“…The limiting yield of azide adduct with increasing azide ion concentration is likely due to a denitrosation reaction of azide at the nitrosiminium nitrogen that is competitive with reaction at carbon that yields the azide adduct, as in eq 10. Azide ion stimulated denitrosation of acyclic nitrosiminium ion has recently been reported . The limiting yield of azide adduct is not due to general base-catalyzed hydration.…”
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.
“…The limiting yield of azide adduct with increasing azide ion concentration is likely due to a denitrosation reaction of azide at the nitrosiminium nitrogen that is competitive with reaction at carbon that yields the azide adduct, as in eq 10. Azide ion stimulated denitrosation of acyclic nitrosiminium ion has recently been reported . The limiting yield of azide adduct is not due to general base-catalyzed hydration.…”
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.
“…We previously studied the pH dependence of the buffer-independent decay of some simple α-(acyloxy)dialkylnitrosamines and observed that in the range of pH = 3−13, the rate law of eq 1 was obeyed . It was concluded that the pH-independent term, k 1 , involved rate-limiting formation of N -nitrosiminium ions, as in eq 2, on the basis of the near-zero values of Δ S ⧧ , structure−activity relations, and the trapping of putative N -nitrosiminium ions after the rate-limiting step by azide ion to yield adducts such as in eq 2. , Others 16a have previously characterized the reaction chemistry of 6a and obtained qualitatively similar evidence for the involvement of an N -nitrosiminium ion. It was also concluded, in accord with earlier suggestions, that the pH-dependent term, k OH , involves hydroxide ion attack at the carbonyl group.…”
Section: Discussionmentioning
confidence: 99%
“…Additional evidence that there is no change in mechanism for the pH independent reaction in the case of 6b is found in Table which indicates a quantitative yield of the azide adduct 7 when 6b is decomposed in the presence of 8 mM sodium azide in the absence of an increase in k obsd of greater than 5%. This data requires that the azide adduct is formed in a reaction subsequent to the rate-limiting step, presumably involving capture of the N -nitrosiminium ion formed in the rate-limiting step of the k 1 process, as in eq 2. , …”
Section: Discussionmentioning
confidence: 99%
“…It was concluded that the pH independent reaction involves the formation of nitrosiminium ion intermediates, as in eq 2. It was also shown that these can be trapped by added nucleophiles, and it has been explicitly assumed that they react with solvent water to yield α-hydroxydialkylnitrosamines, as in eq 2 …”
A kinetic study of the decay of alpha-(acyloxy)dialkylnitrosamines in aqueous solutions, at 25 degrees C, ionic strength 1 M (NaClO(4)), and 4% acetonitrile by volume, is reported. Rate constants for disappearance of the N-NO chromophore or appearance of benzaldehyde product increase with the introduction of electron-withdrawing groups into the acyloxy moiety. For some compounds, in some regions of pH, the kinetics are non-first-order. For these compounds, in other regions of pH, the rate constants are coincident with those previously reported for the decay of the corresponding alpha-hydroxydialkylnitrosamines. These data provide direct evidence that alpha-hydroxydialkylnitrosamines are intermediates in the pH-independent decomposition of the alpha-(acyloxy)dialkylnitrosamines studied.
“…Recently, data, in the form of product analysis and structure activity effects, were summarized that indicated that nitroso oxygen attack at the carbonyl carbon was not a likely mechanism of reaction . It was concluded that the dominant mechanism involved the formation of nitrosiminium ions ( D ) in, or prior to, the rate-limiting step, as in eq 3. − The onset of a carbonyl attack mechanism with electron-withdrawing substituents R N and R C (C, eq 1) was predicted . An alternative mechanism or mechanisms of anchimeric assistance were not addressed, and the implications of the apparent correlation between isomeric composition and stability have not been identified.…”
The decay of α-(acyloxy)dialkylnitrosamines in aqueous solutions has been studied with a view
toward elucidating mechanistic details and effects of structure on mechanism and reactivity. Rate constants
(k
1) for the pH-independent decay of 43 α-(acyloxy)dialkylnitrosamines have been determined. Observations
from these and other experiments rule out decomposition via an anchimeric assistance mechanism involving
the Z isomer that had previously been suggested. All of the reported data for most of the compounds is consistent
with a mechanism involving the formation of N-nitrosiminium ions in or before the rate-limiting step. Structure−reactivity correlations indicate that the stability of α-(acyloxy)dialkylnitrosamines is determined by electronic
properties of substituents at RN and RC as well as by the ability of substituents RC to engage in hyperconjugative
interactions of C−H bonds with the developing cationic center in the transition state for nitrosiminium ion
formation. Attachment of substituents of sufficient electron-withdrawing power at RN and RC results in a
predicted change in mechanism to what appears to be an acyl group attack mechanism.
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