The 5,5-disubstituted barbituric acids are still synthesized by the classical condensation of substituted malonic esters, malonic amides, or cyanoacetic esters with urea, thiourea, guanidine, or dicyanodiamide, followed by the hydrolysis of the resulting imino- or cyanobarbiturate*.
Under acidic or neutral conditions, substituted malonic acids or malonic chlorides can also be used for the condensation with urea or thiourea. It is preferable for the substituents R1 and R2 to be present in the malonic ester or cyanoacetic ester molecule; disubstitution of barbituric acids at the 5-position is only possible with highly reactive halides, such as allyl halides.

[*] R. J. Levina, F. K. Velichko: "Advances in the Chemistry of Barbituric Acids," Russ. Chem. Rev. (Engl. Transl.) 29 (1960) 437.

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