Application of an Oscillatory Plug Flow Reactor to Enable Scalable and Fast Reactions in Water Using a Biomass-Based Polymeric Additive

28 July 2023, Version 1
This content is a preprint and has not undergone peer review at the time of posting.


The utilization of water as a sustainable reaction medium has important advantages over traditional organic solvents. Hydroxypropyl methylcellulose has emerged as a biomass-based polymeric additive that enables organic reactions in water through hydrophobic effects. However, such conditions imply slurries as reaction mixtures, where the efficacy of mass transfer and mixing decreases with increasing vessel size. In order to circumvent this limitation and establish an effectively scalable platform for performing hydroxypropyl methylcellulose-mediated aqueous transformations, we utilized oscillatory plug flow reactors that feature a smart dimensioning design principle across different scales. Using nucleophilic aromatic substitutions as valuable model reactions, rapid parameter optimization was performed first in a small-scale instrument having an internal channel volume of 5 mL. The optimal conditions were then directly transferred to a 15 mL reactor, achieving a three-fold scale-up without re-optimizing any reaction parameters. By precisely fine-tuning the oscillation parameters, the system achieved optimal homogeneous suspension of solids, preventing settling of particles and clogging of process channels. Ultimately, this resulted in a robust and scalable platform for performing multiphasic reactions under aqueous conditions.


Continuous flow
Hydroxypropyl methylcellulose
Oscillatory plug flow reactor
SNAr reaction

Supplementary materials

Supporting Information
The file contains synthetic procedures, additional reaction data, compound characterization data, copies of NMR spectra.


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