Real-Time High-Sensitivity Reaction Monitoring of Important Nitrogen-Cycle Synthons by (15)N Hyperpolarized Nuclear Magnetic Resonance

[Image: see text] Here, we show how signal amplification by reversible exchange hyperpolarization of a range of (15)N-containing synthons can be used to enable studies of their reactivity by (15)N nuclear magnetic resonance (NO(2)(–) (28% polarization), ND(3) (3%), PhCH(2)NH(2) (5%), NaN(3) (3%), and NO(3)(–) (0.1%)). A range of iridium-based spin-polarization transfer catalysts are used, which for NO(2)(–) work optimally as an amino-derived carbene-containing complex with a DMAP-d(2) coligand. We harness long (15)N spin-order lifetimes to probe in situ reactivity out to 3 × T(1). In the case of NO(2)(–) (T(1) 17.7 s at 9.4 T), we monitor PhNH(2) diazotization in acidic solution. The resulting diazonium salt ((15)N-T(1) 38 s) forms within 30 s, and its subsequent reaction with NaN(3) leads to the detection of hyperpolarized PhN(3) (T(1) 192 s) in a second step via the formation of an identified cyclic pentazole intermediate. The role of PhN(3) and NaN(3) in copper-free click chemistry is exemplified for hyperpolarized triazole (T(1) < 10 s) formation when they react with a strained alkyne. We also demonstrate simple routes to hyperpolarized N(2) in addition to showing how utilization of (15)N-polarized PhCH(2)NH(2) enables the probing of amidation, sulfonamidation, and imine formation. Hyperpolarized ND(3) is used to probe imine and ND(4)(+) (T(1) 33.6 s) formation. Furthermore, for NO(2)(–), we also demonstrate how the (15)N-magnetic resonance imaging monitoring of biphasic catalysis confirms the successful preparation of an aqueous bolus of hyperpolarized (15)NO(2)(–) in seconds with 8% polarization. Hence, we create a versatile tool to probe organic transformations that has significant relevance for the synthesis of future hyperpolarized pharmaceuticals.