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.     

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.     

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).     

Copper(I)‐catalyzed multicomponent reactions in sustainable media

Multicomponent reactions including Biginelli reaction and A³ coupling are useful synthetic methodologies as they can provide valuable intermediates and building blocks for the synthesis of bioactive natural compounds. The heterocyclic products of these transformations represent antibacterial, antitumor or anti‐inflammatory properties. In presented study, copper‐mediated protocols for Biginelli reaction and A³ coupling in sustainable solvents were reported. At first, charged NHC copper complexes were synthesized in few steps and characterized using spectroscopic methods followed by preliminary activity tests in sustainable media. Later in this study, Biginelli reaction and A³ coupling were proceeded using prepared copper catalytic systems under mild conditions. Desired nitrogen‐bearing products were obtained with moderate to very high yields. Some attempts to recycle one of the received NHC copper initiators were also investigated.     

溴化镁催化的1,2,3,4-四氢吡啶酮无溶剂合成研究

An efficient and environmentally friendly procedure for the one-pot synthesis of tetrahydropyrimidinones from aldehydes, β-diketones and urea/thiourea by using magnesium bromide as an inexpensive and easily available catalyst under solvent-free conditions was described. Compared with the classical Biginelli reaction conditions, this new method has the advantage of good to excellent yields (74%-94%) and short reaction time (45-90 min). The structure of the Biginelli reaction product from β-diketone, salicylaldehyde and urea has been proposed to possess an oxygen-bridge by cyclization (intramolecular Michael-addition).     

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.     

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%).     

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.     

Studies on the Biginelli Reactions of Salicylaldehyde and 2‐Hydroxy‐l‐naphthaldehyde

The Biginelli reactions of salicylaldehyde and 2‐hydroxy‐l‐naphthaldehyde with ethyl or methyl acetoacetate, ethyl benzoylacetate, and urea have been reinvestigated both in the structures of the reaction products and in the reaction conditions. Salicylaldehyde with ethyl and methyl acetoacetate resulted in oxygen‐bridged tricyclic tetrahydro pyrimidines, whereas with ethyl benzoylacetate afforded the only normal 3,4‐dihydropyrimidin‐2‐one. 2‐Hydroxy‐l‐naphthaldehyde with ethyl and methyl acetoacetate formed the tricyclic compounds. Steric effect is likely to be the principal determinant in governing the formation of product dichotomy. Previous controversial results as to the structure of the Biginelli products have been discussed and settled. The molecular structures of the dihydropyrimidinones and bridged tricyclic products have been fully characterized and confirmed unambiguously by single crystal X‐ray diffraction.     

Synthesis of novel 4‐pyrazolyl‐2‐oxo‐1,2,3,4‐tetrahydropyrimidines promoted by phosphotungstic acid

Phosphotungstic acid, a keggin's type heteropoly acid catatalysed Biginelli reaction was carried out using pyrazole aldehyde, ethyl acetoacetate and urea to synthesis novel 4‐pyrazolyl ‐2‐oxo‐1,2,3,4‐tetrahydropy‐ rimidines.     

Ferric Perchlorate Catalyzed One‐pot Synthesis of 1,2,3,4‐Tetrahydro‐2‐pyrimidinones and ‐thiones: an Expedient Protocol for the Biginelli Reaction

An efficient synthesis of 1,2,3,4-tetrahydro-2-pyrimidinones and -thiones using ferric perchlorate as the catalyst from an aldehyde, ethyl acetoacetate, and urea or thiourea in acetonitrile was described. Compared to the classical Biginelli reaction conditions, this new method consistently has the advantage of full catalysis, good yields and short reaction time.     

Effect of Poly(ethylene glycol)‐400 and Carbon on MoO3 Nanocomposite Materials and Its Catalytic Activity

The effect of addition of poly(ethylene glycol)‐400 (PEG‐400) and carbon (0, 1, 2 and 3 wt%) as substrates were investigated systematically to get the desired phase of carbon‐doped MoO₃ material. The carbon source was prepared from the Acacia arabica plant wood. The resulting samples were calcined at 500°C. The effect of PEG‐400 and carbon composite on the structure, particle size and morphology were investigated. The prepared samples were characterized by XRD, SEM‐EDS and FT‐IR techniques. The samples with PEG‐400 and carbon addition give better control of particle size and porosity. The prepared catalysts were tested for the synthesis of 3,4‐dihydropyrimidones via the Biginelli‐type condensation reaction. This new method consistently has the advantage of excellent yields (88%–93%) and short reaction times (1.5–3 h) than do classical Biginelli reaction conditions.     

Convenient One‐Pot Heterogeneous Catalytic Method for the Preparation of 3,4‐Dihydropyrimidin‐2(1H)‐ones

A new, simple, environmentally friendly synthesis of dihydropyrimidinones from aromatic and aliphatic aldehydes, ethyl acetoacetate, and urea or thiourea using a small‐pore‐size zeolite as catalyst is described. Compared with the classical Biginelli reaction conditions, this method has the advantage of high yield, shorter reaction time, and recyclable and reusable catalyst.     

The Biginelli Reaction with an Imidazolium–Tagged Recyclable Iron Catalyst: Kinetics,Mechanism, and Antitumoral Activity

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, the ion‐tagged catalyst could be recovered and reused up to eight times without any noticeable loss in activity. Mechanistic studies performed by using high‐resolution electrospray‐ionization quadrupole‐time‐of‐flight mass (HR‐EI‐QTOF) spectrometry and kinetic experiments indicate only one reaction pathway and rule out the other two possibilities under the development conditions. The theoretical calculations are in accordance with the proposed mechanism of action of the iron catalyst. Finally, the 37 dihydropyrimidinone derivatives, products of the Biginelli reaction, had their cytotoxicity evaluated in assays against MCF‐7 cancer cell linages with encouraging results of some derivatives, which were virtually non‐toxic against healthy cell linages (fibroblasts).     

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.     

用硼酸作催化剂一锅法合成双（二氢化嘧啶酮-4-基）苯

A simple effective synthesis of bis(dihydropyrimidinone-4-yl)benzene derivatives, using boric acid as catalyst,from isophthalic aldehyde or terephthalic aldehyde, 1,3-dicarbonyl compounds and urea or thiourea in glacial acetic acid was described. As the expansion of the classical Biginelli reaction, this method has the advantage of excellent yields 83%-94% and short reaction time 0.5-1.5 h.     

CoCl_2·6H_2O or LaCl_3·7H_2O Catalyzed Biginelli Reaction. One-Pot Synthesis of 3,4-Dihydropyrimidin-2(1 H)-ones

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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.     

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.     

Rapid Synthesis of 1,2,3,4-Tetrahydropyrimidin-2-ones Using Zn（NH2SO3）2 as a Catalyst under Microwave Irradiation

Rapid synthesis of 1,2,3,4-tetrahydropyrimidin-2-ones （THPO） from aromatic aldehydes, β-ketoester and urea （or thiourea） using zinc sulfamate as the catalyst under microwave irradiation was described here. Compared with the classical Biginelli reaction, this new method consistently has the advantages of good yields （76%-96%）, short reaction time （3-15 min）, no corrosion to equipments, ease of manipulation, and low cost catalyst.