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Cite this: RSC Adv., 2016, 6, 29182

The UiO-66-SO3H metalorganic framework as

a green catalyst for the facile synthesis of dihydro2-oxypyrrole derivatives
Ramin Ghorbani-Vaghei,*a Davood Azarifar,a Saba Dalirana and Ali Reza Oveisib

Received 7th January 2016

Accepted 14th March 2016

The multicomponent domino reaction synthesis of dihydro-2-oxopyrroles has been performed using the

DOI: 10.1039/c6ra00463f

acid catalyst. The MOF can act as both Brnsted (H+) and Lewis acid (Zr4+) active sites. The protocol

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presents an environmentally benign as well as a simple experimental and work-up procedure.

sulfonated metalorganic framework, UiO-66-SO3H (UiO is the University of Oslo), as a highly ecient

Introduction
Multicomponent reactions (MCRs) are dened as convergent
reactions, in which more than two starting materials react
together in a single reaction vessel to form a product, displaying
the features of all or most the atoms in a newly formed product.1
MCRs can provide easy and fast access to large libraries of
chemical compounds with diverse substitutions in comparison
to similar multistep syntheses. Synthesis of dihydro-2oxypyrroles (DPO) is classied as a four-component reaction.
These heterocyclic structures have been attracted because of
a wide range of biological activities such as herbicidal,2a antiHIV,2b inhibitor,2c and antibacterial2d activities. PI-091 (ref. 2c)

Biologically active compounds with the dihydro-2-oxopyrrole structure.

Scheme 1

Faculty of Chemistry, Bu-Ali Sina University, Hamedan, Iran. E-mail: rgvaghei@

yahoo.com; Fax: +98 8138380709; Tel: +98 9183122123

Department of Chemistry, Faculty of Science, University of Zabol, Zabol, Iran

Electronic supplementary
10.1039/c6ra00463f

information

29182 | RSC Adv., 2016, 6, 2918229189

(ESI)

available.

See

DOI:

and thiomarinol B,2d are two examples from the mentioned

structures as shown in Scheme 1.
In the past few years, several catalysts have been used for the
synthesis of dihydro-2-oxopyrrole (DPO) derivatives such as I2,3a
p-toluenesulfonic acid,3b AcOH,3c Cu(OAc)2$2H2O/salicylic
acid,3d and BF3/nano-sawdust.3e These procedures have certain
limitations such as undesirable impacts on the environment,
sequence of the reagents addition, long reaction time, toxic
reaction media, and the lack of recovery and/or reusability of
catalyst. Therefore, in view of sustainable chemistry, the
development of versatile approaches to the synthesis of
dihydro-2-oxopyrrolesis still in demand.
Metalorganic frameworks (MOFs) as a new class of porous
crystalline materials, a class of so porous materials, have been
addressed rapidly because of their potential in areas such as
catalysis,4 sensing,5 gas and chemical storage,6 separation,7
conductivity,8 light harvesting,9 and drug delivery.10 They are
consist of polytopic organic struts coordinated to metal ions or
clusters.10d,11 The advantages of MOFs such as porosity and
extraordinary surface area have received considerable attention
from chemists, because of enhancement of catalytic activity, in
consistent of increasing accessible active sites, and creating
micro-reactor that decrease distribution of pathways, resulting
in high yield of product. Zr-carboxylate MOFs have been
demonstrated to be among the most stable MOFs.12 Towards
acid MOFs,13 UiO-66-SO3H14 can serve as both a Brnsted15 and
Lewis acid (since it is isostructural with UiO-66)12 catalyst. UiO66-SO3H [Zr6O4(OH)4(HSO3BDC)6x(BDC)6
6x, (BDC benzene1,4-dicarboxylate) (x 0.18)] is a 3D porous MOF that is constructed of 12 carboxylates of terephthalate ligands linked to 12coordinateZr6O4(OH)4 nodes. This Zr6-octahedron consist
triangular faces connected with m3O and m3OH ligands originated from water present during the MOF synthesis (Scheme 2).
Very recently, the sulfonated MOF has been used as a solid
catalyst for conversion of fructose into 5-hydroxymethylfurfural,15
albeit by dierent the MOF synthetic procedure, and Friedel
Cras acylation of p-xylene.16 However, application of MOFs as

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Paper

Scheme 2

RSC Advances

Proposed structure of UiO-66-SO3H.

catalysts in chemical reactions especially multicomponent reactions,17 is highly required.

