MIL-101(Fe) as an active heterogeneous solid acid catalyst for the regioselective ring opening of epoxides by indoles

Article abstract of DOI:10.1016/j.mcat.2019.110628

Ring opening of an epoxide by a nucleophile is considered as one of the viable strategies to prepare biologically active molecules using homogeneous or heterogeneous Lewis acid catalysts. Very often, the ring opening of epoxide was performed with oxygen,

Full text of DOI:10.1016/j.mcat.2019.110628

MolecularCatalysis480(xxxx)xxxx
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Molecular Catalysis
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MIL-101(Fe) as an active heterogeneous solid acid catalyst for the
regioselective ring opening of epoxides by indoles
Nagarathinam Nagarjuna, Patricia Concepcionb, Amarajothi Dhakshinamoorthya,*
a School of Chemistry, Madurai Kamaraj University, Madurai, 625 021, Tamil Nadu, India
b Instituto de Tecnologia Quimica CSIV-UPV, Universitat Politecnica de Valencia, Av. De los Naranjos s/n, 46022, Valencia, Spain
A R T I C L E I N F O
A B S T R A C T
Keywords:
Ring opening of an epoxide by a nucleophile is considered as one of the viable strategies to prepare biologically active
molecules using homogeneous or heterogeneous Lewis acid catalysts. Very often, the ring opening of epoxide was
performed with oxygen, sulfur and nitrogen based nucleophiles. Recently, metal organic frameworks (MOFs) were
identified as one of the promising solid heterogeneous catalysts for ring opening of epoxide with oxygen and nitrogen
based nucleophiles, but however, use of carbon nucleophile like indole is limited. Hence, the present work reports the
catalytic performance of MIL-101(Fe) as a highly active regioselective heterogeneous solid Lewis acid catalyst in
promoting the ring opening of styrene oxide by indole. Among the various catalysts employed for this reaction, MIL-
101(Fe) exhibited the highest catalytic activity. A series of control experiments indicated the pivotal role played by
Lewis acids within the frameworks of MIL-101(Fe) and further, the catalytic reaction was found to be heterogeneous in
nature as evidenced by leaching test. Further, MIL-101(Fe) was reused four cycles with no decay in its activity. Also,
MIL-101(Fe) exhibited wide substrate scope in providing series of heterocyclic compounds in moderate to higher yields.
A suitable mechanism was also proposed considering the present results and the knowledge from the literature.
Indole
Heterogeneous catalysis
Ring opening reaction
Metal organic frameworks
Solid acid
1. Introduction
been studied either with acidic or basic catalysts which include nano TiO2
[15], activated silica [16], SbCl3/K-10 [17], HBF4-SiO2 [18], nano MgO
Many natural products including alkaloids [1,2] consist core het-
erocyclic moieties like indole, pyrrole and imidazole moieties or their
derivatives and have been widely used as biologically active compounds
[3], pharmaceutical agents, agrochemicals [4,5] and as receptors [6,7].
Furthermore, alkylated indoles and pyrroles have also been considered as
important molecules due to their antibiotic, anticancer activities [8] and
development of functional organic materials [9]. Scheme 1 provides
some of the biologically relevant active compounds possessing indole
moiety showing multifunctional properties like protein farnesyl trans-
ferase inhibitors that exhibit anticancer properties. Considering these
interesting properties of alkylated indoles, chemists are motivated to
develop catalytic methods that can provide heterocyclic compounds
having these core moieties in high yield under mild reaction conditions.
On the other hand, epoxides are often used as versatile intermediates in
organic synthesis due to electrophilic nature of carbon which can un-
dergo ring opening reactions with series of nucleophiles to afford syn-
thetically important products [10,11].
[19], magnetic nano Fe3O4 and CuFe2O4 [20], sulfated zirconia [21],
MCM-41 [22], cucurbituril [23], RuCl3.nH2O [24], Bi(OTf)3 [25], InBr3
[26], and Cr-salen complexes [27], organocatalysts [28] and high-pressure
conditions [29]. Although the ring opening reaction of epoxides with in-
doles was studied with wide range of catalysts, these methods show some
drawbacks like long reaction time, low yield, formation of polymerized
products, need of toxic solvents and expensive nature of catalysts. Ac-
cording to green chemistry principles and regulations, environmental and
economic considerations have recently created strong interests in re-
designing catalysts processes to eliminate or minimize the use of harmful
substances and the generation of hazardous waste by-products. In this
aspect, the development of heterogeneous catalytic processes is more ad-
vantageous compared to their homogeneous counterparts in the produc-
tion of fine chemicals due to their ease of handling, simple workup pro-
cedures and most importantly their ability to reuse in many cycles [30].
MOFs are porous crystalline materials whose framework is assembled
between the coordination of metal ions and polytopic organic linkers
leading to one, two and three dimensional networks [31,32] with ul-
trahigh porosity and surface areas extending up to 5000 m2/g [33,34].
These unique and remarkable features of MOFs have been reflected in
Besides the use of enzymes and hydrogen bond catalysts for the ring
opening of epoxides to biologically important monomers [12–14], ring
opening reaction of epoxides with nitrogen/oxygen nucleophiles has also
⁎ Corresponding author.
E-mail address: admguru@gmail.com (A. Dhakshinamoorthy).
https://doi.org/10.1016/j.mcat.2019.110628
Received 7 August 2019; Received in revised form 10 September 2019; Accepted 12 September 2019
2468-8231/©2019ElsevierB.V.Allrightsreserved.
Pleasecitethisarticleas:NagarathinamNagarjun,PatriciaConcepcionandAmarajothiDhakshinamoorthy,MolecularCatalysis,
https://doi.org/10.1016/j.mcat.2019.110628

N. Nagarjun, et al.
MolecularCatalysis480(xxxx)xxxx
Scheme 1. Structure of selected indole containing biologically active compounds.
various fields like heterogeneous catalysis [35–38], gas separation [39],
gas storage [40], drug release [41], chemical sensing [42], proton con-
duction [43] and others. Although MOFs have been employed as het-
erogeneous catalysts for the ring opening of epoxides, most of these
MOFs were employed as catalysts with alcohols [44–50] and amines
[51,52] as nucleophiles while the ring opening of epoxide by carbon
nucleophile using MOF as catalysts is rarely explored [53,54].
applying the BET model to the nitrogen adsorption data. Gas chroma-
tography was employed to determine conversion and selectivity with
Agilent 7820 A model using nitrogen as carrier gas. Also, GC–MS was
used to confirm the products using 5890 B instrument. IR spectra of
adsorbed CO were recorded at low temperature (-176 °C) with a Nexus
8700 FT-IR spectrometer using a DTGS detector and acquiring at 4 cm−1
resolution. An IR cell allowing in situ treatments in controlled atmo-
spheres and temperatures from -176 °C to 500 °C has been connected to a
vacuum system with gas dosing facility. For IR studies the samples were
pressed into self-supported wafers and treated at 150 °C in vacuum (10−5
mbar) for 1.5 h. After activation the samples were cooled down to -176 °C
under dynamic vacuum conditions followed by CO dosing at increasing
pressure (0.05–4 mbar). IR spectra were recorded after each dosage.
Discovery of MIL-100 or MIL-101 (MIL: Materials Institute
Lavoisier) families of MOFs by Ferey and coworkers is one of the major
breakthroughs in MOF chemistry due to their high stability [55]. In
brief, the crystal structure of MIL-101(Fe) was constructed by the co-
ordination of inorganic trimeric iron building units connected with 1,4-
benzenedicarboxylate (BDC) linkers leading to porous three-dimen-
sional network with microporous channels (1.2 and 1.45 nm) and two
different mesoporous cages of ca. 2.9 nm and 3.4 nm. Although MIL-
101(Fe) [56–59] and MIL-based catalysts [60–62] have been employed
as heterogeneous catalysts for broad range of organic reactions but no
effort has been made to prepare alkylindoles.
2.3. Synthesis of MIL-101(Fe)
MIL-101(Fe) solids were prepared by following an earlier procedure
reported in the literature [63,64]. Briefly, FeCl3.6H2O (0.675 g, 2.5 mmol)
and BDC (0.206 g, 1.25 mmol) were dissolved in DMF (15 mL) under
vigorous stirring to obtain a clear solution. Then, the resulting solution
was transferred into a Teflon-lined stainless-steel autoclave and heated at
120 °C for 24 h. After this time, the system was cooled to room tempera-
ture and the resulting precipitate was filtered and washed several times
with DMF (3 × 30 mL) and methanol (3 × 30 mL) to remove unreacted
organic species trapped within the pores and finally dried at 80 °C for 8 h.
