The nitration of aromatic compounds is a key reaction in organic chemistry. Conventionally, this reaction is difficult to control due to its exothermic character and the reagents’ high reactivity. As a result, the reaction is often performed by paralleling batch reactions. Direct nitration with nitric acid limits batch scale-up, but it is now shown to be possible in continuous flow. The latter has the added advantage of handling all toxic and corrosive reagents inside a closed system.

Nitration of model substrate

To avoid the use of expensive nitration 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 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.
      2) Automated reaction optimisation.
      3) Out scaling to preparative synthesis

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