1,2,3-triazole derivatives

The usual methods of phenol oxidation were used to prepare derivatives of 220 (or the tautomeric form of the triazole part) (12LA318 12LA345 27LA131 34LA213 34LA241) or of 221 and benzologs (35LA248). When 

Substituted 222 or benzologs of 221 were prepared from 2,3-diaminoqui-nones and nitrous acid (25CB1128 35JA1844 65JCS2727). Alternatively, 

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Primary aromatic diamines cannot be diazotised (tetrazotised) and coupled normally. Thus o-])henylenediamiiie yields a triazole derivative and m-phenylenediamine gives an azo dye (Bismarck brown) by selfcoupling. 

For protection against nonferrous and copper ahoy corrosion, thiadiazole and triazole derivatives have been found especiahy useful (22). 

Because of their limited, activity, small spectmm, and side effects, the older topical antimycotics have generally been surpassed by newer antimycotic chemotherapeutic agents. These newer antimycotics for topical use iaclude the imida2ole derivatives clotrimazole, miconazole, econazole, isoconazole, sulconazole, fenticonazole, oxiconazole, bifonazole, butoconazole, ziaoconazole, tioconazole, and the triazole derivative, terconazole (Table 2) (5—7). The iatroduction of the azole derivatives represents a milestone ia the treatment of mycoses. 

Diacylhydrazines (32) on heating with a primary amine undergo cyclization to the 1,2,4-triazole derivative (38). It is assumed that the amidrazone (37) is an intermediate in the reaction. Most practical syntheses of 1,2,4-triazoles now utilize an amidrazone or a derivative of this alicyclic intermediate containing three nitrogen atoms, and these variations are discussed in Chapter 4.12. 

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). 

Triazole derivatives (diniconazole-M, epoxiconazole, fluhinconazole etc.) are widely used in agricultural practice as fungicides. The low application rates of these formulations require specific conditions for identification of residual quantities in different objects. 

OOOKGSlOO) (Scheme 134). Triazolylfurazans 207 were also prepared by condensation of azidofurazans with active methylene compounds in the presence of MgCOs (99MI1). A variety of azidofurazans and -furoxans reacted similarly to form the corresponding triazole derivatives. 

Triazole derivatives as high-energy compounds 97M14. 

Intramolecular dipolar azide-olefin cycloaddition of 723 took place upon heating in benzene to afford 724 (83JA3273). An alternative rearrangement process can take place upon photolysis of 724 to give 725. Mesylation of 4-(3-hydroxypropyl)-2,4,6-trimethyl-2,5-cyclohexadiene-l-one (78JA4618) and subsequent treatment with sodium azide in DMF afforded the respective azide 726 which underwent intramolecular cycloaddition to afford the triazoline 727 (83JOC2432). Irradiation of 727 gave the triazole derivative 728 (Scheme 126). 

The 1,2,4-triazole derivative 1 reacts in the presence of aluminum trichloride to provide the benzannulated 1,3-diazocine 2.6... 

Simple 1,2,4-triazole derivatives played a key role in both the synthesis of functionalized triazoles and in asymmetric synthesis. l-(a-Aminomethyl)-1,2,4-triazoles 4 could be converted into 5 by treatment with enol ethers <96SC357>. The novel C2-symmetric triazole-containing chiral auxiliary (S,S)-4-amino-3,5-bis(l-hydroxyethyl)-l,2,4-triazole, SAT, (6) was prepared firmn (S)-lactic acid and hydrazine hydrate <96TA1621>. This chiral auxiliary was employed to mediate the diastereoselective 1,2-addition of Grignard reagents to the C=N bond of hydrazones. The diastereoselective-alkylation of enolates derived from ethyl ester 7 was mediated by a related auxiliary <96TA1631>. 

Watanabe N, S Horikoshi, A Kawasaki, H Hidaka, N Serpone (2005) Formation of refractory ring-expanded triazine intermediates during the photocatalyzed mineralization of the endocrine disrupter amitrole and related triazole derivatives at UV-irradiated TiOj/HjO interfaces. Environ Sci Technol 39 2320-2326. 

