The title reaction has been studied in dioxane/water in a large (0.1-14.9) pS+ range, evidencing, together with an uncatalyzed process at intermediate (3.5-8.0) pS+ values, the occurrence of a catalyzed pathway both in the acidic (pS+ 0.1-3.5) and in the basic region (pS+ 8.0-14.9): specific-acid catalysis and general-base catalysis, respectively, have been found to take place by means of kinetic investigations at different buffer concentrations. Mechanisms for the three pathways have been advanced on the grounds of structural features. In a comparison with previous data particular attention has been paid to the acid-catalyzed pathway, herein observed for the first time in an azole-to-azole interconversion. The mechanistic hypotheses seem well supported by ab initio calculations.
A combined kinetic and theoretical study of the monocyclic rearrangements of heterocycles (MRH) has been
carried out. The interconversion of the Z-hydrazone of 3-benzoyl-5-phenyl-1,2,4-oxadiazole into the
corresponding triazole has been experimentally investigated in dioxane/water in the pS
+ range 5.55−13.9.
The uncatalyzed region has been examined at the DFT level using a model system formed by the Z-hydrazone
of 3-formyl-1,2,4-oxadiazole and one or two water molecules. The environmental effect of the solvent has
been emulated using a continuum model (COSMO) approach. The kinetic data suggest a concerted process
where the magnitude of the activation barrier is determined by the interplay of two opposite factors, that is,
the nucleophilicity of the nitrogen atom and the acidity of the nitrogen-bonded protons. The computations
indicate the existence of two multistep reaction pathways. When the solvent environment is taken into account,
the preferred path, which involves two water molecules acting as a base, becomes a concerted highly
asynchronous path, where the nucleophilic attack and the proton transfer occur not simultaneously but in the
same kinetic step.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.