Amine-functionalized Metal-Organic Frameworks: An Efficient and Recyclable Heterogeneous Catalyst for the Knoevenagel Condensation Reaction

Article abstract of DOI:10.1055/s-0035-1561356

A highly efficient and reusable catalyst based on metal-organic frameworks (MOF) has been synthesized by post-functionalization and applied in Knoevenagel condensations of various aldehydes and ketones. The catalytic efficiency was demonstrated by the hig

Full text of DOI:10.1055/s-0035-1561356

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© Georg Thieme Verlag Stuttgart · New York
2016, 27, A–E
letter
A
A. Taher et al.
Letter
Synlett
Amine-functionalized Metal-Organic Frameworks: An Efficient
and Recyclable Heterogeneous Catalyst for the Knoevenagel Con-
densation Reaction
R1
Abu Taher
O
Dong-Jin Lee
R2
Byoung-Ki Lee
+
Ik-Mo Lee*
NH2
X
CN
R1
DMF
80 °C
NH2
Department of Chemistry, Inha University,
Incheon 402-751, Korea
imlee@inha.ac.kr
CN
MOF
X
= Zn4O(CO2)6
R2
16 examples
up to 98% yield
100% selectivity
Catalyst
R1 = H, Me; R2 = H, Cl, Br, HO, Me, MeO, NO2; X = CN, COOEt
Received: 03.12.2016
Accepted after revision: 12.01.2016
Published online: 05.02.2016
es,7 solid-phase reactions,8 and methods using ionic liq-
uids,9 green solvents such as water,10 or grindstones under
solvent-free conditions have been developed.11 All these
protocols have drawbacks, such as use of expensive homo-
geneous catalysts, harsh thermal conditions, disposal of
toxic solvents and catalysts, or long reaction times. As a re-
sult, the development of heterogeneous catalytic systems
for chemical synthesis has attracted increasing attention,
and these systems can lead to novel environmentally be-
nign chemical procedures for academia and industry.12
The newly developed porous MOF structures are a
promising new generation of heterogeneous catalytic mate-
rials13 affording studies in the coordination space provided
by the 3D structure of the MOF due to (i) the well-ordered
size and shape of the pores, (ii) the flexible and dynamic be-
havior in response to guest molecules, and (iii) the design-
able channel surface functionalities. Porous MOFs can be
constructed rapidly from multidentate ligands through self-
assembly, where the ligand topology and coordination ten-
dencies depend on the metal ion. For the optimal catalytic
activity, two types of strategies are used: (a) introduction of
organic groups to provide guest-accessible functional or-
ganic sites14 and (b) formation of coordinatively unsaturat-
ed metal sites.15 If the metal is saturated coordinatively, the
organic moiety incorporating the functionality for non-co-
valent interactions can bind the reactant(s) through
H-bonding, or non-covalent stacking, leading to their acti-
vation. Herein, we report a highly active and recyclable cat-
alyst obtained by post-functionalization of MOF for Knoev-
enagel condensations between an aldehyde or ketone and
malononitrile or ethyl cyanoacetate, catalyzed by the pri-
mary amines embedded inside the well-known MOF [see
Scheme 1 in the Supporting Information (SI)]. The activities
DOI: 10.1055/s-0035-1561356; Art ID: st-2015-u0937-l
Abstract A highly efficient and reusable catalyst based on metal-or-
ganic frameworks (MOF) has been synthesized by post-functionaliza-
tion and applied in Knoevenagel condensations of various aldehydes
and ketones. The catalytic efficiency was demonstrated by the high
conversion (over 85−98%) of the reactants under mild conditions. The
catalyst maintained its unique framework after the reaction and could
be recycled and reused several times without significant loss of activity.
Key words Knoevenagel condensation, metal-organic frameworks,
heterogeneous catalysis, carbon–carbon bond, aldehyde, ketone
The Knoevenagel condensation1 is one of the most im-
portant and widely used methods for the formation of car-
bon–carbon bonds in organic synthesis.2 The condensation
reaction occurs between carbonyl compounds and activat-
ed methylene compounds. This carbon–carbon bond cou-
pling reaction is useful for the preparation of important in-
termediates in drug production. In addition, this reaction is
employed as a classic test reaction to analyze the activity of
a variety of solid base catalysts. The typical pKa values of
hydrogen atoms in β-dicarbonyl compounds are in the
range of 9–11.3 This makes them ideal substrates for test re-
actions utilizing Knoevenagel condensations. Active methy-
lene groups of compounds with different pKa values can be
reacted with benzaldehyde to test the activity of a basic
catalyst. Owing to their importance from an industrial and
synthetic point of view, a large number of methods for
Knoevenagel condensations has been reported employing
Lewis acids or bases,4 microwave assistance,5 or ultrasound
irradiation.6 Furthermore, biotechnology-based approach-
© Georg Thieme Verlag Stuttgart · New York — Synlett 2016, 27, A–E

