Bimolecular Nucleophilic Substitution

The following video clip is an updated version of the bimolecular nucleophilic substitution reaction. It makes use of a generic nucleophile which is an anion reacting with a generic alkyl halide.



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^{Article written by Kwok YL 2011.}

^{Disclaimer and remarks:}

• ^{If you would like to use this source, kindly drop me a note by leaving behind a comment with your name and institution. I am all for sharing as the materials on this blog is actually meant for the education purpose of my students.}
• ^{This material is entirely written by the author and my sincere thanks will be given to anyone who is kind, generous and gracious to point out any errors.}

Alkyl halides, aryl halides, acyl halides

Acid chlorides (aka Acyl Chlorides), alkyl chlorides and aryl chlorides are halogen containing compounds. Generally, when we are asked to perform a chemical test to these three compounds, the aim of the chemical test is to see which of these compounds will be able to produce a AgCl precipitate. Hence, this test presupposes that a nucleophilic substitution must happen to release the Cl^- so that it can be precipitated with a Ag⁺

When comparing alkyl chloride and aryl chloride. The chemical test steps consist of the following:

1. NaOH, heat
2. Cool
3. Add HNO₃
4. Add AgNO₃

The first step is the nucleophilic substitution where chloride ion leaves. Aryl chloride does not undergo nucleophilic substitution reaction.

While when comparing alkyl chloride and acid chloride. The chemical test is.

1. Add AgNO₃.

Acid chloride has a very electron deficient carbon, because it is attached to both the O and the Cl. That makes this carbon very willing for nucleophiles to attack it. Hence, in this chemical test, H₂O is the nucleophile that causes a nucleophilic substitution to occur. Acid chloride is so susceptible to nucleophilic substitution that a weak nucleophile can be used (H₂ vs OH^-) and a milder condition is required (room temperature vs heat).

In addition, this post would also like to serve us a good entry which teaches us how to describe the nucleophilic substitution using acid chloride and a nucleophile. The mechanism is different from S_N1 and S_N2. The picture below describes the mechanism while the video below describes how to draw the mechanism.

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^{Article written by Kwok YL 2010.}

^{Disclaimer and remarks:}

• ^{If you would like to use this source, kindly drop me a note by leaving behind a comment with your name and institution. I am all for sharing as the materials on this blog is actually meant for the education purpose of my students.}
• ^{This material is entirely written by the author and my sincere thanks will be given to anyone who is kind, generous and gracious to point out any errors.}

Alkyl Halides - Stability of Carbocation (SN1)

When an alkyl halide reacts with a nucleophile in a nucleophilic substitution, it has two possible pathway: S_N1 or S_N2. The former is a two steps mechanism, where an intermediate is formed. While the latter is a single step reaction, with no intermediate formed.

Hence, a simple tool to predict whether an alkyl halide reacts in a S_N1 or S_N2 manner, it is dependent on whether an carbocation intermediate can be formed. If the carbocation intermediate can be formed, it must be because it is stable. In an earlier article, we discussed about carbocation and you can read it here.

This entry intends to elaborate further about the possible types of carbocations that can be formed from different alkyl halides. The following illustration gives us some examples of such alkyl halides which undergoes S_N1 mechanism.

The tertiary alkyl halide tends to undergo S_N1 mechanism because it is able to form a tertiary carbocation (as shown below) which is made stable by the 3 alkyl groups it is attached to. The alkyl groups being electron donating, allow the positive charge to be delocalised by induction. The fewer the alkyl groups, the less stable the carbocation would be and hence the less likely for the alkyl halide to undergo S_N1.

However, there are other alkyl halides which are not tertiary and they are able to undergo S_N1. This is because they have other portion(s) of the ion which enables the positive charge to be delocalised and hence making the ion stable.

In the following two cases (carbon with positive charge is attached to a C=C and benzene ring), the carbocation are stable because the positive charge is being delocalised by resonance.  This happens when the p orbital of the carbon with the positive charge and the p orbital of the carbon that makes the alkene (or benzene) can overlap with each other.

The overlapping of all the relevant p orbital enables the pi electrons are able to flow towards the carbon with the positive charge, hence the flow of pi electrons cause the positive charge to be delocalised; This form of delocalisation is delocalisation by resonance. Therefore, it is because these two carbocations are made stable, their correspond alkyl halide would react with a nucleophile in a S_N1 manner.

