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

N-15-Labeled 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 a N-15-labeled diazo-transfer reagent. (TfNNN)-N-15, a gamma-N-15-labeled diazo-transfer reagent, was developed to prepare beta-N-15-labeled azides; these are vibrational probes devoid of strong spectral interference by Fermi resonance. To overcome the stability and safety problems associated with (TfNNN)-N-15, there is a strong demand for the development of a novel gamma-N-15-labeled diazo-transfer reagent. We present a study on the diazo-transfer reaction using o-nitrobenzenesulfonyl azide (o-NsN(3)). o-NsNN(15)N, a gamma-N-15-labeled diazo-transfer reagent, was newly developed and found to be better than (TfNNN)-N-15 with respect to its physicochemical properties and ease of synthesis. Unlike (TfNNN)-N-15, however, o-NsNN(15)N was found to afford a mixture of beta- and gamma-N-15-labeled azides rather than the beta-N-15-labeled azide alone. A mechanism for the diazo-transfer reaction of o-NsNN(15)N with primary amines is proposed to explain the formation of such isotopomeric mixtures.