Triazolides

While the most obvious coordinatimi sites on the 1,4-disubstituted-l,2,3-triazole unit are the N2 and N3 nitrogen atoms, the acidic nature of the hydrogen on the C5 carbon means that it can be readily deprotmiated to provide anionic 1,4-disubstituted-1,2,3-triazolide Ugands. Straub and coworkers [123] were able to isolate a stable copperOD 1,4-disubstituted-l,2,3-triazolide complex (19a) by reacting the bulky NHC-stabdized copper(T) acetyUde 18a with azidodi-4-tolylmethane in toluene at RT for 24 h (Fig. 7). 19a was stable in air and water, and its molecular structure was confirmed by X-ray crystallography (Fig. 7). The copper(I) 1,2,3-triazolide... 

Fig. 7 Synthesis of l,4-disubstituted-l,2,3-triazolide complexes (i) azidodi-4-tolylmethane, toluene, RT, 24 h (ii) RN3, [Cu(MeCN)4](PF6), MeCN, RT, 12 h X-ray structure of the copperO) 1,4-disubstituted-1,2,3 -triazolide complex 19a showing the coordinatitm through the C5 carbon atom of the 1,2,3-triazole unit [123], Hydrogen atoms and counter ions have been ranitted for clarity...

Whereas under the conditions specified above JV-acetylpyrrole, like a typical acetamide, is not detectably hydrolyzed in neutral aqueous medium, the half-life of N-acetylpyrazole is 908 min, and that of A-acetylimidazole is reduced to 41 min for 1-acetyl-1,2,4-triazole and for the isomeric 1-acetyl-1,2,3-triazole, half-lives of 6.4 and 26.6 min, respectively, were observed (for an explanation of the different reactivities of the two pairs of isomers see above). Hydrolysis of TV-acetyltetrazole under the same conditions occurs too rapidly to be measured with conventional spectroscopic techniques. The reaction enthalpy AH was determined for A-acetylimidazole to be — 4.83 kcal/mol for the corresponding 1,2,4-triazolide the value was — 7.29, and for the tetra-zolide — 10.31 kcal/mol. 111... 

The mass spectra of azolides are not very specific, since they depend to a large extent on the structures of the respective acyl groups. Flash vacuum pyrolyses of azolides has been studied for 1-acyl-1,2,4-triazoles and benzotriazolides by tandem mass spectrometry (MS/MS). 461 Rearrangements of triazolides resulted in the formation of oxazoles. 471... 

The reaction of crocetin bisazolide has also been achieved with unprotected ( ) / -D-glucose in excellent yields (67% from the imidazolide 70% from the 1,2,4-triazolide). Esterification takes place exclusively at the anomeric C-atom, and produces only the f -anomer. The higher acidity of the anomeric hydroxyl group compared with the other... 

Analogously prepared are the / -D-glucosyl ester of 8 -apo-/ -carotene-8 -oic acid (as imidazolide and triazolide, obtained in 81 and 66% yield, respectively) and vitamin A acid (as triazolide, obtained in 87% yield) tl95]... 

The reaction with iV-acetyltriazole is about a hundred times faster for example the rate constant of its reaction with dry ammonia saturated in tetrahydrofuran is =0.95 min-1, with T1/2 0.73 0.015min.[3] (For other reactions with triazolides see Section 4.1.2.)... 

Examples of amide syntheses based on the more reactive triazolides are presented below ... 

Examples are given in Table 4—1 for the synthesis of amides of AT-protected amino acids by means of imidazolides and triazolides (where Z and Boc represent the protecting groups benzyloxycarbonyl and terf-butoxycarbonyl) ... 

The alkoxycarbonyl protecting groups can also be introduced into amines by, triazolides (Table 4—7). With A-tert-butoxycarbonyl-1,2,4-triazole the tert-butoxy-carbonyl protecting group (Boc) is transferred readily onto amino functions of primary amines, trimethylbenzyl ammonium salts of amino acids, or peptides.[ 1965 Alternatively, the Boc group can be transferred with terf-butylphenylcarbonate in the presence of 1,2,4-triazole. In this latter approach the triazolide is presumably formed as an intermediate. ... 

Syntheses of Peptides with Other Imidazolides and Triazolides... 

TABLE 5-4 Peptides prepared with other imidazolides and triazolides. 

Solid-Phase Synthesis of Peptides with Triazolides and Imidazolides... 

The amino acid attached to a polymer is treated with an vV-protected, carboxyl-activated amino acid to give the supported peptide. In the following reaction the triazolide was formed in situ from the p-nitrophenyl ester and 1,2,4-triazole 1341... 

The reaction conditions for this peptide synthesis are equimolar amounts of the reagents, five to eight hours, and 75-85 °C.[44J Use of a-isothiocyanatocarboxylic acids caused the yields of peptides to be lower. Instead of A-( 1 -imidazolylcarbonyl)amino acid esters, the corresponding triazolides were also utilized in the peptide synthesis. 

Polycondensation of amino acids with phosphorous diester triazolide are described in references [28] and [53]. Below 80 °C, no racemization was found. 

The following phosphorous triazolides, can also be used for this polycondensation. The most suitable triazolide, however, is the phosphorous acid diethyl ester triazolide because of an easy work-up of the reaction mixture.1281... 

Other polypeptides obtained by polycondensation with phosphorous diester triazolides are N6-Z-polylysine,[28] Na-Z-isopolylysine,t281 and the sequence polypeptides from /J-Ala-/J-Ala-Gly.l53]... 

Sequence polypeptides were obtained by polycondensation of tauryl peptides and 3-aminopropansulfonylpeptides with the two phosphorous acid diester triazolides A and B [54]... 

A different synthesis of oxazoles based on azolides is the flash-vacuum pyrolysis of 1,2,4-triazolides, which includes a shift of the acyl group and elimination of nitrogen 1371... 

If the nucleoside is treated with a threefold excess of phosphoryltristriazole and subsequently with a mixture of triethylamine and water, the ionic nucleotide phosphoric triazolide can be obtained [46]... 

With thiophosphoryltristriazole the corresponding thiophosphoric triazolide was formed in 80% yield.[46]... 

Unreacted support-bound nucleoside hydroxy groups can be blocked with diethoxy-triazolylphosphine. Oxidation of the phosphite triester to phosphate triester was achieved by I2. Yields in the condensation exceeded 95%. Tetrazolide as phosphitylating reagent is superior to a 4-nitroimidazolide, a triazolide, or even a chloride.11061... 

Imidazolides, 1,2,4-triazolides, or tetrazolides of arylsulfonic acids have been used as condensing agents in expedient syntheses of oligodeoxynucleotides. 

Among the 1,2,4-triazolides benzenesulfonyl-, p-toluenesulfonyl-, mesitylenesulfonyl-, triisopropylsulfonyl-, and p-nitrobenzenesulfonyltriazole (IV), the latter is the most reactive one (room temperature, 24 h, pyridine). 1151 341 1261 It was therefore also used for large-scale synthesis of fully protected di-, tri-, and hexadeoxyribonucleotides of defined sequence. 341 1161... 

Fluorophosphates (phosphorfluoridates), which are important for backbone modified oligonucleotides in molecular biology, are generally synthesized from phosphoric imi-dazolides or triazolides and acylfluorides. In these reactions, for example, the azole group (of the phosphoric or phosphinic imidazolide) is substituted by a fluorine atom, forming an acylazole compound as by-product.[202],[2033... 

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