Friedel-crafts acylation catalysed by heteropoly acids

Article abstract of DOI:10.1006/jcat.2002.3592

The acylation of anisole (AN) and toluene with acetic anhydride (AA) in liquid phase catalyzed by bulk and silica-supported Keggin heteropoly acids, e.g., H₃PW₁₂O₄₀ (PW), H₄SiW₁₂O₄₀ (SiW),

Full text of DOI:10.1006/jcat.2002.3592

Journal of Catalysis 208, 448–455 (2002)
doi:10.1006/jcat.2002.3592
Friedel–Crafts Acylation Catalysed by Heteropoly Acids
∗
∗,1
J. Kaur, K. Griffin,† B. Harrison,† and I. V. Kozhevnikov
∗
The Leverhulme Centre for Innovative Catalysis, Department of Chemistry, University of Liverpool, Liverpool, L69 7ZD,
United Kingdom; and †Johnson Matthey, Orchard Road, Royston, Hertfordshire SG8 5HE, United Kingdom
Received December 18, 2001; revised February 11, 2002; accepted February 25, 2002
eral acids (e.g., HF) as catalysts, which results in a sub-
stantial amount of waste and corrosion problems (2). The
overuse of catalyst is caused by product inhibition—the for-
mation of strong complexes between the aromatic ketone
and the catalyst. In view of the increasingly strict environ-
mental legislation, the application of heterogeneous catal-
ysis has become attractive. In the last couple of decades,
considerable effort has been put into developing heteroge-
neously catalysed Friedel–Crafts chemistry using solid acid
catalysts such as zeolites, clays, Nafion-H, and so forth (2),
with zeolites being the most-studied catalysts (2–8 and ref-
erences therein). The acylation of anisole with acetic anhy-
dride using a zeolite catalyst has been commercialised by
Rhodia (2).
Although relatively active catalysts, the zeolites (e.g., H-
beta) are deactivated in the acylation (6–8). The main deac-
tivation is deemed to be reversible; this is attributed to the
strong adsorption of the acylation product on the catalyst,
blocking access to the active sites. Another type of deac-
tivation, which is irreversible, is caused by tar deposition
on the catalyst surface (coking). The carbonaceous deposit
could be removable by aerobic treatment at high temper-
atures (500–550◦C). Deactivation may also be caused by
dealumination of zeolite with by-product acid (e.g., acetic
acid).
The Friedel–Crafts acylation of anisole (AN) with acetic anhy-
dride (AA) in liquid phase catalysed by bulk and silica-supported
heteropoly acids (HPA), mainly H3PW12O40 (PW), has been stud-
ied. The PW exhibit very high activity, yielding up to 98% para and
2–4% ortho isomer of methoxyacetophenone (MOAP) at 90–110◦C
and an AN/AA molar ratio of 10–20. Catalyst pretreatment is essen-
tial; the activity passes a maximum at a pretreatment temperature
of 150◦C. The acylation of anisole appears to be heterogeneously
catalysed; no contribution of homogeneous catalysis by HPA was
observed. PW is almost a factor of 100 more active than the ze-
olite H-beta, which is in agreement with the higher acid strength
of HPA. The PW catalyst is reusable, although gradual decline of
activity was observed due to the coking of the catalyst. The acy-
lation is inhibited by product because of adsorption of MOAP on
the catalyst surface. The ratio of adsorption coefficients of MOAP
and anisole has been found to be 37 at 90◦C. Anisole acylation
is first order in acetic anhydride, the order in catalyst is 0.66,
and the apparent activation energy is 41 kJ/mol in the temper-
ature range of 70–110◦C. In contrast to anisole, the acylation of
toluene with HPA is far less efficient than that with H-beta. Ev-
idence is provided that the activity of HPA in toluene acylation
is inhibited by preferential adsorption of acetic anhydride on the
c
catalyst. ꢀ 2002 Elsevier Science (USA)
Key Words: heterogeneous catalysis; Freidel–Crafts reaction;
acylation; heteropoly acid.
Heteropoly acids (HPAs) are another type of promising
solid acid catalyst for aromatic acylation. Heteropoly acids
are strong Brønsted acids composed of heteropoly anions
and protons as the countercations. The Keggin-type HPAs
typically represented by the formula Hx−8[XM12O40],
where X is the heteroatom, x is its oxidation state, and M
is the addenda atom (usually Mo6+or W6+), are the most
important for catalysis (9–12). They are stronger than many
conventional solid acids such as mixed oxides, zeolites, and
so forth. In the last three decades, HPAs have been widely
used as acid and oxidation catalysts for organic synthesis
and they are found in several industrial applications (9–
11). However, only a few studies on the use of HPAs for
Friedel–Crafts acylation have been published (9, 13).
