1.2.3- Triazolo pyridine ring-opening

Cycloaddition of pyridine Ar-oxides (see Section 11.13.2) led to careful examination of thermodynamic aspects, though no experimental measurement was provided. Thermodynamic profile for the ring-chain isomerization of [l,2,3]triazolo[l,5- ]pyridines via a ring-opening pathway (Equation 2) was calculated. Based on this computational study, a multistep mechanism was proposed <20050BC3905>. 

As depicted in Scheme 11, ylides 39 derived from 4-methyl-[l,2,3]triazolo[l,5- ]pyridine react with Michael acceptors, which, upon nucleophilic attack at C3 and ring opening, lead to nucleophilic displacement of nitrogen. The intermediate diradical led to a mixture of compounds, including alkenes and a cyclobutane derivative when methyl acrylate was used, and the indolizine 40 with methyl propiolate as the electrophile <1998T9785>. Heating 4-methyl triazolopyridine with benzenesulfonyl chloride in acetone also confirmed decomposition via a radical pathway. 

When the quinolizinium salt bears a very powerful electron-withdrawing group, ring opening can occur at low temperatures in aqueous acid. Such a group is the diazonium cation, and attempts to diazotize 1-aminoquino-lizinium salts led, via the ring-opened intermediate 196 to triazolo[l,5- ]-pyridines 197-199.133 170-171 jt js noteworthy that the Z double bond is retained in the side chain, and that the deuterium was fully retained when a [2,4-2H2]-l-amino-3-methylquinolizinium salt was treated with nitrous acid, giving compound 200. 

These facts suggest that the imidazole ring in compounds 86, 330, 334 and 617 is first reversibly covalently hydrated in the acid medium to form 638, and then a hydrolytic ring opening occurs to provide intermediate 639. Then A -nitroso compound 640 forms and ring closes to afford l-methyl-l,2,3-triazolo[4,5-c]pyridine 637 (80KG121). The A -nitrosation occurs with nitrogen oxides formed from nitric acid reduction. 

A mechanistic investigation into the electtophilic ring-opening of [l,2,3]triazolo[l,5-a]pyridines (46) to give regiospecifically 2,6-disubstituted pyridines has been reported. An intermediate diazene is proposed, which decomposes via a diradical intermediate. 

This probably arises from the intermediate (58) by ring opening of the vic-triazole ring, as is suggested by the observation that l,5-dihydro-4H-t ic-triazolo[4,5-c]pyridine-4-thione (57) in refluxing propanol gives rise to an equilibrium mixture of (56) and (57). The reconversion (70%) of (56) into... 

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