Development and applications reported by eric woerly november 24, 2008 introduction the combination of an aldehyde 1. Reagents such as benzaldehyde, ethyl acetoacetate, urea, and ethanol, and concentrated hydrochloric acid was used to conduct the analysis. Catalystfree biginellitype synthesis of new functionalized. Grindstone chemistry a greatly evolved version of todas method of grinding solids together for solventfree chemical reactions has been described and its usefulness illustrated by the successful application of this technique to a simplified process for conducting the multicomponent biginelli reaction for the synthesis of physiologically active tetrahydropyrimidinones.
Conditions that support the formation and reaction of nacyliminium ion provide one route to improving the biginelli reaction. The biginelli reaction is a onepot multicomponent reaction between a 1,3dicarbonyl, an aromatic aldehyde and urea catalyzed by lewis acids, which forms dihydropyrimidinones panda et al. Styler department of chemistry university of toronto green chemistry and engineering conference, 23rd june 2009. Introduction multicomponent reactions mcrs are of increasing importance in organic and medicinal chemistry. However, this method is suffered from drawbacks of the longer reaction time and lower. The author discusses the planning and detailed preparations that are required in order to convert to green laboratory techniques. The biginelli reaction is a condensation of an aldehyde, a 1,3dicarbonyl. Literature reported, 14 biginelli reactions via grindstone chemistry have made use of toxic chemicals like. Because the objective of the present study was to maintain a green approach to the biginelli reaction, five green solvents were evaluated. Microwave, mechanochemistry, green chemistry, biginelli reaction, green solvents, organic synthesis correspondence to author. Minerals such as hydroxylapatite may also catalyze the biginelli reaction according to a recent report moussa et al.
The biginelli and related passerini and ugi reactions. Green protocol for the synthesis of catalyst free biginelli. Regarding the green chemistry principles, carrying out the biginelli. Synthesis of dihydropyrimidinones dhp by biginelli reaction is one among them. The original biginelli reaction was carried out by refluxing a mixture of the three components. The crown and stem portions were removed and the skin. Abstractgrindstone chemistry a greatly evolved version of todas method of grinding solids together for solventfree chemical reactions has been. The biginelli reaction is a ureacatalyzed organocatalytic. Multicomponent reactions the biginelli reaction name. The combined role of catalysis and solvent effects on the. The biginelli reaction was discovered in 1891 by the. The mechanism of this biginelli reaction as its reported by sweet et al. Synthesis of structurally diverse 3,4dihydropyrimidin2. Biginelli reaction involves acidcatalyzed onepot synthesis of 3,4dihydropyrimidin21hones dhpms using easilyaccessible starting materials, namely, aldehyde, active methylene compound and.
The biginelli reaction is a multiplecomponent chemical reaction that creates 3,4 dihydropyrimidin21hones 4 from ethyl acetoacetate 1, an aryl aldehyde such. Citric acid mediated efficient three component synthesis of. A novel green synthesis of pyrimidinone derivatives via biginelli reaction using animal bone meal as catalyst m. This threecomponent reaction for the synthesis of dihydropyrimidinone and corresponding dihydropyrimidinethiones has now been known for more than a century since first reported in 1893. Paola costanzo, monica nardi, manuela oliverio, similarity and competition between biginelli and hantzsch reactions. Role of degree of oxidation of graphene oxide on biginelli reaction kinetics. A simplified green chemistry approach to the biginelli. Pdf green highyielding onepot approach to biginelli reaction. Tetrahedron letters tetrahedron letters 46 2005 19011903 large scale biginelli reaction via waterbased biphasic media. Department of chemistry university of florida, florida fl 32611, usa. Large scale biginelli reaction via waterbased biphasic. Grindstone chemistry a greatly evolved version of todas method of grinding solids together for solventfree chemical reactions has been.
Each clearly structured chapter features indepth coverage of various green protocols for the synthesis of a wide variety of bioactive heterocycles classified on the basis of ringsize andor presence of heteratomss. Catalytic activity of different ion exchange resins in biginelli condensationa. Crouch 10 described a microscale biginelli reaction in this. An efficient onepot green protocol for the synthesis of 5. The improved biginelli reaction not only features a simple procedure, high yields and easy purification of production, but also the recycled. Although numerous methods for the synthesis of 3,4dihydropyrimidin21honesthiones are known, a few bronstedlowry or lewis acids are used as catalyst for the biginelli reaction 410, the use of ionic liquide 11,12, microwave irradiation, solid phase reagent. A green and efficient method for the preparation of 3,4. This acidcatalyzed, threecomponent reaction between an aldehyde, a. The advent of multicomponent reactions has emerged out to be a powerful tool in synthetic organic chemistry 1,2. A literature survey showed that the biginelli dihydropyrimidine synthesis as an. A novel green synthesis of pyrimidinone derivatives via. Development of organocatalytic processes in which the reactions are catalyzed by organic molecules is an important area for the green synthesis. Solventfree biginelli reactions catalyzed by hierarchical.