Hence, the present work reports the synthesis of MIL-101(Fe) and
investigate its catalytic activity as solid Lewis acid catalyst for the ring
opening of epoxides using indoles as the carbon nucleophiles under
solvent-free conditions. Further, some of the objectives of this work are
to develop environmentally benign, robust catalyst for ring opening of
epoxide by carbon nucleophiles to obtain broad range of heterocycles, to
study catalyst stability by reusability, leaching tests and the feasibility of
this method to other substrates. This catalyst offers a direct method to
achieve biologically relevant products in high yields and it can also be
considered as a probe reaction to test solid Lewis acidity of a catalyst.
2.4. Synthesis of MIL-101(Cr)
MIL-101(Cr) was also prepared by adopting an earlier procedure de-
scribed in the literature [63]. Initially, Cr(NO3)3·9H2O (0.4 g, 1 mmol) and
BDC (0.25 g, 1.5 mmol) were added to a Teflon-lined autoclave containing
8 mL of demineralized water and 10 μL of HF. Then, the autoclave was
heated at 200 °C for 8 h. After this time, the system was cooled to room
temperature, the resulting precipitate was washed with DMF (3 × 30 mL)
and methanol (3 × 30 mL) and finally dried at 80 °C for 8 h.
2. Experimental procedure
2.1. Materials
Cu3(BTC)2 and Fe(BTC) are commercially known as Basolite C300 and
Basolite F300 MOFs, respectively, were purchased from Sigma Aldrich.
Similarly, FeCl3.6H2O, Cr(NO3)3.9H2O, Co(NO3)2.6H2O, Zn(NO3)2.6H2O,
terephthalic acid, 2-methylimidazole, indole derivatives, imidazole, ben-
zimidazole, pyrrole and styrene oxide were purchased from Sigma Aldrich
and used as received. Solvents were also received from Sigma Aldrich and
used as received without any further purification.
2.5. Synthesis of Co-ZIF-67
ZIF-67 was synthesized according to a slightly modified literature
procedure [65]. In brief, cobalt nitrate hexahydrate (2.910 g, 10 mmol)
was dissolved in methanol (50 mL) followed by the addition of a solu-
tion of 2-methylimidazole (3.284 g, 40 mmol) in methanol (50 mL).
This mixture was stirred at room temperature for 1 h and then kept for
24 h at room temperature. The resulting purple precipitate was col-
lected by centrifugation, washed with methanol for three times
(3 × 30 mL) and finally dried under vacuum at 80 °C for 8 h.
2.2. Instrumentation
Powder XRD diffraction patterns for these samples were measured
using Philips X’Pert diffractometer with the CuKα radiation
(λ = 1.5417 Å) in the refraction mode. FT-IR spectra were recorded in
the region of 400-4000 cm−1 with 2 cm−1 resolution with a Bruker
tensor 27 series FT-IR spectrometer. SEM images were collected from
Hitachi S-3000H scanning electron microscope. Nitrogen adsorption
isotherms were measured at 77 K on a Micromeritics ASAP 2000 volu-
metric adsorption analyser. The samples were degassed at 423 K for 2 h
prior to the measurements. The specific surface area was calculated by
2.6. Synthesis of Zn-ZIF-8
A solution of zinc nitrate hexahydrate (2.970 g, 10 mmol) dissolved
in 50 mL of methanol and a solution of 2-methylimidazole (3.284 g,
40 mmol) in methanol (50 mL) was mixed. Later, this solution was
2

N. Nagarjun, et al.
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stirred at room temperature for 1 h and then kept for 24 h at room
temperature. The resulting white precipitate was collected by cen-
trifugation, washed with methanol for three times (3 × 30 mL) and fi-
nally dried under vacuum at 80 °C for 8 h.
(0.25 mmol), styrene oxide (0.3 mmol). To this mixture, 1 mL of solvent
was added and then this reaction mixture was placed on a preheated oil
bath maintained at 60 °C. This heterogeneous mixture was stirred for the
required time as shown in Table 1. A known aliquot of sample was
periodically taken from the reaction mixture, diluted with acetonitrile
and filtered with a syringe filter. This aliquot was analyzed by gas
chromatography to determine conversion and selectivity using internal
standard. After the required time, the reaction was stopped and the re-
action flask was allowed to cool to room temperature. Later, the mixture
was diluted with acetonitrile and filtered. This sample was analyzed by
gas chromatography to determine the final conversion and selectivity as
mentioned above. The products were confirmed by GC–MS and 1H-NMR
analyses. A similar procedure was followed without the addition of 1 mL
solvent for reactions under solvent-free conditions.
