Triazoles, from rearrangement

Examples of the Dimroth rearrangement (Section IV, F) include several s3mtheses of monocyclic triazoles from other heterocyclic systems (cf. Scheme 25). Triazole-5-thiols can be prepared by treatment of 5-amino-l,2,3-thiadiazoles with bases.A similar base-induced rearrangement of sydnoneimines provides a synthesis of 4-hydroxy-triazoles. ... 

Examples include the synthesis of 3-amino-l,2,4-oxadiazoles starting from 3-acylamino-5-methyl-l,2,4-oxadiazole <2002H811> and 2-aryl-l,2,3-triazoles from l,2,4-oxadiazole-3-ketone arylhydrazones <1999T12885, 2006JOC5616>. Oximes, hydrazones, formamidines, and thioureas of the furazan series also undergo base-catalyzed mononuclear rearrangements <2004RCB1121>. Nucleophilic attack at N(3) takes place in the benzofuroxan series. For example, reaction with secondary amines leads to o-nitroarylhydrazines (Scheme 55). 

In the case of some fused [l,2,4]triazoles, Dimroth rearrangements to the appropriate isomeric ring systems have been observed. Thus formations of (16) from (15) <84JCS(Pl)993>, (20) from (21) <90JCS(P2)1943>, and (32) from (30) <82JHC1345> have been reported. These transformations are also discussed in the respective sections on synthesis. 

Tosylamino-l,2,3-triazoles from 1-aminothioenolethers via Dimroth rearrangement 4-Acy 1-5-tosy lamino-1,2,3-triazoles... 

The reaction of Af-arylsulfonyl azides with terminal alkynes often leads to the formation of products resulting from rearrangement or loss of nitrogen, However, using copper iodide and 2,6-lutidine (1.2 equivalents) in chloroform at 0 °C affords the l-arenesulfonyl-1,2,3-triazoles 13". ... 

Abstract Although the synthesis of 1,4- or 1,5-disubstituted 1,2,3-triazoles has been popularized by the recent developments of metal-catalyzed 3-1-2 cycloaddition of organic azides and terminal alkynes, the preparation of 1,4,5-trisubstituted triazoles is less popular. The focus of this chapter is the synthesis of these heterocycles, using condensation reactions and rearrangements, selective preparation of trisubstituted triazoles from disubstituted precursors, and formal [3-1-2] cycloaddition reactions involving internal alkynes. 

In the present review, preparation of 1,2,3-triazoles with substituents at positions 1, 4, and 5 has been divided into three parts condensation reactions and rearrangements, selective preparation of trisubstimted triazoles from disubstituted precursors, and formal [3+2] cycloaddition reactions involving alkynes (Fig. 2). Fused polycyclic 1,2,3-triazoles are out of the scope of this review. For simplicity, all the triazoles described in this review will be 1,2,3-triazoles and will be called triazoles. ... 

Within the huge field of heterocyclic rearrangements [53], the Dimroth rearrangement gives 5-mercapto-l,2,3-triazoles from 5-amino-l,2,3-thiadiazoles and allows interconversion of 5-amino-l,2,3-triazoles into a mixture of isomers under basic condition [54]. Thus, this reaction, discovered in 1909, involves a linear intermediate that can cyclize into two isomeric compounds (Scheme 15) [55]. This ring-chain tautomerization is reversible, but the equilibrium can be pushed toward an end if one of the two isomers is stabilized. 

Hydrazine hydrate is known to react with acetonitrile in the presence of sulfur or ethanol to form 4-amino-3,5-dimethyl-l,2,4-triazole or 3,6-disubstitued-l,2-dihydro-l,2,4,5-tetrazines. The initial product, which is disubstituted l,2-dihydro-l,2,4,5-tetrazine, is readily oxidized to the pink colored 1,2,4,5-tetrazine it may also rearrange at elevated temperature or on treatment with an acid to the corresponding 1,2,4-triazole. The triazole compound is obtained by the reaction of hydrazine hydrate and acetonitrile in the presence of CO2. The presence of CO2 in the formation of the six-membered ring intermediate is essential, and has been confirmed by repeating the experiments in the absence of CO2. However, the exact role of CO2 in this reaction is not clear. Figure 6.1 gives a possible mechanism for the formation of the triazole from hydrazinium hydrazine carboxylate and acetonitrile. 

Cyanopyrazole is obtained from treatment of 4-amino-3-halopyridazines with potassium amide in liquid ammonia, while 4-amino-3,6-dihalopyridazines are rearranged under the same conditions to 3-cyanomethyl-l,2,4-triazole. 

The 1-azirines obtained from the vapor phase pyrolysis of 4,5-disubstituted 1-phthalimido-1,2,3-triazoles (157) have been found to undergo further thermal reactions (71CC1S18). Those azirines which contain a methyl group in the 2-position of the ring are cleaved to nitriles and phthalimidocarbenes, whereas those azirines which possess a phenyl substituent in the 2-position rearrange to indoles. 

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... 

Another example of this rearrangement has been used to prepare 1,2,3-triazole 146 from furazanic phenylhydrazone 147 (Scheme 84) [93JCS(P1)2491]. Interestingly, furoxanic Z-phenylhydrazones 150 underwent thermal recyclization to 1,2,3-triazole A-oxides 152, evidently through intermediate 151. Treatment of the hydrazone 150 with rerr-BuOK leads to the nitromethyl derivative 149 [OOOMIl] (Scheme 84). Lead tetraacetate oxidation of 147 with subsequent Lewis acid treatment of the initially formed intermediate afforded indazole 148 (Scheme 84) (85JHC29). 

