1.2.4- Triazolo heterocycles,synthesis

Condensed thiophene systems, tetra- and pentacyclic, 32, 127 Condensed 1,2,4-triazines I. Fused to heterocycles with three-, four-, and five-membered rings, 59, 39 Condensed l,2,4-triazolo[3,4-z] heterocycles, synthesis, 49, 277... 

Synthesis, set also Heterocyclic synthesis and biological activities of condensed heterocycloln.m-tj, b, or cjquinazolines. 52, I and reactions of l-azirines, 13, 45 of condensed l,2,4-triazolo[3,4-z)heterocycles, 49, 277 by ring-closure of o-substituted t-anilines, 14, 211... 

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. 

Two types of addition to pyrimidine bases appear to exist. The first, the formation of pyrimidine photohydrates, has been the subject of a detailed review.251 Results suggest that two reactive species may be involved in the photohydration of 1,3-dimethyluracil.252 A recent example of this type of addition is to be found in 6-azacytosine (308) which forms a photohydration product (309) analogous to that found in cytosine.253 The second type of addition proceeds via radical intermediates and is illustrated by the addition of propan-2-ol to the trimethylcytosine 310 to give the alcohol 311 and the dihydro derivative 312.254 The same adduct is formed by a di-tert-butyl peroxide-initiated free radical reaction. Numerous other photoreactions involving the formation by hydrogen abstraction of hydroxyalkyl radicals and their subsequent addition to heterocycles have been reported. Systems studied include 3-aminopyrido[4,3-c]us-triazine,255 02,2 -anhydrouri-dine,256 and sym-triazolo[4,3-fe]pyridazine.257 The photoaddition of alcohols to purines is also a well-documented transformation. The stereospecific addition of methanol to the purine 313, for example, is an important step in the synthesis of coformycin.258 These reactions are frequently more... 

In 1981 we published the first paper [22] on the synthesis of s-triazolo[4,3-a]pyridinium salts, 4, by the anodic oxidation of hydrazones 3 in the presence of pyridine (Scheme 5). In our working mechanistic scheme we proposed nitrilimine as the possible intermediate and pointed out that this reaction opens the door to a wide range of heterocyclic systems via anodic oxidation of aldehyde hydrazones through 1,3-dipolar cycloaddition reactions of the nitrilimine involved. 

Aminotriazoles which are appropriately substituted at the C(5)-position are important intermediates for the synthesis of 8-azapurines. These reactions have been reviewed <86AHC(39)ll7>. The pharmaceutically useful acyclonucleosides bearing 1,2,3-triazolines and 8-azapurines have been synthesized <888879). 4,5-Diaminotriazoles react with 1,2-dicarbonyl reagents to give 1,2,3-triazolo[4,5- )]pyrazines. 4,5-Diamino-2-phenyltriazole and sulfur monochloride afford the triazolo[4,5-c][l,2,5]thiadiazole (855) <86AHC(40)129>. The synthesis of triazolopyridines from triazoles has been described in a review <83AHC(34)79>. For further applications of substituted triazoles in preparations of complex heterocycles, see Section 4.01.4. 

Castle and co-workers <1996JHC119, 1996JHC185, 1997JHC1597, 1998JHC1441> used 3-chlorothieno [2,3-3]thiophene-2-carbonyl chloride 280 in the synthesis of the appropriate amides, which by oxidative photo-cyclization gave novel polycyclic heterocyclic ring systems thieno[3, 2 4,5]thieno[2,3-f][l,10]phenanthroline 281, thieno[3, 2 4,5]thieno[2,3-f]naphtho[2,iy ]quinoline 282 and thieno[3, 2 4,5]thieno[2,3-f]naphtho[l,2-g]qui-noline 283, thieno[3, 2 4,5]thieno[2,3-f]naphtho[l,2y ]quinoline 284, thieno[3, 2 4,5]thieno[2,3-f]naphtho[l,2 7]-[l,2,4]triazolo[3,4- ]quinoline 286, thieno[3, 2 4,5]thieno[2,3-f]naphtho[l,2-/]tetrazolo[l,5- ]quinoline 288, benzo[ ]thieno[3, 2 4,5]thieno[2,3-f]quinoline 285, benzo /]thieno[3, 2 4,5]thieno[2,3-f]quinoline 287, benzol/] thieno[3, 2 4,5]thieno[2,3-f]tetrazolo[l,5- ]quinoline 289, and benzo[/jthieno[3, 2 4,5]thieno[2.3-f][l,2,4]triazolo[4,3- ]-quinoline 290. 

When the synthesis of a heterocyclic system containing a diazole fused onto l,2,3-triazin-4-one (e.g., imidazo[4,5-i [l,2,3]tnazin-4-one (Section 10.13.9.1.l(i)) and pyrazolo[3,4-rf [l,2,3]triazin-4-one (Section 10.13.9.1.1(ii))) or 1,2,3-triazole fused onto pyrimidin-4(7)-(di)one (e.g., [l,2,3]triazolo[4,5-rf pyrimidin-4(7)-(di)one (Section 10.13.9.1.l(iv))) is required, the synthesis of the six-membered ring is the most reliable method. There are several recent accounts of six-membered annulations onto 1,2,3-triazoles to give [l,2,3]triazolo[4,5-r/ pyrimidines (Section 10.13.9.1.l(iv)), which are valuable alternatives to 1,2,3-triazole annulation using nitrosation techniques <1996CHEC-II(7)489>. 

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