Electronic and Steric Effects in Thermal Denitrosation of N-Nitrosoamides

Abstract

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.

Versatile New Reagent for Nitrosation under Mild Conditions

“…During the course of our studies, we found limited success for intermolecular C–H abstraction using N -nitrososulfonamides as radical precursors but found them to be effective transnitrosating reagents. Although this type of reactivity has been reported, a well known limitation of N -nitrososulfonamides as transnitrosating reagents is their propensity for thermal decomposition . In fact, N -methyl- N -nitroso- p -toluenesulfonamide (Diazald) is a well-known commercial reagent that requires only mild heating under basic conditions to generate an equivalent of diazomethane.…”

Nuclear Magnetic Resonance (NMR) Spectroscopy: A Review and a Look at Its Use as a Probative Tool in Deamination Chemistry

“…Darbeau, et al recently examined the classical roles of steric and electronic (internal) factors on the thermal denitrosations of N-nitrosoamides (11). A series of N-benzyl-N-nitrosocarboxamides and N-benzyl-N-nitrososulfonamides were decomposed in CDCl 3 at 608C.…”

Using N-Nitrosodichloroacetamides to Conveniently Convert Linear Primary Amines into Alcohols

“…N-nitrosodichloroacetamides, which are not as electron deficient as the trifluoroanalogues, avoid these problems by being stable to the conditions of the nitrosylation step and being able to be extracted from the acetic acid solvent into a nonpolar solvent that enables a cleaner rearrangement. As a side note, thermal denitrosylation of N-nitrosoacetamides to form amides has been described, [14] but typically this pathway is favored by acidic or basic aqueous solvents; we did not observe substantial denitrosylation in any of our experiments (<2% produced by 1 …”