This page give some details on the nucleophilic substitution reactions of halogenalkanes with nucleophiles such as: hydroxide ions (OH^-), cyanide ions (CN^-) and the neutral molecule ammonia (NH₃) . If you are not familiar with the mechanism of nucleophilic substitution reactions I would suggest you review this before studying the rest of this page.

Halogenalkanes and hydroxide ions

Alcohols (R-OH) can be produced by the reaction of a halogenalkanes (R-X) when it is warmed with an aqueous solution of sodium hydroxide or potassium hydroxide.

You are probably familiar with potassium and sodium hydroxide from any work you have done on acids, alkalis and neutralisation reactions where the sodium hydroxide and potassium hydroxide would have been used as a base (a Brønsted–Lowry base); that is as hydrogen ion (H⁺) acceptors.

However the hydroxide ion (OH^-) can also behave as a nucleophile. There are many similarities between nucleophiles and bases; for example they both possess lone pairs of electrons. Usually strong bases are also good nucleophiles and vice versa. However with sodium and potassium hydroxide we can adjust the reaction conditions to "make it" behave as a base or a nucleophile.

Potassium and sodium hydroxide: Base or nunclephile?

Nucleophilic substitution reactions

In the reaction shown below sodium hydroxide is reacting with the halogenalkane bromoethane. Now in a warm aqueous solution of sodium hydroxide, the hydroxide ion (OH^-) will behave as a nucleophile; indeed this is a typical nucleophilic substitution reaction where the hydroxide ion uses one of its lone pairs of electrons to attack the partially charged carbon atom in the polar C-Br bond. The product of this reaction is the alcohol ethanol and the salt sodium bromide which of course will be in solution.

Solubility problems

The main problem with the set-up above is that halogenalkanes are pretty much insoluble in water, this means that the reaction is going to be very slow. To improve the solubility problem you could add the alcohol ethanol to the aqueous sodium hydroxide to produce what is often called an ethanolic sodium hydroxide solution. The halogenalkane would be soluble in this alcoholic/aqueous solution but unfortunately this may lead to a different type of reaction occurring; that is an elimination reaction; this elimination reaction we would not produce the desired alcohol but instead lead to the formation of unsaturated alkenes; not what we want!

A better solution to the solubility problem would be to set-up a reflux reaction using the halogenalkane and the aqueous sodium hydroxide, this would allow sufficient time for the reaction to take place and also help force it forwards to produce the product. A typical reflux set-up is shown below in the nitrile section of this page.

Halogenalkanes and cyanide ions- making nitriles

Nitriles contain the functional group R-CN, nitriles are particularly useful in organic synthesis are they are one of the few ways in which it is possible to extend the carbon chain by one carbon atom. Nitriles are also reactive and are easily converted into other useful and reactive molecules such as amines, amides and carboxylic acids. The first two members of the nitriles homologous series are shown below:

Halogenalkanes and ammonia

Ammonia reacts with halogenalkanes to produce amines. Amines are simply molecules of ammonia(NH₃) where one or more of the hydrogen atoms on the ammonia molecule have been replaced by an alkyl group (-R), for example:

• Primary amines are formed when one hydrogen atom on an ammonia molecule is replaced by an alkyl group (see the image below).
• Secondary amines are formed when two of the hydrogen atoms on an ammonia molecule have been replaced by two alkyl groups.
• Tertiary amines are formed when all three hydrogen atoms on an ammonia molecule have been replaced by alkyl groups.

Nucleophile or base?

Before we look at the mechanism of the reaction between ammonia and halogenalkane molecules consider the two reactions of ammonia shown below, study the image below and ask yourself how are these two reactions similar and how are they different? As was mentioned above molecules with lone pairs of electrons can act as either nucleophiles or bases.

• Reaction 1: Here an ammonia molecule acts as a nucleophile and uses it lone pair of electrons to form a dative covalent bond with the carbon atom in the bromomethane, in this case the ammonia lone pair attacks the δ⁺ carbon atom in the C-Br bond. This reaction is a nucleophilic substitution reaction (S_N2)
  
• Reaction 2: In this reaction the ammonia molecule is acting as a base, a base is a substance that can accept a proton or a H⁺ ion. You will meet lots of different definitions of bases in your A-level chemistry course, which can be confusing at first but really the definition used is simply adjusted to help describe the reaction taking place. Here the ammonia is acting as a Brønsted-Lowry base, that is a H⁺ acceptor but it's also acting as a Lewis base, that is an electron pair donor.

Nucleophilicity, nucleophiles and bases

Whether the substance in question acts as a nucleophile or a base will largely depend on the reaction conditions used, that is for example the temperature or the particular solvent used to carry out the reaction in question. In summary we can say that in most cases good bases are also good nucleophiles and that there are several factors affecting nucleophilicity; including:

• Charge: Negatively charged species are usually better nucleophiles than their neutral counterparts (e.g. hydroxide (OH^-) is a stronger nucleophile than water (H₂O).


