Nitriles, reaction with Grignard reagents

Section 20 20 Nitriles are useful starting materials for the preparation of ketones by reaction with Grignard reagents... 

On reaction with Grignard reagents, p-keto nitriles are transformed into enamino ketones." The carbonyl group is protected as the enolate anion. To retain the nitrogen atom, a mild workup is required. 

Nitriles are synthetically versatile functional groups because they are readily converted to carboxylic acids by hydrolysis under addic or basic conditions, reduced with LiAlH4 to form primary amines, and reaction with Grignard reagents leads to the formation of ketones. These reactions are illustrated here ... 

Nitriles are similar in some respects to carboxylic acids and are prepared either by 5 2 reaction of an alkyl halide with cyanide ion or by dehydration of an amide. Nitriles undergo nucleophilic addition to the polar C=N bond in the same way that carbonyl compounds do. The most important reactions of nitriles are their hydrolysis to carboxylic acids, reduction to primary amines, and reaction with Grignard reagents to yield ketones. 

The conversion of a nitrile R —CN into a ketone R —CO—R demonstrates that polarized multiple bonds other than C=0 also react with Grignard reagents, and that such reactions are synthetically useful. Esters 22 and acid chlorides can react subsequently with two equivalents of RMgX the initially formed tetravalent product from the first addition reaction can decompose to a ketone that is still reactive, and reacts with a second RMgX. The final product 23 then contains two substituents R, coming from the Grignard reagent ... 

Nitriles (RC=N) react with Grignard reagents (R MgBr). The reaction produc from 2-methylpropanenitrile with methylmagnesium bromide has the fol lowing spectroscopic properties. Propose a structure. 

Methods of synthesis for carboxylic acids include (1) oxidation of alkyl-benzenes, (2) oxidative cleavage of alkenes, (3) oxidation of primary alcohols or aldehydes, (4) hydrolysis of nitriles, and (5) reaction of Grignard reagents with CO2 (carboxylation). General reactions of carboxylic acids include (1) loss of the acidic proton, (2) nucleophilic acyl substitution at the carbonyl group, (3) substitution on the a carbon, and (4) reduction. 

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