Cyanation

Cyanation of arenes

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:

With arene as two-electron electrophile

While the classical Rosenmund Von-Braun reaction utilizes stoichiometric copper(I) cyanide as a cyanation source, newer variants have been developed that are catalytic in copper:

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:

Nickel-catalyzed cyanations avoid the use of precious metals, and can take advantage of benzyl cyanide or acetonitrile as a cyanide source, via reductive C-C bond cleavage:

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.

With arene as a two-electron nucleophile

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:

With arene as a radical electrophile

Radical approaches to arene C-H cyanation are known. Photoredox mediators (metallic or organic) are most common: