Paal-Knorr reaction catalyzed by metal-organic framework IRMOF-3 as an efficient and reusable heterogeneous catalyst

Article abstract of DOI:10.1016/j.molcata.2012.06.007

A highly porous metal-organic framework (IRMOF-3) was synthesized from the reaction of zinc nitrate hexahydrate and 2-amino-1,4-benzenedicarboxylic acid by solvothermal method. Physical characterizations of the material were achieved by using a variety of different techniques, including X-ray powder diffraction (XRD), scanning electron microscope (SEM), transmission electron microscopy (TEM), thermogravimetric analysis (TGA), Fourier transform infrared (FT-IR), atomic absorption spectrophotometry (AAS), and nitrogen physisorption measurements. The IRMOF-3 was used as an efficient heterogeneous catalyst for the Paal-Knorr reaction of benzyl amine with 2,5-hexanedione. Excellent conversions were obtained under mild conditions in the presence of 3 mol% catalyst. The IRMOF-3 catalyst could be reused several times without a significant degradation in catalytic activity.

Full text of DOI:10.1016/j.molcata.2012.06.007

Journal of Molecular Catalysis A: Chemical 363–364 (2012) 178–185
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Journal of Molecular Catalysis A: Chemical
journal homepage: www.elsevier.com/locate/molcata
Paal–Knorr reaction catalyzed by metal–organic framework IRMOF-3 as an
efficient and reusable heterogeneous catalyst
Nam T.S. Phan∗, Tung T. Nguyen, Quang H. Luu, Lien T.L. Nguyen
Department of Chemical Engineering, HCMC University of Technology, VNU-HCM, 268 Ly Thuong Kiet, District 10, Ho Chi Minh City, Viet Nam
a r t i c l e i n f o
a b s t r a c t
Article history:
A highly porous metal–organic framework (IRMOF-3) was synthesized from the reaction of zinc nitrate
hexahydrate and 2-amino-1,4-benzenedicarboxylic acid by solvothermal method. Physical characteriza-
tions of the material were achieved by using a variety of different techniques, including X-ray powder
diffraction (XRD), scanning electron microscope (SEM), transmission electron microscopy (TEM), ther-
mogravimetric analysis (TGA), Fourier transform infrared (FT-IR), atomic absorption spectrophotometry
(AAS), and nitrogen physisorption measurements. The IRMOF-3 was used as an efficient heterogeneous
catalyst for the Paal–Knorr reaction of benzyl amine with 2,5-hexanedione. Excellent conversions were
obtained under mild conditions in the presence of 3 mol% catalyst. The IRMOF-3 catalyst could be reused
several times without a significant degradation in catalytic activity.
Received 13 January 2012
Received in revised form 8 June 2012
Accepted 12 June 2012
Available online 22 June 2012
Keywords:
Metal–organic framework
IRMOF-3
Paal–Knorr reaction
Heterogeneous catalyst
Recyclable
© 2012 Elsevier B.V. All rights reserved.
1. Introduction
out in the presence of a variety of solid catalysts, including lay-
ered zirconium phosphate and phosphonate [21], silica sulfuric acid
The Paal–Knorr condensation of primary amines with 1,4-
dicarbonyl precursors has been widely employed in the synthesis of
pyrrole, pyrazoles, and their derivatives as important intermediates
for pharmaceutical and fine chemical industry [1,2], as well as for
the development of organic functional materials [3]. Traditionally,
the reaction could effectively proceed in the presence of homoge-
neous Bronsted or Lewis acids such as H2SO4 [4], p-toluene sulfonic
acid [5], Bi(NO3)3 [6], Al2O3 [7], FeCl3 [3], CoCl2 [8], Sc(OTf)3 [9],
ZrOCl2 [10], Yb(OTf)3 [11], indium salts [12], titanium isopropoxide
[13], and zinc tetrafluoroborate [14]. However, these homogeneous
catalysis procedures suffer a number of serious problems, such as
high amounts, toxicity and corrosion of the catalysts, generation
of a large amount of wastes, tedious workup and difficult product
purification [15,16]. With the increasing emphasis on green chem-
istry, more environmentally benign processes should be targeted
to improve the green aspect of the reaction [17,18]. In this context,
several solid catalysts have been investigated for the Paal–Knorr
reaction. Indeed, the use of heterogeneous catalysts offers sev-
eral advantages in terms of facile catalyst recovery and recycling,
simple product separation and purification, minimal contamina-
tion of the desired products with hazardous or harmful metals
[19,20]. Recently, the Paal–Knorr condensation has been carried
[22], zeolite [23], magnetic nanoparticle-supported glutathione
[24,25], nano ␤-PbO [26], polystyrene-supported aluminum chlo-
ride [15], macroporous strongly acidic styrol resin (D001) [27], and
cationic exchange resin [28]. Although promising results have been
achieved, the development of a more efficient catalyst for the reac-
tion is still in great demand.
