelli reaction in materials and polymer science. Finally, we present our perspectives for the further development of the Biginelli reaction in polymer chemistry.     

Protecting Group Free Synthesis of Carboxyl‐substituted Dihydropyrimidines Through Biginelli Reaction

Chlorotrimethylsilane‐promoted Biginelli‐type reaction of benzaldehyde, acetoacetic acid derivatives, and various carboxyl‐containing ureas was explored. It was found that the steric load of the urea substituents influenced strongly the reaction outcome; in particular, the method was efficient only in the case of unbranched mono‐substituted ureas bearing either aliphatic or aromatic groups. The method allows performing a one‐pot, protecting group free synthesis of dihydropyrimidines possessing carboxylic functionality.     

A Rapid and Efficient Biginelli Reaction Catalyzed by Zinc Triflate

An efficient and practiacal procedure for the synthesis of dihydropyrimidinones from aldehydes,1,3-dicarbonyl compounds and urea under solvent-free reaction condition using zinc triflate as a catalyst is described.In comparison with the classical Biginelli reaction,the yields for this new procedure increased from 20%-50% to 75%-98% while the reaction time was significantly shortened from 18h to 20min.     

Biginelli Reaction Synthesis of Novel Multitarget-Directed Ligands with Ca2+ Channel Blocking Ability,Cholinesterase Inhibition,Antioxidant Capacity,and Nrf2 Activation

Novel multitarget-directed ligands BIGI 4a-d and BIGI 5a-d were designed and synthesized with a simple and cost-efficient procedure via a one-pot three-component Biginelli reaction targeting acetyl-/butyrylcholinesterases inhibition, calcium channel antagonism, and antioxidant ability. Among these multitarget-directed ligands, BIGI 4b, BIGI 4d, and BIGI 5b were identified as promising new hit compounds showing in vitro balanced activities toward the recognized AD targets. In addition, these compounds showed suitable physicochemical properties and a good druglikeness score predicted by Data Warrior software.     

Microwave-assisted Solventless Biginelli Reaction Catalyzed by Montmorillonite Clay-SmCl_3 6H_2O System

4-Aryl/alkyl-3,4-dihydro-2(1H)-pyrimidone esters and 5-acetyl-4-aryl/or alkyl-6-methyl- 3, 4-dihydropyrimidin-2(l)-ones were synthesised efficientiy using montmorillonite clay- SmCl3 6H2O system promoted by microwave irradiation in solvenfless condition.     

Bio-Based Solvent Mediated Synthesis of Dihydropyrimidinthiones Via Biginelli Reaction

Abstract

The three-component Biginelli reaction using aldehyde, thiourea, and 1,3-dicarbonyl compounds was performed smoothly in ethyl lactate (EL) with the catalysis of trimethylsilyl chloride (TMSCl). A class of 3,4-dihydropyrimidinthiones (DHPMs) were synthesized in good to excellent yields via the bio-based solvent mediated catalytic protocol.     

Synthesis of 2-selenoxo DHPMs by Biginelli reaction with Hf(OTf)4 as catalyst

By using Hf(OTf)₄ as catalyst, a series of 2-selenoxo DHPMs have been synthesized efficiently in good yields by Biginelli reaction with selenourea as starting material.     

Biginelli Reaction Mediated Synthesis of Antimicrobial Pyrimidine Derivatives and Their Therapeutic Properties

Antimicrobial resistance was one of the top priorities for global public health before the start of the 2019 coronavirus pandemic (COVID-19). Moreover, in this changing medical landscape due to COVID-19, finding new organic structures with antimicrobial and antiviral properties is a priority in current research. The Biginelli synthesis that mediates the production of pyrimidine compounds has been intensively studied in recent decades, especially due to the therapeutic properties of the resulting compounds, such as calcium channel blockers, anticancer, antiviral, antimicrobial, anti-inflammatory or antioxidant compounds. In this review we aim to review the Biginelli syntheses reported recently in the literature that mediates the synthesis of antimicrobial compounds, the spectrum of their medicinal properties, and the structure–activity relationship in the studied compounds.     

The Combined Role of Catalysis and Solvent Effects on the Biginelli Reaction: Improving Efficiency and Sustainability

The traditional Biginelli reaction is a three‐component condensation between urea, benzaldehyde and an acetoacetate ester to give a dihydropyrimidinone. An investigation into catalytic and solvent effects has returned the conclusion that the diketo–enol tautomerisation equilibrium of the dicarbonyl reactant dictates the yield of the reaction. Whereas the solvent is responsible for the tautomerisation equilibrium position, the catalyst only serves to eliminate kinetic control from the reaction. Generally, to preserve reaction efficiency and improve sustainability, bio‐derivable p‐cymene was found to be a useful solvent. The metal–enolate intermediate that results from the application of a Lewis acidic catalyst often cited as promoting the reaction appears to hinder the reaction. In this instance, a Brønsted acidic solvent can be used to return greater reactivity to the dicarbonyl reagent.     

NiCl2·6H2O催化的Biginelli反应－－一锅法合成3，4－二氢嘧啶－2－酮

六水合氯化镍催化下，β－酮酸酯、芳香醛和脲在无水乙醇中进行环化缩合反 应，合成了3，4－二氢嘧啶－2－酮衍生物，改进了Biginelli反应，缩短了反应时 间，且操作简便、产率高。     

Versatility of the Biginelli reaction: Synthesis of new biphenyl dihydropyrimidin-2-thiones using different ketones as building blocks

A multi-component synthesis of biphenyl dihydropyrimidin-2-thiones from 1-phenylthiourea, aldehydes and ketones or di-ketones has been demonstrated. The reaction proceeded well for aldehydes with electron donor or acceptor substituents under mild conditions.     

磺化碳催化Biginelli反应一锅法合成3,4-二氢-2(1H)-酮和硫酮(英文)

A sulfonated carbon material was shown to be a highly efficient,eco-friendly,and recyclable solid acid catalyst for the Biginelli reaction of β-ketoester,aldehyde,and urea or thiourea under solvent-free conditions.It gave 3,4-dihydropyrimidin-2(1H)-ones and-thiones in good to excellent yields.This method has the advantages of a simple procedure with easy work-up,short reaction time,and high yields.The catalyst can be recycled after a simple work-up and was reused four times without substantial reduction in activity.