A facile microwave-assisted Knoevenagel condensation of various aldehydes and ketones using amine-functionalized metal organic frameworks

Article abstract of DOI:10.1016/j.inoche.2020.108092

An amine-functionalized metal organic framework (MOF) was used as highly efficient and recyclable heterogeneous catalyst for Knoevenagel condensation of various aromatic aldehydes and ketones in ethanol. The catalytic efficiency was demonstrated by the hi

Full text of DOI:10.1016/j.inoche.2020.108092

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Short communication
A facile microwave-assisted Knoevenagel condensation of various aldehydes
and ketones using amine-functionalized metal organic frameworks
Abu Taher, Bilkis Jahan Lumbiny, Ik-Mo Lee
PII:
S1387-7003(20)30682-1
DOI:
https://doi.org/10.1016/j.inoche.2020.108092
INOCHE 108092
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Inorganic Chemistry Communications
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Revised Date:
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2 July 2020
Please cite this article as: A. Taher, B. Jahan Lumbiny, I-M. Lee, A facile microwave-assisted Knoevenagel
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Graphical Abstract
A facile microwave-assisted Knoevenagel condensation of various aldehydes and ketones using
amine-functionalized metal organic frameworks
Abu Taher,*a, c Bilkis Jahan Lumbinyb and Ik-Mo Lee*c
a
Department of Industrial and Production Engineering, European University of Bangladesh, Mirpur,
Dhaka-1216, Bangladesh; Tel: +88-01712-681890, E-mail: drtaher@eub.edu.bd.
b Department of Chemistry, University of Rajshahi, Rajshahi-6205, Bangladesh.
c Department of Chemistry, Inha University, Incheon 402-751, South Korea. Tel: +82-32-860-7682; Fax: 82-32-
867-5604; E-mail: imlee@inha.ac.kr.

Contents lists available at Science Direct
Inorganic Chemistry Communications
journal homepage: www.elsevier.com/locate/inoche
Short Communication
A facile microwave-assisted Knoevenagel condensation of various aldehydes and
ketones using amine-functionalized metal organic frameworks
Abu Taher a, c,*, Bilkis Jahan Lumbiny b, Ik-Mo Lee c,*
a Department of Industrial and Production Engineering, European University of Bangladesh, Mirpur, Dhaka-1216, Bangladesh.
b Department of Chemistry, University of Rajshahi, Rajshahi-6205, Bangladesh.
c Department of Chemistry, Inha University, Incheon 402-751, South Korea.
ARTICLE INFO
ABSTRACT
Article history:
Received
Received in revised form
Accepted
An amine-functionalized metal organic framework (MOF) was used as highly efficient and
recyclable heterogeneous catalyst for Knoevenagel condensation of various aromatic aldehydes
and ketones in ethanol. The catalytic efficiency was demonstrated by the high conversion of the
reactants with 100 % selectivity under microwave (µW) irradiation, while dramatically reduced
the reaction time as compared to the conventional heating method. Importantly, the MOF
maintained its structural integrity after catalytic reactions and it could be reused several times
without remarkable loss of activity.
Available online
Keywords:
Amine-functionalized
Metal Organic Framework
Knoevenagel condensation
Microwave
© 2016 Elsevier B.V. All rights reserved.
Catalysis
Modern techniques are focused on the design of new
methodologies able to make more efficient, simpler, faster, and
cheaper chemical transformation processes [1]. Microwave (µW)-
assisted organic synthesis has been recognized as one of the most
powerful and sustainable tools in synthetic organic chemistry [2].
The application of µW energy is superior in comparison with
conventional heating on accelerating chemical processes leading
to radically reduce reaction times and increase yields and product
purities by reducing unwanted side reactions [3]. The advantages
* Corresponding author.
E-mail address: drtaher@eub.edu.bd (A. Taher), imlee@inha.ac.kr (I. Lee).
Metal organic frameworks (MOFs) have emerged as a newly
developed materials with appreciable promise in growth of
effective catalysts for synthetic organic chemistry [10].
Furthermore, MOFs are novel inorganic-organic hybrid materials
that can be easily prepared from available precursors. The porous
MOFs are promising new heterogeneous catalytic materials [11]
due to well-ordered particle size, particle shape, pore size, pore
shape, surface functionality and dynamic behavior in response to
guest molecules. Importantly, MOFs-based catalysts can be
readily recovered and reused after the catalytic reactions [12].
Therefore, MOFs are highly demanded catalytic materials to
perform a variety of catalytic reactions in organic synthesis.
On the other hand, Knoevenagel condensation [13] is one of the
most widely used methods for the formation of new carbon-carbon
bonds [14]. Importantly, these carbon-carbon bond forming
of this enabling technology have subsequently also been exploited
in the past such as medicinal chemistry [4], polymer synthesis [5],
material sciences [6], nanoparticles research [7], and biochemical
synthesis [8]. Importantly, the use of catalysts in conjunction with
a µW may has significant advantages over traditional heating
methods since the inverted temperature gradient under µW
conditions may lead to an increased lifetime of catalyst through
elimination of wall effects [9].

