Knoevenagel condensation reaction catalysed by Al-MOFs with CAU-1 and CAU-10-type structures

Article abstract of DOI:10.1039/c6ce02664h

The metal-organic frameworks (MOFs) CAU-1-NH₂ ([Al₄(OH)₂(OCH₃)₄(p-BDC-NH₂)₃], (p-BDC-NH₂)^2- = 2-aminoterephthalate) and CAU-10-NH₂ ([Al(OH)(m-BDC-NH₂)], (m-BDC-NH₂)^2- = 5-aminoisophthalate) which possess two different pore sizes were studied for their catalytic activity as heterogeneous solid base catalysts in the Knoevenagel condensation reaction between benzaldehyde and malononitrile under mild reaction conditions (40 °C, 7 h, ethanol). For comparison, isoreticular MOFs containing a smaller amount of -NH₂ groups (CAU-1-NH₂/H) or no -NH₂ groups (CAU-10-H) were synthesized. A two-step synthesis route including the synthesis of CAU-1-NH₂ and its use as crystal seeds was developed to obtain the mixed-linker CAU-1-NH₂/H compound. Only for CAU-1-NH₂, up to 100% selectivity towards the desired Knoevenagel condensation product is observed. Hence, the catalytic activity of CAU-1-NH₂ was tested between various benzaldehydes containing different substituents with malononitrile. By employing benzaldehyde and malononitrile as the starting materials, it is found that the mixed-linker MOF CAU-1-NH₂/H catalyses the formation of the acetal (benzaldehyde diethyl acetal), while both CAU-10 materials lead to mixtures of the two products. Furthermore, the catalyst stability was also examined through reusability and leaching experiments and it is observed that the catalyst can be reused with no significant drop in its activity.

Full text of DOI:10.1039/c6ce02664h

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DOI: 10.1039/C6CE02664H
Journal Name
ARTICLE
Knoevenagel condensation reaction catalysed by Al-MOFs with
CAU-1 and CAU-10-type structure
Amarajothi Dhakshinamoorthy,a,b* Niclas Heidenreichb, Dirk Lenzenb and Norbert Stockb*
Received 00th January 20xx,
Accepted 00th January 20xx
The metal-organic frameworks (MOFs) CAU-1-NH2 ([Al4(OH)2(OCH3)4(p-BDC-NH2)3], (p-BDC-NH2)2- = aminoterephthalate) and
CAU-10-NH2 ([Al(OH)(m-BDC-NH2)], (m-BDC-NH2)2- = aminoisophthalate) wich contain two different pore sizes were studied
for their catalytic activity as heterogeneous solid base catalysts in Knoevenagel condensation reaction between
benzaldehyde and malononitrile under mild reaction conditions (40°C, 7 h, ethanol). For comparison isoreticluar MOFs
containing a smaller amount of –NH2 groups (CAU-1-NH2/H) or no –NH2 groups (CAU-10-H) were synthesized for comparison.
A two-step synthesis route including the synthesis of CAU-1-NH2 and their use as crystal seeds, was developed to obtain the
mixed-linker CAU-1-NH2/H compound. Only for CAU-1-NH2 up to 100% selectivity towards the desired Knoevenagel
condensation product is observed. Hence, the catalytic activity of CAU-1-NH2 was tested between various benzaldehydes
containing different substituents with malononitrile. Employing benzaldehyde and molononitrile as the starting materials,
the mixed-linker product CAU-1-NH2/H catalyses the formation of the acetal (benzaldehyde diethylacetale), while both CAU-
10 materials lead to mixtures of the two products. Furthermore, the catalysts stability was also examined in terms of
reusability and leaching experiments and it is observed that the catalyst can be reused with no significant drop in its activity.
DOI: 10.1039/x0xx00000x
www.rsc.org/
compound [Al(OH)(m-BDC)] also known as CAU-10 (m-H2BDC:
1,3-benzenedicarboxylic acid) can be used in heat
transformation applications and is stable towards water
sorption /desorption for at least 10.000 cycles without loss of
Introduction
In the field of catalysis porous crystalline materials are
attractive candidates due to their high specific surface areas and
their well-ordered pore dimensions. In the category of porous
crystalline materials metal-organic frameworks (MOFs) that
consist of inorganic building units (IBUs) bridged by organic
linkers are particularly suited for catalysis.1 MOFs present, in
addition to very large specific surface areas, the option to tailor
the pore surface properties towards the requirements of
certain catalytic processes. This has been accomplished by
direct synthesis using functionalized organic linker molecules or
via post-synthetic modification.2 Both methods preserve the
parent framework structure and leave the porous structure
accessible for the reactants of a chemical reaction.
