Catalytic Friedel-Crafts acylation and benzoylation of aromatic compounds using activated hematite as a novel heterogeneous catalyst

Article abstract of DOI:10.1002/adsc.201000319

Catalytic Friedel-Crafts acylation of benzene and unactivated benzenes such as chlorobenzene and nitrobenzene have been successfully carried out using activated hematite (α-Fe₂O₃) as a new, heterogeneous and green catalyst. Sonication of neat α-Fe₂O₃ in a water bath under air atmosphere at room temperature followed by heating at 200°C, dramatically increase the activity of α-Fe₂O ₃. With the catalyst loading as low as 5.0mol%, a wide variety of benzene derivatives were easily converted into the corresponding acylated products in a clean and high-yielding acylation reaction. It was found that the activated α-Fe₂O₃ could be efficiently recycled and reused several times by simple washing with ethyl acetate, this cannot be attained with most of the traditional catalysts. Copyright

Full text of DOI:10.1002/adsc.201000319

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DOI: 10.1002/adsc.201000319
Catalytic Friedel–Crafts Acylation and Benzoylation of Aromatic
Compounds Using Activated Hematite as a Novel Heterogeneous
Catalyst
Hashem Sharghi,a,* Mahboubeh Jokar,a Mohammad Mahdi Doroodmand,a
and Reza Khalifehb
a
Department of Chemistry, Shiraz University, Shiraz 71454, Iran
Fax : (+98)-711-228-0926; phone: (+98)-711-228-4822; e-mail: shashem@chem.susc.ac.ir
Department of Chemistry, Shiraz University of Technology, Shiraz 75555-313, Iran
b
Received: April 26, 2010; Revised: October 12, 2010; Published online: November 17, 2010
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/adsc.201000319.
Abstract: Catalytic Friedel–Crafts acylation of ben- corresponding acylated products in a clean and high-
zene and unactivated benzenes such as chloroben- yielding acylation reaction. It was found that the ac-
zene and nitrobenzene have been successfully carried tivated a-Fe2O3 could be efficiently recycled and
out using activated hematite (a-Fe2O3) as a new, het- reused several times by simple washing with ethyl
erogeneous and green catalyst. Sonication of neat a- acetate, this cannot be attained with most of the tra-
Fe2O3 in a water bath under air atmosphere at room ditional catalysts.
temperature followed by heating at 2008C, dramati-
cally increase the activity of a-Fe2O3. With the cata- Keywords: activated hematite; aromatic compounds;
lyst loading as low as 5.0 mol%, a wide variety of Friedel–Crafts acylation; heterogeneous catalysis;
benzene derivatives were easily converted into the solvent-free reaction
Introduction
In order to solve the aforementioned problems,
some catalytic Friedel–Crafts acylations have been de-
ACTHNUTRGNEUNG
The Friedel–Crafts (FC) acylation reaction produces veloped. Lanthanide triflates,[4] TiCl(Otf)3-TfOH,[5a]
aromatic ketones, which are important intermediates Re-Br(CO)5,[5b] LiClO4-acyl hydride complex,[6] FeCl3
in a wide variety of fields including manufacturing of over K10,[7a] perfluorinated nafion-modified SBA-
fine chemicals and pharmaceuticals such as naprox- 15,[7b] clay catalysts,[8] inorganic solids,[9] or solid
en[1b] and ibuprofen,[1e] dyes, fragrances and agroche- acids,[10] HZSM-5 zeoilte,[11] metal oxide-promoted
micals.[1a–f]
sulphated zirconia,[12a] ZnO,[12b] aluminium metal pow-
Friedel–Crafts acylation reactions represent one of der,[12c] In(Br)3 using dimethylchlorosilane,[13] P2O5/
the greatest challenges to green chemistry.[1g–h] Tradi- Al2O3,[14a] and MoO2Cl2,[14b] have already been report-
tional methods generally employ large quantities of ed as catalysts for Friedel–Crafts acylations. Although
hazardous soluble Lewis acids, (e.g., AlCl3, TiCl4, and some catalysts which complete the acylation reaction
FeCl3) or strong mineral acids (e.g., HF), which are have been reported,[15] usually the conventional cata-
destroyed in the course of work-up giving poor re- lysts suffer from drawbacks in terms of requirement
source utilization and large volumes of waste.[2] Con- of more than stoichiometric quantities.[12c,16] More-
sidering the ecological and economical problems asso- over, some recipes are based on highly moisture-sen-
ciated with waste management in most countries, the sitive reagents such as, BiACTHNUGTRENNUG ACHTNUGTRENNNUG
(OTf)3,[17a] TiCl
[17c]
[17b]
design of safe and environmentally acceptable pro- Cl4·AgClO4
and SbCl5
cesses for FC reactions is of increasing interest;[1f,3] handle and require rigorously anhydrous reaction
thus, the development of truly catalytic alternatives is media. Therefore, the development of more efficient
highly desirable and constitutes a field of current in- and easy handling catalysts is in strong demand.
terest.