Applications of metal–organic frameworks (MOFs), a new fam-
ily of organic–inorganic hybrid materials, in the field of catalysis
have attracted increasing attention during the past few years
[29]. Combining some special properties of both organic and inor-
ganic porous materials, MOFs possess several advantages such
as high surface areas, well-defined structures, ability to tune
pore size, the ease of processability, and structural diversity
[30–38]. Very recently, MOFs have been investigated as solid cat-
alysts or catalyst supports for several organic transformations
[29,39], including hydrosilylation of 1-hexyne [40], low temper-
ature dehydrogenation [41], nitroaromatic reduction [42], Suzuki
cross-coupling [43,44], “click” reaction [45], carbonyl-ene reaction
[46], oxidation [47–53], alkene epoxidation [54–57], sequential
alkene epoxidation/epoxide ring-opening reactions [58], oxida-
tive cleavage of alkenes [59], cycloaddition of CO2 with epoxides
[60], cyanosilylation [61,62], hydrogenation [63,64], Sonogashira
reaction [65], transesterification reaction [66], aldol condensa-
tion [67], aza-Michael condensation [68], 1,3-dipolar cycloaddition
reactions [45], N-methylation of aromatic primary amines [69],
epoxide ring-opening reaction [70–72], hydrolysis of ammo-
nia borane [73], cyclopropanation of alkene [74], Knoevenagel
∗
Corresponding author. Tel.: +84 8 38647256x5681; fax: +84 8 38637504.
E-mail addresses: ptsnam@hcmut.edu.vn, ptsnam@yahoo.com,
ptsnam@gmail.com (N.T.S. Phan).
1381-1169/$ – see front matter © 2012 Elsevier B.V. All rights reserved.
http://dx.doi.org/10.1016/j.molcata.2012.06.007

N.T.S. Phan et al. / Journal of Molecular Catalysis A: Chemical 363–364 (2012) 178–185
179
condensation [75–77], Henry reaction [78], and Friedel–Crafts alky-
2.3. Catalytic studies
lation and acylation [79–81]. In this work, we wish to report the
utilization of a highly porous metal–organic framework (IRMOF-3)
as an efficient heterogeneous catalyst for the Paal–Knorr reaction.
High activity was observed, and the IRMOF-3 catalyst could be
reused without significant degradation in activity.
The Paal–Knorr reaction of benzyl amine with 2,5-hexanedione
using the IRMOF-3 catalyst was carried out in a magnetically
stirred round-bottom flask. The IRMOF-3 catalyst was activated
under vacuum at 160 ◦C for 6 h prior to use. In a typical reac-
tion, a solution of benzyl amine (0.22 ml, 2 mmol), 2,5-hexanedione
(0.41 ml, 3.4 mmol), and n-dodecane (0.2 ml) as internal standard in
4 ml toluene was added to the flask containing the IRMOF-3 cata-
lyst (0.013 g, 3 mol %). The catalyst concentration was calculated
with respect to the zinc/benzyl amine molar ratio. The result-
ing mixture was stirred at room temperature for 60 min. Reaction
conversion was monitored by withdrawing aliquots from the reac-
tion mixture at different time intervals, quenching with diethyl
ether, drying over anhydrous Na2SO4, analyzing by GC with ref-
erence to n-dodecane, and further confirming product identity by
GC–MS. It should be noted that no further progress of the reac-
tion was observed when the sample in diethyl ether was stored
for another 2 h, indicating the aliquots were completely quenched.
