Reactive Intermediates

In-situ production of Grignard reagents with continuous process control



Status Quo

The use of Grignard reagents has been one of the most effective methods of C-C bond linkage for more than 100 years. About 10% of the top 50 active pharmaceutical ingredients have one or more Grignard reactions in their synthetic pathway. Magnesium activation, undesirable side reactions, and high exotherm with associated intelligent thermal management are among the most common batch challenges.

Our approach allows your chemistry to reach its full potential

Especially the actual Grignard reagent formation can benefit immensely from continuous process control. The ultimate goal of our work is to generate reactive intermediates such as Grignard reagents or other organometallic compounds such as Zn reagents in-situ under continuous processing and, after quality control according to customer requirements, to convert them directly in a subsequent step.



  • Suppression of undesirable side reactions such as Wurtz coupling due to large magnesium excess,
  • No "runaway" of the reaction thanks to improved heat transport,
  • Efficient initiation of the reaction thanks to integrated magnesium activation,
  • Continuous supply of magnesium,
  • Inline analytics via IR measurements,
  • Product quality assessment via thermometric titration and GC analysis,
  • Easy scalability,
  • Short residence times.


Customer's benefit

With our reactors and setups we have successfully synthesized a growing number of Grignard reagents on the laboratory as well as the pilot scale. Furthermore, we have coupled them with follow-up Grignard reactions. Additionally, we have accumulated know-how for the two-step process of synthesis followed by catalyzed and non-catalyzed conversion of Zn organometallic reagents.

This means for you:

  • Safer production,
  • Higher yields/improved product quality/less side product formation (Wurtz coupling),
  • Cost and time savings in work-up,
  • Faster time-to-market,
  • Flexible production amounts (“on demand”), no surplus production of reagents,
  • Innovation lead.


Are you interested in the production of a wide variety of reactive intermediates? You want to go one step further with us in your synthetic pathways? You are interested in a fast and efficient determination of the potential of the technology for your specific problem? Please feel free to contact me.

Contact Press / Media

Dr. Gabriele Menges-Flanagan

Fraunhofer-Institut für Mikrotechnik und Mikrosysteme IMM
Carl-Zeiss-Str. 18-20
55129 Mainz

Phone +49 6131 990-425

Fax +49 6131 990-205