This page covers common nucleophilic substitution reactions of halogenalkanes using 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 page below.

Halogenalkanes and hydroxide ions

Alcohols are formed when halogenalkanes are 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 and alkalis where sodium hydroxide and potassium hydroxide would have been used as a base (a H⁺ acceptor). 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.

Nucleophilic substitution reactions

In the reaction below sodium hydroxide is reacting with the halogenalkane bromoethane. In an aqueous solution of sodium hydroxide, here the hydroxide ion (OH^-) behaves 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.

The main problem with the set-up above is that halogenalkanes are pretty much insoluble in water so the reaction is going to be very slow. You could add the alcohol ethanol to the sodium hydroxide to produce what is often called ethanolic sodium hydroxide solution. The halogenalkane would be soluble in this mixture but unfortunately this may lead to a different type of reaction called an elimination reaction; this elimination we would not produce the alcohol but instead lead to the formation of unsaturated alkenes. A better solution to this 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 reflux set-up is shown below in the nitrile section of this page.

Halogenalkanes and cyanide ions

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 is replaced by an alkyl group, 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 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, how 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)
  


• Nucleophilicity is a term which is often used to describe the ability of a species (a nucleophile) to donate a pair of electrons to form a chemical bond with an electrophile. In simple terms, a nucleophile is a chemical species that seeks positively charged centres (like a carbon atom in a molecule) and donates its electrons to create a bond.


• 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 its 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

The reaction of ammonia with halogenalkanes needs to be carried out in a sealed reaction vessel otherwise the ammonia gas will simply escape. Ammonia is a gas at room temperature and it is very soluble in water however when heated ammonia gas would be given off, so this reaction 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 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 will act as a base and remove one of these 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).

However this is not the end of the story for this reaction. If you follow the mechanism you can clearly see that the ammonia simply swaps a hydrogen atom for a methyl group or if a different halogenalkane was used, for example bromoethane, then an ethyl group would replace a hydrogen atom on the ammonia to form ethylamine.

The problem is the product of the reaction; the primary amine is a stronger base and a better nucleophile than ammonia. So as the reaction proceeds its concentration will increase and it will take over from ammonia in the reaction mechanism. This will mean that one of the hydrogen atoms on the primary amine will be replaced by an alkyl group to form a secondary amine, this is outlined below:

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 and 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 which will 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.

Key Points

• Alcohols are formed when halogenalkanes are warmed with an aqueous solution of sodium or potassium hydroxide.
• Nitriles are formed by reacting halogenalkanes with cyanide ions. Nitriles are useful since they are reactive and are easily converted into many other reagents. This reaction will extend the carbon chain by adding one more carbon atom to it.
• Amines can be made by reacting halogenalkanes with ammonia.

Check your understanding - Questions on Nucleophilic substitution reactions

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