[41864-22-6]  · C5H4N6O  · N,N-Carbonyldi-sym-triazine  · (MW 164.13)

(reagent for peptide synthesis1; preparation of thiol or selenol esters2)

Physical Data: mp 134-136 °C.

Solubility: no information available. Reactions are usually performed in DMF.

Analysis of Reagent Purity: purity has been determined by measuring the amount of CO2 evolved on hydrolysis.

Preparative Methods: from triazole and phosgene in THF, in the presence of one equivalent of pyridine (80% yield).1

Purification: material prepared as above is 95% pure, and is generally used directly.

Handling, Storage, and Precautions: may be stored in a desiccator over P2O5 at room temperature for many months without apparent decomposition.

Peptide Synthesis.

N,N-Carbonyldi-sym-triazine (1) may be used to effect activation of an N-protected amino acid towards amide bond formation, presumably via the acyltriazole intermediate (2) (eq 1).1 Unlike the related reagent N,N-Carbonyldiimidazole, (1) may be used without problems in DMF, a suitable solvent for small and large peptides. Racemization is apparently lower when (1) is used rather than N,N-carbonyldiimidazole; coupling of CbzGly-Phe-OH to glycine ethyl ester (the Anderson test) showed 17% racemization using N,N-carbonyldiimidazole, whereas none was observed using (1) under strictly analogous conditions. This is presumably related to the fact that (2) reacts more rapidly with amines than does the corresponding acylimidazole, as expected based on consideration of the relative acidities of imidazole and triazole.

Thiol and Selenol Esters.

The acyltriazole resulting from activation of a carboxylic acid by (1) can be reacted without isolation with a thiol or selenol, affording a thiol or selenol ester, respectively.2 Racemization is slight when the method is applied to N-protected amino acids (eq 2). N,N-Carbonyldiimidazole can be used in place of (1), with similar results. Reaction with aromatic thiols or selenols is complete within minutes; alkyl thiols require a few hours. The 1,2,4-triazole formed is easily removed by extraction with water.

1. Beyerman, H. C.; Van Den Brink, W. M. RTC 1961, 80, 1372.
2. Gais, H.-J. AG(E) 1977, 16, 244.

Alan Armstrong

University of Bath, UK

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