posted on 2020-03-16, 12:33authored byZinia Jaman, David L. Logsdon, Botond Szilágyi, Tiago J. P. Sobreira, Deborah Aremu, Larisa Avramova, R. Graham Cooks, David H. Thompson
Nucleophilic aromatic
substitution (SNAr) reactions were optimized using high-throughput
experimentation techniques for execution under flow conditions. A
total of 3072 unique reactions were evaluated with an analysis time
of ∼3.5 s per reaction using a system that combines a liquid
handling robot for reaction mixture preparation with desorption electrospray
ionization (DESI) mass spectrometry (MS) for analysis. The reactions
were performed in bulk microtiter arrays with and without incubation.
In-house developed software was used to process the data and generate
heat maps of the results. This information was then used to select
the most promising conditions for continuous synthesis under microfluidic
reactor conditions. Our results show that this HTE approach provides
robust guidance for narrowing the range of conditions needed for optimization
of SNAr reactions.