The IRMOF-3 catalyst was separated from the reaction mixture by
simple decantation, washed with copious amounts of anhydrous
dichloromethane, dried under vacuum at ambient temperature for
1 h, and reused when necessary. For the leaching test, a catalytic
reaction was stopped after 5 min, analyzed by GC, and decanted to
remove the solid catalyst. The reaction solution was then stirred for
a further 55 min. Reaction progress, if any, was monitored by GC as
previously described.
2. Experimental
2.1. Materials and instrumentation
All reagents and starting materials were obtained commer-
cially from Sigma–Aldrich and Merck, and were used as received
without any further purification unless otherwise noted. Nitrogen
physisorption measurements were conducted using
a Quan-
tachrome 2200e system. Samples were pretreated by heating under
vacuum at 150 ◦C for 3 h. A Netzsch Thermoanalyzer STA 409
was used for thermogravimetric analysis (TGA) with a heating
rate of 10 ◦C/min under a nitrogen atmosphere. X-ray powder
diffraction (XRD) patterns were recorded using a Cu K␣ radi-
ation source on a D8 Advance Bruker powder diffractometer.
Scanning electron microscopy studies were conducted on a JSM
740 Scanning Electron Microscope (SEM). Transmission elec-
tron microscopy studies were performed using a JEOL JEM 1400
Transmission Electron Microscope (TEM) at 100 kV. The IRMOF-3
samples were dispersed on holey carbon grids for TEM observation.
Elemental analysis with atomic absorption spectrophotometry
(AAS) was performed on an AA-6800 Shimadzu. Fourier trans-
form infrared (FT-IR) spectra were obtained on a Bruker TENSOR37
instrument, with samples being dispersed on potassium bromide
pallets.
3. Results and discussion
3.1. Catalyst synthesis and characterization
Gas chromatographic (GC) analyses were performed using a Shi-
madzu GC 17-A equipped with a flame ionization detector (FID)
and a DB-5 column (length = 30 m, inner diameter = 0.25 mm, and
film thickness = 0.25 ␮m). The temperature program for GC analy-
sis heated samples from 100 to 190 ◦C at 20 ◦C/min; then heated
them from 190 to 220 ◦C at 25 ◦C/min and finally heated them from
220 to 250 ◦C at 30 ◦C/min. The inlet and detector temperatures
were set constant at 300 ◦C. n-Dodecane was used as an inter-
nal standard to calculate reaction conversions. GC–MS analyses
were performed using a Hewlett Packard GC-MS 5972 with a RTX-
5MS column (length = 30 m, inner diameter = 0.25 mm, and film
thickness = 0. 5 ␮m). The temperature program for GC–MS analy-
sis heated samples from 60 to 280 ◦C at 10 ◦C/min and held them
at 280 ◦C for 2 min. Inlet temperature was set constant at 280 ◦C.
MS spectra were compared with the spectra gathered in the NIST
library.
As
a
member of isoreticular metal–organic frame-
work family, IRMOF-3 consists of Zn4O clusters and
2-aminobenzenedicarboxylate (NH2-BDC) linkers, forming
an extended three-dimensional cubic porous network as
Zn4O(NH2BDC)3 [76,83]. In this work, the IRMOF-3 was syn-
thesized using zinc nitrate hexahydrate and H2NH2BDC by a
solvothermal method, according to a literature procedure [82]. It
was found that the IRMOF-3 was achieved as pale yellow crystals
with a yield of 68% (based on 2-amino-1,4-benzenedicarboxylic
acid). The IRMOF-3 was then characterized using a variety of
different techniques. Elemental analysis with AAS indicated zinc
and nitrogen loadings of 4.3 and 3.6 mmol/g, respectively. The
XRD diffractogram (Fig. 1) indicated that a highly crystalline
material was obtained with a very sharp peak being observed
below 10◦ (with 2Â of 6.8). The overall XRD patterns of the
2.2. Synthesis of IRMOF-3
In a typical preparation [82], a solid mixture of zinc nitrate
hexahydrate (Zn(NO3)2·6H2O) (0.327 g, 1.1 mmol) and 2-amino-
1,4-benzenedicarboxylic acid (H2NH2BDC) (0.078 g, 0.43 mmol)
was stirred for 10 min in 10 ml of N,Nꢀ-dimethylformamide (DMF)
in a 20 ml vial. The tightly capped vial was heated at 100 ◦C in an
isothermal oven for 48 h to yield brown block crystals. After cool-
ing of the vial to room temperature, the solid product was removed
by decanting with mother liquor and washed in DMF (3 × 10 ml)
for 3 days. After the solid product had been obtained, solvent
exchange was carried out with dichloromethane (DCM) (2 × 10 ml)
at room temperature for 2 days. The material was then evacu-
ated under vacuum at 160 ◦C for 6 h, yielding 0.079 g of IRMOF-3
as Zn4O(NH2BDC)3 in the form of pale yellow crystals (68% based
on 2-amino-1,4-benzenedicarboxylic acid).