B
A. Taher et al.
Letter
Synlett
were compared with those of the homogeneous counter-
parts benzylamine and aniline, and the heterogeneous IR-
MOF-3 catalyst.
the azide groups of MOF-N3 were reduced to the primary
amine groups. The complete conversion of the azide groups
was also confirmed by the 1H NMR spectrum after digestion
of the reacted crystals (see Figure S3 in the SI). The signal of
the benzyl protons at 4.3 ppm was shifted to 3.8 ppm. The
XRD pattern of the MOF-NH2 crystals exhibited no appar-
ent changes compared to the XRD pattern of the starting
MOF-N3 as shown in Figure 1, a. The MOF-NH2 and the par-
ent compound showed identical thermal stability (see Fig-
ure S4 in the SI). The BET surface area and pore volume of
MOF-NH2 were 516.18 m2·g–1 and 0.29 cm3·g–1, respectively,
and the modified MOF showed type I N2-adsorption–de-
sorption isotherms (see Figure S5 in the SI), again suggest-
ing that the structure of the parent MOF remained intact af-
ter functionalization. To gain further insights, we also per-
formed XPS analysis. Careful analysis showed the presence
of a split peak with maxima at 400 and 401 eV for the azide
groups18 (Figure 1, c). Maxima at 398 and 399 eV for the
primary amine groups19 (Figure 1, d) suggested the com-
plete conversion of the azide functionalities to amines.
The Knoevenagel condensation of aldehydes with com-
pounds containing activated methylene groups is a robust
reaction often used to test the catalytic activities of basic
catalysts.20 This reaction is catalyzed by alkali metal hy-
droxides or by homogeneous organic bases, such as prima-
ry, secondary and tertiary amines.21 On the other hand, re-
cycling and catalyst recovery have been problems in their
use in the production of fine chemicals. Initially, the Knoeve-
nagel condensation of benzaldehyde was performed using
various amounts of the catalyst MOF-NH2 to screen the
loading. The yield of the reaction gradually increased with
increasing catalyst loading (0–0.15 mmol of –NH2 groups,
see Figure S7 in the SI). In addition, high catalytic activity
was still observed with a very low catalyst loading. Al-
though the reaction yield reached almost 100% with 0.10
mmol of –NH2 groups in MOF-NH2, 0.13 mmol and 0.15
mmol gave 100% yield in the reaction of benzaldehyde at
80 °C in DMF. Therefore, 0.13 mmol loading of –NH2 groups
in MOF-NH2 was determined to be the optimal loading un-
der such reaction conditions. Furthermore, solvents were
screened to reach higher efficiency in the condensations
(Figure 2, a). Water and toluene were poor solvents, and the
crystal structure of MOF-NH2 was deformed when water
was used as a solvent (see Figure S8 in the SI). The Knoeve-
nagel condensation of benzaldehyde reached only 55–65%
conversion in DMA, DME and ethanol. The results showed
that DMF proved the best solvent regarding the catalytic ac-
tivity. With the optimized conditions in hand, the reactions
of various aromatic substituted aldehydes or ketones with
malononitrile or ethyl cyanoacetate were investigated and
the results are listed in Table 1.24
The azide-functionalized MOF-N3 was prepared from an
azide-containing organic linker using zinc nitrate hexahy-
drate in N,N-diethylformamide (DEF) as described earlier.16
The XRD pattern of as-synthesized MOF-N3 (Figure 1, a)
was similar to the literature.16 In the FT-IR spectra, the crys-
tals showed a stretching band of the azide groups at 2100
cm–1 with the C–O stretching band of zinc carboxylate at
1400 cm–1 (Figure 1, b). These facts suggested that two
azide groups were introduced on each organic linker in the
frameworks of MOF-N3.17 Then, we tried reduction of the
azide groups by using triphenylphosphine (PPh3) as reduc-
ing agent in DEF. The optical microscope observation illus-
trated that there was no apparent damage to the shape and
the edges of the MOF crystals after modification (see Figure
S1a in the SI). The progress of the reducing reaction of MOF-
N3 was monitored by FT-IR as shown in Figure 1, b. After 10
hours, the azide stretching band at 2100 cm–1 disappeared
completely, an NH stretching band at 3300 cm–1 was ob-
served, and C=O stretching at ca. 1700 cm–1 showed no
changes (Figure 1, b). Therefore, the C–O band was still
maintained along with Zn (see Figure S2 in the SI) after
modification indicating that the MOF framework was con-
structed by zinc ions and carboxylate anions.
