Nucleophilic substitution reactions of haloalkanes

Uses of haloalkanes

The halogenalkanes or haloalkanes form a homologous series of organic compounds with the general formula CnH_2n+1X; where X is one of the halogens (F, Cl, Br or I). The Haloalkanes have various everyday uses, such as in refrigerants in air conditioners and refrigerators, fire extinguishers (halons for fire suppression) and as solvents (e.g. chloroform in cleaning agents). They also play a role in the synthesis of many pharmaceuticals and pesticides. However due to many environmental concerns like ozone depletion many halogenalkanes (especially CFCs and halons, which used to be found in fire extinguishers) have been phased out and replaced by more environmentally friendly compounds.

Nucleophilic substitution reactions- the art of the swap

Before we start looking at these nucleophilic substitution reactions a quick recap on what a nucleophile is:

Think of the halogenalkanes (or haloalkanes) as the ultimate starting material. On their own they might just be solvents or refrigerants but to a chemist they are an open door. Why? It all comes down to the carbon-halogen (C-X) bond; because the halogens are electronegative or electron-greedy elements; the C-X bond in a haloalkane is a polar bond with the carbon atom bearing a slight positive charge (δ⁺) and the halogen having a slight negative charge (δ^-).

The partial positive charge on the carbon atom attached to the halogen makes it vulnerable to attack by electron rich species; that is nucleophiles. The (δ⁺) charge on the carbon atom in the C-X bond is like a huge open invitation for nucleophiles to come charging in and knock out the halogen atom. The C-X bond is already a polar one due to the fact that the halogens are electronegative elements and they are also good leaving groups simply because they can form stable halide ions. So really the stage is set; all it needs is a suitable nucleophile to come in and kick out or replace the halogen atom.

Nucleophilic substitution reactions

In the diagram shown below a nucleophile (Nu^-) uses its lone pair of electrons to form a new covalent bond to the carbon atom attached directly to the bromine atom (the halogen) in a molecule of bromomethane and at the same time the carbon-bromine bond breaks and a bromide ion (Br^-) leaves, for this reason it is often referred to as the leaving group. The end result is that the bromine atom is replaced or substituted by the nucleophile; this is an example of a nucleophilic substitution reaction.

Now the two most common reaction types that the haloalkanes readily undergo are nucleophilic substitutions and elimination reactions. This page will cover only nucleophilic substitution reactions; click the link above if you would like to visit the page on elimination reactions.

Nucleophilic substitution- common nucleophiles

In a nucleophilic substitution reaction the halogen atom is replaced or substituted with another atom or group for example:

• If the nucleophile is a hydroxide ion (OH^-) this will result in the halogen atom being replaced by the hydroxyl group (-OH) and will lead to the formation of alcohols.


• And if the cyanide ion (CN^-) is used as the nucleophile this will result in the formation of nitriles (RCN).


• And if the neutral molecule ammonia (NH₃) is used as a nucleophile this will result in the formation of amines.

Primary, secondary and tertiary halogenalkanes

Primary halogenalkanes

The way in which a haloalkanes react with a nucleophile can in part be down to their structure; that is whether they are primary, secondary or tertiary haloalkanes. So let us start by looking at some structural isomerism involving haloalkanes.

The image below shows two primary haloalkane molecules. In a primary halogenalkane molecule the carbon atom attached to the halogen atom (X) will have one alkyl group (-R) and two hydrogen atoms attached to it. Whereas the last molecule in the image below is simply a methane molecule where one of the hydrogen atoms has been replaced by a halogen, in this case an iodine atom. Simple haloalkane molecules such as this where the carbon atom attached to the halogen is bonded to only hydrogen atoms are called methyl haloalkanes.

Secondary halogenalkanes

In a secondary haloalkane molecule the carbon atom joined directly to the halogen will have two alkyl groups (-R) and one hydrogen atom attached to it; two examples of secondary haloalkane molecules are shown below:

Tertiary halogenalkanes

The image opposite shows 2-chloro-2-methylpropane, a tertiary haloalkane. In a tertiary haloalkane molecule the carbon atom attached to the halogen has three alkyl groups (-R) directly attached to it; this means that there are no hydrogen atoms attached.

Nucleophiles and electrophiles

The halogens being electronegative elements means that the C-X bond in haloalkane molecules will be a polar one, with the carbon atom in the C-X bond having a partial positive charge (δ⁺) and the halogen atom having a partial negative charge (δ^-). A nucleophile is an electron rich species; nucleophiles can be neutral molecules or ions with lone pairs of electrons which they can donate to an electron deficient molecule/atom (electrophiles); such as the carbon atom in a polar C-X bond. Examples of common nucleophiles were mentioned above but include hydroxide ions (OH^-), cyanide ions (CN^-), ammonia (NH₃) and water (H₂O). All these molecules whether charged or neutral are able to act as nucleophiles simply because they have lone pairs of electrons.

Self-check: Primary, secondary or tertiary?

