THEORETICAL-STUDY OF AZIDO-TETRAZOLE ISOMERISM - EFFECT OF SOLVENT AND SUBSTITUENTS AND MECHANISM OF ISOMERIZATION

We report the results of high-level ab initio calculations for the gas -phase interconversion of azido and tetrazole forms of thiazole[3,2-d] tetrazole. This study is supplemented with an analysis of the solvent effect on the isomerism using self-consistent reaction field (SCRF) an d Monte Carlo-Free Energy Perturbation (MC-FEP) techniques in three di fferent solvents: carbon tetrachloride, chloroform, and water. Finally , the influence exerted by the introduction of substituents on the rel ative population of isomers is also examined. The energy difference be tween azido and tetrazole species is found to be highly sensitive to t he level of theory used to describe the gas-phase reaction. It also fo und that the free energies of solvation of azido and tetrazole species determined from SCRF or MC-FEP calculations allow us to predict the s olvent-induced changes on the equilibrium. The results show that the a zido form of thiazole[3,2-d]tetrazole is clearly disfavored as the sol vent polarity increases. The influence played by substituents is also consistent with the experimental available data, it being shown that e lectron-withdrawing groups favor the azido isomer, while the opposite effect is observed for electron-donating substituents. The study demon strates the capability of high-level quantum mechanical calculations c ombined with SCRF or MC-FEP results to analyze the azido-tetrazole iso merism and its dependence on the solvent and substituents.