Electrochemically promoted Friedel-Crafts acylation of aromatic compounds

Article abstract of DOI:10.1016/j.tetlet.2008.02.084

Friedel-Crafts acylation is carried out with several aromatic substrates in the presence of an electrochemically active aluminium anode to minimize the inorganic reagents. Only a catalytic amount of AlCl₃ (5 mol %) is required to enable the anodic polarization of the aluminium electrode to promote continuous acylation. This process typically gave products in good yields (70-96%).

Full text of DOI:10.1016/j.tetlet.2008.02.084

Available online at www.sciencedirect.com
Tetrahedron Letters 49 (2008) 2625–2627
Electrochemically promoted Friedel–Crafts
acylation of aromatic compounds
G. Karthik a, K. Kulangiappar a, Frank Marken b, M. Anbu Kulandainathan a,*
a Electro-organic Division, Central Electrochemical Research Institute, Karaikudi, India
b Department of Chemistry, University of Bath, Claverton Down, Bath BA2 7AY, UK
Received 3 January 2008; revised 11 February 2008; accepted 15 February 2008
Available online 19 February 2008
Abstract
Friedel–Crafts acylation is carried out with several aromatic substrates in the presence of an electrochemically active aluminium
anode to minimize the inorganic reagents. Only a catalytic amount of AlCl3 (5 mol %) is required to enable the anodic polarization
of the aluminium electrode to promote continuous acylation. This process typically gave products in good yields (70–96%).
Ó 2008 Elsevier Ltd. All rights reserved.
Keywords: Electrosynthesis; Electrochemical acylation; Sacrificial anode; Aluminium; Aromatic compound; Constant current electrolysis
Friedel–Crafts acylation has been used for the acylation
of aromatics since the turn of the last century.1 Friedel–
Crafts acylation of aromatic compounds is a common
process resulting in C–C coupling and is one of the most
fundamental and important reactions in synthetic, indus-
trial and pharmaceutical applications.2,3
meet during the conventional acylation of aromatics: prep-
aration, storage and handling of anhydrous Lewis acids
such as AlCl3. A possible way to overcome these challenges
is in situ generation of the Lewis acid catalyst using a sac-
rificial aluminium anode. Using this novel electrochemi-
cally promoted method, only a relatively small amount of
AlCl3 (5 mol %) is sufficient to catalyze various acylation
reactions at room temperature. In general, aluminium
electrodes are commonly used as anodes to avoid the
oxidation of organic compounds during reactions and here
it is used as a mild source of Lewis acid to promote the
Friedel–Crafts acylation.
In recent years, electroorganic synthesis has become
increasingly attractive as an environmentally friendly pro-
cess. Through the anodic dissolution of aluminium,10
zinc,11 magnesium,12 etc., in situ generation of catalysts
has been observed, which can be used in organic reactions.
The anodic dissolution of aluminium in an appropriate
medium is a versatile method for the electrochemical intro-
duction of active Al(III) species as a catalyst and using this
technique, the acylation of alkenes13 and ferrocene14 as
well as alkylation15 and electrocarboxylation has been
reported.16 Gambino et al. have demonstrated the acyla-
tion of aromatics in the presence of an aluminium anode
with AlCl3 as the electrolyte.17
Friedel–Crafts acylation reactions represent one of the
greatest challenges to ‘green chemistry’. Traditional meth-
ods generally employ more than stoichiometric amounts
of hazardous water soluble Lewis acids such as AlCl3 or
BF3, which are destroyed during the workup leading to
large volumes of waste.4 The loss of inorganic reagents as
waste products is undesirable and thus alternative reaction
conditions are sought to minimize or eliminate the waste
problem. In recent years, the search for suitable catalytic
conditions to replace the need for excess inorganic reagents
has resulted in numerous investigations focusing particu-
larly on the use of novel Lewis acid such as FeCl3,5 ZnCl2,6
7
BiCl3 and other metallic chlorides,6 the application of tri-
flates in ionic liquids8 and heterogeneous processes employ-
ing zeolites.9 There are three main difficulties that chemists
*
Corresponding author. Tel.: +91 4565 227772; fax: +91 4565 227779.
E-mail address: manbu123@yahoo.com (M. Anbu Kulandainathan).
0040-4039/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2008.02.084

