Chemistry Department, Faculty of Science, Minia University, Minia 61519, Egypt.
Chemistry Department, Faculty of Sciences-Al Faisaliah, King Abdulaziz University, Jeddah 21493, Saudi Arabia.
Molecules. 2018 Mar 9;23(3):619. doi: 10.3390/molecules23030619.
A convenient, fast and environmentally benign procedure for the synthesis of a new series of highly functionalized -alkylated pyridines as privileged medicinal scaffolds was developed via a unique three-component reaction of easily available aromatic as well as heteroaromatic aldehydes, -alkyl-2-cyanoacetamides and malononitrile in EtOH in the presence of K₂CO₃ as a base promoter under microwave irradiation. The presented tandem process is presumed to proceed via Knoevenagel condensation, Michael addition, intramolecular cyclization, autoxidation and subsequent aromatization. Particularly valuable features of this protocol, including high product yields, mild conditions, atom-efficiency, simple execution, short reaction times and easy purification make it a highly efficient and promising synthetic strategy to prepare substituted pyridine nuclei. The proposed mechanism of this novel one-pot reaction and structure elucidation of the products are discussed.
开发了一种方便、快速且环境友好的方法，通过独特的三组分反应，以易获得的芳香族和杂芳族醛、β-烷基-2-氰基乙酰胺和丙二腈在 EtOH 中，在 K₂CO₃作为碱促进剂的存在下，在微波辐射下合成了一系列新型高官能化的β-烷基化吡啶作为药物优势骨架。所提出的串联过程被认为是通过 Knoevenagel 缩合、迈克尔加成、分子内环化、自氧化和随后的芳构化进行的。该方法的特点包括高产物收率、温和的条件、原子经济性、简单的操作、短的反应时间和易于纯化，使其成为一种高效、有前途的合成策略，可用于制备取代吡啶核。讨论了这种新型一锅法反应的机理和产物的结构阐明。