Fig. 1. X-ray powder diffractogram of the IRMOF-3.

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N.T.S. Phan et al. / Journal of Molecular Catalysis A: Chemical 363–364 (2012) 178–185
Fig. 4. Pore size distribution of the IRMOF-3.
respect to the zinc/benzyl amine molar ratio. For the reason of
simplicity, the zinc content was used as an elemental tag for the cat-
alyst. Farrusseng and co-workers previously employed IRMOFs as
solid acid catalysts, and proposed that Zn–OH species, which were
formed as structural defects in the synthesis step or upon water
adsorption, could contribute to the catalytic activity of the IRMOFs
[80,88]. Recently, Corma and co-workers also demonstrated that
these defects in IRMOF-3 could be the active sites for acid-catalyzed
organic transformations [89]. However, it should be noted that fur-
ther investigations would be needed to elucidate the real reactive
sites on the surface of the IRMOF-3 catalyst in the Paal–Knorr con-
densation. Aliquots were withdrawn from the reaction mixture at
different time intervals and analyzed by GC, giving kinetic data dur-
ing the course of the reaction. It was found that the reaction rate was
significantly affected by the reagent ratio. The Paal–Knorr reaction
using one equivalent of 2,5-hexanedione afforded 52% conversion
after 60 min, while 60% conversion was observed for that using
the reagent ratio of 1:1.5. Increasing the reagent ratio to 1:1.7 led
to a dramatic enhancement in reaction rate, with 96% conversion
being achieved after 60 min (Fig. 5). It was therefore decided to
use benzylamine: 2,5-hexanedione molar ratio of 1:1.7 for further
studies.
Fig. 2. SEM micrograph of the IRMOF-3.
IRMOF-3 were in good agreement with those previously reported
in the literature [84,85]. FT-IR spectra of the IRMOF-3 showed a
significant difference as compared to that of the free 2-amino-
1,4-benzenedicarboxylic acid, being consistent with the literature
[86,87]. TGA result of the IRMOF-3 indicated that the material
could be stable up to over 400 ◦C. The SEM micrograph showed
that well-shaped cubic crystals with crystal sizes ranging between
approximately 400 and 500 ␮m were obtained (Fig. 2). Langmuir
specific surface areas of up to 3295 m2/g were observed for the
IRMOF-3, as calculated from nitrogen adsorption/desorption
isotherm data (Fig. 3). The pore structure of the IRMOF-3 appeared
to be complex. Indeed, nitrogen physisorption measurements
indicated that the material would contain both microporous
˚
(diameter < 20 A) and mesoporous pores (Fig. 4).
