TfNN¹⁵N: A γ-¹⁵N-Labeled Diazo-Transfer Reagent for the Synthesis of β-¹⁵N-Labeled Azides

Azides are infrared (IR) probes that are important for structure and dynamics studies of proteins. However, they often display complex IR spectra owing to Fermi resonances and multiple conformers. Isotopic substitution of azides weakens the Fermi resonance, allowing more accurate IR spectral analysis. Site-specifically ¹⁵N-labeled aromatic azides, but not aliphatic azides, are synthesized through nitrosation. Both ¹⁵N-labeled aromatic and aliphatic azides are synthesized through nucleophilic substitution or diazo-transfer reaction but as an isotopomeric mixture. We present the synthesis of TfNN¹⁵N, a γ-¹⁵N-labeled diazo-transfer reagent, and its use to prepare β-¹⁵N-labeled aliphatic as well as aromatic azides.