Toluenesulfonyl Cyanide (TsCN)

Introduction

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,[1] carbonyl compounds,[2] and other types of organic compounds.[3] It has been used in radical-mediated cyanation[4] and hydrocyanation[5] reactions. Furthermore, TsCN has been reported to be a good component for [4+2][6] and [3+2][7] cycloaddition reactions. The sulfonyl tetrazoles produced from 1,3-dipolar cycloaddition of TsCN with azides can be further elaborated using nucleophilic aromatic substitution (S_NAr). This two-step process represents an interesting ligation strategy that probably warrants greater exploration in chemical biology.[8] Other uses of TsCN in the recent literature include reactions with allylic alcohols to make allyl sulfones,[9] and palladium-catalyzed C–H activation of arenes to synthesize diaryl sulfides.[10]

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 [1]).[11] Compared to other commonly used CN⁺ equivalents, such as cyanogen bromide [LD₅₀ (rats, orally) = 25–50 mg/kg],[12] TsCN is less toxic [LD₅₀ (rats, orally) = 800–1000 mg/kg][13] and has a longer shelf life. Hence, TsCN will likely continue to serve as an important and versatile reagent for ­organic synthesis.

Scheme 1 Cox and Ghosh’s synthesis of toluenesulfonyl cyanide[11b]

• References

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• 13 Cox JM, Ghosh RD. E. Patent 1930014A, 1969