The synthesis of azides is a key reaction in organic chemistry, as it provides a good pathway towards triazoles through the Huisgen azide-alkyne cycloaddition. Traditionally, this reaction is carried out using a variety of halide or amine substrates and azide reagents, such as triflyl azide and TMS-azide. A more economical reagent, albeit not commercially available, is imidazole-1-sulfonyl azide, which has the added advantage of being shelf-stable in its hydrochloride form.

Diazo transfer on model substrate using imidazole sulfonyl azide

In general, azide chemistry is dangerous: depending on substrate, reagent, temperature etc., azides can decompose violently. To be able to handle these potentially explosive compounds 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 amine 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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