The aim of the present work is to study the acylation
of anisole (AN) and toluene with acetic anhydride (AA)
in liquid phase catalysed by bulk and silica-supported
INTRODUCTION
The Friedel–Crafts acylation of aromatic compounds is
the most important route for the synthesis of aromatic ke-
tones that are intermediates in manufacturing fine and spe-
ciality chemicals as well as pharmaceuticals (1). The reac-
tion occurs by interaction of the aromatic compound with
a carboxylic acid derivative (e.g., acid anhydride, acyl chlo-
ride, or the acid itself) in the presence of an acid catalyst
and involves acylium ion intermediates that are generated
from the acylating agent by interaction with the acid cata-
lyst. Present industrial practice requires a stoichiometric
amount of soluble Lewis acids (e.g., AlCl3) or strong min-
1 To whom correspondence should be addressed. Fax: +44-151-794-
3589. E-mail: kozhev@liverpool.ac.uk.
448
0021-9517/02 $35.00
c
ꢀ 2002 Elsevier Science (USA)
All rights reserved.

FRIEDEL–CRAFTS ACYLATION
449
Keggin heteropoly acids such as H3PW12O40 (PW), pale orange in the colourless solution, and the colour of the
H4SiW12O40 (SiW), and H3PMo12O40 (PMo). Theacylation reaction mixture deepened to brown-red as the reaction
ofanisolewiththestrongestacidPWtoyieldpara-methoxy- progressed. To monitor the reaction, 0.1-ml samples of the
acetophenone (p-MOAP) and ortho-methoxyacetophe- reaction mixture were taken periodically, diluted to 1 ml
none (o-MOAP) (Eq. [1]) has been studied in more with 1,2-dichloroethane, and analysed by gas chromatogra-
detail.
phy (Varian 3380 chromatograph with autosampler) using
a 30 m × 0.25 mm BP1 capillary column.
Characterisation Techniques
[1]
31P MAS NMR spectra were recorded on a Bruker
Avance DSX 400 NMR spectrometer. FTIR spectra were
recorded with KBr pellets using a Nexus FTIR spectrom-
eter. Surface area and porosity of HPA catalysts were
measured by nitrogen physisorption on a Micromerit-
ics ASAP 2000 instrument. Thermogravimetric analy-
ses (TGA) were performed using a Perkin–Elmer TGA
7 instrument under nitrogen flow. Thermogravimetric
temperature-programmed oxidation (TGA/TPO) of coked
catalysts was carried out as described elsewhere (16).
Emphasis is put on the optimisation of catalyst perfor-
mance, product yield, and selectivity, on product inhibition,
on catalyst deactivation and reuse, and on reaction kinetics.
The results for HPA are compared with those for H-beta
zeolite (7, 8).
EXPERIMENTAL
RESULTS AND DISCUSSION
Chemicals
Catalyst Characterisation
H3PW12O40 and H3PMo12O40 from Aldrich, H4SiW12O40
from Fluka, and Aerosil 300 silica from Degussa were
used. Anisole, anisole-d8, and toluene were obtained from
Aldrich and distilled over calcium hydride prior to use.
Acetic anhydride and p-methoxyacetophenone (also from
Aldrich) with greater than 99% purity were used without
further purification. Other reagents and solvents were of
analytical purity.
Bulk and silica-supported HPA catalysts, mainly those
based on PW, were characterised after a standard pretreat-
ment (150◦C/0.1 Torr, 1.5 h) by 31P MAS NMR, FTIR, and
TGA, as well as by surface and porosity measurements.
PW supported (10–50 wt%) on silica and MCM-41 showed
a well-known 31P NMR spectrum (a singlet line at about
−15 ppm referenced to 85% H3PO4) characteristic of the
Kegginstructure(10, 11). Thespectrumdidnotchangeafter
use of the catalysts in anisole acylation, indicating that the
PW structure remained unchanged. FTIR of the bulk and
supported PW contained well-known Keggin bands (1081,
985, 892, and 596 cm−1 for bulk PW, with the bands at 1081
and 596 cm−1 being obscured in supported PW catalysts by
absorption of silica) (10). The BET surface area and poros-
ity of some HPA catalysts are given in Table 1. Bulk HPAs
possess very low surface areas, typically 1–10 m2/g, as well
as very low porosities (10–12). Supporting HPA on silica
or MCM-41 increases the surface area of HPA. It should
Catalysts
Supported HPA catalysts were prepared by impregnating
Aerosil 300 silica (SBET, 300 m2 g−1) or pure-silica MCM-41
(SBET, 1250 m2 g−1) with a methanol solution of HPA. The
mixture was stirred for 6 h at room temperature, followed
by drying using a rotary evaporator, as described elsewhere
(14). The acidic salt Cs2.5H0.5PW12O40 was prepared by the
literature method (15). Prior to the reaction, the catalysts
were heated at 150◦C/0.1 Torr for 1.5 h, unless stated oth-
erwise.