2.7. General procedure for the ring opening of styrene oxide by indole with
and without solvent
In a typical catalytic ring opening reaction, the reaction flask was
charged with 15 mg of catalyst followed by the addition of indole
Reusability experiments were performed identically as shown above
except the use of recovered catalyst obtained by filtration after the
reaction, washed three times with fresh acetonitrile (3 mL) and dried at
100 °C for 3 h.
3. Results and discussion
MIL-101(Fe) was synthesized [63] and characterized by powder
XRD, FT-IR, BET surface area and SEM analysis to reveal the formation
of porous MOFs and to understand its morphology. Fig. 1 shows the
powder XRD pattern of MIL-101(Fe), the crystalline nature and the
peak positions coincide with the previously reported diffraction pat-
terns [64,66,67], thus confirming the existence of MIL-101(Fe). FT-IR
of MIL-101(Fe) is shown in Figure S7 and it agrees with the earlier
report [68]. The specific BET surface area and porosity of MIL-101(Fe)
[63] was measured by gas adsorption-desorption experiments and the
results are presented in Fig. 2. The BET surface area and pore volume of
MIL-101(Fe) were 2293 m2/g and 1.12 cm3/g, respectively. The pore
size of MIL-101 mainly ranges between 8.1–25 Ǻ and the as-synthesized
Fig. 1. Powder XRD of (a) fresh and (b) four times reused MIL-101(Fe).
sample pore size was 22 Ǻ. This value is in agreement with the reported
data of MIL-101(Fe). Furthermore, SEM images were measured to re-
veal the morphology of MIL-101(Fe) sample and exhibit an octahedral
shape (Fig. 3) [67,69]. In a similar way, the synthesis of MIL-101(Cr)
was confirmed by characterizing with powder XRD [70], FT-IR [68]
techniques (Figures S1, S2) and the observed results are in agreement
with the previous studies. Also, structural and morphological studies of
Co-ZIF-67 and Zn-ZIF-8 were also confirmed by powder XRD, SEM
(Figures S3, S4, S5 and S6) [71]. In particular, powder XRD clearly
indicated the characteristic diffraction patterns of ZIF-67 and ZIF-8.
Furthermore, SEM analysis revealed that the particles are like micro-
crystals with polyhedral shape.
Fig. 2. N2 absorption-desorption isotherms of MIL-101(Fe).
Fig. 3. SEM images of (a) before and (b) four times reused MIL-101(Fe).
3

N. Nagarjun, et al.
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After ascertaining the structural formation of MIL-101(Fe), the
studies were performed to evaluate the catalytic performance of MIL-
101(Fe) in the ring opening reaction by choosing styrene oxide and
indole as starting materials. Further, the activity of MIL-101(Fe) was
also compared with other analogous MOF catalysts namely, MIL-
101(Cr), Fe(BTC), Cu3(BTC)2, Co-ZIF-67 and Zn-ZIF-8 under identical
conditions. A blank control experiment in the absence of catalyst under
solvent free conditions afforded 3% yield at 60 °C. The catalytic per-
formance of MIL-101(Fe) was tested in various solvents at 60 °C and the
results are shown in Table 1. The yield of the desired product was 18,
17, 81 and 71% in toluene, acetonitrile, chloroform and dichloroethane
as solvents, respectively. In contrast, the activity of MIL-101(Fe) was
negligible in DMF while 9% yield was observed at 60 °C in ethanol
under identical conditions. The negligible activity of MIL-101(Fe) in
DMF may be due to its ability to coordinate with the Lewis acid sites in
MIL-101(Fe) and in fact, removal of DMF by thermal activation affords
higher activity in many Lewis acid MOFs catalyzed reactions [72]. On
the other hand, the lower activity of MIL-101(Fe) in ethanol is due to
competitive reactivity between carbon and oxygen nucleophiles,
namely indole and ethanol, respectively. Further, blank control ex-
periments in the absence of catalyst in these solvents showed no pro-
duct formation and these data are given in Table 1. Considering low to
moderate activity of MIL-101(Fe) in the ring opening of styrene oxide
by indole in various solvents, an attempt was made to increase the yield
of the desired product by performing the same reaction under solvent-
free conditions. Interestingly, the ring opening of styrene oxide by
indole using MIL-101(Fe) exhibited 46% yield under solvent-free con-
ditions at 40 °C while the yield gradually enhanced to 74% at 50 °C and
to 92% at 60 °C under identical conditions.
