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 h ydrogen bonding on the aminolysis of 6-chloropyrimidine, i.e., the reaction of NH3 with 6-chloropyrimidine to give HCl and 6-aminopyrimidine. The isol ated aminolysis of 6-chloropyrimidine requires 138.1 kJ mol(-1). If the ele ctrondonating species H2CO is hydrogen bonded to the NH3 moiety during amin olysis, the barrier is I educed to 112.2 kJ mol(-1). When H2NCHO is added t o NH3 + 6-chloropyrimidine, the electron-donating -CHO group is able to hyd rogen bond to the NH3 moiety while the electron-accepting -NH2 group hydrog en 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-c hloropyrimidine being reduced to 95.3 kJ mol(-1). Thus, the aminolysis of 6 -chloropyrimidine, as mediated by hydrogen bonding, provides a clear and si mple example of the catalytic possibilities of well-chosen hydrogen bonding .