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Catalysis Letters ISSN 1011-372XVolume 143Number 6 Catal Lett (2013) 143:563-571DOI 10.1007/s10562-013-0995-5
Knoevenagel Condensation ReactionsCatalysed by Metal-Organic Frameworks
Andrew R. Burgoyne & ReinoutMeijboom
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Knoevenagel Condensation Reactions Catalysedby Metal-Organic Frameworks
Andrew R. Burgoyne • Reinout Meijboom
Received: 6 February 2013 / Accepted: 17 March 2013 / Published online: 30 March 2013
� Springer Science+Business Media New York 2013
Abstract Functionalised metal-organic frameworks (MOFs)
which contain amino groups on their secondary building
units (SBUs) are basic catalysts in the Knoevenagel con-
densation. University of Michigan Crystalline Material-1-
amine (UMCM-1-NH2), Isoreticular MOF-3 (IRMOF-3)
and a 5 % IRMOF-3 mixed in Isoreticular MOF-1 (MI-
XMOF) were evaluated as solid basic catalysts and dem-
onstrated to be more active than aniline, their homogenous
anologue. UMCM-1-NH2’s performance was higher than
that of the other MOFs studied. IRMOF-3 and MIXMOF
proved to have equal catalytic ability. Their catalytic per-
formance was monitored at various temperatures and in
different solvents for the reaction between benzaldehyde
and ethyl acetoacetate or ethyl cyanoacetate.
Keywords Heterogeneous catalysis � Catalysis activity �Elementary kinetics � C–C coupling � Organic chemicals
and reactions
1 Introduction
The potential use of porous base catalysts in fine chemical
production is enormous [1–3]. Base-catalysed condensation
and addition reactions are some of the more important
reaction steps employed for building large and complex
molecules, characteristic of the fine chemical and phar-
maceutical industries. The replacement of liquid organic
bases such as piperidine, as well as alkali metal hydroxides,
with solid base catalysts could lead to an easier separation
of catalyst from the product stream, and thus to a cleaner
production. In addition, heterogeneous catalysts are known
to suppress side reactions such as self-condensation and
oligomerization, resulting in better selectivity and reaction
conversion.
The Knoevenagel condensation occurs between a C=O
group and an activated methylene group. This C–C bond
coupling reaction is useful within the drug industry where
important intermediates are prepared. In addition, it is
employed as a classic test reaction to analyse the activity of
a variety of solid base catalysts. The hydrogens in
b-dicarbonyl compounds have typical pKa values in the
range 9–11 [4]. This makes them ideal substrates for test-
reactions utilizing a Knoevenagel condensation. Com-
pounds with active methylene groups, with different pKa
values can be reacted with belzaldehyde to test the
strength of a basic catalyst. A robust study using IRMOF-3
was reported previously using ethyl cyanoacetate (pKa *9)
and ethyl acetoacetate (pKa *10.7) with benzaldehyde
[5].
Here we report on the Knoevenagel condensation
between benzaldehyde and ethyl cyanoacetate or ethyl
acetoacetate as catalysed by the primary amines embedded
inside the well-known metal-organic framework IRMOF-3
[6]. Initial catalyst evaluation resulted in a set of optimized
conditions that was expanded to other MOF frameworks,
namely MIXMOF [7] and UMCM-1-NH2 [8]. All reactions
were compared against the homogeneous counterpart uti-
lizing aniline as the catalyst.
Electronic supplementary material The online version of thisarticle (doi:10.1007/s10562-013-0995-5) contains supplementarymaterial, which is available to authorized users.
A. R. Burgoyne � R. Meijboom (&)
Research Centre for Synthesis and Catalysis, Department of
Chemistry, University of Johannesburg, PO Box 524, Auckland
Park, Johannesburg 2006, South Africa
e-mail: [email protected]
123
Catal Lett (2013) 143:563–571
DOI 10.1007/s10562-013-0995-5
Author's personal copy
2 Experimental
2.1 General Experimental
All chemicals were purchased from Sigma-Aldrich and used
as received. GC runs were performed on a Shimadzu
GC-2010-Plus with an auto injector (AOC-20i), auto sam-
pler (AOC-20s) and a 30 m RTX�-5 fused silica capillary
column. The synthesis of IRMOF-3 [6], MIXMOF [7] and
UMCM-NH2 [8] was performed according to literature
procedures. All characterisation data were in agreement with
literature (see supplementary material).