A. Taher et al. / Inorganic Chemistry Communications
reactions are useful in drug production. Owing to their
importance from the industrial point of view, a large number of
various methods for the Knoevenagel condensation have been
cyanoacetate were investigated in ethanol and the results of the
reactions are summarized in the following Table 2. Control
experiment using compound 1 under exactly the same reaction
conditions were carried out, showing that the 1 was less effective
than compound 2 (Table 2, entry 1 and 2) that also confirmed by
our conventional heating method [21]. However, 1 demonstrates
catalytic activity would be due to coordinatively unsaturated zinc
sites in the MOF networks [22]. Importantly, all
Conventional
heating method
wave irradiation
Entry
1
Substrate
Yield (%)b
Time
4 min
Time
1.5 h
Yield (%)b
99
42
O
2
MeO
6 min
97
2.0 h
23
Table 1 Knoevenagel condensation of aldehydes catalyzed by 2 under µW
irradiation and conventional heating method.a
O
a
Reaction conditions: substrate (1mmol), malononitrile (1 mmol), 2 (0.2
mmol of -NH2 groups), ethanol (4 mL), µWave (200 W); b GC yield.
reported such as Lewis acids/bases [15], ultrasound irradiation
[16], biotechnology [17], solid form [18], ionic material [19], and
grindstone technique [20]. Unfortunately, these reactions often
require harsh conditions such as extended reaction times, extra
care, elevated temperatures and expensive catalysts. Therefore, the
development of suitable energy saving synthetic method for the
Knoevenagel condensation is highly desirable and a hot topic in
current organic synthesis. Recently, amine-functionalized MOFs
(2) (Scheme 1) were found to act as efficient catalysts in
Knoevenagel condensation reactions [21]. The amine-
Table 2 Knoevenagel condensation of various aldehydes and ketones catalyzed
by 2 under µW irradiation in ethanol.a
m.p (oC)
Time
(min)
Yield
(%)b
Entry
c 1
Producta
Found
84
Reported
Scheme
1
Synthesis route of amine-functionalized MOFs (2).
4
4
4
4
4
5
5
6
6
5
6
36
98
95
92
84
91
87
95
94
97
92
8417
CN
CN
functionalized MOFs were prepared from the azide functional
group containing MOF (1) with triphenylphosphine (PPh3) in
diethylformamide (DEF) as described our earlier report and they
can be used as a catalyst for Knoevenagel condensation reaction in
organic synthesis [21]. Herein, we designed and developed very
NC
NC
2
84
8417
Cl
3
159
160
107
187
164
134
133
51
16217
16017
10718
18817
16418
13518
11318
5017
suitable µW-incorporated catalytic system using
2
for
CN
CN
NC
NC
Knoevenagel condensation of various aromatic aldehydes and
ketones (Table 2).
O2N
4
