Metal-organic framework MIL-53(Al): Synthesis, catalytic performance for the Friedel-Crafts acylation, and reaction mechanism

Article abstract of DOI:10.1007/s11426-015-5359-0

Metal-organic framework MIL-53(Al) was synthesized by a solvothermal method using aluminum nitrate as the aluminium source and 1,4-benzenedicarboxylic acid (H₂BDC) as the organic ligand. The structure of samples was characterized by X-ray diffraction (XRD) and Fourier transform infrared spectroscopy (FT-IR). The catalytic activity and recyclability of MIL-53(Al) catalyst for the Friedel-Crafts acylation reaction of indole with benzoyl chloride were evaluated. The reaction conditions were optimized and a reaction mechanism was suggested. The results showed that the MIL-53(Al) catalyst exhibited good catalytic activity and recyclability for the Friedel-Crafts acylation reaction. When the molar ratio of indole and MIL-53(Al) catalyst was 1:0.06 (n ₁:n _catalyst), the molar ratio of indole and benzoyl chloride was 1:3, and the solvent was dichloromethane, the conversion of indole could reach 97.1% and the selectivity of 3-acylindole could reach 81.1% at 25 °C after 8 h. The catalyst can be reused without significant degradation in catalytic activity. After the catalyst was reused five times, the conversion of indole was 87.6% and the selectivity of 3-acylindole was 79.5%.

Full text of DOI:10.1007/s11426-015-5359-0

SCIENCE CHINA
Chemistry
January 2015 Vol.58 No.1: 1–8
doi: 10.1007/s11426-015-5359-0
• ARTICLES •
doi: 10.1007/s11426-015-5359-0
Metal-organic framework MIL-53(Al): synthesis, catalytic
performance for the Friedel-Crafts acylation, and
reaction mechanism
Junlei Yan, Sai Jiang, Shengfu Ji*, Da Shi & Hefei Cheng
State Key Laboratory of Chemical Resource Engineering; Beijing University of Chemical Technology, Beijing 100029, China
Received December 2, 2014; accepted January 15, 2015
Metal-organic framework MIL-53(Al) was synthesized by a solvothermal method using aluminum nitrate as the aluminium
source and 1,4-benzenedicarboxylic acid (H2BDC) as the organic ligand. The structure of samples was characterized by X-ray
diffraction (XRD) and Fourier transform infrared spectroscopy (FT-IR). The catalytic activity and recyclability of MIL-53(Al)
catalyst for the Friedel-Crafts acylation reaction of indole with benzoyl chloride were evaluated. The reaction conditions were
optimized and a reaction mechanism was suggested. The results showed that the MIL-53(Al) catalyst exhibited good catalytic
activity and recyclability for the Friedel-Crafts acylation reaction. When the molar ratio of indole and MIL-53(Al) catalyst was
1:0.06 (n1:ncatalyst), the molar ratio of indole and benzoyl chloride was 1:3, and the solvent was dichloromethane, the conversion
of indole could reach 97.1% and the selectivity of 3-acylindole could reach 81.1% at 25 °C after 8 h. The catalyst can be re-
used without significant degradation in catalytic activity. After the catalyst was reused five times, the conversion of indole was
87.6% and the selectivity of 3-acylindole was 79.5%.
MIL-53(Al), catalyst, Friedel-Crafts, acylation, indole, 3-acylindoles
tions. Thus, the synthesis of 3-acylindoles has gained con-
1 Introduction
siderable attention among heterocyclic organic chemists [3].
Traditionally, a wide variety of 3-acylindoles have been
prepared by several well-known methods such as Vilsmeier-
Haack type reaction [4], Grignard reactions [5], and Friedel-
Crafts acylations. The Vilsmeier-Haack type reaction is
simple and can achieve high yields, but its application
ranges are restricted and are only suitable for active sub-
strate. This method uses unacceptable amounts of environ-
mentally unfriendly POCl3 which acts as a chlorinating
agent in the reaction. Although Grignard reactions can im-
prove the selectivity of 3-acylindole, they also increase the
complexity of the synthesis process and lower the overall
yields. Friedel-Crafts acylations are environmentally frien-
dly and easy to carry out. This method requires Lewis acids
as catalysts, such as AlCl3 [6] and InCl3 [7]. However, the
required amounts of these catalysts generate a great deal of
waste. In order to reduce pressure on the environment,
Friedel-Crafts acylation reactions are important C–C bond-
forming processes [1]. They are the most powerful method
of preparing aromatic ketones, which have advantages of
simplicity and high selectivity. Heterocyclic aromatic ke-
tones are important organic intermediates in the synthesis of
fine chemicals, which are mainly used as medicines and in
prepared spices and agricultural chemicals. Some of these
chemicals also have biological activity [2]. Indole and in-
dole derivatives are the most heterocyclic aromatic com-
pounds found in nature. Specifically, carbonyl groups of
3-acylindoles, synthesized by the Friedel-Crafts acylations
of indole with benzoyl chloride, can readily undergo a vari-
ety of transformations such as C–C and C–N coupling reac-
*Corresponding author (email: jisf@mail.buct.edu.cn)
© Science China Press and Springer-Verlag Berlin Heidelberg 2015
chem.scichina.com link.springer.com

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Yan et al. Sci China Chem January (2015) Vol.58 No.1
porous material-loaded metal or metal oxide, microporous,
and mesoporous molecular sieves are widely synthesized;
these include metal triflate-loaded SBA-15 [8], sulfurized
zirconia-loaded MCM-41 [9], HPA/SiO2 [10], and mesopo-
rous HZMS-5 [11]. However, their catalytic performances
need to be improved.
