ON THE CALCULATION OF TETRAHEDRAL INTERMEDIATE PKA VALUES

The procedure of Fox and Jencks for calculating tetrahedral intermediate pK(a) values, as DELTApK(a) = rho(I)SIGMAsigma(I) relative to that of some defined amine or alcohol, is re-examined in the light of more recent estimates for sigma(I). Using those of Charton, which are explicitly tuned to aqueous or near-aqueous conditions, we derive a value of rho(I) = -9.1 +/- 0.4 for the effect of substituent X on probe Y for a one-carbon separation (X-C-Y). Additionally we derive, for X-C-C-Y, a value of rho(I) = -4.4 +/- 0.4. We also examine the possibility of assigning sigma(I) values to charged substituents. It is shown that this approach can be made to work under strictly defined conditions, and results in a self-consistent set of sigma(I)+/- values that may be used in the present context.