First thermodynamic dissociation constants of 5,5-disubstituted barbituric acids in water at 25 °C. Part 2. Structure–reactivity relationships (SRR). Linear free energy relationships which correlate C(5)-substituent effects with acid strength

Abstract

First thermodynamic dissociation constants have been examined for the effect of C(5)-substituents on acid strength in a series of 14 5,5-disubstituted barbituric acids (Ia; R¹= Me, R²= Me, Et, Prⁱ or Ph; R¹= Et, R²= Et, Prⁱ, Ph, 3-NO₂C₆H₄ or 4-NO₂C₆H₄; R¹= allyl, R²= Prⁱ; R¹= R²= allyl, Ph, Br, or Cl). Taft polar substituent constants, σ*, have been calculated for a number of groups. Steric factors have been investigated as an additional effect on reactivity in these derivatives: Taft steric substituent constants,E_s, and the Newman six-number measure of steric effects have been used. A linear free-energy relationship (LFER) is established by multiple correlation, with the independent variables polar and steric substituent constants, and its significance for the reaction series is discussed.