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

Abstract

N-15-Labeled azides are important probes for infrared and magnetic resonance spectroscopy and imaging. They can be synthesized by reaction of primary amines with a N-15-labeled diazo-transfer reagent. We present the synthesis of N-15-labeled 2-azido-1,3-dimethylimidazolinium salts 1 as a N-15-labeled diazo-transfer reagent. Nitrosation of 1,3-dimethylimidazolinium-2-yl hydrazine (2) with (NaNO2)-N-15 under acidic conditions gave 1 as a 1:1 mixture of alpha- and gamma-N-15-labeled azides, alpha- and gamma-1, rather than gamma-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 beta-N-15-labeled azides beta-4 and unlabeled ones 4'. The efficient and inexpensive synthesis of 1 as a 1:1 mixture of alpha- and gamma-1 using (NaNO2)-N-15 instead of (NaNNN)-N-15 facilitates their wide use as a N-15-labeled diazo-transfer reagent for preparing N-15-labeled azides as molecular probes.