Nucleophilic substitution mechanism

A nucleophile is a species that donates an electron pair to form a new covalent bond.

A nucleophile can react with a polar molecule like a halogenoalkane by 'kicking out' the halogen functional group and taking its place.

This is called a nucleophilic substitution reaction and follows the mechanism below:

The key steps are:

1. A nucleophile (Nuc) approaches the halogenoalkane (RCH₂X), which has a partially positive carbon atom (δ⁺).
2. The nucleophile donates its lone pair of electrons to the δ⁺ carbon, forming a new covalent bond.
3. The original bond between the δ⁺ carbon and the halogen breaks heterolytically as the halogen atom takes both the shared electrons.
4. The halogen departs as a halide ion (X^-), being replaced by the nucleophile.

Halogenoalkanes readily undergo nucleophilic substitution reactions via this mechanism. The nucleophiles that can react via this mechanism include hydroxide ions (OH^-), water (H₂O), cyanide ions (CN^-) and ammonia (NH₃). The nature of the product formed depends on which nucleophile is used.

Reaction with hydroxides to form alcohols

Halogenoalkanes readily undergo nucleophilic substitution with aqueous hydroxide ions (OH^-) from bases like sodium hydroxide or potassium hydroxide when the reaction mixture is warmed.

For example, bromoethane reacts with hydroxide to form ethanol:

CH₃CH₂Br + OH^- ➔ CH₃CH₂OH + Br^-

The reaction mechanism is:

This reaction, which replaces the halogenoalkane with an alcohol product, is a type of hydrolysis reaction. Water molecules can also act as the nucleophile in similar hydrolysis reactions with halogenoalkanes to generate alcohols. However, the reaction rate is much slower with neutral water molecules than with hydroxide ions, which are more nucleophilic.

Reaction with cyanide to form nitriles

Halogenoalkanes also undergo nucleophilic substitution when refluxed with ethanolic potassium cyanide. The cyanide ion (CN^-) acts as the nucleophile, displacing the halogen to form a nitrile product.

For example, bromoethane reacts with cyanide to form ethanenitrile:

CH₃CH₂Br + CN^- ➔ CH₃CH₂CN + Br^-

The reaction mechanism is:

Importantly, this reaction extends the carbon chain length of the original halogenoalkane by one carbon atom.

Reaction with ammonia to form amines

When heated under pressure with excess concentrated ethanolic ammonia, halogenoalkanes undergo nucleophilic substitution to form primary amines.

For example, bromoethane reacts with ammonia to form ethylamine:

CH₃CH₂Br + 2NH₃ ➔ CH₃CH₂NH₂ + NH₄Br

This reaction proceeds through a two-step mechanism:

Initially, ammonia replaces the bromine atom. Subsequently, it abstracts a hydrogen from the intermediate amine, yielding the final amine product alongside the salt ammonium bromide.

Halogenoalkanes eliminate in alkaline conditions

If a halogenoalkane is heated under reflux with an alkali like potassium hydroxide (KOH) dissolved in ethanol, an elimination reaction occurs to form an alkene.

For example, heating 2-iodopropane with KOH gives propene:

CH₃CHICH₃ + KOH ➔ CH₂=CHCH₃ + H₂O + KI

This is an example of an elimination reaction, where a small group is removed from a larger molecule without being replaced.

Anhydrous conditions favour elimination

Halogenoalkanes treated with hydroxide can undergo either substitution or elimination, depending on the choice of solvent.

• Substitution is favoured in aqueous solution. OH^- acts as a nucleophile.
• Elimination is favoured in ethanolic solution. OH^- acts as a base.

Using a solvent mixture of water and alcohol allows both reactions to occur, giving a mixture of products.