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Chapter: Organic Chemistry: Aromatic chemistry

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Electrophilic substitutions of benzene

An electrophilic substitution involves the substitution of one electrophile (a proton) from the aromatic ring with another electrophile. The aromatic ring remains intact.

ELECTROPHILIC SUBSTITUTIONS OF BENZENE

Key Notes

Definition

An electrophilic substitution involves the substitution of one electrophile (a proton) from the aromatic ring with another electrophile. The aromatic ring remains intact.

Mechanism

The mechanism of electrophilic substitution involves two stages. In stage 1, the aromatic ring uses two of its π electrons to form a bond to the electrophile which results in a positively charged intermediate. In stage 2, a proton is lost from the ring and the electrons of the broken C–H bond are used to reform the π bond and restore aromaticity.

Intermediate stabilization

Electrophilic substitution is aided by the fact that the positively charged intermediate is stabilized by resonance, resulting in delocalization of the positive charge. Since the intermediate is stabilized, the reaction takes place more readily.

Halogenation

Benzene can be halogenated with chlorine and bromine. A Lewis acid such as FeBr3 or FeCl3 is required in order to activate the halogen and make it more electrophilic.

Friedel–Crafts alkylation and acylation

Alkyl chains are linked to benzene by the Friedel–Crafts alkylation, using an alkyl chloride and a Lewis acid. The Lewis acid is important in gener-ating a carbocation which acts as the electrophile for the reaction. Primary alkyl chlorides are not ideal for the Friedel–Crafts reaction since the pri-mary carbocations generated can rearrange to more stable secondary or tertiary carbocations. The Friedel–Crafts alkylation can also be carried out using an alkene or an alcohol in the presence of a mineral acid. The Friedel–Crafts acylation involves the reaction of benzene with an acid chloride and a Lewis acid. An acylium ion is generated as the elec-trophile and has the advantage over a carbocation in that it does not rearrange. The product is an aromatic ketone. The ketone group can be reduced to give alkyl chains which would be difficult to attach by the Friedel–Crafts alkylation.

Sulfonation and nitration

Benzene is sulfonated with concentrated sulfuric acid. The reaction involves the generation of sulfur trioxide which acts as the electrophile. Nitration is carried out using concentrated nitric acid and sulfuric acid. The sulfuric acid is present as an acid catalyst in the generation of the electrophilic nitro-nium ion. Both electrophiles in these reactions are strong and a Lewis acid is not required.

 

Definition

Aromatic rings undergo electrophilic substitution, for example the bromination of  benzene  (Fig.  1).  The  reaction  involves  an  electrophile  (Br+ )  replacing another  electrophile  (H+ )  with  the  aromatic  ring  remaining  intact.  Therefore, one electrophile replaces another and the reaction is known as an electrophilic substitution. (At this stage we shall ignore how the bromine cation is formed.)


Mechanism

In the mechanism (Fig. 2) the aromatic ring acts as a nucleophile and provides two of its π electrons to form a bond to Br . The aromatic ring has now lost one of its formal double bonds resulting in a positively charged carbon atom. This first step in the mechanism is the same as the one described for the electrophilic addition to alkenes, and so the positively charged intermediate here is equivalent to the carbocation intermediate in electrophilic addition. However in step 2, the mechanisms of electrophilic addition and electrophilic substitution differ. Whereas the carbocation intermediate from an alkene reacts with a nucleophile to give an addition product, the intermediate from the aromatic ring loses a proton. The C–H σ bond breaks and the two electrons move into the ring to reform the π bond, thus regenerating the aromatic ring and neutralizing the positive charge on the carbon. This is the mechanism undergone in all electrophilic substitutions. The only difference is the nature of the electrophile (Fig. 3).



Intermediate stabilization

The rate-determining step in electrophilic substitution is the formation of the pos- itively charged intermediate, and so the rate of the reaction is determined by the energy level of the transition state leading to that intermediate. The transition state resembles the intermediate in character and so any factor stabilizing the intermediate also stabilizes the transition state and lowers the activation energy required for the reaction. Therefore, electrophilic substitution is more likely to take place if the positively charged intermediate can be stabilized. Stabilization is possible if the positive charge can be spread amongst different atoms – a process called  delocalization.  The  process  by  which  this  can  take  place  is  known  as resonance (Fig. 4).


The resonance process involves two π electrons shifting their position round the ring to provide the ‘top’ carbon with a fourth bond and thus neutralize its posi-tive charge. In the process, another carbon in the ring is left short of bonds and gains the positive charge. This process can be repeated such that the positive charge is spread to a third carbon. The structures drawn in Fig. 4 are known as resonance structures.

