Acid-Catalyzed Decomposition of 1-Alkyltriazolines: A Mechanistic Study

Article abstract of DOI:10.1021/jo00060a027

1-Alkyltriazolines are five-membered cyclic triazenes containing the unusual Z-configuration for the triazene moiety.The hydrolytic decomposition of these compounds in aqueous or mixed acetonitrile-aqueous buffers leads predominantly to the formation of the corresponding 1-alkylaziridines and lesser amounts of 2-(alkylamino)ethanols, alkylamines, and acetaldehyde.The latter two products presumably result from hydrolysis of a rearrangement produkt, N-ethylidenealkylamine.Neither the nature of the 1-alkyl group nor the pH of the medium greatly influences the product distribution, although decomposition in purely aqueous buffers slightly reduces the aziridine yields.The rate of hydrolysis of 1-alkyltriazolines is about twice as fast as that of the analogous acyclic 1,3,3-trialkyltriazenes and varies in the order tert-butyl > isopropyl > ethyl > butyl > methyl > propyl > benzyl.The mechanism of the decomposition is specific acid-catalyzed (A1) involving rapid reversible protonation followed by rate-limiting formation of a 2-(alkylamino)ethyldiazonium ion.The slopes of the log k_obs versus pH plots are near -1.0.The solvent deuterium isotope effect, k_H2O/k_D2O, is in all cases < 1.0 and ranges from 0.58 for 1-methyltriazoline to 0.86 for 1-benzyltriazoline.The rate of decomposition shows no significant dependence on the concentration of the buffer acid.The proposed mechanism involves rate-limiting formation of a 2-(alkylamino)ethyldiazonium ion, which is then partitioned among several competing product formation pathways. 1-Alkyltriazolines are potent direct-acting mutagens in the alkylation-sensitive TA 1535 strain of Salmonella typhimurium.A clear, dose-dependent mutagenicity is observed.At the highest dose level, various 1-alkyltriazolines have activities roughly equivalent to that of the potent methylating agent, 1,3-dimethyltriazene.At low levels of substrate, 1-alkyltriazolines are significantly more active than 1,3-dimethyltriazene, with mutagenicity following the order benzyl > methyl > ethyl.