Retro-Dimroth rearrangement

For the retro-Dimroth rearrangement of a TP, apparently only one example has been found (70JPR254) 5-Amino-6-cyano-TP (24) under the influence of the unusual rearranging agent concentrated sulfuric acid leads to [4,3-a] derivative 25 (Scheme 12). The triazole ring is believed to be polyprotonated in this medium and to have its most nucleophilic site at N-4. 

Muehlstaedt et al. reported an unusual ring transformation in which the thermodynamically more stable 7-amino-6-cyano-l,2,4-triazolo[l,5-a]-pyrimidine (67) underwent an acid-catalyzed retro-Dimroth rearrangement to the thermodynamically less stable 7-amino-6-carboxamido-l,2,4-tria-zolo[4,3-a]pyrimidine (115) (70JPR254). The structure of this product was confirmed by comparison with authentic material obtained (70JPR254) from the acid hydrolysis of the known 7-amino-6-cyano-l,2,4-triazolo[4,3-a]pyrimidine (66) (Scheme 48). 

The reaction of triazoles 46 and 51 with NaOH gave 47 and 48, respectively. The later triazoles were formed by the reaction of 49 with NaOH or NaOH in H202, respectively. When the [l,5-r/]triazole 49 was treated with H2S04, it afforded surprisingly the [4,3-a] isomer 50 and not the amide 47 because a retro-Dimroth rearrangement happened (70JPR254) (Schemes 13, 14, and 15). 

When 5-methylthio-7-amino-l,2,4-triazoIo[l,5-c]pyrimidine 65 was heated in hydrazine hydrate, 5-hydrazino-7-amino-l,2,4-triazolo[l,5-c]pyrimidine 66 was obtained and 66 underwent rearrangement to give isomer 67 (79KGS262). This a rare example of the retro-Dimroth rearrangement (Scheme 20). 

In only one case has a retro-Dimroth rearrangement of l,2,4-triazolo[l,5-c] to [4,3-c]pyrimidine been reported, according to which the 7-amino-5-hy-drazino-l,2,4-triazolo[l,5-c]pyrimidine 76 gave the respective [4,3-c] isomer 77 (79KGS262). 

An aq. soln. of l-methoxy-N6,9-dimethyladenine perdilorate passed through a column of Amberlite IRA-402 (HCOg"), eluted with water, the eluate coned, in vacuo, refluxed 0.5 hr., adjusted to pH 10 with aq. NH3, and again refluxed 40 min. N-methoxy-l,9-dimethyladenine. Y 71%. - This rearrangement is part of a multi-step sequence to achieve a retro-Dimroth rearrangement. T. Fujii et al., Chem. Pharm. Bull. 22, 2211 (1974). 

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