Are you curious about how we can turn a halogenoalkane into an alcohol, nitrile or amine? It's all thanks to nucleophilic substitution reactions! In this article, we'll explain what nucleophilic substitution is and compare it to electrophilic substitution reactions. Then, we'll dive into halogenoalkane nucleophilic substitution reactions, exploring their mechanism and reactivity. Next, we'll look at the stereochemical aspects of nucleophilic substitution reactions. Finally, we'll give you examples of nucleophilic substitution reactions, such as reactions with the hydroxide ion, the cyanide ion, ammonia, and silver nitrate solution. Understanding nucleophilic substitution reactions is crucial in organic chemistry, and we'll show you why by discussing their importance.

Nucleophilic substitution reaction definition

Nucleophilic substitution reactions are reactions in which a nucleophile attacks a molecule and replaces one of its functional groups.

Let's break the term nucleophilic substitution down a little. First, substitution.

A substitution reaction is a reaction in which one functional group on a molecule is replaced by a different functional group.

Next, let's look at nucleophilic. It refers to nucleophiles.

A nucleophile is an electron pair donor.

Nucleophiles are chemical species that react by donating a lone pair of electrons to an electron-deficient species to form a covalent bond. Nucleophiles are all negatively or partially negatively charged (which we represent using the delta symbol, δ) and feature a lone pair of electrons.

An electron-deficient species is simply a molecule or ion that has an area of positive charge. Any fully or partially positively charged species is electron-deficient.

By looking more closely at the term nucleophile, we can form a picture of what these species actually are. -phile comes from the Greek word philos, which means to love, and nucleo-  refers to nuclei, which are the positively charged areas of atoms. Therefore, nucleophiles must ‘love’ positive regions - they are attracted to them.

Examples of nucleophiles include:

The cyanide ion, :CN-.The hydroxide ion, :OH-.Ammonia, NH3.

Note how ammonia is not an ion. However, it is still a nucleophile, because it has a lone pair of electrons and an atom with a partial negative charge. In this case, that atom is nitrogen.

Difference between nucleophilic and electrophilic substitution reactions

You'd be forgiven for getting nucleophilic substitution mixed up with a similar term: electrophilic substitution. Whilst the two types of reactions have some features in common, they involve very different species. It is important that you know the difference between them:

Nucleophilic substitution reactions involve an attack by a nucleophile, an electron-pair donor.Electrophilic substitution reactions, on the other hand, involve an attack by an electrophile, an electron-pair acceptor.

Examples of electrophiles include:

Hydrogen halides, HX.The nitronium ion, NO2+.

However, both nucleophilic substitution and electrophilic substitution are still examples of substitution reactions. This means that they swap one functional group in an organic molecule for a different functional group.

You'll look at an example of an electrophilic substitution reaction in more depth in Reactions of Benzene.

Halogenoalkane nucleophilic substitution reactions

We know that halogenoalkanes are polar molecules (explore Halogenoalkanes to refresh your memory). Because the halogen atom in the C-X bond is a lot more electronegative than the carbon atom, it attracts the shared pair of electrons towards itself. Electrons are negatively charged. This makes the halogen atom partially negatively charged and leaves the carbon partially positively charged.

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Nucleophiles, which we now know ‘love’ positive regions, can attack this partially charged carbon atom, in an example of a nucleophilic substitution reaction.

Halogenoalkane nucleophilic substitution reaction mechanism

Nucleophilic substitution reactions of halogenoalkanes all follow one of two similar mechanisms. The mechanism used depends on the classification of the halogenoalkane.

Primary halogenoalkanes react using an SN2 mechanism. The S stands for substitution, the N stands for nucleophilic, and the number 2 lets us know that the initial reaction step involves two species: the halogenoalkane and the nucleophile.Tertiary halogenoalkanes react using an SN1 mechanism. Once again, the S and N stand for substitution and nucleophilic, but this time the number 1 tells us that the initial reaction step involves just one species: the halogenoalkane itself.Secondary halogenoalkanes use a mixture of both the SN1 and the SN2 mechanisms.