Classical methodology and as a need for sustainable chemistry, this reaction has. Large scale biginelli reaction via waterbased biphasic media. The recently developed artificial force induced reaction afir method was applied to search systematically all possible multicomponent pathways for the biginelli reaction mechanism. Synthesis of structurally diverse 3,4dihydropyrimidin21h. Multi component reaction via grindstone methodology is well known and well documented in literature. These kinds of reactions ensure an essential facet of green chemistry to reduce the risks to humans and. Keywords monolacunary keggin multicomponent reaction onepot manner polyhydroquinolines hantzsch reaction dihydropyrimidones biginelli reaction introduction the application of ef.
Our growing concern for the environment has encouraged the scientists to develop a green and eco friendly protocol for this biginelli reaction. A simplified green chemistry approach to the biginelli reaction using. An efficient onepot synthesis of dihydropyrimidinones. However, the peculiar reactivity and lower stability of hmf have limited its. Stereoselective biginellilike reaction catalyzed by a chiral. Stereoselective biginellilike reaction catalyzed by a.
For biginelli reaction, large number of methods have. The results show that the effect of microwave irradiation on the reaction studied was the shortening of reaction times from 29 h to 24 min and a minor decrease 14% in yields scheme 2. A green and simple protocol onepot biginelli condensation using. This experiment was executed through a reflux technique and by cooling the reaction mixture to collect the product. Remarkably, a second urea molecule catalyzes nearly every step of the reaction. This reaction is nowadays referred to as the biginelli reaction, biginelli condensation or as the biginelli dihydropy rimidine synthesis. In the present communication, under the influence of microwaves, cuprous chloride has been demonstrated to be safe, mild, efficient, and inexpensive catalyst for the biginelli discovered multicomponent reaction mcr between aromatic aldehydes, ureasubstituted urea, and ethyl acetoacetate to produce structurally diverse dihydropyrimidin21hones dhpms and thiones in an. Devaanshi jagwani medicaps group of institutions, pigdamber, rau, indore453331, m. Lithiumacetatemediated biginelli onepot multicomponent. Catalyzed and noncatalyzed synthesis of bioactive monastrol.
Influence of electronic factors on solventfree and catalyst. Apart from the above, another green protocol for the biginelli reaction starting from alcohols 38 instead of aldehydes has been reported 107. To overcome the barriers associated with solvent free reactions, the mechanochemical mixing i. Ganguly, hoang dang, william he and arun mandadi george barasch bioorganic research laboratory, department of chemistry and chemical biology, stevens institute of technology, hoboken. Multicomponent reactions mcr using hmf offer straightforward access to novel fine chemicals. Nov 01, 2004 grindstone chemistry a greatly evolved version of todas method of grinding solids together for solventfree chemical reactions has been described and its usefulness illustrated by the successful application of this technique to a simplified process for conducting the multicomponent biginelli reaction for the synthesis of physiologically active tetrahydropyrimidinones. Institute of chemistry, heinrichstrasse 28, 8010 graz, austria. A simplified green chemistry approaches to organic synthesis in. Green chemistry approaches to the synthesis of 5 alkoxycarbonyl4aryl3.
Green highyielding onepot approach to biginelli reaction. Reaction monitoring through tlc after 90 min showed total consumption of reactants when pure acetic acid and a 1. It is named for the italian chemist pietro biginelli. The biginelli reaction synthesis of 3,4dihydropyrimidin21hones was discovered in 1893 by pietro biginelli biginelli, p. Ionic liquids catalyzed biginelli reaction under solvent. Various biginelli compounds dihydropyrimidinones have been synthesized efficiently and in high yields under mild, solventfree, and ecofriendly conditions in a onepot reaction of 1,3dicarbonyl compounds, aldehydes, and ureathioureaacetyl thiourea using lithiumacetate as a novel catalyst without the addition of any proton source. Full text pdf with links to cited urls and jce articles.
