室温离子液体催化“一锅法”合成3, 4-二氢嘧啶-2-酮

利用室温离子液体作催化剂，芳香醛、尿素和乙酰乙酯或乙酰丙酮三组分缩合制备3,4-二氢嘧啶-2-酮衍生物，反应条件温和，反应时间短，且不需另加有机溶剂，考察了不同取代基对芳香醛、尿素和乙酰乙酸乙酯或乙酰丙酮三组分缩合反应的影响。还考察了不同的室温离子液体的催化性能，发现1-丁基-3-甲基咪唑六氟磷酸盐较1-丁基-3-甲基咪唑四氟硼酸盐的催化效果略好。     

Efficient Biginelli Reaction Catalyzed by Sulfamic Acid or Silica Sulfuric Acid under Solvent‐Free Conditions

Sulfamic acid efficiently catalyzes the three‐component condensation reaction of aldehydes, 1,3‐dicarbonyl compounds, and urea/thiourea under solvent‐free conditions to afford the corresponding dihydropyrimidinones and thio‐derivatives in high yields. Silica sulfuric acid is also found to be an efficient catalyst for the Biginelli reaction under solvent‐free conditions. Compared to the classical Biginelli reaction conditions, this new method consistently has the advantage of giving good yields and requiring short reaction times.     

Synthesis of 3,4‐Dihydropyrimidinones via Phase Transfer Catalysis

3,4‐Dihydropyrimidinone and derivatives were synthesized by the one‐pot, three‐component Biginelli condensation of an aldehyde, β‐dicarbonyl compound and urea. Synthesis was carried out in aqueous sodium hydroxide using Aliquat‐336 as a phase transfer agent. Compared to the classical Biginelli reaction conditions, this new method cousistently has the advantage of excellent yields and short reaction time.     

Magnesium Bromide and Magnesium Chloride Hexahydrate Catalyzed One‐Pot Synthesis of Dihydropyrimidines via Biginelli Reaction under Solvent‐Free Conditions

Biologically important 12 new important 3,4‐dihydropyrimidin‐2‐(1H)‐ones (‐thiones) were synthesized with in one‐pot three‐component Biginelli reaction from the corresponding aromatic aldehydes (5‐methyl‐2‐thiophenecarboxaldehyde and 2‐chloro‐5‐nitrobenzaldehyde), β‐keto esters (ethylacetoacetate, allylacetoacetate, and t‐butylacetoacetate), and urea/thiourea in the presence of catalytic amount of magnesium bromide and magnesium chloride hexahydrate as nontoxic, inexpensive, and easily available catalysts under solvent‐free conditions at 80 and 100°C. Compared with the catalyst‐free three‐component Biginelli reaction conditions, this method consistently has the advantage of short reaction time (45–100 min) and good to excellent yields (75–91%).     

3, 4-二氢嘧啶-2-酮衍生物合成研究进展

综述了近十年来3,4-二氢嘧啶-2-酮衍生物合成的研究进展,包括催化合成、固相合成、微波促进合成及天然产物合成中的一些最新研究进展。     

Advances in Biginelli reaction: A comprehensive review

The Biginelli reaction, a conventional three-component reaction provides 3,4-dihydropyrimidin-2(1H)-ones/thiones via one-pot acid catalyzed cyclocondensation of an aldehyde, a β-keto ester, and urea or thiourea. Dihydropyrimidones are well-known scaffolds having a wide range of pharmacological activities. So far classical Biginelli reaction has witnessed several modification and studies are still continuing in this field to develop greener and efficient methodologies. In this review, we summarize the recent advances in Biginelli reaction covering literature from 2020 to 2023.     

The Three‐Component Biginelli Reaction: A Combined Experimental and Theoretical Mechanistic Investigation

Biginelli reactions have been monitored by direct infusion electrospray ionization mass spectrometry (ESI‐MS) and key cationic intermediates involved in this three‐component reaction have been intercepted and further characterized by tandem MS experiments (ESI‐MS/MS). Density functional theory calculations were also used to investigate the feasibility of the major competing mechanisms proposed for the Biginelli reaction. The experimental and theoretical results were found to corroborate the iminium mechanism proposed by Folkers and Johnson, whereas no intermediates directly associated with either the more energy demanding Knoevenagel or enamine mechanisms could be intercepted.     