Figure 1 (a) XRD patterns, (b) FT-IR spectra, (c) and (d) XPS spectra of
the nitrogen N 1s peaks of MOF-N3 and MOF-NH2, respectively
Furthermore, the formation of amine functionalities in
the MOF crystals was qualitatively confirmed by a ninhy-
drin test according to a literature procedure.17 A red color
developed that the starting MOF-N3 did not display (see Fig-
ure S1b in the SI). This observation strongly suggested that
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A. Taher et al.
Letter
Synlett
Table 1 (continued)
Entry Product
Table 1 Knoevenagel Condensation of Various Aldehydes and Ketones
Catalyzed by MOF-NH2 in DMFa
Time (h) Yield (%)b Mp (°C)
Found Reported
R1
R1
CN
X
MOF-NH2
CN
O
+
CN
13
5
90
91
9322
DMF, 80 °C
X
R2
R2
COOEt
Cl
R1 = H, Me; R2 = H, Cl, Br, HO, Me, MeO, NO2; X = CN, COOEt
CN
17322
13122
Entry Product
Time (h) Yield (%)b Mp (°C)
Found Reported
14
6
4
96
95
173
130
COOEt
HO
CN
CN
CN
1c
2
4.5
4.5
51
98
84
84
8422
8422
15
COOEt
CN
CN
O2N
CN
16
6.5
90
143
14422
COOEt
O2N
CN
CN
3
4
97
159
16222
CN
Cl
CN
17
6.5
86
83
8422
COOEt
Br
4
5
90
86
97
85
187
164
160
107
18822
16423
16022
10723
CN
a Reaction conditions: aldehyde or ketone (1 mmol), malononitrile or ethyl
cyanoacetate (1 mmol), MOF-NH2 (0.13 mmol of –NH2 groups), DMF (6 mL),
80 °C.
HO
HO
CN
b Isolated yields.
5
4.5
4
c Control experiment using MOF-N3: MOF-N3 and MOF-NH2 were calculated
to have the same amount of Zn2+ ions, selectivity 100%.
CN
CN
6
Control experiments using MOF-N3 under exactly the
same reaction conditions were carried out, showing that
the MOF-N3 material was less effective than MOF-NH2 (Ta-
ble 1, entries 1 and 2). The catalytic activity of MOF-N3 pre-
sumably results from coordinatively unsaturated zinc
sites.25 All reactions proceeded smoothly to give the corre-
sponding Knoevenagel condensation products in high yield
with 100% selectivity under those conditions (entries 2–
17). The catalytic activity of MOF-NH2 for benzaldehyde, 4-
chlorobenzaldehyde, 4-hydroxybenzaldehyde, 3-hydroxy-
benzaldehyde, 4-nitrobenzaldehyde, 3-nitrobenzaldehyde,
acetophenone, 4-methylbenzaldehyde, and 4-methoxyl-
benzaldehyde with malononitrile was high in DMF (entries
2–10). The electron-withdrawing groups (EWG) promoted
this condensation efficiently and reduced the reaction time
(entries 3, 6, 7) as compared to the electron-donating
groups (EDG) (entries 4, 5, 9 and 10). In addition, the cata-
lytic system could be extended to various aldehydes and ke-
tones in reaction with ethyl cyanoacetate, and showed high
activity in DMF (entries 11–17). The Knoevenagel conden-
sation of benzaldehyde with ethyl cyanoacetate was close to
quantitative in yield (98%, entry 11). Electron-withdrawing
derivatives, such as 4-chlorobenzaldehyde, 1-(4-chlorophe-
nyl)ethanone, 4-nitrobenzaldehyde, 1-(4-nitrophenyl)etha-
none, and 1-(4-bromophenyl)ethanone (entries 12, 13, 15,
CN
O2N
O2N
CN
7
3.5
CN
CN
CN
CN
8
9
7
88
91
9222
CN
6.5
7
92
87
98
91
134
133
51
13523
11323
5022
CN
10
CN
MeO
CN
11
5
COOEt
CN
COOEt
12
6.5
88
8822
Cl
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16, and 17), along with the electron-donating derivatives,
such as 4-hydroxybenzaldehyde (entry 14), showed satis-
factory yields of 86–98%. Interestingly, the EWG gave the
products in shorter time as compared to the EDG. Further-
more, the catalyst also performed well for ketones to give
the corresponding condensation products in up to 90% yield
(entries 8, 13, 16 and 17). These results demonstrate that
MOF-NH2 successfully promoted the Knoevenagel conden-
sation reactions of various aldehydes and ketones, having
either EWGs or EDGs.