the reaction were all studied in this work.
2 Experimental
2.1 Synthesis of MIL-53(Al)
Metal-organic frameworks (MOFs) are formed by self-
assembly of polydentate organic ligands and metal ions, for
which they construct 3D porous network structures. In re-
cent years, because of their unique properties such as un-
saturated metal active sites, easy functionalization, and
large surface area, they are widely used in the field of ca-
talysis [12,13]. Nguyen et al. [14] used the metal active site
of Zn in IRMOF-8 to catalyze a Friedel-Crafts acylation
reaction of toluene and benzoyl chloride. After 6 h of reac-
tion, the conversion of toluene reached 95.0% and the
IRMOF-8 catalyst could be reused without significant deg-
radation of its catalytic activity. Li et al. [15] used Zn-
BTC@SiO2@Fe3O4 as catalyst to catalyze Friedel-Crafts
acylation of toluene with toluoyl chloride. When the amount
of the Zn-BTC catalyst was 3.7% (mass fraction), the con-
version of toluene was 78.8% at 120 °C for 4.5 h and
showed high catalytic activity. The catalyst also had a good
superparamagnetism that could facilitate recycling.
The metal-organic framework (MIL-53(Al)), which is
built up by the interconnection of infinite trans chains of
corner-sharing (via OH groups) AlO4(OH)2 octahedra with
BDC ligands, has a 3D skeleton structure composed of 1D
rhombus channels. MIL-53(Al) has Lewis acid sites (Al3+)
of uniform distribution, specific surface area [16], and re-
markable thermal and chemical stability [17] and has been
used as heterogeneous catalyst. Garibay et al. [18] catalyzed
alcoholysis of epoxides reaction in presence of epoxides
maleic acid-functionalized MIL-53(Al)-AMMal. In that
work, the conversion of ethylene oxide could reach 100%
and the MIL-53(Al)-AMMal catalyst could be reused with
consistent catalytic activity over three runs. Ishida et al. [19]
used Au/MIL-53(Al) to catalyze oxidation of benzyl alcohol
reaction. Compared to Au/CPL-1 catalyst, Au/MIL-53(Al)
could effectively improve the conversion of reaction and
selectivity of the main product, methyl benzoate. Huang
et al. [20] reported that Pd@MIL-53(Al) and Pd@MIL-
53(Al)-NH3 catalyzed a Heck reaction of bromobenzene
with styrene. Due to the increase of their surface area, these
catalysts exhibited efficient catalytic activity for Heck reac-
tion and could be easily recovered and reused. However, it
has not been reported that the Friedel-Crafts acylation of
indole with benzoyl chloride is catalyzed by MIL-53(Al) to
produce 3-acylindole.
MIL-53(Al) was synthesized by a solvothermal method
following literature procedures [21,22]. First, 13 g (35
mmol) aliquot of aluminum nitrate (Al(NO3)3·9H2O) and
2.88 g (17.5 mmol) 1,4-benzenedicarboxylic acid (H2BDC)
were mixed with 50 mL deionized water in a 100 mL
Teflon-lined stainless steel autoclave, then placed in an
oven at 220 °C for 72 h. After completion of the reaction,
the autoclave was cooled down to room temperature. The
product was filtered, and washed four times with deionized
water. It was then purified by a solvent extraction method
using N,N′-dimethylformamide (DMF) to remove uncoor-
dinated H2BDC. The resultant white powder was washed
with methanol three times to remove the DMF molecules
trapped inside its cavities. Finally, the powder was dried in
vacuum at 80 °C for 2 h. MIL-53(Al) was obtained in a
yield of 82.4%. The elemental C and H analysis was carried
out using the CARLO ERBA 1106. The respective per-
centages of C and H were 45.23% and 2.56 (Calculated C:
46.15, H: 2.40).