• Electronegativity: Less electronegative atoms are more nucleophilic because they are less likely to hold onto their electrons tightly, for instance sulfur (S) is a better nucleophile than oxygen (O).


• Solvent: Polar protic solvents (such as water or ethanol) can reduce nucleophilicity by forming hydrogen bonds with nucleophiles, while polar aprotic solvents (like propanone) increase nucleophilicity by not interacting with nucleophiles as strongly.


• Steric hindrance: Smaller, less bulky nucleophiles are generally more reactive because they can approach the electrophile more easily.

Aminolysis- making amines from ammonia

Now amines can be made by reacting ammonia with halogenalkanes, this is a typical nucleophilic substitution reaction. However you need to consider the fact that ammonia is a gas at room temperature, it is also very soluble in water however when heated any dissolved ammonia gas would be given off, so any reaction involving ammonia gas needs to be carried out in sealed vessels.

The mechanism for the nucleophilic substitution reaction of bromomethane and ammonia is shown below; you should note that 2 moles of ammonia are used for every mole of the halogenalkane.

One mole of the ammonia acts as a nucleophile and attacks the δ⁺ carbon atom in the halogenalkane while the other mole of ammonia acts as a base and abstracts a proton (H⁺) from the quaternary ammonium salt. The final product in this case is methylamine.

Explanation of mechanism:

• Step 1: Here the ammonia molecule is acting as a nucleophile and attacking the δ⁺ carbon atom in the C-Br bond.


• Step 2: Once the ammonia molecule has used both its electrons to form a dative covalent bond to the carbon atom it is left with a positive charge.


• Step 3: Nitrogen is a very electronegative element and having a positive charge will mean that it will be withdrawing electron density in any bonds it makes to an even greater extent than normal. This will mean that the hydrogen atoms attached to the nitrogen will have a particularly large δ⁺ charge, so next another ammonia molecule can act as a base and remove one of these δ⁺ hydrogen atoms.


• Step 4: The end result of this reaction is that one of the hydrogen atom on the ammonia molecule has been replaced by a methyl group from the bromomethane. The final products in this case are the primary amine; methylamine and the quaternary ammonium bromide salt (quaternary means there are 4 groups attached to the nitrogen atom).

Self-check: Quick review of main points in the Mechanism covered so far

On we go...........

I am sure you can see where this going! The product of the reaction above, the dimethylamine is a better nucleophile than the primary amine; methylamine. This means that as the concentration of the secondary amine; dimethylamine increases it will take over from the methylamine to form the tertiary amine trimethylamine. Even here the reaction will not stop! The trimethylamine will continue to react with the bromomethane and form the quaternary ammonium salt where all the hydrogen atoms from the original ammonia molecule have been replaced by -methyl groups.

This ultimately leads to a mixture of products; primary, secondary, tertiary amines as well as a quaternary ammonium salt. This mixture of products will ultimately reduce the usefulness of this particular reaction. We can of course try to stop the reaction at the first step and only produce the methylamine, to do this we simply try to block out the methylamine by using a large excess of ammonia. This will work to a certain extend by sheer weight of numbers the ammonia molecules will simply block the methylamine and limit the reaction to produce only the primary amine methylamine.

Self-check: What factors decide on the reaction outcome?

Summary table: nucleophilic substitution reactions of haloalkanes

Self-check: One minute quick quiz

The exam-trap: What not to do or say in the exam

Key Points

• Nucleophilic substitution happens when a nucleophile uses a lone pair of electrons to attack the δ⁺ carbon atom in a polar C–X bond and replacing the halogen atom.
• Hydroxide (OH^-) ions can act as a nucleophile or a base, the reaction conditions decide on the type of reaction that will take place: warm aqueous sodium hydroxide favours a substitution reaction to make an alcohol, while hot ethanolic sodium hydroxide favours elimination to make an alkene.
• Solubility matters: haloalkanes are generally poorly soluble in water, so reactions can be slow. Reflux is used to heat the reaction for longer without losing volatile reactants, helping the reaction go to completion.
• Cyanide ions (CN^-) react with primary haloalkanes to form nitriles, this is a key synthesis step because it extends the carbon chain by one carbon.
• Ammonia reacts with haloalkanes to form amines (aminolysis). The mechanism uses two ammonia molecules: one acts as the nucleophile, the other acts as a base to remove a proton.
• A common exam point: the amine product is a stronger base and often a better nucleophile than ammonia, so further substitution reactions can take place; unfortunately this leads to a mixture of primary, secondary, tertiary amines and a quaternary ammonium salt. Using excess ammonia helps favour the primary amine.

Check your understanding - Questions on Nucleophilic substitution reactions

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