Graphite as an effective catalyst for Friedel-Crafts acylation

Article abstract of DOI:10.1039/a703947f

Graphite is found to promote Friedel-Crafts acylation of aromatic compounds such as anisole, toluene and o-xylene with acyl halides to give the corresponding acylated products in high yields.

Full text of DOI:10.1039/a703947f

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Graphite as an effective catalyst for Friedel–Crafts acylation
Mitsuo Kodomari,* Yoshitada Suzuki and Kouji Yoshida
Department of Industrial Chemistry, Faculty of Engineering, Shibaura Institute of Technology, Shibaura, Minato-ku, Tokyo 108,
Japan
Graphite is found to promote Friedel–Crafts acylation of
aromatic compounds such as anisole, toluene and o-xylene
with acyl halides to give the corresponding acylated
products in high yields.
However, it has limitations with regard to generality and
efficiency. Recently, it has also shown that alumina promotes
the acylation of reactive aromatics such as anisole and
Table 3 Graphite catalysed Friedel–Crafts acylationa
Friedel–Crafts acylation of aromatic compounds is one of the
most important syntheses of aryl ketones. In contrast to Friedel–
Crafts alkylation, which proceeds readily in the presence of
catalytic amounts of Lewis acid, acylation requires more than
one equivalent, e.g. of AlCl3. This is due to the complexation of
AlCl3 by the ketone product. The catalyst used cannot easily be
recovered and recycled; therefore, a large amount of toxic waste
is generated. In order to solve this problem, some catalytic
Friedel–Crafts acylations have recently been developed.
Ln(OTf)3–LiClO4,1 TiCl(OTf)3–TfOH 2 and ReBr(CO)53 have
been reported as catalysts for Friedel–Crafts acylation. In
addition, the use of inorganic solid supported reagents4 or solid
acids5 as catalysts, resulting in higher selectivity, easier work-
up and environmentally safe reactions, has been reported. For
instance, HZSM-5 zeolite has been reported to promote the
liquid-phase acylation of anisole with carboxylic acid.5b
graphite
?
ArH + PhCOBr —————— PhCO-Ar
benzene, reflux
Run ArH
t/h
Product
Yield (%)b
OMe
OMe
PhCO
OMe
OMe
1
8
89
2c
16
8
70
92
60
PhCO
OMe
OMe
OMe
PhCO
OMe
3
PhCO
MeO
Table 1 Acylation of anisole using the various inorganic solidsa
MeO
4
OMe
OMe
8
OMe
OMe
inorganic solid
OMe
PhCO
OMe
+
PhCOBr
benzene, reflux
5
8
93
Inorganic solid
Yield (%)b
PhCO
None
Graphite
Active charcoal
Molecular sieves (5 Å)
Al2O3 (neutral)
Silica gel
0
89
trace
41
9
6d
86
Me
Me
24
24
3
(o :p = 1:4)
PhCO
Me
Me
0
7e
97
84
Me
Me
PhCO
Me
Me
a A mixture of anisole (2 mmol), benzoyl bromide (3 mmol) and inorganic
solid (1 g) in benzene (5 ml) was refluxed for 8 h. b Yields were determined
by GLC.
Me
Me
Me
PhCO
8
9
Table 2 Acylation of anisole with acyl chloridesa
OMe
Me
Me
Me
PhCO
O
Me
Me
O
Graphite
+
R
OMe
ClCH2CH2Cl, reflux
R
Cl
Me
Me
Me
3
3
85
83
R
t/h
Yield (%)b
Me
Me
Me
Me
Me
Phc
Cyclohexyl
Pri
8
8
3
8
8
8
85
84
89
66
63
61
Me
PhCO
Me
10
C5H11
C
12H25
Me
Me
Me
Me
PhCH2
a ArH (2 mmol), benzoyl bromide (3 mmol), graphite (1 g) and benzene (5
a
b
Conditions: anisole (2 mmol), acyl chloride (3 mmol), graphite (1 g),
ClCH2CH2Cl (5 ml). b Yields were determined by GLC. c The reaction was
carried out at 120 °C in chlorobenzene.
ml). Yields were determined by the internal standard method via GLC.
c
d
Addition of sodium carbonate (6 mmol). Solvent: toluene (5 ml).
e Solvent: o-xylene (5 ml).
Chem. Commun., 1997
1567

