Syntheses from Triazoles

Other 4,5-disubstituted triazoles used as precursors for triazolopyridines are the diacid 118 or its anhydride, reacting with aniline (83IJC(B)125) and the ketoamide 119 (90IZV1392). 

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The synthesis from triazoles that, in spite of the poor yield (19%), most shaped future practice was that of Yamada who, by heating 4-amino-l,2,3-triazole-5-carboxamide (73a) with urea (165°C, 5 h), obtained 8-aza-purine-2,6-dione (74) plus the intermediate 4-ureido-l,2,3-triazole-5-car-boxamide. 

Intramolecular 1,3-dipolar cydoadditions to acceptor-substituted allenes are rare [357]. The synthesis of triazole 386 from the precursor 384 is one of the few examples [120]. 

Scheme 19 A three-step synthesis of triazole using Bestmann-Ohira reagent starting from an alcohol [42]...

The synthesis of triazoles from organic azides and active methylene compounds under basic conditions is well known. Although the condensation is stepwise, the reaction is usually regiospecific,... 

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. 

Studies on the potential of the electrochemical approach to pyrazolotriazoles 117 showed that under the conditions of bicycle synthesis from 3-amino-4-hydrazonopyrazoles the N-l-unsubstituted triazole ring of 117 was further oxidized in a one-electron peak, followed by proton removal to yield the bis-(l,l )-2-phenylpyrazolo[3,4-i/][l,2,3]triazoles 118. This observation is significant, since in spite of pronounced pharmaceutical applications of pyrazoles, the redox characteristics of substituted pyrazoles have received limited attention (Scheme 13) <2001MI1022>. 

The original synthesis of triazole 3 began with the reaction of chloropyrazine 6 with hydrazine (Scheme 5.2). While these two compounds readily react at elevated temperature, the reachon possessed several unsafe aspects. First, heating 6 in isopropanol (IPA) with an excess of hydrazine allowed for a high potenhal for dangerous free hydrazine to be present in the head space.Second, the thermal profile of this step showed the potential for an uncontrollable reachon at elevated temperatures with a large amount of gas evoluhon. ) ) Lastly, the hydrazine adduct 7 was observed to crystallize from the reaction as a toxic and explosive hydrazine co-crystal. 

Heating 5h with aniline leads to the formation of 6-phenylcarbamoyl-2-methyl-3-phenylpyrazoIo[5, l-c][ 1,2,4]triazole 255 (87AP850). The structure of the latter was supported by its alternative synthesis from 176 and aniline (87AP850). 

The convenient method of 3 -nitro-5-cloto-1,2,4-triazole synthesis from corresponding 3-aminoderivative [447] was worked out. The aforementioned way [348] is very laborious and dangerous (Scheme 58). 

E. Grigat and R. Putter, Angew. Chem., Int. Ed. Engl. 6, 206-218 (1967). Triazoles, synthesis from amidrazones ... 

Synthesis of Triazole Rings from Other Heterocyclic Systems... 

Synthesis of Triazole Rings from Acyclic Compounds 4.12.4.2,1 Methods employing hydrazine derivatives... 

This reaction principle has considerable scope, as shown by the synthesis of various heterocyclic annu-lated 1,4-benzodiazepines. [l,2,3]Triazolo[l,5-fl][l,4]benzodiazepines 23 are prepared from triazole derivatives 22 which are accessible by a 1,3-dipolar cycloaddition of o-azidobenzophenones with (aminomethyl)alkines pyrrolo[2,l-c][l,4]benzodiazepines 25 are formed from l,2-dihydro-3,l-benzoxazinediones 24 and proline ... 

General Procedure for the Synthesis of Triazole-Fused Tetrahydropyr-azin-6-ones To a solution of chloroacetylated alkyne (1 mmol) in DMF (5 mL) was added NaN3 (5 mmol). The mixture was heated to 100 °C for appropriate time. After the reaction was complete (monitored by TLC) DMF was evaporated under vacuum, and the compound was extracted from the reaction mixture with CH2CI2 (25 mL). The combined organic layer was then dried with anhydrous Na2S04, filtered, and concentrated to obtain the corresponding triazole-fused tetrahydropyrazin-6-ones. 

Synthesis of Triazoles from Cyclic Acyl Ketene Aminals. 50... 

Triazole Derivatives. Triazole derivatives are known to possess tumor necrosis factor-a (TNF-a) production inhibitor activity. The synthesis of triazole derivatives can be achieved from alkynes or diynes by a tandem cascade reaction involving 1,3-dipolar cycloaddition, anionic cyclization and sigmatropic rearrangement on reaction with sodium azide. Some of the benzoyl triazole derivatives were considered to be potent local anaesthetics and are comparable with Lidocaine. The triazoles can also be prepared from benzoyl acetylenes,triazoloquina-zoline derivatives, 2-trifluoromethyl chromones, aliphatic alkynes, 2-nitroazobenzenes, ring opening of [ 1,2,4]triazolo [5,1-c] [2,4]benzothiazepin-10 (5//)-one, alkenyl esters and dendrimers. A number of these reactions are outlined in eqs 44 8. 

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