Synthesis of pyrimidine-based heterocyclic compounds via multicomponent reactions of various enamines

Pyrimidines play a vital role in biology, serving as fundamental building blocks of nucleic acids. They also hold significant pharmacological importance, as their derivatives exhibit a wide array of biological activities, including anticancer, anti-inflammatory, antitubercular, and antimicrobial effects. Specifically, dihydropyrimidines (DHPM) and 1,2,3,4-tetrahydropyrimidine (THPM) derivatives are utilized as calcium channel blocker and antihypertensive drug agents. Moreover, multicomponent reactions (MCRs) are extensively used in various studies for their efficiency in synthesizing diverse pyrimidine compounds. The aim of the present dissertation was to combine the Mannich-based MCR method with innovative green synthesis techniques to efficiently produce new THPM derivatives (62) using enaminonitriles (61) and to evaluate their activities. So, polyethylene glycol (PEG) derivatives were selected as a safe and environmentally friendly alternative to organic solvents for the synthesis of new THPMs. To achieve this goal, first of all, new aryl substituted enaminonitriles as suitable precursors were prepared by a base-catalyzed reaction of aryl nitriles with acetonitrile and characterized by IR, NMR analyses. In the second part of the study, novel tetrahydropyrimidine carbonitriles were efficiently synthesized through Mannich cyclizations of enaminonitriles with formaldehyde and amine derivatives under heating in PEG-400 in hours. The structures of all the tetrahydropyrimidine products were confirmed by IR, NMR and HRMS analyses.