7-Hydroxy-1,2,4-triazolo pyrimidine

According to the systematic nomenclature these substances were first named l-f-triazolo[d] pyrimidines in compliance with the general principles of the Ring Index/ More recent papers and Chemical Abstracts indexes use the term i -triazolo[4,5-d]pyrimidine (147) in accord with the lUPAC nomenclature. The numbering of substituents when using the last-mentioned name is different from that of the 8-aza analogs. For the formulas of oxygen and sulfur derivatives names derived from the lactim or thiolactim form are almost exclusively in use (in common with the purine derivatives). These derivatives are thus described as hydroxy and mercapto derivatives, respectively. The name 1,2,3,4,6-pentaazaindene is used only rarely for this system. 

The examples in the fourth column (Table IX) concern the protonation of purine and adenine and their derivatives while those of the last column mainly reflect Kleinpeter s contributions (Table VIII) to the functional tau-tomerism of 7-hydroxy-l,2,4-triazolo[l,5-a]pyrimidines. 

Likewise, l-[4-methylbenzyl]-4,7-dihydroxy-l,2,3-triazolo[4,5-d]pyridazine 275 reacts with phenylhydrazine, HMDS 2, and (NH4)2S04 to give the monoamino product 276 in 60% yield [83]. Reaction of l-benzyl-3-n.-butyl-4-hydroxy-l,2,3-triazo-lo[4,5-d]-pyrimidine 277 for 8 h at 120°C with cyclopentylamine, HMDS 2, and (NH4)2S04 affords the aminated product 278 in 49% yield [84] (Scheme 4.33). 

Some interesting fused 1,2,3-triazole ring systems have been reported. A series of 5-piperidyl-substituted 7-hydroxy-3f/-l,2,3-triazolo[4,5-d]pyrimidines 143 has been synthesized from pipecolinate esters, benzylazides, and cyanoacetamide <06CHE246>. 4-Alkylidene-5,6-dihydro-4//-pyrrolo-[l,2-c][l,2,3]triazoles 144 were prepared from alkylidenecyclopropanes via diiodogenation/Cu(I)-catalyzed 1,3-dipolar cycloaddition/intra-molecular Heck reaction sequence <06SL1446>. 6,6-Dimethyl-2-phenyl-4,5,6,7-tetrahydro-27/-benzotriazol-4-one 145 were prepared from A-(5,5-dimethyl-3-oxocyclohexenyl)-S,S-diphenylsulfilimine and... 

Kleinpeter et al. carried out ab initio and semi-empirical (PM3) calculation in order to rationalize the tautomeric equilibria of 7-hydroxy-5-methyl[l,2,4]triazolo[l,5- ]pyrimidine <1995JST(335)273, 1997JST(435)65>. This compound can exist in four tautomeric forms a-d (Figure 1). The authors concluded that the high computational level available can sufficiently reproduce the position of tautomeric equilibria in solution and, thus, can serve as a useful tool instead of time-consuming experimental studies. 

Figure 1 Tautomeric forms of 7-hydroxy-5-methyl[1,2,4]triazolo[1,5-a]pyrimidine.

Ethyl 2-(3-pyridyl)-7-hydroxy-1,2,4-triazolo[ 1,5-a ]pyrimidine-6-car-boxylate was obtained in the reaction of 3-amino-5-(3-pyridyl)-1,2,4-triazole and EMME in boiling acetic acid for 4 hr in 22% yield [89IJC(B)242]. 

A(nino-a-vic-triazolo-[d]-pyrimidin-5 ol 7-Am ino-5 hydroxy-1H-1,2,3-tr ia zolo-[d]-pyrimi-dine or 7-Amfno-5-hydroxy-lH-l,2,3-triazolo-[d]-4,6-diazine, N=C(NHa)-C-NH-N. Its... 

Heating 5-hydroxy-3-mercapto-7-phenyl-1,2,4-triazolo[4,3-a]pyrimidine (145) with aniline gave the 2-anilino-4-hydroxy-6-methylpyrimidine (144)... 

C-Alkyl-l,2,4-triazolo[4,3-a]pyrimidines are distinguished from their respective [l,5-a]isomers by their UV absorption at longer wavelength. The UV spectra (at pH 2 and pH 10) have been used to differentiate the isomeric 5- and 7-hydroxy-l,2,4-triazolopyrimidines this differentiation may be confirmed by the IR stretching frequency of the CO group. The isomeric A-alkyl-l,2,4-triazolopyrimidines are more readily distinguished by their IR spectra (68T2839). H and 13C NMR and UV spectroscopy have been... 

A one-pot synthesis of 3,5-disubstituted 7-hydroxy-3//-l,2,3-triazolo[4,5-d]pyrimidines (130) has been carried out by using benzyl azide, cyano-acetamide, ethyl or methyl esters of the appropriate carboxylic acid, and sodium ethoxide as catalyst. The reaction proceeds via a 5-amino-l-benzyltriazole-4-carboxamide intermediate (85JHC1607). 7-Amino-3H-l,2,3-triazolo[4,5-d]pyrimidines 133 (R2 = H) were prepared starting from benzyl azide, malononitrile, and an aliphatic or aromatic nitrile, or by reaction of 130 with phosphorus oxychloride followed by amination. Compound 132 was formed in most reactions from two molecules of the 5-amino-4-cyano-l-benzyltriazole intermediate by an intermolecular nucleophilic at-... 

A number of 5- and 7-monosubstituted and 5,7-disubstituted [l,2,4]triazolo[l,5-a]pyrimidines have resulted from reactions on the 5,7-dihydroxy, -aminohydroxy and -hydroxymercapto derivatives. The hydroxy derivatives were amenable to chlorination which was followed by a variety of nucleophilic substitution reactions or hydrogenolyses. The mercapto groups were susceptible to alkylation and subsequent nucleophilic substitution (61CPB801,63CPB845). 

A tandem aza-Wittig/heterocumulene-mediated annulation route was developed for the efficient production of 6,7,8,9-tetrahydro-benzothieno[2,3-r/]-l,2,4-triazolo[l,5-a]pyrimidin-10(3F/)-ones <05S1601>, and an amine oxide rearrangement was key to the regioselective preparation of pyrrolo[2,3-J]pyrimidines <0581164>. Hexahydro-2-phenacylidene-pyrimidines gave -lactam fused 8-aroyl-2,3,4,5-tetrahydro-7-hydroxy-6//-pyrrolo[l,2-a]py-rimidine-6-ones when treated with (COCl), in the presence of NaH <05IJH87>, and methyl... 

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