Synthesis of new aza-heterocyclic based on 2-pyridone

The 2-pyridones have at least three active sites based on the presence of the non-substituted "NH ", "C=O", and "CN" groups. The regioselectivity of N- versus O-alkylation depends on various factors, including the nature of metals, the structure of alkyl halides, the substituents on the 2-pyridone ring, solvents, and temperature. Due to the ambiditious nucleophilic characters of 2-pyridones, we have paid considerable attention to these fragments synthesis which can be versatile reagents for accessing bioactive compounds.
In this work, we present new methods of synthesis of different molecules including a 2-pyridone nucleus under ecological conditions, including effective multi-component syntheses, solvent-free, and under microwave irradiation. The products were successfully obtained in a very short reaction time. First, we prepared a series of 1H-free 2-pyridones and N-alkyl 2-pyridones from ethyl cyanoacetate, aromatic aldehydes, various acetophenone derivatives and ammonium acetate or diamino-alkane. These molecules have served as building blocks that, in conjunction with acyl chloride derivatives, glycoside derivatives, etc. have resulted in various heterocyclic hybrid structures carrying a 2-pyridone ring. Moreover, based on the cyano group reactivity of the 2-pyridone ring, we synthesized 5-pyridone 1H-tetrazole in a single step by a cycloaddition reaction [3+2] between 3-cyano-2-pyridone nitriles and sodium azide in the presence of metal-free L-proline.