Electrophilic substitution

Electrophilic substitution reactions are chemical reactions in which an electrophile displaces another group, typically but not always hydrogen. Electrophilic substitution is characteristic of aromatic compounds. It is an important way of introducing functional groups on benzene rings.

Contents

1 General mechanism 2 Common electrophilic substitution reactions 2.1 Nitration 2.2 Sulfonation 2.3 Halogenation 2.4 Friedel-Crafts acylation 2.5 Friedel-Crafts alkylation

General mechanism

Key Steps:

• Benzene, a nucleophile reacts with an electrophile (Y⁺)
• Addition of an electrophile to the ring forms a carbocation
• The carbocation loses a proton from the site of the electrophilic attack and the electrons are added to the ring
• Aromaticity is reformed

Notes:

• B and HB⁺ represent a base present in the mixture (water, solvent, conjugate base)
• An electrophilic addition reaction does not occur because aromatic compounds are more stable. The ΔG° is close to zero for an electrophilic substitution reaction with benzene.
• The cyclohexadienyl cation intermediate goes by the name of Wheland intermediate.

Electrophilic substitution on benzene results in a predictable outcome in the case of monosubstitution. When working with a substituted benzene compound regioselectivity becomes an issue. Will the nucleophile add to a position next the already existing substituent (meta) or once removed (ortho) or twice removed (para)?. It turns out that substituents can be grouped into two classes, those that activate the aromatic ring towards further electrophilic substitution - the activating groups - and those that deactivate the compound. Each group also drives the direction to a specific position on the ring. For example the orientation in toluene nitration is towards the aromatic ortho position and aromatic para position.

Common electrophilic substitution reactions

All of the following reactions follow the same general mechanism as above. If present, catalysts are used to form electrophiles and do not react with benzene. Ar = aryl (an aromatic; benzene)

Nitration

Aromatic nitrations to form nitro compounds take place by generating a nitronium ion from nitric acid and sulfuric acid.

Sulfonation

Reaction:

The formation of sulfur trioxide (the electrophile) from concentrated sulfuric acid when heated is shown below:

Halogenation

Typical reaction of halogenation of benzene:

Where X is the halogen, [catalyst] represents the catalyst (if needed) and HX represents the protonated base.

For Bromination / Chlorination
X = Br₂ / Cl₂
[catalyst] = FeBr₃ / FeCl₃
HX = HBr / HCl

The mechanism for bromination of benzene:

The mechanism for chlorination of benzene is the same as bromination of benzene, except as noted above. Ferric Bromide and ferric chloride become inactivated if they react with water, including moisture in the air. Therefore, they are generated in situ by adding iron fillings and bromine or chlorine.

The mechanism for iodination is slightly different: iodine (I₂) is treated with an oxidizing agent (such as nitric acid) to obtain the electrophilic iodine (2 I⁺). Unlike the other halogens, iodine does not serve as a base since it is positive.

Halogenation of aromatic compounds differs from the halogenation of alkenes, which do not require a Lewis Acid catalyst. The formation of a carbocation in benzene results in the loss of aromaticiy, which has a higher activation energy compared to carbocation formation in alkenes. In other words, alkenes are more reactive and don't need to have the Br-Br or Cl-Cl bond weakened.

If the ring contains a a strongly activating substituent such as -OH, -OR or amines, a catalyst is not necessary. However, if a catalyst is used with excess bromine, then a tribromide will be formed.

Friedel-Crafts acylation

Reaction:

The formation of an acylium ion (the electrophile) from an acyl chloride with aluminium trichloride is shown below:

Benzene reacts with the resonance contributor with a positive charge on the carbon. Friedel-Crafts acylation must be carried out with more than one equivalent of aluminium trichloride since it will complex with the carbonyl group. Once the reaction is over, water is added to free the product from the complex.

Friedel-Crafts alkylation

Reaction:

The formation of the carbocation (the electrophile) from an alkyl halide with aluminium trichloride is shown below:

Alkyl fluorides, alkyl chlorides, alkyl bromides, and alkyl iodides can all be used with aluminium trichloride. Since an alkyl substituted benzene is more reactive, large amounts of benzene are added so it is more likely that aluminium trichloride will encounter unsubstituted benzene. Carbocation rearrangement can occur if it leads to a more stable form. In this case, the major product will contain the more stable carbocation.

Both the Friedel-Crafts acylation and alkylation are named after Charles Friedel and James Crafts.de:Elektrophile Substitution it:Sostituzione elettrofila