Nebulization prior to ionization for mechanistic studies of chemical reactions

Many important chemical transformations proceed by way of ionic and/or neutral intermediates. Great effort has been expended to understand the mechanism, with only minimum attention given to separate associated ionic and neutral intermediates. Herein, we present a nebulization method followed by on-line ionization to isolate and characterize the ionic and neutral intermediates. The separation of nebulization and ionization and electrical deflection of ionic species guarantee that only neutrals undergo the subsequent on-line ionization. We present data that show the formation of neutral intermediates and iminium ions with short lifetime in Eschweiler-Clarke methylation of di-n-butylamine, as well as data that provide evidence for the formation of carbocation and its isomer lactone products resulting from copper-mediated oxidative cyclization of 4-phenylbutyric acid. Experiments in which dissociation behavior of these two isomers varied at the same collision energy confirmed the carbocation during the cyclization. The nature of this process, which online isolates the ionic and neutral intermediates prior to ionization, greatly advances in mechanistic studies.