The activity of MOF-NH2 was compared to that of ben-
zylamine, aniline and IRMOF-3 at 80 °C in DMF (Figure 2, b),
considering that the total number of amino groups was
equal in all cases. These results clearly demonstrate that the
reactivity of the benzylamino groups is enhanced when in-
corporated into the MOF structure, and the reactivity of the
benzylamine is superior to that of aniline. Therefore, the
high activity of MOF-NH2 is most likely due to an enhance-
ment of the basicity of the benzylamino groups upon incor-
poration into the MOF framework, along with the coordina-
tively unsaturated zinc sites.25 Furthermore, this enhance-
ment would be due to the structure of pores and the
surface functionalization of the MOF frameworks (see Fig-
ures S5 and S6 in the SI).
was carried out in presence of the catalyst until the conver-
sion was 41%, and then the solid part of the reaction mix-
ture was filtered off. The liquid phase was then transferred
to another clean reaction vial and allowed to react further,
but no significant change in conversion was observed (Fig-
ure 2, c). After 4.5 hours, 43% conversion was noted which
indicates that no active species was present in the reaction
vial. In addition, the reusability of the catalyst was exam-
ined.
The major advantage of the catalyst was the easy recov-
ery by filtration or centrifugation. The recycling of the cata-
lyst was examined by the coupling of benzaldehyde with
malononitrile (Figure 2, d). Similar yields (100–98%) were
obtained by performing five runs without any significant
loss of activity. The XRD patterns of the catalyst after reuse
were indistinguishable from those of the fresh catalyst (see
Figure S8 in the SI), suggesting that no structural deteriora-
tion or organic and metal complex decomposition had oc-
curred after the catalytic reaction and filtration. Therefore,
MOF-NH2 most likely maintained a similar structural
framework that could be helpful for using it as a heteroge-
neous catalyst.
The present work focused on a well-known and import-
ant type of metal-organic framework, MOF-NH2, which
possesses exceptionally high catalytic activity. The repeated
reactions performed with the recycled catalyst maintained
similar yields without significant loss of activity or selectiv-
ity. Interestingly, MOF-NH2 showed the highest catalytic ac-
tivities among benzylamine, aniline and IRMOF-3 in all cas-
es. The advantages of the present method are the simplicity
of work-up, high yields and recyclability. Moreover, the ex-
ceptional reactivity of the novel composites prompted our
concurrent inquiry into applications of these catalytic ma-
trices in a multitude of catalytic reactions and engineering
processes.
Acknowledgment
This work is supported by Inha University Research Grant (Inha 2014)
Supporting Information
Figure 2 Knoevenagel condensation of benzaldehyde with malononi-
trile catalyzed by MOF-NH2. (a) Screening of different solvents. (b)
Comparative catalytic study with the same catalyst loading (0.13 mmol
–NH2 groups). (c) Hot filtration test. (d) Recyclability test. In all cases
the reaction conditions are the same as given in Table 1.
Supporting information for this article is available online at
http://dx.doi.org/10.1055/s-0035-1561356.
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References and Notes
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leached molecules would become responsible for a signifi-
cant contribution to the catalytic activity. Two reactions
with benzaldehyde were carried out, with continuous
monitoring of the conversion after 1.5 hours. One reaction
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Catalyst corresponding to 0.13 mmol –NH2 groups (based on
the total amount of amino groups in the catalytic material) was
added to a solution of malononitrile or ethyl cyanoacetate (1
mmol) and aldehyde or ketone (1 mmol) in DMF (6 mL) at 80 °C
under a nitrogen atmosphere. After the reaction was complete,
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© Georg Thieme Verlag Stuttgart · New York — Synlett 2016, 27, A–E