Abstract

The present paper reports the synthesis, NMR study, and detailed computational investigation of various novel s-triazine analogues 9–12 of medicinal interest embellished with bioactive heterocyclic scaffolds such as isoxazole, pyrazole, and pyrimidine, linked to triazine backbone through an oxyphenyl spacer. The synthesis of 9–12 was performed by exploiting the synthetic potential of the chalcone 4 which resulted from the reaction of benzaldehyde and s-triazine bound aryl ketone derivative 3. The later was in turn obtained by the reaction of p-hydroxyacetophenone with 6‑chloro-2,4-dicyclopropylamino-1,3,5-triazine(2). This strategy allowed the s-triazine to act as a three-pronged stencil to embrace three bioactive motifs jointly in the same molecular framework in 9–12.Detailed density function theory (DFT) study corroborated the experimental findings. It was shown that the molecules of the synthesized compounds would be quite uncrowded and therefore would be packed quite loosely in the crystalline phase. The molecular orbital (MOs) analysis showed that all the synthesized compounds should have quite pronounced thermodynamic stability and thatthe modification of the substituting group would allow to finely tune the reactivity of the s-triazine derivatives. Also, possible formation of various noncovalent interactions between the molecules of the studied compounds within their crystals or between the molecules of these compounds with various polar solvents and biologically important molecules was suggested. Moreover, potential reactivity of these compounds towards various electrophiles and nucleophiles suggesting possibility of their successful employment for medical purposes was proposed. Further, the global reactivity parameters (GRP) analysis suggested that the compound studied would be quite stable in redox processes, with the pyridine derivatives showing higher stability.