Aromatic Acylation
TABLE 1
The acylations were carried out in liquid phase in a 50-ml
glass reactor equipped with a condenser and a magnetic
stirrer. The reactor was charged with aromatic substrate
(100 mmol) and acetic anhydride, the substrate taken in
excess over the acylating agent. No solvent was used. De-
cane was added as a GC internal standard. The system was
purged with nitrogen to expel air and moisture and heated
to a required reaction temperature (70–110◦C). The pre-
activated catalyst was added to the reactor in an appropri-
ate amount. Initially a white powder, the catalyst turned
Surface Area and Porosity of HPA Catalysts
BET surface area Pore volume Pore diameter
(m2/g)
(cm3/g)
(A)
˚
Catalyst
H3PW12O40
7
3
111
130
184
416
0.01
0.01
0.8
0.4
0.5
59
68
138
135
126
23
H3PMo12O40
50% PW/SiO2
40% PW/SiO2
20% PW/SiO2
40% PW/MCM-41
0.47

450
KAUR ET AL.
50
40
30
20
10
0
0.06
0.05
0.04
0.03
0.02
0.01
0
be noted that the total surface area decreases with HPA
loading (cf. 20 and 50% PW on silica).
Acylation of Anisole
Catalyst pretreatment. Control of water content in het-
eropoly acid catalysts proved essential for their efficient
performance in aromatic acylation. This can be achieved
by thermal pretreatment of the catalysts, which is typically
done at 130–200◦C (11). Figure 1 shows the derivative TGA
for bulk PW hydrate. Three main peaks can be observed: (i)
a peak at a temperature below 100◦C corresponding to the
loss of physisorbed water (a variable amount depending on
the number of hydration water molecules in the sample);
(ii) a peak in the temperature range of 100–280◦C centred at
about 200◦C accounting for the loss of ca. 6H2O molecules
per Keggin unit, corresponding to the dehydration of a rel-
atively stable hexahydrate H3PW12O40 · 6H2O in which the
watersarehydrogenbondedtotheacidicprotons;and(iii)a
peak in the range of 370–600◦C centred at about 470◦C due
to the loss of 1.5 H2O molecules corresponding to the loss
of all acidic protons and the beginning of decomposition of
the Keggin structure (12).
Figure 2 shows the effect of catalyst pretreatment on the
yield of p-MOAP and on the initial rate of anisole acyla-
tion with bulk PW and 50% PW/SiO2. It can be seen that
both curves pass a maximum at an optimum pretreatment
temperature of 150◦C. This justifies our choice of this pre-
treatment temperature throughout this work. From TGA,
the amount of water remaining in the bulk PW after pretre-
atment at 150◦C is about 3–4 H2O molecules per Keggin
unit. Apparently, these waters are hydrogen bonded to the
acidic protons. The effect of water may be attributed to the
HPA acid strength and the number of proton sites as well
as to catalyst deactivation (11). The amount of acetic an-
hydride that may be consumed reacting with this water is
(a) yield
(b) rate
50
100
150
200
250
o
Temperature, C
FIG. 2. Effect of catalyst pretreatment (specified temperature/
0.1 Torr, 1.5 h) in the acylation of anisole: (a) yield of p-MOAP (50% PW/
SiO2 (0.83 wt%), AN/AA = 10 mol/mol, 50◦C, 2 h); (b) initial rate (bulk
PW (0.83 wt%), AN/AA = 10 mol/mol, 70◦C).
negligible (ca. 1% of AA). Excess water causes a decrease
in the HPA acid strength—and thus in its catalytic activity.
Dehydration of the catalyst increases the acid strength but
decreases the number of acid sites, which will reduce the
catalytic activity unless the reaction is highly demanding
for the catalyst acid strength. In addition, too strong acid
sites thus created tend to deactivate (coke) faster.
Product yield and selectivity. Table 2 illustrates the per-
formance of various bulk and supported HPAs at 70–110◦C
and anisole-to-acetic anhydride molar ratios, AN/AA, of
10–20. The para-acylation by far dominates, with only a few
percent of the ortho-acylation product being formed, which
is typical of this reaction. The selectivity towards monoacy-
lation is practically 100%; no other aromatic products were
found. The strongest acid, PW, is the most efficient catalyst,
as expected, closely followed by SiW, which is a slightly
weaker acid than PW (11). With PW, the yield of p-MOAP
is up to 98%, with only 2–4% o-MOAP being formed. In
contrast, PMo shows a very poor performance. This is prob-
ably due to reduction of this HPA by the reaction medium
(11). The acylation of anisole appears to be a truly het-
erogeneously catalysed reaction. No contribution of homo-
geneous catalysis by HPA was observed when the catalyst
(40%PW/SiO2)wasfilteredoffatthereactiontemperature.
