On-line Process Monitoring

Project ContiNMR

On-line NMR analysis for the continuous synthesis of fluorine fine chemicals

Flow cell in NMR spectrometer
© Fraunhofer IMM

Flow cell installed in benchtop NMR spectrometer

Pharmaceutical products often contain fluorine fine chemicals as essential components. Their fluorine groups are responsible for the enhanced activity of the substances. The composition of the drug, its purity and, of course, its consistent quality are of utmost importance. Here the use of NMR spectroscopy, one of the most important methods for the structural determination of chemical compounds, is helpful. A first step towards a method that combines the advantages of continuous synthesis with integrated on-line NMR analysis we have taken together with our partners Hansa Fine Chemicals and Nanalysis Corporation.


In the course of the project we have developed and built a laboratory unit for the continuous synthesis of four fluorine compounds. All necessary reagents are provided by an integrated cartridge system.  We use the compact benchtop NMR spectrometer NMReadyTM 60 of the Canadian company Nanalysis Corporation as analytical platform. The required flow cells have been developed and adapted to the NMR spectrometer by ourselves. They are integrated into a control system that enables, based on magnetic valves, the continuous filling of the flow cell with reaction solution (continuous measurement) or the bypassing of the solution at the spectrometer to achieve a longer measurement during the process development (stopped-flow-measurement).

Properties and application areas of the lab system

The production of chemicals in small reactor volumes in combination with a contactless analysis method, such as NMR spectroscopy, allows a safe handling and, thus, reduces the risk potential of the active ingredients for the laboratory staff. The design we have chosen opens up the realization of several different routes for the synthesis of fluorine chemicals. The laboratory plant can basically be used for phosphorous compounds as well. From the signals in the NMR measurement we derive information such as level of conversion and, associated therewith, quality of the solution and structure.

Our research & development services

We offer to our customers the development, construction and manufacturing of milli- and microstructured flow reactors which are perfectly adapted to the respective process. This covers reactors suited for lab scale up to the production process. We as well integrate NMR spectroscopy into the system in terms of an on-line process control as NMR spectroscopy is a highly effective analysis method. Our research and development work thereby is applied in pharmaceutical and agrochemical industry.

Further possible application area of this lab system is:

  • Production and analysis of agrochemical products.


Funded by: AiF Arbeitsgemeinschaft industrieller Forschungsvereinigungen, reference number KF2104409NT4.