Fluorous multi-phase bromination reaction of alkenes could be successfully transformed to a continuous microflow system in which a fluorous polyether, Galden® HT135, is employed as a recyclable molecular bromine support. This microflow bromination of alkenes could be carried out without any temperature control or an inert gas atmosphere. The circulatory continuous microflow reaction system for bromination of cyclohexene was created which gave 8.3 g (85%) of dibromocyclohexane after continuous operation for 6 h.
1. Reviews on fluorous solvents: (a) Maul, J. J.; Ostrowski, P. J.; Ublacker, G. A.; Linclau, B.; Curran, D. P.Top. Curr. Chem. 1999, 206, 79;
Reviews on fluorous solvents: (a) Maul, J. J.; Ostrowski, P. J.; Ublacker, G. A.; Linclau, B.; Curran, D. P.Top. Curr. Chem. 1999, 206, 79;)| false
10. Continuous microflow bromination of cyclohexene with a circulatory recycling of Galden: a hexane solution of cyclohexene (75 mmol, 6.16 g) was loaded into a container (0.75 M, 100 mL). Galden HT135 (50 mL), bromine (excess), and water were loaded into another container. Saturated Br2 solution in Galden HT135 was prepared with gentle stirring. Flow rates were adjusted to 0.15 mL/min for cyclohexene solution and 1.2 mL/min for saturated bromine solution, and the two solutions were mixed in a T-shaped micromixer (MiChS®α-400, 400 μm i.d.). The mixture was then fed into the residence time unit (500 μm i.d. × 3.4 m, residence time: 2 min). The reaction mixture was then mixed with 0.3 M basic Na2S2O3 aqueous solution in another T-shaped mixer (MiChS®α-400, 400 μm i.d.), and the entire mixture was collected in a Y-shaped flask, where a small amount of CHCl3 was placed. The bottomed fluorous solvent was pumped back to the container containing bromine. This system was operated for 6 hours, and consumed 40.5 mmol of cyclohexene. The top organic phase was separated from the aqueous phase, and the aqueous phase was extracted with hexane. Combined organic phase was dried over MgSO4. The solvent was removed under reduced pressure to give colorless oil (8.91 g), which was purified by short silica gel column chromatography to give pure dibromocyclohexane (8.3 g, 85%).