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, Δ G ‡ , 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, Δ G ‡ was measured to be 17.5-19.3 kcal/mol upon protonation across a range of solvents (D 2 O, DMSO- d 6 , MeCN- d 3 , MeOD- d 4 , tetrahydrofuran- d 8 , trifluoroethanol- d 3 ). Furthermore, Δ G ‡ 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, Δ G ‡ for the neutral molecule is smaller by ∼2-3 kcal/mol, ranging from 15.3-16.1 kcal/mol. In pyridine, Δ G ‡ does not correlate with the solvent dielectric for the "protonated" model. The lower barrier is attributed to competitive protonation: the p K a of the protonated triazine (∼6) is similar to that of protonated pyridine- d 5 (5.8). As additional acid is added, Δ G ‡ increases. Adding additional acid to the protonated model in D 2 O or DMSO- d 6 does not significantly affect Δ G ‡ .