Biginelli reaction is one of the most essential multicomponent reactions mcrs. The use of the renewable platform molecule 5hydroxymethylfurfural hmf in the multicomponent biginelli reaction has been investigated. Jun 01, 2020 applications of multicomponent reactions mcrs in the preparation of diverse types of heterocyclic compounds carries a unique place in chemical synthesis. Copper supported on acidactivated vermiculite as an.
Multicomponent reactions mcrs are of great importance in both organic and medicinal chemistry for various reasons. Biginelli reaction, dihydropyrimidinones, onepot, solventfree. Green synthetic approaches for biologically relevant. They allow the assembly of complex molecules in one pot, leading to a product that ideally contains all atoms of the reactants. These kinds of reactions ensure an essential facet of green chemistry to. Grindstone technique is considered to be environmentally benign method as this method completely avoids the usage of any solvent. This reaction was developed by pietro biginelli in 1891. Efficient synthesis of 3,4dihydropyrimidin2ones in low melting tartaric acidurea mixtures. A practical and green approach towards synthesis of 3, 4dihydropyrimidin2 1honesthiones. The reaction mechanism of the biginelli reaction is a series of bimolecular reactions leading to the desired dihydropyrimidinone.
Our interests have been focused on the chemistry of unusual biginelli type compounds 14 and, particularly. Influence of electronic factors on solventfree and. However, method is limited and mostly required long time. Lemine, green highyielding onepot approach to biginelli reaction under catalystfree and solventfree ball milling conditions, applied sciences, 10. Hmf in multicomponent reactions tel archives ouvertes. A green p erspective current organic chemistry, 2012, vo l. Nov 23, 2016 biginelli reaction has emerged as a very useful tool in polymer chemistry due to the following reasons. So the solventfree and catalystfree green chemistry of biginelli reaction has been reported by the researchers11. The biginelli reaction synthesis of 3,4dihydropyrimidin21hones was discovered in 1893 by pietro 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 biginelli reaction multicomponent reactions wiley.
Although the biginelli reaction was firstly discovered over a century ago 10, little attention was given to asymmetric pathways. In the present communication, under the influence of microwaves, cuprous chloride has been demonstrated to be safe, mild, efficient, and inexpensive catalyst for the biginelli discovered multicomponent reaction mcr between aromatic aldehydes, ureasubstituted urea, and ethyl acetoacetate to produce structurally diverse dihydropyrimidin21hones dhpms and thiones in an ecofriendly solvent. International journal of advanced chemistry, 2014 46 ascorbic acidcatalyzed onepot threecomponent biginelli reaction. The biginelli reaction is a onepot acid catalysed cyclocondensation of.
An investigation into catalytic and solvent effects has returned the conclusion that the diketoenol tautomerisation equilibrium of the dicarbonyl reactant dictates the yield of the reaction. Biginelli reaction, among the loop of multicomponent reactions, provide an efficient way to access of highly functionalized dihydropyrimidones thiones dhpms. The most favorable pathway starts with the condensation of the urea and benzaldehyde, followed by the addition of ethyl acetoacetate. Covering a wide range of reactions, including solid state, photochemical, enzymatic, and sonication, this book explains the need for and the principles of green chemistry, including applications relevant to researchers and students. Biginelli reaction catalysed by heteropolyacids hpas can be one of the. The generation of dihydropyrimidine libraries utilizing. In connection with this, multicomponent biginelli and biginelli like reactions of aldehydes, ureathiourea, and enolizable carbonyls revealed as very efficient tools to prepare dhpms 3. Among the multicomponent reactions, biginelli reaction is one of the most studied reactions since the product of this reaction is dihydropyrimidinones dhpms which are vital medicinal synthones that display a wide range of biological activities such as antibacterial, antiinflammatory, antiviral, antitumour 35. Unlimited viewing of the articlechapter pdf and any associated. Visible light induced biginelli reaction in fruit juice. Ionic liquids catalyzed biginelli reaction under solventfree conditions jiajian peng and youquan deng state key laboratory for oxo synthesis and selective oxidation and centre for ecological and green chemistry, lanzhou institute of chemical physics, chinese academy of sciences, lanzhou 730000, china.
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. The biginelli reaction was discovered in 1891 by the chemist pietro biginelli. Onepot, solventfree synthesis via biginelli reaction. Recently our group has focused to develop some green methodologies for synthesizing dhpms via green biginelli reactions.
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