Multicomponent biginellis synthesis of 3,4dihydropyrimidin. This means that they block calcium ion flow through membrane channels in cells. A collection of mono and biscglycosylated dihydropyrimidinones has been prepared by a parallel synthesis approach using the threecomponent promoter cuclacohbf3et2o. Threecomponent biginelli cyclocondensation reaction using. The biginelli reaction is a onepot threecomponent organic reaction between a. The biginelli reaction is an acidcatalyzed threecomponent condensation of an aldehyde, a bketoester, and an urea leading. With a deeper mechanistic understanding of the biginelli reaction, several advancements were made to address the poor and variable yields 2070% and limited substrate scope often associated with this reaction. The biginelli reaction is a multiplecomponent chemical reaction that creates 3. The product structure was confirmed by nmr and noe analysis, and the proposed. This reaction begins with protonation of the aldehyde by the acid and is followed by attack of the amine from urea. The biginelli reaction is a multiplecomponent chemical reaction that creates 3,4dihydropyrimidin2 1 h ones 4 from ethyl acetoacetate 1, an aryl aldehyde such as benzaldehyde 2, and urea 3.
Biginelli reaction using propylene carbonate as green. Ndonor ligand activation of titanocene for the biginelli reaction via the imine mechanism shaohua zheng,a yajun jian,a shan xu,a ya wu,ab huaming sun,a guofang zhang,a weiqiang zhang a and ziwei gao a the remarkable activation of stable titanocene dichloride cp 2ticl 2 was achieved using ndonor ligand. A novel green synthesis of pyrimidinone derivatives via biginelli reaction using animal bone meal as catalyst m. An elegant methodology for the synthesis of dihydropyrimidinones and dihydropyrimidinthiones. Recent times have witnessed the exploitation of biginelli reaction in asymmetric synthesis. The biginelli reaction was discovered in 1891 by the chemist pietro biginelli. A novel green synthesis of pyrimidinone derivatives via. Though the conventional bronsted acidcatalyzed biginelli reaction provides a.
Acyl pyruvates as synthons in the biginelli reaction sergey v. However, when thiourea was used, no theoretical calculations were reported. An elegant methodology for the synthesis of dihydropyrimidinones and dihydropyrimidinthiones volume. Scheme 2 our report of themicrodropletcatalyzed biginelli reaction using theta tip. Ugi reaction the ugi fourcomponent condensation u4cc between an aldehyde, an amine, a carboxylic acid and an isocyanide allows the rapid preparation of. In the past decades, the asymmetric variants of this reaction have. The reaction mechansim can therefore be classified as an. Studies on the biginelli reactions of salicylaldehyde and 2.
Biginelli reaction is one of the most essential multicomponent reactions. Reviews and accounts arkivoc 2012 i 663 97 100 101 nahso4, diacetoxyiodobenzene,98 tmscl,99 tio2, hbf4sio2, hcletoh,102 mgso47h2o,103 bmimhso4,104 1,3dichloro5,5dimethylhydantoin,105 yoac3,106 nickel nanoparticles,107 tributyl borate,108 vhso43,109 nafionh,110 cucl2,111 dodecylphosphonic acid,112 paminobenzene sulfonic acid,1 phosphoric. Biginelli reaction using propylene carbonate as green solvent. Curran has prepared fluorinated ureas 30, which underwent the biginelli reaction and were cleanly extracted into fluorinated hexanes. Various synthetic methods have been used to catalyze the biginelli reaction, some of them the include use of lewis acid catalysts such as bf 3 oet, 11 cocl 2 6h 2 o, 12 fecl 3 6h 2 o nicl 2 6h 2 o, in iii halides, 14 sncl 2 2h 2 o, 15 lacl 3 7h 2 o, 16 cecl 3 7h 2 o, 17 zrcl 4, 18 metal triflates such as znotf 2, 19 cuotf. Amphiphilic fluorescent copolymers via onepot synthesis of raft polymerization and multicomponent biginelli reaction and their cells imaging applications volume 34 issue 17 zengfang huang, runze wang, yali chen, xiaobo liu, liucheng mao, jinying yuan, lei. The biginelli reaction in different solvents and in presence of.
