Dissociation constants of 2‐azidoethanamines in aqueous solution

Aqueous‐phase dissociation constants (K_a) for the conjugate acids of a series of 2‐azidoethanamine bases: R¹N(R²)CH₂CH₂N₃ ( 1 , R¹ = CH₃, R² = H; 2 , R¹ = CH₃, R² = CH₃; 3 , R¹ = CH₂CH₃, R² = CH₂CH₃; 4 , R¹/R² =  CH₂CH₂CH₂CH₂ ; 5 , R¹/R² =  CH₂CH₂OCH₂CH₂ ; 6 , R¹ = CH₂CH₃, R² = CH₂CH₂N₃) were measured and found to fall between those for analogous unfunctionalized and cyano‐functionalized ethanamines. To explore the possibility of a relationship existing between the constants and molecular geometry, a theoretically based study was conducted. In it, the Gibbs free energies of aqueous‐phase (equilibrium) conformers of the bases and their conjugate acids were determined via a density functional theory/polarizable continuum model method. The results indicate that an attractive interaction between the amine and azide groups that underlies the lowest‐energy gas‐phase conformer of 2 is negated in an aqueous environment by solvent–solute interactions. The magnitudes of the free energy changes of solvation and −TS (entropic) energies of the conformers of the 2‐azidoethanamines and their conjugate acids are observed to correlate with the magnitude of the separation between the conformers' amine and azide groups. However, those correlations are not by themselves sufficient to predict the relative free energies of a molecule's conformers in an aqueous environment. That insufficiency is due to the influence of the correlations being mitigated by three other parameters that arise within the thermodynamic framework employed to compute the observable. The nature of those parameters is discussed. © 2009 Wiley Periodicals, Inc. Int J Quantum Chem, 2010