In the initial studies, we attempted the condensation of
benzaldehyde with malononitrile under µW irradiation and
conventional heating, respectively. The reactions were conducted
in the presence of 0.2 mmol of 2 at 90 ℃ in ethanol. By employing
µW irradiation, the reaction time was shortened from 1.5 h to 4
min in reaching full conversion (Table 1, entry 1). It is well-known
that methoxy functional groups containing substrates are much
more difficult to activate than other substrates. Remarkably, the
condensation of 4-methoxybenzaldehyde with malononitrile
proceeded faster and achieved high yield upon 6 min by µW
irradiation, whereas the usual thermal heating gave very poor yield
for 2 h (Table 1, entry 2). To our delight, the µW irradiation system
showed good activity at very short reaction time for Knoevenagel
condensation with 100% selectivity. With these encouraging result
in hand, we next optimized the µwave conditions for the best
performance of the catalyst. At first, the Knoevenagel
condensation of benzaldehyde was performed with various
amounts of 2 to screen the catalyst loading. As shown in Fig. 1a,
the yield of the reaction gradually increased with increasing
catalyst loading (0 to 0.2 mmol of –NH2 groups). In addition, high
catalytic activity was still observed with a very low catalyst
loading. Although the reaction yield reached almost 100 % with
0.16 mmol of 2, 0.2 mmol gave 100% yield for benzaldehyde at
90°C. Therefore, 0.2 mmol loading of 2 was determined to be the
optimal loading. Furthermore, the effective solvent was screened
to obtain higher efficiency under µW irradiation (Fig.1b). Water
and toluene were poor solvents (14 to18% conversion) and the
crystal structure of MOF material was deformed when water was
used as a solvent. The Knoevenagel condensation of benzaldehyde
was demonstrated only 45 to 58% conversion in acetonitrile, DMF
and DME. The results showed that ethanol was the best solvent for
the catalytic activity of the solvent used in condensations under
µW irradiation. Having these optimized results in hand, the
reactions of various aromatic substituted aldehydes with
malononitrile
5
CN
CN
O2N
HO
NC
NC
6
7
CN
CN
CN
HO
Me
NC
NC
NC
8
MeO
9
10
11
COOEt
COOEt
COOEt
NC
NC
Cl
Cl
88
8817
Me
12
13
14
6
5
8
87
94
91
91
9317
NC
O2N
O2N
130
143
13117
14417
COOEt
COOEt
NC
Me
Me
NC
Br
15
8
6
82
94
83
8417
COOEt
COOEt
NC
NC
HO
16
173
17317
a
Reaction conditions: aldehyde/ketone (1mmol), malononitrile/ethyl
cyanoacetate (1 mmol), 2 (0.2 mmol of -NH2 groups), ethanol (4 mL),
µWave (200 W); b isolated yield; c Calculated to have the same amount of
Zn2+ (when comparing MOF-NH3 and MOF-NH2).
or
ethyl

