Pentacyclic aromatic heterocycles from Pd-catalyzed annulation of 1,5-diaryl-1,2,3-triazoles

A series of pentacyclic aromatic heterocycles representing functionalized phenanthridines, naphthyridines, and phenanthrolines were prepared via Pd-catalyzed annulation of 1,5-diaryl-1,2,3-triazoles. Analogs with triazole N1-connected <i>ortho</i>-bromobenzene subunits successfully underwent annulation under microwave irradiation in yields of 31-90%. In contrast, annulations of triazole C1-connected <i>ortho</i>-bromobenzene subunit analogs failed under microwave irradiation but were successful using conventional thermal heating in yields of 31-65%. The expanded nature of the aromatic ring system following annulation was reflected by the downfield shifting of aromatic ¹H NMR signals and the red-shifting of UV-visible absorbance signals relative to their non-annulated counterparts. Structural rigidity of annulated systems compared to non-annulated counterparts was reflected by emission signals with increased intensity and decreased Stokes shifts. Five benzotriazolophenanthroline regioisomers sharing structural similarity regarding N center placement showed antimicrobial activity, as measured by minimum inhibitory concentration assays. MIC values of 2-16 μM towards Gram-positive bacteria <i>Staphylococcus epidermidis</i> and <i>Bacillus subtilis</i> and 8-16 μM towards <i>Saccharomyces cerevisiae</i> yeast were observed for these annulated molecules, while their analogous non-annulated control compounds were not bioactive.