title: Detection of intermediates for the Eschweiler-Clarke reaction by liquid-phase reactive desorption electrospray ionization mass spectrometry.
abstract: Desorption electrospray ionization mass spectrometry (DESI-MS) has been developed dramatically as a powerful tool for the rapid analysis of samples in their native environment. Here a novel application of DESI-MS was demonstrated for direct probing of the reactive intermediates in the liquid-phase Eschweiler-Clarke reaction, a reductive amination reaction whereby a primary (or secondary) amine is successively N-methylated using excess formaldehyde and formic acid. The intermediates ion species of sodiated amino alcohol ([I + Na](+)) and iminium ([II](+)), along with the corresponding protonated molecules of amine reactant ([M + H](+)) and end product ([III + H](+)), were simultaneously and unambiguously characterized by the positive ion DESI-MS in the native liquid-phase reactive condition. The operating variables were optimized for better analytical performance including the spray solvent composition (such as formic acid concentration, proportion of methanol-water), voltage applied, spray spatial distance and incident angle. The feasibility of the reactive DESI-MS detection of acid-formaldehyde methylations was further validated using amines of a large variety of chemical types (2 primary and 3 secondary amines). Thus, the liquid-phase reactive DESI-MS technique allows the direct analysis of reaction intermediates occurring in complex liquid solutions without sample preparation to provide a valuable insight into chemical reaction mechanisms.
authors.affiliation: Engineering Center for Biomedicine, College of Chemistry and Chemical Engineering, Hunan University, Changsha 410081, China.
authors.forename: Guangming
authors.initials: G
authors.lastname: Xu
authors.forename: Bo
authors.initials: B
authors.lastname: Chen
authors.forename: Bin
authors.initials: B
authors.lastname: Guo
authors.forename: Dongxiu
authors.initials: D
authors.lastname: He
authors.forename: Shouzhuo
authors.initials: S
authors.lastname: Yao
mesh_terms: D000586:Amination; D000588:Amines / Q000737:chemistry*; D000605:Amino Alcohols / Q000737:chemistry*; D007097:Imines / Q000737:chemistry*; D008745:Methylation; D012996:Solutions / Q000737:chemistry; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*
chemical_list: D000588:Amines; D000605:Amino Alcohols; D007097:Imines; D012996:Solutions