As delocalisation of the positive charge into the benzene ring is quite extensive, if the carbon with the positive charge is attached to a cyclohexene (as shown below). The stabilising effect from benzene will make the carbocation more stable than the latter's case.

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^{Article written by Kwok YL 2010.}

^{Disclaimer and remarks:}

• ^{If you would like to use this source, kindly drop me a note by leaving behind a comment with your name and institution. I am all for sharing as the materials on this blog is actually meant for the education purpose of my students.}
• ^{This material is entirely written by the author and my sincere thanks will be given to anyone who is kind, generous and gracious to point out any errors.}

Halogen Derivatives - Unimolecular Nucleophilic Substitution.

Previously we have discussed about Bimolecular Nucleophilic Substitution, also known as S_N2. In this mechanism, the rate of the reaction is dependent on the concentration of the alkyl halide and the concentration of the nucleophile. Hence, this also implies that both alkyl halide and the nucleophile are involved in the slow step of the reaction.

However, sometimes the rate of nucleophilic substitution reaction between an alkyl halide and nucleophile (note: aryl halides are STILL unable to undergo this reaction. Click here to find out why.) can be dependent on the concentration of the alkyl halide and independent on the concentration of the nucleophile.

Therefore, the above paragraph suggested that there is an alternative mechanism (or you could call it reaction route) for the nucleophilic substitution reaction. This reaction is called unimolecular nucleophilic substitution, S_N1.

There are two steps in this mechansim. The first step is the breaking of the C-X bond to generate the carbocation.

While the second step, which is the fast step, is where the nucleophile is attracted to the carbocation.

The rationale to why S_N1 is possible is because there are reasons to support the formation of a carbocation. If a stable carbocation can be formed, the S_N1 mechanism would be likely to occur. (Click here to read how the carbocation can be stablised.)

As such, generally 2^o alkyl halide, 3^o alkyl halide and phenyl-halo-methane (e.g. a benzene ring with a -CH₂X substituent), will support a S_N1 mechanism because it can form a stable carbocation. How C₆H₅CH₂⁺ carbocation is stablise by the phenyl group follows the same principle as this.

In conclusion, if you need to describe the mechanism of Unimolecular Nucleohilic Substitution, S_N1, both the fast and slow steps must be drawn. Hence, the following illustration shows the requirements needed.

The video below provides the steps and some basic explanation to S_N1 mechanism.

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^{Article written by Kwok YL 2009. Updated in Feb 2010.}

^{Disclaimer and remarks:}

• ^{If you would like to use this source, kindly drop me a note by leaving behind a comment with your name and institution. I am all for sharing as the materials on this blog is actually meant for the education purpose of my students.}
• ^{This material is entirely written by the author and my sincere thanks will be given to anyone who is kind, generous and gracious to point out any errors.}

Halogen Derivatives - SN1 vs SN2

When one understand the two nucleophilic substitution reactions, S_N1 and SN2, it is the feasibility of the formation of the carbocation that determines whether the nucleophilic substitution reaction occurs by the former means or by the latter method.

However, the best way to determine the mechanism is to perform a kinetics experiment; by finding out how the rate of reaction is affected by the concentration of the reaction; we can conclude whether it is S_N1 or S_N2. Hence, this entry aims to compare the two different mechanisms.

In S_N1, we expect that the rate of the reaction to be affect by the concentration of the alkyl halide only. In addition, if the initial alkyl halide is chiral, the product produced will be a racemic mixture. This is because in this mechanism, the carbocation formed is planar. Hence, the attacking nucleophile can attack the carbocation on either side of the plane, in equal probability. Hence, resulting in a racemic mixture to be formed.

In S_N2, the rate of reaction is affected by both the concentration of the alkyl halide and the concentration of the nucleophile. From the mechanism of the reaction, if the initial alkyl halide chiral, the product formed will also be chiral and no racemic mixture is formed.

In addition, when we compare the energy profile diagrams of S_N1 and S_N2, we can see that the former has two peaks, hence two transition states and 1 intermediate, while the former has just one peak, hence 1 transition state and no intermediate formed.


