Amide Hydrolysis in Acid Solution

Steps 1 through 3 show the formation of the tetrahedral intermediate. Step 1 Protonation of the carbonyl oxygen of the amide 

Step 2 Nucleophilic addition of water to the protonated amide 

Step 3 Deprotonation of the oxonium ion to give the neutral form of the tetrahedral intermediate 

Dissociation of the tetrahedral intermediate is shown in steps 4 through 6. Step 4 Protonation of the tetrahedral intermediate at its amino nitrogen 

Step 5 Dissociation of the A -protonated form of the tetrahedral intermediate to give ammonia and the protonated form of the carboxylic acid 

First Stage Formation of the tetrahedrai intermediate Steps 1-3 are analogous to the mechanism of acid-catalyzed hydration of aldehydes and ketones and acid-catalyzed hydrolysis of esters. 

Second Stage Dissociation of the tetrahedral intermediate Just as steps 1-3 corresponded to addition of water to the carbonyl group, steps 4-6 correspond to elimination of ammonia or an amine from TI and restoration of the carbonyl group. 

Chapter 19 Carboxylic Acid Derivatives Nucleophilic Acyl Substitution 

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On the basis of the general mechanism for amide hydrolysis in acidic solution shown in Figure 20.7, write an analogous sequence of steps for the... 

A more reactive equivalent for ketone synthesis is a nitrile 28. Addition of a Grignard reagent gives an intermediate 29, stable under the reaction conditions, rather like 21. Hydrolysis in acid solution releases the ketone 2. The exactly analogous reagent to DMF would be a tertiary amide... 

Amide hydrolysis in aqueous solution is also catalyzed by acid. Marlier and co-workers reported a detailed kinetic isotope effect study of the acid-catalyzed hydrolysis of formamide (Figure 7.31). The large deuterium... 

The amide group is readily hydrolyzed to acrylic acid, and this reaction is kinetically faster in base than in acid solutions (5,32,33). However, hydrolysis of N-alkyl derivatives proceeds at slower rates. The presence of an electron-with-drawing group on nitrogen not only facilitates hydrolysis but also affects the polymerization behavior of these derivatives (34,35). With concentrated sulfuric acid, acrylamide forms acrylamide sulfate salt, the intermediate of the former sulfuric acid process for producing acrylamide commercially. Further reaction of the salt with alcohols produces acrylate esters (5). In strongly alkaline anhydrous solutions a potassium salt can be formed by reaction with potassium / /-butoxide in tert-huty alcohol at room temperature (36). 

The instability of primary nitramines in acidic solution means that the nitration of the parent amine with nitric acid or its mixtures is not a feasible route to these compounds. The hydrolysis of secondary nitramides is probably the single most important route to primary nitramines. Accordingly, primary nitramines are often prepared by an indirect four step route (1) acylation of a primary amine to an amide, (2) A-nitration to a secondary nitramide, (3) hydrolysis or ammonolysis with aqueous base and (4) subsequent acidification to release the free nitramine (Equation 5.17). Substrates used in these reactions include sulfonamides, carbamates (urethanes), ureas and carboxylic acid amides like acetamides and formamides etc. The nitration of amides and related compounds has been discussed in Section 5.5. 

The amide of alanine can be resolved by pig kidney acylase. Which enantiomer of alanine is acylated faster with acetic anhydride In the enzyme-catalysed hydrolysis, which enantiomer hydrolyses faster In the separation, why is the mixture heated in acid solution, and what is filtered off How does the separation of the free alanine by dissolution in ethanol work ... 

The obvious hydrolysis of the nitrile must be carried out carefully to avoid racemisation.39 42 Two successful ways are direct conversion into esters 134 in acid solution or a two step process to the acids 132 via the much less easily racemised amides 133. 

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