Aminolysis of an N-Diazeniumdiolated Amidine as an Approach to Diazeniumdiolated Ammonia

[Image: see text] Recent theoretical studies have suggested that the parent diazeniumdiolate ion, H(2)N–N(O)=NO(–) (“diazeniumdiolated ammonia”), might be stable enough to be isolated and that it could potentially serve as a uniquely advantageous prodrug form of bioactive nitroxyl (HNO). Here, we report on an attempt to isolate its O(2)-benzylated derivative by aminolysis of the C=N bond in PhC(NH(2))=N–N(O)=NOBn. The reaction proved remarkably sluggish in comparison to aminolysis of unsubstituted benzamidine, and the desired product could not be isolated, apparently because of base sensitivity of the NH(2) group. Consistent with this interpretation, O-benzylhydroxylamine and N(2)O were recovered from the reaction mixture in high yields, along with N,N′-dibutylbenzamidine. Theoretical calculations rationalize the observed slow aminolysis by demonstrating that the diazeniumdiolate group greatly suppresses the electrophilicity of the adjacent C=N carbon center, rendering attack at that position endothermic. The data provide significant insights into the challenges inherent to the pursuit of diazeniumdiolated ammonia.