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

Abstract

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-d 6, MeCN-d 3, MeOD-d 4, tetrahydrofuran-d 8, trifluoroethanol-d 3). 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-d 5 (5.8). As additional acid is added, ΔG ‡ increases. Adding additional acid to the protonated model in D2O or DMSO-d 6 does not significantly affect ΔG ‡.