Among many others, we have recently demonstrat-
ed that heterogeneous reagent systems have several
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advantages such as simplicity in handling, mild reac- (Table 1), while the reaction performed in the absence
tion conditions, environmentally safe disposal and the of the catalysts, resulted in the formation of no prod-
minimization of chemical wastes compared to their uct (Table 1, entry 1). a-Fe2O3 demonstrated the
homogeneous phase counterparts.[18] The above facts greatest activity among the eight catalysts tested, af-
encouraged us to investigate a heterogeneous system fording quantitative conversion within 15 min, with
for the Friedel–Crafts acylation of aromatic com- 91% yields; while CuO, NiO, CoO, Cr2O3, Mn2O3 dis-
pounds.
played reduced activity, and afforded 15 min conver-
As a part of our ongoing research projects to devel- sions of 50, 55, 59, 56 and 59%, respectively, as evi-
1
op new synthetic methodologies, particularly with a denced by H NMR as of the crude product (Table 1).
potential for using metal oxides,[12b] we have been in- SnO was least active, producing a 15 min conversion
terested in iron oxide (Fe2O3 or hematite) as an inex- of only 28%.
pensive, high corrosion resistive and commercially
As shown in the Table 1, a-Fe2O3 was found to be
available inorganic solid as a potential reaction cata- the most effective catalyst in terms of reaction rate,
lyst. It is worth mentioning that a-Fe2O3 has attracted selectivity and isolated yield of product (Table 1,
considerable attention due to its wide applications in entry 9). Results in Table 1 indicate that the optimal
diverse fields such as transistors,[19a] catalysis,[19b,c] pho- metal oxide loading for achieving the highest yield is
toelectrolysis reactors,[19d,e] batteries,[19f,g] magnetic 5.0 mol% of a-Fe2O3.
storages,[19h] gas sensors,[19i,j] and as drug carriers for
magnetically guided drug delivery etc.[19k,l,m]
Later, the effects of a variety of conditions for in-
creasing the catalytic activity of a-Fe2O3 were investi-
Herein we wish to report that activated a-Fe2O gated (Table 1, entries 10–15). As is obvious from
promoted the convenient, simple and selective Frie- entry 15 of Table 1, the best result was obtained with
del–Crafts acylation of benzene and unactivated ben- the activating use of ultrasound (650 kHz) radiation
zenes under solvent-free conditions, as shown in of neat a-Fe2O3 in a water bath under an air atmos-
Scheme 1.
phere at room temperature for 1.0 h followed by heat-
ing the solid powder at 2008C for 72 h.
The reactivity and regioselectivity of the activated
a-Fe2O3 as catalyst in the acylation of chlorobenzene
under solvent-free condition compares favorably with
those observed in various solvents. Solvents having
strong coordination ability such as 1,4-dioxane and
THF gave no products (Table 2, entries 1 and 2).
In fact, under solvent-free conditions, the ketone
was obtained quantitatively within 5.0 min with an ex-
cellent o/p ratio of 2/98. In contrast, in CH2Cl2 and
CHCl3, lower conversions and o/p ratios were ob-
Scheme 1.
Results and Discussion
In order to establish the most convenient catalyst, we tained (Table 2, entries 3, 4), and the reaction re-
used eight commercially available metal oxides (CuO, quired much longer time periods to go to completion
NiO, CoO, Cr2O3, Mn2O3, SnO, ZnO, a-Fe2O3) for the and led to two ketones with an o/p ratio of 20/80 and
study of Friedel–Crafts acylation reactions. The acyla- 15/85, respectively. In the case of use of toluene as a
tion of chlorobenzene was used as a model reaction non-polar solvent, the desired ketone was obtained
to compare the catalytic ability of each metal oxide.
quantitatively within 120 min with an o/p ratio of 8/92
In a typical reaction, metal oxide was added to a in 60% yields along with 30% of acylated toluene
mixture of acetyl chloride (1a) (1.0 mmol) and chloro- (Table 2, entry 9). Solvent studies indicated that the
benzene (1.0 mmol). The reaction was performed at solvent-free condition serves as the most suitable
room temperature under solvent-free conditions system for the FC reaction using 5.0 mol% of the acti-
(Scheme 2).
vated a-Fe2O3 (Table 2, entry 12).
It was observed that all of the investigated metal
Encouraged by our preliminary results, the activat-
oxides were able to catalyze the FC acylation ed a-Fe2O3 was subsequently used to catalyze a range
Scheme 2.