Fig. 4 shows the effect of temperature in the ring opening of styrene
oxide by indole using MIL-101(Fe) as a heterogeneous catalyst. The
yield of the product increases as a function of time at all temperatures
up to 12 h and no further increase in the yield is noticed in all cases.
This may be due to inability of reactants to reach the active site due to
steric hindrance imposed by high population of products. The recovered
MIL-101(Fe) catalyst after the reaction indicated no noticeable differ-
ences in the crystallinity, structural morphology and stretching fre-
quency than that of fresh solid by powder XRD, SEM and FT-IR re-
spectively. These results confirm that the physical, mechanical and
chemical state of MIL-101(Fe) is retained during the course of the re-
action. Further, iron content between the fresh and the recovered MIL-
101(Fe) after the reaction remains unchanged.
The activity of MIL-101(Fe) was significantly decreased to 48%
yield upon lowering the catalyst loading from 15 to 5 mg under iden-
tical conditions while the increase of catalyst from 15 to 25 mg showed
almost similar yield of the product (entries 10 and 12, Table 1), thus
suggesting the optimum loading of the catalyst as 15 mg. In all cases, no
significant increase in the yield was observed after 12 h. Fig. 5 shows
the effect of catalyst loading on the formation of the desired product in
the ring opening of styrene oxide by indole.
MIL-101(Cr) was demonstrated as a solid Lewis acid catalyst mainly
Table 1
Optimization of reaction conditions for the ring opening of styrene oxide by
indole under various reaction conditions.a
Entry
Catalyst
T
Solvent
Yieldb
(%)
(oC)
1
–
60
60
60
60
60
60
60
40
50
60
60
60
60
60
60
60
60
60
60
60
–
3
2
MIL-101(Fe)
MIL-101(Fe)
MIL-101(Fe)
MIL-101(Fe)
MIL-101(Fe)
MIL-101(Fe)
MIL-101(Fe)
MIL-101(Fe)
MIL-101(Fe)
MIL-101(Fe)
MIL-101(Fe)
MIL-101(Fe)
MIL-101(Fe)
MIL-101(Fe)
MIL-101(Cr)
Fe(BTC)
Toluene
18 (0)
17 (0)
81 (0)
71 (1)
0 (0)
9 (0)
46
3
ACN
4
CHCl3
Fig. 4. The ring opening of styrene oxide by indole using MIL-101(Fe) as a solid
5
DCE
catalyst at (a) 40, (b) 50 and (c) 60 °C.
6
DMF
7
Ethanol
8
–
–
–
–
–
–
–
–
–
–
–
–
–
9
74
10
11c
12d
13e
14f
15g
16h
17h
18h
19h
20h
92
48
91
65
85
–
76
40
Cu3(BTC)2
Co-ZIF-67
33
14
Zn-ZIF-8
4
a
Reactions conditions: indole (0.25 mmol), styrene oxide (0.3 mmol),
catalyst (15 mg), solvent (1 mL), 60 °C, 12 h.
b
Yield was determined by GC. Values in parentheses indicate the yield ob-
tained in the absence of catalyst.
c
d
e
f
g
h
MIL-101(Fe) (5 mg).
MIL-101(Fe) (25 mg).
indole (1 mmol), styrene oxide (1 mmol), catalyst (15 mg), neat, 60 °C, 12 h.
Fig. 5. Time conversion plot for the ring opening of styrene oxide by indole
using (a) 5 (black line), (b) 15 (red line) and (c) 25 mg (blue line) (For inter-
pretation of the references to colour in this figure legend, the reader is referred
to the web version of this article).
after fourth reuse.
in presence of pyridine (0.25 mmol).
15 mg of catalyst.