2.2 Catalytic reaction
Friedel-Crafts acylation of indole with benzoyl chloride
using MIL-53(Al) catalyst was carried out in a flask reactor
with a reflux condenser and continuous stirring. In a typical
catalytic reaction, solvent dichloromethane (CH2Cl2, 3 mL)
was first put into the reactor, then indole (0.468 g, 4 mmol),
benzoyl chloride (1.680 g, 12 mmol), and n-dodecane
(0.136 g, 0.8 mmol) as an internal standard were added
successively to a 50 mL reactor containing the MIL-53(Al)
(counted on the basis of the molar ratio with the reactant
indole, n1:ncatalyst, 1:0.05–1:0.07). Then the mixture was
stirred at a certain temperature (15–40 °C) for several hours.
After the reaction, the catalyst was separated from the sol-
vent by simple centrifugation and the liquid layer was ana-
lyzed with reference to n-dodecane by a gas chromatog-
raphy-flame ionization detector (GC-FID) (Beijing Beifen-
Ruili Analytical Instrument Co., Ltd., SP-2100, China). The
GC instrument was equipped with a capillary column (HJ.
PONA, 50 m×0.2 mm×0.50 m). The conversion of indole
(X), selectivity of 3-acylindole (S3), yield of 3-acylindole
(Y3), selectivity of N-acylindole (S4), yield of N-acylindole
(Y4), and recovery of catalyst (R) were also calculated. After
the first run of the Friedel-Crafts acylation reaction, the cat-
alyst was separated from the reaction mixture, washed with
CH2Cl2 (4×10 mL), dried under vacuum at 80 °C for 12 h,
and reused for the next run. Catalyst recycling performance
was evaluated according to the above reaction procedure.
In this work, the MIL-53(Al) catalyst was synthesized
and characterized by XRD, FT-IR. The catalytic perfor-
mance of MIL-53(Al) was evaluated for Friedel-Crafts ac-
ylation reaction of indole and benzoyl chloride. The effects
of temperature, time, catalyst contents, molar ratio of the
reactants, solvent, substituents, and reusability of catalyst on

Yan et al. Sci China Chem January (2015) Vol.58 No.1
3
2.3 Characterizations
The X-ray diffraction (XRD) pattern was collected on a
D/Max 2500 VB 2+/PC diffractometer (Rigaku, Japan) with
Cu-K irradiation (=1.5418 Å, 40 kV, 200 mA) in the 2
range of 5° to 50°. Fourier transform infrared spectroscopy
(FT-IR) was recorded on a Bruker model Tensor-27 (Ger-
many) in the KBr/MIL-53(Al) pellets. The spectra were
collected after accumulation of 64 scans with a resolution of
1 cm1, at a scan range of 400–4000 cm1.
3 Results and discussion
3.1 MIL-53(Al ) structure
Figure 2 FI-IR spectra for the synthesized MIL-53(Al) (a), H2BDC (b).
The XRD patterns of the MIL-53(Al) before and after the
reaction, and those of the simulated MIL-53(Al), are shown
in Figure 1. The XRD pattern of the experimentally synthe-
sized MIL-53(Al) shows main diffraction peaks at 2=
9.30°, 12.58°, 17.76°, 23.24°, 25.10°, 27.16°. Similarly, the
characteristic diffraction peaks of the simulated MIL-53(Al)
were found at 2=9.34°, 12.54°, 17.88°, 23.36°, 25.20°,
27.26° [23]. Overall characteristic peaks of the synthesized
MIL-53(Al) were consistent with the simulated patterns.
Comparison of the experimental and the simulated XRD
patterns illustrated that crystalline structure of MIL-53(Al)
was obtained under the applied synthesis conditions and that
the catalyst exhibited a good crystal structure. The XRD
patterns of the MIL-53(Al) before and after the reaction
show the same characteristic diffraction peaks, at a slightly
lower intensity. This result shows that MIL-53(Al) exhibits
remarkable stability after catalytic reactions.
be assigned to –C=O asymmetric stretching; the bands at
1446.4 and 1416.0 cm1 could be assigned to –C=O sym-
metric stretching [24]. These values were consistent with
the presence of –C=O coordinated to aluminum. There was
no absorption peak in the 1700.0 cm1 region, which shows
that BDC had been completely removed from the pores of
the structure. However, because MIL-53(Al) absorbed
moisture from the air, the vibrational bands at 1632.0 cm1
and in the 3600–3500 cm1 region respectively correspond
to the bending and stretching modes of water. For the BDC
material, a strong absorption peak was observed at 1700
cm1; this could be attributed to stretching vibration of
–COOH. When we compared the two FT-IR spectra, we
found that the stretching vibrations of –COOH of the syn-
thetic MIL-53(Al) shifted to a lower wave number. In addi-
tion, the asymmetric stretching and symmetric stretching of
–COOH showed different wavelengths, which illustrated
the coordination between –COOH and Al. In summary, the
synthesized samples showed similar structures to the sam-
ples of standard MIL-53(Al).
