Welcome to the preparation of amines! Amines are incredibly versatile nitrogen-containing compounds used to manufacture everything from polymers and pharmaceuticals to synthetic dyes. In this section, we will look at how to build them in the lab and in industry.

What you'll learn:

• How to synthesize primary aliphatic amines from halogenoalkanes and nitriles.
• Why making amines from nitriles often yields a purer product.
• How to prepare aromatic amines from nitro compounds, and what they are used for.

Making Aliphatic Amines from Halogenoalkanes

We can prepare primary aliphatic amines directly by reacting a halogenoalkane with ammonia (${NH}_3$).

Because the nitrogen atom in ammonia has a lone pair of electrons, it acts as a nucleophile. It attacks the electron-deficient (${\delta }^{+}$) carbon atom in the halogenoalkane.

Reagents and conditions

To make this reaction work efficiently, we heat the halogenoalkane with excess ethanolic ammonia in a sealed copper tube under pressure. We use ethanol as the solvent rather than water. If we used water, the halogenoalkane could undergo a hydrolysis reaction with the water to form an alcohol instead.

Here is the nucleophilic substitution mechanism for the reaction between bromoethane and ammonia:

Notice that the reaction happens in two stages. First, an ammonia molecule attacks the bromoethane to form an intermediate ethylammonium ion. Then, a second ammonia molecule acts as a base (a proton acceptor) to remove a hydrogen ion from the intermediate, generating the primary amine (ethylamine) and an ammonium ion (${NH}_4^{+}$).

Making Aliphatic Amines from Nitriles

Because the direct reaction with a halogenoalkane can lead to a messy mixture of primary, secondary, and tertiary amines, chemists often prefer an alternative two-step route: converting a halogenoalkane into a nitrile, and then reducing the nitrile.

Step 1: Forming the nitrile

First, the halogenoalkane is reacted with potassium cyanide ($KCN$) dissolved in aqueous ethanol. The mixture is heated under reflux. The cyanide ion (${CN}^{-}$) acts as a nucleophile, replacing the halogen to form a nitrile.

Step 2: Reducing the nitrile

Once we have our nitrile, we need to convert the carbon-nitrogen triple bond ($C\equiv N$) into a single bond ($C-N$) while adding hydrogen atoms. This is a reduction reaction.

There are two main ways to reduce a nitrile to a primary amine:

1. Catalytic hydrogenation (Industrial preference) Hydrogen gas ($H_2$) and a nickel ($Ni$) catalyst are added to the nitrile at a high temperature and pressure.

$${CH}_3{CH}_{2}CN+2H_2\to {CH}_3{CH}_2{CH}_2{NH}_2$$

This is the preferred method in industry because it is cheaper and greener; the only byproduct is empty space, and hydrogen gas is relatively inexpensive.

2. Chemical reduction (Laboratory preference) The nitrile is reduced using a strong reducing agent called lithium tetrahydridoaluminate (${LiAlH}_4$), dissolved in a non-aqueous solvent like dry ether. This is followed by the addition of some dilute acid.

$${CH}_3{CH}_{2}CN+4[H]\to {CH}_3{CH}_2{CH}_2{NH}_2$$

Here, we use $[H]$ in the equation to represent hydrogen from the reducing agent. This method is too expensive for large-scale industrial use, but it is excellent for small-scale lab work.

Making Aromatic Amines from Nitro Compounds

Aromatic amines, like phenylamine ($C_6{H}_5{NH}_2$), have the amine group directly attached to a benzene ring. We cannot make these using nucleophilic substitution because the electron-rich delocalised ring repels incoming nucleophiles. Instead, we prepare them by reducing aromatic nitro compounds.

The reduction of nitrobenzene

To make phenylamine, we start with nitrobenzene ($C_6{H}_5{NO}_2$). The reduction is carried out by heating nitrobenzene under reflux with a mixture of tin ($Sn$) and concentrated hydrochloric acid ($HCl$).

Tin and hydrochloric acid react to generate hydrogen in situ, which reduces the nitro group (${-NO}_2$) to an amine group (${-NH}_2$). The overall equation using $[H]$ for the reducing agent is:

$$C_6{H}_5{NO}_2+6[H]\to C_6{H}_5{NH}_2+2H_{2}O$$

Because the reaction takes place in heavily acidic conditions (concentrated $HCl$), the amine is initially protonated to form a salt, phenylammonium chloride ($C_6{H}_5{NH}_3^{+}{Cl}^{-}$).

To liberate the free, neutral amine, we must cool the mixture and add a strong alkali, such as sodium hydroxide ($NaOH$).

$$C_6{H}_5{NH}_3^{+}{Cl}^{-}+NaOH\to C_6{H}_5{NH}_2+H_{2}O+NaCl$$

Uses of aromatic amines

Why go through the trouble of making phenylamine? Aromatic amines are highly prized in chemical industry as precursors for making azo dyes. These are brightly coloured synthetic compounds used extensively to dye fabrics, plastics, and paints.