Amides base-induced hydrolysis

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. 

Treatment of proteins with alkali can alter their conformation, with the extent of alteration depending on concentration of the base, duration of treatment and the temperature. Hydroxide ions can denature the protein and Induce hydrolysis of amide groups of glutamine and asparagine, causing the protein to be more water soluble. 

Anhydrides react with water to generate carboxylic acids, with alcohols to give esters, and with amines to form amides. Esters behave similarly. There are both acid-catalyzed and base-induced reactions of esters with water (ester hydrolysis) to give carboxylic acids. There are both acid- and base-catalyzed versions of the reaction of esters with alcohols (transesterification) that generate new esters. Esters also react with amines to form amides. 

Even though amides are the least reactive of the acyl compounds, they can nevertheless be hydrolyzed in either acid or base. The mechanisms of these reactions are directly related to those of acid- or base-induced ester hydrolysis. In base, the carbonyl carbon of an amide is attacked to give tetrahedral intermediate A (Fig. 18.39). 

The perfection of this strategy makes use of the L-threonine-derived 2S,ZR acid 61 and tert-h xiy iV-(p-methoxybenzyl)glycinate as the active methylene partner [28d]. After condensation to amide 62, base treatment (LHMDS) induced epoxydation (at 0 °C) and then (25 °C) cyclization. This double inversion mechanism produced a single epimer, 63a, which, through acid 63b, was converted to target 11 by silylation, ester hydrolysis, lead tetraacetate and CAN (or peroxydisulfate) oxidation. 

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