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 pKa 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‡.