Fraunhofer Institute for Microengineering and Microsystems IMM
In-situ production of Grignard reagents with continuous process control
FASTER, SAFER, MORE SELECTIVE!
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.
Advantages
- 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.