Complete the quick activity below to correctly identify whether the molecule is a primary, secondary or tertiary haloalkane molecule.

Note

S_N1 and S_N2 reactions

The nucleophilic substitution reactions that haloalkanes undergo can follow one of two different mechanisms or routes. These mechanisms are called S_N1 and S_N2; this is short for substitution nucleophilic unimolecular (S_N1) and substitution nucleophilic bimolecular (S_N2). The mechanism, either the S_N1 or S_N2 route that is followed by the haloalkane when it reacts with a nucleophile will depend on whether it is a primary, secondary or tertiary haloalkane.

Primary halogenalkanes and S_N2 reactions

S_N2- The one step sneak attack from behind

The image below shows the hydroxide ion (OH^-) using one of its lone pairs of electrons to attack the δ⁺ carbon atom in a bromomethane molecule to form the alcohol methanol and a bromide ion (Br^-). Now at any given temperature and concentration of the two reactants, the hydroxide ion and the bromomethane; the reaction occurs at a certain rate. If we were to double the concentration of the hydroxide ion then the rate of reaction would also double. Similarly if we double the concentration of the bromomethane then the rate of reaction also doubles. This tells us that the rate of reaction depends on the concentration of both starting reagents; that is it is a second order reaction. The rate of the reaction will change if we alter the concentration of either the hydroxide ion or the bromomethane.

The mechanism put forward to explain this observation is called the S_N2 mechanism or substitution nucleophilic bimolecular. The main features of this mechanism are outlined in the image below and can be broken down into a number of steps:

• Step 1: The nucleophile uses its lone pair of electrons to attack the δ⁺ carbon atom in the C-X bond. The incoming nucleophile attacks the δ⁺ carbon atom from 180⁰ away, that is a sneaky attack from behind!


• Step 2: The attack by the nucleophile is fast, coordinated and well timed, as the nucleophile starts to bond to the δ⁺ carbon atom the halogen atom is already being pushed out. This sort of half in half out state for the incoming nucleophile and departing halogen is called a transition state, it is a very short-lived, high-energy arrangement of atoms that cannot be isolated or detected as a real intermediate. Here the new bond between the carbon atom and the incoming nucleophile is forming at the same time as the C–X (the bond between the carbon and the leaving halogen atom) is breaking


• Step 3: The final step is the complete formation of the C-Nu bond and the breaking of the C-X bond to form the products of the reaction; this is outlined in the image below.

Factors affecting S_N2 reactions

There are a number of factors that affect how quickly these S_N2 reactions proceed; one of the most obvious factors is anything which can block or at least slow or hinder the incoming nucleophile as it attacks the δ⁺ carbon atom in the C-X bond will obviously affect how quickly this reaction can take place. Since the incoming nucleophile (Nu) needs to approach the δ⁺ carbon atom from the side opposite to the leaving group (often described as a 180° approach), then any large bulky groups attached to the carbon atom will could slow its approach or even block it. This blocking action of the attached groups is often referred to as steric hindrance.

S_N1 or S_N2 ?

In the example shown in the image above the δ⁺ carbon atom in the C-X bond is bonded to three very small hydrogen atoms; so what do you think would happen to the rate of the reaction if one of these hydrogen atoms was replaced by a larger group such as a methyl group (-CH₃) or an ethyl group (-C₂H₅) or even larger groups? As you might expect as the groups become larger and more of them are added they do indeed block the incoming nucleophile and slow the reaction rate.

This is summarised in the diagram below which starts with a methyl haloalkane molecule which undergoes a rapid S_N2 reaction and the final image shows a tertiary haloalkane molecule which does not undergo an S_N2 reaction but instead reacts via a S_N1 reaction mechanism.

S_N1 reactions- the two step break-up

Nucleophilic substitution reactions involving primary haloalkanes readily take place by an S_N2 mechanism; since the incoming nucleophile is not blocked or hindered in any way from attacking the δ⁺ carbon atom; however as the size of the groups attached to the carbon atom bonded to the halogen increase the rate of reaction slows down because these larger groups block the incoming nucleophile from approaching the δ⁺ carbon atom effectively.

Now consider secondary haloalkanes which have two alkyl groups attached to the carbon bonded to the halogen; these groups are more effective at blocking the incoming nucleophile and so secondary haloalkanes react more slowly than primary halogenalkanes. So what about tertiary haloalkanes? You will probably have figured out that tertiary haloalkanes do not react with nucleophiles by an S_N2 mechanism, the incoming nucleophile is simply blocked by the three alkyl groups. We can summarise this as shown below:

Nucleophilic substitution and tertiary haloalkanes

So how do tertiary haloalkanes react with nucleophiles? The mechanism suggested for these reactions involving tertiary haloalkanes is called an S_N1 reaction ( substitution nucleophilic unimolecular).

