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24.4: Hydrolysis of Amides

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    Generally, amides can be hydrolyzed in either acidic or basic solution. The mechanisms are much like those of ester hydrolysis (Section 18-7A), but the reactions are very much slower, a property of great biological importance (which we will discuss later):

    Roberts and Caserio Screenshot 24-4-1.png

    As we have indicated in Section 23-12, amide hydrolysis can be an important route to amines. Hydrolysis under acidic conditions requires strong acids such as sulfuric or hydrochloric, and temperatures of about \(100^\text{o}\) for several hours. The mechanism involves protonation of the amide on oxygen followed by attack of water on the carbonyl carbon. The tetrahedral intermediate formed dissociates ultimately to the carboxylic acid and the ammonium salt:

    Roberts and Caserio Screenshot 24-4-2.png

    In alkaline hydrolysis the amide is heated with boiling aqueous sodium or potassium hydroxide. The nucleophilic hydroxide ion adds to the carbonyl carbon to form a tetrahedral intermediate, which, with the help of the aqueous solvent, expels the nitrogen as the free amine:

    Roberts and Caserio Screenshot 24-4-3.jpg

    Biological amide hydrolysis, as in the hydrolysis of peptides and proteins, is catalyzed by the proteolytic enzymes. These reactions will be discussed in Chapter 25.

    An indirect method of hydrolyzing some amides utilizes nitrous acid. Primary amides are converted easily to carboxylic acids by treatment with nitrous acid. These reactions are very similar to that which occurs between a primary amine and nitrous acid (Section 23-10):

    Roberts and Caserio Screenshot 24-4-4.png

    Secondary amides give \(\ce{N}\)-nitroso compounds with nitrous acid, whereas tertiary amides do not react:

    Roberts and Caserio Screenshot 24-4-5.png

    A brief summary of important amide reactions follows:

    Roberts and Caserio Screenshot 24-4-6.png

    Of the many other types of organonitrogen compounds known, the more important include

    Roberts and Caserio Screenshot 24-4-7.png

    Although it is impractical to discuss all of these compounds in detail, we now will discuss briefly several that have not been given much attention heretofore.

    Contributors and Attributions

    John D. Robert and Marjorie C. Caserio (1977) Basic Principles of Organic Chemistry, second edition. W. A. Benjamin, Inc. , Menlo Park, CA. ISBN 0-8053-8329-8. This content is copyrighted under the following conditions, "You are granted permission for individual, educational, research and non-commercial reproduction, distribution, display and performance of this work in any format."

    24.4: Hydrolysis of Amides is shared under a not declared license and was authored, remixed, and/or curated by John D. Roberts and Marjorie C. Caserio.

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