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.

SN1 and SN2 mechanisms

Nucleophilic substitution reactions of halogenoalkanes can proceed via two distinct mechanisms:

1. S_N2 (bimolecular nucleophilic substitution).
2. S_N1 (unimolecular nucleophilic substitution).

The mechanism followed depends on the structure of the halogenoalkane.

SN2 mechanism for primary halogenoalkanes

In primary halogenoalkanes with the halogen bound to a carbon with just one other alkyl (R) group, nucleophilic substitution follows an S_N2 mechanism.

This mechanism is characterised by a single, concerted step in which the nucleophile bonds to the carbon atom while the halogen simultaneously leaves.

The reaction rate is influenced by the concentrations of both the halogenoalkane and the nucleophile, as the slow step involves both reactants.

S_N1 mechanism for tertiary halogenoalkanes

In tertiary halogenoalkanes with the halogen bound to a carbon with three alkyl (R) groups, nucleophilic substitution follows a two-step S_N1 mechanism.

The key steps are:

1. The slow, heterolytic cleavage of the carbon-halogen bond, resulting in a stable tertiary carbocation intermediate.
2. A rapid nucleophilic attack on the carbocation, leading to the formation of the final product. Therefore, the S_N1 mechanism's rate is determined solely by the concentration of the halogenoalkane, as shown in the slow initial step.

Secondary halogenoalkanes can undergo nucleophilic substitution via both S_N1 and S_N2 mechanisms, depending on the reaction conditions.