The synthesis of α-ketone bromides is a useful reaction in organic chemistry, as it provides a good pathway towards α-substituted ketones through bromide substitution. Traditionally, this reaction is difficult to control due to its fast reaction rate and exothermic character. As a result, the brominated ketone easily reacts further to the double-brominated product. In batch, side product formation is largely overcome by controlled reagent addition and the use of mild bromination reagents (instead of bromine) such as N-bromosuccinimide, whose synthesis again requires the use of bromine. Direct α-ketone bromination with bromine limits batch scale-up, but has been shown to be possible in continuous flow. The latter has the added advantage of handling all toxic and corrosive reagents inside a closed system.

Bromination of model substrate

To avoid the use of expensive bromination reagents while keeping a high throughput at the same time, FutureChemistry has translated this reaction from a batch process to a continuous flow process. FutureChemistry’s typical three-tier approach led to a protocol which can be adapted to any viable ketone substrate:

       1) Translation of batch process to continuous flow process:
           a) Stock solutions approach, yielding a homogeneous reaction mixture.
           b) Quenching solution to follow the reaction in time.
           c) Flow markers approach to accurately assess reaction parameters.
      2) Automated reaction optimisation.
      3) Out scaling to preparative synthesis

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