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.     

Training the old dog new tricks: the applications of the Biginelli reaction in polymer chemistry

Recently, the Biginelli reaction, one of the most famous multicomponent reactions, has been introduced into the polymer chemistry to highly efficiently synthesize some interesting functional polymers. In this mini-review, several applications of the Biginelli reaction in polymer chemistry have been summarized, including polycondensation, post-polymerization modification, one-pot synthesis of well-defined polymer, etc. Meanwhile, the utilization of the Biginelli reaction in material science and chemical biology, and the future development of the Biginelli reaction in polymer chemistry have also been discussed.     

Novel and Efficient Synthesis of DHPMs Catalyzed by di‐DACH‐Pyridylamide Ligands

Di‐DACH‐pyridylamide ligands, symmetrical bridged bis‐Schiff base, and spiro pyrrolizines as catalysts in the synthesis of dihydropyrimidinethiones (DHPMs) using the Biginelli reaction is first reported. This new protocol has the advantages of environmental friendliness, short reaction time, excellent yields, and simple post‐treatment procedure. A series of DHPMs were obtained in high yields (up to 98%) in only 6 h. Moreover, based on the optimized condition, a novel Biginelli‐like reaction was first developed.     

Stereoselective synthesis of new dihydropyrimidinone glycoconjugates #

Stereoselective synthesis of dihydropyrimidinone glycoconjugates in high yields, from different sugar aldehydes, by a three‐component coupling (Biginelli) reaction is reported. In this new method, HC1 generated ‘in situ’ from2,4,6‐trichloro[l,3,5]triazine(TCT; 10 mol%), was used under mild and solvent free reaction conditions.     

A new biginelli reaction procedure using potassium hydrogen sulfate as the promoter for an efficient synthesis of 3,4‐dihydropyrimidin‐2(1H)‐one

Simple and improved 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 ethylene glycol solution. Compared with the classical Biginelli reaction conditions, this new method has the advantage of excellent yields (85–95%) and short reaction time (0.5–2 h).     

Catalytic effect of nanosized metal oxides in the Biginelli reaction

The effect of nanosized metal oxides on the regio- and stereoselectivity of the multicomponent Biginelli reaction and the reaction mechanism under conditions of heterogeneous catalysis were studied. It was found that the considerable activation of reagents occurred on the surface of metal nanooxides. The Biginelli reaction occurred by two mechanisms: a carbocationic mechanism took place along with the generally accepted mechanism (through the N-acyliminium ion). Nanosized metal oxides in the presence of chiral inductors increased the regio- and stereoselectivity of the Biginelli reaction.     

Concise synthesis of guanidine-containing heterocycles using the Biginelli reaction

Two general methods for the synthesis of 2-imino-5-carboxy-3,4-dihydropyrimidines were developed using the three-component Biginelli reaction. The first method utilizes pyrazole carboxamidine, a beta-ketoester, and an aldehyde in an initial Biginelli reaction. After Boc protection, these products undergo aminolysis and acidic deprotection to generate 2-imino-5-carboxy-3,4-dihydropyrimidines in a four-step sequence. The second method utilizes a triazone-protected guanidine, a beta-ketoester, and an aldehyde in a Biginelli reaction. Acidic cleavage of the triazone yields 2-imino-5-carboxy-3,4-dihydropyrimidines in a two-step sequence. We also describe the further elaboration of several of these products using a tethered Biginelli reaction to give triazaacenaphthalene structures similar to those found in crambescidin and batzelladine alkaloids.     