2.2 Catalytic Runs
All catalytic runs were performed in a similar manner. A
representative example is given here. A given amount of the
amino containing catalyst, corresponding to 0.2 mmol –NH2,
was added to a solution of ethyl acetoacetate or ethyl cya-
noacetate (7 mmol) in solvent (5 cm3) in a round bottom flask
(50 cm3). The reactor was encapsulated in a water jacket for
temperature control, while being shaken under an inert atmo-
sphere (N2) to avoid oxidation. After temperature equilibrium
was reached, benzaldehyde was added (8 mmol) while keep-
ing the reaction mixture under a static nitrogen atmosphere.
The reaction mixture was sampled at predetermined time-
intervals. A 40 ll sample was diluted with CH2Cl2 (1.9 cm3)
and of this mixture 0.5 ll was injected into the GC. The
analysis was performed immediately after sampling to avoid
any additional conversion in the reaction mixture.
2.3 Computational Details
The averages of triplicate catalytic runs were modelled onto
a line of best fit using the equation y = -A e(-Rx) ? c using
Kinetic Studio. The gradient of these exponential slopes
provided the kobs for each catalytic run with a corresponding
standard deviation. Manipulation of these provided infor-
mation to calculate the activation energy from the Arrhenius
equation and the enthalpy and entropy from the Eyring Plot.
An ANOVA statistical analysis, using Microsoft Excel 2010,
was performed on the final conversion of the homogenous vs
heterogeneous, solvent and temperature studies to statisti-
cally analyse their differences. A Student’s t test was per-
formed on the final conversion of the MeOH/EtOH at 353
and 333 K, the order of addition of substrates and different
substrates studies to compare two different variables.
3 Results and Discussion
The Knoevenagel condensation, of aldehydes with com-
pounds containing activated methylene groups, is a robust
reaction often used to test catalytic abilities of basic cata-
lysts [9] and in the production of fine chemicals as well as
heterocyclic compounds of biological significance [10].
Conventionally, this reaction is catalysed by alkali metal
hydroxides or by homogeneous organic bases like primary,
secondary and tertiary amines [11]. However, recycling
and catalyst recovery are problems which arise from their
use.
The amine catalysed Knoevenagel condensation reac-
tion, Scheme 1, involves the nucleophilic attack of the
amine onto the methylene substrates resulting in a carbo-
cation intermediate. The carbo-cation intermediate then is
involved in a nucleophilic addition with benzaldehyde
resulting in the formation of the product and water with
100 % selectivity and regeneration of the amine catalyst.
The metal-organic frameworks IRMOF-3, UMCM-1-
NH2 and MIXMOF were tested as potential basic catalysts
in the Knoevenagel condensation reaction between benz-
aldehyde and different methylene substrates in a range of
solvents at different temperatures. Initial tests were per-
formed using diethyl malonate which has a pKa of 13.3 and
benzaldehyde utilizing IRMOF-3 as the catalyst. The pKa
of this substrate, however, proved to be too high and only
1.6 ± 0.9 % of the diethyl malonate was converted to the
desired product after 130 min in DMSO at 318 K. The
reaction was allowed to continue up to 20 h where it
revealed that only 5.9 ± 1.1 % conversion was achieved
with 100 % selectivity.
Subsequently, ethyl acetoacetate was utilized as a sub-
strate, with a pKa of 10.7. The lowered pKa resulted in
increased conversion. In the absence of a catalyst, some
product formed (3.9 ± 1.8 %), similar to the reaction using
diethyl malonate as a substrate (1.6 ± 0.9 %). A compar-
ison was thus performed to analyse the performance of
IRMOF-3, a porous heterogenous catalyst, against aniline,
a homogenous analogue similar to that found within the
MOF structure.
The products of the Knoevenagel condensation between
benzaldehyde and ethyl acetoacetate were characterized
using conventional spectroscopic techniques. Filtration, to
remove the IRMOF-3 catalyst, and subsequent removal of
the solvent in vacuo resulted in a clean product. Conven-
tional FT-IR and NMR analyses on the yellow oil obtained
confirmed the presence of the proposed condensation
product.
