Inline IR Monitoring

Flow processing presents some unique analytical challenges when compared to their typical batch reaction equivalent. Corresponding innovative solutions and opportunities arise to solve these issues. Accordingly, we have entered into an early collaboration with expert manufacturers Mettler-Toledo to develop the FlowIR flow cell as a new device for in-line IR analysis. IR spectroscopy represents a non-destructive, substrate specific analytical technology that can be readily incorporated into flow chemistry sequences.

We have demonstrated the use of these new IR flow cells  for reaction monitoring [1, 2], mechanistic investigations [3] and quantitative measurements of product dispersion during segmented flow [4, 5, 6]. This last application also facilitates additional pump control during multistep processing [7]. We have recently found it to be a useful tool to monitor the preparation and behavior of arylmagnesium reagents in flow [6].

Publications

1. ReactIR flow cell: a new analytical tool for continuous flow chemical processing
Org. Process ResDev201014, 393-404
C. F. Carter, H. Lange, S. V. Ley*, I. R. Baxendale, B. Wittkamp, J. G. Goode, N. L. Gaunt

2. A continuous flow process using a sequence of microreactors with in-line IR analysis of the preparation of NN-diethyl-4-(3-fluorophenylpiperidin-4-ylidenemethyl) benzamide as a potent and highly selective δ-opioid receptor agonist
Chem. Eur. J. 201016, 12342-12348
Z. Qian, I.R. Baxendale, S.V. Ley*

3. Preparation of arylsulfonyl chlorides by chlorosulfonylation of in situ generated diazonium salts using a continuous flow reactor
Org. Biomol. Chem., 20108, 5324-5332
L. Malet-Sanz, J. Madrzak, S.V. Ley, I.R. Baxendale

4. Fully automated, multistep flow synthesis of 5-amino-4-cyano-1,2,3-triazoles
Org. Biomol. Chem20119, 1938-1947
C.J. Smith, I.R. Baxendale, H. Lange, S.V. Ley

5. Teflon AF-2400 mediated gas-liquid contact in continuous flow methoxycarbonylations and in-line FTIR measurement of CO concentration
Org. Biomol. Chem20119, 6903-6908
P. Koos, U. Gross, A. Polyzos, M. O’Brien, I.R. Baxendale, S.V. Ley

6. Continuous preparation of arylmagnesium reagents in flow with inline IR monitoring
Org. Process Res. Dev. 2012, 16, 1102-1113
T. Brodmann, P. Koos, A. Metzger, P. Knochel,* S. V. Ley*

7. A breakthrough method for the accurate addition of reagents in multi-step segmented flow processing
Chem. Sci. 2011, 2, 765-769
H. Lange, C. F. Carter, M. D. Hopkin, S. V. Ley*