2626
G. Karthik et al. / Tetrahedron Letters 49 (2008) 2625–2627
Table 1
COR
Electrochemical Friedel–Crafts acylation of various aromatic compounds
Al anode, RCOCl, DCM
r.t , 3-6 mA/cm2
Yielda
(%)
R
Entry Reactant
Product
Charge
passed
(F/mol)
R
Scheme 1. Electrochemical acylation of benzene.
H
COCH3
1
2
1
70
CH3
In this Letter, we describe the electrochemically pro-
moted acylation of a number of aromatic compounds using
an Al anode and tetrabutylammonium bromide (Bu4NBr)
as electrolyte along with a catalytic amount (5 mol %) of
AlCl3 (Scheme 1).
All experiments were carried out galvanostatically (con-
stant current electrolysis) in a simple undivided cell under a
nitrogen atmosphere. An aluminium anode and stainless
steel cathode were used in all the reactions and the current
density was maintained at 3–6 mA/cm2.
The Friedel–Crafts acylation was carried out by electro-
lyzing a solution of tetrabutylammonium bromide in
DCM, containing 5 mol % of AlCl3, 1.2 equiv of acetyl
chloride and alkylarenes at room temperature. After pass-
ing 1 F/mol charge, the corresponding acylated product
was obtained in 70–96% yield (Table 1).18 In the case of tol-
uene, anisole and ethylbenzene, 0.7–0.8 F/mol of charge
was sufficient to obtain the best yields. On passing addi-
tional charge, side product formation was observed. It is
believed that the catalytic amount of AlCl3 induces anodic
polarization and corrosion of the aluminium electrode,
which leads to more facile formation of the ionic alumin-
ium species at the anode resulting in better yields of acyl-
ated products.
CH3
0.7
1.0
95
93
COCH3
OMe
OMe
COCH3
3
4
0.7
1.0
75
70
CH3
CH3
0.8
1.0
81
78
COCH3
CH3
CH3
H3C
H3C
5
6
1
1
75
95
COCH3
CH3
CH3
COCH3
CH3
CH3
Under these electrochemical conditions, the Friedel–
Crafts acylation consists of two steps involving an electro-
chemical reaction followed by a chemical reaction. The
anodic production of Al(III) is an electrochemical process.
The aluminium(III) species is chemically reactive towards
halogenated molecules, and its reaction with acetyl halide
affords the product.
In an appropriate supporting electrolyte medium (tetra-
butylammonium bromide) and in the presence of AlCl3, the
aluminium metal surface is activated and anodically more
polarized (vide infra),17 hence the dissolution of aluminium
is more facile.
CH3
CH3
CH3
CH3
COCH3
7
8
1
1
1
74
90
CH3
CH3
COCH3
H3C
CH3 H3C
CH3
CH3
CH3
COCH3
9
96
Activated aromatics such as toluene, anisole and para-t-
butyltoluene gave high acylation yields (Table 1, entries 2,
3 and 9) and the ring deactivated molecule chlorobenzene
gave a very low yield (Table 1, entry 10). Highly deacti-
vated nitrobenzene did not give any product (Table 1, entry
11). When the reaction was carried out in the presence of
AlCl3 without passing any current, the yield of acylated
product obtained from toluene was only 11%. The above-
mentioned reaction was carried out electrochemically with-
out adding AlCl3 and the yield of the product was 28%.
Therefore, the electrochemical step is essential in promot-
ing the acylation reaction leading to the desired products
in high yield with minimum of waste products. A simplified
Cl
Cl
COCH3
10
1
1
5
NO2
11
—
No
product
was
formed
a
Isolated yield.

