26.6 Chemical Properties of Amines and Amides

Learning Objectives

By the end of this section, you will be able to:

  • Identify the typical reaction that amides undergo.
  • Identify and describe the substances from which most amines and amides are prepared.
  • Describe the preparation procedure for amines and amides.

Organic functional groups can be converted into other functional groups through reactions. A map of some of the more common reactions to convert functional groups can be found in Section 19.6 – General Reactions of Carbon in Infographic 19.6a.

Reactions of Amides

Generally, amides resist hydrolysis in plain water, even after prolonged heating. In the presence of added acid or base, however, hydrolysis proceeds at a moderate rate. In living cells, amide hydrolysis is catalyzed by enzymes. Amide hydrolysis is illustrated in Figure 26.6a.

Hydrolysis reaction of an amide (CH3CH2CONH2) and water (H2O) using enzymes in an acid solution to form a carboxylic acid (CH3CH2COOH) and ammonia (NH3).
Figure 26.6a. Hydrolysis of an amide in acid solution actually gives a carboxylic acid and the salt of ammonia or an amine (the ammonia or amine initially formed is neutralized by the acid). Basic hydrolysis gives a salt of the carboxylic acid and ammonia or an amine. (Credit: Intro Chem: GOB (V. 1.0)., CC BY-NC-SA 3.0)

Example 26.6a

Write the equation for the hydrolysis of each compound.

  • butyramide
  • benzamide

Solution

    1. The hydrolysis of a simple amide produces an organic acid and ammonia. Butyramide thus yields butyric acid and ammonia.
      Butyramide (CH3CH2CH2CONH3) and water (H2O) react to form a carboxylic acid, butyric acid, (CH3CH2CH2COOH) and ammonia (NH3).
      Figure 26.6b. Solution for reaction of butyramide and water.
    1. The hydrolysis of an amide produces an organic acid and ammonia. Benzamide thus yields benzoic acid and ammonia.
      Benzamide and water (H2O) react to form a carboxylic acid, benzoic acid and ammonia (NH3).
      Figure 26.6c. Reaction of benzamide and water.

       

Exercise and Image Source: Intro Chem: GOB (V. 1.0)., CC BY-NC-SA 3.0

Exercise 26.6a

What are the products of the hydrolysis of an amide?

Check Your Answers:[1]

Exercise 26.6b

When the amide CH3CH2CH2CH2CONH2 is hydrolyzed in an NaOH solution, the products are CH3CH2CH2CH2COO−Na+ and NH3. What products are obtained when CH3CH2CH2CH2CONH2 is hydrolyzed in an hydrochloric acid solution?

Check Your Answers:[2]

Formation of Amides

Amides can be produced when carboxylic acids react with amines or ammonia in a process called amidation. A water molecule is eliminated from the reaction, and the amide is formed from the remaining pieces of the carboxylic acid and the amine (note the similarity to formation of an ester from a carboxylic acid and an alcohol discussed in the previous section).

When a carboxylic acid reacts with ammonia (NH3) a primary amide is formed. But the reaction is very slow at room temperature. Water molecules are split out, and a bond is formed between the nitrogen atom and the carbonyl carbon atom (Figure 26.6d.).

The reactions shows acetic acid (CH3COOH) reacting with ammonia (NH3) to form acetamide (CH3CONH2) and water (H2O).
Figure 26.6d. (Credit: Intro Chem: GOB (V. 1.0)., CC BY-NC-SA 3.0)

When a carboxylic acid reacts with primary or secondary amines, secondary or tertiary amides are produced, respectively (Figure 26.6e.).

The chemical reaction shows a carboxylic acid (CH3CH2COOH) reacting with an amine (CH3NH2) to form an amide (CH3CH2CONHCH3) and water (H2O).
Figure 26.6e. Reaction of a carboxylic aid and amine produce an amide and water. (Credit: Chemistry (OpenStax), CC BY 4.0)

Tertiary amines do not have a hydrogen attached to the nitrogen and therefore do not form amides when mixed with carboxylic acids. However, an acid-base reaction does occur with the amine accepting a proton (acts as a base) and the carboxylic acid donating a proton. In this case the ammonium and carboxylate salts are formed.

In living cells, amide formation is catalyzed by enzymes. Proteins, which make up all enzymes, are polyamides; they are formed by joining amino acids into long chains. In proteins, the amide functional group is called a peptide bond.

Carboxylic acids will react with alcohols and amines following a similar pattern. In both cases, the –OH group of the carboxylic acid will be replaced by a different group to form either an ester or an amide, with water formed as a by-product. When the reaction involves an alcohol, the –OH of the acid is replaced by the –OR’ of the alcohol (Figure 26.6f.). When the reaction involves an amine, the –OH of the acid is replaced by the –NH2, or –NHR’, or –NR’2 of the amine (Figure 26.6g.).

Here we see the reaction of a carboxylic acid and an alcohol to form an ester and water.
Figure 26.6f. Formation of an ester. (Credit: Intro Chem: GOB (V. 1.0)., CC BY-NC-SA 3.0)
Here we see the reaction of acetic acid (CH3COOH), a carboxylic acid, with ammonia (NH3) to form an amide, acetamide (CH3CONH2) and water (H2O).
Figure 26.6g. Formation of an amide. (Credit: Intro Chem: GOB (V. 1.0)., CC BY-NC-SA 3.0)

Amides can also be prepared from the reaction of an acid chloride with ammonia.  Refer to Section 25.3 Formation and Reactions of Carboxylic Acids where the formation of acid chlorides is discussed as well as their reaction with ammonia.

