Standardization and Control of Grignard Reactions in a Universal Chemical Synthesis Machine using online NMR

Autor: Klas Meyer, Jakob Wolf, Artem Leonov, Martin Bornemann-Pfeiffer, Simon Kern, Davide Angelone, Franziska Emmerling, Leroy Cronin
Rok vydání: 2021
Předmět:
Zdroj: Angewandte Chemie (International Ed. in English)
ISSN: 1521-3773
1433-7851
Popis: A big problem with the chemistry literature is that it is not standardized with respect to precise operational parameters, and real time corrections are hard to make without expert knowledge. This lack of context means difficult reproducibility because many steps are ambiguous, and hence depend on tacit knowledge. Here we present the integration of online NMR into an automated chemical synthesis machine (CSM aka. “Chemputer” which is capable of small‐molecule synthesis using a universal programming language) to allow automated analysis and adjustment of reactions on the fly. The system was validated and benchmarked by using Grignard reactions which were chosen due to their importance in synthesis. The system was monitored in real time using online‐NMR, and spectra were measured continuously during the reactions. This shows that the synthesis being done in the Chemputer can be dynamically controlled in response to feedback optimizing the reaction conditions according to the user requirements.
A universal chemical synthesis platform was extended by online NMR to allow adjustments of the encoded reactions on the fly. The approach was demonstrated on the class of Grignard reactions showing robust analytical results under harsh conditions. Real‐time process analytics and the use of straightforward feedback control algorithm enhance the usability of available synthesis formula considering existing deviations.
Databáze: OpenAIRE
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