As MOFs contain organic moieties that decompose at higher
temperatures, these compounds are primarily applicable for
catalytic processes at lower temperatures. The thermal stability
of a MOF strongly depends on its composition and the structure
of the IBU and some Al-based MOFs have been shown to be
both thermally and chemically stable.3 For example, the
crystallinity and water adsorption capacity.4 This compound can
also be directly synthesized with various functional groups on
the linker molecule and the sulfonated derivative (CAU-10-
SO3H) has been successfully used as a catalyst in the gas phase
dehydration of ethanol.5 The structure of CAU-10 is comprised
of helical chains consisting of cis-corner sharing AlO6-polyhedra
which are connected to four adjacent chains via m-BDC2- ions.
Accordingly CAU-10 exhibits a framework with square-shaped
one-dimensional modulated pores with a diagonal opening of
~3.6 Å taking van der Waals radii into account (Fig. 1). CAU-1-
NH2 ([Al4(OH)2(OCH3)4(p-BDC-NH2)3] · xH2O) is an Al-MOF with a
three-dimensional pore system and two different pore sizes.
The structure consists of eight-membered rings composed of
corner- and edge-sharing AlO6-polyhedra. Each IBU is bridged
via 2-aminoterephthalate (p-BDC-NH22-) ions to 12 other IBUs.
The resulting structure possesses tetrahedral and octahedral
cavities with diameters of ~5 and ~10 Å, respectively (Fig. 1).6
a.School of Chemistry, Madurai Kamaraj University, Madurai-625 021, Tamil Nadu,
India. E-mail: admguru@gmail.com; Mobile: +91 99764 73669
b.Institut fur Anorganische Chemie Christian-Albrechts-Universität, Max-Eyth
Strasse 2, 24118 Kiel, Germany. E-mail: stock@ac.uni-kiel.de; Fax: +49
4318801775; Tel: +49 4318801675
c.
d.Address here.
† Footnotes relating to the title and/or authors should appear here.
Electronic Supplementary Information (ESI) available: [details of any supplementary
information available should be included here]. See DOI: 10.1039/x0xx00000x
This journal is © The Royal Society of Chemistry 20xx
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Experimental
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DOI: 10.1039/C6CE02664H
Materials and methods
The chemicals used for the synthesis of CAU-1-NH2, CAU-1-
NH2/H, CAU-10 and CAU-10-NH2 are commercially available and
were used without further purification. The powder X-ray
diffraction (PXRD) measurements were carried out on a STOE
Stadi-P powder diffractometer equipped with a MYTHEN1K
detector system (Cu Kα1 radiation). MIR spectra were recorded
on an ATI Matheson Genesis spectrometer equipped with an
ATR unit in the spectral range of 400-4000 cm-1. Sorption
experiments were carried out using a Belsorp-max instrument
(BEL JAPAN INC.). Before the sorption experiments, all samples
Figure 1. Section of the crystal structure of CAU-1 (left) and CAU-10 (right, view
along the channel axis ([001])). H-atoms have been omitted for clarity.
o
were activated at 150 C under vacuum (102 kPa) over night.
The Knoevenagel condensation is one of the fundamental
reactions in organic chemistry for the formation of carbon–
carbon bonds.7 The condensation reaction occurs between
carbonyl compounds and activated methylene compounds. This
carbon-carbon bond coupling reaction is widely used for the
production of important drug intermediates. Furthermore, this
reaction is employed as a classic test reaction to examine the
These conditions were chosen to prevent the exchange of
methoxy- by hydroxyl-groups in the case of CAU-1 type
samples.20 Gas chromatography (6890N network Agilent
Technologies, FID detector) was used for determining the
conversion and selectivity. The product was confirmed by
GC-MS measurements on a Hewlett 5971A Packard GC-MS
instrument. CAU-1-NH2/H was prepared using an Anton Paar
Synthos 3000 multimode microwave oven. The EDX-
spectroscopic measurements were carried out on a Philipps
ESEM-XL 30 while 1H-NMR spectra were collected using a Bruker
DRX 500.