Formation of Amines

Reduction of Amides

Like other carboxylic acid derivatives, amides can be reduced by LiAlH4. The product of the reduction, however, is an amine rather than an alcohol (Figure 26.6h.). The net effect of an amide reduction is thus the conversion of the amide carbonyl group into a methylene group (C=O⟶CH2). This kind of reaction is specific to amides and does not occur with other carboxylic acid derivatives.

The reduction reaction of N-methyldodecanamide with lithium aluminum hydride followed by hydrolysis gives dodecylmethylamine (ninety-five percent). The carbonyl group is reduced to C H 2.
Figure 26.6h. Reaction of an amide with lithium aluminum hydride and hydrolysis to form an amine (Credit: Organic Chemistry (OpenStax), CC BY-NC-SA 4.0).

Example 26.6b

Synthesizing an Amine from an Amide

How could you prepare N-ethylaniline by reduction of an amide with LiAlH4?

The structure of N-ethylaniline, a derivative of aniline where an ethyl group replaces one of the hydrogen atoms of the amine.
Figure 26.6i. Reduction of an amide with lithium aluminum hydride to produce N-ethylaniline (Credit: Organic Chemistry (OpenStax), CC BY-NC-SA 4.0).

Strategy

Reduction of an amide with LiAlH4 yields an amine. To find the starting material for synthesis of N-ethylaniline, look for a CH2 position next to the nitrogen atom and replace that CH2 by C═O. In this case, the amide is N-phenylacetamide.

Solution

The reaction shows the reduction of N-phenylacetamide using lithium aluminum hydride in ether followed by addition of water to form N-ethylaniline.
Figure 26.6j. Reduction of an amide with lithium aluminum hydride and hydrolysis to form an N-Ethylaniline. (Credit: Organic Chemistry (OpenStax), CC BY-NC-SA 4.0).

Reduction of Nitriles

Using lithium aluminum hydride (LiAlH4), a nitrile can be reduced to a primary amine (Figure 26.6k.). The process to predict the product of a hydride reduction is shown in Figure 26.6l. (Farmer et al., n.d.).

Reaction of a nitrile with lithium aluminum hydride to produce a primary amine.
Figure 26.6k. Reduction of a nitrile to form a primary amine. (credit: Organic Chemistry (Morsch et al.), CC BY-SA 4.0. )

 

In this reaction of a nitrile, the two pi bonds are removed and two sigma bonds are added to the carbon and nitrogen. Lastly a hydrogen is added to each bond to produce the primary amine. The hydrogens come from a hydride source.
Figure 26.6l. Prediction of product of nitrile reduction (credit: Organic Chemistry (Morsch et al.), CC BY-SA 4.0).

Example 26.6c

Write the product from this reaction.

Reaction of Benzonitrile with LiAlH4 and water produces what?
(credit: Organic Chemistry (Morsch et al.), CC BY-SA 4.0.)

Solution:

Following the process outlined in Figure 26.6l, the answer is

The structure of benzyl amide which is a benzene ring with an adjoining methyl amine group
(credit: Organic Chemistry (Morsch et al.), CC BY-SA 4.0.)

 

Source: Example 26.6c is adapted from “20.7: Chemistry of Nitriles” by Steven Farmer, Dietmar Kennepohl, Layne Morsch, William Reusch In Organic Chemistry (Morsch et al.), CC BY-SA 4.0. / Image cut in two.

The formation of nitriles (R-C≡N) can be found in Section 25.3 – Formation and Reactions of Carboxylic Acids.

Alkylation of Ammonia

Another way to produce an amine is to react an alkyl halide (also called haloalkane) with ammonia.  This reaction substitutes one hydrogen of the ammonia with the alkyl portion of the alkyl halide.  It can be completed with ammonia to produce a 1o amine or with a 1o amine to produce a 2o amine or with a 2o amine to produce a 3o amine.

 

 

Reaction 1 shows ethyl bromide reacting with ammonia to produce a primary amine. Reaction 2 sows ethyl bromide with ethyl amine to produce a secondary amine. Reaction 3 shows ethyl bromide reacting with diethyl amine to produce a tertiary amine.
Figure 26.6m. Formation of primary amine from ammonia, secondary amine from primary amine, and tertiary amine from secondary amine through alkylation (credit: Supplemental Modules, CC BY-NC 4.0 / Adapted by Samantha Sullivan Sauer / Biovia Draw)

Exercise 26.6c

Write the structures of the amide and the nitrile that when reduced produce this amine.

Write the structures of the amide and the nitrile that when reduced produce this amine (NH2CH2CHCH3(CH3))
(credit: Samantha Sullivan Sauer / Biovia Draw, CC BY-NC 4.0)

Check Your Answers:[3]

Source: Exercise 26.6c created by Samantha Sullivan Sauer, images drawn using Biovia Draw, CC BY-NC 4.0

Attribution & References

Except where otherwise noted, this page is written and adapted by Caryn Fahey and Samantha Sullivan Sauer from

References cited in-text

Farmer, S., Kennepohl, D., Morsch, L., & Reusch, W. (n.d.). 20.7: Chemistry of Nitriles. In Organic Chemistry (Morsch et al.). LibreTexts. CC BY-SA 4.0.

  1. a carboxylic acid and ammonia or an amine ↵
  2. CH3CH2CH2CH2COOH and NH4Cl ↵
  3. Answer for the amide and the nitrile

    ↵

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Organic and Biochemistry Supplement to Enhanced Introductory College Chemistry Copyright © 2024 by Gregory Anderson; Caryn Fahey; Adrienne Richards; Samantha Sullivan Sauer; David Wegman; and Jen Booth is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License, except where otherwise noted.

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