The FT-IR spectra of the (MIL-53(Al) and BDC) materi-
als at room temperature in the skeletal region of 400–4000
cm–1 are shown in Figure 2. Two absorption bands of MIL-
53(Al) material, located at 1606.4 and 1508.8 cm–1, could
3.2 Catalytic performance of MIL-53(Al)
Based on the above characterization and analysis, MIL-53
(Al) catalyst was used in a Friedel-Crafts acylation reaction
of indole with benzoyl chloride. Different reaction temper-
atures, times, and catalyst contents were measured, as well
as catalyst recycling ability. The reaction equation of indole
with benzoyl chloride is shown in Scheme 1.
3.2.1 Effect of different temperatures
Table 1 shows the effect of temperature on the conversion
of indole, product selectivity, and yield for Friedel-Crafts
Figure 1 XRD patterns for the MIL-53(Al) after and before the reaction,
and the pattern for the simulated MIL-53(Al).
Scheme 1 The Friedel-Crafts acylation reaction of indole with benzoyl
chloride.

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Yan et al. Sci China Chem January (2015) Vol.58 No.1
Table 1 Conversion, selectivity, and yield at different temperatures over
MIL-53(Al) catalyst a)
Entry
t (°C)
15
X (%)
97.1
97.1
97.1
89.2
81.3
S3 (%)
68.1
77.4
81.1
81.0
80.9
Y3 (%)
78.8
89.6
93.9
86.2
78.4
S4 (%)
31.9
22.6
18.9
19.0
19.1
Y4 (%)
21.2
10.4
6.1
1
2
3
4
5
20
25
30
13.8
21.6
40
a) Reaction conditions: n1:ncatalyst=1:0.06, indole (4 mmol), benzoyl
chloride (12 mmol), CH2Cl2 (3 ml); reaction time 8 h.
acylation. When the temperature was 15 °C, the conversion
of indole was 97.1%; the selectivity of 3-acylindole was
68.1%; the yield of 3-acylindole reached 78.8%; and the
selectivity of N-acylindole was 31.9%. When the tempera-
ture was increased from 15 to 25 °C, the conversion of
indole decreased but the selectivity of 3-acylindole showed
an increasing trend; accordingly, the selectivity of N-
acylindole showed a decreasing trend. When the tempera-
ture was increased from 25 to 40 °C, the conversion of in-
dole dropped to 81.3% and the selectivity of the two prod-
ucts remained almost constant. With the increasing of tem-
perature, the yield of 3-acylindole increased first and then
dropped; its maximum yield reached 93.9% at 25 °C. These
results were consistent with [25], which used Et2AlCl to
catalyze the Friedel-Crafts acylation of indole with benzoyl
chloride. Wynne et al. [25] found the same trends of the
conversion of indole and the selectivity of 3-acylindole. The
reason for these results might be that the active Al3+ sites of
MIL-53(Al) were more conducive to reacting with electro-
phile benzoyl chloride and forming acylium ion at low
temperature, which could further induce electrophilic sub-
stitution [26].
The results in Table 1 show that the conversion of indole
and the selectivity of 3-acylindole were higher when the
reaction temperature was 25 °C. When MIL-53(Al) exhib-
ited high catalytic activity, the conversion of indole achie-
ved 97.1% and the selectivity of 3-acylindole reached
81.1%. These results were consistent with [1], in which a tr-
aditional Lewis acid catalyst, ZnCl2, was used for a Friedel-
Crafts acylation reaction. In conclusion, the reaction oc-
curred under milder reaction conditions when a Friedel-
Crafts acylation of indole with benzoyl chloride was cata-
lyzed by MIL-53(Al).
Figure 3 Effect of the MIL-53(Al) catalyst on the Friedel-Crafts acyla-
tion reaction at different times. Reaction conditions: n1:ncatalyst=1:0.06,
25 °C, indole (4 mmol), benzoyl chloride (12 mmol), CH2Cl2 (3 mL).
3-acylindole increased to 81.1%; and the selectivity of N-
acylindole dropped to 18.9%. Before the reaction time
reached 8 h, the conversion of indole obviously increased as
the reaction time increased. This result indicated that the
reaction rate between the indole and benzoyl chloride was
faster during this period of time. After the reaction time
reached 8 h, the conversion of indole and the selectivity of
3-acylindole did not show obvious changes with the exten-
sion of reaction time.
