1.2.4- Triazolo pyrazine. rearrangement

Ring contractions of six- or seven-membered fused systems have sometimes been used to synthesize azapentalenes. Taylor et a/.158 found that triazolo[4,3-a]pyrazines (164) rearrange in acid to imidazotriazoles 165 following initial fission of the six-membered ring at the point shown (164). The kinetics,58b of this reaction have revealed the intermediacy of covalently hydrated species. 

Dihydro-2iT-thiazolo[2,3-c][l,2,4]triazine-3,4-dione rearranges in dilute base to give an unstable acid which decarboxylates on acidification of the sodium salt to give 5,6-dihydrothiazolo[2,3-c]-s-triazole (equation 68) (81CB1200). Kinetic evidence has been put forward in favor of covalently hydrated intermediates in the acid-catalyzed rearrangement of triazolo[4,3-a]pyrazines to 1H-imidazo[2,1 -c]-s-triazoles. The intermediate triazole has been isolated and characterized (equation 69) (72JCS(P2)4). 

As will be described in the synthesis section, [l,2,4]triazolo[4,3-a]pyrazines can be induced to rearrange to their [1,5-a] isomers in basic or acidic solution (7UHC643). On the... 

For example, when 5,8-dimethyl-[l,2,4]triazolo[4,3- ]pyrazine was refluxed with 10% sodium hydroxide solution for 60 hours, a 20% yield of the isomeric 5,8-dimethyl-[l,2,4]triazolo[l,5-a]pyrazine was obtained. No rearrangement occurred in acid or under the influence of heat (68JHC485). The poor yield obtained in this isomerization may be due to two factors (i) electronic deactivation and steric crowding caused by the 5-methyl group and/or (ii) the great tt-electron density associated with C-5 (as determined by HMO calculations) for [l,2,4]triazolo[4,3-a]pyrazines in general (68JHC485). 

The 1,2,4-triazolo[4,3-fl]pyrazine system underwent rearrangement to the isomeric l,2,4-triazolo[l,5-fl]pyrazine system, although in poor yield (66JOC265). 

The l,2,4-triazolo[4,3-a]quinoxaline system failed to undergo rearrangements (66JOC265) similar to those found with 1,2,4-triazolopyridines, -pyrazines, and -pyrimidines. 

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