A new synthetic route to authentic N-substituted aminomaleimides

A number of compounds reported in the literature as N-aminomaleimides (2) are, instead, isomeric N-aminoisomaleimides (3). The ubiquity of this mischaracterization and its propagation within the literature are discussed. In addition, the first general synthetic route to aliphatic and aromatic N-substituted aminomaleimides is described. As an illustration, the compound reported to be N-(4-bromophenylamino)maleimide (2b) was prepared and determined to be N-(4-bromophenylamino)isomaleimide (3b). The authentic compound was synthesized by the condensation of 4-bromophenylhydrazine (7b) and the exo-furan/maleic anhydride Diels-Alder adduct (8) in acetic acid to produce the furan-protected aminomaleimide 10b, followed by heating to remove furan through the retro Diels-Alder reaction. The structures of 2b, 3b, and 10b were established unequivocally by X-ray crystallography and other spectroscopic techniques.