Name: Sai Sandeep Bhagwandas Lachmandas

Matric No: A0118840H

Friedel-Crafts Alkylation and Acylation

Introduction
The Friedel-Crafts reactions were developed by Charles Friedel and James Crafts in 1877 to add
substituents to an aromatic ring. The benzene ring is highly stable and it is not easy to add in
substituents to it compared to alkanes and alkenes. This stability arises from the delocalisation of
electrons across the six pi electrons, which is possible due to the overlap of six p orbitals. These
reactions are one of the most important ones in organic chemistry and can be broadly categorised
under two categories: alkylation reactions and acylation reactions.
History and Development
The discovery of the Friedel-Crafts reaction was made when the discoverers were studying the
effect of aluminium on different organic chlorides. They noticed that a small amount of iodine
allowed the reaction to start and hydrogen chloride along with hydrocarbons with high boiling
points were being formed. However, what was a more interesting observation was if a large
amount of aluminium chloride were formed in the reaction, the reaction would be more active
(Ashdown 1063). This accidental discovery led to the conclusion that aluminium chloride and
not aluminium was the activating agent for the reaction.
In order to verify this hypothesis, the scientists performed the same reaction using amyl chloride
and aluminium chloride instead of aluminium. As expected, the reaction occurred without any
heat added and was vigorous. The products formed where hydrogen chloride gas, a dense brown
liquid and some gaseous hydrocarbons not absorbed by bromine. Some of the hydrocarbon
products had boiling points above of mercury. Almost all of the chlorine atoms from the amyl
chloride were present in the hydrochloric gas recovered. The scientists concluded that it was
likely that the hydrogen chloride was formed by two molecules giving hydrogen and chlorine
atoms respectively and then the two molecules combine together.
The scientists were optimistic that aluminium chloride could be used to produce an infinite
number of hydrocarbons (Ashdown 1064). They reacted amyl chloride with excess benzene
with small amounts of aluminium chloride added and performed what is now called FriedelCrafts alkylation. Just as the previous reaction, hydrogen chloride gas was formed and a brown
layer was formed again. The products also had hydrocarbons, which boiled, at a relatively low
temperature and a liquid, which boiled at about 185o and had the properties of amyl benzene. The
scientists proposed that the reaction could be described by the following equation: C6H6 +
C5H11Cl = C6H5.C5H11 + HCl. They repeated this experiment with organic bromides and noted
that other products such as xylene (dimethylbenzene), mesitylene (1,3,5-trimethylbenzene) and
tetramethylbenzene were formed besides toluene (methylbenzene).
After publishing the above experiments in their first paper to LAcademic des Sciences on June
11, 1877, the scientists presented another one after one week. While the first paper comprised of

Name: Sai Sandeep Bhagwandas Lachmandas

Matric No: A0118840H

the discovery of Friedel-Crafts alkylation, the second one described a variety of reactions such as
producing diphenylmethane from benzyl chloride and benzene, acetophenone from acetyl
chloride and benzene and etc. Friedel-Crafts acylation is the reaction mentioned in the second
paper that produces acetophenone from acetyl chloride and benzene. In the third paper, the
scientists presented that other metallic chlorides such as zinc chloride or ferrous chlorides could
be used to catalyse such reactions as well. The third paper proposed a mechanism for the
reactions that involved aluminium C6H5.Al2Cl5 but the scientists had no evidence to support this.
The real mechanisms are outlined below.
Mechanistic Study
The reaction for both Friedel-Crafts Alkylation and Friedel-Crafts Acylation is electrophilic
aromatic substation.
Friedel-Crafts Alkylation
Step 1
Aluminium chloride, which is a Lewis acid catalyst, reacts
with 2-chloro-2-methylpropane to form [AlCl4]-. A
carbocation is formed as a result of this. The carbocation may
undergo rearrangement so that it becomes more stable and so
the substituent on the benzene ring may not be the same.
Step 2
This is the rate-determining step as it involves the temporary
disruption of the aromatic system. The carbocation is the
electrophile in this reaction and is attacked by the electrons.
This causes the hybridisation of the carbon in the benzene ring
that forms a bond with the carbocation to change from sp2 to
sp3. This delocalized cation is less stable than the reactant or
the product but it is not too unstable since the positive charge
can delocalise across the six-membered ring.
Step 3
In the last step, the hydrogen atom is removed, allowing the
carbon atom that is attached to the substituent to regain its sp2
hybridisation. The benzene ring has now got back its
aromaticity. The catalyst (AlCl3) is regenerated and hydrogen
chloride gas is evolved. The problem with alkylation is that
the product formed is more susceptible to electrophilic attack
than benzene and so this means that usually a mixture of
compounds is obtained. Friedel-Crafts acylation is a better
reaction because this problem does not arise.
2

Name: Sai Sandeep Bhagwandas Lachmandas

Matric No: A0118840H

Friedel-Crafts Acylation

St
ep 1
Aluminium chloride reacts with acyl chloride to form the acyllium ion and [AlCl4]-. An acid
anhydride can also be used instead of an acyl chloride to form the acyllium ion. More Lewis acid
catalyst is added in acylation compared to alkylation. The Lewis acid can complex to any oxygen
present and adding more of the catalyst can prevent this. Unlike, the carbocation formed in
alkylation, the acyllium ion is resonance stabilised and does not undergo rearrangement,
allowing for only one product to be formed.
Step 2

This is the rate-determining step as it involves the temporary disruption of the aromatic system
of the benzene ring. The acyllium ion is the electrophile in this reaction and is attacked by the
electrons to form one complex. This causes the hybridisation of the carbon in the benzene ring
that froms a bond with the carbocation to change from sp2 to sp3.

