Application of 1,3-disubstituted thioureas as a key synthons for the synthesis of novel 5,7-disubstituted perhydroimidazo[4,5-e][1,2,4]triazinethiones

Abstract

A series of 1-alkyl-3-arylureas and thioureas, a key synthons for the synthesis of various heterocycles, have been synthesized. The corresponding 4,5-dihydroxyimidzolidin-2-ones and thiones were prepared from (thio)ureas with glyoxal, and the selectivity of their reaction with thiosemicarbazide was studied. Regioisomeric 7-alkyl-5-aryl- and 5-alkyl-7-aryl-3-thioxoperhydroimidazo[4,5-e][1,2,4]triazin-6-ones(thiones) were prepared and separated by fractional crystallization. Intermediate 3-alkyl-2-(1-(4-chlorophenyl)-5-ethoxy-2-oxoimidazolidin-4-yl)hydrazinecarbothioamides were also isolated. The structures of the regioisomers and intermediates were unambiguously determined by two-dimensional NMR NOESY spectral data and X-ray diffraction studies.