Mono C-Alkylation and Mono C-Benzylation of Barbituric Acids Through Zinc/Acid Reduction of Acyl, Benzylidene, and Alkylidene Barbiturate Intermediates

Through systematic exploration of reaction conditions, very efficient preparative procedures for obtaining large quantities of substituted 5-alkyl and 5-benzylbarbituric acids were developed. The procedure involves a two step preparation in which the second step is zinc dust/acid reduction. For preparation of 5-alkylbarbiturates, the first step is the preparation of either 5-acyl or 5-alkylidenebarbiturate. If 5-benzylbarbiturate is the target product, then the first step includes the preparation of 5-benzylidene. Regardless of the nature of the first step, all reactions presented synthetic yields around 90% and isolation and purification involves only crystallization.