Cyclization of Isothiosemicarbazones. 5. Triazolopyrimidines

Article abstract of DOI:10.1021/jo00333a005

The 4-<2-cyano-2-(ethoxycarbonyl)vinyl>-3-methylisothiosemicarbazones of aromatic aldehydes underwent cyclization upon being heated in 1-butanol, N,N-dimethylformamide, dioxane, or pyridine to give 2,5-disubstituted <1,2,4>triazolo<1,5-c>pyrimidine-8-carboxylates in moderate yields.Competitive formation of ethyl 4-amino-2-(methylthio)pyrimidine-5-carboxylate occured in this cyclization with elimination of benzonitriles probably through a nonionic pathway.Treatment of the aromatic ketone analogues with hot acetic acid or pyridine gave 2,2,5-trisubstituted 2,3-dihydro<1, ,2,4>triazolo<1,5-c>pyrimidine-8-carboxylates by intramolecular cycloaddition.These compounds exist as a chain-ring tautomeric mixture in pyridine at elevated temperatures and gradually lose the substituents at the 2-position to give the same bicyclic pyrimidines as those from aldehyde isothiosemicarbazones.A mechanism was proposed in which the ring closure of the 2,3,5,9-tetraaza-1,3,6-nonatrien-8-yne systems may involve a ten-electron cyclic transition state.