Triazole Rings

The equivalence of the inner NH protons (Sm = - 2.35) as well as correlation signals with the pyrrolic carbons only (5c = 143.8, 141.6, 139.8 and 136.7) provide evidence for the diaza[18]-annulene tautomer 4a. Two separate NT/ proton signals and cross signals with the a-carbon atoms (5c = 159.3) of the triazole ring are expected, in contrast, for the tetraaza[18]annulene tautomer 4b. 

For the preparation of triazolopyrimidines three main types of synthesis are in use. The first of these proceeds from a pyrimidine derivative (especially the 4,5-diamino derivatives) and closes the triazole ring. The second method proceeds, on the contrary, from derivatives of u-triazole to close the pyrimidine ring. The third method finally is one which yields the derivatives through substitution or replacement of substituents in compounds prepared by one of the first-named procedures. 

More interesting are the substitution reactions on the triazole ring where a characteristically different course can be expected from that of analogous reactions in the purine series. These reactions were studied in more detail only in connection with the preparation of the glycosyl derivatives, and the experimental material does not permit the drawing of general conclusions. 

Two interesting cases of quaternary salt formation are illustrated by compounds 88 and 90 (Z = CH) which contain fused quinoline and triazole rings. In these compounds both of the nitrogen atoms unique to the triazole ring possess lone pairs of electrons which are available for reaction. With compound 88 reaction occurs to give 89, but in... 

A. Synthesis by Annulation of the 1,2,4-Triazole Ring ONTO A Pyrimidine Structure... 

Assignment of the l,2,4-triazolo[l,5-c]pyrimidine structures to the products obtained from the previously described cyclizations and not the alternative [4,3-c] structures has been rationalized and corroborated on the basis of (a) preference of cyclization at the more nucleophilic triazole ring N2 rather than at its less nucleophilic N4 (65JOC3601 88JMC1014), (b) inability of the obtained products to undergo acid- or base-catalyzed Dimroth rearrangement, a property characteristic of the thermodynamically less stable [4,3-c] isomers (91JMC281), (c) comparison with unequivocally prepared... 

Triazole ring cleavage of the 7-amino-5-benzyl-5-mercapto-l,2,4-triazolo-[l,5-c]pyrimidinium iodide 135 at the N3-N4 bond occurred upon treatment with potassium carbonate to give the 4-amino-2-benzylmercapto-l-methyl-... 

Heteropentalenes with annelated imidazole or 1,2,4-triazole ring and one bridge nitrogen atom 98AHC(69)271. 

Arylsulfenyl azides in this reaction mainly give the product of the triazole ring opening 380, which is isomeric to the expected triazole 381 detected only in negligible quantities (72S571). 

Three elasses of triazoloquinolines may exist based on the fusion of the triazole ring on faee a, ij or j. This eould lead to eight isomerie eompounds as shown in Fig. 9. 

Insertion of a triazole ring in place of an imidazole ring is consistent in some cases with retention of antifungal activity. The synthesis of one such agent, azoconazole (64), proceeds simply by displacement of halide with 1,2,4-triazole. The route to terconazole (65) is rather like that to ketoconazole (34). ... 

Ribavirin, an antiviral agent used against hepatitis C and viral pneumonia, contains a 1,2,4-triazole ring. Why is the ring aromatic ... 

Cyclization of the hydrazone derivatives of 4-benzoyl[ 1,2,3]triazole 695 by reaction with one carbon inserting agent such as an orthoester, an aldehyde, a ketone, or a phosgene afforded triazolotriazine 696 or 697 (88JHC743). The newly created C—N bond displays particular sensitivity due to the electron-attracting effect of the triazole ring (Scheme 147). 

In [l,2,4]triazolo[4,3-a]pyrazine (174) bromination took place at the 5-position rather than in the triazole ring (77JOC4197). It was not possible to convert the 3-hydroxy derivative into the 3-chloro analogue (68JHC485). The isomeric [1,5-a] compound (175) was also brominated at C-5 (74TL4539), whereas its 7-oxide gave the 8-chloro derivative under Meisenheimer conditions [80JCS(P1)506]. 

The Cu(I)-catalyzed Huisgen [3 + 2] dipolar cycloaddition was also utilized by Van der Eycken and co-workers to obtain a new class of glycopep-tidomimetics based on the 1,2,3-triazole ring system 78 starting from glu-copyranosyl azide 75 and the pyrazinone compound 76 (Scheme 26) [58]. 

A few syntheses of the 1,2,4-triazole ring were reported in 1996. Treatment of the (1,1-dichloropropyl)azo compound 8 with SbCls gave the chloro-substituted allenium salt 9. This salt was found to undergo cycloaddition with MeCN to give a 76% yield of the 1,2,4-triazolium salt 10 <96S274>. Reaction of 3-[3-chlorophenyl]-l-[4-(3,4-... 

The triazole derivative, in turn, produces an intensely colored substance, III, with a diazonium compound under the experimental conditions devised for this analysis. The reactions leading to the formation of the colored substance have not yet been fully elucidated, but it appears that opening of the triazole ring as well as coupling is involved. The chemistry of the color formation will be discussed in another publication. 

Tetranitro derivative 90 (z-TACOT Section 12.10.15.5) treated with methanolic sodium methoxide at ambient temperature does not lead to simple product of nucleophilic substitution of a nitro group but provides compound 92. Its formation can be rationalized by introduction of the methoxy group into the 1-position, followed by scission of the remote triazole ring of 91 to give the final product. Compound 90 subjected to the vicarious nucleophilic substitution (VNS) conditions using either hydroxylamine or trimethylhydrazinium iodide gives a very insoluble red solid, which was identified as l,3,7,9-tetraamino-2,4,8,10-tetranitrobenzotriazolo[2,l- ]benzotriazole 93 (Scheme 5) <1998JOC3352>. 

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>. 

Structurally related to the xanthine series, a triazole ring was employed to tether either one of the two carbonyl groups of the xanthine with the side chain, resulting in two patent applications [89,90]. This... 

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