Table 3 compares our results for PW/SiO2 with those for
H-beta zeolite (8) under similar reaction conditions. Both
systems give comparable yields; however, the HPA is much
more active. Catalyst turnover numbers (TON) were cal-
culated as the number of moles of p-MOAP obtained per
mole of protons in the catalyst. For 10% PW/SiO2, it was as-
sumed to be three active H+ per Keggin unit, and for H-beta
the number of active protons was taken to be equivalent to
the Al content (Si/Al = 12.5). For the HPA, TON is found
to be 14 times greater than that for H-beta. The turnover
frequency (TOF) for HPA, corresponding to the reaction
50
150
250
350
450
550
650
750
Temperature, oC
FIG. 1. TGA of H3PW12O40 hydrate.

FRIEDEL–CRAFTS ACYLATION
451
dried (150◦C/0.1 Torr, 1.5 h), and subjected to elemental
and TGA/TPO analyses. From the elemental analysis, the
carbon content was found to be 3.2%. The TGA/TPO of
the catalyst showed a weight loss of 2.5% at 530◦C, which
can be attributed to hard coke (16).
TABLE 2
Acylation of Anisole with Acetic Anhydride Catalysed
by Heteropoly Acidsa
Yieldc (%)
Catalyst
AN/AA
T
Entry
(amount, wt%)b
(mol/mol) (◦C) p-MOAP o-MOAP
Reaction kinetics. The time course for the HPA-
catalysed acylation of anisole was found to depend greatly
on reaction conditions, i.e., the catalyst type (bulk or sup-
ported), the temperature, and the AN/AA molar ratio
(Figs. 3 and 4). With bulk PW at higher temperatures and
higher AN/AA ratios, the acylation fits quite well first-order
kinetics (Fig. 3),
d
1
2
3
4
5
6
7
8
9
PW (0.83)
PW (0.83)
PW (0.30)
PW (0.30)
50% PW/SiO2 (0.83)
50% PW/SiO2 (0.60)
50% PW/SiO2 (0.60)
40% PW/SiO2 (0.83)
40% PW/SiO2 (0.75)
10
10
20
20
10
20
20
10
20
20
20
10
20
20
10
20
20
10
20
20
10
10
10
10
10
10
10
70
90
70
90
90
70
90
90
70
90
110
90
70
90
90
70
90
90
70
90
70
70
70
70
70
70
90
67
96
67
90
88
77
89
88
80
89
98e
82
64
92
79
71
89
78
64
85
70
61
72
0
3.8
2.0
3.5
4.0
2.7
3.3
4.0
2.8
3.3
2.1
3.7
2.3
3.4
3.3
2.5
3.0
3.5
2.3
d[P]/dt = k[AA],
[2]
10 40% PW/SiO2 (0.75)
11 40% PW/SiO2 (0.88)
12 30% PW/SiO2 (0.83)
13 30% PW/SiO2 (1.0)
14 30% PW/SiO2 (1.0)
15 20% PW/SiO2 (0.83)
16 20% PW/SiO2 (1.5)
17 20% PW/SiO2 (1.5)
18 10% PW/SiO2 (0.83)
19 10% PW/SiO2 (3.0)
20 10% PW/SiO2 (3.0)
21 SiW (0.83)
where P is p-MOAP and k is the rate constant. Otherwise,
the reaction obeys a more complex time course, with a rel-
atively fast initial stage followed by a slower stage (Fig. 4).
This complexity can be attributed to product inhibition (see
below).
In general, as found from the initial rates, the acylation
of anisole is almost first order in acetic anhydride, as exem-
plified by the results for the reaction with 40% PW/SiO2
(0.45 wt%) at [AN] ꢁ [AA], 70◦C.
3.7
d
d
d
22 40% SiW/SiO2 (0.83)
23 40% SiW/MCM-41 (0.83)
24 PMo (0.83)
25 40% PMo/SiO2 (0.83)
26 40% PMo/MCM-41 (0.83)
27 Cs2.5H0.5PW12O40 (0.83)
0
0
AN/AA, mol/mol: 10 20 50 75 100.
2
3
0
102k, min−1
:
7.2 12 12 15 12.
