Direct Reaction of Amides with Nitric Oxide To Form Diazeniumdiolates

We
report the apparently unprecedented direct reaction of nitric oxide
(NO) with amides to generate ions of structure R­(CO)­NH–N­(O)NO–, with examples including R = Me (1a)
or 3-pyridyl (1b). The sodium salts of both released
NO in pH 7.4 buffer, with 37 °C half-lives of 1–3 min.
As NO-releasing drug candidates, diazeniumdiolated amides would have
the advantage of generating only 1 equiv of base on hydrolyzing exhaustively
to NO, in contrast to their amine counterparts, which generate 2 equiv
of base.