New protocols for the synthesis of 5-amino-7-(4-phenyl)-4,7-dihydro-[1,2,4]triazolo[1,5-a]pyrimidine-6-carboxylate esters using an efficient additive

Abstract

This work introduces a new additive named 4,4’-trimethylenedipiperidine for the practical and ecofriendly preparation of ethyl 5-amino-7-(4-phenyl)-4,7-dihydro-[1,2,4]triazolo[1,5-a]pyrimidine-6-carboxylate derivatives. This chemical is commercially available and easy to handle. It also possesses a low melting point and a broad liquid range temperature, high thermal stability, and good solubility in water. Based on green chemistry principles, the reaction was performed in a) a mixture of green solvents i.e. water and ethanol (1:1 v/v) at reflux temperature, and b) the additive was liquefied at 65 ◦ C and the reaction was conducted in the liquid state of the additive. High yields of the desired triazolo-pyrimidines were obtained under both aforementioned conditions. Our results demonstrated that this additive, containing 2 Lewis base sites and able to act as an acceptor-donor hydrogen bonding group, is a novel and efficient alternative to piperidine, owing to its unique properties such as its reduced toxicity, nonflammable nature, nonvolatile state, broad liquid range temperature, high thermal stability, and ability to be safely handled. Furthermore, this additive could be completely recovered and exhibited high recyclability without any change in its chemical structure and no significant reduction in its activity.