For example if we use 2-bromo-2-methylpropane as an example of a tertiary haloalkane (as shown in the image above), then in its reaction with a nucleophile the rate of reaction depends only on the concentration of the haloalkane and not the nucleophile. This is different from the S_N2 mechanism where the reaction rate depends on both the concentration of the nucleophile and the haloalkane. The mechanism for the S_N1 is outlined below. The reaction of tertiary haloalkanes via this S_N1 mechanism occurs in two steps:

• Step 1- This is the rate limiting (slow) step. The C-X bond in the tertiary haloalkane breaks to form a relatively stable tertiary carbocation. The concentration of this intermediate carbocation at any one time is likely to be low. Now the presence of the three alkyl groups around the central carbocation helps to stabilise it due to the positive inductive effect from the alkyl groups, which push electron density towards the carbocation and stabilise it long enough for step 2 to occur.
• Step 2- The nucleophile attacks the carbocation. This is a fast step.

Since step 1 is the slow step, this holds up the reaction. Step 2 can be very fast, but it makes no difference to the overall rate of the reaction; this depends only on step 1 (the rate limiting step).

Example of the S_N1 mechanism

Secondary haloalkanes: The annoying middle child

If primary haloalkanes molecules are the masters of S_N2 nucleophilic substitution reactions and tertiary haloalkane molecules are the kings of S_N1 reactions then where does that leave secondary haloalkanes?

Secondary haloalkane molecules are like the annoying "middle children" of organic chemistry, in that they can actually undergo both S_N2 and S_N1 mechanisms. So how is this possible? Well they have two alkyl groups so they have a bit of steric hindrance (blocking the S_N2 attack) but they also a bit of inductive stabilisation from the two alkyl groups which helps stabilise the intermediate carbocation in the S_N1 reaction. So how does the secondary haloalkane molecule decide which path to take- S_N2 or S_N1? Well it comes down to a battle of conditions.

The battle for the mechanism

When a secondary halogenalkane is sitting on the fence trying to decide whether to follow a S_N2 or S_N1 route, the environment and the type of nucleophile tips the scale. The reaction will follow a:

• S_N2 pathway if the nucleophile is a powerhouse! Strong, small nucleophiles like hydroxide ions (OH^-) or cyanide ions CN^- don't want to hang about and wait. They will force their way in for a "backside attack" on the C-X bond before the halogen even has a chance to leave.
• Weak nucleophiles such as water (H₂O) and alcohols such as ethanol (C₂H₅OH) aren't strong enough to force an attack. They’ll wait for the "breakup of the haloalkane" molecule to form a carbocation and then attack it. That is using weak nucleophiles will result in a S_N1 reaction.

The solvent effect

Self-check: 🔍Crowded or Clear? Can the Nucleophile Get In?

The ultimate showdown: Bond Enthalpy vs. Polarity

There are two other factors that are important when discussing the rates of S_N1 and S_N2 reactions, these are:

• the polarity of the carbon-halogen bond
• the strength of the carbon-halogen bond

Bond polarity

As you move down group 7 from the very electronegative fluorine to the much less electronegative iodine, the polarity of the carbon-halogen bond decreases and so the electron deficient carbon atom is less strongly δ⁺.

Based on bond polarity alone you might predict fluoroalkanes would react more readily than iodoalkanes, since the incoming nucleophile would be more strongly attracted to the larger partial positive charge on the carbon atom; however in practice fluoroalkanes react extremely slowly in nucleophilic substitution reactions because the C-F bond is very strong (see the image below), so if the halogen won't leave the nucleophile cannot come in and bond to the carbon atom in the C-X bond. However the C-I bond is the weakest of the carbon halogen bonds and this is why iodoalkanes are generally the most reactive overall.

Bond strength

The general trend in the strength of the C-X bond is that bond strength decreases as you move from F to Cl to Br to I. This is mainly because the bond length increases due to the larger atomic size of the halogen, and longer bonds generally mean weaker bonds, as outlined in the image below:

Quick summary

Of the two factors, it is the strength of the C-X bond (bond enthalpy) rather than bond polarity that has the major effect on the overall rate of reaction of haloalkanes, and we can say that the rates of reaction of haloalkanes follow the pattern:

Summary table

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Key Points

• Haloalkanes form structural isomers to give primary, secondary and tertiary molecules.
• Haloalkanes undergo nucleophilic substitution reactions with nucleophiles such as hydroxide ions, cyanide ions and ammonia.
• There are two different mechanisms for these nucleophilic substitution reactions:
• Primary haloalkanes react by an S_N2 mechanism. Here the reaction rate depends on the concentration of the halogenalkane and the nucleophile.
• Tertiary haloalkanes react by an S_N1 mechanism. Here the reaction rate depends only on the concentration of the haloalkane.
• Secondary haloalkanes can react by both S_N1 and S_N2 mechanisms, depending on the particular haloalkane molecule and the reaction conditions, but the S_N1 mechanism is favoured when carbocation formation is more likely to occur.

Check your understanding - Questions on Nucleophilic substitution reactions

Check your understanding - Additional questions on Nucleophilic substitution reactions

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