44
1.5
a Anisole (AN), 100 mmol (10.8 g), reacted with acetic anhydride (AA)
in the presence of a solid HPA catalyst without solvent in a stirred batch
reactor for 2 h to yield para-methoxyacetophenone (p-MOAP) and ortho-
methoxyacetophenone (o-MOAP).
The reaction order in the catalyst was found to be 0.66 (40%
PW/SiO2, AN/AA = 20, 90◦C). That the order is not equal
to 1 may be explained by catalyst deactivation caused by
product adsorption (see below). In the temperature range
of 70–110◦C, the acylation has an apparent activation en-
ergy of 41 kJ/mol (40% PW/SiO2 (0.83 wt%), AN/AA =
b The amount of catalysts per total reaction mixture.
c Yield based on acetic anhydride.
d The yield of o-MOAP ca. 2–3%.
e Yield in 10 min.
TABLE 3
Acylation of Anisole with Acetic Anhydride: HPA Versus Zeolitea
Catalyst
halftime, is almost two orders of magnitude greater that for
H-beta. This is not unexpected because PW is a stronger
acid than zeolite (11).
Reaction conditions
10% PW/SiO2 10% PW/SiO2 H-betab (8)
Catalyst reuse. The PW catalyst was found to be reu-
sable, although gradual decline of activity was observed.
Better results were obtained when, after the first run,
the catalyst was filtered off, washed with CH2Cl2, and re-
run. Apparently, the treatment with CH2Cl2 removed tars
more efficiently from the catalyst surface. Such procedure
allowed obtainment of 82% of the initial p-MOAP yield
in the second run (40% PW/SiO2 (0.83 wt%), AN/AA =
100/10 mmol, 90◦C, 2 h). Coking may cause partial deac-
tivation of the PW catalyst, which was evident from the
dark brown colour of the catalyst. After the first run, the
Catalyst amount (wt%)
AN/AA (mol/mol)
Yield of p-MOAP c (%)
TONd
0.83
10
0.83
6
1.33
6
78
780
78
50
830
75
61
1.2
TOFe (min−1
)
a 90◦C, 2 h.
b Si/Al = 12.5.
c Yield based on acetic anhydride.
d Turnover number: moles of product obtained per mole of protons in
the catalyst.
e Turnover frequency corresponding to reaction halftime, i.e., half of
40% PW/SiO2 catalyst was separated, washed with CH2Cl2, the total conversion of AA.

452
KAUR ET AL.
100
80
60
40
20
0
can obtain the rate and KIE equations [17]:
a
d[P]
dt
k1k2[AN][E+]
=
=
,
k
−1 + k2
ꢀ
ꢀ
ꢁ
k
k
−1 + k2D k2H
ꢁ
kH/kD
.
−1 + k2H k2D
p-MOAP
o-MOAP
In many typical aromatic electrophilic substitutions (e.g.,
nitration), kH/kD = 1, indicating that k2 ꢁ k−1. The mod-
erate KIE value of 1.6 found here indicates that the rate of
the HPA-catalysed acylation is determined by both k1 and
k2, i.e., k2 ∼ k−1(17).
0
20
40
60
80
100
120
Time, min
100
0
-1
-2
-3
-4
-5
a
80
b
p-MOAP
o-MOAP
60
40
20
0
0
10
20
30
40
50
60
70
Time, min
100
b
FIG. 3. Product yield versus time (a) and first-order kinetic plot (b)
for the acylation of anisole (Table 2, Entry 2, bulk PW (0.83 wt%),
AN/AA = 10 mol/mol, 90◦C; P is the yield of p-MOAP, P◦ is the yield
at an infinite time; k = 0.078 min−1).
80
60
40
20
20). This value is close to that reported for the reaction with
H-beta (46 kJ/mol) (7).
From concurrent acylation of a 50/50 mol% mixture
of deuterated (d8) and nondeuterated anisole (90◦C, AN/
AA = 10 mol/mol, 0.91 wt% of 40% PW/SiO2, 1 h), mea-
suring the product ratio MOAP-d0/MOAP-d8 by GS-MS,
0
100
c
the kinetic isotope effect (KIE) was found to be kH/kD
=
80
1.6 0.1. No isotope scrambling was observed under such
conditions. The acylation can be represented by the general
two-stage mechanism of aromatic electrophilic substitution
(17):
60
40
20
0
0
20
40
60
80
100
120
Time, min
FIG. 4. Yield-time plots for the acylation of anisole with 40% PW/
SiO2 (0.83 wt%): (a) 90◦C, AN/AA = 10 mol/mol; (b) 70◦C, AN/AA =
10 mol/mol; (c) 70◦C, AN/AA = 5 mol/mol. Yields are based on acetic
Here E+ is the acylium ion, and k1, k−1, and k2 are the rate
constants. Applying the steady-state approximation, one anhydride.