activity of newly synthesised Brønsted-base catalysts. Due to
their significance from an industrial and synthetic point of view,
a large number of catalytic systems have been reported for
Knoevenagel condensation reactions. For example, the reaction
of benzaldehyde with malononitrile has been studied using
[Cd(4-btapa)2(NO3)2]·6H2O·2DMF
benzenetricarboxylic acid
(4-btapa:
1,3,5-
tris[N-(4-pyridyl)amide)8,
Synthetic procedures
[Gd2(tnbd)3(DMF)4]·4DMF·3H2O (tnbd2-: 2,6,2’,6’-tetranitro-
biphenyl-4,4’-dicarboxylate)9, ZIF-810, ZIF-911, Cu3(BTC)2 or
Fe(BTC) (BTC3-: 1,3,5-benzenetricarboxylate)12 as solid Lewis-
acid catalysts. In contrast, the same reaction was also catalyzed
Synthesis of CAU-1-NH2
CAU-1-NH2
([Al4(OH)2(OCH3)4(p-BDC-NH2)3] · xH2O)
was
synthesized with a slightly altered synthesis based on the
method reported previously.20 Briefly, CAU-1-NH2 was
synthesised using MW-assisted heating (Biotage Initiator). A
mixture of AlCl3·6H2O (232 mg, 0.961 mmol) and p-H2BDC-NH2
(58 mg, 0.312 mmol) was suspended in methanol (3.175 mL) in
a 5 mL glass vial. After sealing, the reaction mixture was heated
under stirring (300 rs-1) at 145 oC for 6 min. The reaction mixture
was rapidly cooled to room temperature and a yellow
microcrystalline dispersion was obtained. After centrifugation,
the product was redispersed in water (25 mL) to remove Cl- ions.
This procedure was repeated (three times) until no residual Cl-
ions could be detected by EDX-spectroscopy. The final product
was dried in air to yield CAU-1-NH2. To evaluate the methylation
of the amino-groups a small amount of the MOF was dissolved
in a solution of NaOD/D2O (5%) and analysed via 1H-NMR-
spectroscopy. The degree of methylation was determined as ~4
%. Elemental analysis of the washed phase: observed, C: 41.22,
H: 3.65, N: 5.46; calculated (based on [Al4(OH)2(OCH3)4(p-BDC-
NH2)3]), C: 41.84, H: 3.64, N: 5.22%.
by basic Brønsted sites available in MOFs like DETA-Cr-MIL-
14
10113
(DETA:
diethylenetriamine),
Fe-MIL-101-NH2
,
15
Zn2(tpt)2(p-BDC-NH2)I2 (tpt: tris(4-pyridyl)triazine), p-H2BDC-
NH2: 2-aminoterephthalic acid) and others.16
Al-MOFs have also been tested in catalysis. Thus Gascon et al.
have reported the basic properties of IRMOF-3 and Al-MIL-53-
NH2 in the Knoevenagel condensation of benzaldehyde with
ethyl cyanoacetate in where the later catalyst is less active than
the former one.17 Furthermore, the catalytic activities of Fe-
MIL-101-NH2, Al-MIL-101-NH2 and CAU-1-NH2 were tested in
the Knoevenagel condensation of benzaldehyde with
malononitrile and with ethyl cyanoacetate, respectively.14 Al-
MIL-101-NH2 has been reported as a bifunctional Lewis-acid /
Brønsted-base heterogeneous catalyst in a tandem Meinwald
rearrangement
/
Knoevenagel condensation reaction.18
Recently, a post-synthetic modification strategy was employed
for the introduction of a primary alkyl amino group in Al-MIL-53
and its activity was examined in Knoevenagel condensation.19
Herein, we report a highly active and selective recyclable
catalyst namely CAU-1-NH2 for Knoevenagel condensation
reaction between various benzaldehyde derivatives and
malononitrile which are catalyzed by the primary amine groups.
The activities were compared with those of the CAU-10, CAU-
10-NH2 and CAU-1-NH2/H heterogeneous catalysts under mild
reaction conditions. The catalyst stability is also ascertained by
performing leaching and reusability experiments.
