Friedel-Crafts reactions allow us to add alkyl and acyl groups to benzene providing a way of adding carbon atoms to the ring and building side chains. This is particularly useful in the synthesis of pharmaceutical drugs, detergents, dyes and other large aromatic molecules.
1. Friedel-Crafts alkylation
An alkylbenzene is formed when benzene reacts with a bromoalkane or a chloroalkane in the presence of a catalyst such as FeBr3, FeCl3 or AlCl3. Once again, this is an electrophilic substitution mechanism with the catalyst converting the halogenoalkane into a strong electrophile.
If the reaction is between benzene and a primary halogenoalkane, the halogenoalkane and the catalyst form a coordination complex. Electrons from the delocalised ring of electrons in benzene attack the 𝛅+ carbon atom in the complex forming an alkylbenzene and regenerating the catalyst.
If the reaction is between benzene and a tertiary halogenoalkane, the coordination complex formed in the preliminary step of the reaction breaks down into a stable carbocation which is a strong electrophile (tertiary carbocations are more stable than secondary carbocations which are more stable than primary carbocations because the the central positively charged carbon atom is stabilised by electron donating alkyl groups).
2. Friedel-Crafts acylation
Benzene reacts with acyl chlorides in the presence of a catalyst such as FeCl3 or AlCl3 to form an acylbenzene. This is a useful way to introduce a ketone group onto a benzene ring.
The mechanism is similar to that shown above. In the first step the acyl chloride forms a coordination complex with the catalyst which breaks down into a stable, positively charged acylium ion.
Practice questions
- Compound X, shown below, is formed by the reaction of benzene with an electrophile.
(a) Write an equation to show the formation of the electrophile from iron(III) bromide and 2-bromopropane.
(b) Outline a mechanism for the reaction between the electrophile and benzene to compound X.
- 1-naphthol is an important starting material for the beta-blocker propranolol which is used in the prevention of heart attacks. The synthesis of 1-naphthol from benzene is shown below:
(a) Draw the structure of molecule P.
(b) Reactions 1 and 3 are both Friedel-Crafts acylations. Explain the role of AlCl3 in a Friedel-Crafts acylation.
(c) Draw the full mechanism for the Friedel-Crafts acylation in which molecule S is converted to molecule T (reaction 3). What is the name of this mechanism?
(d) What type of reaction is reaction 4?
Answers
- (a) FeBr3 + (CH3)2CHBr ⇾ (CH3)2CH+ + FeBr4–
(b)
- (a)
(b) AlCl3 is a catalyst. It accepts electrons from a chlorine atom forming a coordination complex which breaks down to from a strong electrophile. The electrophile is attacked by the electrons from the benzene ring.
(c) The mechanism is electrophilic substitution.
(d) Conversion of a ketone to an OH group is a reduction reaction.