title: A scalable procedure for light-induced benzylic brominations in continuous flow.
abstract: A continuous-flow protocol for the bromination of benzylic compounds with N-bromosuccinimide (NBS) is presented. The radical reactions were activated with a readily available household compact fluorescent lamp (CFL) using a simple flow reactor design based on transparent fluorinated ethylene polymer (FEP) tubing. All of the reactions were carried out using acetonitrile as the solvent, thus avoiding hazardous chlorinated solvents such as CCl4. For each substrate, only 1.05 equiv of NBS was necessary to fully transform the benzylic starting material into the corresponding bromide. The general character of the procedure was demonstrated by brominating a diverse set of 19 substrates containing different functional groups. Good to excellent isolated yields were obtained in all cases. The novel flow protocol can be readily scaled to multigram quantities by operating the reactor for longer time periods (throughput 30 mmol h(-1)), which is not easily possible in batch photochemical reactors. The bromination protocol can also be performed with equal efficiency in a larger flow reactor utilizing a more powerful lamp. For the bromination of phenylacetone as a model, a productivity of 180 mmol h(-1) for the desired bromide was achieved.
authors.affiliation: Institute of Chemistry, University of Graz , Heinrichstrasse 28, A-8010 Graz, Austria.
authors.forename: David
authors.initials: D
authors.lastname: Cantillo
authors.forename: Oscar
authors.initials: O
authors.lastname: de Frutos
authors.forename: Juan A
authors.initials: JA
authors.lastname: Rincon
authors.forename: Carlos
authors.initials: C
authors.lastname: Mateos
authors.forename: C Oliver
authors.initials: CO
authors.lastname: Kappe
mesh_terms: D000096:Acetone / Q000031:analogs & derivatives* / Q000737:chemistry; D001593:Benzyl Compounds / Q000138:chemical synthesis* / Q000737:chemistry; D001974:Bromosuccinimide / Q000737:chemistry; D002384:Catalysis; D054879:Halogenation; D008027:Light; D015394:Molecular Structure; D055668:Photochemical Processes; D011138:Polytetrafluoroethylene / Q000737:chemistry*
chemical_list: D001593:Benzyl Compounds; D000096:Acetone; D011138:Polytetrafluoroethylene; D001974:Bromosuccinimide; C008863:1-phenyl-2-propanone