Real‐Time Reaction Monitoring of an Organic Multistep Reaction by Electrospray Ionization‐Ion Mobility Spectrometry

Abstract

The capability of electrospray ionization (ESI)‐ion mobility (IM) spectrometry for reaction monitoring is assessed both as a stand‐alone real‐time technique and in combination with HPLC. A three‐step chemical reaction, consisting of a Williamson ether synthesis followed by a hydrogenation and an N‐alkylation step, is chosen for demonstration. Intermediates and products are determined with a drift time to mass‐per‐charge correlation. Addition of an HPLC column to the setup increases the separation power and allows the determination of further species. Monitoring of the intensities of the various species over the reaction time allows the detection of the end of reaction, determination of the rate‐limiting step, observation of the system response in discontinuous processes, and optimization of the mass ratios of the starting materials. However, charge competition in ESI influences the quantitative detection of substances in the reaction mixture. Therefore, two different methods are investigated, which allow the quantification and investigation of reaction kinetics. The first method is based on the pre‐separation of the compounds on an HPLC column and their subsequent individual detection in the ESI‐IM spectrometer. The second method involves an extended calibration procedure, which considers charge competition effects and facilitates nearly real‐time quantification.

Computer Vision for Understanding Catalyst Degradation Kinetics

“…42,43 These methods are often used in combination to provide the fullest possible reaction understanding, covering different levels of analyte specificity and limits of detection. 44 In this study, we investigated the development and application of computer vision as a camera-based method (an in-line complement to existing off-line analytical methods) for providing data-rich, real-time, and non-contact kinetic information on the widespread problem of Pd catalyst degradation processes. Our colorimetric kinetics method is explored as an operationally cheap and simple method (relative to the setup of more common spectroscopic reaction monitoring methods) of obtaining macroscopic kinetic information from the reaction bulk.…”

Coupling Droplet Microfluidics with Ion Mobility Spectrometry for Monitoring Chemical Conversions at Nanoliter Scale

“…In recent years, IMS has experienced a renaissance, especially through the combination with electrospray mass spectrometers and the commercial availability of corresponding instruments. − While such IMS-MS systems are extremely powerful analytical tools, they have lost the advantages of stand-alone IMS systems such as their small size, instrumental simplicity, robustness, and comparatively low cost. − Typical drift tube IMS, for example, has a tube length of only 5–20 cm and can nowadays already be 3D-printed. − Although the main focus of IMS is still presented in the gas-phase analysis, − it has been demonstrated that IMS is an attractive detector for monitoring liquid-phase chemical and biochemical reactions. − Zühlke et al presented a qualitative and quantitative determination of all reaction components of an organic three-step synthesis . Very recently, IMS was also applied for monitoring photocatalyzed isomerization reactions performed on a continuous-flow microchip reactor …”

In situ monitoring of photocatalyzed isomerization reactions on a microchip flow reactor by IR-MALDI ion mobility spectrometry

“…The combination of these properties makes IM spectrometry attractive for reaction monitoring. IM spectrometry in combination with ESI was previously used for reaction monitoring of a three-step synthesis [ 29 ]. The coupling of a microchip-based HPLC separation and IM spectrometry was also shown [ 30 ], demonstrating the potential of chip-HPLC/IM spectrometry as a miniaturized two-dimensional separation method for separating three isomeric antidepressants.…”