A carbon fiber ionization (CFI) technique was developed for the mass spectrometric analysis of various organic compounds with different polarities. The design of the CFI technique was based on the good compatibility and dispersion of samples and solutions in different solvents on carbon fiber. As a fast, convenient, and versatile ionization method, CFI-MS is especially efficient for analyzing many low/nonpolar organic compounds, such as polycyclic aromatic hydrocarbons, long-chain aliphatic aldehydes, sensitive steroids, terpenoids, and organometallic compounds. Some of these compounds may not be well-analyzed by electrospray ionization or electron ionization mass spectrometry. On the basis of our experimental results, the major ion formation mechanism of CFI-MS was suggested to involve desorption in a steam-distillation-like process, and then, ionization occurred mainly via corona discharge under high voltage. CFI-MS could not only work alone but also be coupled with separation techniques. It works well when coupled with supercritical fluid chromatography (SFC) as well as in the analysis of exhaled human air. The high flexibility and versatility of CFI-MS has extended its applications in many areas, such as fast chemical screening, clinical testing, and forensic analysis.

Reactive solvent-assisted electrospray ionization coupled to ion-mobility mass spectrometry (reactive SAESI-IM-MS) was used to study the reactive intermediates in organocatalytic asymmetric amination reactions. The transient intermediates including two isomers of carbinolamine and iminium species in the early stage of enamine formation and previously unrecognized triazane species appearing before the formation of iminium intermediates 6 were successfully intercepted and characterized by reactive SAESI-IM-MS. Moreover, the ratio of Z- and E-enamine intermediates in situ was obtained rapidly and accurately by IM-MS. Thus, a more clear and detailed landscape for understanding the mechanisms of organocatalytic asymmetric amination reactions and the origin of enantioselectivity was given, which demonstrates the remarkably increased ability of reactive SAESI-IM-MS in detecting and characterizing reaction intermediates.

A silver-catalyzed intramolecular amination of alkynl-imine substrates has been extensively studied to build various isoquinoline derivatives efficiently. However, most of these transformations are limited to hydroamination, and the related oxidative reaction is quite rare. Importantly, the mechanistic details are still unknown, which retarded further progress in the field. In this work, a novel abnormal mesoionic carbene silver complex (MIC)nAg(I) was isolated and fully characterized as the key intermediate. Further investigation on the oxidative transformation of the silver complex reveals that successful oxidative halogenation could be achieved with NXS (X = Cl, Br, and I), as well as F+ reagent. Surprisingly, the fluorination reaction occurred in the presence of both strong (SelectFluor) and weak (NFSI) fluorinating reagents, although the F-Py-type reagent, whose oxidative potential lies between, is ineffective. Further mechanistic studies disclosed that (1) from kinetic data, the (MIC)Ag(I) complex was proved to be the reactive intermediate in the fluorination reaction, and pyridyl-oxazoline (Pyox) ligand could significantly improve this transformation; (2) from DFT calculation results, two different mechanistic pathways were suggested to be involved, a metathesis process in the case of NFSI promoted by the chelation of sulfonyl group toward the silver center and a redox process in the case of SelectFluor due to its strong oxidative potential.Keywords: abnormal mesoionic carbene; alkynl-imine; fluorination; oxidative; silver complex

An unexpected gas phase Gutknecht self-condensation of D-glucosamine hydrochloride to 2,5-deoxyfructosazine (2,5-DOF) in atmospheric pressure chemical ionization mass spectrometry (APCI-MS) was described. Mechanistic studies indicated that the thermospray conditions in APCI largely accelerate the irreversible Gutknecht self-cyclocondensation reaction of amino-sugars. Our observations provide a promising clue for a new borate-free synthetic method of 2,5-DOF by mimicking the APCI conditions.

