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Updated: Sep 24, 2025

A Scalable Balz-Schiemann Reaction Protocol in a Continuous Flow Reactor
Published on: February 10, 2023
Recyclable cooperative catalyst for accelerated hydroaminomethylation of hindered amines in a continuous segmented
Malek Y S Ibrahim1, Milad Abolhasani2
1Department of Chemical and Biomolecular Engineering, North Carolina State University, Raleigh, NC, 27695, USA.
Abstract:
Synthesis of hindered amines using the atom-efficient hydroaminomethylation (HAM) route remains a challenge. Here, we report a general and accelerated HAM in segmented flow, achieved via a cooperative effect between rhodium (Rh)/N-Xantphos and a co-catalyst (2-Fluoro-4-methylbenzoic acid) to increase the reactivity by 70 fold when compared to Rh/Xantphos in batch reactors. The cooperation between Rh and the co-catalyst facilitates the cleavage of the H-H bond and drives the equilibrium-limited condensation step forward. Online reaction optimization expands the scope to include alkyl, aryl, and primary amines. In-flow solvent tuning enables selectivity switching from amine to enamine without the need for changing the ligand. Furthermore, leveraging the ionic nature of the catalyst, we present a robust Rh recovery strategy up to 4 recycles without loss of activity.
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