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ucts in high yields. In the present reactions, benzoyl bromide
was a better acylating reagent than benzoyl chloride. For
example, anisole reacted with benzoyl bromide to afford
p-methoxybenzophenone in 89% yield, whereas a 50% yield
was obtained in the reaction with benzoyl chloride under the
same conditions; the yield was improved to 85% when the
reaction was carried out at 120 °C in chlorobenzene. These
graphite-promoted acylations proceeded even after addition of
sodium carbonate, which traps hydrogen bromide generated
during the reaction, although the rate of the reaction was slower
than that in the reaction without sodium carbonate (Table 3, run
2). Polymethylbenzenes such as mesitylene, 1,2,3,5-tetra-
methylbenzene and pentamethylbenzene gave the correspond-
ing benzoylated products in high yields. However, benzoylation
of toluene and o-xylene was very slow in refluxing benzene,
giving methylbenzophenone (a mixture of o- and p-isomers)
and 3,4-dimethylbenzophenone in low yield, respectively; the
yields were improved when the reaction was performed using
toluene and o-xylene as both substrate and solvent. Benzene
was hardly benzoylated under similar conditions. The reaction
of benzene with benzoyl bromide was heated to reflux for 24 h
to give benzophenone in 20% yield.
thiophene with carboxylic acid in the presence of trifluoroacetic
anhydride.6 During the course of our studies aimed at
developing supported reagents as catalysts for Friedel–Crafts
reaction,7 we found that graphite, without any treatment,
promotes the Friedel–Crafts acylation of aromatic compounds
with acyl halides to afford the corresponding acylated products
in high yields.
Graphite was shown to have a remarkably high activity for
the acylation of active aromatic compounds such as anisoles and
polymethylbenzenes with acyl halide to give the corresponding
acylated compounds in high yields, without any of the
environmental disadvantages of using toxic homogeneous
reagents such as AlCl3. In a typical experiment, graphite† was
added to a mixture of anisole (2 mmol) and benzoyl bromide (3
mmol) in benzene. The mixture was heated under reflux for 8 h.
Graphite was removed by filtration, and the filtrate was washed
with aqueous sodium hydrogen carbonate, to remove the excess
benzoyl bromide, and concentrated under reduced pressure. The
crude product was chromatographed on silica gel to afford
p-methoxybenzophenone (80%). The products obtained were
analysed by GLC, IR and NMR spectroscopy. The amount of
graphite used relative to benzoyl bromide was between 0.5 and
2 g. The optimum yield of p-methoxybenzophenone was
obtained with 1 g of graphite, whereas 2 g gave a slightly lower
yield. When a large amount of graphite was used, the yields
were decreased due to absorption of an appreciable amount of
the product and starting material on the graphite. Empirical
testing of five inorganic solids revealed that graphite was most
effective in promoting the reaction. MS-5A, though less
effective than graphite, was also effective, whereas active
charcoal, silica gel and alumina were entirely ineffective (see
Table 1). Alkanoyl and cycloalkanecarbonyl chlorides could be
used as acylating reagents in the reactions, and the correspond-
ing acylated products were obtained in good yield (Table 2).
The reaction of anisole with isobutyl chloride and with
cyclohexanecarbonyl chloride gave isopropyl 4-methoxyphenyl
ketone and cyclohexyl 4-methoxyphenyl ketone, respectively,
in high yields. However, the acylation of anisole with acetyl
chloride gave p-methylacetophenone in low yield. This is
probably due to evaporation (low boiling point of acetyl
chloride). Benzoylation of several anisoles and polyme-
thylbenzenes with benzoyl bromide in the presence of graphite
was carried out and the results are summarised in Table 3.
Anisole, veratrole and a-methoxynaphthalene reacted with
benzoyl bromide to give the corresponding benzoylated prod-
Further understanding of the catalysis by graphite and the
application of graphite to other synthetic reactions are now
under investigation.
Footnotes and References
* E-mail: kodomari@sic.shibaura-it.ar.jp
† Graphite powder was from Aldrich (Catalogue no. 28, 286-3) and was
employed without further purification.
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Received in in Cambridge, UK, 6th June 1997; 7/03947F
1568
Chem. Commun., 1997