2- Phenyl-7-methyl triazolo pyridine

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>. 

As previously mentioned, the methyl group of 2-(p-tolyl)-s-triazolo-[l,5-a]pyridine is inert under the conditions of the Anil Synthesis. However, introduction of a chlorine atom in ortho position to this methyl group enables reaction to be carried out at 20°-30°C (Section II,E,3). Thus, for example, from 2-(3-chloro-4-methylphenyl)-j-triazolo[l,5-a]pyridine (19) and Schiff s base 171, the stilbene 172 is formed. In the case of 2-phenyl-7-methyl-j-triazolo[l,5-a]pyridine (173), however, reaction with 171 gives the styryl derivative 174, without additional activation of the methyl group.19... 

Reaction of the sulfoxide (174) with phenyl azide gave 3a,8b-dihydro-5-methyl-1 -phenyl-1H-1,2,3-triazolo[4,5 4,5]thieno[2,3-c]pyridine 4-dioxide (64) which, on aerial oxidation, gave 5-methyl-l-phenyl-l/M,2,3-triazolo[4,5 4,5]thieno[2,3-c]pyridine 4-dioxide (175) <80HCA1719>. 

In an approach to direct C-functionalization of triazolo[4,5-c]pyridines, shown in Scheme 3, 1-methyl (or phenyl)[l,2,3]triazolo[4,5-c]pyridines (26,33) are alkylated exclusively at C-4 by radicals generated by decarboxylation of carboxylic acids (ammonium persulfate-sulfuric acid-silver nitrate) <90ZOB683>. However, with /-butanol various products are obtained depending on the catalyst employed. For example, with ammonium persulfate-sulfuric acid-silver nitrate, exclusive C(4)-methylation (34) was observed, while ammonium persulfate-sulfuric acid gave exclusively C(4)-/ -hydroxy-/ ,/ -dimethylethylation (cf. (36)). The /-butyl analogue (35) was obtained by decarboxylation of pivalic acid. 

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