Scope and limitations of a 1H NMR method for the prediction of substituted phenols pKa values in water, CH3CN, DMF, DMSO and i-PrOH

Simple empirical correlations were proposed between phenol pK(a) in various solvents (H2O, DMF, CH3CN, DMSO, and i-PrOH) and their chemical shifts delta(OH) measured in DMSO-d(6). The following method permits to predict pKa values for most phenols in the studied solvents with a good accuracy when intramolecular interactions (hydrogen bonds, steric hindrance, and tautomeric resonance) can be neglected. To illustrate the scope of the method we applied it to nine complex monoprotic phenols for which Hammett substituent constants sigma(-) were not compiled. The results obtained in water were in good agreement with the results obtained from ACD/pK(a) software and allowed to extend the calculation to their sigma(-) Hammett substituent constants and pK(a), values in other solvents. (C) 2013 Elsevier Ltd. All rights reserved.