FT-IR analysis of the substrates, benzaldehyde and ethyl
acetoacetate, and product gave vital information about the
recognition of their disappearance of substrates and the
appearance of the product. The product showed identifiable
absorption peaks at mC=C = 1,624 cm-1 for the newly
formed C=C bond; mC=O = 1,727 and 1,705 cm-1 for the
b-dicarbonyl system which shifted from mC=O = 1,737 and
1,713 cm-1 in ethyl acetoacetate; m=C–H = 2,995 cm-1
564 A. R. Burgoyne, R. Meijboom
123
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and d=C–H = 696 cm-1 for the newly formed proton on the
alkene; mC–O–C = 1,044 cm-1 which shifted from mC–O–C =
1,040 cm-1 in ethyl acetoacetate. The product showed an
absence of peaks in the region 2,720–2,850 cm-1 typical for
the methylene hydrogens in ethyl acetoacetate, m=C–H =
2,984 cm-1. Also absent in the product were m=C–H = 2,818
and 2,737 cm-1 and mC=O = 1,698 cm-1, which represent
the benzaldehyde’s carbonyl hydrogen and the carbonyl.1H NMR analysis of the reaction mixture was performed
at the start of a reaction and then again upon completion of
the 130 min. The singlet at 10.13 ppm (CHO) for benzal-
dehyde was of lower intensity than that of the peaks of the
product. New absorbance peaks at 1.29 ppm (t, 3H, CH3,
J = 6.8 Hz), 2.39 ppm (s, 3H, CH3), 4.28 ppm (q, 2H,
CH2, J = 7.2 Hz), 7.34–7.40 ppm (m, 3H, CH), 8.01 ppm
(d, 2H, CH) and 8.40 ppm (s, 1H, C=CH) were present,
confirming the presence of the product.
The heterogeneous catalyst, IRMOF-3, gave significantly
higher conversion rates in DMSO at 353 K and was faster,
kobs = (6.71 ± 1.21) 910-2 s-1, than the homogenous
equivalent, aniline which had a kobs = (0.30 ± 0.01)
910-2 s-1, even with the amount of amino groups being
equal in both cases (Table 1). Aniline closely resembles the
2-aminoterephthalic acid which contains the amino group
within the MOF material. Gascon et al. [5] also observed a
similar trend when working with ethyl cyanoacetate in
DMSO. This indicates that the reactivity of the amino groups
is increased by being contained within the MOF structure. In
the absence of a catalyst only 3.9 ± 1.8 % of the substrates
were converted to product, kobs = (0.00 ± 0.17) 910-2 s-1.
The turn-over-frequencies (TOFs) given are based on the
initial data points (10 min into reaction) and based on the
assumption that all –NH2 groups are catalytically active cen-
tres, no matter how deep within the porous MOF network.
3.1 Optimization of Reaction Conditions
A range of conditions could potentially influence the
Knoevenagel condensation reaction. Thus, in order to be
able to compare the various potential catalysts, we opti-
mized the conditions for IRMOF-3. Subsequently, the
different MOF materials were compared under optimized
conditions. The following parameters were studied: solvent
dependence, temperature and order of addition.
A solvent dependence study was performed at 353 K to
determine which factors would influence the activity of the
catalysts. The reaction rate of a homogenous basic catalyst
depends on several aspects, including:
• Polarity: when polar reagents are involved, the transi-
tion-state complex is better able to be solvated by polar
solvent molecules. This behaviour of the solvent influ-
encing the transition state is accounted for in the ability of
the catalyst to transfer protons. The general rule is that the
more polar solvents show higher reaction rates [12, 13].
• Amphiprotic properties: a protic solvent (i.e. ethanol or
methanol) might also increase the activation of the slightly
basic benzaldehyde, resulting in higher activities.
The solvents selected, for solvent dependence study of
the MOF catalysed reaction between benzaldehyde and
ethyl acetoacetate, were solvents with a range of dielectric
constants (e): DMSO (e = 48.9), DMF (e = 36.7), MeOH
H
O
O
O O
O
O
CN
O
O O
O
O
CN
H2O
(i)
(ii)
(ii)
(i)
NH2
NH3O
O O
O
O
CN
(i)
(ii)
O
O O
O
O
CN
(ii)
(i)
O
O
+
Scheme 1 Catalytic cycle for
Knoevenagel condensation
between benzaldehyde and
i ethyl acetoacetate or ii ethyl
cyanoacetate, catalysed by a
primary amine as contained in
the MOF materials
Knoevenagel Condensation Reactions 565
123
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(e = 33), EtOH (e = 24.3) and toluene (e = 2.4). Solvents
with higher dielectric constants were assumed to have a
higher polarity.
