Flow Chemistry

Flow chemistry is an approach that harnesses the use of channels or tubing to conduct chemical reactions in a continuous stream rather than in a flask. Over the last decade developing chemical reactions under flow conditions has had a considerable impact on organic chemistry. This innovative technology has revolutionized the way organic chemists conduct critical chemical reactions by offering a high level of control over parameters such as temperature, pressure, and residence times. This precise control has enabled the efficient and safe use of challenging chemistries including those with azides and diazonium compounds in continuous manufacturing mode that aredifficult to execute in batch mode. 

At Symeres, we have applied a wide range of methodologies to a flow chemistry setup, both as small-scale custom synthesis and continuous manufacturing, this has enabled us to support our clients’ IND-enabling studies and beyond. Some areas of application of flow chemistry are described below.

Custom Synthesis: We utilize flow chemistry for tailored, small-scale syntheses. This approach is advantageous when working with complex molecules or when rapid optimization of reaction conditions is required. Flow chemistry’s ability to precisely control reaction parameters ensures reproducible results.

Continuous Manufacturing: Flow chemistry serves as a cornerstone to our continuous manufacturing efforts. Conducting reactions in a continuous flow system enables efficiency, unparalleled scalability, and safety. 

Challenging Chemistry: Flow chemistry’s unique capabilities enable us to tackle chemistries that are traditionally considered difficult or hazardous. For instance, we can manage azide and diazonium chemistry with a level of safety and control that is often unattainable in batch processes.

At Symeres with have experience with:

  • aromatic nitration reactions;
  • low-temperature organometallic chemistry;
  • photochemistry, including photoredox catalysis;
  • gas/liquid reactions
  • chemical steps using hazardous/highly energetic reagents, such as azides or diazonium compounds.

The flow-chemistry setups used at Symeres are purpose built for the specific needs of projects using a wide range of available pumps, mixers, and tubular or plate reactors (HANU 2X 15 reactor) with specific features, as exemplified in the schematic setup below for singlet-oxygen-mediated oxidations by using a photosensitizer, oxygen, and light. The safety concern of using oxygen in combination with an organic solvent is mitigated by the small size of the reactor (and dilution with nitrogen gas at the quench), and the progress of the reaction can be monitored by the disappearance of oxygen (or air) bubbles along the tubular reactor.

Flow chemistry setup at Symeres
HANU 2X 15 reactor Symeres

Several singlet-oxygen-mediated oxidations have been successfully developed using such a continuous-flow setup, for example, en route to (1R,4S)-4-hydroxycyclopent-2-en-1-yl acetate.[1]  The optically pure building block was obtained by an enzymatic desymmetrization process (100% theoretical yield).

Enzymatic desymmetrization process Symeres

For any inquiries involving continuous-flow chemistry, Symeres is your partner of choice, including scaleup and the production of kilogram amounts. Just fill in the form below to get in direct contact with our experts.  

[1] E. Herrero-Gomez et al., Org. Proc. Res. Dev. 2020, 24 , 2304 DOI: https://doi.org/10.1021/acs.oprd.0c00066

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