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

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