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due to the existence of coordinately unsaturated position around Cr3+
within the crystal structure [73–75]. In this context, the catalytic ac-
tivity of MIL-101(Cr) was also studied in the ring opening of styrene
oxide by indole under solvent-free conditions at 60 °C and observing
76% yield. This activity data of MIL-101(Cr) was comparatively lower
than with MIL-101(Fe). Under identical conditions, Fe(BTC) resulted
40% yield which is two-fold decrease in the activity of MIL-101(Fe).
This lower activity of Fe(BTC) may be explained due to its lower surface
area (860 m2/g) and pore volume (0.462 cm3/g) compared to MIL-
101(Fe). Further, Cu3(BTC)2 solid gave 33% yield under identical
conditions. In contrast, the activity of Co-ZIF-67 and Zn-ZIF-8 was
significantly low under identical reactions conditions (Fig. 6). The ac-
tivity was not enhanced further for all these catalysts after 12 h.
A control experiment was performed with pyridine as a catalyst
poison to provide some insights on the nature of active sites in MIL-
101(Fe). Interestingly, the ring opening of styrene oxide by indole using
MIL-101(Fe) as catalyst afforded no product in the presence of pyridine.
This result indicates that pyridine is acting as a catalyst poison by
strongly coordinating with the Lewis acid site, namely Fe3+ and in-
hibiting the interaction of styrene oxide. In another experiment, the
ring opening of styrene oxide by indole was performed with Fe
(NO3)3.9H2O as homogeneous catalyst with similar iron loading and
observed 50% yield. This result further confirms the active participa-
tion of Fe3+ as Lewis acid sites as active sites to promote this reaction.
Hot-filtration or leaching test is one of the ways to ascertain the
stability of heterogeneous catalysts. The ring opening of styrene oxide
by indole was started with MIL-101(Fe) in chloroform as shown in
Table 1 and the solid was removed by filtration under the reaction
temperature after 15 min. Then, the resulting reaction mixture without
MIL-101(Fe) was continued for the remaining time (12 h). The catalytic
performance was significantly inhibited upon removal of MIL-101(Fe)
(Fig. 7). These data clearly infer the absence of Fe3+ in the solution thus
emphasizing the leaching of iron and high stability of MIL-101(Fe)
under the present experimental conditions. Furthermore, the iron
content of the fresh and the recovered MIL-101(Fe) was analyzed by
ICP-OES and confirmed the absence of Fe leaching.
Fig. 7. Time versus yield plot for the ring opening of styrene oxide by indole (a)
in the presence of MIL-101(Fe) and (b) upon filtration of MIL-101(Fe) solid after
15 min and the reaction mixture stirred without catalyst under identical con-
ditions. Reaction conditions: indole (0.25 mmol), styrene oxide (0.3 mmol),
MIL-101(Fe) (15 mg), CHCl3 (1 mL), 60 °C.
Reusability experiments are performed in heterogeneous catalysis to
ascertain the stability of solid catalyst under the optimized reaction
conditions. In this context, MIL-101(Fe) was separated from the reac-
tion mixture and repeatedly washed with acetonitrile, dried at 100 °C.
The recovered solid was reused four cycles with a minimal decrease in
the yield (Fig. 8). These data clearly proved that MIL-101(Fe) is a robust
solid catalyst which can promote ring opening of styrene oxide by in-
dole without a significant drop in its activity. Furthermore, four times
reused MIL-101(Fe) was characterized by powder XRD, FT-IR and SEM
Fig. 8. Reusability data for the ring opening of styrene oxide with indole using
MIL-101(Fe) as a heterogeneous solid catalyst.
techniques. The identical structural integrity between the fresh and four
times reused MIL-101(Fe) in powder XRD indicated that the crystalline
nature is retained during the consecutive reuses (Fig. 1). Similarly, no
significant differences in the stretching frequencies by FT-IR spectra
were seen between the fresh and four times reused MIL-101(Fe) (Figure
S7), thus indicating the absence of metal linker cleavage. On the other
hand, SEM images of the fresh and four times reused MIL-101(Fe)
showed almost similar morphology with clear octahedral crystals
(Fig. 3). All these characterization results of the reused solid confirm
that the structural integrity and morphology of MIL-101(Fe) is pre-
served during the repeated uses.