无溶剂条件下用于合成3,4-二氢嘧啶-2(1H)-酮的高效、可磁性回收Fe_3O_4纳米粒子催化剂(英文)

The catalytic activity of Fe3O4 nanoparticles (NPs) in a one-pot three component condensation reaction consisting of an aromatic aldehyde, urea or thiourea, and a β-dicarbonyl under solvent-free conditions was investigated. This reaction affords the corresponding dihydropyrimidinones (thiones) in high to excellent yields. Compared with the classical Biginelli reactions this method consistently gives a high yield, easy magnetic separation, a short reaction time, and catalyst reusability.     

Efficient,Green, Solvent-Free Synthesis of 3,4-Dihydropyrimidin-2(1H)-ones via Biginelli Reaction Catalyzed by Cu(NO3)2·3H2O

The synthesis of 3,4-dihydropyrimidin-2-(1H)-ones derivatives via a three-component Biginelli reaction using copper nitrate as a catalyst under solventless conditions is reported, providing a green, rapid, efficient, and convenient method for the preparation of Biginelli compounds in good yields.     

Magnetically reusable nanocatalysts in biginelli synthesis of dihydropyrimidinones (DHPMs)

Abstract

Molecules containing dihydropyrimidinone (DHPMs) structures are very important in pharmaceutical and medicinal chemistry due to their excellent biological activities application in synthesis of natural products. Biginelli condensation reaction between an aldehyde, urea/thiourea and a carbonyl compound is the most popular strategy for the synthesis of dihydropyrimidinones. Magnetic recoverable nanocatalysts can be readily separated from reaction medium by using an external magnet, without the need for filtration, centrifugation or other tedious workup processes. In recent times, the catalytic potential of magnetically recoverable nanocatalysts was evaluated in a variety of Biginelli reactions. In this review, we focus on the application of magnetically recoverable gold nanocatalysts in Biginelli synthesis of dihydropyrimidinone derivatives.     

Manganese‐Containing Periodic Mesoporous Organosilica with Ionic‐Liquid Framework (Mn@PMO‐IL): A Powerful,Durable, and Reusable Nanocatalyst for the Biginelli Reaction

The catalytic application of a novel manganese‐containing periodic mesoporous organosilica with ionic‐liquid framework (Mn@PMO‐IL) in the Biginelli reaction was investigated. First, the Mn@PMO‐IL nanocatalyst was prepared and characterized by TEM, SEM, X‐ray photoelectron spectroscopy, and nitrogen‐sorption analysis. The catalyst was then used in the one‐pot Biginelli condensation of various aldehydes with urea and alkyl acetoacetates under solvent‐free conditions. The corresponding dihydropyrimidone products were obtained in high to excellent yields and selectivities at short reaction times. Moreover, the catalyst was recovered and successfully reused many times with no notable decrease in activity and selectivity.     

Silica-bonded N-propyl sulfamic acid as an efficient recyclable catalyst for the synthesis of 3,4-dihydropyrimidin-2-(1H)-ones/thiones under heterogeneous conditions

Silica-bonded N-propyl sulfamic acid(SBNPSA) catalyzed one-pot three component Biginelli condensation of different substituted aromatic aldehydes with ethyl acetoacetate and urea/thoiurea to the respective 3,4-dihydropyrimidin-2-(1H)-ones and thiones in environment friendly procedure is described. The facile reaction conditions, simple isolation and purification procedures of this method make it a good option for the synthesis of dihydropyrimidinones.     

Asymmetric organocatalytic Biginelli reactions: a new approach to quickly access optically active 3,4-dihydropyrimidin-2-(1H)-ones

The Biginelli reaction, known for over 100 years, is an important multicomponent reaction for accessing dihydropyrimidinones (DHPMs). The individual enantiomers of DHPMs exhibit different or even opposite pharmaceutical activities, which require synthetic methods to easily access the optically pure DHPMs. In recent decades, many efforts have focused on developing procedures for the preparation of optically active Biginelli products. In this article, we will summarize the developments in the synthetic methods to access optically active DHPMs with an emphasis on the recent advances in the asymmetric catalytic Biginelli reactions, along with concepts to design the organocatalytic asymmetric variants.