Ferricyanide, nucleophilic substitution

Hydroxy-[l,2,4]triazolo[4,3-fl]pyridine (91) was reluctant to react with the common hydroxylic chlorinating agents, giving at best, the 3-chloro compound in only 15% yield with pWphorus oxychloride-dimethylaniline. Methylation of (91) produced 2-methyl-[l,2,4]triazolo[4,3-n]pyrid-3-one (92) whereas methylation of the 3-thiol (93) resulted in methyl [l,2,4]triazolo[4,3-a]pyrid-3-yl sulfide (94), a molecule also resistant to nucleophilic substitution (66JOC265). Potassium ferricyanide oxidation of (93) resulted in the corresponding disulfide. 

The naphthalene-like, aromatic stmcture of 1,2,3-benzothiadiazole imparts stability to the system that survives exposure to 20% potassium hydroxide at 150°C or 27% sulfuric acid at 200 °C. It is not oxidized by potassium permanganate, potassium ferricyanide, chromic acid, or dilute nitric acid <1996CHEC-II(4)289>. Electrophilic substitution occurs in the benzo ring, predominantly at the 4-position. Chlorine in the 6-position is displaced by a variety of nucleophiles <1975SST670>. 

Carbon nucleophiles in general react at the least hindered position. Thus 1,3-ketones add to 2,6-diphenylthiopyrylium salts to give the expected 4-substituted 4H-products, but if the diketone is part of a six-membered ring it is further oxidized in situ to the thiopyrany-lidene product, while the other adducts require treatment with ferricyanide to convert them to the unsaturated products (76CB1549). 

---