Novel analogues of Ebselen -: Preparation of 2-alkylthieno[2,3-d]isoselenazol-3(2H)-ones by peroxide-mediated ring-closure of 3,3′-diselenobis(N-alkylthiophencarboxamides)

Studies toward the preparation of novel thiophen analogues of the anti-inflammatory compound Ebselen are presented. We report that treatment of 3,3'-diselenobis(N-alkylthiophen-2-carboxamides) (13; R = Me, Pr-i, Bu-t, Ph) with benzoyl peroxide in benzene under reflux affords the corresponding 2-alkylthieno[2,3-d]isoselenazol-3(2H)-ones (7) in 10-73% yield, except for the phenyl derivative (13; R = Ph) which proved too insoluble to react. Irradiation of the PTOC imidate esters of 2-benzylseleno-N-butylthiophen-3-carboxamide (9) and 3-benzylseleno-N-butylthiophen-2-carboxamide (12) provides none of the expected Ebselen analogues. This failure to ring-close is discussed in terms of conformational rigidity in amidyl radicals (22) and (23).