一个简单、环境友好的硅胶固载硫酸催化Biginelli反应体系(英文)

A protocol for the synthesis of 3,4-dihydropyrimidin-2(1H)-ones and-thiones was developed by means of a three-component condensation of an aldehyde,a β-dicarbonyl compound,and urea or thiourea in acetic acid catalyzed by silica-bonded S-sulfonic acid.Compared to the classical Biginelli reaction conditions,this new protocol has the advantages of consistently excellent yields and short reaction times.After the reaction,the catalyst could be recovered easily and reused with little change in its activity.     

Ca(NO3)2•4H2O-catalysed Biginelli Reaction: One-pot Synthesis of 1,2,3,4-Tetrahydropyrimidin-2-ones/pyrimidine-2-thiones under Solvent-free Conditions

The synthesis of 1,2,3,4-dihydropyrimidinone/thione derivatives was achieved in good to excellent yields using calcium(II) nitrate as catalyst to promote the Biginelli three-component condensation reaction from a diversity of aromatic aldehydes, β-keto compounds and urea or thiourea. The reaction was carried out under solvent-free conditions.     

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.     

An efficient Biginelli one-pot synthesis of new benzoxazole-substituted dihydropyrimidinones and thiones catalysed by trifluoro acetic acid under solvent-free conditions

An efficient synthesis of benzoxazole-substituted 3,4-dihydropyrimidinones(DHPMs) using trifluoro acetic acid as the catalyst for the first time from an aldehyde,β-keto ester and benzoxazole-substituted urea/thiourea under solvent-free conditions is described.Compared to the classical Biginelli reaction conditions,this new method consistently has the advantage of excellent yields(80-91%) and short reaction time(40-130 min) at reflux temperature.     

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.     

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.     

One—Pot Synthese of 3,4—Dihydropyrimidine—2（1H）—thiones Catalyzed by La（OTf）3

A general and practical procedure for the syntheses of 3,4-di-hydropyrimidine-2(1H)-thiones by a one-pot condensation of aldehyde,β-ketoester or β-diketone and thiourea using La(OTf)3 as the catalyst is described.Mild reaction conditions,excellent yields as well as the environmentally friendly character of La(OTf)3 make it an important alternative to the classic acid-catalyzed Biginelli‘s reaction.     

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.     

A Convenient Synthesis of Conjugated Acetylenic Ketones by Copper(l)-Catalyzed under Microwave Irradiation

Alkynyl ketones are useful precursors and intermediates in synthetic organic chemistry1 and has evoked considerable interest. A number of methods for the synthesis of conjugated acetylenic ketones involve the reaction a metal acetylide with an acyl chlorides or another carboxylic acid derivative have been developed 2. Recently, the synthesis of α, β-conjugated acetylenic ketones catalyzed by Pd(Ⅱ) or by copper(Ⅰ)pd(Ⅱ) reaction of 1-alkynes and acyl chlorides have been described. The acylation of terminal alkynes by acyl chlorides in the presence of catalytic amounts copper(Ⅰ) salts leading to α, β-conjugated acetylenic ketones has also been reported. However, many of these reactions suffer from lack of high pressure (17 atm), long reaction time (30 h)and require low temperatures (-78℃). Our work involves the synthesis of conjugated acetylenic ketones via the reaction of terminal alkynes with aroyl chlorides in the presence of cuprous iodide under microwave irradiation conditions.     

One-Pot Synthesis of 5-Alkoxycarbonyl-4-aryl-3,4-dihydropyrimidin-2- ones Catalyzed by Phosphotungstic Acid

Many dihydropyrimidinones and their derivatives play an important role in medicine due to their therapeutic and pharmacological properties. [1] They have emerged as the integral backbones of several calcium channel blockers, antihypertensive agents, alpha-1α-antagonists. [2] Strategies for the synthesis of dihydropyrimidinone nucleus have varied from one-pot to multistep approaches. Although high yields can be achieved by the following complex multistep procedures, these methods lack the simplicity comparing with Biginelli protocol which firstly reported by Biginelli by one-pot condensation of aryl aldehyde, β-ketoesters and urea with catalytic acid in 1993, and these multistep methods suffer from low yields particularly for substituted aromatic aldehyde.     

Green Biginelli‐type Reaction: Solvent‐free Synthesis of 5‐unsubstituted 3,4‐dihydropyrimdin‐2(1H)‐ones

The Biginelli‐type compounds, 5‐unsubstituted 3,4‐dihydropyrimdin‐2(1H)‐ones were synthesized by a one‐pot three‐component condensation of aromatic aldehydes, aromatic ketones and urea in the presence of SnCl₄ · 5H₂O under solvent‐free conditions. The advantages of this method are short reaction time (4–10 min), excellent yields (74–97%), inexpensive catalyst and solvent‐free conditions. A plausible mechanism was proposed.     

