NMR Spectroscopy: A Useful Tool in the Determination of the Electrophilic Character of Benzofuroxans - Case Examples of the Reactions of Nitrobenzofuroxans with Dienes and Nucleophiles

2,1,3-Benzoxadiazoles 1 and related 1-oxides 2, commonly referred to as benzofurazans and benzofuroxans, respectively are heteroaromatic 10-electron ring systems whose carbocyclic ring is intrinsically very susceptible to nucleophilic attack.1-9 Most importantly, the introduction of a NO2 group at C-4 enhances the electrophilic reactivity of this ring by several orders of magnitude, making it comparable to that of a trinitro substituted benzene ring. This property has raised considerable interest in the 1970-1980’s, mostly in connection with the recognition that the ease of covalent nucleophilic addition to the carbocyclic ring is responsible for the inhibitory effect exerted by some mononitrobenzofurazans and – benzofuroxans on the biosynthesis of nucleic acid and protein in leucocytes, and the observed activity against leukaemia. Also much attention was directed to the SNAr reactivity of compounds like 4-chloroand 4-fluoro-7-nitrobenzofurazans (3-4) which have become commonly used as fluorogenic reagents for detection and quantification of amino and thiol residues on proteins, drugs and biologically active molecules.