A theoretical investigation of the mechanism for the reaction between a quebrachitol derivative and N3-

The reaction between a mesylated compound and sodium azide was previously studied experimentally at a temperature of 140 degreesC using dimethylformamide as a solvent. The product was assigned on the basis of the analysis of the NMR spectra. In this work semiempirical (AM1 and PM3), ab initio (Hartree-Fock and MP2) and density functional theory (BLYP functional) quantum mechanical calculations, using continuum models for describing the solvent effect, were carried out for this process to better understand the reaction mechanism. Three distinct mechanisms involving a carbocation and epoxide intermediates, and a transition-state structure for direct attack of the N-3(-) species to the reactant were investigated. The theoretically calculated preferred reaction pathway passing through an epoxide intermediate agrees nicely with the experimental proposal, providing a good example of where theoretical calculations can be of great help to definitively elucidate the reaction mechanism.