Category Archives: Organic Chemistry

Electrophilic Aromatic Substitution

Benzene rings are rich in electrons, which exist in an electron cloud over the conjugated ring. Being so electron rich, they are attractive to electrophilic reagents. There are five main types of EAS, which are listed below:

Halogenation

Nitration

Sulphonation

Friedel-Crafts Alkylation

Friedel-Crafts Acylation

All of these processes occur via the same mechanism, but you will need to know what reagents and solvents are required for each reaction.

The general mechanism is as follows:

General mechanism for EAS reactions

Halogenation, (for the purposes of this example, bromination) will not occur if benzene and Br2 are mixed together, the reaction requires the presence of a Lewis acid.

FeCl3 or AlCl3 are used for chlorinations, and they follow the same procedure. Fluorination of benzene is difficult as fluorine reacts rapidly with benzene and requires special equipment and an indirect method of reaction. You don’t need to know that reaction mechanism. Iodine is very unreactive towards benzene and so reaction has to take place in the presence of an oxidising agent, such as nitric acid.

Nitration of benzene can occur by mixing hot nitric acid with benzene, but the reaction is very slow. It can be sped up by adding sulphuric acid, which increases the concentration of the electrophile, (NO2+).

Sulphonation of benzene requires “fuming sulphuric acid”, which is sulphuric acid with extra SO3 added. The sulphuric acid produces even more SO3, which is the electrophile in this reaction.

Friedel-Crafts alkylations, (named after the chemists who discovered this method, Charles Friedel and James Crafts) are valuable reactions as they form a carbon-carbon bond – a very important thing in organic syntheses. The first step in connecting an alkyl group to a benzene ring is forming a carbocation, here achieved by reacting an alkyl chloride with AlCl3. The reaction then proceeds as normal.

 

 

If the R-X is a primary alkyl chloride, (meaning that it will form an unstable primary carbocation when the chloride is removed) the AlCl3 will instead form a complex with the alkyl group, which behaves as if it were a carbocation.

 

Friedel-Crafts acylation is much the same as an alkylation, requiring an acid chloride and Lewis acid to react, although it will also react with acetic anhydride, (remember back to first semester and the preparation of paracetamol).

Effect of substituents on reactivity and substituent direction:

 

Benzene’s reactivity is can be affected by any substituents attached, and this will determine the site of attack if any more substituents are added. If a substituent makes the benzene more reactive, it is referred to as an activating group, and it if makes it less reactive, a deactivating group. So far, so good.

 

 

 

Activating groups are anything that will donate electrons into the ring, increasing the electron density of the benzene and making it more attractive to electrophiles. These groups increase the rate of EAS reaction. You are looking for any group with lone pairs, or alkyl groups:

Electron withdrawing groups will deactivate the benzene and generally have a partial or full positive charge adjacent to the ring or electonegative atoms to remove electron density from the benzene ring.

Activating groups are orth-para directing, as any additional substituents will be directed to the ortho or para positions due to the resonance effect of the electron donating group, which can form a relatively stable fourth resonance form.

Deactivating groups are meta-directing, as ortho/para substituents lead to unstable resonance forms with the positive charge on the ring directly next to the partial or full positive charge on the substituent.

The exception to this rule are the halogens, despite being electron withdrawing due to strong electronegativity, they still have lone pairs, which can be donated into the ring, making them ortho/para directing.

 

Some links:

 

http://www.chem.ucalgary.ca/courses/351/Carey5th/Ch12/ch12-0.html

http://www.chem.ucla.edu/harding/cfqpp/EAS30.pdf (pdf link)

 

 

 

 

 

 

 

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Chem 2 tute sheet for week 3 (11/08)

This is a copy of the sheet I handed out in the week 3 tute:

1.  Identify the substrate, nucleophile and the leaving group:

a.    CH3CH2Br + CH3S → CH3CH2SCH3 + Br

b.   (CH3)2CHCH2OSO2F + NH3 → (CH3)2CHCH2NH3+ + FSO3

2. Show the major products for the addition reactions of a) propene and b) methylcyclohexene with the following:

i) H2/Pd

ii) HBr

iii) Br2

iv) H2O/H2SO4

3. Indicate the type of reaction shown below:

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Addition reactions

One example of nucleophilic/electrophilic reactions, (known as polar reactions) are additions to double bonds.

Alkenes are electron rich, so they behave as nucleophiles in polar reactions and attack electrophiles.

The placement of the new substituents is important and dictated by Markovnikov’s rule.

Vladimir Markovnikov: one of the two Russians we'll talk about during this course. This is the one with the better beard.

Markovnikov’s rule, according to McMurry’s Organic Chemistry:

In the addition of HX to an alkene, the H attaches to the carbon with fewer alkyl substituents, (the one with more hydrogens) and the X attaches to the carbon with more alkyl substituents.

In other words: the rich get richer.

The reason for this is pretty simple. Addition reactions occur in two steps, via a carbocation intermediate. The reaction won’t proceed unless the carbocation is as stable as possible, requiring the charged carbon to be the one with the most substituents.

Some further links and questions:

http://www.chemguide.co.uk/mechanisms/eladd/whatis.html#top

http://www.chemguide.co.uk/mechanisms/eladd/unsymprob.html#top

http://www.chem.ucalgary.ca/courses/350/Carey5th/Ch06/ch6-0.html

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Nucleophiles, Electrophiles and Leaving Groups: A Spotter’s Guide

Nucleophiles and electrophiles are important classes of molecules as they are involved with a large number of organic reactions. Success and happiness in organic chemistry relies on you being able to identify which is which.

Nucleophiles:

Nucleophile means “nucleus lover” and is pretty much what it says on the tin – these are c0mpounds that are strongly attracted to positive charge. It follows that they themselves are electron rich, sometimes with a formal negative charge.  Good nucleophiles are also very reactive. You know of another class of compounds that are reactive and electron rich – bases. Nucleophiles are generally strong bases,  or the conjugate base of a weak acid.

Electrophiles:

Electrophiles are the counterpart to nucleophiles. They crave electrons as they are electron poor, (sometimes positively charged). You won’t see the term “electrophile” as much as you will “nucleophile”, but you will see “electrophilic site”, which refers to the reactive, electron poor part of the substrate.

Leaving Groups:

Leaving groups are the part of the molecule that is booted off during a substitution or elimination reaction. They must be stable on their own, and not too tightly bound to the substrate. They are generally negatively charged, as they take the electrons with them when they leave. A good leaving group is a weak base, or a conjugate base of a strong acid. Note the difference between a g0od nucleophile and a good leaving group. This is an important distinction.

See? I told you, you need to know about acids and bases!

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