Joining Microfluidics with Infrared Photodissociation: Online Monitoring of Isomeric Flow-Reaction Intermediates

Abstract

A cryogenic ion trap vibrational spectrometer is combined with a microfluidic chip reactor in a proof-of-principle experiment on the Hantzsch cyclization reaction forming 2-amino-4-phenyl thiazole from phenacyl bromide and thiourea. First, the composition of the reaction solution is characterized using electrospray-ionization mass spectrometry combined with two-color infrared photodissociation (IRPD) spectroscopy. The latter yields isomer-specific vibrational spectra of the reaction intermediates and products. A comparison to results from electronic structure calculations then allows for an unambiguous structural assignment and molecular-level insights into the reaction mechanism. Subsequently, we demonstrate that isomeric and isobaric ions can be selectively monitored online with low process time, i.e., using a single IRPD wavelength per isomer, as the chip reaction parameters are varied.

How electrospray potentials can disrupt droplet microfluidics and how to prevent this

“…before it enters the chip or via make-up flow channels. 59 This is, however, not compatible with droplet microfluidics, where in most cases, the continuous oil phase is electrically non-conductive. Another approach for the electrical contacting of the emitter is the chip integration of electrodes, e.g., by sputtering, which we also realized in our earlier reports on chip-HPLC.…”

Telescoping the Synthesis of the [18F]CABS13 Alzheimer's Disease Radiopharmaceutical via Flow Microfluidic Rhenium(I) Complexations

“…Further considerations for increasing the yield of [ 18 F]CABS13, which were not implemented herein, could involve the use of an acid primed solid supported reagent to assist in dissociation of the metal centre or the use of light‐induced photodissociation in flow . Photodissociation methods, specifically, have been widely applied in the decomplexation of similar group VII manganese(I) tricarbonyl complexes, typically in application to carbon monoxide therapies and anti‐bacterial activity .…”

Unravelling the configuration of transient ortho-quinone methides by combining microfluidics with gas phase vibrational spectroscopy

“…13 Briefly, ions were transferred from solution into the gas phase using the microchip-ESI setup. 12 The ion beam was collimated and compressed in phase space in a He-buffer-gas filled radio frequency (RF) ion-guide, held at room temperature. Subsequently, they were massselected using a quadrupole mass filter and focused in a RF ring-electrode ion-trap.…”

“…Pahl et al have recently combined a microfluidic chip reactor with a cryogenic ion trap vibrational spectrometer to determine the structure of isomeric flow-reaction intermediates. 12 We build upon this work and now report on the in situ formation and spectroscopic characterization of o-QMs using such a setup. Four different ortho-hydroxy benzhydryl alcohols 1 were routinely converted into o-QMs with 1 equiv.…”