An efficient method for the multicomponent synthesis of multisubstituted pyridines, a rapid procedure using Au/MgO as the catalyst Ramakanth Pagadala, Suresh Maddila, Vashen Moodley, Werner E. van Zyl, Sreekantha B. Jonnalagadda ⇑ School of Chemistry & Physics, University of KwaZulu-Natal, Westville Campus, Chiltern Hills, Durban 4000, South Africa article info Article history: Received 26 March 2014 Revised 14 May 2014 Accepted 22 May 2014 Available online 2 June 2014 Keywords: Multicomponent reactions Multisubstituted pyridines Heterogeneous catalyst Au/MgO Green chemistry Reusable catalyst abstract Au/MgO proved to be a highly efficient and reusable catalyst for multicomponent coupling reactions at 70 °C. The synthesized multisubstituted pyridines were obtained in high yields and in short reaction times. With facile work-up, the novel catalyst can be readily recovered after the reaction and reused without any loss of its catalytic activity. Ó 2014 Elsevier Ltd. All rights reserved. Eco-efficient and eco-friendly methodologies for heterocyclic chemistry are vital for the continued preparation of functional organic molecules and materials. 1 For the sake of economic outlook and pollution prevention, multicomponent reactions (MCRs) are very attractive research endeavors in organic synthesis due to the formation of CAC and C-heteroatom bonds in one pot. 2 This approach has garnered considerable interest, as it addresses the fundamental principles of synthetic efficiency and reaction design arising from minimization of waste, time, energy, and cost. Mini- mizing the consumption of auxiliary substances, energy, and time required in achieving separations, results in significant economic and environmental benefits owing to the new strategies for recy- cling heterogeneous solid catalysts. 2a,b Assembling N-heterocycles is important in synthetic organic chemistry. The synthesis of polysubstituted pyridines is of particu- lar interest because such compounds constitute partial or complete structures of many natural products and organic functional materials, as well as in many synthetic compounds of pharmaceuti- cal interest. 3 Additionally, 2-amino-3-cyanopyridine derivatives (Fig. 1) have raised considerable attention as potent inhibitors of HIV-1. 4 The development of highly efficient methods for the prepara- tion of polysubstituted pyridine derivatives is of considerable interest. Most of the existing synthetic routes to pyridines are based on reactions between amines and carbonyl compounds. 5 Despite the numerous studies and methods that have appeared in the literature, most of the protocols still suffer from one or more important limitations such as long reaction times, low yields, use of toxic solvents, 6 high temperatures, or microwave assistance. 7 However, a straightforward and efficient one-pot synthesis of multisubstituted pyridine structures is often a challenge. So there is still a great demand to develop new approaches to multifunc- tionalized pyridines. The reported use of MgO supported Au catalysts for oxidation and coupling reactions 8 has prompted our choice of catalyst. To our knowledge, no reports are available in http://dx.doi.org/10.1016/j.tetlet.2014.05.089 0040-4039/Ó 2014 Elsevier Ltd. All rights reserved. ⇑ Corresponding author. Tel.: +27 31 260 7325/3090; fax: +27 31 260 3091. E-mail address: jonnalagaddas@ukzn.ac.za (S.B. Jonnalagadda). N CN NH 2 N H N NC H 2 N CN S O Br Br O O O OH Figure 1. Polysubstituted pyridines with adjacent amino and nitrile functionalities having diverse pharmacological properties. Tetrahedron Letters 55 (2014) 4006–4010 Contents lists available at ScienceDirect Tetrahedron Letters journal homepage: www.elsevier.com/locate/tetlet