These encouraging catalytic results and high stability of MIL-
101(Fe) prompted us to screen the scope of this solid with other deri-
vatives. The observed catalytic data are given in Table 2. The ring
opening of styrene oxide with N-methylindole in the presence of MIL-
101(Fe) exhibited 87% yield after 12 h at 60 °C. Similarly, the reaction
of 2-methylindole with styrene oxide also afforded 90% yield under
identical conditions. Further, the ring opening reaction of styrene oxide
by 5-methoxyindole with MIL-101(Fe) exhibited 86% yield. Interest-
ingly, a bulky substrate like 5-bromoindole and styrene oxide afforded
88% yield. These results clearly suggest that the reaction occurs within
the pores of MIL-101(Fe) due to its higher surface area and pore volume
compared to Fe(BTC). Although the reaction of 5-chloroindole and
Fig. 6. Time versus yield plot for the ring opening of styrene oxide by indole
using (a) Zn-ZIF-8 (b) Co-ZIF-67 (c) Cu3(BTC)2 (d) Fe(BTC) (e) MIL-101(Cr) and
(f) MIL-101(Fe) as heterogeneous solid catalysts.
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Table 2
Ring opening of styrene oxide with different nucleophiles using MIL-101(Fe) as a heterogeneous
solid Lewis acid catalyst.a
aReaction conditions: Nucleophile (0.25 mmol), electrophile (0.3 mmol), MIL-101(Fe) (15 mg),
60 °C, 12 h.
bYield was determined by GC.
6

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styrene oxide resulted in 89% yield, but however, the ring opening
reaction between 5-nitroindole and styrene oxide did not provide any
product under identical conditions. The ring opening of styrene oxide
was also efficient with other heterocyclic nucleophiles like pyrrole,
imidazole and benzimidazole showing 74, 81 and 68% yields, respec-
tively under identical conditions. Moderate yields with these carbon
nucleophiles may be due to electronic influences of the heteratoms in
these heterocycles, but, however, further studies are required to con-
firm this hypothesis.
the activated MIL-101(Fe) sample at 150 °C. IR spectra of CO adsorption
at −176 °C (Fig. 9) over activated MIL-101(Fe) show the presence of IR
bands at 2179 and 2166 cm−1 associated to Lewis acid sites arising
from Fe3+ and Fe2+ sites, respectively [76,77] in addition to a band at
2134 cm−1 due to physisorbed CO. Further, the presence of Fe2+ in the
IR spectra is believed due to the partial reduction of Fe3+ to Fe2+ site
upon adsorption of CO [78].
4. Conclusions
Considering the results observed in the present work and previous
reports, a suitable reaction mechanism is proposed for the ring opening
of styrene oxide by indole using MIL-101(Fe) as catalyst as shown in
Scheme 2. Styrene oxide interacts with the coordinatively unsaturated
sites available in MIL-101(Fe) catalyst through oxygen, thus making
electron deficient carbon centers [44,53]. Subsequently, carbon nu-
cleophile attacks styrene oxide to a carbon with more electron defi-
ciency to give the desired product.
In the present work, MIL-101(Fe) was shown to be an efficient
heterogeneous solid Lewis acid catalyst among other analogous cata-
lysts like MIL-101(Cr), Fe(BTC), Cu3(BTC)2, ZIF-8 and ZIF-67 in the ring
opening of styrene oxide by indole with very high yield and regios-
electivity under mild reaction conditions. The high activity of MIL-
101(Fe) compared to other solids was due to the high population of
Lewis acid sites, high surface area and pore volume than other catalysts.
Further, leaching test indicated the heterogeneity of the reaction and
MIL-101(Fe) was reused four cycles without any significant loss in its
activity. In addition, four times reused MIL-101(Fe) was characterized
by powder XRD, FT-IR, SEM analyses and observing that the structural
integrity and morphology of the reused sample are almost identical in
respect to fresh solid. Also, MIL-101(Fe) exhibited wide substrate scope
by showing high product yields and regioselectivity in the ring opening
of styrene oxides with other indole derivatives.
Acknowledgements
AD thanks the University Grants Commission, New Delhi, for the
award of an Assistant Professorship under its Faculty Recharge
Programme. AD also thanks the Department of Science and Technology,
India, for the financial support through Extra Mural Research Funding
(EMR/2016/006500).
Appendix A. Supplementary data
Supplementary material related to this article can be found, in the
online version, at doi:https://doi.org/10.1016/j.mcat.2019.110628.
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