Facile and green synthesis of a series of dihydro-[1,2,4]triazolo[1,5-a]pyrimidine scaffolds

Abstract

This work presents a new catalytic application of 4,4′-trimethylenedipiperidine for the efficient synthesis of a series of dihydro-[1,2,4] triazolo[1,5-a]pyrimidines. According to the principles of green chemistry, the reaction was performed (a) in a solvent mixture comprised of water and ethanol (1:1 v/v) at reflux temperature and (b) solvent-free grinding in a mortar by a pestle. The organocatalyst could be reused up to 10 runs, and no reduction of catalytic activity was detected. A variety of substituted dihydro-[1,2,4] triazolo[1,5-a]pyrimidines were obtained in good to excellent yields under eco-friendly conditions. 4,4′-Trimethylenedipiperidine is commercially available and easy to handle, and it also shows high thermal stability and good solubility in water. This work revealed that this organocatalyst, a hydrogen bond donor to active carbonyl groups and simultaneously a Lewis base through the nitrogen atom of second piperidine moiety, could play a vital role in the promotion of the one-pot multi-component reactions. The main merits of the current methodology include short reaction time, wide substrate scope, use of a metal-free catalyst and green solvents, and simple work-up process. Furthermore, this organocatalyst can be an alternative to piperidine for organic transformations.