Coaxial Dielectric Spectroscopy as an In-Line Process Analytical Technique for Reaction Monitoring

Desiree M Dalligos; Michael J Pilling; Georgios Dimitrakis; Liam T Ball

doi:10.1021/acs.oprd.3c00081

Coaxial Dielectric Spectroscopy as an In-Line Process Analytical Technique for Reaction Monitoring

Org Process Res Dev. 2023 May 30;27(6):1094-1103. doi: 10.1021/acs.oprd.3c00081. eCollection 2023 Jun 16.

Authors

Desiree M Dalligos^{1

2}, Michael J Pilling³, Georgios Dimitrakis¹, Liam T Ball²

Affiliations

¹ Department of Chemical and Environmental Engineering, University of Nottingham, Coates Building, Nottingham NG7 2RD, U.K.
² School of Chemistry, University of Nottingham, Nottingham NG7 2RD, U.K.
³ Chemical Development, Pharmaceutical Technology & Development, Operations, AstraZeneca, Macclesfield SK10 2NA, U.K.

Abstract

The suitability of broadband dielectric spectroscopy (DS) as a tool for in-line (in situ) reaction monitoring is demonstrated. Using the esterification of 4-nitrophenol as a test-case, we show that multivariate analysis of time-resolved DS data-collected across a wide frequency range with a coaxial dip-probe-allows reaction progress to be measured with both high precision and high accuracy. In addition to the workflows for data collection and analysis, we also establish a convenient method for rapidly assessing the applicability of DS to previously untested reactions or processes. We envisage that, given its orthogonality to other spectroscopic methods, its low cost, and its ease of implementation, DS will be a valuable addition to the process chemist's analytical toolbox.