Hence, in continuation of our research on the synthesis of
heterocyclic compounds,18 and catalysis by porous material,4a,19
we encouraged to use the catalytic potential of UiO-66-SO3H
MOF, which can act as both a Brnsted and Lewis acid active
catalyst, for the synthesis of dihydro-2-oxypyrrole derivatives.

N) were performed by Quantitative Technologies (Intertek),

Whitehouse, NJ. NMR spectra were recorded on 250 MHz, 300
MHz, and 400 MHz using CDCl3 as solvent and tetramethylsilane as the internal standard. Fourier-transformed infrared
(FTIR) spectroscopy spectra were recorded using a Perkin Elmer
Spectrum-FTIR Version 10.01.00. Melting points were determined on a Stuart Scientic SMP3 apparatus and are uncorrected. UiO-SO3H was prepared based on the literature.14

Experimental
Materials and instrumentation

General procedure for the synthesis of dihydro-2-oxopyrroles

All reagents were purchased from Sigma-Aldrich and used

without further purication. Powder X-ray diraction (PXRD)
patterns were recorded on a Rigaku XDS 2000 diractometer
over a range
using nickel-ltered Cu Ka radiation (l 1.5418 A)
of 5 < 2q < 50 . Samples for scanning electron microscopy
(SEM) were sputtered with a layer of Os (5 nm thickness) prior to
taking images on a Hitachi S-4800 SEM. Mass spectra (MS) were
recorded on an Agilent Technologies (HP), MS model:
5973Network Mass Selective Detector, ion source: electron
impact (EI) 70 eV, program rate: 70  C min
1, nal temperature:
350  C, and analyzer: quadrupole. Elemental analyses (C, H, and

To a mixture of dimethyl acetylenedicarboxylate (1 mmol),

amine (2 mmol), and aldehyde (1 mmol) in acetonitrile (5 ml),
UiO-66-SO3H (12 mg, equivalent to 0.74 mol% H+ and 4.11
mol% Zr), was added and stirred at room temperature. Aer
completion of the reaction (monitored by TLC), the UiO-66SO3H separated by centrifugation and washed with acetone and
chloroform. The remaining solution was evaporated to dryness
under reduced pressure to give crude product. The desired
product was obtained aer recrystallization from ethanol. The
products were characterized by comparing their physical and
spectral (IR, NMR) data with those of known samples or by their

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Table 1

Paper

Synthesis of dihydro-2-oxopyrrole (1a) in the presence of dierent catalystsa

Entry

Catalyst (mg)

1
2
3
4
5
6
7

UiO-66-SO3H
UiO-66-SO3H
UiO-66-SO3H
UiO-66-SO3H
UiO-66-SO3H
UiO-66 (10)
ZrCl4 (10)

(5)
(8)
(10)
(12)
(15)

Time (h)

Yieldb (%)

12
8
6
3
3
18
18

40
55
75
85
84
26
32

Reaction conditions: dimethyl acetylenedicarboxylate (1 mmol), 4-chloroaniline (2 mmol), formaldehyde 37% (1 mmol), acetonitrile (5 ml) and
catalyst at room temperature. 12 mg of UiO-SO3H is equivalent to 0.74 mol% H+ and 4.11 mol% Zr. b Separated yields.

physical, spectral (IR, NMR, and Mass spectrometry) and

elemental analysis data as shown in ESI.

