THERMODYNAMICS OF PROTONATION AND HYDRATION OF ALIPHATIC AMIDES

The protonation equilibria of a series of aliphatic amides of the type R-CO-NH2, R-CO-NHCH3 and R-CO-N(CH3)2 (R = H, Me, Et, Pr(i), Bu(t)) have been studied in aqueous H2SO4 in the temperature range 25-60-degrees-C, thus determining the protonation (m* and pK) and the thermodynamic parameters of the ionization equilibrium (DELTAG-degrees, DELTAH-degrees, DELTAS-degrees). These solution data have been combined with basicities in the gas phase and energies of hydration of neutrals, thus evaluating the enthalpies and free energies of hydration of protonated amides. The structures, energies and atomic charges for the primary derivatives and their protonated forms have been calculated by ab initio theoretical methods. Structural and solvation effects on basicities are discussed: increased substitution around the amide group causes a decrease in the basicity at the standard state (pK) and a concurrent decrease in the solvation of BH+ because of better charge dispersal, which is reflected in activity coefficient behaviour (m*). The two effects counteract each other, the outcome being that generally tertiary amides are 100% protonated at lower acid concentrations than less substituted ones. The energetics of gas phase to water transfer for neutral and protonated amides are discussed and compared with other bases (particularly thioamides) and onium ions.