Synthesis of CAU-1-NH2/H
The synthesis of CAU-1-H containing only unfunctionalized
terephthalate ions has not yet been reported. Hence a two-step
procedure was developed for the formation of the mixed-linker
2 | J. Name., 2012, 00, 1-3
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MOF CAU-1-NH2/H containing predominantly p-BDC2- ions. In a which is due to the replacement of -NH2 groups by HVie-watAortmicles.OTnlhinee
typical synthesis, 4 mg of previously synthesized CAU-1-NH2 was N2-sorption isotherms are presented in FDigOuIr: e10S.1303a9n/Cd6TCaEb0l2e66S42H.
used as crystallization seeds and added to 8.2 mg terephthalic The other two MOFs CAU-10-H and CAU-10-NH2 were also
acid (p-H2BDC). Subsequently, 1235 µl of a 0.12 mol/l solution obtained as microcrystalline samples (Fig. S5). The presence of
of AlCl3·6H2O in methanol were added and the mixture was amino group and other characteristic stretching frequencies
heated to 120 °C under stirring using MW-assisted heating. corresponding to CAU-10 and CAU-10-NH2 are visible in the IR
After a reaction time of 60 min the product was filtered and spectra (Fig. S6 and S7). The results of the N2 sorption
washed twice with DMF to remove any remaining unreacted measurements (Fig. S8) for CAU-10 are in agreement the ones
linker. As in the case of CAU-1-NH2 part of the product was reported previously with a specific surface area of 656 m2/g and
dissolved in NaOD/D2O (5%) and analysed by 1H-NMR- a micropore volume of 0.25 cm3/g.5a On the other hand, the BET
spectroscopy. The ratio of p-BDC2- to p-BDC-NH22- in the product surface area of CAU-10-NH2 was measured to be 159 m2/g with
was evaluated by integrating and comparing the signals the micropore volume of 0.08 cm3/g (Fig. S6). The hysteresis in
1
corresponding to each linker in the H-NMR-spectrum (SX in the N2 sorption curve is due to the small pore size in CAU-10-
supporting info). The amount of linkers in the product was NH2 and low measurement temperature (77K).
2-
quantified as ~76% p-BDC2- and ~24 % p-BDC-NH2
.
The Knoevenagel condensation (Scheme 1) reaction is one of
the well-known C-C bond forming reactions in organic chemistry
which occurs between aldehydes with activated methylene
Synthesis of CAU-10-H and CAU-10-NH2
The unfunctionalized and the amino-functionalized form of
CAU-10 were obtained according to the published literature
procedure.5a
compounds containing two electron withdrawing groups.21 22
,
This condensation reaction is often catalysed by bases or acids
and it requires high reaction temperatures or microwave
irradiation.23 24 25 26 Although many catalytic systems have
been reported,15,27 it is very challenging to develop a catalyst
which can promote this reaction without the formation of
byproducts due to consecutive self-condensation and
oligomerization reactions of the primary reaction product.
In addition to these byproducts often reaction between the
solvent and the aldehyde is observed (Scheme 1).
,
,
,
Experimental procedure for Knoevenagel condensation
A 25 mL round-bottomed flask was charged with the catalyst (25
mg) and ethanol (3 mL). To this slurry, benzaldehyde (0.5 mmol)
and malononitrile (0.5 mmol) were added. The reaction mixture
was stirred for the required time. The reaction was monitored
periodically by analyzing the sample by GC until the completion
of reaction. The percentage conversion and selectivity was
determined by GC analysis. The product was confirmed by GC-
MS analysis. Prior to the experiments, the respective sample
was activated at 120 °C for 3 h under reduced pressure.
Leaching experiment
The Knoevenagel condensation reaction was started as
mentioned in the experimental procedure. Then, the catalyst
was removed by filtration using 0.45µm syringe filter after
15 min and the resulting reaction mixture was continued for
7 h. Then, the reaction mixture was dissolved with water and
dichloromethane. The aqueous layer was submitted for AAS
analysis to detect the leached Al3+ into the reaction mixture.
Results and Discussion
Four different Al-MOFs, CAU-1-NH2, CAU-1-NH2/H, CAU-10-H
and CAU-10-NH2 were synthesized and used in the Knoevenagel
condensation reaction at low reaction temperature of 40 °C.
While CAU-1-NH2, CAU-10 and CAU-10-NH2 were obtained
according to literature procedures, the synthesis of the mixed-
linker compound CAU-1-NH2/H was accomplished using a two-
step approach using CAU-10-NH2 as crystal seeds. Thus highly
crystalline CAU-1-NH2/H was obtained with ~76% of BDC2- ions
as the linker (Fig. S1). IR-spectroscopy unequivocally proves the
presence of -NH2 groups in CAU-1-NH2 and CAU-1-NH2/H (Fig.
Scheme 1.
