Chemical synthesis generally requires labor-intensive, sometimes tedious trial-and-error optimization of reaction conditions. Here, we describe a plug-and-play, continuous-flow chemical synthesis system that mitigates this challenge with an integrated combination of hardware, software, and analytics. The system software controls the user-selected reagents and unit operations (reactors and separators), processes reaction analytics (high-performance liquid chromatography, mass spectrometry, vibrational spectroscopy), and conducts automated optimizations. The capabilities of this system are demonstrated in high-yielding implementations of C-C and C-N cross-coupling, olefination, reductive amination, nucleophilic aromatic substitution (SNAr), photoredox catalysis, and a multistep sequence. The graphical user interface enables users to initiate optimizations, monitor progress remotely, and analyze results. Subsequent users of an optimized procedure need only download an electronic file, comparable to a smartphone application, to implement the protocol on their own apparatus.

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Flow chemistry is an enabling technology that can offer an automated and robust approach for the generation of reaction kinetics data. Recent studies have taken advantage of transient flows to quickly generate concentration profiles with various online analytical tools. In this work, we demonstrate an improved method where temperature and flow are transient throughout the reaction. It was observed that only two orthogonal temperature ramp experiments under the same transient flow condition were sufficient to characterize a Paal-Knorr (one step bimolecular) reaction within our chosen reaction space. This method further shortens the time and decreases the materials needed to collect sufficient kinetic data and provides a framework with which more complex kinetic studies could be performed.

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