3.2. Catalytic studies
The IRMOF-3 was used as a solid catalyst for the Paal–Knorr
reaction of benzyl amine with 2,5-hexanedione to form 1-benzyl-
2,5-dimethyl-1H-pyrrole as the major product (Scheme 1). Initial
studies addressed the effect of reagent molar ratio on the reac-
tion conversion. The Paal–Knorr reaction was carried out in toluene
at room temperature in the presence of 2 mol% IRMOF-3 catalyst,
using benzylamine: 2,5-hexanedione molar ratio of 1:1, 1:1.5, and
1:1.7, respectively. The catalyst concentration was calculated with
With this result in mind, we then decided to investigate the
effect of catalyst concentration on the reaction conversion, having
carried out the Paal–Knorr reaction in toluene at room temperature,
using benzylamine: 2,5-hexanedione molar ratio of 1:1.7 in the
presence of 2 mol%, 3 mol%, 1 mol%, and 0.5 mol% IRMOF-3 catalyst,
respectively. It was observed that decreasing the catalyst concen-
tration to 1 mol% and 0.5 mol% resulted in a significant drop in the
800
700
600
500
400
300
200
100
0
100
80
60
40
1:1
1:1.5
1:1.7
20
0
0.0
0.2
0.4
0.6
0.8
1.0
0
10
20
30
40
50
60
Pressure (bar)
Time (min)
Fig. 3. Nitrogen adsorption/desorption isotherm of the IRMOF-3. Adsorption data
are shown as closed circles and desorption data as open circles.
Fig. 5. Effect of benzylamine:2,5-hexanedione molar ratio on reaction conversion.

N.T.S. Phan et al. / Journal of Molecular Catalysis A: Chemical 363–364 (2012) 178–185
181
Scheme 1. The Paal–Knorr reaction using the IRMOF-3 catalyst.
reaction conversion, with 77% and 67% conversions being obtained
after 60 min. As expected, increasing the catalyst concentration led
to an enhancement in the reaction conversion. The reaction using
3 mol% catalyst afforded 99% conversion after 60 min. It should be
noted that a conversion of 16% was observed after 60 min in the
absence of the catalyst, indicating the necessity of the IRMOF-3
catalyst for the reaction (Fig. 6). The catalyst concentrations used
for the Paal–Knorr reaction in this study were comparable to those
in the literature. Indeed, a variety of catalysts were previously
employed for the Paal–Knorr reaction, in which the catalyst con-
centrations could vary from less than 5 mol% to more than 50 mol%,
depending on the nature of the catalyst as well as that of the sub-
strate. These catalysts included Bi(NO3)3·5H2O (50–100 mol%) [6],
nano lead oxide (20 mol%) [26], polystyrene-supported aluminum
chloride (15 mol%) [15], potassium exchanged layered zirconium
phosphate (12 mol%), UO2(NO3)2·6H2O (10 mol%) [90], sulfamic
acid (10 mol%) [91], zirconium sulfophenyl phosphonate (6 mol%)
[21], Yb(OTf)3 (5 mol%) [11], CoCl2 (5 mol%) [8], ZrOCl2·8H2O
(2.5 mol%) [10], and Sc(OTf)3 (1 mol%) [9].
For liquid-phase organic transformations using solid catalysts,
there is a possibility that some of active sites could migrate into
the solution phase during the course of the reaction. In several
cases, these leached species from the solid phase could contribute
significantly to the total conversion of the reaction, thus indicat-
ing that the reaction would not proceed under real heterogeneous
catalysis conditions [92]. In order to test if active species leached
from the solid IRMOF-3 catalyst could play an important role in
the catalytic activity for the Paal–Knorr reaction, an experiment
was performed using a simple decantation during the course of
the reaction. After the solid catalyst was removed from the reac-
tion mixture, if the catalytic reaction continued this would indicate
that the reaction occurred either under totally homogeneous or
under partially heterogeneous and partially homogeneous condi-
tions. The Paal–Knorr reaction was carried out in toluene at room
temperature, using benzylamine: 2,5-hexanedione molar ratio of
1:1.7, in the presence of 3 mol% of fresh IRMOF-3 catalyst. After
5 min reaction time, the toluene phase was separated from the
solid IRMOF-3 by simple decantation, transferred to a new reactor
vessel, and stirred for an additional 55 min at room temperature
with aliquots being sampled at different time intervals, and ana-
lyzed by GC. As expected, experimental results showed that no
further conversion was observed for the Paal–Knorr reaction after
the solid IRMOF-3 catalyst was removed from the reaction mixture.
This observation clearly confirmed that the Paal–Knorr reaction
could only occur in the presence of the solid IRMOF-3 catalyst, and
there was no contribution from leached active species, if any, in the
liquid phase (Fig. 7).
