On the calculation of tetrahedral intermediate pK a values

Abstract

The procedure of Fox and Jencks for calculating tetrahedral intermediate pKa values, as ΔpKa=ρI∑σI; relative to that of some defined amine or alcohol, is re-examined in the light of more recent estimates for σI. Using those of Charton, which are explicitly tuned to aqueous or near-aqueous conditions, we derive a value of ρI=–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 ρI=–4.4 ± 0.4.We also examine the possibility of assigning σI 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 σI± values that may be used in the present context.