Alkaline hydrolysis of 1,3-dimethylphenobarbital

The reaction of 1,3-dimethylphenobarbital (I) with 0.02-0.32 M KOH in aqueous methanol was studied. The barbiturate ring cleaved reversibly at the 1,6-position, forming a malonuric acid which was stable to further hydrolysis but which could readily recyclize to I. N,N-Dimethylethylphenylmalondiamide arose from decarboxylation of the carbamic acid formed by a 1,2-ring opening; this irreversible decarboxylation determined the diamide as the only final reaction product. The malonuric acid, which could be isolated in solid form, appeared as N-methyl-2-phenylbutyramide (GLC) following thermal decarboxylation and degradation of the acid. The I disappearance rate was biphasic, and the kinetics were consistent with the described reaction. The individual rate constants and the equilibrium constant for the reaction between I, the malonuric acid, and hydroxide were determined.