Digest paper Biginelli reaction: an overview Honnappa Nagarajaiah, Arindam Mukhopadhyay, Jarugu Narasimha Moorthy ⇑ Department of Chemistry, Indian Institute of Technology Kanpur, Kanpur 208016, India article info Article history: Received 15 July 2016 Revised 29 August 2016 Accepted 13 September 2016 Available online 14 September 2016 Keywords: Biginelli reaction Dihydropyrimidinones Multicomponent reaction Aldehyde Urea Active methylene compound abstract Biginelli reaction involves acid-catalyzed one-pot synthesis of 3,4-dihydropyrimidin-2(1H)-ones (DHPMs) using easily-accessible starting materials, namely, aldehyde, active methylene compound and (thio)urea. DHPMs have stimulated resurgence of interest in the past two decades due to their wide rang- ing pharmacological activities and presence of diverse natural products. Presently, green approaches to asymmetric Biginelli reaction are being explored for bioactive chiral DHPMs. In materials chemistry, DHPMs are increasingly finding applications in the development of materials such as polymers, adhe- sives, fabric dyes, etc. In view of the ease with which the Biginelli reaction is conducted, many exciting prospects await for its exploitation in various fields. Ó 2016 Elsevier Ltd. All rights reserved. Contents Introduction.......................................................................................................... 5135 Discovery ............................................................................................................ 5136 Mechanistic details .................................................................................................... 5137 Structural landscape/diversity ........................................................................................... 5139 Applications of Biginelli reaction ......................................................................................... 5139 Pharmacological activities of DHPMs .................................................................................. 5139 Asymmetric Biginelli reactions: access to chiral DHPMs .................................................................. 5142 DHPMs as applied to calcium channel modulation....................................................................... 5142 Natural product synthesis........................................................................................... 5145 Materials chemistry ............................................................................................... 5147 Functional polymers ......................................................................................... 5147 Adhesives .................................................................................................. 5147 Fabric dyes ................................................................................................. 5148 Conclusions .......................................................................................................... 5148 Acknowledgements .................................................................................................. 5148 References and notes ................................................................................................. 5148 Introduction Multicomponent reactions (MCRs) involve a combination of three or more reactants in a single vessel to produce a final product with features of all the reactant components. 1 MCRs have been a fascination for chemists for well over a century, as they serve as versatile tools for construction of heterocycles. MCRs are also often termed as ‘cascade’, ‘domino’ and ‘one-pot’ processes. The initial contribution to the development of multicomponent chemistry was made by Strecker in 1850. 2 Since then, a variety of MCRs have been reported, which include Hantzsch reaction, Passerini reaction, Ugi reaction, etc. In 1893, after a year of Hantzsch’s discovery of dihydropyridine (DHP), Pietro Biginelli reported the acid-catalyzed three-component one-pot synthesis of 3,4-dihydropyrimidin-2 http://dx.doi.org/10.1016/j.tetlet.2016.09.047 0040-4039/Ó 2016 Elsevier Ltd. All rights reserved. ⇑ Corresponding author. E-mail address: moorthy@iitk.ac.in (J.N. Moorthy). URL: http://home.iitk.ac.in/~moorthy/ (J.N. Moorthy). Tetrahedron Letters 57 (2016) 5135–5149 Contents lists available at ScienceDirect Tetrahedron Letters journal homepage: www.elsevier.com/locate/tetlet