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 online 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 plant for the continuous synthesis of four fluorine compounds. Necessary reagents are provided by an integrated cartridge system prior or after the thermal continuous flow reactor. As analytical platform we use the compact benchtop NMR spectrometer NMReadyTM 60 of the Canadian company Nanalysis Corporation. The required flow cells have been developed and adapted to the NMR spectrometer by ourselves. The flow cells are integral part of a fluidity control system that enables either continuous measurement of the reaction solution or stopped-flow measurement with a longer analysis time during the process development.

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 fluorinated 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 as well as for the online analysis development for other NMR-active nuclei like 31P or 7Li.


Funded by: Arbeitsgemeinschaft industrieller Forschungsvereinigungen (AiF), funding code KF2104409NT4.