1.2.4- Triazoles fused-ring systems

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... 

Structurally unique 1,2,4-triazole fused-ring systems were reported. Parent names and references of the scaffolds are shown below. 

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>. 

Three major routes to the v-triazole-fused ring system (38) have been published. Reaction of (195) with ) -diketones leads to the neutral product (196) (Equation (50)) <83JHC735>, whereas oxidative... 

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... 

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. 

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. 

Attempts to synthesize l,2-diazacycl[3.2.2]azines (l,2,4-triazolo)[3,4,5-ti/]indolizines, for example, 337, have met with very limited success. To date the ring system is known only when fused on its ef-faces to a cycloheptatriene ring (see Section 12.16.6.4). It may be that the 1,2-diazacyclazine system is more strained than that of the parent cyclazines, since the N-N bond of the triazole ring is expected to be shorter than a C-C or C-N bond. Similarly, all attempts to form the N-N bond as the final step in a synthesis of the 1,2,4-triazacyclazine ring system, 359, have been unsuccessful <1987J(P1)1159>. 

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... 

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. 

Mercapto-4-amino[l,2,4]triazole can also be transformed to derivatives of the title ring system by 1,3-dioxo reagents. These transformations are summarized in Table 6. In most of these cases, 5,5-dimethylcyclohexane-l,3-dione was used, and, accordingly, this procedure can lead to some cyclohexenyl-fused derivatives. 

Three different ring systems with 3-fusion of the [l,2,4]triazine ring (a fused thiadiazole and two different triazoles) have been described during the past period. 

Ring contraction reaction of the benzthiazolo[2,3-f][l,2,4]triazin-one derivative 95 has been reported by Kuberkar et al. <2005JCM632> (Scheme 13). This compound when heated in aqueous sodium hydroxide underwent ring opening and a subsequent ring closure to result in formation of the fused [l,2,4]triazole ring system 96 in good yield (60%). 

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