Base-catalyzed hydrolysis of amides

The amide bonds in peptides and proteins can be hydrolyzed in strong acid or base Treatment of a peptide or protein under either of these conditions yields a mixture of the constituent amino acids. Neither acid- nor base-catalyzed hydrolysis of a protein leads to ideal results because both tend to destroy some constituent ammo acids. Acid-catalyzed hydrolysis destroys tryptophan and cysteine, causes some loss of serine and threonine, and converts asparagine and glutamine to aspartic acid and glutamic acid, respectively. Base-catalyzed hydrolysis leads to destruction of serine, threonine, cysteine, and cystine and also results in racemization of the free amino acids. Because acid-catalyzed hydrolysis is less destructive, it is often the method of choice. The hydrolysis procedure consists of dissolving the protein sample in aqueous acid, usually 6 M HC1, and heating the solution in a sealed, evacuated vial at 100°C for 12 to 24 hours. 

Problem-Solving Strategy Proposing Reaction Mechanisms 1007 Mechanism 21-8 Transesterification 1008 21-7 Hydrolysis of Carboxylic Acid Derivatives 1009 Mechanism 21-9 Saponification of an Ester 1010 Mechanism 21-10 Basic Hydrolysis of an Amide 1012 Mechanism 21-11 Acidic Hydrolysis of an Amide 1012 Mechanism 21-12 Base-Catalyzed Hydrolysis of a Nitrile 1014 21-8 Reduction of Acid Derivatives 1014... 

Base-Catalyzed Hydrolysis of a Nitrile 1014 Hydride Reduction of an Ester 1015 Reduction of an Amide to an Amine 1016 Reaction of an Ester with Two Moles of a Grignard Reagent 1018... 

A structurally well-defined and water-soluble PVAm is available by acid or base catalyzed hydrolysis of PVFA (Scheme 2) [58, 59] because form-amide groups are readily hydrolyzed to amino groups. The degree of hydrolysis of PVFA can be used to produce adaptable copolymers, poly(vinyl form-amide-co-vinyl amine) (PVFA-co-PVAm) with different formamide/amino group ratios. Hence, the degree of hydrolysis of the formamide groups is an excellent tool to control the desired charge density of the polyelectrolyte. 

The chemistry behind amino acid analysis is nothing more than acid-catalyzed hydrolysis of amide (peptide) bonds. The peptide is hydrolyzed by heating in 6 M hydrochloric acid for about 24 h to give a solution that contains all the amino acids. This mixture is then separated by ion-exchange chromatography, which separates the amino acids mainly according to their acid-base properties. As the amino acids leave the chromatography column, they are mixed with ninhydrin and the intensity of the ninhydrin... 

The mechanism for acid-catalyzed hydrolysis of amides involves attack by water on the protonated amide. Amides are weak bases with pK values in the range from 0 to -2A An important feature of the chemistry of amides is that the most basic site is the carbonyl oxygen. Very little of the N-protonated form is present. The major factor that favors the O-protonated form is the retention of Tr-electron delocalization over the O-C-N system. No such delocalization is possible in the N-protonated form. 

Hydrolysis of a nitrile and an amide have both been converted for use in undergraduate laboratory classes (Scheme 6.13). The base-catalyzed hydrolysis of o-tol-unitrile can be performed using either a monomode (150 C for 10 min) or multimode unit (150 °C for 6 min) in sealed-vessel format. The shorter time required at the target temperature when using a multimode unit as opposed to the monomode systan is at first counterintuitive. However, the time taken to reach 150 C is significantly... 

Volumes of Activation for the Acid-Catalyzed and Base-Catalyzed Hydrolysis of Esters and Amides... 

FIGURE 15.17 Mechanism of base-catalyzed hydrolysis of unsubstituted amides. 

Sn2 reactions with anionic nucleophiles fall into this class, and observations are generally in accord with the qualitative prediction. Unusual effects may be seen in solvents of low dielectric constant where ion pairing is extensive, and we have already commented on the enhanced nucleophilic reactivity of anionic nucleophiles in dipolar aprotic solvents owing to their relative desolvation in these solvents. Another important class of ion-molecule reaction is the hydroxide-catalyzed hydrolysis of neutral esters and amides. Because these reactions are carried out in hydroxy lie solvents, the general medium effect is confounded with the acid-base equilibria of the mixed solvent lyate species. (This same problem occurs with Sn2 reactions in hydroxylic solvents.) This equilibrium is established in alcohol-water mixtures ... 

The depolymerization of nylon-6,6 and nylon-4,6 involves hydrolysis of the amide linkages, which are vulnerable to both acid- and base-catalyzed hydrolysis. In a DuPont patent,9 waste nylon-6,6 was depolymerized at a temperature... 

Further evidence for this mechanism is that a small but detectable amount of 0 exchange (see p. 425) has been found in the acid-catalyzed hydrolysis of benz-amide. (The exchange has also been detected for the base-catalyzed... 

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