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Synthesis and Toxicity of New Ring‐Fused Imidazo[5,4‐ f ]benzimidazolequinones and Mechanism Using Amine N ‐Oxide Cyclizations
Author(s) -
Fagan Vincent,
Bonham Sarah,
McArdle Patrick,
Carty Michael P.,
Aldabbagh Fawaz
Publication year - 2012
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.201101687
Subject(s) - chemistry , amine gas treating , ring (chemistry) , imidazole , quinone , formic acid , adduct , medicinal chemistry , oxide , stereochemistry , combinatorial chemistry , organic chemistry
A new synthetic route to ring‐fused imidazo[5,4‐ f ]benzimidazoles is reported that can be used to access symmetrical and unsymmetrical quinone anticancer agents. Oxone in formic acid allows cyclisation of o ‐ tert ‐aminoacetanilides to give ring‐fused benzimidazoles and imidazobenzimidazoles in superior yields. A mechanism for these oxidative cyclisations is proposed that proceeds through a hydrogen‐bonded amine N ‐oxide intermediate. The amine N ‐oxide is shown to act as an oxidant in the aromatisation to the imidazole ring. X‐ray crystal structures of the dimorpholine N ‐oxide intermediate and bis[1,4]oxazinoimidazo[5,4‐ f ]benzimidazolequinone bis(trifluoroacetate) adduct are included. Two unsymmetrical quinones are shown to have greater cytotoxicity than the previously reported imidazobenzimidazolequinones.