The results for the solvent dependence study are shown
in Fig. 1 where benzaldehyde was reacted with ethyl ace-
toacetate at 353 K in 5 cm3 of different solvents with IR-
MOF-3 as a catalyst. DMSO, with the highest dielectric
constant, had the highest conversion of 64.5 % ± 4.4 with
kobs = (10.53 ± 0.52) 910-2 s-1. This can be explained
by the hydrogen bond acceptor power of DMSO, which
stabilises the –NH2 group in the protonated form, and thus
increases the rate of proton transfer [12] from the methylene
substrate to the amine catalyst. As a result, the intermediate
is stabilized by the more polar solvents. In all runs, typical
first order kinetic plots were obtained, as shown in Fig. 1.
The calculated rates of reaction, kobs, for the various sol-
vents studied in the Knoevenagel condensation of benzal-
dehyde and ethyl acetoacetate at 353 and 333 K catalysed by
IRMOF-3 are listed in Table 2.
The hydrophilic character of a catalyst support determines
the performance of supported homogeneous catalysts [5, 10].
A relationship occurs such that: the higher the hydrophilicity
of the catalyst support, the lower the effect of the solvent and
thus the faster diffusion can occur within the material. Not all
Zn atoms in IRMOF-3 are fully coordinated [9], i.e. have a
full coordination sphere, resulting in IRMOF-3 being a
hydrophobic catalyst support. Hence, a large effect on the
catalytic ability of many Zn based MOFs is due to the effect
of solvents. However, it was noted that at 353 K in the more
polar solvents the amount of catalyst able to be recycled, by
filtration and washing with fresh DMF, was significantly less
than in solvents with lower polarities. Nguyen et al. [14]
showed that zeolite imidazolate frameworks (ZIFs), a novel
subclass of MOFs, also suffers from a decrease in the crystal
size, in THF (e = 7.6), due to the crystals breaking into small
fragments. Thus, a sacrificial balance between activity and
recyclability needs to be made.
Figure 1 also showed similar activities for both MeOH
(Table 2, entry 3) and EtOH (Table 2, entry 4) at 353 K,
which was notably above each of their boiling points under
atmospheric pressure. To achieve these observations the
reaction vessel was fitted with a reflux condenser while
being capped to conserve the static nitrogen atmosphere.
A second evaluation of MeOH (Table 2, entry 6) and EtOH
(Table 2, entry 7) as solvents was performed, this time at
333 K, which is lower than each of the solvents’ boiling
points. A similar trend to what was previously seen was
observed again at the lower temperatures, being that the more
Table 1 Reaction conversions, calculated kobs values and TOFs for solvents studied in Knoevenagel condensation of benzaldehyde and ethyl
acetoacetate catalysed by IRMOF-3, aniline and without catalyst in DMSO at 353 K
Catalyst Solvent Temperature (K) Reaction conversion (%) kobs (10-2 s-1) Initial TOF (min-1)
IRMOF-3 DMSO 353 64.5 ± 4.4 67.08 ± 12.08 0.44
Aniline 28.0 ± 3.6 3.00 ± 0.99 0.02
No catalyst 3.9 ± 1.8 0.00 ± 1.65 –
Fig. 1 Knoevenagel
condensation of benzaldehyde
and ethyl acetoacetate in DMSO
(filled diamond); DMF (filledsquare); MeOH (filled triangle);
EtOH (white circle) or toluene
(times) at 353 K catalysed by
IRMOF-3; n = 3 repeats
566 A. R. Burgoyne, R. Meijboom
123
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polar solvent, MeOH, showed a higher activity with a con-
version of 53.5 ± 2.2 % and kobs = (4.76 ± 0.50) 9
10-2 s-1. It was also noted that the conversion in MeOH was
raised at 333 K, in comparison to the conversion at 353 K. The
conversion in EtOH at 333 K, 34.7 ± 4.5 %, was lower than
its conversion at 353 K, 42.3 ± 1.4 %. However the rate of
reaction was faster, kobs = (6.96 ± 0.92) 910-2 s-1, at
353 K than at 333 K where kobs = (2.32 ± 0.55) 910-2 s-1.
Studies at 353, 333 and 313 K (Table 1, entries 8–10)
were performed on the Knoevenagel condensation between
benzaldehyde and ethyl acetoacetate in DMF under a static
nitrogen atmosphere catalysed by IRMOF-3. DMF was
selected as the best solvent even though DMSO showed
higher activities at 353 K, but it was observed that the
amount of catalyst which could be recovered, by filtration
and washing with fresh DMF, after a catalytic run was
higher in DMF than it was in DMSO. Thus a sacrifice
between activity and recyclability was made in the aim to
optimise the catalytic reaction conditions of the catalyst.
