[288-88-0]  · C2H3N3  · 1,2,4-Triazole  · (MW 69.08)

(transacylating agent used for ester and amide synthesis, especially in peptide synthesis; cyclization reactions; oligonucleotide synthesis)

Physical Data: mp 120-121 °C; bp 260 °C (dec above 187 °C); fp 140 °C.

Solubility: sol water, alcohol.

Form Supplied in: white powder.

Acylating Reagent.

The great ability of triazole to accept and transfer acyl groups has made it a catalyst for the synthesis of esters and amides. In particular, triazole has been used in peptide synthesis, for the formation of peptide links as well as for the introduction of amino-protecting groups. It acts as a bifunctional catalyst, accelerating the aminolysis of p-nitrophenyl esters1 and p-thiocresyl esters.2 The catalytic effect is both by a general base mechanism (eq 1) and a specific mechanism (eq 2).

It has been used to introduce the Boc group onto an amino acid from t-butyl carbonates (eq 3), and it allows the coupling of an N-protected amino acid with a fully unprotected amino acid (eq 4). Interestingly, racemization is not observed during coupling of amino acids in the presence of 1,2,4-triazole.1 Nevertheless, its coupling efficiency depends on the reaction medium and in solvents like DMF, which increase the rate of aminolysis, its usefulness is limited. 1,2,4-Triazole is now seldom used in peptide synthesis, whereas other catalytic additives like 1-Hydroxybenzotriazole are widely used as activated esters as well as in conjunction with coupling reagents like 1,3-Dicyclohexylcarbodiimide.

Catalysis of Ring Formation.

1,2,4-Triazole can induce the formation of isoxazole rings from conjugated ketones and hydroxylamine (eq 5).3

Oligonucleotide Synthesis.

Sulfonyl derivatives of 1,2,4-triazole, e.g. (1), are used as efficient coupling reagents in oligonucleotide synthesis by the phosphotriester method.4 A nitro derivative (2) allows esterification of amino acids onto hydroxymethyl polymers.5

1. Beyerman, H. C.; Massen van den Brink, W.; Weygand, F.; Prox, A.; König, W.; Scmidhammer, L.; Nintz, E. RTC 1965, 84, 213.
2. Wieland, T.; Kahle, W. LA 1966, 691, 212.
3. Rentzea, C. N. AG(E) 1981, 20, 885.
4. Reese, C. B.; Titmas, R. C.; Yau, L. TL 1978, 2727.
5. Blankemeyer-Menge, B.; Nintz, M.; Frank, R. TL 1990, 31, 1701.

Jean-Claude Gesquière

Institut Pasteur, Lille, France

Copyright 1995-2000 by John Wiley & Sons, Ltd. All rights reserved.