Synthesis and cyclization of dialkylmalonuric esters.
A novel method for the synthesis of methyl dialkylmalonuric esters was developed using the base-catalyzed ring opening of an isopropylidene malonic ester with urea as the key step. The rates of cyclization of these malonuric esters to the corresponding barbituric acids then were studied at buffer concentrations ranging from 0.01 to 1.00 M. The reaction was shown to be general base catalyzed, and the reaction rate was found to be subject to a deuterium isotope effect, kH2O/kD2O=1.3. The thermodynamic activation parameters also were determined. A three-step mechanism for the conversion of malonuric esters to barbituric acids was proposed; it involved a rapid cyclization step, followed by proton removal by a general base catalyst and a rate-determining collapse of the resulting tetrahedral intermediate aided by a general acid.
D001463:Barbiturates / Q000138:chemical synthesis*; D003500:Cyclization; D007700:Kinetics; D008314:Malonates; D013816:Thermodynamics; D014508:Urea
D001463:Barbiturates; D008314:Malonates; D014508:Urea