To emphasize the advantages of using the solid IRMOF-3 as cat-
alyst for the Paal–Knorr condensation, the catalytic activity of two
components of the IRMOF-3 (i.e. Zn(NO3)2·6H2O and 2-amino-1,4-
benzenedicarboxylic acid) as well as two popular metal–organic
frameworks (i.e. MOF-5 and ZIF-8) was investigated for the reac-
tion. The MOF-5 and the ZIF-8 were synthesized and characterized
as previously reported [79,93]. The Paal–Knorr reaction was car-
ried out in toluene at room temperature, using benzylamine:
2,5-hexanedione molar ratio of 1:1.7, in the presence of 3 mol%
catalyst. It was found that 2-amino-1,4-benzenedicarboxylic acid
was totally inactive for the reaction under this condition, with no
trace amount of the product being detected by GC. The reaction
using 3 mol% Zn(NO3)2·6H2O as catalyst afforded 89% conversion
after 60 min, revealing that the metal centers would be the active
sites on the solid IRMOF-3 catalyst. Indeed, zinc-based catalyst
was previously reported to exhibit high activity in the Paal–Knorr
reaction [14]. Fe(NO3)3 exhibited similar activity to the IRMOF-
3 in the reaction. However, it is apparent that this Lewis acid
catalyst cannot be reused. It was found that the ZIF-8 offered
lowest activity for the reaction, and a conversion of 83% was
obtained after 60 min for the reaction using 3 mol% ZIF-8. Inter-
estingly, the MOF-5 exhibited lower activity than the IRMOF-3,
with 93% and 99% conversions being achieved after 60 min for
the reaction using the former and the latter, respectively (Fig. 8).
It should be noted that the MOF-5 (composition of Zn4O(BDC)3
in which BDC = 1,4-benzenedicarboxylate) is topologically similar
to IRMOF-3 (composition of Zn4O(NH2BDC)3 in which NH2BDC
is 2-amino-1,4-benzenedicarboxylate), and the MOF-5 possessed
100
80
100
80
60
60
0.5 mol%
40
1 mol%
3 mol% IRMOF-3
40
20
2 mol%
3 mol%
no catalyst
Leaching test
20
0
0
0
10
20
30
40
50
60
0
10
20
30
40
50
60
Time (min)
Time (min)
Fig. 7. Leaching test indicated no contribution from homogeneous catalysis of active
Fig. 6. Effect of catalyst concentration on reaction conversion.
species leaching into reaction solution.

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N.T.S. Phan et al. / Journal of Molecular Catalysis A: Chemical 363–364 (2012) 178–185
100
80
60
40
20
0
100
80
60
40
3 mol% IRMOF-3
3 mol% MOF-5
3 mol% ZIF-8
20
0
Toluene
p-xylene
Anisole
3 mol% Zn(NO3)2
3 mol% Fe(NO3)3
Ethylbenzene
Chloroform
0
10
20
30
40
50
60
0
10
20
30
40
50
60
Time (min)
Time (min)
Fig. 8. Effect of different catalysts on reaction conversion.
Fig. 9. Effect of different solvents on reaction conversion.
on the rate of the Paal–Knorr reaction using the IRMOF-3 catalyst
is complex, and needs further investigation.
higher surface areas (3800 m2/g) than those of the IRMOF-3
(3295 m2/g). These results indicated that the amino groups on the
linkers in the MOF structure would play an important role in the
catalytic activity for the Paal–Knorr reaction. In this case, the reac-
tants (i.e. benzylamine and 2,5-hexanedione) were significantly
more polar than the solvent of the reaction (i.e. toluene). Therefore,
the partitioning of the reactants away from the solvent to the cat-
alyst would be enhanced when the polarity of the catalyst surface
increased. As the free linker (i.e. 2-amino-1,4-benzenedicarboxylic
acid) showed almost no activity for the reaction under identical
condition, the higher polarity of the catalyst surface would be one
of reasons leading to the higher activity of the IRMOF-3 as com-
pared to that of the MOF-5. However, the role of the amine moiety
in the catalyst structure still needs further investigation.