Catalytic reactions performed at 353 K not only gave
higher conversions, 54.0 ± 0.0 % within the 130 min
where the reaction was monitored, but also a higher
kobs = (9.58 ± 0.43) 910-2 s-1 was observed. At 333 K,
a lower temperature, a lower conversion of 39.0 ± 1.4 %
was obtained with a kobs = (2.11 ± 0.20) 910-2 s-1. The
lowest temperature studied, 313 K, resulted in a conversion
of 27.7 ± 4.3 % with a kobs = (0.51 ± 0.38) 910-2 s-1.
To ascertain as to whether the order of addition was
important in the Knoevenagel reaction, between benzalde-
hyde and ethyl acetoacetate catalysed by IRMOF-3 in DMF
at 313 K, a comparative reaction was performed where the
ethyl acetoacetate (Table 2, entry 12) was added first as
opposed to the addition of benzaldehyde first (Table 2, entry
11). This was performed to rule out the concept of the for-
mation of amides, where the ethyl acetoacetate would react
with the benzaldehyde, which would thus deactivate the
catalyst. No significant difference in the percent conversion
was observed in the catalytic ability of IRMOF-3. Gascon
et al. [5] similarly saw this occurring in the Knoevenagel
catalysed reaction of ethyl cyanoacetate and benzaldehyde.
A higher conversion might be expected when benzalde-
hyde is added first, as this would inhibit the formation of the
deactivating amides. However, this was not observed and the
conversion achieved by adding ethyl acetoacetate first was
27.7 ± 1.9 % with kobs = (0.51 ± 0.38) 910-2 s-1, where
upon adding the benzaldehyde first the conversion attained
was 27.6 ± 2.8 % with kobs = (0.52 ± 0.41) 910-2 s-1.
From the Arrhenius equation the activation energy, Ea,
can be calculated and states that:
k ¼ Ae�EaRT
where k is the observed rate constant (s-1), A the pre-
exponential factor, Ea the activation energy (J mol-1),
R the Universal gas constant (8.3144621 J mol-1 K-1) and
T the temperature (K). Thus a plot of 1/T versus ln kobs
produces a straight line where the product of the gradient
and the Universal gas constant equate to the Ea.
From the Eyring-Polanyi equation the enthalpy, DH, and
entropy, DS, can be calculated and states that:
k ¼ kbT
he�DG�
RT
where k is the observed rate constant (s-1), kb the Boltzmann
constant (1.3806488 9 10-23 J K-1), T the temperature
Table 2 Reaction conversions, calculated kobs and TOFs for the Knoevenagel condensation of benzaldehyde and ethyl acetoacetate catalysed by
IRMOF-
Run Solvent Temperature (K) Reaction conversion (%) kobs (10-2 s-1) Initial TOF (min-1)
1 DMSO 353 64.5 ± 4.4 10.53 ± 0.52 0.44
2 DMF 54.0 ± 0.5 9.58 ± 0.43 0.39
3 MeOH 43.0 ± 5.2 7.38 ± 1.07 0.22
4 EtOH 42.3 ± 1.4 6.96 ± 0.92 0.29
5 Toluene 15.8 ± 2.4 1.17 ± 0.55 0.15
6 MeOH 333 53.5 ± 2.2 4.76 ± 0.50 0.39
7 EtOH 34.7 ± 4.5 2.32 ± 0.55 0.29
8 DMF 353 54.0 ± 0.0 9.58 ± 0.43 0.39
9 DMF 333 39.0 ± 1.4 2.11 ± 0.20 0.27
10 DMF 313 27.7 ± 4.3 0.51 ± 0.38 0.10
11 DMFa 313 27.6 ± 2.8 0.52 ± 0.41 0.10
12 DMF 313 27.7 ± 1.9 0.51 ± 0.38 0.08
For all runs, the solvent volume was 5 cm3 and the values are the average of n = 3 repeats. Reaction conversions are reported at the end of the
run (130 min)a Benzaldehyde added first
Knoevenagel Condensation Reactions 567
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(K), h the Planck’s constant (6.62606957 9 10-34 J s), DG*
the Gibbs energy of activation (J mol-1), R the Universal gas
constant (8.3144621 J mol-1 K-1) and T the temperature
(K). Thus a plot of 1/T versus ln (k/T) produces a straight line
with gradient equal to –DH/R and with a y-intercept of ln
(kb/h) ? DS/R.
