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Simple and safe method for using prussic acid as a precursor for valuable chemical compounds

Researchers from professor Troels Skrydstrup group publish new paper in Chemical Science describing a more safe and simple setting for performing chemical reactions with the highly toxic and explosive hydrogen cyanide

PhD Steffan K. Kristensen, Assoc. Prof. Anders Lindhardt and Prof. Troels Skrydstrup publish results from a project under BIOVALUE SPIR funded by Innovation Fund Denmark.

The class of compounds, benzonitriles are highly valuable within a broad range of applications serving as important substructures in many agrochemicals, pharmaceuticals, dyes, polymers and other organic materials. The nitrile group (C:::N) is also a precursor to a variety of important functionalities in organic molecules. However, there is a reluctance to applying hydrogen cyanide (HCN or prussic acid) in an academic setting or an R&D laboratory, which is undoubtedly linked to the high toxicity and explosive nature of this gaseous one-carbon reagent, thereby complicating its handling, storage and transportation

The work published by PhD Steffan K. Kristensen, Assoc. Prof. Anders Lindhardt and Prof. Troels Skrydstrup describes a simple setup whereby HCN is delivered in stoichiometric amounts by ex situ generation in a two-chamber reactor, thereby providing a safe setting for handling gaseous HCN in small-scale reactions, without the need for an HCN cylinder.

They demonstrate the usefulness of this setup not only for the Pd-catalysed cyanation of aryl bromides, but also for the Ni-mediated hydrocyanation of styrenes as a test reaction. With respect to the cyanation reactions, good functional group tolerance was obtained, and the method proved amenable to scale-up, but also to carbon-13 isotope labelling applying H13CN. The methodology was tested on the synthesis of three pharmaceuticals containing a benzonitrile subunit, including dapivirine, citalopram and letrozole, providing isolated yields from 86–97%.

This work is funded under the SPIR initiative by The Innovation Fund Denmark (http://biovalue.dk/), and Haldor Topsøe A/S.

For direct access to the paper: http://pubs.rsc.org/en/content/articlelanding/2017/sc/c7sc03912c#!divAbstract