Chemistry (9701) | Amides

Welcome to the World of Amides!

Hello future chemist! The topic of Amides is a fascinating corner of Organic Chemistry, especially because the functional group found here—the Amide Linkage—is the very backbone of life, forming the links between amino acids in proteins.

In these notes, we will define amides, learn how to make them (spoiler: they involve highly reactive acyl chlorides!), and explore their key reactions, including how they differ greatly in basicity compared to their cousins, the amines.

1. Defining the Amide Functional Group

1.1 Structure and Formula

Amides are compounds derived from carboxylic acids, where the hydroxyl ($\text{-OH}$) group of the carboxyl group ($\text{-COOH}$) is replaced by an amine group ($\text{-NH}_2$, $\text{-NHR}$, or $\text{-NR}_2$).

• The functional group is the carboxamide group: $\text{-CONH}_2$.
• The general formula for an unsubstituted (primary) amide is \(\text{RCONH}_2\).

Key Term: The \(\text{C=O}\) and \(\text{N-H}\) unit forms the Amide Linkage (or Peptide Bond).

1.2 Nomenclature (Naming)

Amides are named by taking the name of the corresponding carboxylic acid and replacing the suffix -oic acid with -amide.

Example: Ethanoic acid ($\text{CH}_3\text{COOH}$) $\rightarrow$ Ethanamide ($\text{CH}_3\text{CONH}_2$)

2. Preparation of Amides

The syllabus focuses on one primary method for forming amides: the reaction of ammonia or an amine with an acyl chloride.

2.1 Reaction with Acyl Chlorides

Acyl chlorides ($\text{RCOCl}$) are the most reactive class of carboxylic acid derivatives. They react readily with ammonia ($\text{NH}_3$) or amines ($\text{RNH}_2$) at room temperature.

This reaction is known as condensation or nucleophilic addition-elimination (Syllabus 33.3.2(d) & 34.3.1).

Step-by-Step Reaction

1. Reagents: Acyl chloride (e.g., Ethanoyl chloride) + Ammonia (or a Primary/Secondary Amine).
2. Conditions: Room temperature.
3. Products: Amide + Hydrogen Chloride ($\text{HCl}$).

Since $\text{HCl}$ is a strong acid, it immediately reacts with excess ammonia/amine present to form a salt. Therefore, the reaction is often carried out in excess ammonia/amine to mop up the $\text{HCl}$ produced.

General Equation (using Ammonia): \[ \text{RCOCl} + 2\text{NH}_3 \longrightarrow \text{RCONH}_2 + \text{NH}_4\text{Cl} \]

Example (Ethanamide formation): \[ \text{CH}_3\text{COCl} + 2\text{NH}_3 \longrightarrow \text{CH}_3\text{CONH}_2 + \text{NH}_4\text{Cl} \]

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Key Takeaway: Amides are formed rapidly from reactive acyl chlorides and ammonia or amines at room temperature.

3. Reactions of Amides

Amides are generally quite stable but can be made to undergo two key reactions: hydrolysis (breaking the bond with water) and reduction.

3.1 Hydrolysis of Amides (Syllabus 34.3.2(a))

Hydrolysis means breaking a bond using water. Amides can be hydrolysed back into their constituent parts under harsh conditions (heating with acid or alkali).

(a) Hydrolysis with Aqueous Acid (Aqueous Acid, Heat, followed by acidification)

Heating an amide with aqueous acid (like dilute $\text{H}_2\text{SO}_4$) breaks the amide linkage, resulting in a carboxylic acid and an ammonium salt.

Equation: \[ \text{RCONH}_2 + \text{H}^+ + \text{H}_2\text{O} \xrightarrow{\text{Heat}} \text{RCOOH} + \text{NH}_4^+ \]

Think of it: In acidic conditions, the amine part ($\text{NH}_2$) gets protonated to form the stable $\text{NH}_4^+$ ion.

(b) Hydrolysis with Aqueous Alkali (Aqueous Alkali, Heat)

Heating an amide with aqueous alkali (like dilute $\text{NaOH}$) produces a carboxylate salt and ammonia (or an amine, if a substituted amide was used).