The aforementioned plots were performed and Ea was
found to be 973 J mol-1, DH was calculated as 933 J mol-1
and DS as -84 J K-1 mol-1 for the IRMOF-3 catalysed
Knoevenagel condensation of benzaldehyde and ethyl ace-
toacetate in DMF.
3.2 Comparative Reactions Using IRMOF-3, UMCM-
1-NH2 and MIXMOF
The ability of these basic MOFs to deprotonate different
methylene hydrogens was tested in the Knoevenagel cata-
lysed reaction between benzaldehyde and diethyl malonate
(pKa *13.3 [15]); ethyl acetoacetate (pKa *10.7) and
ethyl cyanoacetate (pKa *9.0 [16]) at 313 K in DMF. In
most cases, the Knoevenagel reaction is used as a test
reaction to shed light on the catalytic abilities of basic
solids, particularly MOFs and zeolites [6].
None of the MOF materials were able to catalyse the
Knoevenagel reaction between benzaldehyde and diethyl
malonate with any significant conversion, as the pKa was
too high for the –NH2 groups present in the MOF. Selecting
a different substrate, ethyl acetoacetate, resulted in lowering
the pKa of the substrate from 13.3 to 10.7 allowed for sig-
nificantly higher results as shown in Table 3, which could
then be used for comparison of the different MOF catalysts.
For IRMOF-3 it was observed that only 1.2 ± 0.4 %
conversion was achieved when reacting diethyl malonate
with benzaldehyde; 27.7 ± 2.8 % conversion could be
achieved when reacting ethyl acetoacetate with benzalde-
hyde and 73.1 ± 1.6 % could be achieved when reacting
ethyl cyanoacetate with benzaldehyde after 130 min at
313 K in DMF. The difference in conversions is large, due
to the various strengths of the C–H bond of the methylenes
in the different substrates.
For the same catalyst loading, as in IRMOF-3, a large
mass of MIXMOF was required. To provide 0.18 mmol –
NH2 in IRMOF-3 only 36 mg is required. However, for
Table 3 Reaction conversions, calculated kobs and TOFs in Knoevenagel condensation of benzaldehyde and ethyl acetoacetate or ethyl cya-
noacetate or diethylmalonate catalysed by IRMOF-3, UMCM-1-NH2 and MIXMOF
Run Substrate Catalyst Solvent Temperature
(K)
Reaction
conversion (%)
kobs
(10-2 s-1)
Initial TOF
(min-1)
Reference
Ethyl acetoacetate UMCM-1-NH2 44.0 ± 3.4 3.04 ± 0.23 1.01
1 IRMOF-3 DMF 27.7 ± 2.8 0.46 ± 0.40 0.10 This work
MIXMOF 30.0 ± 2.1 0.55 ± 0.38 0.07
Ethyl cyanoacetate UMCM-1-NH2 73.1 ± 1.6 11.58 ± 0.13 2.02
2 IRMOF-3 DMF 62.3 ± 1.7 2.87 ± 0.24 1.21 This work
MIXMOF 62.9 ± 3.2 3.26 ± 0.22 1.13
3 Diethyl malonate IRMOF-3 DMF 1.2 ± 0.4 – – This work
4 Ethyl cyanoacetate IRMOF-3 DMSO 313 99 – 2.9 [5]
5 Ethyl acetoacetate IRMOF-3 DMSO 353 58 – 0.33 [5]
6 Ethyl cyanoacetate Ethyldiamine
grafted MIL-101
Cyclo
hexane
353 80 – 0.37 [17]
7 Ethyl acetoacetate BEA Xylene 403 82 – – [18]
8 Ethyl acetoacetate TS-1 Xylene 403 41 – – [18]
9 Ethyl acetoacetate CuBTC Xylene 403 40 – – [18]
