Hydrolysis of amide and nitrile

The enantioselective enzymatic hydrolysis of amides is widely studied. These reactions are catalyzed by acylases, amidases and lipases. Some examples are shown in Fig. 10.32. Aspartame, an artificial sweetener, is synthesized by thermo lysin, a protease (Fig. 10.32(a)). 

Enantioselective hydrolysis of nitriles into amides or acids has primarily been catalyzed by various Rhodococus and Pseudomonas species (Fig. 10.33). Prochiral compounds were also hydrolyzed to give the corresponding acid in high yield and ee (Fig. 10.33(d), (e) and (g)). - In the reaction of substituted malononitrile with Rhodococcus rhodochrous, the first hydrolysis step leading to diamide proceeded without enantiodiscrimination, but further hydrolysis of the diamide proceeded with high enantioselectivity, affording the (Placid in 92% yield and 96% ee (Fig. 10.33(g)). 

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The hydrolysis of amides and nitriles may be conducted not only in acid solution but also in the presence of alkali. When dealing with substances soluble in water only with difficulty, it is customary to use alcohol as a solvent. In the latter instance, in connection with acid hydrolysis, the organic acid formed in the reaction is partially converted into an ester, whereas ammonia, or a substituted ammonia, will be present in the form of a salt with the inorganic acid used. When the hydrolysis is conducted in the presence of alkali, the organic acid is present as the sodium or potassium salt, whereas the amine is liberated and, if volatile, may be lost when the reaction mixture is refluxed. Type experiments are illustrated in connection with the laboratory work, page 146. 

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