Synthesis, characterization, and quantum chemistry local chemical reactivity description of new phosphorylated derivatives of piperazine

We report a fast, safe, and efficient procedure for the synthesis of phosphorylated derivatives of piperazines through a multicomponent reaction (MCR) strategy. Our key reagents were the piperazines 1-(2-methoxyphenyl) piperazine and 3-(4- (2-methoxyphenyl) piperazin-1-yl) propan-1-amine which reacted with five different phosphorous chlorides. A total of ten new derivatives were obtained, all confirmed by NMR spectroscopy (¹H, ¹³C, and ³¹P) and mass spectrometry. Then, the reactivity profile of our new compounds was characterized through the new theoretical framework of the Local Electronic Temperature of Atoms in Molecules (LT-AIMs), from which we identified the most reactive sites of each of our derivatives. Furthermore, some of the quantities defined within this context were used to reproduce trends observed in our NMR records. A brief discussion about the advantages of performing a combined experimental and theoretical chemical characterization of recently synthesized compounds is also presented, particularly for those compounds with potential therapeutic features.