engleski

Unexpected reactivity of propiolic acid and triazoles

Peptide coupling reactions are one of the most well-known and ubiquitous reactions in chemical synthesis. Among the more common reagents used for amide bond formation are triazole compounds, such as the TBTU/HOBT couple, HATU and others. Propiolic acid is the simplest alkyne carboxylic acid and presents a logical choice for modification of pseudo peptide NH groups for pericyclic click reactions with azides. Continuing our work on pseudo peptide we have aimed to prepare their click analogues. However, we have observed unexpected reactivity of propiolic acid in mild conditions of peptide bond formation (DCM, DIPEA, R.T.). In the performed reactions unusual products were isolated which were identified and characterised using spectroscopic methods (NMR, IR), x-ray crystallography and mass spectrometry. Reactions were conducted using different ratios of HOBT and TBTU, and both N- addition and O-addition of triazolic reagents to triple bond were observed. N-addition occurred in tandem with peptide coupling when unprotected propiolic acid was used ; while in reactions with the ester of propiolic acid O- addition was observed. In these reactions both Z- and E-isomers were isolated. Structurally different products, formed by double addition of propiolic acid or its ester, were also isolated in some of the reactions. The goal of this research is to determine the scope of reactions of propiolic acid and triazole compounds and optimise reaction conditions in order to develop synthetically valuable reactions.

triazoles ; NMR spectroscopy ; X-ray crystallography

nije evidentirano