Flow chemistry, the use of channels or tubing to conduct chemical reactions in a continuous stream rather than in a flask, has had a considerable impact on organic chemistry in recent years. The high level of control over parameters such as temperature, pressure, and residence times has enabled the safe use of chemistries including those with azides and diazonium compounds in continuous manufacturing mode that are challenging 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 by flow, to support IND-enabling studies and beyond. These include
- aromatic nitration reactions;
- low-temperature organometallic chemistry;
- photochemistry, including photoredox catalysis;
- gas/liquid reactions; and
- 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.
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).
For any inquiries involving continuous-flow chemistry, Symeres is your partner of choice, including scaleup and the production of kilogram amounts. 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
