In this study, the photocatalytic degradation of seven sulfur compounds (2-methylthiophene, 3-methylthiophene, 2-phenylthiophene, 3-phenylthiophene, 2,5-diphenylthiophene, 2-(2-thienyl) pyridine, and 2-(3-thienyl) pyridine in semiaqueous medium are compared to thiophene. The apparent-reaction-rate constant (k) is found to decrease in the following order: 2,5-diphenylthiophene > 2-(2-thienyl) pyridine > 2-penhylthiophene > 3-penhylthiophene > 2-(3-thienyl) pyridine > 3-methylthiophene > 2-methylthiophene > thiophene. From the data obtained by UV light absorption (Λmax) measurements and electronic structure calculations (frontier orbitals energy, global hardness, and global softness), the kinetic parameters of the reaction have been determined. Among the studied compounds, thiophene with a high Λmax and low calculated LUMO-HOMO gap energy has showed higher activity under UV irradiation. Interestingly, a lower activity is observed with low Λmax and high LUMO-HOMO gap energy. This demonstrates, for the first time, that the reactivity depends essentially on the thermodynamic stability of the sulfur compound rather than on the nature or the position of the substituent on the ring. © 2018 American Chemical Society.