Elimination 1,2,4-triazole ring

Animals. Rapidly absorbed and also rapidly and almost completely eliminated with urine and feces. Residues in tissues were generally low and there was no evidence for accumulation or retention of propiconazole or its metabolites. The major sites of enzymic attack are the propyl side-chain and the cleavage of the dioxolane ring, together with some attack at the 2,4-dichlorophenyl and 1,2,4-triazole rings... 

The triazol ring-opening reaction of the sulphoxides 97, 101 and 103 gave 2-sulphinylp5uidines, previously unknown. These reactions were performed with acetic acid or sulphuric acid as electrophiles. Treatment of 97 with aqueous sulphuric add gave alcohol 107 (95%) as a diastereoi-someric mixture, 5% d.e. (determined by NMR), and with acetic add the acetate 108 (89%, 7% d.e.) was obtained. Small quantities of the elimination product, the vinylpyridine 109 were also formed (Scheme 22). 

D-Xylose has been converted to (25)-3-(indol-3-yl)propane-l,2-diol 237 by two different routes, one involving direct Fischer indolization of 238. The dibenzyl-dithioacetal 239 was elaborated to the fused triazoline 240 following reaction with MCPBA. Initial oxidation was followed by elimination of acetic acid allowing intramolecular 1,3-dipolar cycloaddition reaction to construct the triazole ring. The bicyclic iV,S -acetals 242 and 241 were prepared by reaction of the 2,3-0-isopropylidene-D-ribofuranose with 2-aminoethane thiol followed by Mitsunobu reaction. These products are considered analogues of castanosper-mine and australine. ... 

This transformation starts with the addition of amine to C-5 of 94 resulting in the formation of the cr -adduct 96 (Scheme 62). Subsequent opening of the pyrimidine ring, rotation around C(4)-N(exo) in the intermediate 97, recyclization with participation of the triazole ring (97 98—>99), and elimination of HBr comprise the set of steps to form the final product 95. 

N-Condensed 1,2,4-triazole ring by elimination of sulfur dioxide... 

An interesting application of a phosphorus ylide in heterocyclic synthesis is in a ring annulation. The diazopyrazole (592) when treated with various phosphorus ylides gave the 3//-pyrazolo[5,l-c][l,2,4]triazole derivatives (593) with elimination of triphenylphosphine (79TL1567). 

Scheme 33 illustrates the difference in reactivity between triazolines obtained from cyclohexanone and cyclo-pentanone enamines. Thus, the reactions of azidophosphonates 239 with cyclohexanone enamines produce unstable aminotriazolines 240 that cannot be isolated due to their spontaneous elimination of amines to provide triazoles 241. Contrary to that, triazolines 242, derived from cyclopentanone enamines, are isolated in good yield (76-88%) and cannot be converted to the corresponding triazoles even by thermolysis <1995H(40)543>. Probably, introduction of a double bond between two five-membered rings would involve too much molecular strain. 

In a study on [l,2,4]triazolo[3,4-3][l,3,5]thiadiazines, mass spectral fragmentation of the 3-aryl-6-methyl derivative 33 (see Scheme 2) has been determined by Wang et al. <2001SC2841>. These authors found that elimination of the methylimine formaldehyde takes place first to form a thiazetidine ring 34 and, finally, removal of a CH2 group the 2-mercapto-5-aryl[l,2,4]triazole 35 can be observed. 

Several ring-closure reactions for [l,2,4]triazolo[3,4- ][l,3,4]thiadizines have been described, and all these procedures started from 3-mercapto-4-amino[l,2,4]triazole 135 (Scheme 26). A common structural feature of the reagents is the presence of the CH2X (X = halogen atom) moiety which allows the alkylation at the sulfur atom followed by a ring-closure reaction via an elimination step. Some typical ring closures are shown in Scheme 26. 

Since 1,4-dihydropyrazine itself is unknown, various substitutions of the ring system are required to produce stable isolable molecules. Carbonyl-stabilized 1,4-dihydropyrazines are synthesized by self-condensation of 3-chloromethyl-5,6-dihydro-l,5,5-trimethyl-2(l//)-pyrazinone <1998J(P1)289>. Another carbonyl-stabilized example is provided by WA -BOC-protected 1,4-dihydropyrazine 102, which can undergo Michael addition with nucleophiles such as 1,2,4-triazole, 3-formylindole, 4-bromothiophenol, benzylamine, or sodium methoxide to yield tetrahydropyrazines 103 (Scheme 26) <2004T8489>. Treatment of the di- and tetrahydropyrazines with trifluoroacetic acid leads to cleavage of BOC groups and/or elimination of the nucleophile to both afford dimethyl 2,5-pyrazinedicarboxylate 104. 

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