FRIEDEL–CRAFTS ACYLATION
453
0.07
0.06
0.05
0.04
0.03
0.02
0.01
0
60
50
a
b
1
40
30
20
10
2
3
0
10
20
30
40
50
60
70
80
90
100
0
PW loading, %
0
20
40
60
80
100
120
Time, min
FIG. 5. EffectofPWloadinginthePW/SiO2 catalystontheinitialrate
of anisole acylation at AN/AA = 20 mol/mol and a constant total amount
of PW (0.010 mmol): (a) 90◦C; (b) 70◦C.
FIG. 6. Inhibition by product in the acylation of anisole (40%
PW/SiO2 (0.83 wt%), AN/AA = 10 mol/mol, 70◦C, 2 h): (1) no p-MOAP
added; (2) p-MOAP added initially, AA/p-MOAP = 2 mol/mol; (3) p-
MOAP added initially, AA/p-MOAP = 1 mol/mol. Yields are based on
acetic anhydride.
The effect of PW loading on silica upon the initial rate of
anisole acylation at 70 and 90◦C is shown in Fig. 5. In these
experiments, the total amount of PW was kept constant.
The activity of PW increases with the loading, passing a
maximum at about 50% loading. It should be noted that
the specific catalytic activity (per Keggin unit) of supported
HPA is greater than that of bulk HPA. This demonstrates
that the reaction occurs via the surface-type catalysis in
terms of Misono’s classification (“bulk vs surface type”)
(10). Similar dependencies have been reported for other
HPA-catalysed reactions (9, 18). Such a behaviour has been
explained as a result of increasing the HPA acid strength
on the one hand, and as the loading increases decreasing
the HPA surface area on the other (11).
product yield. As the HPA catalyst is reusable, the product
inhibition is largely reversible. Choosing higher tempera-
tures and higher AN/AA ratios as well as bulk HPA cata-
lysts can reduce the inhibition.
Langmuir–Hinshelwood model. This model has been
proved useful for the acylation of anisole over zeolites
(7), although another mechanism may be possible. It may
include the reaction of nonchemically adsorbed anisole
with chemisorbed AA molecules, with anisole, however,
competing with AA for adsorption on the acid sites. It is
imperative that with HPA, in contrast to zeolites, there be
no diffusion limitations related to the motions of reactants
or products in micropores. Following the line of reasoning
given elsewhere (7), the acylation of anisole catalysed by
HPA may be assumed to occur via a bimolecular Langmuir–
Hinshelwood mechanism with product inhibition. The re-
action rate is given by Eq. [3], where k is the rate constant,
Inhibition by product. The inhibition of heterogeneous
aromatic acylation by the acylation product has been re-
ported (2, 6–8). It is caused by product adsorption on the
surface of the catalyst (e.g., zeolite) and is, therefore, similar
to the reaction inhibition by complex formation when AlCl3
is used as the catalyst. As found here, the product inhibi-
tion plays a significant role in the HPA-catalysed acylation
as well.
The reaction time course shown in Fig. 4 is typical of a
process gradually inhibited by the product formed. A simi-
lar course has been found for anisole acylation with zeolite
catalysts (7, 8). It can be seen that the inhibition inten-
sifies at lower temperatures and lower AN/AA ratios as
the product adsorption increases. Also it grows stronger
when supported PW is used as compared to bulk PW (cf.
Figs. 3 and 4). Apparently, this is because the bulk PW has
a much smaller surface area (Table 1). The product inhibi-
tion is further demonstrated by the addition of p-MOAP
to the initial reaction mixture, showing that the yield
decreases as the product is added (Fig. 6). Similarly, the
yield sharply decreases as the AN/AA ratio decreases
(Fig. 7). It should be noted that the addition of by-product
acetic acid (AcOH/AA = 1 : 2 mol/mol) had no effect on the
100
80
60
40
20
0
0
10
20
30
40
50
AN/AA molar ratio
FIG. 7. Effect of the AN/AA molar ratio on the yield of p-MOAP
(40% PW/SiO2 (0.75 wt%), 70◦C, 2 h).

454
KAUR ET AL.
TABLE 4
Acylation of Toluene with Acetic Anhydride Catalysed by HPAa
Yieldc (%)
and K1, K2, and Kp are the adsorption coefficients for acetic
anhydride, anisole, and p-MOAP, respectively.
d[P]
dt
kK1 K2[AA][AN]
(1 + K1[AA] + K2[AN] + Kp[P])2
Catalyst
PhMe/AA
T
Time
(h)
r =
=
.
