Detection of intermediates for the Eschweiler–Clarke reaction by liquid-phase reactive desorption electrospray ionization mass spectrometry

摘要

Desorption electrospray ionization mass spectrometry (DESI-MS) has been developed dramatically asna powerful tool for the rapid analysis of samples in their native environment. Here a novel applicationnof DESI-MS was demonstrated for direct probing of the reactive intermediates in the liquid-phasenEschweiler–Clarke reaction, a reductive amination reaction whereby a primary (or secondary) amine isnsuccessively N-methylated using excess formaldehyde and formic acid. The intermediates ion species ofnsodiated amino alcohol ([I + Na]+) and iminium ([II]+), along with the corresponding protonatednmolecules of amine reactant ([M + H]+) and end product ([III + H]+), were simultaneously andnunambiguously characterized by the positive ion DESI-MS in the native liquid-phase reactivencondition. The operating variables were optimized for better analytical performance including thenspray solvent composition (such as formic acid concentration, proportion of methanol–water), voltagenapplied, spray spatial distance and incident angle. The feasibility of the reactive DESI-MS detection ofnacid–formaldehyde methylations was further validated using amines of a large variety of chemical typesn(2 primary and 3 secondary amines). Thus, the liquid-phase reactive DESI-MS technique allows thendirect analysis of reaction intermediates occurring in complex liquid solutions without samplenpreparation to provide a valuable insight into chemical reaction mechanisms.