Acid-base initiated cyclization and retrocyclization reactions of ethyl 2-(3-acylselenoureido)benzoates, -thiophene-3-carboxylates and the corresponding 2-(3-acylisoselenoureido) derivatives

Acid and base initiated cyclization and retrocyclization reactions of the s elenoureas 1-6 and isoselenoureas 7-12 to fused 4H-1,3-selenazine and 1,2,3 ,4-tetrahydropyrimidine-4-one skeletons are reported. Fused 2-acylamino-4H- 1,3-selenazine-4-ones 13-18 were formed by the action of concentrated sulfu ric acid on acylselenoureas 1-6 or on 2,2-dimethylpropanoylisoselenoureas 1 0-12 at room temperature. On the other hand, benzoylisoselenoureas 7-9 were not obtained in this cyclocondensation under the same conditions. The reac tion of potassium ethoxide on selenazines 13-18 in the ethanol solution evo ked retrocyclization to the starting acylselenoureas 1-6. Both types of the title compounds, i.e. selenoureas 1-6 and isoselenoureas 7-12, were deprot onated in a methanol solution of potassium hydroxide used in an equimolar a mount, giving rise to potassium salts 19-24, which were isolated only for t he thiophene series. By heating the separated potassium salts 20, 21, 23 an d 24 in the methanol solution provided, deacylation and isoselenoureas 26, 27 were formed. The in situ prepared salts 19, 22 cyclized under the same c onditions with deacylation to 4-selanyl-3,4-dihydroquinazoline-4-one 28. Th e title compounds 1-6, 7-12 and products of their deacylation 26, 27 on boi ling in methanolic potassium hydroxide cyclized to the corresponding fused 2-selenoxo-1,2,3,4-tetrahydropyrimidine-4-one potassium salts. These compou nds provided pyrimidine-4-ones 28-30 on acidification. Acid initiated retro cyclization 28-30 to the corresponding 2-amino-4H-1,3-selenazine-4-ones was unsuccessful. C, H, N, Se elemental analyses, FTIR, 1H-NMR, and 13C-NMR sp ectroscopies supported the structure of synthesized compounds. A short revi ew on cardiotonic steroids and their analogues is presented. The natural, s emisynthetic and synthetic derivatives, as well as their mechanism of actio n and structure-activity relationships are shown, with a special reference to aminoguanidine derivatives.