1.2.4- Triazole ring, construction

Chloromethyl-l,2,4-triazoles can be valuable intermediates in the synthesis of more complex compounds containing a 1,2,4-triazole moiety, and they can be accessed using a number of established methods for the synthesis of the triazole ring system. However, these processes often give variable yields and require much work to construct the starting material. A more convenient procedure has been developed, by which a hydroxymethyl-1,2,4-triazole is converted to the chloromethyl derivative by reaction with thionyl chloride (Equation 20 and Table 6) <2006S156>. 

The large increase in potency that is obtained by fusing an additional heterocychc ring onto the seven-membered ring of benzodiazepines is observed as well in the heterodiazepines. The required diazepinone (67-2) is prepared from the thiopheno-phenone (67-1) by exactly the same sequence as that used above. Construction of the fused triazole ring follows the method used for triazolam (Chapter 12). The... 

The 1,2,4-triazole ring of 2,3,5,6,7,8-hexahydro-l,2,4-triazolo[4,3-a] pyrimidin-3-ones (60) was constructed by cyclocondensation of the 1-ethoxycarbonyl-2-methylthio-l,4,5,6-tetrahydropyrimidine 58 with hydrazine (86JPR331), arylhydrazines [86H(24)93, 86KGS1350 88JPR753], or thiosemicarbazide (87KGS1540) (Scheme 24). 

The [l,2,4]triazolo[l,5- ]pyridine system is usually constructed by the closure of the triazole ring either by oxidative formation of the NN bond or by condensation of the N-aminopyridine derivatives . Various compounds 78 were obtained by the oxidation of the amidine 77 with Mn02 (Scheme 47) <2003IJB2901, 2005ARK(xiii)21>. A dehydrative cyclization by treatment of formamidoximes 79 with trifluoroacetic anhydride (TFAA) has been used in the synthesis of 80 (Scheme 48), which are key building blocks in the preparation of DPP (IV) inhibitors <2005EJ03761, 2006JME3614>. 

Wang s group constructed a coumarin library by using so-called click chemistry, which involves Cu(I)-catalyzed Husigen 1,3-dipolar cycloaddition of azides with alkynes to afford quantitative formation of a triazole ring under mild conditions.20 They prepared seven 3-azidocoumarin derivatives and one 4-azidocoumarin, each of which was reacted with 24 acetylenes (Fig. 18.5). 

D-Xylose has been converted to (25)-3-(indol-3-yl)propane-l,2-diol 237 by two different routes, one involving direct Fischer indolization of 238. The dibenzyl-dithioacetal 239 was elaborated to the fused triazoline 240 following reaction with MCPBA. Initial oxidation was followed by elimination of acetic acid allowing intramolecular 1,3-dipolar cycloaddition reaction to construct the triazole ring. The bicyclic iV,S -acetals 242 and 241 were prepared by reaction of the 2,3-0-isopropylidene-D-ribofuranose with 2-aminoethane thiol followed by Mitsunobu reaction. These products are considered analogues of castanosper-mine and australine. ... 

Advances in the construction of 1-monosubstituted 1,2,3-triazole ring 13CJ01884. 

The syntheses of 1,2,3-triazolium salts consists of two major steps, which are construction of the 1,2,3-triazole ring system and then its N-alkylation (Scheme 1). While l-amino-1,2,3-... 

Synthesis of this ring may be achieved by the construction of one of the heterocycles followed by using it as a basis to build the other ring onto it or by the Dimroth rearrangement of l,2,4-triazolo[4,3-a]pyrimidines. 1,2-Diaminopyrimidines are general precursors, and they can be generated from 1-amino or 2-aminopyrimidines. The 3- and 5-amino-l,2,4-triazoles are alternative precursors that can act as a source of three carbons to complete the pyrimidine ring. 

Triazolopyrimidine rings may also be formed by constructing the pyrimidine ring onto a preformed triazole. Reaction of ethyl acetoacetate with 3-amino-5-substituted-l,2,4-triazoles in glacial acetic acid led to the for-... 

Two strategies have been used to construct the pyrimidine ring onto a triazole structure in order to produce l,2,4-triazolo[l,5-c]pyrimidines ... 

The construction of a heterocyclic ring from two reagents, one of which contains a nitro group, is widely used in the synthesis of the nitro derivatives of pyrazole, isoxazole, and 1,2,3-triazole. Thus, for example, the reaction of sodionitromalonal-dehyde with substituted hydrazines leads to the corresponding derivatives of 4-nitropyrazole [33, 61, 471 173] (Scheme 63). 

The ring system to be destroyed may be constructed as a measure of synthetic strategy as illustrated (Scheme 92) by the preparation of a triazole (194) used to synthesize fused rings of pharmacological interest. The dihydroquinazoline (195) provides the amidrazone intermediate and the aromatic substituent required (75JHC717). 

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