Evidence for the Formation of α-Hydroxydialkylnitrosamines in the pH-Independent Solvolysis of α-(Acyloxy)dialkylnitrosamines

Abstract

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.

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.…”

Lifetimes of Dialkylcarbocations Derived from Alkanediazonium Ions in Solution: Cyclohexadienyl Cations as Kinetic Probes for Cation Reactivity1

“…There are several different classes of carcinogenic nitroso compounds including N -nitrosamines, N -nitrosamides, N -nitrosoureas, and N -nitro- N -nitrosoguanidines. In some cases, N -nitrosamines are hydroxylated enzymatically at one of the α-aminocarbons. , Decomposition of the resulting intermediates give rise to alkanediazoic acids. The ( E )- and ( Z )-isomers of alkanediazoates and their conjugate acids have been shown to decompose in aqueous medium yielding alkanediazonium ions. , The resulting alkanediazonium ions then react with nucleophiles by either S N 1 or S N 2 pathways (Scheme ). , Reactions with biological nucleophiles, including DNA, give rise to intracellular damage.…”

Ab InitioQuantum-Mechanical Study of the Stability of Cyclic α-Acetoxy-N-nitrosamines: Amine N→NO Dative Bonding in α-Hydroxy-N-nitrosaminesversusN→Carbocation Dative Bonding inN-Nitrosiminium Ions

“…The elucidation of the mechanism of the decomposition of α-acetoxy- N -nitrosamines presents a central issue. For acyclic α-acetoxy- N -nitrosamines, it is thought that N -nitrosiminum ions are formed in an S N 1 process . Cyclic α-acetoxy- N -nitrosamines have been studied less, even though they play an important role in the chemistry and toxicology of nitrosamines, and of nitrosopyrrolidine and nitrosopiperidine in particular, , and nucleophilic attack on the acetyl group's carbonyl carbon was discussed …”