pKa calculation for monoprotonated bipiperidine, bimorpholine and their derivatives in H2O and MeCN

Density-functional theory has been used to estimate the proton affinity (PA) and the acidity constants pKa of monoprotonated bipiperidine, bimorpholine and their derivatives in water and in acetonitrile (MeCN). Five different conformations of derivatives of bimorpholine and bipiperidine were explored. Monoprotonated bimorpholine has lower pKa values (9.1 in H2O and 17.4 in MeCN) than monoprotonated bipiperidine (12.8 in H2O and 21.0 in MeCN). For N-iPr derivatives of bimorpholine, the pKa values are 8.8 in H2O and 17.0 in MeCN and for N-iPr derivatives of bipiperidine the values are 12.5 in H2O and 20.8 in MeCN.