Introduction of Cyanide into Organic Substrates

Cyanide ion, because of its powerful nucleophilic character, forms C—CN bonds with reaction partners either by displacement of a leaving group or by nucleophilic addition to appropriate acceptors. Reactions of an electrophilic character (i.e., attack of nucleophilic partners on the cyano carbon) are achievable when cyanide is converted into derivatives such as cyanogen bromide (Section 7.2.2), cyanate (Section 7.2.3), thiocyanate (Section 7.2.4) and orthoformate (Section 7.2.5). 

Alkali metal (K, Na) [ CJcyanides have been extensively employed in the formation of alkyl [ CJnitriles via nucleophilic displacement of leaving groups such as primary halides, sulfonates and trialkylammonium salts in examples too numerous to mention. In special cases (e.g., 1) other leaving groups have been used, such as benzotriazol-l-yl. The most important considerations in the choice of leaving group are often the ease of substrate preparation and the compatibility of the displacement reaction with substrate ancillary functional groups. 

With secondary halides or sulfonates only moderate yields are obtained, while tertiary substrates fail due to side reactions involving elimination. The most effective solvents are usually polar ones such as DMF, DMSO, aqueous methanol or ethanol and 2-metho-xyethanol. Tertiary nitriles can be prepared by SnCLi-catalyzed reaction of the 

In contrast to [ CJcarboxylations commonly used for one-[ C]carbon homologations, [ ]cy anations can be performed on precursors containing unprotected hydroxy, amino and 

Aromatic and heteroaromatic halides fail to react with alkali metal cyanides under the conditions normally used for aliphatic nucleophilic displacement reactions. Traditionally, the preparation of aryl [ CJnitriles has been accomplished either by the Sandmeyer reaction or the Rosenmund-von Braun reaction. In the former, cyano-dediazoniation of aryl diazonium salts is accomplished with Cu CN or a mixture of and CuCN (or CuCl) 

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