These time-linked changes of reaction conversion and
selectivity were consistent Phan et al. [27], who catalyzed a
Friedel-Crafts acylation reaction in the presence of MOF-5
catalyst. This catalytic activity of MIL-53(Al) can be ex-
plained by the fact that its active sites were abundant before
8 h, during which time the reactants could come into full
contact with catalyst. Therefore, with the increasing of reac-
tion time, both the conversion and selectivity of the reaction
increased rapidly. During the prolonged reaction time,
however, some parts of the active sites became covered with
solvent or product molecules. Conversion and selectivity of
the reaction thus did not change with further increase of
reaction time, due to a deactivation of active sites or a de-
crease in the effective concentration of reactants [28].
The results in Figure 3 show that the optimal reaction
time was 8 h, during which MIL-53(Al) exhibited high cat-
alytic activity; the conversion of indole achieved 97.1%;
and the selectivity of 3-acylindole reached 81.1%. Com-
pared with [29], MIL-53(Al) showed better catalytic activity
than the AlCl3 used as catalyst for the Friedel-Crafts acyla-
tion reaction of indole. This behavior could be explained by
the fact that –COOH groups would provide more Lewis
acid catalytic sites, which could enhance the catalytic activ-
ity of MIL-53(Al). Most importantly, the Friedel-Crafts
acylation reaction between indole and benzoyl chloride over
MIL-53(Al) catalyst could yield a higher conversion of
indole and a higher selectivity of 3-acylindole after a short
3.2.2 Effect of different reaction times
Figure 3 shows the effect of reaction time on the conversion
of indole and products selectivity. As we may see, after 2 h
of reaction time, the conversion of indole rose to 80.4%; the
selectivity of 3-acylindole reached 67.4%; and the selectiv-
ity of N-acylindole was 32.6%. With the extension of reac-
tion time, the conversion of indole and the selectivity of
3-acylindole increased and the selectivity of N-acylindole
decreased. When the reaction time was extended to 12 h, the
conversion of indole increased to 98.1%; the selectivity of

Yan et al. Sci China Chem January (2015) Vol.58 No.1
5
reaction time at room temperature.
reaction. The effect of catalyst content on the reaction was
observed first. When the catalyst content was 1:0.05, the
conversion of indole was 90.3%; the selectivity of 3-
acylindole was 75.5%; and the yield of 3-acylindole was
81.8%. With the increasing of MIL-53(Al) content, the
conversion of indole, the selectivity of 3-acylindole, and the
yield of 3-acylindole first increased quickly and then re-
mained almost constant.
When catalyst content was increased to 1:0.07, the con-
version of indole rose to 97.2%; the selectivity of 3-
acylindole rose to 81.0%; and the yield of 3-acylindole rose
to 93.8%. This result might be due to an effective absorptive
properties effect of MIL-53(Al) [30] in which the excess of
catalyst content contributes to the absorption of reactants
and thus decelerates the speed of the reaction. In compari-
son with [26], which reported the use SnCl4 as catalyst for
Friedel-Crafts acylation reaction of indole, our yield was
95.0% when catalyst content was 1.20 mmol (1:1.2). How-
ever, we used only 0.06 mmol (1:0.06) MIL-53(Al) to cata-
lyze the reaction but obtained a yield of 93.9%, which
showed that MIL-53(Al) has higher catalytic activity than
traditional Lewis acid catalysts. Clearly, MIL-53(Al) show-
ed high catalytic activity for Friedel-Crafts acylation reac-
tion: the optimal content of catalyst was 1:0.06; the conver-
sion of indole was 97.1%; the selectivity of 3-acylindole
was 81.1%; and the yield was 93.9%.
The effect of different solvents on the reaction perfor-
mance is also list in Table 3. The content of catalyst was
fixed at 1:0.06. When dichloromethane and trichloro-
methane were used as solvents, the respective conversions
of indole were 97.1% and 96.2%; the respective selectivities
of 3-acylin-dole were 81.1% and 80.3%; and the respective
yields of 3-acylindole were 93.9% and 92.5%. However,
when the nonpolar cyclohexane was used as solvent, the
conversion of indole was only 89.6%; the selectivity of
3-acylindole dropped to 79.5%; and the yield of 3-acylin-
dole decreased to 86.2%. These results were consistent with
previous literature [31] in that polar solvents were more
beneficial to a Friedel-Crafts acylation of indole with ben-
zoyl chloride (because indole and benzoyl chloride are both
polar materials). According to the theory of similar com-
patibility, it is easy to dissolve reactants in polar solvents—
a situation that favors full contact between two reactants
3.2.3 Effect of mole ratio of the reactants
Table 2 shows the effect of the molar ratio of reactants in-
dole with benzoyl chloride on the conversion of indole and
on the selectivity and yield of two products. The reagent
molar ratio is also a main factor that must be taken into
consideration during the reaction. When the molar ratio of
the indole and benzoyl chloride was 1:1, the conversion of
indole was 89.2%; the selectivity of 3-acylindole was 66.7%;
and the yield of 3-acylindole was 66.4%. With the increas-
ing of the molar ratio of indole and benzoyl chloride, the
conversion of indole and the yield of 3-acylindole increased
first and then dropped, whereas the selectivity of 3-acylin-
dole increased first and then remained almost constant.
