Experimental Setup: 'Chemputer' and additional analytical module with a Benchtop NMR

Experimental Setup of the modula, automated chemical synthesis platform (‘Chemputer’) including the additional analytical module with a Benchtop NMR

Source: BAM, division Process Analytical Technology

A universally applicable chemical synthesis platform, with which a wide variety of process steps can be carried out fully automatically, ranging from the reaction to the purification of the intermediate and end products, in order to produce desired chemical compounds - a vision of the future ? This future has become reality with the development of the “Chemputer” in the laboratory of Leroy Cronin at the University of Glasgow. Researchers from BAM division Process Analytical Technology and division Structural Analytics have now enhanced the already existing modular platform with suitable process analytics as well as powerful evaluation algorithms in such a way that insights into the chemical transformations currently taking place during operation are possible. This system allows individual synthesis steps to be analyzed in real time, monitored and manipulated in response - for example, by varying the reactant addition and process temperature. Based on the scientifically and industrially relevant class of Grignard reactions, the synthesis platform was further developed, and its performance demonstrated.

The developed analytical module currently accommodates a benchtop nuclear magnetic resonance spectrometer but can be equipped or expanded with other or additional analytical methods. During the development, a universal, modular approach was considered, which guarantees the interchangeability of the analytical instruments as well as the underlying evaluation algorithms.

With this work it was shown that NMR spectroscopy can be used successfully as a modern, high-performance process analytic even under harsh process conditions. This is an important contribution proving that even established synthesis routes can benefit from real-time monitoring and optimization and that process analytical monitoring of chemical syntheses is an essential part of fully automated plants.

Standardization and control of Grignard reactions in a universal chemical synthesis machine using online NMR
Martin Bornemann-Pfeiffer, Jakob Wolf, Klas Meyer, S. Kern, D. Angelone, A. Leonov, L. Cronin, Franziska Emmerling
published in Angewandte Chemie - International Edition, issue 60, article no. 202106323, pages 1 - 6
BAM, division Process Analytical Technology and division Structure Analysis