The lH-l,2,4-triazole compounds possess important pharmacological activities such as antifimgal and antiviral activities [18-20]. In the present study, the reactive intermediates 45a-c, prepared in situ from the dichlorides 44a-c, were reacted via the cycloaddition reaction with ethyl cyanoacetate 40 to give, after spontaneous rearrangement, the triazole hydrazides 41a-c. These compoimds were used as starting materials for the synthesis of the... 

Other non-traditional preparations of 1,2,3-triazoles have been reported. The rearrangement in dioxane/water of (Z)-arylhydrazones of 5-amino-3-benzoyl-l,2,4-oxadiazole into (2-aryl-5-phenyl-27/-l,2,3-triazol-4-yl)ureas was investigated mechanistically in terms of substituents on different pathways <06JOC5616>. A general and efficient method for the preparation of 2,4-diary 1-1,2,3-triazoles 140 from a-hydroxyacetophenones 139 and arylhydrazines is reported <06SC2461>. 5-Alkylamino-] //-], 2,3-triazoles were obtained by base-mediated cleavage of cycloadducts of azides to cyclic ketene acetals <06S1943>. Oxidation of N-... 

Azide 367 is prepared from 4-r -butyl-2-nitroaniline in 76% yield by its diazotization followed by treatment with sodium azide. In a 1,3-dipolar cycloaddition with cyanoacetamide, azide 367 is converted to triazole 368 that without separation is directly subjected to Dimroth rearrangement to give derivative 369 in 46% yield. Reduction of the nitro group provides ortfc-phenylenediamine 371 in 91% yield <2000EJM715>. Cyclocondensation of diamine 371 with phosgene furnishes benzimidazol-2-one 370 in 39% yield, whereas its reaction with sodium nitrite in 18% HC1 leads to benzotriazole derivative 372, which is isolated in 66% yield (Scheme 59). Products 370 and 372 exhibit potassium channel activating ability <2001FA841>. 

Azides 1253 obtained from propargyl halides or sulfonates 1252 undergo sigmatropic rearrangement to azidoal-lenes 1254, which subsequently undergo cyclization to triazafulvenes 1255. Under the reaction conditions, species 1255 react with another molecule of sodium azide to furnish triazoles 1256. Products 1256 are isolated in 65-97% yield (Scheme 209) <2005S1514>. 

X-Ray analyses of azapentalenes have been used to determine the structure of products from reactions with ambiguous reaction sites or with concomitant rearrangements. Thus, the X-ray structure of the /3-D-[l,2,4]triazolo[4,3-3][l,2,4]triazole 2 establishes that glycosylation has occurred at the N-l position furthermore, it also shows that the compound is the ft-anomer. In addition to intermolecular hydrogen bonds in the crystal structure an intramolecular hydrogen bond is extended from OH-5 to N-7 <1984NN187>. The X-ray structure of the inner salt of compound 1 has been determined... 

In the presence of various metal ions, 2-(fluoroenone)benzothiazoline has been found to rearrange to A-2-mercaptophenylenimine, while a free radical mechanism involving the homolysis of C-S and C-N bonds has been invoked to explain the formation of 3-phenyl-1,2,4-triazole derivatives from the thermal fragmentation and rearrangement of 2-(arylidenehydrazino)-4-(5//)-thiazolone derivatives. The cycloadducts (36) formed from the reaction of 3-diethylamino-4-(4-methoxyphenyl)-5-vinyl-isothiazole 1,1-dioxide (34) with nitric oxides or miinchnones (35) have been found to undergo pyrolytic transformation into a, jS-unsaturated nitriles (38) by way of pyrrole-isothiazoline 1,1-dioxide intermediates (37). 

Amino-cephalosporin sulphones, generated in situ from the appropriate 7-/3-fBoc-amino derivatives (374) and diazotized in a one-pot reaction in aqueous HC104-Me0H-NaN02, have been shown to rearrange exclusively to triazoles (375). The multi-step process postulated for this transformation is shown in Scheme 112. 

Interesting synthetic applications of these degenerate rearrangements are the preparation of l-alkyl-4-formyl-l,2,3-triazole 110 from l-phenyl-4-... 

Imines derived from ketones with an a-methylene group can react via their enamine tautomers, and mixtures of triazoles are also isolated from these systems. The triazoline adducts of the enamine tautomers are aromatized by treating with acid, and in these conditions the triazoline appears to undergo a Dimroth rearrangement before elimination of the amine, because two triazoles are obtained, one of which has... 

From Other Heterocyclic Systems 4-Arylazoisoxazoles can rearrange to 2-aryltriazoles, and 4-amino-2//-triazoles can be prepared by reaction of 4-nitrosoimidazoles with hydrazines (Scheme 34). The hydrazones of 3-benzoyloxadiazoles are intermediates in the latter reaction.The generality of rearrangements of this type has been discussed, and a further example, involving the rearrangement of a 1,2,5-oxadiazole to a triazole, has been described. 

Very few 2/f-triazole syntheses involve azides, apart from those (such as 2-acetyl derivatives) which involve prior formation and rearrangement of IjEf-triazoles. Some vinyl diazides react with triphenyl-phosphine in mild conditions to give iminophosphoranes of 2-amino-triazoles (Scheme 36). ... 

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