ReactIR Flow Cell: A New Analytical Tool for Continuous Flow Chemical Processing

Abstract

A newly developed ReactIR flow cell is reported as a convenient and versatile inline analytical tool for continuous flow chemical processing. The flow cell, operated with ATR technology, is attached directly into a reaction flow stream using standard OmniFit (HPLC) connections and can be used in combination with both meso- and microscale flow chemistry equipment. The iC IR analysis software (version 4.0) enables the monitoring of reagent consumption and product formation, aiding the rapid optimisation of procedures. Short-lived reactive intermediates can also be observed in situ, giving further mechanistic insight into complex transformations.

Online Monitoring of Polymerizations: Current Status

“…[31] Gaunt and coworkers reported an inline ReactIR flow cell as a convenient analytical tool for continuous flow chemical processing as shown in Figure 2, which enables efficient monitoring of reagent consumption and product formation. [32,33] Baxendale and coworkers recently reviewed the synthesis of active pharmaceutical ingredients using continuous flow chemistry where inline analysis methods (UV and IR) are discussed. [34] FTIR online monitoring is a very powerful technique due to its high sensitivity.…”

Real-Time Feedback Control Using Online Attenuated Total Reflection Fourier Transform Infrared (ATR FT-IR) Spectroscopy for Continuous Flow Optimization and Process Knowledge

“…Our system is solvent-free, unlike the recently reported reactions, 17,19 which means that the concentrations of the different components vary widely as the algorithm changes the flow rates of the reactants and as gaseous byproducts are generated in the reactor. Therefore, our apparatus combines online FT-IR with online GLC, which not only allows the FT-IR to be calibrated for varying reactant concentrations, but also provides independent validation of the FT-IR analysis.…”

The route from problem to solution in multistep continuous flow synthesis of pharmaceutical compounds

“…7,72,73 Several different analytical systems were used successfully, such as in-line FT-IR (predominantly with Attenuated Total Reflectance (ATR) cells), [74][75][76][77][78][79][80] NIR, 81,82 Raman 83 and NMR spectroscopy, 84,85 as well as on-line MS 86,87 and HPLC. 88,89 However, everyday application of these approaches is hindered by the fact that off-line solutions are usually more convenient, since a wider toolbox (consisting of existing equipment) is available for the analysis of less demanding analytes (i.e.…”

“…66,90 Instable, short-lived intermediates, such as highly reactive acyl azide 75 and diazonium 86 species, as well as the VilsmeierÀHaack reagent, 91 can be directly studied in situ using IR spectroscopic or mass spectrometric methods (Fig. 14).…”