One‐pot Synthesis of 3,4‐Dihydropyrimidin‐2(1H)‐ones Catalysed by Cupric Acetate under Solvent‐free Conditions

A solvent‐free synthesis of 3,4‐dihydropyrimidin‐2(1H)‐ones from aromatic aldehydes, β‐keto ester/acetyl acetone and urea catalysed by cupric acetate under thermal condition is reported as a simple and an efficient protocol. Compared with classical Biginelli reaction reported in 1893, this new method provides much improved modification in terms of yield and reaction time. The usage of milder catalyst, environmental friendly procedures and excellent yields within a very short time (5–15 min) are the advantages of the method in which the involvement of solvent‐free condition adds an edge to the method. Thus, the efficiency of the protocol enabled the rapid synthesis of 3,4‐dihydropyrimidin‐2(1H)‐one derivatives in a short duration.     

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%).     

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).     

固相β-环糊精包结物诱导7-羟基-2-甲氧基-2-甲基色满的不对称合成

研究了室温下间苯二酚和甲基乙烯基酮分别与β-环糊精（ β-CD）形成包结物后的几种不同固相反应,结果表明包结物A（间苯二酚/β-CD）与包结物B（甲基乙烯基酮/β-CD）反应能够很好地得到目的产物,产率及ee值分别为82.8%和78.4%;间苯二酚与包结物B反应仅得到低光学活性产物（ee值为19.5%）;包结物A与甲基乙烯基酮反应却没有得到手性目的产物。以熔点、X-粉末衍射、固相核磁碳谱及ROESY多种方法对所形成的包结物进行了表征,包结物中主客体的比例（1：1）通过¹H NMR (400 MHz)得以确定,文章对固相环加成反应的机制也进行了初步探讨。     

Gallium(III) Iodide‐catalyzed Biginelli‐type Reaction Under Solvent‐free Conditions: Efficient Synthesis of Dihydropyrimidine‐2(1H)‐one Derivatives

The Biginelli‐type condensation of ethyl acetoacetate/cycloketone, aldehyde and urea/thiourea under solvent‐free condition catalyzed by 10% gallium(III) iodide to form dihydropyrimidine‐2(1H)‐one derivatives was described. This process offered one way to constructing dihydropyrimidine‐2(1H)‐ones in good to excellent yields with simple procedure and short reaction time.     

Synthesis of tetrahydropyrimidino[4,3‐a]isoquinolines via regiospecific N‐alkylation‐annulation of 4‐aryldihydropyrimidinones

4‐Aryldihydropyrimidinones were obtained in excellent yields via solid‐phase Biginelli reaction of arylaldehydes, β‐ketoester and urea, using bismuth nitrate, immobilized on Al₂O₃ as catalyst. Subsequently, the products were converted into corresponding tetrahydropyrimidino[4,3‐a]isoquinolines (69–73% yield) by one‐pot regiospecific N‐alkylation‐annulation reaction using sodium hydride and dimethylaminopyridine. J. Heterocyclic Chem., (2011).     

Effective Methods for the Synthesis of N‐Methyl β‐Amino Acids from All Twenty Common α‐Amino Acids Using 1,3‐Oxazolidin‐5‐ones and 1,3‐Oxazinan‐6‐ones

N‐Methyl β‐amino acids are generally required for application in the synthesis of potentially bioactive modified peptides and other oligomers. Previous work highlighted the reductive cleavage of 1,3‐oxazolidin‐5‐ones to synthesise N‐methyl α‐amino acids. Starting from α‐amino acids, two approaches were used to prepare the corresponding N‐methyl β‐amino acids. First, α‐amino acids were converted to N‐methyl α‐amino acids by the so‐called ‘1,3‐oxazolidin‐5‐one strategy’, and these were then homologated by the Arndt–Eistert procedure to afford N‐protected N‐methyl β‐amino acids derived from the 20 common α‐amino acids. These compounds were prepared in yields of 23–57% (relative to N‐methyl α‐amino acid). In a second approach, twelve N‐protected α‐amino acids could be directly homologated by the Arndt–Eistert procedure, and the resulting β‐amino acids were converted to the 1,3‐oxazinan‐6‐ones in 30–45% yield. Finally, reductive cleavage afforded the desired N‐methyl β‐amino acids in 41–63% yield. One sterically congested β‐amino acid, 3‐methyl‐3‐aminobutanoic acid, did give a high yield (95%) of the 1,3‐oxazinan‐6‐one ( 65 ), and subsequent reductive cleavage gave the corresponding AIBN‐derived N‐methyl β‐amino acid 61 in 71% yield (Scheme 2). Thus, our protocols allow the ready preparation of all N‐methyl β‐amino acids derived from the 20 proteinogenic α‐amino acids.     

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.