Linear free energy–steric strain energy relationships for the gem-di-methyl effect. Acid-catalysed ring closure of methyl-substituted 3-ureidopropionic acids

Abstract

The rate data for the acid-catalysed ring closure of eight methyl-substituted 3-ureidopropionic acids constitute an isokinetic series according to Exner's statistical criteria. Linear relationships were obtained for the free energies in the reaction series for rates and equilibria exhibiting the gem-dimethyl effect with steric strain energies estimated from enthalpies of formation of homomorphic hydrocarbons. These estimates were obtained by means of Istomin and Palm's procedure and are of two kinds, the P values measuring the total strain energy and ΔP values measuring the strain between two fragments in the model hydrocarbon. Some reaction series correlated with ΔP values when one of the functional groups was taken as an invariable fragment and the rest of the molecule as a variable substituent. Other reaction series correlated with P values. The approach has the advantage that it takes into account directly the non-additivity of gauche-interactions and permits evaluation of the data for substituents at various positions of the chain in a single correlation. For cyclization to five- and six-membered rings, the data form a single reaction series when the rates for the parent compounds are close in value. Only certain hydrocarbon models and manners of fragmentation lead to satisfactory correlations. These, and the correlation with P or with ΔP values, or whether a correlation can be obtained at all, indicate the steric requirements of the reaction and thus its mechanism. Linear relationships with strain energies were obtained for reaction series where the rate accelerations have been attributed to entropy effects.