[3]
(amount, wt%)b
(mol/mol) (◦C)
p-MAP o-MAP
PW (5.5)
20
10
20
20
20
110
90
6
2
2
2
20
2
22
24
24
3.0
0.3
1.1
2.0
3.5
5.2
23
37
40
Cs2.5H0.5PW12O40 (1.1)
Cs2.5H0.5PW12O40 (1.1)
40% PW/SiO2 (1.1)
40% PW/SiO2 (1.1)
40% PW/SiO2 (1.1)
40% PW/SiO2 (1.1)
40% PW/SiO2 (1.1)
H-beta (1.9) f
As there is no solvent and anisole is present in large excess,
its concentration remaining practically constant during the
reaction, Eq. [3] can be rearranged to [4]. Here a is an
effective first-order rate constant and b = Kp/K2[AN].
150d
110
110
150d
110
110
110
20
200
100e
20
4.0
4.8
kK1 K2[AA][AN]
(K2[AN] + Kp[P])2
a[AA]
(1 + b[P])2
r =
≈
.
[4]
a Toluene, 100 mmol (9.21 g), reacted with acetic anhydride (AA)
in the presence of a solid HPA catalyst without solvent in a stirred
batch reactor to yield para-methylacetophenone (p-MAP) and ortho-
methylacetophenone (o-MAP).
Now consider two limiting cases: t → 0 and t → ∞.
b The amount of catalyst per total reaction mixture.
c Yield based on acetic anhydride.
t → 0; r = a[AA]o.
a[AA]
[5]
[6]
d Reaction was carried out in a stainless steel autoclave.
t → ∞; r =
.
e Acetic anhydride added dropwise.
(b[P])2
f
From Ref. (8).
Applying Eq. [5] to the data shown in Fig. 4a (Table 2,
Entry 8) gives a = 0.11 min−1. The same data for the time
range from 10–120 min give a very good linear plot (regres-
sion coefficient, 0.999) in accordance with Eq. [6] (Fig. 8),
yielding b = 4.3 L/mol. As [AN] = 8.5 mol/L, Kp/K2 = 37
at 90◦C. Thus the product adsorbs 37 times stronger than
anisole, inhibiting the reaction.
Our results on the HPA-catalysed acylation of toluene
with acetic anhydride to yield para- and ortho-methyla-
cetophenone (p-MAP and o-MAP) are given in Table 4.
Surprisingly, the reaction with HPA catalysts was found
to be much less efficient than that with zeolite (e.g., H-
beta) despite the stronger acidity of HPA. Bulk and silica-
supported PW yielded only 3–5% p-MAP and traces of o-
MAP at 90–150◦C, PhMe/AA = 5–20 mol/mol, 2–20 h. The
acidic salt Cs2.5H0.5PW12O40 performed even more poorly.
Similar results were obtained for the acylation of p-xylene
with acetic anhydride. In contrast, H-beta zeolite under
similar conditions gives a 40% p-MAP yield (8) (Table 4).
These results could be explained by the well-known
strong affinity of bulk HPA towards polar oxygenates
(10, 11), which would lead to the preferential adsorption
of acetic anhydride on HPA, blocking access for toluene
to the catalyst surface. To overcome this, the acylation
should be carried out at higher PhMe/AA molar ratios.
Indeed, at PhMe/AA = 100–200 and with dropwise addi-
tion of acetic anhydride, a total acylation yield of 42%
was obtained (Table 4). This proves that the preferen-
tial adsorption of the more polar acylating agent plays
an important role in the acylation of toluene over HPA.
It should be noted that this is not the case in the acy-
lation of anisole over HPA because both the aromatic
substrate and the acylating agent have comparable polar-
ities. It appears that the hydrophobic acid zeolites with
high Si/Al ratios less strongly differentiate the adsorption
than the hydrophilic HPA and, therefore, are more suit-
able catalysts for the acylation of nonpolar aromatics like
toluene.
Acylation of Toluene
Toluene is less reactive than anisole towards electrophilic
substitution. The acylation of toluene over zeolite catalysts,
although feasible, is more difficult to achieve than that of
anisole (8).
0.014
0.012
0.01
0.008
0.006
0.004
0.002
0
0
0.5
1
1.5
2
2.5
[AA]/[P]2, l/mol
FIG. 8. Plot of the reaction rate versus [AA]/[P]2 (40% PW/SiO2
(0.83 wt%), AN/AA = 10 mol/mol, 90◦C).

FRIEDEL–CRAFTS ACYLATION
455
CONCLUSION
REFERENCES
1. Olah, G. A., in “Friedel–Crafts and Related Reactions,” Vols. I–IV.
Wiley–Interscience, New York, 1963–1964; Olah, G. A., in “Friedel–
Crafts and Related Reactions.” Wiley–Interscience, New York,
1973.