G. Karthik et al. / Tetrahedron Letters 49 (2008) 2625–2627
2627
mechanism can be proposed for this electrochemical pro-
cess (Eqs. 1–3):
References and notes
1. (a) Olah, G. A. Friedel–Crafts Chemistry; Wiley: New York, 1973; (b)
Friedel–Crafts and Related Reactions; Gore, P. H., Olah, G. A., Eds.;
Wiley-Interscience: New York, 1964; Vol. III.
2. Franck, G.; Stadelhofer, J. W. Industrial Aromatic Chemistry;
Springer: Berlin, 1988.
Al ! Al3þ þ 3eꢀ
ð1Þ
ð2Þ
4RCOCl þ Al3þ ! AlCl4ꢀ þ 4RCOþ
RCOþ þ Ar–H ! ArCOR þ Hþ
ð3Þ
3. Sheldon, R. A. Chem. Ind. 1992, 7, 903; Harvey, G.; Mader, G.
Collect. Czech. Chem. Commun. 1992, 57, 862.
4. Furniss, B. S.; Hannaford, A. J.; Smith, P. W. G.; Tatchell, A. R.
Vogels Text Book of Practical Organic Chemistry, 5th ed.; Longman:
Singapore, 1989; Kirk-Othmer, Encyclopedia of Chemical Technology,
5th ed.; 1997; Vol. 24, p 38.
5. Go¨ndo¨s, Gy.; Kapocsi, I. J. Phys. Chem. Solids 1996, 57, 855.
6. Pivsa-Art, S.; Okuro, K.; Miura, M.; Murata, S.; Nomura, M. J.
Chem. Soc., Perkin Trans. 1 1994, 1703.
7. Repichet, S.; Roux, C. L.; Roquesb, N.; Dubac, J. Tetrahedron Lett.
2003, 44, 2037.
8. Ross, J.; Xiao, J. Green Chem. 2002, 4, 129.
One equivalent of electrochemically generated alumin-
ium ions can combine with 4 equiv of acyl halide to pro-
duce reactive acylium ions and AlCl4ꢀ, which catalyzes
the reaction and hence a minimum amount of current is
required. The theoretical loss of aluminium, from the
anode is 0.050 g/F charge transferred but the observed
weight loss was 0.120 g and therefore the mechanism is
probably even more complex than proposed.
9. Kantam, M. L.; Ranganath, K. V.; Sateesh, M.; Balaji, K. S.;
Choudary, B. M. J. Mol. Catal. A: Chem. 2005, 225, 15.
10. Canizares, P.; Carmona, M.; Lobato, J.; Martinez, F.; Rodrigo, M.
A. Ind. Eng. Chem. Res. 2005, 44, 4178.
11. Louati, A.; Vataj, R.; Gabelica, V.; Lejeunec, M.; Mattc, D.
Tetrahedron Lett. 2005, 46, 7499.
Nitrogen gas was passed into the reaction mixture
throughout the experiment to remove HCl, which is
evolved during the course of the reaction. If HCl is not
promptly removed, it reacts with the product and leads
to the formation of side products such as diphenylethane
(Eqs. 4 and 5):
12. Yee, R.; Mallory, J.; Parrish, J. D.; Carroll, G. L.; Little, R. D. J.
Electroanal. Chem. 2006, 593, 69.
13. Vukicevic, R. D.; Joksovic, L.; Konstantinovic, S.; Markovic, Z.;
Mihailovic, M. L. Bull. Chem. Soc. Jpn. 1998, 71, 899.
14. Vukicevic, R. D.; Ratkovic, Z. R.; Vukicevic, M. D.; Konstantinovic,
S. K. Tetrahedron Lett. 1998, 39, 5837.
15. Silvestri, G.; Gambino, S.; Filardo, G. Electrochim. Acta 1987, 32,
965.
C6H5COCH3 þ 2eꢀ þ 2Hþ ! C6H5CHðOHÞCH3
ð4Þ
C6H6 þ C6H5CHðOHÞCH3 ! ðC6H5Þ2CHCH3 þ H2O ð5Þ
The water formed during the side alkylation process will
further deactivate an equivalent amount of catalyst leading
to a reduced yield of the Friedel–Crafts acylated product.
In summary, the electrochemically promoted Friedel–
Crafts acylation of aromatic compounds by in situ genera-
tion of Al3+ from an aluminium anode in the presence of
tetrabutylammonium bromide as electrolyte gives acylated
products in good yields (70–95%). This reaction is carried
out at room temperature with a catalytic amount of AlCl3
instead of a stoichiometric amount applying a minimum
amount of current. There are considerable advantages in
this electrochemically promoted reaction compared to con-
ventional Friedel–Crafts conditions.
16. Ahmed Isse, A.; Scialdone, O.; Galia, A.; Gennaro, A. J. Electroanal.
Chem. 2005, 585, 220.
17. Gambino, S.; Filardo, G.; Silvestri, G. J. Mol. Catal. 1989, 56, 296.
18. Representative procedure for electrochemical acylation:
Tetrabutylammonium bromide was crystallized from ethyl acetate
and was dried under vacuum. The aluminium electrode was prepared
by means of the following standard procedure: Polished with emery
paper, degreased with acetone, etched with an aqueous solution of
HCl (5%) + HF (2%), rinsed with distilled water and methanol and
finally dried with warm air. This activation treatment was performed
immediately before use. Stainless steel was used as the cathode. A
solution of toluene (10 mmol) in 20 ml of dichloromethane was added
to an undivided cell containing 1 g of electrolyte (tetrabutylammo-
nium bromide), acetyl chloride (12 mmol) and 0.065 g of AlCl3
(5 mol %). An aluminium anode (12.5 cm2) and stainless steel cathode
(10 cm2) were placed in the solution and 50 mA of current was passed
for 3 h at room temperature (30–35 °C). Nitrogen gas was purged
throughout the reaction to remove HCl vapour.
Acknowledgements
After completion of the reaction, the reaction mixture was poured
into 50 ml of cold water and 5 ml of concd HCl was added with
constant stirring. The product was extracted with diethyl ether
(3 ꢁ 25 ml) and the ethereal layer was washed with water and dried
over anhydrous sodium sulfate. The organic solvent was removed
under reduced pressure and the product was identified by HPLC, IR
and NMR spectroscopy.
The authors thank Professor A. K. Shukla, Director,
CECRI, for his support and encouragement and also thank
Dr. M. Noel and Mr. A. Muthukumaran for useful
discussions. We thank Mr. S. Radhakrishnan for NMR
assistance.