As we mentioned, the SN1 and the SN2 reaction mechanisms are similar, but they do have their differences. We explore them both fully in the article Nucleophilic Substitution Mechanism. There, you'll be able to see mechanism diagrams showing electron movement to help you differentiate between the two processes.You should also note that if your exam board doesn't specifically refer to SN1 or SN2 mechanisms, then when it mentions nucleophilic substitution, it means the SN2 mechanism that is used by primary and secondary halogenoalkanes. And if you don't know the difference between primary, secondary and tertiary halogenoalkanes, check out Halogenoalkanes.

The overall equation for both mechanisms is the same:

RCH2X + Nu- → RCH2NU + X-

We've shown the equation using a primary halogenoalkane for simplicity, but it is easy enough to adapt it to fit other halogenoalkane classifications. You merely need to swap one or both of the halogenoalkane's hydrogen atoms with an extra one or two R groups.

Reactivity of halogenoalkanes in nucleophilic substitution

In chemistry, the halogen or halide ion is called the leaving group. It's called that because it's a part of a molecule that breaks away during a chemical reaction. When the bond between the leaving group and the parent molecule is broken, the electrons move over to the leaving group. Some halogens are better at being a leaving group than others. This means they react more easily in nucleophilic substitution reactions. As you move down the periodic table, the ability for halogens to act as leaving groups increases. This is because the atomic radius, or size, of the halogen increases. For example, fluoroalkanes with C-F bonds don't undergo nucleophilic substitution, while iodoalkanes with weak C-I bonds react quickly with nucleophiles. Iodine is bigger than fluorine, so the C-I bond is longer and more reactive. As you move down the periodic table, bond lengths increase, making the bonds more reactive.

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For more information on halogenoalkanes and their reactivity, see Halogenoalkanes.

Stereochemical aspects of nucleophilic substitution reactions

Above, we saw how nucleophilic substitution can have an SN1 or SN2 mechanism. These two different mechanisms produce products with different stereochemical aspects:

SN2 mechanisms produce just one product. The bonds in this product are inverted compared to the bonds in the original reacting molecule.SN1 mechanisms produce two enantiomers. Enantiomers are stereoisomers with the same structural formulae but different arrangements of atoms around a central carbon. These two enantiomers are produced in a 50:50 mixture known as racemic mixture, or a racemate.

We've shown these stereochemical aspects using a halogenoalkane nucleophilic substitution reaction:

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Notice how in the SN2 mechanism above, the bonds in the product are inverted compared to the original reacting molecule. Compare this to the SN1 mechanism, which produces two different enantiomer products. One of the products is inverted, whilst the other keeps the original arrangement of bonds.

Once again, stereochemical aspects of nucleophilic substitution will all become clearer in Nucleophilic Substitution Mechanism. You can also learn more about stereoisomers and racemic mixtures in Optical Isomerism.

Examples of nucleophilic substitution reactions

Let's now move on to examples of nucleophilic substitution. We'll focus on nucleophilic substitution reactions involving halogenoalkanes.

Halogenoalkanes can react with the hydroxide ion, cyanide ion and ammonia molecule in nucleophilic substitution reactions. These reactions all use either the SN2 or SN1 mechanism that we looked at earlier, depending on the classification of the reacting halogenoalkane. Remember:

Primary halogenoalkanes use an SN2 mechanism.Tertiary halogenoalkanes use an SN1 mechanism.Secondary halogenoalkanes use both an SN2 and SN1 mechanism.

Nucleophilic substitution reaction with the hydroxide ion

Halogenoalkanes react with aqueous sodium or potassium hydroxide (NaOH or KOH) to form an alcohol (ROH) and a halide ion (X-). Alcohols have the hydroxyl functional group (-OH) and are represented by the general formula CxH2x+1OH. The potassium/sodium ion acts as a spectator ion and is not shown in the mechanism.