the reactions proceeded smoothly to give the corresponding
products in high yield with 100 % selectivity under the defined
W irradiation conditions. The high catalytic activity of 2 for
benzaldehyde, 4-chlorobenzaldehyde, 4-nitrobenzaldehyde, 3-
Acknowledgements
This work is supported by Inha University Research Grant
(2017)
nitrobenzaldehyde,
hydroxybenzaldehyde,
4-hydroxybenzaldehyde,
4-methylbenzaldehyde,
3-
4-
Supplementary Material
and
methoxylbenzaldehyde with malononitrile was still maintained in
ethanol (Table 2, entries 2-9). The electron withdrawing groups
(EWG) somewhat reduced the reaction time (Table 2, entries 3-5)
as compared to the electron donating groups (EDG) (Table 2,
entries 6-9).
Experimental details, TGA, XPS, pore volume vs diameter
graphs, N2 adsorption-desorption isotherms and comparison table.
Electronic supplementary information (ESI) to this article can be
found online at http://dx.doi.org/10.1016/j.inoche
In further studies, extension of the scope of the Knoevenagel
condensations catalyzed by
2 was explored to various
aldehyde/ketone derivatives with ethyl cyanoacetate under µW-
irradiation. Interestingly, the reaction of benzaldehyde with ethyl
cyanoacetate proceeded smoothly to provide the corresponding
product in high yield, 97% (Table 2, entry 10). The substrates with
EWGs, such as 4-chlorobenzaldehyde, 1-(4-
chlorophenyl)ethanone,
4-nitrobenzaldehyde,
1-(4-
nitrophenyl)ethanone, 1-(4-bromophenyl)ethanone (Table 2,
entries 11-15), along with the derivatives of EDGs, such as 4-
hydroxybenzaldehyde (Table 2, entry 16) showed satisfactory
yields up to 94% and EWGs gave the products in shorter time as
compared to the EDGs. Furthermore, a variety of aromatic ketones
also performed well to give the corresponding yields, affording up
to 92% isolated yields by µW conditions (Table 2, entries 12, 14
and 15). These results were consistent with our hypothesis and
suggested that the amine moieties together with structure of MOF
can facilitate the formation of product for EWG/EDG substituents,
thus enhancing the catalytic reactivity as depicted in Fig. S1.
Moreover, EWGs along with EDGs promoted Knoevenagel
condensation efficiently, whereas dramatically reduced the
reaction time as compared to the conventional heating method
[23]. Importantly, these results reveal that the use of µW
irradiation into the catalysis leads to much higher rates within a
very short reaction time than those which are achieved in
conventional heating.
In order to further evaluate the catalyst’s reactivity, we also
compared catalyst 2 with some catalysts reported in the literature
for the Knoevenagel condensation under µW irradiation.
Interestingly, as shown in Table S1 (ESI), catalyst 2 (Table S1,
entry 1) has many advantages over reported catalysts. Importantly,
the high activity of catalyst 2 would be due to basicity, pore
structure, thermal stability, surface functionality along with
coordinatively unsaturated metal site of the MOF framework (Fig.
1c, and Fig. S2-S6; ESI) [21, 22].
Fig.
1 Knoevenagel condensation of benzaldehyde with malononitrile
catalysed by 2 (a) different catalyst loading, (b) in different solvents, and (d)
recyclability test; in all cases the reaction conditions are same as Table 2 (entry
2); (c) XRD patterns of catalyst 2 (fresh & after 5th run).
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Graphic

A. Taher et al. / Inorganic Chemistry Communications
Highlights

A highly efficient and reusable amine-
functionalized metal organic frameworks
(MOFs) for the Knoevenagel condensation of
various aldehydes and ketones in ethanol.


The catalytic efficiency was demonstrated by
the high conversion of the reactants with 100 %
selectivity under microwave irradiation.
The electron withdrawing groups along with
electron donating groups promoted this
Knoevenagel condensation efficiently and
dramatically reduced the reaction time as
compared to the conventional heating method

This work provides a very simple, energy saving
as well as easy way for organic synthesis

Declaration of interests
☒ The authors declare that they have no known
competing financial interests or personal
relationships that could have appeared to influence
the work reported in this paper.
☐The authors declare the following financial
interests/personal relationships which may be
considered as potential competing interests:
'Declarations of interest: none'

A. Taher et al. / Inorganic Chemistry Communications
Author Statement
Abu Taher: Conducted experimental work,
analyzed the data, and Writing- Original draft
preparation; Ik-Mo Lee: Supervision, reviewing and
worked as project administrator; Bilkis Jahan
Lumbiny: Initiated the project, designed
experiments to develop this reaction, investigated
the work.