10 Ethyl acetoacetate FeBTC Xylene 403 58 – – [18]
11 20-hydroxyacetophenone
SBA-NH2-10-P DMSO 413 52 – – [19]
12 C6H5–
NO2
413 53 – – [19]
13 C6H5–CN 413 35 – – [19]
14 Hexyl
alcohol
413 12 – – [19]
15 1,3,5-
CH3–
C6H3
413 55 – – [19]
16 – 413 84 – – [19]
Solvent DMF, n = 3 repeats
568 A. R. Burgoyne, R. Meijboom
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MIXMOF, as the percentage of ABDC is only 5 % amongst
the organic linkers, 720 mg MIXMOF is required to supply
0.18 mmol –NH2. This increase in mass made using
MIXMOF, as a catalyst, less desirable than IRMOF-3, as
twenty times the mass is required and the conversion of ethyl
cyanoacetate at 313 K in DMF was only 62.9 ± 3.2 % after
130 min. This was significantly larger than the conversion of
ethyl acetoacetate, which only achieved 30.0 ± 2.1 % at
313 K in DMF after 130 min. MIXMOF and IRMOF-3 both
have similar catalytic abilities to catalyse the Knoevenagel
reaction between ethyl acetoacetate or ethyl cyanoacetate
and benzaldehyde.
It is of note that UMCM-1-NH2, with a larger surface
area and pore sizes, in both cases provided the highest
Fig. 2 Knoevenagel
condensation of benzaldehyde
and ethyl cyanoacetate (dasheddotted line) or ethyl
acetoacetate (dotted line) in
DMF at 313 K catalysed by
UMCM-1-NH2 (filled triangle);
MIXMOF (filled square);
IRMOF-3 (filled diamond);
n = 3 repeats
Table 4 Reaction conversions, calculated kobs and TOFs in Knoevenagel condensation of benzaldehyde and ethyl acetoacetate or ethyl cya-
noacetate catalysed by recycled IRMOF-3, UMCM-1-NH2 and MIXMOF
Run Catalyst Substrate Solvent Temperature (K) Reaction conversion (%)
1 UMCM-1-NH2 Ethyl acetoacetate DMF 313 44.0 ± 3.4
2 41.5 ± 2.7
3 39.9 ± 1.5
1 UMCM-1-NH2 Ethyl cyanoacetate DMF 313 73.1 ± 1.6
2 72.6 ± 2.1
3 70.4 ± 1.9
1 IRMOF-3 Ethyl acetoacetate DMF 313 27.7 ± 2.8
2 27.5 ± 1.8
3 25.8 ± 2.2
1 IRMOF-3 Ethyl acetoacetate DMF 313 62.3 ± 1.7
2 60.9 ± 2.3
3 60.1 ± 2.5
1 MIXMOF Ethyl acetoacetate DMF 313 30.0 ± 2.1
2 29.8 ± 1.8
3 27.6 ± 3.2
1 MIXMOF Ethyl acetoacetate DMF 313 62.9 ± 3.2
2 61.7 ± 2.7
3 59.2 ± 1.9
Solvent DMF, n = 3 repeats
Knoevenagel Condensation Reactions 569
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reaction rates with kobs = (11.58 ± 0.13) 910-2 s-1 for
the Knoevenagel condensation between ethyl cyanoacetate
and benzaldehyde and kobs = (3.04 ± 0.23) 910-2 s-1 for
ethyl acetoacetate and benzaldehyde. This large difference
in kobs, shown in Table 3, can be explained by the relative
ease by which the more acidic hydrogens of ethyl cya-
noacetate can be removed than the less acidic hydrogens of
ethyl acetoacetate. Of interest also are the similar yet
slightly larger kobs of MIXMOF, in both cases, compared to
that of IRMOF-3. This difference was analysed statistically
using the Student’s t test to compare the differences
between the data.
