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Toluenesulfonyl Cyanide (TsCN)
21 August 2013 (online)
Toluenesulfonyl cyanide (TsCN) is a convenient and versatile cyanide source that has great potential in organic synthesis. It displays useful reactivity for electrophilic cyanation of aromatic compounds, carbonyl compounds, and other types of organic compounds. It has been used in radical-mediated cyanation and hydrocyanation reactions. Furthermore, TsCN has been reported to be a good component for [4+2] and [3+2] cycloaddition reactions. The sulfonyl tetrazoles produced from 1,3-dipolar cycloaddition of TsCN with azides can be further elaborated using nucleophilic aromatic substitution (SNAr). This two-step process represents an interesting ligation strategy that probably warrants greater exploration in chemical biology. Other uses of TsCN in the recent literature include reactions with allylic alcohols to make allyl sulfones, and palladium-catalyzed C–H activation of arenes to synthesize diaryl sulfides.
TsCN is a white crystalline solid (mp 49–50 °C) that is available from dozens of commercial sources. It can be readily prepared in the lab by several methods (Scheme ). Compared to other commonly used CN+ equivalents, such as cyanogen bromide [LD50 (rats, orally) = 25–50 mg/kg], TsCN is less toxic [LD50 (rats, orally) = 800–1000 mg/kg] and has a longer shelf life. Hence, TsCN will likely continue to serve as an important and versatile reagent for organic synthesis.
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