Study On The Synthesis Of2-Amino-3-Cyanopyridine Derivatives

2-Amino-3-cyanopyridine derivatives constitute a class of polyfunctionalnitrogen-containing heterocyclic compounds. Especially, they can serve as versatile syntheticprecursors that can be widely applied in the field of pharmaceutical and chemical engineering.Clearly, the development of efficient methodologies for the synthesis of such a class ofcompounds is of significant importance. The project of this research mainly focused ontandem multi-component reactions to construct2-amino-3-cyanopyridine derivatives, some ofthese obtained compounds were further explored for N-arylation by using Ullmann C-Ncoupling reaction catalyzed by copper catalyst.Initially, the study focuses on the four-component condensation reactions from aldehydes,ketones, malononitrile and ammonium acetate. After optimization of reaction conditions, aseries of2-amino-3-cyanopyridines were successfully synthesized. The methodology has themerits of solvent-free conditions, easily experimental work-up procedure, short reaction time,high yields from simple and readily-available substrates in a single step. Moreover, the studyhas analyzed the reaction law and its possible mechanism in a certain extent, and thefluorescent properties of representative products were also simply studied.Alternatively, we have studied the four-component reactions of alkynoates, aldehydes,amines and malononitrile, which provided an efficient and green route for the synthesis of2-amino-3-cyanopyridine derivatives. The synthetic method employed bits of potash ascatalyst, it has merits of short reaction time and high yields. A number of polyfunctionaldihydropyridines were efficiently synthesized by employing our developed method fromvarious starting materials. Interestingly, these obtained heterocyclic products bearing anamino acid structural unit are widely applied in medicinal chemistry. Meanwhile, the law andpossible mechanism of the reaction were briefly discussed, and the fluorescent properties ofrepresentative products were analyzed.Finally, the copper-catalyze C-N coupling reaction was employed for N-arylation of2-amino-3-cyanopyridines with aryl halides. During the exploration of the optimized reactionconditions, we have tested a variety of copper-based catalytic systems. After screening ofsuitable copper catalyst precursors and ligands, a highly efficient copper(I) complex catalyst[(Phen)2Cu+BF4-] has been developed. A series of new2-arylamino-3-cyanopyridines havebeen successfully obtained. This work has provided the first example of N-arylation of2-amino-3-cyanopyridines by using this ionic copper catalyst in relatively low catalystloading. Most of the obtained products are new compounds, and the fluorescence properties ofrepresentative products have been analyzed. Notably, the resulted products have broadpotential applications in organic synthesis and organometallic chemistry, and they can be usedfor further preparation of biologically interesting products or useful ligands for metalcatalysis.