Electronic and steric effects in thermal denitrosation of N-nitrosoamides

N-Alkyl-N-nitrosoamides undergo competitive reactions whose rates are dependent upon the interplay of a number of factors. There already exists a significant body of work delineating the effects of pH on the partitioning of the nitrosoamides along their deaminative (-N(2)) and denitrosative (-"NO(+)") pathways. In this paper, the issue of pH dependence is discussed with particular attention to nitrosoamide decompositions in nonaqueous media. The role of the acidity of the medium in the partitioning of the nitrosoamide between deamination and denitrosation and in the choice of deaminative pathways is revisited. In nonaqueous media under near-neutral conditions, the partitioning's pH dependence is evidently accompanied by a sensitivity to structural features in the nitrosoamide. Thus, diminution of steric crowding around the N-nitroso moiety as well as the presence of strongly electron-withdrawing acyl units (i.e., those derived from strong acids, e.g., tosyl and trifyl) increase the relative yield of amides by encouraging the denitrosative pathway. A mechanism for thermal denitrosation of nitrosoamides under near-neutral conditions is proposed in which rapid protonation at the acyl O rather than slow protonation at the amidic N is the first step in the reaction profile. A rate-limiting, bimolecular reaction between the O-conjugate acid and adventitious nucleophiles at the nitrosyl group then occurs followed by rapid tautomerization to amide.