The effect of different solvents on the reaction rate is nor-
mally an important issue that should be taken into accounts. A
variety of solvents were previously employed for the Paal–Knorr
condensation, significantly depending on the nature of the cat-
alyst. Banik et al. carried out the reaction in dichloromethane
in the presence of Bi(NO3)3·5H2O as catalyst [6]. Rahmatpour
and co-workers used ZrOCl2·8H2O catalyst for the reaction and
found that the yield increased with the order: tetrahydrofu-
ran < methanol < ethylacetate < chloroform < dichloromethane
< acetonitrile < solvent-free condition [10]. Methanol was previ-
ously reported to be the solvent of choice for the reaction using
UO2(NO3)2·6H2O catalyst, offering higher conversions than that
carried out in ethanol, acetonitrile, chloroform, dichloromethane,
and solvent-free condition, respectively [90]. For the reaction
employing polystyrene-supported aluminum chloride as catalyst,
toluene, dichloromethane, dichloroethane, tetrahydrofuran, and
solvent-free condition were reported to be totally ineffective,
while high yields were observed for the case of acetonitrile [15].
It was therefore decided to investigate the effect of different sol-
vents on the Paal–Knorr reaction using the IRMOF-3 catalyst. The
reaction was carried out at room temperature, using benzylamine:
2,5-hexanedione molar ratio of 1:1.7, in the presence of 3 mol%
catalyst. It was found that polar solvents like methanol and ethanol
were not suitable for the process, as the IRMOF-3 crystals were
broken into fine powders in these solvents. Experimental results
showed that the reaction rate of the Paal–Knorr condensation
using the IRMOF-3 catalyst decreased in the order of solvents:
toluene > anisole > p-xylene > ethylbenzene > chloroform (Fig. 9).
The reaction carried out in toluene could proceed to completion
after 60 min, while 88%, 81%, 76%, and 47% conversions were
observed for the case of anisole, p-xylene, ethylbenzene, and
chloroform, respectively. However, the effect of different solvents
The study was then extended to the condensation reaction of
several reagents in the presence of the IRMOF-3 as catalyst. The
reactions of 2,5-hexanedione with eight amines, including ben-
zylamine, 1,2-phenylenediamine, p-toluidine, aniline, phenylhy-
drazine, p-anisidine, 4-florobenzylamine, 4-methylbenzylamine,
respectively, were carried out at room temperature using the
reagent molar ratio of 1:1.7, in the presence of 3 mol% IRMOF-3
catalyst. The reaction of benzylamine with 2,5-hexanedione pro-
ceeded to completion after 60 min under this condition. However,
it was observed that the effect of substituents in the aromatic
ring on the Paal–Knorr condensation was unclear. The presence of
either an electron-donating group (i.e. 4-methylbenzylamine) or
an electron-withdrawing group (i.e. 4-florobenzylamine) in ben-
zylamine both accelerated the reaction rate, with quantitative
conversions being achieved after 20 min and 10 min, respectively.
Indeed, Chen et al. previously reported similar observation for
the Paal–Knorr condensation, in which high conversions were
obtained for both benzylamines containing electron-withdrawing
or electron-donating groups [9]. It was also found that the IRMOF-3
catalyst could be suitable for the condensation of 2,5-hexanedione
with phenylhydrazine to form a pyrazole derivative, where the
reaction could afford more than 99% conversion after 30 min.
Although the IRMOF-3 exhibited high activity in the Paal–Knorr
reaction of benzylamine, it was observed that the condensation
reaction of aniline with 2,5-hexanedione using this catalyst pro-
ceeded with difficulty. Conversions of 12%, 28%, and 39% were
obtained after 60 min for the case of aniline, p-toluidine, and p-
anisidine, respectively (Fig. 10). Curini et al. previously carried
out the Paal–Knorr reaction using zirconium-based catalysts and
found that benzylamine was significantly more reactive than ani-
line [21]. Aniline also exhibited lower reactivity than benzylamine
in the Paal–Knorr reaction using ZrOCl2·8H2O [10], and silica sul-
furic acid [22] as catalysts. However, it was previously reported
that the Paal–Knorr reaction of aniline afforded higher yields than
the case of benzylamine in the presence of other catalysts, includ-
ing CoCl2 [8], ZrCl4 [94], UO2(NO3)2·6H2O [90], nano ␤-PbO [26],
Bi(NO3)3·5H2O [6], and macroporous strongly acidic styrol resin
(D001) [27]. With this result in mind, we then decided to carry
out the Paal–Knorr reaction of benzylamine with different dike-
tones, including 2,5-hexadione, 1-phenyl-1,4-pentandione, and
1,2-dibenzoylethane, respectively. It was found that the reaction
occurred slowly for the case of 1-phenyl-1,4-pentandione and 1,2-
dibenzoylethane, while quantitative conversion was achieved for
the reaction of 2,5-hexadione under the same condition (Fig. 11).