When the ratio was increased to a certain level (1:3), it ex-
hibited the optimal catalytic activity: the conversion of in-
dole reached 97.1%; the selectivity of 3-acylindole was
81.1%; and the yield was 93.9%.
From Table 2, we may see that both the conversion and
the selectivity of 3-acylindole increased gradually, and then
remained almost constant when the molar ratio increased to
a certain value with the increasing of the molar ratio of the
reactants. The reason might be that when the molar ratio
between indole and benzoyl chloride was small, sufficient
contact could not be obtained between the catalyst and the
reactants. At this time, the conversion and the selectivity of
3-acylindole would increase with the increasing of molar
ratio. In a heterogeneous reaction, mass-transfer limitation
might have a significant effect on the reaction rate in the
reaction system [14]. However, when the molar ratio be-
tween indole and benzoyl chloride rose to a certain value
(1:3), because of the presence of a large amount of benzoyl
chloride, the benzoyl chloride would have a solvent effect
and change the distribution of indole between catalyst sur-
face and liquid phase [27]. Thus, the conversion and selec-
tivity of 3-acylindole remained almost constant. In summary,
when MIL-53(Al) was used as catalyst for a Friedel–Crafts
acylation reaction of indole and benzoyl chloride, the opti-
mal mole ratio was 1:3.
3.2.4 Effect of different catalyst contents and solvent
Table 3 shows the effect of different catalyst contents and
solvents on the conversion, selectivity, and yield of the
Table 3 Conversion, selectivity, and yield at different catalyst contents
and solvents over MIL-53(Al) catalyst a)
Table 2 Conversion, selectivity, and yield at different molar ratios of the
reactants over MIL-53(Al) catalyst a)
Entry n1: ncatalyst
Solvent
CH2Cl2
X (%) S3 (%) Y3 (%) S4 (%) Y4 (%)
Entry
Molar ratio
1:1
X (%) S3 (%) Y3 (%) S4 (%) Y4 (%)
1
2
3
3
4
5
1:0.05
1:0.06
1:0.07
1:0.06
1:0.06
1:0.06
90.3 75.5 81.8 24.5 18.2
1
2
3
4
5
89.2
91.1
94.2
97.1
94.8
66.7
70.1
76.3
81.1
80.0
66.4
71.5
86.9
93.9
91.6
33.3
29.9
23.7
18.9
20.0
33.6
28.5
13.1
6.1
CH2Cl2
97.1 81.1 93.9 18.9
97.2 81.0 93.8 19.0
96.2 80.3 92.5 19.7
6.1
6.2
7.5
CH2Cl2
1:2
CHCl3
1:2.5
1:3
cyclohexane
89.6 79.5 86.2 20.5 13.8
nitrobenzene 84.4 73.4 74.8 26.6 25.2
1:4
9.4
a) Reaction conditions: 25 °C, indole (4 mmol), benzoyl chloride (12
mmol); reaction time 8 h.
a) Reaction conditions: n1:ncatalyst=1:0.06, 25 °C, CH2Cl2 (3 mL); reac-
tion time 8 h.

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Yan et al. Sci China Chem January (2015) Vol.58 No.1
and thus improves conversion. When nitrobenzene was used
as solvent, the conversion of indole was only 84.4% and the
selectivity of 3-acylindole sharply dropped to 73.4%. The
reason could be a possible reaction of weak nucleophilic
nitrobenzene with electrophilic benzoyl chloride [32],
which would have caused the decline in both the conversion
of indole and the selectivity of 3-acylindole. In summary,
the experimental results of Friedel-Crafts acylation of in-
dole and benzoyl chloride over MIL-53(Al) catalyst demon-
strated that the optimal solvent was dichloromethane with
the highest conversion of indole (97.1%), the highest selec-
tivity of 3-acylindole (81.1%), and the highest yield
(93.9%).
