Correlation of Rotational Barriers with Substituent Electronic Effects and Positional Selectivity in 2/3-Monosubstituted Pyrroles, Furans, and Thiophenes

The rotational barrier (RB) around substituent-ring bond of monosubstituted pyrrole, furan, and thiophene with electron-withdrawing (EW) and electron-donating (ED) groups was calculated using ωB97X-D/6-31G** level of theory. The RB method was found to be a successful measure for substituent and heteroatom effects, and positional selectivity since RB was in consistent trend with geometric, molecular, spectroscopic, and energetic properties that reflect the extent of resonance stabilization and charge distribution in these 5-membered heterocyclic compounds. EW substituents at the 2- and 3-positions lead to markedly increased RBs and enhanced conformational stability relative to ED substituents, with the effect being particularly pronounced at the 2-position. Furthermore, pyrrole exhibited a slightly greater reactivity toward EW substituents compared to furan and thiophene. The present results are consistent with available experimental data and provide a foundation for systemic investigation of substituent effects in heterocyclic compounds bearing one or multiple heteroatoms.