Rediscovering Cyanogen Gas for Organic Synthesis: Formation of 2-Cyanothiazole Derivatives

The expeditious synthesis of an API building block, 2-cyanothiazole,from cyanogen gas and a readily available dithiane is reported. Apreviously undisclosed partially saturated intermediate is formed,which can be further functionalized and isolated by the acylationof the hydroxy group. Dehydration using trimethylsilyl chloride furnished2-cyanothiazole, which could be further converted to the correspondingamidine. The sequence provided a 55% yield over 4 steps. We envisionthat this work will spark further interest in cyanogen gas as a reactiveand cost-effective synthetic reagent.

Automated summary

This study reports the fast synthesis of 2-cyanothiazole, an API building block, from cyanogen gas and a readily available dithiane. A previously undisclosed partially saturated intermediate is formed and can be further functionalized and isolated by acylation of the hydroxy group. Dehydration using trimethylsilyl chloride yields 2-cyanothiazole, which can be converted to the corresponding amidine. The overall process provides a 55% yield over 4 steps. It is anticipated that this research will generate further interest in cyanogen gas as a reactive and cost-effective synthetic reagent.