UMCM-1-NH2 also required a higher mass, than IRMOF-3,
of catalyst to keep the catalyst loading constant. Although in
this case only 144 mg UMCM-1-NH2 is needed to provide
0.18 mmol –NH2. The catalytic ability of UMCM-1-NH2
was higher than IRMOF-3 and MIXMOF. UMCM-1-NH2
resulted in a larger conversion, over the 130 min, of
44.0 ± 3.4 % in the reaction between benzaldehyde and
ethyl acetoacetate and of 73.1 ± 1.6 % in the reaction
between benzaldehyde and ethyl cyanoacetate. These con-
versions are competitive with literature results, as shown in
Table 3. IRMOF-3 has been shown to be able to achieve a
remarkable 99 % conversion of substrate in DMSO at 313 K
when ethyl cyanoacetate was used as a substrate and with
ethyl acetoacetate only 58 % was observed [5]. Ethyldi-
amine grafted MIL-101 yielded 80 % reaction conversion of
ethyl cyanoacetate at 353 K [17], which is higher than all the
observed reaction conversions in this study although the
solvent DMSO was used at 353 K, which was higher than the
studies performed on ethyl cyanoacetate. In the work of
Opanasenko et al. [18] BEA, TS-1, CuBTC and FeBTC were
shown to give 82, 41, 40 and 58 %, respectively, in the cat-
alysed reaction of benzaldehyde and ethyl acetoacetate at
403 K in xylene. Although, in this study IRMOF-3 and
MIXMOF did result in lower reaction conversions than the
study performed by Opanasenko et al., this is most likely due
to the temperature it was performed at, 313 K, as opposed to
403 K. Similarly, the amine containing SBA-15 zeolite was
shown to have basic catalytic abilities in catalysing the car-
bon coupling of the 20-hydroxyacetophenone and benzalde-
hyde, as shown in Table 3, in a variety of solvents. The
reaction conversions were of a similar magnitude to the
results obtained in this study, despite the lower surface
area of the zeolitic basic catalyst and the higher reaction
temperature, 413 K [19] (Fig. 2).
3.3 Recyclability
A large loss of mass, up to as much as half the mass in
some cases due to attrition and dissolution, of the hetero-
geneous catalyst at 353 K and DMSO as a solvent was
observed. Consequently, less harsh conditions were chosen
for the recyclability study. The Knoevenagel condensation
of benzaldehyde and ethyl acetoacetate in DMF at 313 K
showed similar results, as shown in Table 4, for the first
three catalytic runs. GC analysis to quantify reaction con-
version for recyclability studies were performed only at
130 min for comparison of each catalytic run after recy-
cling of the catalyst. Upon completion of a catalytic run,
the catalyst was filtered from the reaction mixture and
washed in DMF at 313 K overnight and then washed with
CHCl3. Activation of the catalyst and removal of CHCl3was achieved by drying the catalyst in a vacuum oven at
373 K at 560 mm Hg. Gascon et al. [5] also observed such
catalytic capabilities over the first three runs for IRMOF-3
in the Knoevenagel condensation of benzaldehyde and
ethyl cyanoacetate. Nguyen et al. [14] provided evidence
that for the first three catalytic runs ZIF-9 had the same
reaction rate in the Knoevenagel condensation of benzal-
dehyde and malononitrile.
4 Conclusions
In this study IRMOF-3, UMCM-1-NH2 and MIXMOF
were compared as basic heterogeneous catalysts in the
Knoevenagel condensation between benzaldehyde and
ethyl acetoacetate or ethyl cyanoacetate. IRMOF-3 was
found to yield higher conversion rates than the homoge-
neous analogue, aniline. This suggests the idea that the
basicity of the amine group within the MOF structure is
enhanced when within the MOF material [5].
UMCM-1-NH2 in all cases had higher catalytic activities
than IRMOF-3 and MIXMOF which had near identical
catalytic activities in all cases. Optimization of the reaction
conditions found that 353 K was the optimal temperature for
higher substrate conversion, but lower temperatures, 313 K,
allowed for better catalyst recovery. Substrates with lower
pKa values yielded high conversions. From the Arrhenius
equation it was found that Ea = 973 J mol-1 and from the
Eyring-Polanyi equation that DH = 933 J mol-1 and
DS = -84 J K-1 mol-1 for the IRMOF-3 catalysed Knoe-
venagel condensation between benzaldehyde and ethyl
acetoacetate.
Acknowledgments Funding from the South African NRF, Sasol
R&D and the research fund from the University of Johannesburg are
gratefully acknowledged. ARB is grateful to the NRF-DAAD for a
scholarship. Mr. D. Harris and Dr. R. Meyer (Shimadzu South Africa)
are acknowledged for use of their equipment.
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