S2). As expected, CAU-1-NH2 exhibits a smaller specific surface Knoevenagel condensation reaction between benzaldehyde (
1
) and malononitrile
in ethanol as solvent to benzylidene malononitrile (
2) and the undesired product
area and micropore volume compared to CAU-1-NH2/H benzaldehyde diethylacetal (
3).
20
(1300 m2/g and 0.54 cm3/g vs. 1400 m2/g and 0.58 cm3/g)
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Table 1. Knoevenagel condensation reaction catalyzed by the different title compounds.a
To evaluate the catalytic activity of the four Al-MOFs at first the
Knoevenagel condensation reaction was performed by taking
View Article Online
DOI: 10.1039/C6CE02664H
S. No
Catalyst
Conversion
of 1 (%)b
Product Selectivity
(%)b
benzaldehyde (
ethanol as the solvent. The reaction afforded the desired
benzylidene malononitrile ( ) and benzaldehyde diethylacetal
through Brønsted-base and Lewis-acid catalysis,
1) and malononitrile as model substrates in
2
100
100
-
56
54
3
-
-
95
43
45
2
1
2
3
4
5
CAU-1-NH2
98
98
84
99
99
(3)
c
CAU-1-NH2
CAU-1-NH2/H
CAU-10
respectively, under the present experimental conditions. This
observation is well supported by earlier precedents in the
literature in where Knoevenagel condensation can be
performed either with acidic or basic MOFs.1c The time
CAU-10-NH2
a
b
Reaction conditions: benzaldehyde (0.05 mL), malononitrile (0.03 mL),
catalyst (25 mg), EtOH (3 mL), 40 °C, 7 h.
Determined by GC. Conversion was determined by using nitrobenzene as
internal standard.
Second reuse.
conversion plot for the reaction between benzaldehyde (1) and
malononitrile in the presence of these catalysts is shown in
Figure 2. The selectivity of the reaction products is shown in
Table 1. The reaction using CAU-1-NH2 as catalyst resulted in
c
98% conversion with complete selectivity towards
while CAU-1-NH2/H showed 84% conversion of
product selectivity to
study the activity of pure CAU-1-H, such studies cannot be
carried out since we have not been able to synthesize this
compound. Recently, the activity of Fe-MIL-101-NH2 and Al-
MIL-101-NH2 was compared with CAU-1-NH2 in the
2
1
after 7 h,
with 95%
Furthermore, Table 2 provides the comparison of the catalytic
data using CAU-1-NH2 with those catalysts reported in the
literature in terms of reaction temperature, time, conversion,
selectivity and various evidences supported to ascertain the
stability of catalysts under the experimental conditions.
3
. Although it would be interesting to
Table 2. Comparison of the activity of CAU-1-NH2 with those catalysts reported for the
Knoevenagel condensation between benzaldehyde and Knoevenagel condensation reaction between 1 and malononitrile.
malononitrile at 80 oC in toluene. The former catalysts exhibited
Catalyst
T (oC)
Time
12 h
Conv. Selec. Stability
Ref.
8
around 90 % yields after 3 h, while CAU-1-NH2 shows low
activity (25% yield) under identical reaction conditions.14 This
was attributed due to narrow pore dimensions of CAU-1-NH2
compared to MIL-101 catalysts. In any case, the present data
clearly show that CAU-1-NH2 can also promote Knoevenagel
condensation if the substrate fits within the pore limits. In
contrast, CAU-10 and CAU-10-NH2 afforded complete
(%)
(%)
[Cd(4-btapa)2
(NO3)2]·6H2O·2DMF
[Gd2(tnbd)3(DMF)4] RT
·4DMF·3H2O
ZIF-8
RT
98
100
XRD
20
min
1 h
96
97
99
88
97
90
99
98
94
100
100
100
100
100
100
100
100
100
3 reuses,
XRD
9
RT
RT
60
RT
80
60
80
40
5 reuses,
leaching
5 reuses,
XRD, IR
XRD,
leaching
3 reuses,
XRD
10
11
12
13
14
15
16
ZIF-9
2 h
6 h
1 h
3 h
2 h
4.5 h
1 h
conversion of
1 but a mixture of 2 and 3 is obtained with very
Cu3(BTC)2
similar product selectivities in both catalytic systems. This may
be explained from the fact that the Brønsted-base catalysed
reaction is only dominant when the amino groups of the
functionalized linker molecules are readily accessible as in CAU-
1-NH2. In contrast, the mixed-linker MOF CAU-1-NH2/H which
contains ca. 26 % of functionalized linker molecules possess
DETA-Cr-MIL-101
Fe-MIL-101-NH2,
Al-MIL-101-NH2
Zn2(tpt)2(p-BDC-
NH2)I2
leaching,
XRD
XRD, TGA
a
sufficient Lewis acidity thus giving 3 as the main product. Hence,
Zn-MOF-NH2
5 reuses,
XRD
2 reuses,
XRD, IR,
leaching
the nature of the active sites and the pore properties in the
respective catalyst determines the product selectivity as well as
the conversion.