Electrospray ionization (ESI) is a powerful ionization technique with a wide range of applications. However, the analytes in low/nonpolar solvents cannot be analyzed directly in electrospray ionization–mass spectrometry (ESI-MS), because low/nonpolar solvents are incompatible with ESI, because of their low conductivity. To circumvent this problem, we introduce an electrospray-based ionization method termed solvent-assisted electrospray ionization (SAESI). With the help of electrospray solvents at the tip of the spray needle, compounds in “non-electrospray ionization-friendly” solvents can be ionized directly using solvent-assisted electrospray ionization–mass spectrometry (SAESI-MS). The key features that the assistant solvent can be chosen flexibly and makes little interference to samples lead to better ionization performance in detection of organic reaction intermediates and real-time analysis of polymers and chiral drugs separated by gel permeation chromatography (GPC) and normal phase liquid chromatography (NPLC). Furthermore, it can achieve online hydrogen/deuterium (H/D) exchange reaction and even mitigate the signal suppression caused by strong acid modifiers in liquid chromatography. In addition, all parts of this device are commercially available and it only requires two parameters to be optimized, which makes SAESI easy to handle.

An increasing number of fluorinated drugs, pesticides, and fine chemicals are now produced and applied, especially those containing polyfluorinated aromatic moieties. However, at present, the extent of literature covering the special mass spectrometric behaviors of these compounds remains limited. Herein, we report an unexpected but also general gas-phase dissociation mode of polyfluorinated aromatics in mass spectrometry: expulsion of difluorocarbene (50-Da neutral loss). Results from accurate mass measurements, tandem mass spectrometric experiments, and density functional theory (DFT) calculations support an intramolecular F-atom “ring-walk” migration mechanism for gas-phase CF2 loss. Based on an assessment of the electron ionization-mass spectrometry (EI-MS) data of more than 40 polyfluorinated aromatic compounds from the National Institute of Standards and Technology data bank, we generalized on the substitution group effects on the difluorocarbene dissociation process of polyfluorinated aromatic compounds in EI-MS. These studies have enriched our knowledge of the special gas-phase reactivity of polyfluorinated aromatics and will provide valuable information in further analytical research of these compounds by mass spectrometry.

Gas phase decarbonylation and cyclization reactions of protonated N-methyl-N-phenylmethacrylamide and its derivatives (M·H+) were studied by electrospray ionization-tandem mass spectrometry (ESI-MS/MS). MS/MS experiments of M·H+ showed product ions were formed by loss of CO, which could only occur with an amide Claisen rearrangement. Mechanisms for the gas phase decarbonylation and cyclization reactions were proposed based on the accurate m/z measurements and MS/MS experiments with deuterated compounds. Theoretical computations showed the gas phase Claisen rearrangement was a major driving force for initiating gas phase decarbonylation and cyclization reactions of M·H+. Finally, the influence of different phenyl substituents on the gas phase Claisen rearrangement was evaluated. Electron-donating groups at the para-position of the phenyl moiety promoted the gas phase Claisen rearrangement to give a high abundance of fragment ions [M − CO + H]+. By contrast, electron-withdrawing groups on the phenyl moiety retarded the Claisen rearrangement, but gave a fragment ion at m/z 175 by loss of neutral radicals of substituents on the phenyl, and a fragment ion at m/z 160 by further loss of a methyl radical.

Reactive solvent-assisted electrospray ionization coupled to ion-mobility mass spectrometry (reactive SAESI-IM-MS) was used to study the reactive intermediates in organocatalytic asymmetric amination reactions. The transient intermediates including two isomers of carbinolamine and iminium species in the early stage of enamine formation and previously unrecognized triazane species appearing before the formation of iminium intermediates 6 were successfully intercepted and characterized by reactive SAESI-IM-MS. Moreover, the ratio of Z- and E-enamine intermediates in situ was obtained rapidly and accurately by IM-MS. Thus, a more clear and detailed landscape for understanding the mechanisms of organocatalytic asymmetric amination reactions and the origin of enantioselectivity was given, which demonstrates the remarkably increased ability of reactive SAESI-IM-MS in detecting and characterizing reaction intermediates.