Cyclic α-Acetoxynitrosamines:  Mechanisms of Decomposition and Stability of α-Hydroxynitrosamine and Nitrosiminium Ion Reactive Intermediates

Abstract

A study of the kinetics and mechanism of the decay of R-acetoxy-N-nitrosopyrrolidine and R-acetoxy-N-nitrosopiperidine are reported. The compounds differ in reactivity by more than 2 orders of magnitude at physiological pH. On the basis of thermodynamic parameters, common ion inhibition and azide ion trapping experiments, both compounds appear to decompose under these conditions by the formation of N-nitrosiminium ion intermediates. The differences in reactivity are rationalized on the basis of results from an ab initio study, described in the accompanying paper. The first direct study of the kinetics of decay of cyclic R-hydroxynitrosamines of nitrosopiperidine and nitrosopyrrolidine and a third compound, 2-hydroxy-2-methylnitrosopyrrolidine is also summarized. These prove to be highly unstable reactive intermediates, in contrast to what might be expected on the basis of earlier reports concerning cyclic R-hydroxynitrosamines.

Comparative theoretical investigation of the formation of DNA interstrand crosslinks induced by two kinds of N‐nitroso compounds: nitrosoureas and nitrosamines

“…This indicates that the α‐hydrolyzed nitrosamines are more facile to break down to aldehydes and alkydiazohydroxide than CENUs. The experimental results of Fishbein and colleagues lend strong support to this conclusion, which demonstrated that almost all α‐hydroxynitrosamines were unstable in aqueous environments and decomposed spontaneously with a half life of less than 1 min at 37 °C.…”

Reexamination of the Aqueous Chemistry of N-Nitroso-3-hydroxymorpholine, a Metabolite of the Carcinogen N-Nitrosomorpholine

“…N-Nitroso-3-Hydroperoxymorpholine (10). The hydroperoxy compound was synthesized by group exchange analogous to what has been reported (29,30,35). To a solution of 9 (30 mg) in 2 mL of MeCN was added 2 mL of 50 wt % H2O2 in water.…”

“…The first R-hydroxynitrosamines were synthesized and characterized by Okada, Mochizuki, and co-workers (23)(24)(25)(26). syntheses and study of R-hydroxymethylene-(4) and an R-hydroxymethinyl-nitrosamine (5) have been reported, and these compounds are substantially more reactive, some with millisecond half-lives at neutral pH (27)(28)(29)(30). Among these, the maximum half-life of R-hydroxynitrosopiperidine ( 6) is several seconds at 25 °C (30).…”

“…syntheses and study of R-hydroxymethylene-(4) and an R-hydroxymethinyl-nitrosamine (5) have been reported, and these compounds are substantially more reactive, some with millisecond half-lives at neutral pH (27)(28)(29)(30). Among these, the maximum half-life of R-hydroxynitrosopiperidine ( 6) is several seconds at 25 °C (30). In contrast, there is one report of surprisingly stable R-hydroxynitroso indoles (7); these are isolable solids (31).…”

Structural Stability and Vibrational Analyses of Haloselenonyl Azides, XSeO2-NNN, where X is F, Cl, Br

“…The very high reactivity and the application of organoazides in synthetic chemistry and many important industries [21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36] has drawn the attention to investigate the structure and conformational behavior of vinyl azide, CH2=CH-NNN [37] and formyl azide, CHO-NNN [38], by DFT and ab initio MP2 calculations. Both molecules were predicted to have a cis/trans conformational equilibrium with the gauche form being the transition state.…”