Results and discussion

At the outset, we optimized the reaction conditions of the
synthesis of dihydro-2-oxopyrrole 1a via reaction of 4-chloroaniline with formaldehyde, and dimethyl acetylenedicarboxylate
(DMAD) at room temperature, as a model reaction, in the presence of dierent catalysts such as UiO-66-SO3H, UiO-66, and

Table 2

ZrCl4 (Table 1). UiO-66-SO3H gave higher yield and shorter

reaction time than the other catalysts, increasing the activity
because of the incorporation of Brnsted acid sites in addition to
Lewis acid zirconium sites (Table 1, entries 15). The amount of
UiO-66-SO3H was optimized to be 12 mg (equivalent to 0.74
mol% H+ and 4.11 mol% Zr) since the dihydro-2-oxopyrrole was
produced in the highest yield and shortest reaction time as
compared with the other ones (Table 1, entry 4). As expected,
decreasing the catalyst loading to 5 mg led to a signicant falling
o in the reaction rate, 40% yield aer 12 h (entry 1). ZrCl4 and

Synthesis of dihydro-2-oxopyrrole (1a) in the presence of dierent conditionsa

Entry

Solvent

Condition

Time (h)

Yieldb (%)

1
2
3
4
5
6
7
8

Ethanol
Ethanol
Ethanol
Methanol
Acetonitrile
Dichloromethane
Solvent-free
Solvent-free

r.t.
50  C
Reux
r.t.
r.t.
r.t.
r.t.
50  C

20
20
20
20
3
7
20
20

Trace
30
30
85
69

Reaction conditions: dimethyl acetylenedicarboxylate (1 mmol), 4-chloroaniline (2 mmol), formaldehyde 37% (1 mmol), solvent (5 ml) and
dierent conditions. b Separated yield.

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Table 3

RSC Advances
Synthesis of dihydro-2-oxopyrroles using UiO-66-SO3H as a heterogeneous catalysta

Time (h)/TOFb (h
1)

Yieldc (%)

4-ClC6H4

3/11.33

85, 82,d 81e

4-MeC6H4

3.5/9.36

82

4-OMeC6H4

3.5/8.91

78

4-BrC6H4

4.5/6.75

76

C6H4

3/10.67

80

C6H5

4-MeC6H4

3.5/9.37

82

C6H5

4-ClC6H4

3.5/9.25

81

C6H5

4-MeOC6H4

5/5.84

73

Entry

R1

R2

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Product

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Table 3

Paper

(Contd. )

Time (h)/TOFb (h
1)

Yieldc (%)

C6H4

4.5/7.11

80

4-MeC6H4

C6H4

4/8.2

82

4-ClC6H4

C6H4

3.5/9.14

80

Entry

R1

R2

C6H5

10

11

Product

a
Reaction conditions: dimethyl acetylenedicarboxylate (1 mmol), substituted aniline (2 mmol), aldehyde (1 mmol), UiO-66-SO3H (12 mg, equivalent
to 0.74 mol% H+ and 4.11 mol% Zr) and acetonitrile (5 ml) at room temperature. b TOF (turnover frequency) TON per time (h); TON yield/
catalyst (mol%). c Yields refer to the isolated pure products. d Reusability of catalyst in the second run. e Reusability of catalyst in the third run.

UiO-66 (include open zirconium sites) as Lewis acid catalysts,

showed lower activity for the reaction than that UiO-66-SO3H
(entries 6 and 7). These experiments conrmed that the reaction
could proceed by both Brnsted and Lewis acid sites.
Investigation of the eect of solvent (ethanol, methanol,
acetonitrile, and dichloromethane) and solvent-free condition
showed that acetonitrile was found to be the most suitable
reaction medium, aording the highest yield (85%) of the
product with less time-consuming than that solvent and
solvent-free ones (Table 2, entry 5). In case of ethanol and
methanol as solvent, dimethyl 2-((4-chlorophenyl)amino)maleate was the main product (Table 2, entries 14, Fig. S1, ESI). In
solvent-free condition, a complex mixture was obtained in
addition to dimethyl 2-((4-chlorophenyl)amino)maleate (entries
7 and 8).
Then, the optimal reaction condition was explored for the
synthesis of dihydro-2-oxopyrrole derivatives. Accordingly, the
dihydro-2-oxopyrroles were obtained in high yield, showing
high versatility of this procedure for both bearing electronwithdrawing and electron-donating groups (Table 3).

