Nuclear
magnetic resonance (NMR) spectroscopy of small molecules
protonated in a solvent-free environment was successfully demonstrated.
The method is referred to as solvent-free protonation NMR (SoF-NMR). Leveraging matrix-assisted
ionization (MAI), we generated protonated species of aniline, 4-chloroaniline,
4-aminobiphenyl, and benzocaine for NMR analysis under mild pressure
and temperature conditions. The SoF-NMR spectra were compared to traditional
solution NMR spectra, and the shift changes in nuclear spin resonance
frequencies verify that these small molecules are protonated by 3-nitrobenzonitrile
(3-NBN). As the sample pressure decreased, new spectral features appeared,
indicating the presence of differently charged species. Several advantages
of SoF-NMR are highlighted, such as the elimination of H/D exchange
in labile protons, resulting in the precise observation of protons
that are otherwise transient in solution. Notably, the data on benzocaine
show evidence of neutral, N-protonated, and O-protonated species all in the same spectrum. SoF-NMR eliminates
the solvent effects and interactions that can hinder important spectral
features. Optimizing SoF-NMR will result in more cost-effective and
efficient NMR experimentation to monitor high-temperature, solvent-free
reactions. SoF-NMR has a viable future application for studying exchangeable
protons, intermediates, and products in gas-phase chemistry.