Equation: \[ \text{RCONH}_2 + \text{OH}^- \xrightarrow{\text{Heat}} \text{RCOO}^- + \text{NH}_3 \]

Think of it: In alkaline conditions, the carboxylic acid part immediately reacts with the base ($\text{OH}^-$) to form a salt.

3.2 Reduction of Amides (Syllabus 34.3.2(b))

Amides can be reduced to form amines. This is an important way to synthesize long-chain amines or amines that are otherwise difficult to access.

Reagent and Conditions:

• Reagent: Lithium aluminium hydride ($\text{LiAlH}_4$).
• Conditions: In a dry organic solvent (like ether), followed by hydrolysis with dilute acid or water.

Crucial point: The reduction converts the carbonyl group ($\text{C=O}$) into a methylene group ($\text{CH}_2$), but the nitrogen atom remains attached.

Product: A primary amide reduces to a primary amine.

General Equation: \[ \text{RCONH}_2 + 4[\text{H}] \xrightarrow{\text{LiAlH}_4} \text{RCH}_2\text{NH}_2 + \text{H}_2\text{O} \]

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Key Takeaway: Amides can be broken down by hot acid/alkali (hydrolysis) or reduced by $\text{LiAlH}_4$ to form amines ($\text{RCH}_2\text{NH}_2$).

4. Basicity of Amides: Why They Are Very Weak Bases

This is a major concept required by the syllabus (34.3.3) and is often tested in comparison with amines.

4.1 Review: Basicity of Amines

Amines (like $\text{RNH}_2$) are basic because the nitrogen atom has a localised lone pair of electrons. This lone pair is readily available to accept a proton ($\text{H}^+$), acting as a Brønsted-Lowry base.

4.2 Why Amides Are Weak Bases

Amides are much weaker bases than amines and even weaker than ammonia. This is due to the neighboring carbonyl group ($\text{C=O}$).

The Explanation (Delocalisation):

1. The $\text{C=O}$ group is strongly electronegative.
2. The lone pair on the nitrogen atom in the amide is delocalised (drawn) towards the electrophilic carbon atom of the carbonyl group.
3. This delocalisation allows the nitrogen lone pair to participate in resonance, stabilizing the molecule.
4. Because the lone pair is pulled into the $\text{C=O}$ system, it is no longer fully available to bond with an external proton ($\text{H}^+$).

In simple terms: The nitrogen atom is "sharing" its electrons with the oxygen, so it can't easily act as an electron pair donor (base).

Summary of Basicity Comparison (High Basicity $\rightarrow$ Low Basicity)

Amines ($\text{RNH}_2$) > Ammonia ($\text{NH}_3$) > Amides ($\text{RCONH}_2$)

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Key Takeaway: The lone pair on the nitrogen in an amide is delocalised into the adjacent carbonyl group, making it unavailable to accept protons. Therefore, amides are very poor bases.

5. Amides and Amino Acids (Connecting Concepts - Syllabus 34.4)

While the chemical reactions of amino acids are detailed in Syllabus 34.4, it is essential to recognize the link between amides and proteins.

5.1 The Peptide Bond

Amino acids (which contain both an amine ($\text{-NH}_2$) and a carboxylic acid ($\text{-COOH}$) group) react via a condensation reaction to form chains called peptides and proteins.

The bond that forms between two amino acids is exactly an amide linkage. When it links amino acids, it is specifically called a peptide bond.

\[ \text{Amino Acid}_1 + \text{Amino Acid}_2 \xrightarrow{\text{Condensation}} \text{Dipeptide} + \text{H}_2\text{O} \]

Hydrolysis of proteins (using strong acid or strong alkali, heat) reverses this process, breaking the amide/peptide bonds back into the individual amino acids. This links back directly to the hydrolysis reaction of simple amides (Section 3.1)!

5.2 Zwitterions and Amino Acids

Unlike simple amides, amino acids can also exist as zwitterions (molecules containing both positive and negative charges). This is because the weakly basic amine group ($\text{-NH}_2$) and the weakly acidic carboxyl group ($\text{-COOH}$) can react internally.

The amine group takes the $\text{H}^+$ from the carboxyl group, forming $\text{RNH}_3^+$ and $\text{RCOO}^-$.

This ability to protonate and deprotonate depending on the surrounding pH is critical to protein structure, but fundamentally relies on the same acid/base chemistry you learned when comparing amides and amines.