Month 2017 Microwave-Assisted, One-Pot Multicomponent Synthesis of Some New Cyanopyridines Amer A. Amer and Antar A. Abdelhamid* Chemistry Department, Faculty of Science, Sohag University, Sohag 82524, Egypt * E-mail: drantar25@yahoo.com Received February 7, 2017 DOI 10.1002/jhet.2926 Published online 00 Month 2017 in Wiley Online Library (wileyonlinelibrary.com). An efficient and facile synthesis of cyanopyridines via a one-pot four-component reaction of aromatic aldehydes, acetophenones, malononitrile, or 2-aminoprop-1-ene-1,1,3-tricarbonitrile in presence of sodium alkoxide or ammonium acetate under both microwave and thermal reaction conditions was introduced. J. Heterocyclic Chem., 00, 00 (2017). INTRODUCTION The improvement of synthetic methods for functionalized pyridines is a significant research matter in organic chemistry due to their importance in the topics of chemistry and biology. Pyridines are openly dispersed and found in natural products, pharmaceuticals, vitamins, and other functional as well as important materials [1–5]. In fact, the pyridine moiety system emerged integral backbone of more than thousands existing drugs [6–8]. Among a broad range of pyridines, cyanopyridine achieved a special attention due to it great therapeutic importance as antihypertensive [9], anticonvulsant [10], antihypertensive [11], antibacterial [12], anti-inflamatory [13], antifungal [14], cardiovascular [15], anti-Alzheimer ’ s disease [16], antitumor [17], and antiallergic [18] properties. Therefore, the synthesis of cyanopyridinesis of current benefit owes to their massive occurrence in biologically active derivatives. From an environmental and economic perspective, it is becoming obvious that the traditional methods of proceeding chemical synthesis are unsustainable and have to be changed. Multicomponent coupling reactions provide a solution because they are more cost effective, efficient, and less wasteful than traditional methods [19]. Microwave (MW) produces a powerful way to do synthetic chemistry in the light of the current paradigm shift to “green chemistry.” Not only can it reduce chemical reaction times from hours to minutes but it can also reduce side reactions, increase yields, and enhance reproducibility compared with conventional heating conditions [20]. According to the current synthetic requirements, environmentally benign multicomponent procedures employing MW methodology are particularly welcome. In view of the aforementioned facts, we have developed and designed a strategy to perform and achieve highly substituted pyridines in high yields applying the MW irradiation technique and using multicomponent coupling reaction. RESULTS AND DISCUSSION In this work, a simple one-pot and efficient method has been described for the synthesis of substituted cyanopyridines through a four-component reaction of aromatic aldehydes, acetophenones, malononitrile, and sodium alkoxide (molar ratio 1:1:1:1.3) in ethanol or methanol under MW (method A). Products of 4,6-diaryl- 2-alkoxypyridine-3-carbonitriles 2a–m were procured (Scheme 1) within a few minutes (1–5 min) of irradiation. The optimized results are summarized in Table 1. Good yields were obtained (72–84%), and problems associated with toxic solvent use were avoided. The same products 2a–m were also produced in good yields under reflux conditions (68–82%) (method B). The reactions proceeded © 2017 Wiley Periodicals, Inc.