Nitriles and nitroalkanes can be alkylated

The second is a substitution reaction attack of the nucleophilic anion on an electrophilic alkyl halide. All the factors controlling S l and 5 2 reactions, which we discussed at length in Chapter 15, are applicable here. 

In each case, we shall take one of two approaches to the choice of base. 

The second approach is easier practically (just mix the starting material, base, and electrophile), but works only if the base and the electrophile are compatible and don t react together. With the first approach, which is practically more demanding, the electrophile and base 

Problems that arise from the electrophilicity of the carbonyl group can be avoided by replacing C=0 by functional groups that are much less electrophilic but are still able to stabilize an adjacent anion. We shall consider two examples, both of which you met in Chapter 20. 

The nitrile does not have to be deprotonated completely for alkylation with sodium hydroxide only a small amount of anion is formed. In the example below, such an anion reacts with propyl bromide to give 2-phenylpentanenitrile. 

Firstly, the nitrile group, which mirrors the carbonyl group in general reactivity but is much less easily attacked by nucleophiles (N is less electronegative than O). 

The anion formed by deprotonating a nitrile using strong base will not react with other molecules of nitrile but will react very efficiently with alkyl halides. The slim, linear structure of the anions makes them good nucleophiles for Sn2 reactions. 

Nitrile-stabilized anions are so nucleophilic that they will react with alkyl halides rather well even when a crowded quaternary centre (a carbon bearing no H atoms) is being formed. In this example the strong base, sodium hydride, was used to deprotonate the branched nitrile completely and benzyl chloride was the electrophile. The greater reactivity of benzylic electrophiles compensates for the poorer leaving group. In DMF, the anion is particularly reactive because it is not solvated (DMF solvates only the Na+ cation). 

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