The synthetic route to obtain the pyrazino polypyridinic type of ligands generally involves a condensation reaction between a diaminne and a dione. In the case of pyrazino[2,3-f][1,10]phenanthroline, ppl, and pyrazino[2,3-f][4,7]phenanthroline. ppz. a notoriously lower yield for the condensation reaction of the later has been observed. In this work, experimental results along with DFT methods allowed us to elucidate and improve the synthetic pathways involved in these ligands. Intermediary molecules for the corresponding condensation of dione and ethylenediamine were detected. By a continuous dialogue between theory and experiments the limiting reaction step was established as the formation of a "non -aromatic" intermediate, which was shown to be the cause for the lower yield observed for ppz. This intermediate was theoretically and experimentally characterized, thereby permitting us to facilitate its conversion to the desired product and obtain close to quantitative yield for the reaction.