Synthesis of Perfluoroalkyl[1,2,4]triazolo[1,3]thiazinones

Abstract

It is known that 1,3-thiazines are most commonly synthesized by reactions of thioamides, thioureas inclusive, with acetylenecarboxylic acid derivatives that play the role of a three-carbon bulding block for constructing the thiazine ring [1 4]. According to [5], N-aminothiourea (thiosemicarbazide) reacts with methyl propynoate in methanol to give methyl 3-thiosemicarbazonopropanoate. We found [6] that in boiling ethanol thiosemicarbazide reacts with methyl phenylpropynoate, forming initially methyl 3-phenyl3-thiosemicarbazonopropanoate whose subsequent heterocyclization provides a monocyclic 1,3-thiazinone, methyl 3-[(4-oxo-6-phenyl-4H-1,3-thiazin-2-yl)hydrazono]-3-phenylpropanoate. Since thiosemicarbazide is easily acetylated in acetic acid, nucleophilic addition to its triple bond of 3-phenylpropynoate gets impossible and the reaction goes through the thioamide group, yielding the bicyclic 3-methyl-7-phenyl5H-[1,2,4]triazolo[3,4-b][1,3]thiazin-5-one [6]. Therefore, proceeding with searching for synthetic approaches to potentially biologically active 1,3-thioazinones and their fusion products, we turned to reactions of 1-(perfluoroacyl)thiosemicarbazides Ia, Ib and 5-(perfluoroalkyl)triazole-3-thiols IIa, IIb with methyl phenylpropynoate (III) in view of the increasing interest heterocyclic systems with perfluoroalkyl substituents have attracted over the past years [7]. This interest is explained by changes in chemical properties and biological activity produced by perfluoroalkyl substituents.