Nucleophilic substitution

Nucleophilic substitution is a reaction in which a nucleophile, an electron pair donor, replaces an atom or group in a molecule. At A-level it is the key reaction of halogenoalkanes: a nucleophile such as OH⁻, CN⁻ or NH₃ attacks the slightly positive carbon atom, and the halogen leaves as a halide ion.

What is a nucleophilic substitution reaction?

The name tells you what happens. A nucleophile ("nucleus loving") is a species with a lone pair of electrons that it can donate to form a new covalent bond. It is attracted to a positive or slightly positive atom. Substitution means one atom or group swaps for another.

Halogenoalkanes react this way because the carbon to halogen bond is polar. The halogen is more electronegative than carbon, so it pulls the bonding electrons towards itself, leaving the carbon δ+ and the halogen δ−. The δ+ carbon is open to attack, and the halogen can leave as a stable halide ion, taking both electrons from the bond with it. The species that leaves is called the leaving group.

Nucleophilic substitution mechanism

Here is the mechanism for bromoethane with hydroxide ions, the example most textbooks start with. Overall:

CH₃CH₂Br + OH⁻ → CH₃CH₂OH + Br⁻

A mechanism shows how the electrons move, using curly arrows. Each curly arrow shows a pair of electrons moving, and it starts where the electrons are and ends where they go. This mechanism needs two:

1. The nucleophile attacks. Draw a curly arrow from a lone pair on the oxygen of OH⁻ to the δ+ carbon. This pair of electrons forms the new C-O bond.
2. The halogen leaves. Draw a curly arrow from the middle of the C-Br bond to the bromine atom. The bond breaks heterolytically: both electrons go to bromine, which leaves as Br⁻.
3. The products. Ethanol, CH₃CH₂OH, and a bromide ion, Br⁻.

In your drawing, show the δ+ on the carbon and δ− on the bromine, the lone pair on the oxygen, and the negative charge on the hydroxide ion. Start the first arrow from the lone pair, not from the minus sign.

The three reactions you need

AQA's A-level specification lists three nucleophiles that halogenoalkanes undergo substitution with: OH⁻, CN⁻ and NH₃. You should be able to outline the mechanism for each. The conditions below are the usual laboratory ones.

Hydroxide ions: making alcohols

This reaction is also called hydrolysis of the halogenoalkane. Warming 1-iodobutane with aqueous sodium hydroxide, for example, gives butan-1-ol and iodide ions. Heating under reflux means the mixture can be boiled for a long time without the volatile organic compounds escaping.

Cyanide ions: making nitriles

The cyanide ion attacks through the lone pair on its carbon, so the product gains a carbon atom: 1-bromopropane (three carbons) becomes butanenitrile (four carbons, counting the carbon of the C≡N group). This is useful in synthesis for making a carbon chain longer. The solvent is ethanol, not water, because in water you would also get substitution by OH⁻ and form an alcohol instead.

Ammonia: making amines

Ammonia is a neutral nucleophile with a lone pair on nitrogen. After it attacks, the nitrogen carries a positive charge, so a second ammonia molecule removes an H⁺ from it. That is why the overall equation uses two ammonia molecules:

CH₃CH₂Br + 2NH₃ → CH₃CH₂NH₂ + NH₄Br

The amine made still has a lone pair on its nitrogen, so it can attack another halogenoalkane molecule and give secondary and tertiary amines. Using a large excess of ammonia makes it much more likely that each halogenoalkane meets an ammonia molecule rather than an amine, so the primary amine is the main product. The tube is sealed because ammonia is a gas and would escape from an open flask.

Why the halogen affects the rate

You might expect the most polar bond, C-F, to react fastest, because its carbon is the most δ+. It is the other way round. The rate depends mainly on how easily the carbon to halogen bond breaks, and bond enthalpy falls down the group:

AQA asks you to explain exactly this: the carbon to halogen bond enthalpy influences the rate. You can see it in the lab by warming each halogenoalkane with aqueous ethanol containing silver nitrate. As halide ions are released they form a precipitate: yellow silver iodide appears first, then cream silver bromide, and white silver chloride takes the longest.

SN1 and SN2

There are two ways nucleophilic substitution can happen. The names come from substitution, nucleophilic, with 2 meaning bimolecular (two species in the slow step) and 1 meaning unimolecular (one species in the slow step). AQA's A-level specification doesn't name them, but other courses do, so check yours.

Primary halogenoalkanes mostly react by SN2, tertiary ones by SN1, and secondary ones by a mixture of both. In SN2, the nucleophile comes in from directly behind the halogen, 180° away from it, and the other three groups flip over like an umbrella turning inside out. A tertiary carbon has three bulky groups in the way, so SN2 is blocked, but those groups help stabilise the carbocation that SN1 needs.

The rate equations come from experiments: in SN1, changing the concentration of the nucleophile has no effect on the rate, because the slow step involves only the halogenoalkane. The Reaction Kinetics course covers rate equations and orders.

Substitution or elimination?

Hydroxide ions can do two jobs. As a nucleophile, OH⁻ attacks the δ+ carbon and substitution gives an alcohol. As a base, OH⁻ removes an H⁺ from the carbon next to the C-X carbon, and elimination gives an alkene. AQA asks you to explain this dual role, for example in 2-bromopropane with potassium hydroxide. Both reactions happen at once: water as the solvent favours substitution, while hydroxide dissolved in ethanol and hotter conditions favour elimination.

Common mistakes

• Arrows from the minus sign. The first arrow starts at a lone pair on the nucleophile.
• Arrow heads on the wrong atom. The second arrow goes from the C-X bond to the halogen, not the other way.
• Saying C-F reacts fastest because it is most polar. Bond enthalpy controls the rate, so iodoalkanes react fastest.
• Using water with cyanide. KCN must be dissolved in ethanol, or you get an alcohol as well.
• Forgetting the second ammonia. The equation with ammonia uses 2NH₃ and gives NH₄⁺ (as NH₄Br).
• Miscounting nitrile carbons. The carbon of the CN group counts in the name: CH₃CH₂CH₂CN is butanenitrile.

To practise organic mechanisms alongside the rest of the course, try today's A-level Chemistry: Year 1 or Year 2 short timed paper.

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Chemistry · Organic chemistryNucleophilic addition: mechanism, NaBH₄ and KCNNucleophilic addition for A-level Chemistry: why aldehydes and ketones react this way, the curly arrow mechanism, reduction with NaBH₄ and KCN with acid.