29186 | RSC Adv., 2016, 6, 2918229189

Fig. 1 PXRD patterns of UiO-66-SO3H before (bottom, red) and after

using (top, blue).

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The catalytic activity and reusability of the MOF were tested

up to three consecutive cycles for the synthesis of dihydro-2oxopyrrole (1a) (Table 3, entry 1) (aer the completion of the
reaction, the catalyst was separated by centrifugation, washed
with acetone, and chloroform, dried, and reused for the next
time), showing a slight loss of the activity aer three cycles

Fig. 2

(85%, 82% and 81%yield, respectively). The TOF (turnover

frequency) is quite impressive for a heterogeneous catalyst
(Table 3). To determine that the observed catalysis of UiO-66SO3H is heterogeneous, ltration leaching test was performed
for the synthesis of 1a (Table 3, entry 1), as a model reaction.
Accordingly, the reaction was ran under the optimal condition
reaction and the solid catalyst was separated from the solution
aer 1 h (40% yield), and then the solution was stirred for 3
more hour. The reaction was not proceeded to completion aer
the mentioned time, albeit with a slightly increment in the
product formation (from 40% to 44% yield), which is negligible
(in comparison with entry 1), suggesting the heterogeneity
nature of the catalyst.
As shown in Fig. 1, the XRD pattern of the recovered UiO-66SO3H matched well that of the fresh one (signicant changes
were not observed) as reported in literature,13,15 indicating that

SEM images of UiO-SO3H fresh (a, left) and reused (b, right).

Scheme 3

Proposed mechanism for the synthesis of dihydro-2-oxopyrroles using UiO-66-SO3H.

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the framework of the reused catalyst was well retained. The

slightly lower intensity of the main PXRD peak (strong peak at
2q  7.2 , the 111 reection) could be in consecutive of some
blocking the pores or apertures by the various chemicals or
a slight degradation during the reaction. Since the 111 reection is in agreement with the largest d spacing of the MOF, it
might be attributed to a change in the super-octahedral cages
content (the 200 reection is consistent with the smaller supertetrahedral pores).20
As indicated in Fig. 2, scanning electron microscopy (SEM)
images of UiO-66-SO3H, before and aer using, are the same,
and include agglomerates of spheroid particles in the size 4590
nm. This demonstrate that the morphology of the catalyst is
maintained during the reaction.
Based on literature survey,3a,c we proposed a mechanism for
the synthesis of dihydro-2-oxopyrroles (a domino reaction: onepot 1,4-additioncondensation1,4-additioncyclization sequential steps) as shown in Scheme 3. At rst, DMAD reacts with the
rst molecule of amine (R2NH2) in the presence of UiO-66-SO3H
through the 1,4-addition reaction to form enamine A. B is
produced through the condensation reaction A with the activated aldehyde. 1,4-Addition reaction between B and the second
molecule of amine (R2NH2), result information of intermediate
C, followed by tautomerism to give D. The intermediate D
undergoes a cyclization reaction through the elimination of
a molecule of methanol of F, aords the target product G. It
should be noted that the formation of E is not observed during
the synthesis.

Paper

Conclusion
Porous UiO-66-SO3H MOF was used as a highly ecient acid
catalyst for the multicomponent synthesis of dihydro-2oxopyrroles. The catalyst can act as both Brnsted and Lewis
acid active sites, which can be recycled without a signicant
decrease in its activity. The performance not only introduces an
environmentally benign, and simple experimental procedure,
but also outlines new research directions, helping researchers
to explore the potential of MOFs as heterogeneous catalysts in
multicomponent reactions.

8
9

Acknowledgements
The authors gratefully acknowledge the nancial support for
this work from the Bu-Ali Sina University, Hamedan, Iran.
10

Notes and references

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