Synthesis of novel isoxazolines bearing 1,2,4-oxadiazole group via nitrile oxide cycloadditions

Nitrile oxide cycloaddition reactions are one of the most effective methods for producing new heterocyclic molecules. Besides, 1,2,4-oxadiazoles and isoxazolines are significant in the field of medicinal and pharmaceutical chemistry because they have shown anticancer, antidepressant, antioxidant, anti-inflammatory, antiviral, anti-HIV, antibacterial, and antitumor properties. From this point of view, in this dissertation study, the cycloaddition reactions of some aryl nitrile oxides were studied to synthesize new isoxazoline-1,2,4-oxadiazole hybrid molecules (84a-y) and their antibacterial properties were investigated. For this purpose, in the first section of the study, p-substituted benzaldehydes 77 were reacted with hydroxylamine hydrochloride in basic conditions to yield the corresponding p-substituted benzaldoximes bearing EWGs 78a-e. Meanwhile, several electron-rich nitriles 79 were converted into corresponding benzamidoximes 80 which were subsequently reacted with acryloyl chloride and heated to afford the precursors, electron-rich vinyl 1,2,4 oxadiazoles (83a-e). Afterward, in the second section, new 3,5-disubstituted-1,2,4-oxadiazolyl diarylisoxazolines 84a-e were synthesized in moderate to good yields by the reaction of in situ generated electron-deficient nitrile oxides from benzaldehyde oximes 78 with vinyl 1,2,4 oxadiazoles 83a-e in the presence of the sodium hypochlorite (NaOCl) and triethylamine. The structures of all newly synthesized precursors (78a-e, 83a-e) and products (84a-y) were elucidated using IR, 1H NMR, 13C NMR analyses and also confirmed with literature data. In the last section of our study, an antibacterial susceptibility test for the target compounds (84a-y) has been performed against gram-(-) (S. aureus, S. epidermidis, S. pyogenes) and gram-(+) bacteria (E. coli, P. aeruginosa, S. Typhimurium, S. marcescens, P. Vulgaris, E. cloacae, K. pneumonia) bacteria, however, no considerable inhibitory effect of 84a-y derivatives have been observed against any bacterial strain used.