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Catalytic Friedel–Crafts Acylation and Benzoylation of Aromatic Compounds
Table 1. Investigation of the activity of various metal oxides on the synthesis of 1-(4-chlorophenyl)ethanone from chloroben-
zene (1.0 mmol), acetyl chloride 1a (1.0 mmol) under solvent-free conditions at room temperature.
Entry Catalyst
Mmol of Conversion[a] Time o/p
catalyst [%]
[min] [%][c]
AHCTUNGTRENNUNG
1
2
3
4
5
6
7
8
–
–
0
0
5
0
0
15
15
30
15
30
15
40
15
45
15
60
15
40
30
15
10
15
20
30
35
15
13
13
12
10
CuO
0.05
0.20
0.05
0.20
0.05
0.20
0.05
0.20
0.05
0.20
0.05
0.20
0.05
0.20
0.50
0.05
0.10
0.15
0.20
0.05
0.05
0.05
0.05
0.05
50
41
55
49
59
48
56
41
59
39
28
20
60
78
85
91
90
86
85
92
94
91
93
93
8/98
10/90
2/98
5/95
6/94
8/94
3/97
9/91
4/96
11/89
10/90
15/85
2/98
4/96
4/96
3/97
3/97
4/69
4/96
3/97
3/97
3/97
4/96
3/97
NiO
CoO
Cr2O3
Mn2O3
SnO
Commercial ZnO12b
9
a-Fe2O3
10
11
12
13
14
a-Fe2O3/heating for 1 day at 1008C
a-Fe2O3/heating for 3 days at 2008C
a-Fe2O3/sonication (650 kHz)/1 h
a-Fe2O3/microwave irradiation/300 W/15 min
a-Fe2O3/microwave irradiation/300 W/15 min and then heating for 3 days at
2008C
15
16
a-Fe2O3/sonication (650 kHz)/1 h and then heating for 3 days at 2008C
g-Fe2O3
0.05
0.05
95
70
5
15
2/98
3/97
[a]
[b]
1
Conversion of acetyl chloride, measured by H NMR.
ortho/para ratio measured by GC.
of Friedel–Crafts acylation reactions under solvent- alytic conditions, the acylation of toluene afforded a
free conditions (Table 3). All activated and unactivat- mixture of ortho/para-regioisomers with a high para-
ed aromatic compounds reacted very rapidly with a selectivity (Table 3, entry 5), and acylation of o-xylene
variety of acid chlorides along with a catalytic amount gave the corresponding ketone in excellent yield
of activated a-Fe2O3 within 5–85 min at room temper- (Table 3, entry 8). Mesitylene was also reacted with
ature
acetyl chloride in the presence of activated a-Fe2O3 in
The analysis of the results showed that the highest excellent yield (Table 3, entry 9). Obviously, the me-
yields were obtained with substrates bearing electron- thoxy group of anisole has a stronger activating effect
donating groups such as alkoxy substituents on the ar- on the aromatic system than the three methyl groups
omatic ring (Table 3, entries 6, 7 and 22-2-8). It is of mesitylene. Thus, the acylation of anisole is com-
indeed gratifying to note that the reaction conditions pleted after 5 min in 98% yield, whereas the complete
are mild enough since they do not induce any dealky- acylation of mesitylene requires a reaction time of
lation of an ether group located at an ortho position 10 min, affording the desired product in 96% yield
to the introduced acyl group (Table 3, entry 7) as ob- (Table 3, entry 6 vs. 9). Acylation occurs exclusively at
served in the acylation reaction with carboxylic acid the position para to OMe, Me, and Cl substituents for
catalyzed by BF3.[20]
all of the compounds studied, in almost quantitative
The acylation of alkyl-substituted benzenes such as yields. However, in cases where the para positions are
toluene is more difficult, and some of the methods re- blocked, the acyl group is introduced in the ortho po-
ported in the literature are not applicable to this sub- sition (Table 3, entries 7 and 17).
strate or give poor yields of ketone.[21] Under our cat-
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Table 2. Investigation of various solvents effect on the syn-
thesis of 1-(4-chlorophenyl) ethanone from chlorobenzene
(1.0 mmol), acetyl chloride 1a (1.0 mmol), activated a-Fe2O3
(0.05 mmol) at room temperature.
An important feature of this procedure is the sur-
vival of a variety of functional groups such as ethers,
nitro, amide, cyanide, etc. under the reaction condi-
tions. Acid-sensitive substrates such as acetamide also
reacted in high yields without the formation of any
side products (Table 3, entry 19).
