A novel synthetic strategy to obtain acylhydrazone-oxazole hybrids in three-step reactions in moderate to good yields is reported. The key step reaction consists in a Van Leusen reaction using a bifunctional component of both an aldehyde and a functional group. The target molecules were evaluated via in-silico by molecular docking with the main protease enzyme of SARS-Cov-2, where two acyl hydralazine-oxazoles yielded good predicted free energy values in comparison to the cocrystalized ligand.

Six 1,3-oxazoles were synthetized in moderate to good yields by Van Leusen reaction in a pressure reactor. The methodology allowed to decrease the reaction times reported in the literature from hours to 20 min. In addition, preliminary qualitative recognition of cations with some synthetized oxazoles such as Hg2+, Ni2+, Zn2+, Ag+, Cu2+, Pb2+ was done and a “turn off” effect was observed with Ni2+. Finally, the 1,3-oxazoles could be of biological relevance because they are considered privileged nucleus in medicinal chemistry and therefore will be useful to obtain pharmacophoric hybrid molecules.