Synthesis of 5-(functionalized acyl)-1,3-dialkyl-substituted barbituric and 2-thiobarbituric acids

A sodium derivative of 1,3-dimethylbarbituric acid or 1,3-diethyl-2-thiobar bituric acid undergoes an efficient monoacylation at C5 by the reaction wit h omega -chloroalkanoyl chloride or diacid dichloride in the presence of py ridine in tetrahydrofuran. A nucleophilic displacement of the chlorine in a 5-chloroacetylbartiburate can be accomplished by using a one-pot procedure . By contrast, a similar transformation of a 5-(chlorobutanoyl)barbituric a cid requires intramolecular cyclization in the presence of a nonnucleophili c base followed by treatment with a nucleophile of the resultant 5-[4,5 -di hydro(3H)-2-furylidene]barbiturate.