A versatile and convenient method for the syntheses of pyrimido[4,5-b][1,4]thiazine and -thiazepine ring systems

Abstract

Treatment of 5-hydroxyuracil 1 and 5-hydroxyisocytosine 2 with N-bromosuccinimide in ethanol followed by the thermal condensation with β- and γ-amino thiols such as 2-aminothiophenol, cysteamine, L-cysteine and D,L-homocysteine resulted in the formation of the corresponding pyrimido[4,5-b][1,4]thiazin-4(3H)-ones, 3-8, and pyrimido[4,5-b][1,4]thiazepin-4(3H)-ones, 9 and 10. The new method for the construction of pyrimido[4,5-b][1,4]thiazine and -thiazepine ring systems was shown to involve the condensation of 5,6-diethoxy-5-hydroxy-5,6-dihydropyrimidin-4(3H)-one intermediates, 11 and 12, with the β- and γ-amino thiols which is accelerated in the presence of an acid-catalyst.