Synthesis of 1,3-Dialkyl- and 1,3-Diphenyl-5-cyano-2-thiouracil Derivatives

Nucleophilic vinylic substitutions of ethyl (E)-and (9-3-aryl-3chloro-2-cyanopropenoates ( l a ) and ( l b ) with symmetrically substituted thioureas afforded, after spontaneous cyclisation, 1,3-dialkyl-and 1,3diphenyl-5-cyano-2-thiouracil derivatives (3a-3h) in moderate to good yields Pyrimidine derivatives have proven to be active antit~mor,'.~antipyretic and antiinflammatory agents."Synthesis of some 5-cyano-2-thiouracil derivatives has previously been reported.'-"Recently we reported the synthesis of 1,3-thiazin-4-one derivatives obtained by reacting ethyl (0and (Z)-3-aryl-3-chloro-2-cyanopropenoates with thioureas bearing at least one primary amino g r o ~p .' ~In this article we report the synthesis of 2-thiouracils (3a-3h) starting from the same substrates (la, l b ) as in the above mentioned 1,3-thiazin-4-one synthesis but now by using symmetrically substituted thioureas as reagents.(Scheme 1, Table 1).