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A Scalable Balz-Schiemann Reaction Protocol in a Continuous Flow Reactor
Published on: February 10, 2023
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A scalable procedure for light-induced benzylic brominations in continuous flow.
David Cantillo1, Oscar de Frutos, Juan A Rincon
1Institute of Chemistry, University of Graz , Heinrichstrasse 28, A-8010 Graz, Austria.
The Journal of Organic Chemistry
|November 23, 2013
Summary
A new continuous-flow method enables efficient bromination of benzylic compounds using N-bromosuccinimide (NBS) and a compact fluorescent lamp (CFL). This greener approach avoids chlorinated solvents and scales easily for multigram synthesis.
Area of Science:
- Organic Chemistry
- Photochemistry
- Chemical Engineering
Background:
- Traditional benzylic bromination often employs hazardous solvents and batch photochemical reactors.
- Continuous-flow chemistry offers advantages in safety, control, and scalability for photochemical reactions.
Purpose of the Study:
- To develop a continuous-flow protocol for benzylic bromination using N-bromosuccinimide (NBS).
- To utilize a readily available compact fluorescent lamp (CFL) for radical initiation.
- To demonstrate a scalable and environmentally friendlier alternative to batch photochemical methods.
Main Methods:
- A simple flow reactor constructed from fluorinated ethylene polymer (FEP) tubing was employed.
- Radical bromination was initiated using light from a compact fluorescent lamp (CFL).
- Acetonitrile was used as the solvent, replacing hazardous chlorinated solvents like carbon tetrachloride (CCl4).
Main Results:
- The protocol successfully brominated 19 diverse benzylic substrates with good to excellent isolated yields.
- Only a slight excess of NBS (1.05 equiv) was required for complete substrate conversion.
- The flow protocol demonstrated scalability to multigram quantities with a throughput of 30 mmol/h, and up to 180 mmol/h for phenylacetone.
- High efficiency was maintained when using a larger flow reactor with a more powerful lamp.
Conclusions:
- A robust and scalable continuous-flow protocol for benzylic bromination has been established.
- The method offers a greener and safer alternative by avoiding chlorinated solvents and enabling efficient photochemical radical reactions.
- The system is readily adaptable for larger-scale synthesis, overcoming limitations of batch photochemical reactors.
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