Synthesis and Glutathione Peroxidase‐Like Activities of Isoselenazolines

The aromatic nucleophilic substitution (S N Ar) reactions of N ‐(2‐bromo‐3‐nitrobenzyl)aniline ( 18 ), N ‐(2‐bromo‐3‐nitrobenzyl)‐4‐methylaniline ( 19 ) and N ‐(2‐bromo‐3‐nitrobenzyl)‐4‐nitroaniline ( 20 ) with [ n BuSeNa] afford N ‐[2‐(butylselanyl)‐3‐nitrobenzyl]aniline ( 21 ), N ‐[2‐(butylselanyl)‐3‐nitrobenzyl]‐4‐methylaniline ( 22 ) and N ‐[2‐(butylselanyl)‐3‐nitrobenzyl]‐4‐nitroaniline ( 23 ), respectively. The bromination of 21 results in the formation of cyclic isoselenazolines 7‐nitro‐2‐phenyl‐2,3‐dihydrobenzisoselenazole ( 27 ) and 2‐(4‐bromophenyl)‐7‐nitro‐2,3‐dihydrobenzisoselenazole ( 28 ). The bromination of 22 affords isoselenazolines 2‐(4‐methylphenyl)‐7‐nitro‐2,3‐dihydrobenzisoselenazole ( 29 ) and 2‐(2‐bromo‐4‐methylphenyl)‐7‐nitro‐2,3‐dihydrobenzisoselenazole ( 30 ) along with some other products. The bromination of 23 under identical conditions gave 2‐(2‐bromo‐4‐nitrophenyl)‐7‐nitro‐2,3‐dihydrobenzisoselenazole ( 31 ). The oxidation reaction of 21 – 22 with H 2 O 2 yielded isoselenazoline Se ‐oxides 7‐nitro‐2‐phenyl‐2,3‐dihydrobenzisoselenazole 1‐oxide ( 33 ) and 2‐(4‐methylphenyl)‐7‐nitro‐2‐phenyl‐2,3‐dihydrobenzisoselenazole 1‐oxide ( 34 ), respectively. The new isoselenazolines and isoselenazoline Se ‐oxides, stabilized by intramolecular secondary Se ··· O interactions, have been structurally characterized by single‐crystal X‐ray diffraction studies and investigated by computational studies. In addition to the synthesis and characterization, the glutathione peroxidase (GPx)‐like activities of isoselenazolines and isoselenazoline Se ‐oxides have been evaluated by coupled reductase assays.