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  • Primer
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Continuous flow chemistry for molecular synthesis

Nature Reviews Methods Primers volume 5, Article number: 44 (2025) Cite this article

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Abstract

Continuous flow techniques have become important tools for molecular synthesis, both in academia and across the fine chemicals industry. The success of these methods has been in part due to their interdisciplinary nature, bringing together chemists and engineers to design and construct creative solutions for the novel synthesis and scale-up of molecules, with applications in pharmaceuticals, agrochemistry, materials chemistry and crystallization. The advantages of flow chemistry include the high surface-area-to-volume ratio of narrow tubing, which improves temperature control, and the ability to scale by increasing reaction time rather than vessel volume. Further, the use of flow enables improved safety protocols, reduces waste and has the potential to telescope downstream work-up processes. Perceptions of flow chemistry as a field with a high barrier to entry remain, and these techniques have not yet become a standard option for most chemists owing to the lack of exposure in academic settings. To help reduce this barrier, this Primer introduces the field, covering the fundamental considerations of assembling a lab-scale flow experiment, using literature examples to illustrate their practical application. We conclude with an outlook for the field, highlighting opportunities for potential and existing users of the technique alike.

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Fig. 1: Comparisons between batch and flow chemistry.
Fig. 2: Various fundamentals of flow reactors.
Fig. 3: Examples of flow set-ups described in the ‘Experimentation’ section with relevant apparatuses.
Fig. 4: Recent examples of flow set-ups demonstrating capabilities in organic synthesis.
Fig. 5: Recent examples of flow set-ups demonstrating capabilities in industrial applications.
Fig. 6: Recent examples of flow set-ups demonstrating capabilities in materials applications.

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Acknowledgements

We dedicate this article to S. V. Ley on the celebration of his 80th year, with gratitude for his enduring contributions, guidance and inspiration in this field.

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Authors and Affiliations

  1. Department of Pharmaceutical and Biological Chemistry, School of Pharmacy, University College London, London, UK

    Sarah E. Raby-Buck & Duncan L. Browne

  2. School of Chemistry, University College Dublin, Dublin, Ireland

    Jonathan Devlin & Marcus Baumann

  3. Department of Chemistry and Materials Innovation Factory, School of Physical Sciences, University of Liverpool, Liverpool, UK

    Prachi Gupta & Anna G. Slater

  4. Syngenta Crop Protection AG, Stein, Switzerland

    Claudio Battilocchio

  5. School of Chemistry, The University of Melbourne, Parkville, Victoria, Australia

    Anastasios Polyzos

  6. CSIRO Manufacturing, Clayton, Victoria, Australia

    Anastasios Polyzos

Authors
  1. Sarah E. Raby-Buck
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  2. Jonathan Devlin
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  3. Prachi Gupta
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  4. Claudio Battilocchio
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  5. Marcus Baumann
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  6. Anastasios Polyzos
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  7. Anna G. Slater
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  8. Duncan L. Browne
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Contributions

Introduction (D.L.B. and S.E.R.-B.); Experimentation (D.L.B. and S.R-B.); Results (D.L.B., A.P. and S.E.R.-B.); Applications (C.B., M.B., J.D., P.G. and A.G.S.); Reproducibility and data deposition (P.G. and A.G.S.); Limitations and optimizations (D.L.B and A.P.); Outlook (D.L.B., C.B., M.B., P.G., S.E.R.-B. and A.G.S.).

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Correspondence to Duncan L. Browne.

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Nature Reviews Methods Primers thanks Anita Rose Maguire, who co-reviewed with Jacob Turner-Dore; Rodrigo Octavio Mendonça Alves De Souza; and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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Related links

Asynt: https://www.asynt.com/products/flow-chemistry

ChemDraw flow symbols: https://github.com/itc/chemdraw-templates

Reaxys: https://www.reaxys.com/#/search/quick/query

Scifinder: https://scifinder-n.cas.org/

Step-by-step flow tutorials and videos: https://www.youtube.com/watch?v=sx5VR6oJWaY&list=PLX53bZT1uB5lPl_5kWw40hWeIYNU5rnih

Syrris: https://www.syrris.com

Thalesnano: https://thalesnano.com

Vapourtec: https://www.vapourtec.com

Glossary

Catch-and-release

A technique where a molecule is temporarily adhered to a solid support (caught), allowing impurities to be washed away. The desired molecule is then released allowing further derivatization or work-up.

Continuous stirred tank reactor

(CSTR; also known as a vat or back mix reactor). CSTRs are large tanks with inlet and outlets connected to the flow system. The material in the tank is continuously stirred by an agitator as the reaction mixture flows through. They allow the use of stoichiometric solids in the flow system by confining them to the stirred reactor tank.

Ferrules

Small ring or cap-shaped components, which allow the formation of secure leak-free joins between tubes and other reactor components.

Flash chemistry

Extremely fast chemical reactions enabled by the high degree of control over reaction parameters possible in flow reactors.

Laminar flow

A type of flow where the fluid moves along in smooth parallel layers.

Mass flow controller

(MFC). A device that precisely controls the flow rate of a fluid.

Mass-transfer limited

A reaction where the rate is primarily limited by the movement of the reagent to the reaction site, meaning mixing or diffusion becomes the limiting factor.

Pulsing

Changes in flow pressure fluctuating around a non-zero mean value.

Residence time

The average time a reagent molecule spends in the reactor, calculated from the flow rate and the reactor volume.

Segment

The discrete sections in segmented flow are referred to as segments, slugs or plugs.

Segmented flow

A technique where reactions are run in discrete sections carried along in a carrier fluid.

Split-and-recombine-shaped mixers

This shape of mixer works by splitting the reaction down into smaller streams, increasing the surface-area-to-volume ratio between reagents. The smaller streams are then recombined back into one tube.

Turbulent flow

A type of flow characterized by chaotic changes in pressure and flow velocity leading to the fluid moving in a swirling pattern instead of parallel layers.

Union

A fitting with thread on the inside that allows it to join tubing and other components of the flow reactor by screwing on to nuts.

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Raby-Buck, S.E., Devlin, J., Gupta, P. et al. Continuous flow chemistry for molecular synthesis. Nat Rev Methods Primers 5, 44 (2025). https://doi.org/10.1038/s43586-025-00414-x

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