Solution conformations of barbituric acid derivatives: a 3J(13C,1H) NMR study.

The conformations of the 5-alkyl chains of 5,5-dialkylbarbituric acid derivatives in polar and nonpolar media were determined from the magnitudes of the vicinal heteronuclear coupling constants between the alpha-alkyl hydrogens and the carbonyl carbons. The experimental 3J values have been compared to theoretical values, and the conformational populations of the alkyl side chains with respect to the trioxopyrimidine ring have been determined. The results show that all these compounds have a very low barrier to rotation for both butyl and ethyl side chains. The barbiturates that do not have a 1'-methyl group in the butyl side chain, butobarbital and amobarbital, have no preferred conformation for either the butyl or ethyl side chains. However, the compounds with a 1'-methyl group, pentobarbital and alpha-methylamobarbital, exhibit preferred conformation for both alkyl chains. The significance of these results to the relationship between conformations and pharmacological activity is discussed.