Optimal strategy of new 6H-1,3,4-thiadiazines synthesis in search of the promising antidiabetic agents

Abstract

In this work, we report a convenient method for the preparation of new 2-hydroxyethylamino-substituted 6Н-1,3,4-thiadiazine hydrobromides for the search of new agents with pleiotropic (antioxidant and antiglycating) activity. The synthesis is based on the cyclocondensation reaction of 4-substituted thiosemicarbazide with various α-haloketones. We compared approaches to the key intermediate for the synthesis of the 6H-1,3,4-thiadiazine system – 4-substituted thiosemicarbazide. The approach we proposed was modified to obtain the intermediate and is based on the reaction of a substituted carbamothioylthioacetate with hydrazine. This approach has a number of advantages, like fewer stages, atom economy, elimination of stages with the isolation of undesirable by-products, availability of starting materials and simplicity of the procedure. New 2-hydroxyethylamino-5-substituted 6H-1,3,4-thiadiazine hydrobromides were characterized by ¹H NMR, ¹³C NMR and elemental analysis.