Step 3
In the third step, the hydrogen atom is removed, allowing the carbon atom that is attached to the
substituent to regain its sp2 hybridisation. The benzene ring has now got back its aromaticity. The
catalyst (AlCl3) is regenerated and hydrogen chloride gas is evolved. The ketone substituent
causes the benzene ring to be deactivated since it withdraws electrons from thesystems,
inhibiting further substitution to occur on the same ring.

Name: Sai Sandeep Bhagwandas Lachmandas

Matric No: A0118840H

Step 4
Water is added to liberate the benzaldehyde in the final step.
Application
The products of both Friedel-Crafts reactions have many industrial uses. This is why these
reactions are one of the most important ones in the field of organic chemistry. Acylation is
carried out usually to form alkyl benzenes instead of alkylation in order to obtain a specific alkyl
benzene. After acylation of the benzene ring, the carbonyl group is reduced to the methylene
group. The alkyl benzenes from alkylation have many industrial applications. The linear
alkylbenzenes (LABs) are a family of organic compounds that are intermediates in the
production of detergents. Alkylbenzenes are also used as lubricants, as components in
pharmaceuticals and pesticides. They are used as liquid scintillators in neutrino detectors.
Recent developments
In the last 15 years, there have been significant advances in the development of more efficient
and environmentally friendly alkylations of arenes and heteroarenes as part of the green
revolution taking place in all fields of synthetic chemistry (Giovanni & Raimondo 4). For
example, the traditional method of producing 1,1-diarylalkanes required using toxic benzyl
halides. Uemura et al. discovered accidentally that benzyl alcohols could be used in FC
alkylations in 1986. A new catalyst would be required for this new electrophile. Fukuzawa and
Shimizu used Sc(OTf)3 and 10%mol Mo(CO)6 (Rueping & Nachtsheim 4) respectively as
catalysts for this. Many other more efficient catalysts have been developed as well such as
bismuth salts. However, using benzyl alcohol creates a lot of water and wastewater treatment is
costly. Scientists have decided to work on hydroarylations and hydroalkylation reactions as a
solution to this problem. Styrenes are one of the best potential substrates for this and Shimizu
and co-workers discovered a Lewis-acid-catalysed substitution of arenes with olefins. There have
also been developments in enantio- and diastereoselective FC alkylations (Rueping &
Nachtsheim 2). The drawback of the initial methods is the requirement of stoichiometric amounts
of HBF4 and low temperatures. Bach et al. improved this by using AuCl3 to catalyse this reaction.
Nishibayashi and co-workers achieved a milestone when they developed the first catalytic
enantioselective alkylation using propargyl alcohols as electrophiles.

Name: Sai Sandeep Bhagwandas Lachmandas

Matric No: A0118840H

Recent developments involving acylation reactions focus on finding a better catalyst so that the
chemical reaction is more green and efficient. The problem with acylation reactions is that
more than stoichiometric amounts of catalyst are required since the metal halide and ketone
products form a strong complex and the work-up reaction drains the catalyst away and produces
a corrosive waste stream (Giovanni & Raimondo 3). The development of ionic liquids as
solvent catalysts is a recent improvement since the liquids can be reused because there is no
reason to dispose them. However, most of the research on enhancing this reaction has been
devoted to developing heterogeneous catalysts since they can be easily separated from the
reaction mixture. Zeolites (acid treated), heteropoly acids and metal oxides have been used in the
reactions.
Prospects
In alkylation, there are still a lot of breakthroughs that need to be made. Friedel-Crafts alkylation
of arenes with free amines or nitrogen-containing heterocycles would represent a significant
discovery in this area. This will allow an increase in the functional group tolerance (Rueping &
Nachtsheim 22) and ease the production of pharmaceutical compounds. For acylation, scientists
are studying the use of clays, perfluorinated resinsulfonic acids and supported (fluoro) sulfonic
acids in order to enhance acylation for the production of fine chemicals (Giovanni &
Raimondo 5).
References
1. Chen, M.C. The SNO Liquid Scintillator Project Nuclear Physics B. Vol. 145 (2005):
65-8. Print.
2. Litherland, Neal. Alkyl Benzene Uses eHow. n.p, n.d. Web. 3 April 2014.
3. Elaine, Burridge. ICIS Chemical Business. ICIS, 23 February 2004. Web. 3 April 2014
4. UCDAVIS ChemWiki, University of California. Web. 3 April 2014
5. Carey. Chapter 12: Reactions of Arenes. Electrophilic Aromatic Substitution. McGraw
Hill. Web. 3 April 2014.
6. Clayden, Greeves, Warren and Wothers. Organic Chemistry. New York: Oxford
University Press, 2001. Print.
7. Ashdown, Avery A. Earliest History of the Friedel-Crafts Reaction. Industrial and
Engineering Chemistry. 19.9 (1927): 1063-65. Print.

Name: Sai Sandeep Bhagwandas Lachmandas

Matric No: A0118840H

8. Sartori, Giovanni & Maggi, Raimondo. Advances in Friedel-Crafts Acylation Reactions:

Catalytic and Green Processes. United States: CRC Press, 2010. Print.
9. Nachtsheim & Rueping. A review of new developments in the Friedel-Crafts alkylation
From green chemistry to asymmetric catalysis. Beilstein Journal of Organic
Chemistry. 6.6 (2010): 1 24. Print.