First thermodynamic dissociation constants of barbituric acid derivatives in water at 25 °C. Part 3. 5,5-Alkylenebarbituric acid derivatives. A comparison with 5,5-dialkylbarbituric acids, and with mono- and di-carboxylic acids

Abstract

The synthesis and determination of the first thermodynamic dissociation constants for three 5,5-alkylenebarbituric acid derivatives (II; n= 2–4) is described. A pK₁ value for a fourth derivative (II; n= 5) is also reported. In a previous study the steric effect of the 5-substituents in 5,5-disubstituted barbituric acids, e.g.(I; R¹= R²; Me to Et), was found to be acid strengthening. This acid strengthening effect has been attributed to solvent exclusion in the undissociated molecule. In the derivatives (II) steric effects of the 5-substituents are minimized and remain essentially constant. These derivatives all have high pK₁ values (8.73–8.88), similar to that, 8.51, of (I; R¹= R²= Me). Polar effects of the 5-substituents in the derivatives (II) were small but in keeping with those expected for 5,5-alkylene groups and pK₁ values followed the expected inductive order for electron release in derivatives (II)(n= 5 > n= 4 > n= 3 > n= 2). Comparison of the pK₁ values for the barbituric acid derivatives with those for certain mono- and di-carboxylic acids reveal similarites in substituent effects which are very pronounced in the barbituric acid reaction series, although not as pronounced as in the malonic acid series.