A quantum chemical approach to the physical interpretation of the classical substituent effect in the 2,4-diaryl-4H-1,4-thiazine derivatives

Substituent effect (SE) significantly influences the electronic structure of molecules. This study focuses on analyzing SEs in the 2,4-diaryl-4H-1,4-thiazine, with a specific emphasis on their impact on aromaticity and reactivity. The density functional theory (DFT) calculations, the harmonic oscillator model of aromaticity (HOMA) index, and frontier molecular orbital analysis are employed to compare SEs at two selected positions, R¹ and R², which correspond to the para positions of two phenyl rings in the parent 2,4-disubstituted-4H-1,4-thiazine. Our investigation reveals that the presence of any substituent (electron-withdrawing or electron-donating) at the R¹ position induces more significant changes in the molecule. The correlation between the Hammett constant (R) and HOMA suggests that electron-donating groups at the R¹ position activate the heterocyclic ring, leading to decreased aromaticity. These findings offer valuable insights into designing synthesis pathways for thiazine derivatives and other related physical and chemical properties.