The issue still needs further studies, though it could be proposed

N.T.S. Phan et al. / Journal of Molecular Catalysis A: Chemical 363–364 (2012) 178–185
183
Benzylamine
1,2-Phenylenediamine
p-Toluidine
Phenylhydrazine
p-Anisidine
4-Floro benzylamine
100
(a)
Aniline
4-Methylbenzylamine
80
100
80
60
40
20
0
60
40
20
0
1
2
3
4
5
6
7
8
Run
0
10
20
30
40
50
60
100
80
60
40
20
0
(b)
Time (min)
Fig. 10. Effect of different amines on reaction conversion.
that the bulky phenyl groups on the diketone might have a negative
effect on the transformation.
1st
2nd
3rd
4th
5th
6th
7th
8th
As mentioned earlier, the replacement of traditional homo-
geneous Lewis acids with solid catalysts would offer several
advantages, including easy catalyst recovery and recycling. In the
best case the solid catalyst can be recovered and reused several
times before it eventually deactivates completely. It was there-
fore decided to investigate the recoverability and reusability of
the IRMOF-3 catalyst in the Paal–Knorr reaction of benzylamine
with 2,5-hexadione by repeatedly separating the IRMOF-3 from
the reaction mixture, washing it and then reusing it. The reaction
was carried out in toluene at room temperature using the reagent
molar ratio of 1:1.7, in the presence of 3 mol% IRMOF-3 catalyst.
After each run, the catalyst was separated from the reaction mix-
ture by simple decantation, then washed with copious amounts of
dichloromethane to remove any physisorbed reagents. The recov-
ered IRMOF-3 was dried under vacuum at room temperature for 1 h,
and then reused in further reactions under identical conditions to
those of the first run. It was found that the IRMOF-3 could be recov-
ered and reused several times without a significant degradation in
catalytic activity. Indeed, a conversion of 92% was still achieved in
the 8th run (Fig. 12a). In a second experiment, aliquots were with-
drawn from the reaction mixture at different time intervals and
analyzed by GC, giving kinetic data during the course of the reaction
0
10
20
30
40
50
60
Time (min)
Fig. 12. Catalyst recycling studies.
using the fresh and recycled catalyst, respectively. It was observed
that the activity of the IRMOF-3 catalyst in the Paal–Knorr reaction
decreased slightly after each run. However, it was apparent that the
catalyst could still be recycled and reused (Fig. 12b). Although it was
previously reported that almost no loss of activity was observed
for reused solid catalysts in the Paal–Knorr reaction, no kinetic
data was provided [15,22,25,27]. Indeed, only conversions at the
end of the experiment were mentioned. However, stable activity
should not be demonstrated by reporting only similar reaction con-
versions at long times. Kinetic studies are the true test of catalyst
deactivation [92].
100
80
2,5-hexanedione
1-phenyl-1,4-pentandione
60
1,2-dibenzoylethane
40
20
0
0
10
20
30
40
50
60
Time (min)
Fig. 11. Effect of different diketones on reaction conversion.
Fig. 13. FT-IR spectra of the fresh (a) and reused (b) IRMOF-3.

184
N.T.S. Phan et al. / Journal of Molecular Catalysis A: Chemical 363–364 (2012) 178–185
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was characterized using a variety of different techniques, includ-
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measurements. The material was used as an efficient heteroge-
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2,5-hexanedione to form 1-benzyl-2,5-dimethyl-1H-pyrrole as the
major product. Excellent conversions were obtained under mild
conditions in the presence of 3 mol% catalyst, and the IRMOF-3 cat-
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in activity. Moreover, the Paal–Knorr reaction could only occur in
the presence of the solid IRMOF-3 catalyst, and there was no contri-
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