Therefore, the energy profile diagram reinforce that the S_N1 is a two-steps reaction while the S_N2 is a single step reaction.

In conclusion, these post highlights three differences the two mechanisms possess. Do you think there are any further differences?

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Article written by Kwok YL 2009.}

^{Disclaimer and remarks:}

• ^{If you would like to use this source, kindly drop me a note by leaving behind a comment with your name and institution. I am all for sharing as the materials on this blog is actually meant for the education purpose of my students.}
• ^{This material is entirely written by the author and my sincere thanks will be given to anyone who is kind, generous and gracious to point out any errors.}

Halogen Derivatives - Alkyl Halides vs Aryl Halides

The difference between alkyl halides and aryl halides can be subtle that those without a discerning eye will not be able to distinguish the two compounds. Taking the following two compounds (A and B) as example.

The presence of the large benzene ring (the correct term is phenyl substituent) gives the artificial illusion that both are aryl halides. However, A is an alkyl halide while B is the aryl halide.

If you notice carefully, the chlorine in A is attached to a sp³ carbon hence it is an alkyl halide. When the chlorine is attached to a benzene's carbon it is an aryl halide.

To distinguish the two compounds. The following is the chemical test performed. (1) Add NaOH, heat. (2) Cool the mixture. (3) Add excess HNO₃. (4) Add AgNO₃. The observation is: A produces a white precipitate while B does not. The following picture describes the significant chemical reactions occuring for A.

The inability of B to produce the precipitate stems from the fact that aryl halides have difficulties in undergoing nucleophilic substitution. The approaching nucleophile has to overcome the repulsion from the pi electron cloud before it can reach the back of the C-Cl bond - that is something unfavourable. Hence, without substituting the halogen, we will not get the silver halide precipitate.

In addition, the p orbital on C and the p orbtial on Cl can overlap with each other. Hence, the lone pair of electrons from Chlorine can be contributed into the benzene ring. This results in the C-Cl bond to develop a partial double bond characteristics and making the C-Cl's carbon less electron deficient (since chlorine donates its electron).

Interestingly, the above reasons can be used to account for why when a halogen is bonded to a C=C's carbon, it is also unwilling to undergo nucleophilic substitution reaction.

In conclusion, would you think that heating both A and B with acidified KMnO₄ is a good way to distinguish both compounds? Click here to discuss!

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^{Article written by Kwok YL 2009.}

^{Disclaimer and remarks:}

• ^{If you would like to use this source, kindly drop me a note by leaving behind a comment with your name and institution. I am all for sharing as the materials on this blog is actually meant for the education purpose of my students.}
• ^{This material is entirely written by the author and my sincere thanks will be given to anyone who is kind, generous and gracious to point out any errors.}

Halogen Derivatives - Bimolecular Nucleophilic Substitution

Nucleophilic substitution reactions are a group of chemical reactions which are very important in the production of other organic compounds. You are first introduced to this set of reactions through the chemical properties of alkyl halides.

Alkyl halides are reactive because the C-X bond is relatively weak (compared to the C-H bonds in the hydrocarbon chapters) and it is a polar bond. Yes, in the chapter of intramolecular bonding, you learned that the existence of polarity makes the bond stronger.(e.g. the triple bond between C and O in carbon monoxide is stronger than the triple bond between N atoms in nitrogen). This is because there is an added electrostatic attraction between the partial charges.

However, the presence of partial charges, such as a d+ carbon makes the carbon electron deficient. Hence, this makes the carbon susceptible to attacks by a nucleophile - hence alkyl halides are reactive because of its C-X bond. Therefore, alkyl halides undergo nucleophilic substitution.

The following video uses two examples to describe the mechanism of nucleophilic substitution. It is worthwhile to take note that there are two types of nucleophilic substitutions, S_N1 and S_N2. In this articles, I will be focusing on the latter.

If you have further question, you are encouraged to post your questions for discussion.

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^{Article written by Kwok YL 2009.}

^{Disclaimer and remarks:}

• ^{If you would like to use this source, kindly drop me a note by leaving behind a comment with your name and institution. I am all for sharing as the materials on this blog is actually meant for the education purpose of my students.}
• ^{This material is entirely written by the author and my sincere thanks will be given to anyone who is kind, generous and gracious to point out any errors.}