Amides acid-induced hydrolysis

The acid-induced nucleophilic addition of a nitrile to a carbenium ion, followed by hydrolysis to the corresponding amide. 

FIGURE 18.39 The base-induced hydrolysis of amides gives carboxylate anions. Acidification of the carboxylate at the end of the reaction would give the carboxylic acid. 

Both acid- and base-induced hydrolysis of a nitrile gives the amide, but rather severe conditions are required for the reactions, and further hydrolysis of the intermediate amides gives the carboxylic acids (p. 902). In acid, the first step is protonation of the nitrile nitrogen to give a strong Lewis acid (A, Fig. 18.45), which is attacked by water. A series of proton shifts then gives an amide that is hydrolyzed to the carboxylic acid. 

Patricelli MP, Patterson JE, Boger DL, Cravatt BF (1998) An Endogenous Sleep-Inducing Compound is a Novel Competitive Inhibitor of Fatty Acid Amide Hydrolysis. Bioorg Med Chem Lett 8 613... 

Either (S)-specific aminopeptidase catalyzed hydrolysis of racemic PGA11 or crystallization-induced asymmetric transformation of racemic PGA with (.S l-mandelic acid as resolving agent12 can be used to prepare (R)-PGA. As a result of its ready availability on large scale within DSM, we envisaged the application of (R)-PGA for the production of enantiomerically pure amine functionalized compounds using the chirality transfer concept. Obviously, (S)-phenylglycine amide is also available and can be used for the preparation of the opposite enantiomer of the amines described. 

The most prominent green example, the regioselective hydrolysis of an amide on an industrial scale, is the production of penicillin. PenG acylase selectively hydrolyses the more stable amide bond, leaving the /Mactam ring intact [75, 76]. For a full discussion of this example see Chapter 1 (Fig. 1.37) and Chapter 8. Since the starting material is already enantiopure the enzyme induces no stereoinformation. In other industrial processes the enantioselectivity of the enzymes is used. This is, in particular, the case in the production of natural and unnatural amino acids. 

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