Kolbe nitrile synthesis

The Kolbe nitrile synthesis is a method for the preparation of alkyl nitriles by reaction of the corresponding alkylhalide with a metal cyanide [Organikum, 22. Edition (German), Wiley-VCH, Weinheim, 2004, ISBN 3-527-31148-3] . A side-product for this reaction is the formation of an isonitrile because the cyanide ion is an ambident nucleophile and according to Kornblum's rule capable of reaction with carbon or with nitrogen. The reaction is named after Hermann Kolbe.

The ratio in which both isomers form depends on solvent and reaction mechanism. With application of alkali cyanides such as sodium cyanide and polar solvents the reaction type is an S_N2 reaction whereby the alkylhalide is attacked by the more nucleophilic carbon atom of the cyanide ion. This type of reaction with dimethyl sulfoxide as solvent is a convenient methode for the synthesis of nitriles. [cite journal
title = Preparation of Nitriles from Halides and Sodium Cyanide. An Advantageous Nucleophilic Displacement in Dimethyl Sulfoxide
author =L. Friedman, Harold Shechter
journal = Journal of Organic Chemistry
pages = 877–879
doi = 10.1021/jo01076a001
year = 1960
volume = 25]

With silver cyanide in diethyl ether as solvent the reaction runs according to a S_N1 reaction mechanism: the product is mainly the isonitrile by attack of the more nucleophilic nitrogen atom.

In particular primary alkyl halogenides and benzyl halogenides react with good chemical yields with alkali cyanides to nitriles. Secondary alkylhalides on the other hand only react in poor yields and tertiary halides not in the desired way.

Once formed the nitriles can de converted to the corresponding carboxylic acids by hydrolysis and from then on to more functional groups. In this way the Kolbe Nitrile synthesis is an important method in homologization.

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