3.2.5 Effect of different substrates
The efficiency of this catalyst was studied in Friedel-Crafts
acylations of various indole derivatives with benzoyl chlo-
ride under the optimized reaction conditions. The results are
summarized in Table 4, where we may see that the reaction
conversion was higher when the indole had electron-
donating groups such as H, CH3, and OCH3. When these
groups reacted with benzoyl chloride, the respective con-
versions of indole were 97.1%, 98.4%, and 99.0. At the
same time, the electron-drawing group NO2 decreased the
conversion to 79.6%. But the differences between reactants
did not have obvious influence upon the selectivity of 3-
acylindole, which was nearly 81.0%. These results were in
accordance with the mechanism of acylation reaction that
stipulates an electron-donating group within idole improves
its nucleophilic property [33]. Conversely, a strong electro-
philic group can decrease the nucleophilic properties of in-
dole and hinder a Friedel-Crafts acylation reaction of the
indole with carbonyl-positive ions of benzoyl chloride.
When MIL-53(Al) was used as catalyst, electron-donating
groups on the indole were beneficial to the Friedel-Crafts
acylation reaction and electron-drawing groups hindered
reaction, which showed that the catalyst conformed to the
reaction mechanism of classic Friedel-Crafts acylation reac-
tion.
Figure 4 Recycling of the MIL-53(Al) catalyst in a Friedel-Crafts acyla-
tion of benzene with benzoyl chloride. Reaction conditions: 25 °C, indole
(4 mmol), benzoyl chloride (12 mmol), CH2Cl2 (3 mL); reaction time 8 h.
acylindole, the yield, and the recycle rate of the catalyst
were considered. Generally, catalyst recycling is an im-
portant issue in industry.
Figure 4 shows that after the fifth run, the conversion of
indole, the selectivity of 3-acylindole, and the yield of 3-
acylindole respectively fell to 87.6%, 79.5%, and 84.2%. In
parallel, the recycling rate of MIL-53(Al) catalyst fell from
99.1% to 87.5%. This indicated that MIL-53(Al) could be
reused without significant degradation in catalytic activity,
and shows that MIL-53(Al) catalyst has excellent chemical
stability. Additional investigations were undertaken to ana-
lyze the MIL-53(Al) catalyst deactivation in the Friedel-
Crafts acylation reaction. The catalytic activity had been
lost over repeated uses, and the recovery dropped fell below
100%. Reduction of the catalyst caused the decrease in the
conversion of indole and the selectivity of 3-acylindole.
Most importantly, MIL-53(Al) maintained high catalytic
activity after the fifth run, which shows it has stable cata-
lytic performance and great recycling ability for the Friedel-
Crafts acylation reaction of indole with benzoyl chloride.
3.3 Reaction mechanism
3.2.6 Catalyst recovery and recycling
Figure 4 shows the results of MIL-53(Al) catalyst recovery
and recycling in a Friedel-Crafts acylation over five succes-
sive runs. The conversion of indole, the selectivity of 3-
The Friedel-Crafts acylation reactions use Lewis acids as
catalysts to form organic compounds of carbon-carbon
bonds. Friedel-Crafts acylation reactions mostly use homo-
geneous catalysts such as AlCl3 [34] and ZrCl4 [31]. The
Lewis acid sites of the catalysts are catalytic-active centers,
as when AlCl3 was used as a Lewis acid catalyst for Friedel-
Crafts acylation and the Lewis acid Al3+ sites were found to
be catalytic-active centers. During the reaction, Lewis acid
catalysts first react with benzoyl chloride to form an acti-
vated complex; this transient complex then produces the
acylium ion. The nucleophilic aromatic benzene then at-
tacks the acylium ion to form the products, and the removed
hydrogen interacts with halogen to form hydrogen halide.
Table 4 Conversion, selectivity, and yield of different substrates over
MIL-53(Al) catalyst a)
Entry Substrates
R
H
X (%) S3 (%) Y3 (%) S4 (%) Y4 (%)
1
2
3
3
1a
1b
1c
1d
97.1
98.4
81.1
80.9
81.0
80.8
93.9
95.4
96.0
77.5
18.9
19.1
19.0
19.2
6.1
4.6
2-CH3
5-OCH3 99.0
6-NO2 79.6
4.0
22.5
a) Reaction conditions: 25 °C, n1:ncatalyst=1:0.06, CH2Cl2 (3 mL); reac-
tion time 8 h.

Yan et al. Sci China Chem January (2015) Vol.58 No.1
7
Table 5 Catalytic performance of different Lewis acids
Although the traditional homogeneous Lewis acid catalysts
exhibit high activity for this reaction, they suffer from dif-
ficult recovery, high usage amounts, and high economic
cost, all of which limit their applications in industry.
To solve the problem of catalyst recovery, various loaded
Lewis acid catalysts are desirable for Friedel-Crafts acyla-
tion reactions. Selvakumar et al. [8] used the Zn-triflate
molecule-loaded SBA-15 silicate to catalyze a Friedel-
Crafts acylation of naphthalene with p-toluoyl chloride.