CAU-1-NH2
This
work
100
100
The stability of the catalysts was studied by PXRD, atomic
adsorption spectroscopy and hot filtration test (Fig. S9).
PXRD and IR spectroscopy of fresh and recovered catalysts
shows no significant changes (Fig. S10 - S12). Also, atomic
absorption spectroscopy analysis revealed that no detectable
amount of Al3+ is present in the reaction mixture after 7 h. These
experiments clearly indicate the framework stability of CAU-1-
NH2 during the course of the reaction.
80
80
60
60
40
40
20
20
0
0
0
0
1
1
2
2
3
3
4
4
5
5
6
6
7
7
8
8
Time (h)
Time (h)
Due to the good catalytic performance and the high selectivity,
CAU-1-NH2 was used in a consecutive reaction (Fig. 2). No
degradation of the activity or selectivity was observed and the
activity is retained with a similar initial reaction rate.
Figure 2. Time conversion plots for the reaction between
1 and malononitrile in
the presence of CAU-1-NH2 (black square) and CAU-1-NH2/H (blue triangle) as
catalysts and the time conversion plot for the first (black square) and second (red
circle) reuse using CAU-1-NH2. Conversion was determined by GC refers to the
disappearance of 1 and the selectivity data is given in Table 1.
The preliminary results on the catalytic activity of CAU-1-NH2
between benzaldehyde and malononitrile prompted us to
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a
Reaction conditions: benzaldehyde (0.05 mL), malononVitireiwleAr(t0ic.0le3OnmlinL)e,
expand the scope of this catalyst with substituted
benzaldehydes having electron donating or withdrawing
substituents and aldehydes with larger substrates like
phenylacetaldehyde and 1-naphthaldehyde. In addition the
reaction products were isolated and washed before the yield
was determined. The observed results are given in Table 3.
The reaction between benzaldehyde and malononitrile
resulted in a yield of 91% (entry 1, Table 3) of the corresponding
product after 7h in the presence of CAU-1-NH2 and also the use
of other aldehydes (substrates) resulted predominantly in the
formation of the Knoevenagel condensation product (60-92 %
yield). In comparison to homogeneous catalysis where the
presence of a substituent on the benzaldehyde strongly
influences the reactivity, with electron withdrawing groups
leading to higher reactivities, but however, in heterogeneous
catalysis of microporous porous materials, the pore size also
plays an important role in determining the reaction pathway
and selectivity in addition to the electronic effects of
substrates. In the present case the use of electron withdrawing
groups afforded high yields except 4-bromobenzaldehyde
(entries 2-5, Table 3). On the other hand, benzaldehyde with
electron donating groups also showed a comparable yield only
with 4-methoxybenzaldehyde but in other two cases lower
yields were obtained (entries 6-8, Table 3). Apart from the
electronic nature of the substrates, molecular size and the
position of carbonyl group can also determine the yield (entries
9-11, Table 3).
Our results demonstrate that the product yield in Knoevenagel
condensation can be influenced not only by the electronic
factors on the substrate but also the molecular size of a
substrate and position of the aldehyde group under the present
experimental conditions. Thus, a size-selectivity screen has
been studied to reveal the relationship between the size of the
aldehyde substrate and the catalytic activity of CAU-1-NH2.
Benzaldehyde has a size of 5x5.6 Å, which can freely penetrate
inside the pores of CAU-1-NH2 having pores of 5 and 10 Å.
Similarly, malononitrile has a molecular size of 6.9x4.5 Å which
again can diffuse inside the pores of CAU-1-NH2. On the other
hand, use of a slightly larger aldehyde substrate, such as 1-
naphthaldehyde (5.6x7.5Å), which is again within the pore limit
of CAU-1-NH2. Hence, the comparison of the pore natures of
CAU-1-NH2 with that of the reactants employed in the present
work clearly suggest that the reaction takes place mostly inside
the pores without having any diffusion limitations. However,
moderate yields were observed when 4-bromobenzaldehyde
and cinnamaldehyde as substrates, thus suggesting the
diffusion limitation experienced in these substrates.19
catalyst (25 mg), EtOH (3 mL), 40 °C, 7 h.
