Gas phase basicity of biguanides - Comparison of the equilibrium and the kinetic methods

The gas-phase basicities (GB) of 7 biguanides were measured by the equilibrium and the entropy corrected kinetic methods. The experimental data were compared with the GB values calculated at B3LYP/6-311+G(2df,p)//B3LYP/6-31G(d) level of theory. Calculated GB values for biguanides correlate well with the experimental data and lie on the same regression line as guanidine derivatives. All biguanides belong to the class of superbases having GB above 1000 kJ mol(-1) and being comparable or more basic than the most basic guanidines known. The highest GB of 1103 kJ mol(-1) was determined for the bis-dimethylaminomethylene-2,3-bis-(3-dimethylaminopropyl)guanidine (biguanide 4) in which two intramolecular hydrogen bonds (IMHB) can be formed in the protonated form. For selected biguanides and guanidines, contribution of IMHB to the GB was calculated for two conformations with different hydrogen bonding motifs (6- and 8- membered pseudocyclic substructure). In conjugated acids of biguanides having two 3-dimethylaminopropyl or 3-methoxypropyl substituents, conformational preference is determined by maximizing number of possible IMHBs. Hydrogen bond stabilization enthalpies were also calculated using aforementioned B3LYP as well as M06-2X/6-311++G(3df,2p)//B3LYP/6-31G(d) model and compared to the values obtained for guanidine derivatives. Slightly weaker hydrogen bonds in biguanides with respect to guanidines were ascribed to larger steric congestion while the impact of more extensive delocalization area was found negligible. (C) 2018 Elsevier B.V. All rights reserved.