During the reaction, the Lewis acid sites Zn2+ of the triflate
molecules were the catalytic active centers, and the hydroxyl
groups of SBA-15 structure increased the acid sites of the
catalyst. The reaction mechanism can be expressed by two
reaction steps. The first step is that toluoyl chloride interacts
with the metal triflate (Zn2+) to form an acyl cation-zinc
triflate-activated complex. This transient complex promotes
the formation of acylium ion, which is a highly active spe-
cies. In the second step, the acylium ion reacts with the nu-
cleophilic naphthalene, which gives rise to the formation of
2-acylnaphthalene and eventual regeneration of the catalyst.
However, the catalytic performances of the loaded cata-
lysts are not satisfactory. MOFs have a regular pore struc-
ture and a large specific surface area. Metal ions of some
MOFs have highly dispersed Lewis acid sites, which exhibit
excellent catalytic performance for Friedel-Crafts acylation
reactions.
b)
Lewis acids a) n1:ncatalyst T (h) c) Yield (%) d)
Ref.
[6]
TOF (h1) e)
0.07
AlCl3
Et2AlCl
ZrCl4
1:6
2
2
4
2
4
88.0
80.0
71.0
80.4
90.3
1:1.5
1:1.2
0.27
[35]
[31]
0.15
6.70
This work
This work
MIL-53(Al)
1:0.06
3.77
a) Reaction conditions: AlCl3: 25 °C, solvent CH2Cl2; Et2AlCl: 0 °C,
solvent CH2Cl2; ZrCl4: 30 °C, solvent anhyd DCE; MIL-53(Al): 25 °C,
solvent CH2Cl2; b) catalyst contents, counted on the basis of the molar ratio
with the reactant indole; c) reaction time; d) yield of isolated product; e)
turn over frequency by the amount of reactants converted per atom per
hour.
reaction. At first, the Al3+ of MIL-53(Al) participates in the
direct bonding of the benzoyl chloride (1) to form activated
complex (2), after which this unstable complex converts to
an acylium ion (3). Next, a nucleophile indole (4) attacks
the acyl ion (3) and an electrophilic substitution reaction
occurs to generate the indole intermediate (5). After the
charge transfer to the chlorine ion occurs, the HCl and
product 3-acylindole (7) is formed. The MIL-53(Al) catalyst
can be regenerated and reused for catalytic reactions.
4 Conclusions
The structure unit of MIL-53(Al) is shown in Figure 5.
Based on the characteristics of MIL-53(Al) with Lewis acid
(Al3+) catalytic active centers of uniform distribution, a
study of the Friedel-Crafts acylation reaction between in-
dole and benzoyl chloride was initiated.
Table 5 shows a comparison of catalytic performance for
the Friedel-Crafts acylation reactions of indole with benzoyl
chloride using the traditional Lewis acid catalysts AlCl3 [6],
Et2AlCl [35], ZrCl4 [31], and the MIL-53(Al) produced in
this work.
From Table 5, it can be seen that, compared with the tra-
ditional Lewis acid catalysts, the MIL-53(Al) catalyst has a
higher TOF. This shows that when MIL-53(Al) was used
for the Friedel-Crafts acylation reaction of indole with ben-
zoyl chloride, the Lewis acid (Al3+) catalytic-active centers
in MIL-53(Al) showed higher activity. The proposed reac-
tion mechanism is shown in Scheme 2. During the reaction,
the metal cations Al3+ of MIL-53(Al) are the catalytic active
centers, and ligands BDC that surround Al3+ promote the
MIL-53(Al) catalyst was synthesized by a solvothermal
method and characterized by XRD and FT-IR. The catalytic
activity of MIL-53(Al) was evaluated for a Friedel-Crafts
acylation reaction between indole and benzoyl chloride. The
results showed that the synthesized catalyst was MIL-
53(Al). The optimal reaction conditions included a 1:3 mo-
lar ratio of indole and benzoyl chloride, a 1:0.06 catalyst
content, dichloromethane as solvent, 25 °C reaction temper-
ature, and 8 h reaction time. Under these conditions, MIL-
53(Al) exhibited better catalytic activity with its highest
conversion at 97.1% as well as an 81.1% selectivity of 3-
acylindole and a 93.9% yield of 3-acylindole. Electron-don-
ating groups on the indole were beneficial to the Friedel-
Crafts acylation reaction and electron-drawing groups
Scheme 2 Proposed reaction mechanism for Friedel-Crafts acylation of
indole with benzoyl chloride.
Figure 5 Structure model of MIL-Al3+.

8
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mechanism of the classic Friedel-Crafts acylation reactions.
In addition, MIL-53(Al) could be separated from the reac-
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China (21136001, 21173018).
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