Efficient and Inexpensive Synthesis of ¹⁵N-Labeled 2-Azido-1,3-dimethylimidazolinium Salts Using Na¹⁵NO₂ Instead of Na¹⁵NNN

¹⁵N-Labeled azides are important probes for infrared and magnetic resonance spectroscopy and imaging. They can be synthesized by reaction of primary amines with a ¹⁵N-labeled diazo-transfer reagent. We present the synthesis of ¹⁵N-labeled 2-azido-1,3-dimethylimidazolinium salts 1 as a ¹⁵N-labeled diazo-transfer reagent. Nitrosation of 1,3-dimethylimidazolinium-2-yl hydrazine (2) with Na¹⁵NO₂ under acidic conditions gave 1 as a 1:1 mixture of α- and γ-¹⁵N-labeled azides, α- and γ-1, rather than γ-1 alone. The isotopomeric mixture thus obtained was then subjected to the diazo-transfer reaction with primary amines 3 to afford azides 4 as a 1:1 mixture of β-¹⁵N-labeled azides β-4 and unlabeled ones 4′. The efficient and inexpensive synthesis of 1 as a 1:1 mixture of α- and γ-1 using Na¹⁵NO₂ instead of Na¹⁵NNN facilitates their wide use as a ¹⁵N-labeled diazo-transfer reagent for preparing ¹⁵N-labeled azides as molecular probes.