Theoretical and Experimental Study of the Effect of Functional Groups on the Thiazole-5H Proton Chemical Shift in ¹H NMR Spectroscopy

The relationship between the position of the thiazole-5H proton signal and the presence of various substituents in the molecule was investigated in detail from an experimental and theoretical point of view. For this purpose, twenty 2,4-disubstituted thiazole derivatives were carefully chosen and synthesized, and their NMR spectra were recorded. Density functional theory calculations of ¹H NMR chemical shifts, frontier molecular orbitals, and molecular electrostatic potential surfaces were performed. The position of the thiazole-5H proton signal in the NMR spectrum is shown to strongly depend on the type and position of substituents in the molecule. Based on the obtained results, we can conclude that compounds with the smallest values of thiazole-5H proton shift are simultaneously those with small electron affinity, ionization potential and molecular electronegativity values, while compounds with the largest values of thiazole-5H proton shift have large electron affinity, ionization potential, and molecular electronegativity and a small HOMO-LUMO energy gap. These relationships become less clear in the case of compounds with intermediate values of the proton shift. Present research is a step towards an easy-to-use tool for predicting electronic effects in materials containing thiazole, based on the position of the thiazole-5H proton NMR signal.