A spectator ion is an ion that remains in the same form on both sides of the reaction equation. It keeps the same physical state, charge, and oxidation state. If we write out all the ions involved in a reaction, we can see which are spectators. For example, in the reaction between hydrochloric acid (HCl) and sodium hydroxide (NaOH) , the sodium ions (Na+) and chloride ions (Cl-) are all spectators - they stay in the same state and aren’t changed in the reaction. HCl(aq) + NaOH(aq) → NaCl(aq) + H2O(l) H+(aq) + Cl-(aq) + Na+(aq) + OH-(aq) →  Na+(aq) + Cl-(aq) + H2O(l)

Let’s look at the conditions for nucleophilic substitution with hydroxide ions. Halogenoalkanes do not readily mix with water, so ethanol is used as a solvent for the substitution reaction. The mixture is warmed under reflux to increase the rate of reaction:

Warming the mixture increases the kinetic energy of the molecules. This means that not only do they move faster and so have more collisions, but on average they also have more energy when they collide. This means that they are more likely to have the activation energy needed for a reaction. There will be a higher proportion of successful collisions and thus a faster reaction.Reflux is a reaction technique that involves heating the mixture in a sealed vessel. When volatile components in the mixture evaporate, they are trapped in a condenser and cannot escape out of the system, and instead condense back into the container. We can reach higher temperatures and carry the reaction out over a longer period. This increases the opportunity for a successful reaction.

For more on rates of reaction, see Collision Theory and Increasing Rates.

For example, bromoethane (CH3CH2Br) reacts with potassium hydroxide to form ethanol (CH3CH2OH) and a bromide ion. The bromide ion then reacts with the potassium ion to form potassium bromide. This can be shown by the following overall equation:

CH3CH2Br + KOH → CH3CH2OH + KBr

Remember to use structural formulae when writing equations to show the molecule’s structure and the position of the new functional group.

Another example is the nucleophilic attack of 2-chloro-2-methylpropane (CH3CCl(CH3)CH3) by sodium hydroxide, forming 2-methylpropan-2-ol (CH3COH(CH3)CH3) and sodium chloride. Here's the equation:

CH3CCl(CH3)CH3 + NaOH → CH3CCl(CH3)CH3 + NaCl

There is another type of reaction involving halogenoalkanes and hydroxide ions. It is called an elimination reaction. In elimination reactions, the hydroxide ion acts as a base instead of a nucleophile. It produces an alkene, water and a halide ion. The conditions are slightly different too - we use hot and concentrated ethanolic potassium (or sodium) hydroxide. Explore this in Elimination Reactions.

Nucleophilic substitution reaction with the cyanide ion

Potassium or sodium cyanide (KCN or NaCN) react with halogenoalkanes in ethanolic solution to form a nitrile (RCN) and a halide ion. Nitriles have the functional group -CN, which contains a C≡N triple bond. Once again, the reaction mixture is heated under reflux. This nucleophilic substitution reaction is important industrially as it increases the length of the carbon chain.

For example, chloromethane (CH3Cl) heated in ethanolic potassium cyanide produces ethanenitrile (CH3CN) and a chloride ion. The chloride ion then reacts with potassium to form potassium chloride. The overall equation is as follows:

CH3Cl + KCN → CH3CN + KCl

For more information on nitriles, see the article specifically dedicated to them: Nitriles.

Nucleophilic substitution reaction with ammonia

The reaction between halogenoalkanes and an excess of ammonia (NH3) produces a primary amine (RNH2), a halide ion and an ammonium ion (NH4+). Amines are ammonia derivatives, where one or more of the hydrogen atoms has been replaced by an alkyl group.