Since the disclosure of biginelli reaction by the chemist pietro biginelli, functionalized 3,4dihydropyrimidin21honesthiones dhpms have emerged as prototypes for the design of compounds with a broad variety of biological activities. Reviews and accounts arkivoc 2012 i 663 97 100 101 nahso4, diacetoxyiodobenzene,98 tmscl,99 tio2, hbf4sio2, hcletoh,102 mgso47h2o,103 bmimhso4,104 1,3dichloro5,5dimethylhydantoin,105 yoac3,106 nickel nanoparticles,107 tributyl borate,108 vhso43,109 nafionh,110 cucl2,111 dodecylphosphonic acid,112 paminobenzene sulfonic acid,1 phosphoric acids,114 ammonium carbonate,115. Organocatalytic asymmetric biginellilike reaction involving isatin cheminform 2016, 47 29 doi. Organocatalytic asymmetric biginellilike reaction involving. The biginelli reaction is a onepot acid catalysed cyclocondensation of. Files are available under licenses specified on their description page.
Ndonor ligand activation of titanocene for the biginelli reaction via the imine mechanism shaohua zheng,a yajun jian,a shan xu,a ya wu,ab huaming sun,a guofang zhang,a weiqiang zhang a and ziwei gao a the remarkable activation of stable titanocene dichloride cp. Marr, queens university belfast, united kingdom 0 1 department of chemistry, university of delhi, delhi, india, 2 department of microbiology and immunology, columbia university medical center, new. This threecomponent reaction for the synthesis of dihydropyrimidinone and corresponding dihydropyrimidinethiones has now been known. Andrea nuzzi, alessandro massi, alessandro dondoni. Biginelli reaction, multicomponent reactions, green process. Amphiphilic fluorescent copolymers via onepot synthesis of raft polymerization and multicomponent biginelli reaction and their cells imaging applications volume 34 issue 17 zengfang huang, runze wang, yali chen, xiaobo liu, liucheng mao, jinying yuan, lei tao, yen wei, xiaoyong zhang. Multicomponent reactions mcrs 14 are of great importance in organic synthesis. Pdf he biginelli reaction is a onepot acid catalysed cyclocondensation of. This acidcatalyzed, threecomponent reaction between an aldehyde, a. The biginelli reaction scheme 3 is an acid catalyzed, threecomponent reaction between an aldehyde, bketoester, and urea that produces tetrahydropyrimidones, which have potential pharmaceutical applications. Amphiphilic fluorescent copolymers via onepot synthesis. Garlic clove catalyzed biginelli reaction in water at.
Aug 24, 2018 a new multicomponent condensation was discovered during the reaction of a urea. Biginelli reaction, this onepot condensation reaction generates compounds with pharmacological activity, including calcium channel modulation, mitotic kinesin eg5 inhibition, and antiviral and antibacterial activity. Of the three substrates involved in the biginelli reaction, the aldehyde component is the most commonly explored regarding structural variation. An enantioselective biginelli reaction catalyzed by a simple chiral secondary amine and achiral bronsted acid by a dualactivation route. The ugi reaction products can exemplify a wide variety of substitution patterns, and constitute peptidomimetics that have potential pharmaceutical applications. Media in category biginelli reaction the following 8 files are in this category, out of 8 total.
Synthesis of structurally diverse 3,4dihydropyrimidin2. The biginelli reaction, reported by pietro biginelli in 1893,1 is a. An efficient and greener synthesis of a series of dihydropyrimidinone dhpms derivatives were accomplished via threecomponent onepot cyclocondensation between substituted aryl aldehydes, diketoneke toester and urea. The biginelli reaction, involving a threecomponent reaction of an aromatic aldehyde, urea and ethyl acetoacetate, has emerged as an extremely useful synthetic tool to organic chemists for the synthesis of 3,4dihydropyrimidine21hones and related heterocyclic compounds.