DOI: 10.1039/C6CE02664H
b
Isolated yield.
S.
No
Yieldb
[%]
Substrate
Product
1
91
2
3
4
92
90
69
5
82
77
6
7
80
92
70
8
9
10
85
60
11
Conclusions
Table 3. Knoevenagel condensation reaction between substituted benzaldehydes and
malononitrile catalyzed by CAU-1-NH2
The catalytic activity of CAU-1-NH2 was tested in
Knoevenagel condensation reactions and its activity was
compared with analogous catalysts like CAU-10 and CAU-10-
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 5
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ARTICLE
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NH2 and CAU-1-NH2/H. The observed data explain that the CAU-
1-NH2 exhibits high activity and selectivity towards Knoevenagel
condensation product while CAU-10 and CAU-10-NH2 result in a
mixture of products derived through acid and base catalyzed
products namely, acetal and Knoevenagel condensation
products. The available catalytic data clearly establish that the
product selectivity mainly depends on the nature of MOFs and
the reaction occurs within the pores of CAU-1-NH2 as evidenced
from the comparison of molecular dimension of the reactants
with the pores of CAU-1-NH2. In addition CAU-1-NH2 was reused
and no significant change in its activity is observed. PXRD
measurements of the fresh and reused catalyst show no
structural changes and a leaching experiment indicates the
absence of Al3+ thus, proving the catalyst stability under the
present experimental condition. Future work will be aimed to
synthesize CAU-1-H and also the methoxy-free CAU-1-NH2 in
order to fully evaluate the influence of methoxy and amino
groups of the catalysts in Knoevenagel condensation reactions.
View Article Online
DOI: 10.1039/C6CE02664H
Acknowledgements
ADM thanks University Grants Commission, New Delhi for the
award of Assistant Professorship under its Faculty Recharge
Program and also thanks Department of Science and
Technology, India for the financial support through Fast Track
project (SB/FT/CS-166/2013). ADM thanks DFG for the financial
support for three months research stay at University of Kiel,
Germany under INSA-DFG bilateral exchange program.
Notes and references
1 a) D. Farrusseng, S. Aguado and C. Pinel, Angew. Chem. Int. Ed.
Engl., 2009, 48, 7502; b) A. Corma, H. Garcıa and F. X. Llabres i
Xamena, Chem. Rev., 2010, 110, 4606; c) A. Dhakshinamoorthy, M.
Opanasenko, J. Čejka and H. Garcia, Adv. Synth. Catal., 2013, 355,
247.
9 R. K. Das, A. Aijaz, M. K. Sharma, P. Lama and P. K. Bharadwaj,
Chem. Eur. J., 2012, 18, 6866.
10 U. P. N. Tran, K. K. A. Le and N. T. S. Phan, ACS Catal., 2011, 1,
120.
11 L. T. L. Nguyen, K. K. A. Le, H. X. Truong and N. T. S. Phan, Catal.
Sci. Technol., 2012, 2, 521.
2 K. K. Tanabea and S. M. Cohen, Chem. Soc. Rev., 2011, 40, 498.
3 a) N. Stock, Metal-Organic Frameworks: Aluminium-Based
Frameworks. In Encyclopedia of Inorganic and Bioinorganic
Chemistry, John Wiley & Sons, Ltd: 2011; b) T. Loiseau, C.
Volkringer, M. Haouas, F. Taulelle and G. Férey, C. R. Chim., 2015,
18, 1350; c) L.-H. Schilling, H. Reinsch and N.; Stock, Synthesis,
Structure, and Selected Properties of Aluminum-, Gallium-, and
Indium-Based Metal–Organic Frameworks. In The Chemistry of
Metal–Organic Frameworks, Wiley-VCH Verlag GmbH & Co. KGaA:
2016, 105-135.
12 M. Opanasenko, A. Dhakshinamoorthy, M. Shamzhy, P.
Nachtigall, M. Horcek, H. Garcia and J. Cejka, Catal. Sci. Technol.,
2013, 3, 500.
13 S.-N. Kim, S.-T. Yang, J. Kim, J.-E. Park and W.-S. Ahn,
CrystEngComm, 2012, 14, 4142.
14 M. Hartmann and M. Fischer, Microporous Mesoporous Mater.,
2012, 164, 38.