Although the benzoylation of chlorobenzene led to
80% conversion after 20 min in the presence of acti-
vated a-Fe2O3, the benzoylation of activated aromat-
ics yielded the ketones in excellent yields (Table 3,
entries 22–27).
Entry
Solvent
Conversion[a]
[%]
Time
AHCTUNGTERG[NNUN min]
o/p[b]
To establish the generality and applicability of this
method, the FC acylation of anisole with different
acyl chlorides was investigated. The reaction with 2-
chlorobenzoyl chloride produced a mixture of isomers
with an o/p ratio of 2/98 in 90% yield (Table 3,
entry 23). Similarly, acylation of anisole with p-toluoyl
and 2-phenylacetyl chloride afforded exclusively the
para-isomers in 95% and 91% yields, respectively
(Table 3, entries 24 and 25), indicating a high selectiv-
ity with these acyl chlorides. In contrast, the reaction
between anisole and benzoyl chloride was regioselec-
tive, yielding to the para-isomer (Table 3, entry 22).
Furthermore, we have elaborated our study with
heteroaroyl chlorides such as thiophenyl chloride to
establish their reactivity with anisole. This study dis-
closed that this procedure is also good enough for the
preparation of the corresponding 2-acylated product
in excellent yield (Table 3, entry 26). Finally, the acy-
1
2
3
4
5
6
7
8
1,4-dioxane
THF
chloroform
dichloromethane
acetonitrile
EtOAc
xylene
water
toluene
DMF
0
0
120
120
130
120
120
120
120
120
120
120
120
5.0
0
0
40
50
10
15
30
10
60
10
5
15/85
20/80
5/95
6/94
7/93
90/10
8/92[c]
20/80
10/90
2/98
9
10
11
12
diethyl ether
–
95
[a]
1
Conversion of acetyl chloride, measured by H NMR.
ortho/para ratio measured by GC.
Acylated toluene was obtained in 30% yield.
[b]
[c]
The acylation of anthracene with acetyl chloride lation reaction of diaroyl chlorides such as isophthalo-
seemed to be more difficult to perform (Table 3, en- yl dichloride and anisole was studied. It was found
tries 10 and 11). Our attempt to prepare 9,10-diacetyl- that the reaction undergoes acylation predominantly
ACHTUNGTRENNUNGanthracene (2k) using the activated a-Fe2O3 for direct at the para-position (Table 3, entry 27). To access the
FC acylation, after vigorous stirring of reaction at feasibility of applying this method on a preparative
808C, resulted the corresponding diacylated product scale, we carried out the reaction of anisole with
in only 54% yield (Table 3, entry 11).
acetyl chloride on a 100-mmol scale in the presence
In the case where the aromatic ring is fused to a of the heterogeneous catalyst (Table 3, entry 6). As
crown ether, a potential difficulty is apparent. The expected, the reaction proceeded similarly to the case
Lewis acid catalyst and/or the reactive electrophilic with a smaller scale, and the desired product was ob-
intermediate may be complex and consequently deac- tained in 98% isolated yield in 5 min.
tivated by the crown ether.[22] Interestingly, our proce-
The effects of activation process applied on the ini-
dure is good enough for the acylation of crown ethers tial powder of a-Fe2O3 were evaluated by measuring
such as benzo-18-crown-6 and dibenzo-18-crown-6 the active surface area of the catalyst via the nitrogen
(Table 3, entries 13 and 14), producing the corre- adsorption method using a home-made thermogravi-
sponding acylated products in excellent yield. Diacy- metric analysis (TGA) instrumentation system, and
lation of dibenzo-18-crown-6 lead to two isomeric the results are shown in Figure 1.
products, which could not be separated with recrystal-
lization.
The active surface areas, measured according to the
Knudsen equation[23a], were as follows: 1.18E+2 m2
The acylation of ferrocene with acetyl chloride (1a) kgÀ1 for initial a-Fe2O3; 6.19E+2 m2 kgÀ1 for a-Fe2O3
was also studied in the presence of activated a-Fe2O3, after sonication for 1 h; 7.02E+2 m2 kgÀ1 for a-Fe2O3
it proceeded with highly chemoselectively and fur- after sonication (650 kHz) for 1 h and then heating
nished monoacylated ferrocene in 64% yield (Table 3, for 3 days at 2008C.
entry 15).
It is believed that the contaminant adsorption ca-
The presence of NO2 as a strong electron-withdraw- pacity of an adsorbent is largely determined by the
ing group on the aromatic ring reduced the yield of surface area available for adsorption[23b] and nitrogen
the acylation reaction, so that the corresponding adsorption of the initial and activated a-Fe2O3 show
ketone was isolated in 69% yield (Table 3, entry 4).
that high specific surface areas were directly prepared
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Adv. Synth. Catal. 2010, 352, 3031 – 3044