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We saw earlier in the article that although ammonia is not a negative ion, it is still a nucleophile. It contains a partially negatively charged atom, Nδ-, with a lone pair of electrons. When the nitrogen atom donates its lone pair of electrons to the carbon atom, the nitrogen atom becomes positively charged. This isn’t great for the molecule - it wants to be neutral, as that’s a lot more stable. To solve this problem, it kicks out a hydrogen atom, but keeps the bonded pair of electrons. The hydrogen atom is now a positive ion, and reacts with a second molecule of ammonia to form a positive ammonium ion. This positive ammonium ion can then react with the bromide ion produced in the substitution reaction, forming an ammonium salt. Overall, the reaction requires two moles of ammonia for each mole of halogenoalkane.

The reaction is carried out heated in ethanolic solution, in a sealed container under pressure.

For example, bromoethane (CH3CH2Br) and ammonia react together to form ethanamine (CH3CH2NH2), a bromide ion, and an ammonium ion. The ammonium ion reacts with the bromide ion to form an ammonium salt, ammonium bromide (NH4Br):

CH3CH2Br + 2NH3 → CH3CH2NH2 + NH4Br

Nucleophilic substitution reaction with silver nitrate solution

Let's talk about how we can use silver nitrate solution (AgNO3(aq)) mixed with ethanol to identify the halogen in a halogenoalkane. This process is called a nucleophilic substitution reaction. The ethanol dissolves everything, and the water in the silver nitrate solution acts as the nucleophile. This produces an alcohol, a hydrogen ion (H+), and a halide ion (X-). The halide ion then reacts with the silver nitrate to create a coloured precipitate. The colour of the precipitate tells us which halogen is present in the halogenoalkane.

This reaction is a great way to compare the reaction rates of different halogenoalkanes. For example, iodoalkanes produce a precipitate much faster than chloroalkanes. This is because the C-X bond enthalpy decreases as you move down the halogen group in the periodic table. This makes the halogenoalkane more reactive and leads to a faster reaction rate. Additionally, tertiary halogenoalkanes produce a precipitate faster than primary halogenoalkanes. This is because tertiary halogenoalkanes use the SN1 mechanism, which is faster than the SN2 mechanism used by primary halogenoalkanes.

Importance of nucleophilic substitution reactions

Nucleophilic substitution reactions are crucial in organic chemistry because they allow us to swap one functional group for another in certain organic molecules. In these reactions, a nucleophile attacks an organic molecule and replaces one of its functional groups with a different functional group. A nucleophile is an electron-pair donor with a negative or partially negative charge and a lone pair of electrons. Common nucleophiles include the hydroxide ion (:OH-), cyanide ion (:CN-), ammonia (NH3), and water (H2O). These nucleophiles can all react with halogenoalkanes in nucleophilic substitution reactions, releasing a halide ion.

Some specific nucleophilic substitution reactions, such as the reaction with the cyanide ion (:CN-), can increase the length of the carbon chain. This is important in industrial processes and can be quite challenging in organic chemistry.

In summary, nucleophilic substitution reactions are essential in organic chemistry as they allow us to swap functional groups and increase the length of carbon chains. This opens up a world of possibilities for industrial processes and organic synthesis.

Nucleophilic Substitution Reactions

What is a nucleophilic substitution reaction?

A nucleophilic substitution reaction is a reaction in which a functional group on a molecule is replaced by a nucleophile. Nucleophiles are electron pair donors with a negative or partial negative charge and a spare pair of electrons.

Does benzene undergo nucleophilic substitution reactions?

Benzene derivatives, such as chlorobenzene, can undergo nucleophilic substitution reactions. However, benzene itself undergoes electrophilic substitution instead. This is because the high charge density of its ring of delocalised electrons is appealing to electrophiles.

What are the types of nucleophilic substitution reactions?

There are multiple types of nucleophilic substitution reactions. Examples include the substitution of halogenoalkanes using hydroxide ions or cyanide ions.

What are important factors in a nucleophilic substitution reaction?

Factors affecting nucleophilic substitution reactions include the partial charge of the carbon atom, the strength of the bond between the carbon and the leaving group, and the strength of the nucleophile.

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