1.2.4- Triazolo pyridine electrophilic substitution

Compounds 4 and 5 would be expected to be inert toward electrophilic substitution, and, in fact, sulfonation of the 2-phenyl derivative 201234 and nitration of the 1-phenyl derivative 202l69b lead to substitution on the phenyl rings. A series of electrophilic substitutions on the product (203) from 1 -(n-butyl)[l,2,3]triazolo[4,5-c]pyridine and dimethyl sulphate give 7-bromo-, 7-nitro-, and 7-chlorotriazolopyridin-4-ones the electrophilic attack may, in each case, be on the triazolopyridinone.169... 

As with the [1,5-a] analog mentioned above, 3-amino-[l,2,4]triazolo[4,3-n]pyridine underwent typical diazonium reactions. It could be acylated and transformed into Schiff bases. The 3-amino group had little influence as an electron-donating group for stimulating electrophilic substitution of the fused triazole nucleus (66JOC265). 

In contrast to the ease of N-functionalization, shown in Scheme 1, the triazolopyridine nucleus is resistant to direct nuclear oxidation or electrophilic additions. Electrophilic additions will occur on aryl substituents for example, nitration of l-phenyltriazolo[4,5-c]pyridine (26) and sulfonation of 2-phenyl-2i/-triazolo[4,5-6]pyridine (28) occur exclusively in the para position of the phenyl ring <34LA(514)279, 38MI 710-01). Nuclear functionalization was observed when l-( -butyl)-5-methyl-tri-azolo[4,5-c]pyridinium iodide (30) was treated with potassium ferricyanide to afford triazolopyridin-4-one (31), as shown in Scheme 2. Similarly, the iodide (30) is converted by either phosphorus oxychloride-phosphorus pentachloride, or bromine or nitric acid to 7-substituted triazolopyridin-4-ones (32) <37LA(529)288>. 

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