Synthesis of dihydropyrimidinones via biginelli multi. Past, present and future of the biginelli reaction. The first asymmetric, bronsted acid catalyzed biginellilike reaction of a ketone has been developed, employing nsubstituted isatins as carbonyl substrates, and urea and alkyl acetoacetates as further components. Desilylation affords n1 substituted dihydropyrimidines 31. In the presence of catalytic indium bromide, a biginelli dihydropyrimidinone intermediate was further converted to a fivecomponent condensation product through a formal hetero dielsalder reaction. It is named for the italian chemist pietro biginelli. Biginelli reaction multicomponent chemical reaction.
Amphiphilic fluorescent copolymers via onepot synthesis of. View the article pdf and any associated supplements and figures for a period of. As one of the most prominent multicomponent reactions mcrs, biginelli reaction has been utilized for the synthesis of 3,4dihydropyrimidin2. Onepot multicomponent synthesis of dihydropyrimidinones. Aromatic aldehydes with donor groups or groups that remove electron density at the meta or parapositions usually provide the desired products. In the past decades, the asymmetric variants of this reaction have been at the forefront of investigations. Three possible pathways proposed for the reaction are the iminium route, an enamine intermediate, and the knoevenagel pathway. The biginelli and related passerini and ugi reactions. This solvent free approach is totally nonpolluting having several advantages such as shorter reaction time, mild reaction conditions, simple workup and reduced. The reaction was carried out in acetonitrile or ethanol as solvents in neutral media and represents an improvement of the classical biginelli protocol and an advantage in comparison with fecl3.
A new multicomponent condensation was discovered during the reaction of a urea. The biginelli reaction synthesis of 3,4dihydropyrimidin21hones was discovered in 1893 by pietro biginelli. In general, the reaction works best with aromatic aldehydes that are ortho, meta, or parasubstituted. Biginelli reaction catalyzed by copper nanoparticles pdf. The biginelli reaction synthesis of 3,4dihydropyrimidin21hones was discovered in 1893 by pietro biginelli biginelli, p. Ndonor ligand activation of titanocene for the biginelli. The biginelli reaction is a threecomponent reaction between an aldehyde in many cases aromatic aldehydes give much better results than aliphatic ones, a. The synthesis of 3,4dihydropyrimidinones was achieved in good to excelent yields. Green highyielding onepot approach to biginelli reaction under. The other methods are rely on condensation of carbonyls with amines for example the synthesis of 2thio6methyluracil using ethylacetoacetate and thiourea.
Development and applications reported by eric woerly november 24, 2008 introduction the combination of an aldehyde 1. A combined experimental and theoretical mechanistic investigation. The biginelli dihydropyrimidone synthesis using polyphosphate. Pdf dihydropyrimidinones and their corresponding derivatives were synthesized.
Onepot, solventfree synthesis via biginelli reaction cogent oa. A fivecomponent biginellidielsalder cascade reaction. The italian chemist biginelli 1891a, 1891b, observed the reaction between an ammonia source and. Manhasa ageorge barasch bioorganic research laboratory, department of chemistry and chemical biology, stevens institute of technology, hoboken, nj 07030, usa. In this account, update on catalyst variations, asymmetric synthesis, scaffold variations and biginelli like reactions aspect of this reaction is presented. A read is counted each time someone views a publication summary such as the title, abstract, and list of authors, clicks on a figure, or views or downloads the fulltext.
The reaction mixture was purified by a liquidliquid extraction method since the byproducts were not soluble in the fluorinated solvent. Scheme 3 a acidcatalyzed biginelli produced products in high yields. The biginelli reaction was discovered in 1891 by the. The biginelli reaction 912 is an acidcatalyzed, threecomponent reaction between a. Threecomponent biginelli cyclocondensation reaction using c. Postlab questions questions 1, 3, and 4 on separate paper 2 3,4dihydropyrimidones are calcium channel blockers. The biginelli reaction is a multicomponent reaction for obtaining dihydropyrimidinthiones quickly, with multiple substitution patterns. Synthesis of structurally diverse 3,4dihydropyrimidin21h. Acyl pyruvates as synthons in the biginelli reaction.
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