2. Metivier, P., in “Fine Chemicals through Heterogeneous Catalysis”
(R. A. Sheldon and H. van Bekkum, Eds.), p. 161. Wiley–VCH,
Weinheim, 2001.
3. Chiche, B., Finiels, A., Gauthier, C., Geneste, P., Graille, J., and
Pioch, D., J. Org. Chem. 51, 2128 (1986).
4. Corma, A., Ciment, M. J., Garcia, H., and Primo, J., J. Appl. Catal. 49,
109 (1989).
5. Spagnol, M., Gilbert, L., and Alby, D., Ind. Chem. Lib. 8, 29
(1996).
6. Rohan, D., Canaff, C., Fromentin, E., and Guisnet, M., J. Catal. 177,
296 (1998).
7. Derouane, E. G., Dillon, C. J., Bethell, D., and Abd Hamid, S. B.,
J. Catal. 187, 209 (1999).
8. Derouane, E. G., Crehan, G., Dillon, C. J., Bethell D., He, H., and
Abd Hamid, S. B., J. Catal. 194, 410 (2000).
Keggin-type heteropoly acid H3PW12O40, bulk or silica
supported, is a highly efficient solid acid catalyst for the
liquid-phase acylation of anisole with acetic anhydride to
yield up to 98% p-MOAP and 4% o-MOAP (90–110◦C,
AN/AA = 10–20 mol/mol). The catalyst can be reused af-
ter a simple workup, with a gradual decline of its activity
being observed, however. The acylation of anisole appears
to be heterogeneously catalysed; no contribution of homo-
geneous catalysis by HPA is observed when the catalyst is
filtered off at the reaction temperature. HPA is nearly a fac-
torof100moreactivethanzeoliteH-betaforthisreaction—
that is in line with the stronger acidity of HPA. Similarly to
the reaction with zeolite catalysts, the HPA-catalysed acy-
lation is inhibited by product because of strong adsorption
of MOAP on the catalyst surface. The ratio of adsorption
coefficients of p-MOAP and anisole is found to be 37 at
90◦C. The inhibition is reduced at higher temperatures and
higher AN/AA ratios as well as when using bulk instead of
supported HPA. In contrast to anisole, the HPA-catalysed
9. Izumi, Y., Urabe, K., and Onaka, M., “Zeolite, Clay and Heteropoly
Acid in Organic Reactions.” Kodansha/VCH, Tokyo, 1992.
10. Okuhara, T., Mizuno, N., and Misono, M., Adv. Catal. 41, 113
(1996).
acylation of toluene with acetic anhydride is far less efficient 11. Kozhevnikov, I. V.,Chem. Rev. 98, 171 (1998).
12. Moffat, J. B., “Metal-OxygenClusters. TheSurfaceandCatalyticProp-
than that with H-beta. Evidence is provided that the activity
of HPA in toluene acylation is inhibited by preferential ad-
sorption of acetic anhydride on the catalyst. Apparently, the
hydrophobic acid zeolites (e.g., H-beta) less strongly differ-
entiate the adsorption of aromatic substrate and acylating
agent than the hydrophilic HPA and, therefore, are more
suitable catalysts for the acylation of nonpolar aromatics
like toluene.
erties of Heteropoly Oxometalates.” Kluwer, New York, 2001.
13. Castro, C., Primo, J., and Corma, A., J. Mol. Catal. A 134, 215
(1998).
14. Kozhevnikov, I. V., Kloetstra, K. R., Sinnema, A., Zandbergen, H.,
and van Bekkum, H., J. Mol. Catal. A 114, 287 (1996).
15. Izumi, Y., Ono, M., Kitagawa, M., Yoshida, M., and Urabe, K., Micro-
porous Mater. 5, 255 (1995).
16. (a) Siddiqui, M. R. H., Holmes, S., He, H., Smith, W., Coker,
E. N., Atkins, M. P., and Kozhevnikov, I. V., Catal. Lett. 66, 53 (2000);
(b) Kozhevnikov, I. V., Holmes, S., and Siddiqui, M. R. H., Appl. Catal.
A 214, 47 (2001).
ACKNOWLEDGMENTS
17. (a) Berliner, E., Progr. Phys. Org. Chem. 2, 253 (1964); (b) Zollinger,
H., Adv. Phys. Org. Chem. 2, 163 (1964).
18. Nowinska, K., Fiedorow, R., and Adamiec, J., J. Chem. Soc. Faraday
Trans. 87, 749 (1991).
The authors thank Johnson Matthey Chemicals, Royston, UK, and The
Leverhulme Centre for Innovative Catalysis, Liverpool University, for
support.