Reactions employing diazomethane as a methylating agent are very useful in organic synthesis, due to their high selectivity and yields. However, preparing diazomethane from one of the available precursor compounds requires much care, since it is a highly reactive species which can spontaneously explode on contact with sharp edges. Also, the reagent is very toxic, requiring good ventilation and safety measures to handle any unwanted liberation of diazomethane.

Methylation of benzoic acid with diazomethane

In general, diazomethane chemistry is dangerous. To be able to handle this explosive and toxic compound in a closed system, 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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