In organic synthesis, cyanation is the attachment or substitution of a cyanide group on various substrates. Such transformations are high-value because they generate C-C bond. Furthermore nitriles are versatile functional groups.
Typically, alkyl nitriles are formed via SN1 or SN2-type cyanation with alkyl electrophiles. Illustrative is the synthesis of benzyl cyanide by the reaction of benzyl chloride and sodium cyanide. In some cases cuprous cyanide is used instead of sodium cyanide.
Cyanation of ketones or aldehydes yields the corresponding cyanohydrins, which can be done directly with the cyanide ion (the cyanohydrin reaction) or by using bisulfite, followed by displacement of sulfite:
A related reaction is hydrocyanation, which installs the elements of H-CN.
Cyanation of arenes offers access to benzoic acid derivatives, as well as the utility of aryl nitriles themselves in as fine chemicals:
A variety of mechanistically distinct pathways are known to cyanate arenes:
In addition, palladium-catalyzed cyanations of aryl halides have been extensively explored. Generally, KCN or its less toxic surrogate Zn(CN)2 are used as nucleophilic cyanide sources. To further diminish toxicity concerns, potassium ferricyanide has also been used as a cyanide source. Catalytic cycles are believed to proceed through a standard Pd (0/II) pathway with reductive elimination forging the key C-C bond. Deactivation of Pd(II) with excess cyanide is a common problem. Palladium catalysis conditions for aryl iodides, bromides, and even chlorides have been developed:
Sandmeyer cyanation is a means of converting aniline derivatives to benzonitriles. The cyanation is generally postulated to be two-electron, while with radical mediators in absence of metals, the reaction is likely radical.
Metalated arenes can be cyanated with electrophilic cyanide sources, including cyanamides, cyanates, dimethylmalononitrile, or ethyl (ethoxymethylene)cyanoacetate. These methods can proceed with or without transition metal mediation: