Impact of Solvent and Protonation State on Rotational Barriers in [s]-Triazines

Amine-substituted [s]-triazines display hindered rotation around the triazine-N bond. While this barrier, ΔG^‡, has been measured to be between 15.1 and 17.7 kcal/mol for neutral triazines, the impacts that solvent and protonation state have not been addressed. Using a dimethylamine substituent as a reporter, ΔG^‡ was measured to be 17.5-19.3 kcal/mol upon protonation across a range of solvents (D₂O, DMSO-d₆, MeCN-d₃, MeOD-d₄, tetrahydrofuran-d₈, trifluoroethanol-d₃). Furthermore, ΔG^‡ increases as the solvent dielectric decreases (p < 0.01). This trend is consistent with the role that solvent plays in stabilizing the increased charge density on the triazine ring resulting from a loss of conjugation with the dimethylamine substituent. Across these solvents, ΔG^‡ for the neutral molecule is smaller by ∼2-3 kcal/mol, ranging from 15.3-16.1 kcal/mol. In pyridine, ΔG^‡ does not correlate with the solvent dielectric for the "protonated" model. The lower barrier is attributed to competitive protonation: the pK_a of the protonated triazine (∼6) is similar to that of protonated pyridine-d₅ (5.8). As additional acid is added, ΔG^‡ increases. Adding additional acid to the protonated model in D₂O or DMSO-d₆ does not significantly affect ΔG^‡.