Topic 18B: Amines, amides, amino acids and proteins

Welcome to Topic 18B: Amines, Amides, and Amino Acids

Welcome! In this chapter, we are moving beyond simple carbon-oxygen chemistry and diving into the world of nitrogen. Nitrogen-containing compounds are the "engines" of biology—they make up the proteins in your muscles, the DNA in your cells, and many of the medicines we use every day. Don't worry if it looks like a lot of reactions at first; we will break them down into simple patterns so you can master them easily.

This topic is part of Further Organic Chemistry, which builds on what you learned about halogenoalkanes (Topic 6D) and carboxylic acids (Topic 17C).

1. Amines: Structure and Basicity

Amines are essentially derivatives of ammonia (\( NH_3 \)) where one or more hydrogen atoms have been replaced by organic groups (like \( CH_3 \)).

• Primary (\( 1^{\circ} \)) amine: One \( R \) group attached to \( N \) (e.g., butylamine, \( CH_3CH_2CH_2CH_2NH_2 \)).
• Secondary (\( 2^{\circ} \)) amine: Two \( R \) groups attached to \( N \).
• Tertiary (\( 3^{\circ} \)) amine: Three \( R \) groups attached to \( N \).

The Strength of the Base

In Chemistry, a base is a proton (\( H^+ \)) acceptor. Amines are basic because the nitrogen atom has a lone pair of electrons that can form a dative covalent bond with an \( H^+ \) ion.

However, not all amines are equally "strong." The strength depends on how available that lone pair is:

The Basicity Trend:
Aromatic Amines (e.g., phenylamine) < Ammonia < Aliphatic Amines (e.g., butylamine)

1. Aliphatic Amines (Strongest): Alkyl groups (like butyl groups) are "electron-pushing" (they have an inductive effect). This pushes electron density onto the nitrogen, making the lone pair more attractive to protons.
2. Ammonia: The middle ground. No groups pushing or pulling electrons.
3. Aromatic Amines (Weakest): The lone pair on the nitrogen becomes delocalised into the benzene ring. This means the lone pair is "busy" being part of the ring's electron cloud and is less available to bond with a proton.

Quick Review: Think of the lone pair as a magnet for protons. Alkyl groups make the magnet stronger; benzene rings make the magnet weaker.

2. Reactions of Butylamine

The syllabus specifically highlights butylamine (\( C_4H_9NH_2 \)). Here are the key reactions you need to know:

A. With Water

Butylamine reacts slightly with water to form an alkaline solution:
\( C_4H_9NH_2 + H_2O \rightleftharpoons C_4H_9NH_3^+ + OH^- \)

B. With Acids

As a base, it reacts with acids to form salts:
\( C_4H_9NH_2 + HCl \rightarrow C_4H_9NH_3^+Cl^- \) (Butylammonium chloride)

C. With Halogenoalkanes (Nucleophilic Substitution)

The lone pair on the nitrogen attacks the partial positive charge on a halogenoalkane. This can continue until all hydrogens are replaced by alkyl groups, eventually forming a quaternary ammonium salt.

D. With Ethanoyl Chloride (Acylation)

This is a vigorous reaction at room temperature. The amine attacks the acyl chloride (Topic 17C) to form an N-substituted amide and \( HCl \) gas (seen as white misty fumes).
\( CH_3COCl + C_4H_9NH_2 \rightarrow CH_3CONHC_4H_9 + HCl \)

E. With Copper(II) Ions

This is a "ligand exchange" reaction. When you add butylamine to a solution containing \( [Cu(H_2O)_6]^{2+} \) (pale blue):

1. Initially, it acts as a base, pulling protons off the water ligands to form a blue precipitate of \( Cu(OH)_2 \).
2. In excess butylamine, the amine acts as a ligand. It replaces some water molecules to form a deep blue solution.

3. Preparing Amines

How do we make these nitrogen compounds? There are three main routes you must know:

Route 1: From Halogenoalkanes

Reagents: Excess ethanolic ammonia (\( NH_3 \)).
Conditions: Heated in a sealed tube.
Note: Using excess ammonia helps prevent further substitution, ensuring you get mostly the primary amine.

