Estimation of dissociation constants (pKa's) of oximes from proton chemical shifts in dimethyl sulfoxide solution.

In connection with structure-activity studies of insecticidal methyl carbamoyloxime acetylcholinesterase inhibitors, a straight-forward approach to estimating pKa values of a series of precursor oximes and thiohydroximates has been developed. The pKa values of oximes correlate well with the proton chemical shifts of the oximino proton (delta OH) in dilute dimethyl sulfoxide-d6 solution. The relationship pKa = 29.10 - 1.63 delta OH was developed from delta OH and pKa data for 20 compounds available either from the literature or derived experimentally from half-neutralization potentials (delta HNP). Using this relationship, pKa values of more than 200 hydroximino compounds were calculated. The relationship has been extended to also include phenols: pKa = 28.15 - 1.55 delta OH - 3.96I(phenol), where I(phenol) is an indicator variable indicating application of the equation to either a phenol [I(phenol) = 1] or an oxime [I(phenol) = 0].