15 Y. Tan, Z. Fu and J. Zhang, Inorg. Chem. Commun., 2011, 14, 1966.
16 A. Taher, D.-J. Lee, B.-K. Lee and I.-M. Lee, Synlett, 2016, 27, 1433.
17 J. Gascon, U. Aktay, M.D. Hernandez-Alonso, G.P.M. van Klink and
F. Kapteijn, J. Catal., 2009, 261, 75.
4 D. Fröhlich, E. Pantatosaki, P. D. Kolokathis, K. Markey, H. Reinsch,
M. Baumgartner, M. A. van der Veen, D. E. De Vos, N. Stock, G. K.
Papadopoulos, S. K. Henninger and C. Janiak, J. Mater. Chem. A,
2016, 4, 11859.
18 R. Srirambalaji, S. Hong, R. Natarajan, M. Yoon, R. Hota, Y. Kim, Y.
Ho Ko and K. Kim, Chem. Commun., 2012, 48, 11650.
19 Y. Luan, Y. Qi, H. Gao, R. S. Andriamitantsoa, N. Zheng and G.
5 a) H. Reinsch, M. A. van der Veen, B. Gil, B. Marszalek, T. Verbiest,
D. de Vos and N. Stock, Chem. Mater., 2013, 25, 17; b) H. Reinsch, S. Wang, J. Mater. Chem. A, 2015, 3, 17320.
Waitschat and N. Stock, Dalton Trans., 2013, 42, 4840; c) H.
Reinsch, F.M. Hinterholzinger, P. Jäker, F. Hesse, B. Reimer, T. Bein,
M. Položij, D. Nachtigallová, P. Nachtigall and N. Stock, J. Phys.
Chem. C, 2015, 119, 26401; d) A. Weiss, N. Reimer, N. Stock, M.
Tiemann and T. Wagner, J. Phys. Chem., 2015, 17, 21634; e) A.
Weiss, N. Reimer, N. Stock, M. Tiemann and T. Wagner, Micropor.
Mesopor. Mat., 2016, 220, 39; f) N. Reimer, B. Bueken, S. Leubner,
C. Seidler, M. Wark, D. De Vos and N. Stock, Chem. Eur. J., 2015, 35,
12517.
20 T. Ahnfeldt, D. Gunzelmann, J. Wack, J. Senker and N. Stock,
CrystEngComm, 2012, 14, 4126.
21 F. Freeman, Chem. Rev., 1981, 80, 329.
22 L. F. Tietze, Chem. Rev., 1996, 96, 115.
23 S. A.-E. Ayoubi, F. Texier-Boullet and J. Hamelin, Synthesis, 1994,
258.
24 D. Prajapati, K. C. Lekhok, J. S. Sandhu and A. C. Ghosh, J. Chem.
Soc., Perkin Trans., 1996, 1, 959.
25 S. Saravanamurugan, M. Palanichamy, M. Hartmann and V.
6 T. Ahnfeldt, N. Guillou, D. Gunzelmann, I. Margiolaki, T. Loiseau, G. Murugesan, Appl. Catal., A, 2006, 298, 8.
Férey, J. Senker and N. Stock, Angew. Chem. 2009, 121, 5265.
7 a) E. Knoevenagel, Ber. Dtsch. Chem. Ges., 1898, 31, 2585; b) G.
Jones, Org. React. (N. Y.), 1967, 15, 204.
26 J. S. Yadav, B. V. Subba Reddy, A. K. Basak, B. Visali, A. V. Narsaiah
and K. Nagaiah, Eur. J. Org. Chem., 2004, 546.
27 Y. K. Hwang, D.-Y. Hong, J.-S. Chang, S. H. Jhung, Y.-K. Seo, J. Kim,
A. Vimont, M. Daturi, C. Serre and G. Ferey, Angew. Chem. Int. Ed.
2008, 47, 4144.
8 S. Hasegawa, S. Horike, R. Matsuda, S. Furukawa, K. Mochizuki, Y.
Kinoshita and S. Kitagawa, J. Am. Chem. Soc., 2007, 129, 2607.
6 | J. Name., 2012, 00, 1-3
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View Article Online
DOI: 10.1039/C6CE02664H
Graphical Abstract
This manuscript reports the Knoevenagel condensation reaction between benzaldehyde and
malononitrile using CAU-1-NH2 as a reusable heterogeneous catalyst under mild reaction conditions.