A Study on the Diazo-Transfer Reaction Using o-Nitrobenzenesulfonyl Azide

15N-Labled azides have a great potential as practical and effective tags for vibrational probing and hyperpolarized magnetic resonance imaging of biomolecules. They can be synthesized by reaction of primary amines with 15N-labeled diazo-transfer reagent. TfNN15N, a γ-15N-labeled diazo-transfer reagent was developed to prepare β-15N-labled azides, a vibrational probe devoid of strong spectral interference by Fermi resonance. To overcome the stability and safety problems of TfNN15N, however, the development of a novel γ-15N-labeled diazo-transfer reagent is strongly demanded. We present the study on the diazo-transfer reaction using o-nitrobenzenesulfonyl azide (o-NBSA, o-NsN3). o-NsNN15N, a γ-15N-labeled diazo-transfer reagent, was newly developed and found to be better than TfNN15N with respect to physicochemical properties and ease of synthesis. Unlike TfNN15N, however, o-NsNN15N was found to afford a mixture of β- and γ-15N-labled azides rather than β-15N-labled azide alone. A mechanism for the diazo-transfer reaction of o-NsNN15N with primary amines was proposed to explain the formation of such isotopomeric mixture.