¹³C CPMAS NMR as a Tool for Full Structural Description of 2-Phenyl Substituted Imidazoles That Overcomes the Effects of Fast Tautomerization

Tautomerization of 2-phenylimidazolecarbaldehydes has not been studied in detail so far, although this process is a well-known phenomenon for imidazole derivatives. That is why we focus our study on a series of 2-phenylimidazolecarbaldehydes and their parent alcohols that were synthesized and studied by detailed ¹H and ¹³C NMR in solution and in the solid state. The apparent problem is that the fast tautomerization impedes the full structural description of the compounds by conventional ¹³C NMR measurements. Indeed, the ¹³C NMR spectra in solution exhibit poor resolution, and in most cases, signals from the imidazole ring are not detectable. To avoid this problem, we used ¹³C CP-MAS NMR as an alternative spectroscopic method for unambiguous spectroscopic characterization of the studied series of 2-phenylimidazoles. The data were analyzed in combination with quantum chemical DFT-GIAO methods by considering the tautomerization process and the intermolecular interactions. The DFT (B3LYP/6-31G(d,p)) calculations allowed to identify and suggest the preferred tautomer in the gas phase and in DMSO solvent, which for alcohols are (2-phenyl-1H-imidazol-4-yl)methanol and its analogs, and for the aldehydes are the 2-phenyl-1H-imidazole-5-carbaldehydes. The gas-phase calculated energy differences between the two possible tautomeric forms are in the range 0.645-1.415 kcal/mol for the alcohols and 2.510-3.059 kcal/mol for the aldehydes. In the DMSO solvent, however, for all compounds, the calculated energy differences go below 1.20 kcal/mol. These data suggest that both tautomeric forms of the studied 2-phenylimidazoles can be present in solution at room temperature. Our data from detailed 2D NMR measurements in the solid state (¹H-¹³C HETCOR and ¹H-¹H double-quantum coherence MAS NMR) suggested that also in the solid state both tautomers coexist in different crystalline domains. This fact does not obscure the ¹³C CP-MAS NMR spectra of the studied 2-phenyl substituted imidazoles and suggests this spectroscopic method as a powerful tool for a complete structural description of tautomeric systems with aromatic conjugation.