Catalysis Mediated by Hydrogen Bonding: A Computational Study of the Aminolysis of 6-Chloropyrimidine

Density functional theory has been employed to investigate the effects of hydrogen bonding on the aminolysis of 6-chloropyrimidine, i.e., the reaction of NH 3 with 6-chloropyrimidine to give HCl and 6-aminopyrimidine. The isolated aminolysis of 6-chloropyrimidine requires 138.1 kJ mol - 1 . If the electron-donating species H 2 CO is hydrogen bonded to the NH 3 moiety during aminolysis, the barrier is reduced to 112.2 kJ mol - 1 . When H 2 NCHO is added to NH 3 + 6-chloropyrimidine, the electron-donating −CHO group is able to hydrogen bond to the NH 3 moiety while the electron-accepting −NH 2 group hydrogen bonds to the N of the pyrimidine ring that is adjacent to the carbon at which substitution occurs. This results in the barrier to aminolysis of 6-chloropyrimidine being reduced to 95.3 kJ mol - 1 . Thus, the aminolysis of 6-chloropyrimidine, as mediated by hydrogen bonding, provides a clear and simple example of the catalytic possibilities of well-chosen hydrogen bonding.