Tetrazoles physicochemical properties

Annular tautomerism inherent to NH-unsubstituted tetrazoles and tetrazolium ions governs many chemical and physicochemical properties of these compounds. Since the 1950s, this type of protolytic equilibrium has been investigated by various teams. In this section, we analyze the results of experimental and theoretical studies on the annular tautomerism of NH-tetrazoles and their conjugate acids. The results of investigations published within the last decade are considered from the viewpoint of the classical concepts based on earlier research. 

Within the last decade, ab initio and hybrid quantum-chemical methods were in considerable use in tetrazole chemistry, and the level of calculations significantly improved with extended basis sets used for quite complex polyatomic molecules. During this time, theoretical methods were exploited in the study of several fundamental properties of the terazole ring, such as aromaticity and capability to be involved in various kinds of tautomerism, including the effects of substituents and media on these parameters. It was demonstrated that many physical and physicochemical characteristics of tetrazoles could be successfully estimated by these methods not only for the gas phase but also for the condensed state (solvents, crystals). 

The direct incorporation of a fluorine atom in the ring essentially affects versatile physicochemical and chemical characteristics of the heterocyclic system, in particular, its tautomerism, dipole moment, and the acid-base properties. For instance, tautomeric equilibria involving NH-unsubstituted fluoro derivatives of 1,2,3-triazoles [22, 23], 1,2,4-triazoles [24], and tetrazoles [25-28] were explored in a series of theoretical studies. The acid-base properties of these heterocycles (in particular, the CH-acidity of some among them) were also studied [28-30]. These investigations showed that the fluorine atom attached to the heterocyclic system changed significantly the character of the electron density distribution and consequently the polarity of the heterocycle, strongly increased its acidity and decreased its basicity. 

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