Synthesis of Thiadiazoles Based on Phloroglucinol Derivatives and Their Glycosylation

4-(2,4,6-Trimethoxyphenyl)-1,2,3-thiadiazole was synthesized by the Hurd–Mori reaction starting from 2,4,6-trimethoxyacetophenone. Demethylation of 4-(2,4,6-trimethoxyphenyl)-1,2,3-thiadiazole in presence of aluminum trichloride proceeds chemoselectively to give 4-(2-hydroxy-4,6-dimethoxyphenyl)-1,2,3-thiadiazole. The latter is glycosylated with 1-α-bromo-2,3,4,6-tetra-O-acetyl-D-glucopyranose and 1-α-bromo-2,3,4,6-tetra-O-acetyl-D-galactopyranose under the conditions of the phase transfer variant of the Kennigs–Knorr reaction to form corresponding α-glycosides. Nitration of 4-(2-hydroxy-4,6-dimethoxyphenyl)-1,2,3-thiadiazole with nitric acid gives 4-(2-hydroxy-3-nitro-4,6-dimethoxyhenyl)-1,2,3-thiadiazole, which, under the above-mentioned conditions, is glycosylated with 1-α-bromo-2,3,4-tri-O-acetyl-D-xylopyranose to corresponding β-glycoside. Under the condition of Fries rearrangement, 3,5-dimethoxyphenyl acetate forms two products, 2-hydroxy-4,6-dimethoxyacetophenone (xantoxylin) and 1,1′-(2-dihydroxy-4,6-dimethoxy-1,3-phenylene)bis(ethan-1-one). Formation of xantoxylin carbethoxyhydrazone proceeds difficultly. When heated with thionyl chloride it converts to labile 4-(2-hydroxy-3,5-dichloro-4,6-dimethoxyphenyl-1,2,4-thiadiazole. 1,1′-(2-Dihydroxy-4,6-dimethoxy-1,3-phenylene)bis(ethan-1-one) under the conditions of the Hurd–Mori reaction gives 3,5-dimethoxy-2,6-bis(1,2,3-thiadiazol-4-yl)phenol.