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. 

Armand, J. et al., J. Chem. Res. Synop., 1980, 304 Microf. 1980, 3853-3869 The dioxime exploded on melting, as did the cyclised isomeric triazole derivative, l-hydroxy-2-hydroxylamino-l,3,4-triazole. 

Triazole derivatives also result from the cycloaddition of DEAZD to azomethine ylids derived from electrocyclic ring opening of aziridines.117 121 For example, the tetrahydro-1,2,4-triazole 73 was prepared by thermolysis of the cts-aziridine in the presence of DEAZD in 96% yield (Eq. 8), and... 

Triazole derivatives are very interesting compounds that can be prepared by 1,3-dipolar cycloadditions between azides and alkynes. Loupy and Palacios reported that electron-deficient acetylenes react with azidoethylphosphonate 209 to form the regioisomeric substituted 1,2,3-triazoles 210 and 211 under microwaves in solvent-free conditions (Scheme 9.65) [114]. This procedure avoids the harsh reaction conditions associated with thermal cycloadditions (toluene under reflux) and the very long reaction times. 

Table 1 Selected bond lengths (in A) for 1,2,3-triazole derivatives 5-12...

A convenient synthetic method for 1,2,3-triazoles unsubstituted at C-4 and C-5 utilizes a reaction of azides with norbornadiene, for example, Scheme 29 <2004JOC1081>. The process is performed in refluxing dioxane. In the first step, norbornadiene undergoes 1,3-dipolar cycloaddition to glucose-derived azide 225 to give triazoline 226. The following retro Diels-Alder reaction results in the elimination of cyclopentadiene to furnish triazole derivative 227 in 79% yield. 

Esters of 1,2,3-triazolecarboxylic acids are the most common derivatives of triazole (Section 5.01.9) therefore, their conversions to other, more useful, functionalities are of great importance. In an example given in Scheme 48, 4-triazolecarbocylic ester 317, obtained from a reaction of (3-ketoester 316 with 4-chloro-2-nitrophenyl azide, is hydrolyzed to free acid 318 (82% yield) by 4% KOH. Heated to reflux in DMF for 3 h, acid 318 undergoes decarboxylation to triazole derivative 319 with 81% isolated yield <2004FA397>. 

Due to its wide application in peptide synthesis, 1-hydroxybenzotriazole 1001 is the most commonly used benzo-triazole derivative with hundreds of references in Chemical Abstracts each year. Utility of compound 1001 comes from its readiness to form esters with carboxylic acids in the presence of dehydrating agents (DAs). Obtained esters 1002 react eagerly with amines to produce amides 1003 in high yields (Scheme 165). More details about this application are given in Section 5.01.12. 

Reactivity of azides towards acetylenedicarboxylates is very dependent on their electron density (energy HOMO). Thus, strongly electron-deficient 3,5-dicyano-2,4,6-triazidopyridine 1039 reacts slowly with dimethyl acetylenedicarboxylate to give triazole derivative 1038 in 34% yield with most of the starting material recovered unchanged. Under comparable conditions, less electron-deficient 3,5-dichloro-2,4,6-triazidopyridine 1040 reacts with dimethyl acetylenedicarboxylate to provide 2,6-bis(l,2,3-triazol-lyl)pyridine derivative 1041 in 75% yield (Scheme 171) <2001CHE861>. 

Use of unsubstituted acetylene as a substrate in 1,3-dipolar cycloadditions with azides results in 4,5-unsubstituted triazoles. The reactions have to be carried out under pressure. In an example given in Equation (23) showing synthesis of an antibacterial agent, a solution of azide 1049 in dimethoxyethane is transferred to a pressure bomb that is then charged with acetylene and heated at 90 °C for 12 h to give triazole derivative 1050 in 74% yield <2003BMC35>. 

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