Of condensed 1,2,4-triazolo

The other three chapters in the present volume all deal with bicyclic heterocycles. Dr. H. K. Pujari of Kurukshetra University in India describes condensed 4-thiazolidinones, and Professor M. A. E. Shaban and A. Z. Nasr of Alexandria University in Egypt survey the synthesis of condensed 1,2,4-triazolo heterocycles. Finally, Professor T. A. Crabb of Portsmouth, England has covered saturated bicyclic 6/5 ring-fused systems with a bridgehead nitrogen and a single additional heteroatom. None of these groups of bicyclic heterocycles has been comprehensively reviewed before. 

An overview on condensed 1,2,4-triazolo[3,4-z]heterocycles has appeared in which the synthesis of numerous condensed tricyclic systems has been reported <90AHC(49)277>. 

Orthoesters can be used for the synthesis of condensed 1,2,4-triazines, provided the appropriate N-N-C-C-N fragment with terminal amino groups is donated by another reactant. For instance, l-amino-5-arylaminomethyl-l,2,3-triazoles 283 were shown to react with triethyl orthoformate to give the intermediate dihydro compounds 284, which can be oxidized with cerium(iv) ammonium nitrate into the corresponding triazolo-[5,iy][l,2,4]-triazine 285. It is worth noting that aromatization of 284 is accompanied by elimination of the iV-aryl group (Scheme 170) <1996JHC599>. 

Several polyheterocyclic compounds containing a condensed 1,2,4-triazole nucleus, such as 3,5-disubstituted thiazolo [2,3-r][ 1,2,4] triazoles, are thermostabilizers for polypropylene and polycaproamide <2003MI2>. Triazolo[3,4-A][l,3]benzothiazoledicarbonitrile derivatives are used to prepare hexazocyclanes-fluorophores as active media for liquid and solid lasers, scintillators, and for transformation of short-wave radiation to long-wave radiation <2004RUP2238276>. 

An example of synthesis A is that of 5-methyl-1,2,4-triazolo[l,5-a] pyrimidin-7-on (MOT) (3) by Bulow and Haas (09CB4638) given in Scheme 1. This reaction is a pyrimidine synthesis The C3-synthon condenses with a N—C—N moiety, which is a part of an AT. Apparently the reaction passes through the nonisolable intermediate 2 (Section II,A,2). 

Similarly, cyclization of 3-amino-l, 2,4-triazoles (65) with methyl propio-late or methyl phenylpropiolate gave a mixture of the l,2,4-triazolo[4,3-a]pyrimidin-7-ones 97 and the l,2,4-triazolo[l,5-a]pyrimidin-7-ones 98 (70CB3266 71CB2702). In addition, methyl tram-3-(3-amino-l,2,4-triazol-l-yl)acrylates (99) were also obtained. Production of the 1,2,4-triazolopy-rimidines 97 and 98 started by condensation of the ester function with the amino group of 65, followed by cycloaddition of the triazole N4 or N1 of the two tautomeric intermediates 96a and 96b, respectively, onto the carbon-carbon triple bond of the side chain. In contrast, formation of the triazolyl acrylates 99 took place through addition only of the triazole N1 onto the propiolate carbon-carbon triple bond. The relative amounts of products were found to depend on the reaction conditions (temperature, solvent, and time) (70CB3266) (Scheme 42). 

On heating the condensed [l,2,4]-triazolo[4,3- ]pyridazine-6(577)-one-3(27/)-thione 91 with dialkyl acetylenedi-carboxylates in DMF, the subsequent ring transformations yielded the novel tetracyclic 1,3-diazepine cis-92, which can further be converted to 93 in a number of steps involving elimination, decarboxylation, and cyclization oxidation upon heating (Scheme 15) <2001T7191>. 

A possibility of formation of 5,7-diaryl-4,7-dihydro-1,2,4-triazolo[l,5-a]pyr-imidines 182 in reactions of 3-amino-l,2.4-triazole 147 with synthetic precursors of unsaturated ketones—aldehydes 179 and ketones 180—or in condensation of acetophenones 180 and azomethynes 183 was established in [176, 177]. It was shown that in the first case the multicomponent procedure was not an independent method but resulted in the initial formation of unsaturated ketones 181 themselves and their further reaction with aminoazol (Scheme 3.53). 

The condensation of 3-(substituted)-l,2,4-triazoles with an A-cyanocarbonimidate at high temperatures gives (1,2,4]triazolo 1,5-a [ 1,2,3]triazines (34) which are converted to other such products by standard metatheses. At lower temperatures l,2,4Jtriazolo[4,3- ][l,3,5]-triazines (35) can also be obtained which rearrange to the more stable (1,5-a] isomers on heating. Cyclisation of the hydrazides (36) also leads to [1,5-a] fiised triazines (Scheme 20) [95JCS(P1)801],... 

A efficient three-component solution-phase condensation of a 3-amino-5-alkylthio-1,2,4-triazoles with an aromatic aldehyde and an acetoacetamide was developed by Qiebanov and co-workers [100] for the rapid synthesis of 7-ary 1-2-alkylthio, 7-dihydro-1,2,4- triazolo[l,5-a]pyrimidine-6-carboxamides 54. All reactions were completed within 5 min of microwave irradiation at 120°C and provided the desired dihydroazolopyrimidines 54 in high yields and with excellent purities. The cyclocondensation reactions were performed in ethanol and a significant decrease of the product yield was observed when switching the solvent to acetic acid or DMF or when an acidic catalysts was added (Scheme 40). 

Condensations of 1,3-dicarbonyl synthons (99JCS(P1)1527) or equivalents (e.g., 33 or 34b) (99CHE708) and 4-substituted ATs provide an approach to quaternary 1,2,4-triazolo[l,5-a]pyrimidinium salts substituted onto N-3, such as 32 and 35 (Scheme 10). 

The condensed 1,2,4-triazole ring of 577 was formed as a result of condensing the jS-D-ribofuranosylcarbodithioate 512 with 2-hydrazino-4-hydroxy-6-methylpyrimidine. Unlike the l,2,4-triazolo[l,5-c]pyrimidine analog 568, the l,2,4-triazolo[4,3-fl]pyrimidin-3-yl C-nucleoside 577 did not undergo Dimroth rearrangement (89MI5) (Scheme 154). 

Condensation of 3,6-dichloropyridazine with hydrazides, best with microwave heating, produces [1,2,4] triazolo[4,3- ]pyridazines, in which the remaining chlorine can be displaced with amines. ... 

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