CHAPTER XX - Dissociation Constants

Abstract

Beckett determined pKa values of 20 compounds of structure (I) in water at 25°C and ionic strength of approximately 0.013 M. Marshall reported on the dissociation constants of 18 such compounds. The replacement of the cyano group by a proton has a base strengthening effect of 0.8 to 1.2 pKa units. Replacement by a ketonic group has a similar but smaller effect. The dissociation constants of ketones, acids, and esters are apparently of the same order of magnitude. Cyano, ketonic, acid, and ester groups are electronegative in character; therefore, the observed differences in basic strength may be attributed to the inductive effect along the chain separating these groups from the basic center or a field effect operating through space or solvent if the interacting groups are in close proximity, which is probably achieved by a mechanism in which the lone pair orbital of the nitrogen atom of the basic group interacts with the electropositive carbon atom of substituent R. Dimethylamino compounds are stronger bases than the corresponding piperidine analogs, and the piperidine analogs are stronger bases than their morpholino analogs.