Synthesis of Cyclic Selenenate/Seleninate Esters Stabilized by<i>ortho</i>‐Nitro Coordination: Their Glutathione Peroxidase‐Like Activities

The syntheses of selenenate/seleninate esters and related derivatives by aromatic nucleophilic substitution (S N Ar) reactions of 2‐bromo‐3‐nitrobenzylalcohol ( 13 ) and 2‐bromo‐3‐nitrobenzaldehyde ( 17 ) with Na 2 Se 2 / n BuSeNa are described. The reaction of 13 with Na 2 Se 2 at room temperature afforded 7‐nitro‐1,2‐benzisoselenole(3 H) ( 15 ) instead of the desired diaryl diselenide 14 . Oxidation of selenenate ester 15 with hydrogen peroxide afforded the corresponding selenium(IV) derivative, 7‐nitro‐1,2‐benzisoselenole(3 H) selenium oxide ( 18 ). 2‐(Butylselanyl)‐3‐nitrobenzaldehyde ( 19 ) was synthesized by treating compound 17 with in situ generated n BuSeNa. The bromination reaction of selenide 19 did not afford the expected arylselenenyl bromide 20 , instead, it resulted in the formation of the unexpected 7‐nitro‐1,2‐benzisoselenol(3 H)‐3‐ol ( 21 ) and 3,3′‐oxybis(7‐nitro‐1,2‐benzisoselenole(3 H)) ( 22 ), respectively. The facile formation of heterocycles 21 and 22 is rationalized in terms of the aromatic ring strain in selenenyl bromide 20 . The presence of intramolecular secondary Se⋅⋅⋅O interactions in esters 15 , 18 , 21 , 22 , and selenenic anhydride 29 has been confirmed by single‐crystal X‐ray diffraction studies as well as computational studies. The presence of an intramolecular Se⋅⋅⋅O interaction in esters 4b , 8 , 15 , 18 , 21 , and 22 has been further proved by natural bond orbital (NBO) and atoms in molecules (AIM) calculations. Glutathione peroxidase‐like (GPx) antioxidant activities of 15 , 18 , 21 , 22 , and related heterocycles such as 7‐nitro‐1,2‐benzisoselenol(2 H)‐3‐one selenium oxide ( 4b ), 7‐nitro‐1,2‐benzisoselenol(2 H)‐3‐one ( 8 ), and 29 have been determined by the coupled reductase assay.