Route 2: Reduction of Nitriles

Nitriles (\( R-C \equiv N \)) can be reduced to primary amines.
Reagent: \( LiAlH_4 \) in dry ether (represented as \( 4[H] \)).
\( R-CN + 4[H] \rightarrow R-CH_2NH_2 \)

Route 3: Making Phenylamine (Aromatic)

To make phenylamine from nitrobenzene (\( C_6H_5NO_2 \)):
Reagents: Tin (\( Sn \)) and concentrated hydrochloric acid (\( HCl \)).
Conditions: Reflux, followed by adding \( NaOH \) to liberate the free amine from its salt.

4. Amides

Amides contain the functional group \( -CONH_2 \). They are less basic than amines because the lone pair on the nitrogen is delocalised by the adjacent \( C=O \) group.

Preparation: The most common way to make amides in the lab is by reacting an acyl chloride with either ammonia (to make a simple amide) or a primary amine (to make an N-substituted amide).
\( R-COCl + NH_3 \rightarrow R-CONH_2 + HCl \)

5. Amino Acids and Proteins

Amino acids are the building blocks of life. They contain both an amine group (\( -NH_2 \)) and a carboxylic acid group (\( -COOH \)).

Zwitterions

Because amino acids have an acidic end and a basic end, they perform an internal "handshake." The \( -COOH \) group loses a proton to the \( -NH_2 \) group. This creates a zwitterion: a molecule with both a positive and a negative charge, but a net charge of zero.
\( H_2N-CH(R)-COOH \rightarrow H_3N^+-CH(R)-COO^- \)

Did you know? Because they exist as zwitterions, amino acids behave like ionic salts. They have much higher melting points than you would expect for molecules of their size!

Optical Activity

Except for glycine (where \( R = H \)), all naturally occurring amino acids have a chiral centre (the alpha-carbon is bonded to four different groups). This means they exist as optical isomers (enantiomers) and can rotate plane-polarised light. (See Topic 17A for more on chirality).

Peptide Bonds and Proteins

When two amino acids join, the \( -NH_2 \) of one reacts with the \( -COOH \) of another. A molecule of water is lost (this is a condensation reaction), forming a peptide bond (\( -CONH- \)).

• Two amino acids = A dipeptide.
• Many amino acids = A polypeptide or protein.

Hydrolysis and Chromatography

If we want to see which amino acids make up a protein, we must break it down:
1. Hydrolysis: Heat the protein with concentrated \( HCl \). This breaks the peptide bonds, giving you a mixture of individual amino acids.
2. Chromatography: Use Paper or Thin Layer Chromatography (TLC) to separate them. Since amino acids are colourless, we spray them with ninhydrin (which turns them purple/blue) or use UV light to see the spots.

6. Condensation Polymers

While addition polymers (like polyethene) involve breaking double bonds, condensation polymers involve losing a small molecule (usually \( H_2O \) or \( HCl \)) as monomers join together.

A. Polyamides

These are made from:
- A dicarboxylic acid and a diamine.
- Example: Nylon-6,6.
- They are held together by peptide (amide) links.

B. Polyesters (Brief Cross-Reference)

As seen in Topic 17C, these are made from a dicarboxylic acid and a diol, held together by ester links.

Key Takeaway: Polyamides and polyesters are biodegradable because the amide and ester links can be broken down by hydrolysis (adding water, usually catalyzed by acid or alkali). This is a major advantage over addition polymers like polyethene!

Quick Summary Checklist

• Can you explain why butylamine is a stronger base than phenylamine?
• Do you know the reagents for reducing a nitrile (\( LiAlH_4 \)) vs reducing nitrobenzene (\( Sn/HCl \))?
• Can you draw a zwitterion?
• Do you remember that ninhydrin is used to "see" amino acids on a chromatogram?
• Do you know that condensation polymers are biodegradable via hydrolysis?

Don't worry if this seems tricky at first—organic chemistry is all about practice. Try drawing out the mechanisms for acylation and nucleophilic substitution to see how the nitrogen lone pair always starts the "attack"!