Synthesis, characterization, biological and DFT studies of new 4-substituted phthalonitriles

Herein, we describe the synthesis, characterization and computational studies of novel 4-substituted phthalonitriles: (1) 4-(4-((benzothiazole)methyleneamino)phenoxy)phthalonitrile, (2) 4-(4-(3-phenylallylideneamino)phenoxy)phthalonitrile and (3) 4-(4-(4-isopropylbenzylideneamino)phenoxy)phthalonitrile. Compound 1 was obtained from the equimolar condensation reaction of 4-(4-aminophenoxy)phthalonitrile with benzothiazole-2-carboxaldehyde while compounds 2 and 3 were isolated from the reactions of 4-aminophenol with either cinnamaldehyde or cuminaldehyde followed by the nucleophilic substitution reactions of their respective Schiff bases and 4-nitrophthalonitrile. The spectral characterization of 1–3 was done using ¹H NMR, IR and UV–Vis spectroscopy, while structural confirmation could be affirmed from single TOF mass spectrometry and single crystal X-ray crystallography (for 1 and 2). Molecular geometry optimizations were conducted using the DFT method and the simulated IR frequencies data concurred well with the experimental data and the respective vibrational assignments. Similarly, TD-DFT studies provided an interesting perspective on the nature of the intra-ligand electronic transitions found within the experimental electronic spectra of the respective Schiff base phthalonitriles. Compound 3 showed the highest Human African sleeping sickness trypanocidal potency.