Halogenation

The stable aromatic ring means that aromatic compounds are less reactive than alkenes to electrophiles. For example, an alkene will react with Br2 whereas an aromatic ring will not. Therefore, we have to activate the aromatic ring (i.e. make it a better nucleophile) or activate the Br2 (i.e. make it a better electrophile) if we want a reaction to occur. Laterly, we will explain how electron-donating substituents on an aromatic ring increase the nucleophilicity of the aromatic ring. Here, we shall see how a Br2 molecule can be activated to make it a better electrophile. This can be done by adding a Lewis acid such as FeCl3, FeBr3, or AlCl3 to the reaction medium. These compounds all contain a central atom (iron or aluminum) which is strongly electrophilic and does not have a full valence shell of electrons. As a result, the central atom can accept a lone pair of electrons, even from a weakly nucleophilic atom such as a halogen. In the example shown (Fig. 5) bromine uses a lone pair of electrons to form a bond to the Fe atom in FeBr3 and becomes positively charged. Bromine is now activated to behave as an electrophile and will react more easily with a nucleophile (the aromatic ring) by the normal mechanism for electrophilic substitution.

An aromatic ring can be chlorinated in a similar fashion, using Cl2 in the presence of FeCl3.


Friedel–Crafts alkylation and acylation

Friedel–Crafts alkylation and acylation (Fig. 6)  are  two  other  examples  of electrophilic substitution requiring the presence of a Lewis acid, and are par- ticularly important because they allow the construction of larger organic mol-ecules by adding alkyl (R) or acyl (RCO) side chains to an aromatic ring.


An example of Friedel–Crafts alkylation is the reaction of benzene with 2-chloropropane (Fig. 7). The Lewis acid (AlCl3) promotes the formation of the car-bocation required for the reaction and does so by accepting a lone pair of electrons from chlorine to form an unstable intermediate which fragments to give a carbo-cation and AlCl4- (Fig. 8). Once the carbocation is formed it reacts as an elec-trophile with the aromatic ring by the electrophilic substitution mechanism already described (Fig. 9).


There are limitations to the Friedel–Crafts alkylation. For example, the reaction of 1-chlorobutane with benzene gives two products with only 34% of the desired product (Fig. 10). This is due to the fact that the primary carbocation which is gen-erated can rearrange to a more stable secondary carbocation where a hydrogen (and the two sigma electrons making up the C–H bond) ‘shift’ across to the neigh-boring carbon atom (Fig. 11). This is known as a hydride shift and it takes place because the secondary carbocation is more stable than the primary carbocation. Such rearrangements limit the type of alkylations which can be carried out by the Friedel–Crafts reaction.


Bearing this in mind, how is it possible to make structures like 1-butylbenzene in good yield? The answer to this problem lies in the Friedel–Crafts acylation (Fig.12). By reacting benzene with butanoyl chloride instead of 1-chlorobutane, thenecessary 4-C skeleton is linked to the aromatic ring and no rearrangement takes place. The carbonyl group can then be removed by reducing it with hydrogen over a palladium catalyst to give the desired product.


The mechanism of the Friedel–Crafts acylation is the same as the Friedel–Crafts alkylation involving an acylium ion instead of a carbocation. As with the Friedel–Crafts alkylation, a Lewis acid is required to generate the acylium ion (R–C=O)+ , but unlike a carbocation the acylium ion does not rearrange since there is resonance stabilization from the oxygen (Fig. 13).


Friedel–Crafts alkylations can also be carried out using alkenes instead of alkyl halides. A Lewis acid is not required, but a mineral acid is. Treatment of the alkene with the acid leads to a carbocation which can then react with an aromatic ring by the same electrophilic substitution mechanism already described (Fig. 14). As far as the alkene is concerned, this is another example of electrophilic addition where a proton is attached to one end of the double bond and a phenyl group is added to the other.


Friedel–Crafts reactions can also be carried out with alcohols in the presence of mineral acid. The acid leads to the elimination of water from the alcohol resulting in the formation of an alkene which can then be converted to a carbocation as already described (Fig. 15).


Sulfonation and nitration

Sulfonation and nitration are electrophilic substitutions which involve strong electrophiles and do not need the presence of a Lewis acid (Fig. 16).


In sulfonation, the electrophile is sulfur trioxide (SO3) which is generated under the acidic reaction conditions (Fig. 17). Protonation of an OH group generates a protonated intermediate (I). Since the oxygen gains a positive charge it becomes a good leaving group and water is lost from the intermedi-ate to give sulfur trioxide. Although sulfur trioxide has no positive charge, it is a strong electrophile. This is because the sulfur atom is bonded to three elec-tronegative oxygen atoms which are all ‘pulling’ electrons from the sulfur, and making it electron deficient (i.e. electrophilic). During electrophilic substitution (Fig. 18), the aromatic ring forms a bond to sulfur and one of the π bonds between sulfur and oxygen is broken. Both electrons move to the more electronegative oxy-gen to form a third lone pair and produce a negative charge on that oxygen. This will finally be neutralized when the third lone pair of electrons is used to form a bond to a proton.


In nitration, sulfuric acid serves as an acid catalyst for the formation of a nitronium ion (NO2 ) which is generated from nitric acid by a very similar mechanism to that used in the generation of sulfur trioxide from sulfuric acid (Fig. 19).

The mechanism for the nitration of benzene is very similar to sulfonation (Fig. 20). As the aromatic ring forms a bond to the electrophilic nitrogen atom, aπbond between N and O breaks and both electrons move onto the oxygen atom. Unlike sulfonation, this oxygen keeps its negative charge and does not pick up a proton. This is because it acts as a counterion to the neighboring positive charge on nitrogen.


 

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