Fused-1,3-triazole systems

Pyranopyridines. The chlorobenzopyranoquinolone 325 reacts with hydrazides to give a triazole-fused ring system, such as in compound 326. Likewise, reaction with sodium azide gives the tetrazolo-fused product 327 (Scheme 79) <2003IJB2567>. 

Several interesting 1,2,4-triazole fused-ring systems have been reported. A facile synthesis of 3,5-dihydro-677-imidazo[l,2-fc]-l,2,4-triazol-6-ones 162 was obtained by an iminophosphorane-mediated annulation <06EJ04170>. 8-Trifluoromethyl-l,2,4-triazolo[4,3- >]pyridazines 163 has been prepared from 4-trifluoromethyl-4,5-dihydropyridazin-3-one... 

In view of the nature of this edition as a whole, the content of this chapter is restricted to describing the chemistry of monocyclic 1,2,4-triazole systems. Readers are directed to the relevant chapters elsewhere in this edition for details of the chemistry of fused heterocyclic systems that contain a 1,2,4-triazole moiety examples of fused systems are only cited in this chapter where relevant. 

Fused heterocyclic systems derived from 3-mercapto-l,2,4-triazole can be obtained by heterocyclization of 4-allyl-l,2,4-triazole-3-thione derivatives by treatment with halogens or mineral acids <1996T791>. Compounds 342 react with bromine yielding thiazolium halides 28 in good yield (Equation 64) <2000RJOC1033>. 

The same type of ring-closure reaction that leads to the [3,2- ]-fused 50 can also result, in principle, in formation of a [3,4- ]-fused ring system (see Sections 11.16.5.2 and 11.16.7). This case has been found when an amino group was present in the triazole ring, and formation of 51 has been supported by X-ray diffraction. The crystalline structure... 

Ring opening of also a fused [l,2,4]triazole system by secondary amines has been reported. Chupakhin et al. described that 5-methyl-6-nitro[l,2,4]triazolo[l,5-r ]pyrimidin-7(8/f)one 122 underwent ring opening when treated with various secondary amines to yield pyrimidyl ureas 123 in medium to good yield <2001IZV655>, as shown in Scheme 14. 

In this section, synthesis of benzologues of various triazolopyrimidines discussed in Sections 11.16.6.6.1-11.16.6.6.3 is summarized. Because of the heteroatom arrangements, benzologues of these three kinds of fused triazoles can have either linearly ( -fused quinazole) or angularly fused (tf-fused quinazole) ring systems. Recent synthetic work on fused [l,2,3]triazolo[l,5- ]quinazoles is shown in Scheme 62. 

Reaction of 4-aminotriazole-5-carboxamide and 4-amino-5-phenyl-triazole with acetylacetone and piperidine gives a different type of fused triazole, the t>-triazolo[3,4-a]p5Timidine system (Scheme 48). 

Numerous structures containing the thiocarbonyl ylide dipole are conceivable. Incorporation of the thiocarbonyl ylide dipole into a bicyclic heterocyclic system is possible by the conversion of the cyclic thione (203) into the ring-fused mesoionic system (204). The thiocarbonyl ylide dipole (205) undergoes cycloaddition with both alkenic and alkynic electron-poor dipolarophiles in refluxing benzene or xylene so that, after extrusion of hydrogen sulfide or sulfur, respectively, from the initial 1 1 cycloadducts (206) and (207), a ring-fused pyridinone is formed. The method has been used for the annelation of pyridinones to the imidazole, 1,2,4-triazole, thiazole and 1,3,4-thiadiazole systems... 

Two reviews cover the first 70 years of the chemistry of 1,2,4-triazoles (61CRV87) deals not only with the simple triazoles discussed in this Chapter but also with their fused polynuclear systems (see Chapter 4.15) (B-61MI41200) considers both s- and u-triazoles (for the latter see Chapter 4.11). 

Methods of this type are best considered as reactions of the fused ring-systems in question (see Chapter 4.15). The example illustrated in Scheme 91 is of potential interest in pharmacology (75T1363, cf. 74CPB1938). The conversion of the 1-aminoadenosine (192) into the imidazolyltriazole (193) amounts to triazole formation from an amidrazone intermediate and a formyl group derived from the pyrimidine moiety. 

Other triazole syntheses by hydrazinolysis, hydrolysis or oxidation of fused ring systems are briefly treated in (81HC(37)l). 

Of about 300 publications dealing with the synthesis of mono-, di- and tri-alkyl- or aryl-triazoles, 76% establish the functions by method (i), 18% by (ii) and 6% by (iii) (i) is broken down further into 63% for amidrazone methods, 3% for 1,3-cycloadditions and 16% for other procedures, mainly the cleavage of fused ring systems. This rough analysis will be modified if extended to include current and future references but it may serve as a heuristic guide for those intending to devise triazole syntheses. 

In addition to the rearrangement of the [4,3-a] systems into the [1,5-a] analogs in a Dimroth process (70X3357), several methods have been employed for this series of compounds, often viewed as 5-azapurines. In one case, the 5,7-dimorpholino derivative (363) was synthesized by treating the oxime derivative (364) with polyphosphoric acid (74JOC2143). This method has been used extensively for fused triazoles and is described in many sections of this chapter for other ring systems. 

Suitably functionalized phenyl isothiocyanates (e.g. 127) have been used as starting materials for the synthesis of this fused heterocyclic system the rest of the skeleton is provided by acid hydrazides [74JOC3506 75GEP(O)2509843 79H1I71], The intermediate l-acyl-4-arylthiosemi-carbazides (128) and 3-mercapto-1,2,4-triazoles (129) underwent base-catalyzed cyclization to ],2,4-triazolo[3,4-a]l,3-benzothiazoles 130. 

Without considering their use as synthons in preparations of fused ring systems and compounds with mixed heterocyclic portions, 1,2,4-triazoles find synthetic uses in four kinds of reaction. 

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