Merging metal-organic framework catalysis with organocatalysis: A thiourea functionalized heterogeneous catalyst at the nanoscale

Article abstract of DOI:10.1039/c3cy00864a

A new thiourea-containing metal-organic framework (MOF) catalyst was synthesized. It overcomes recycling, self-aggregation and solvation issues that exist in homogeneous thiourea catalysts. Nanomorphology was introduced to increase the dispersion of the solid catalyst in solvent. Acetalization and Morita-Baylis-Hillman reactions were catalyzed using the new thiourea MOF catalyst. This journal is the Partner Organisations 2014.

Full text of DOI:10.1039/c3cy00864a

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Merging metal–organic framework catalysis with
organocatalysis: A thiourea functionalized
heterogeneous catalyst at the nanoscale†
Cite this: Catal. Sci. Technol., 2014,
, 925
4
Received 31st October 2013,
Accepted 31st December 2013
Yi Luan, Nannan Zheng, Yue Qi, Jia Tang and Ge Wang*
DOI: 10.1039/c3cy00864a
www.rsc.org/catalysis
A new thiourea-containing metal–organic framework (MOF) catalyst
was synthesized. It overcomes recycling, self-aggregation and solvation
issues that exist in homogeneous thiourea catalysts. Nanomorphology
was introduced to increase the dispersion of the solid catalyst in
solvent. Acetalization and Morita–Baylis–Hillman reactions were
catalyzed using the new thiourea MOF catalyst.
metal–organic materials. Effective surface areas for catalytic
performance can be enhanced by the nanomorphology of
11
MOFs in comparison to their macroscopic counterparts. Further-
more, nanoscale metal–organic materials show well-defined
and uniform sizes and morphologies, which improve disper-
sion in aqueous media or other solvents.
Organocatalysis is used to describe reactions promoted by
a small molecule organic catalyst, which offers great advan-
tages in availability, cost and toxicity relative to homogeneous
Metal–organic frameworks (MOFs) are crystalline materials
with extended structures which can be utilized in many fields, such
1
as gas sorption, sensing, drug delivery and catalysis. In recent
12
metal-catalyzed reactions. Thiourea catalysts, which operate
years, MOFs were studied as novel heterogeneous catalysts
via double hydrogen-bonding interactions with the substrates,
2
because of their porous and tunable nature. However,
13
are a milestone achievement of modern organocatalysis.
A
established MOF structures have relatively little catalytic
reactivity due to the limited selections of metals and organic
variety of organic transformations have been promoted by
thiourea catalysts in a racemic or asymmetric fashion such
as Diels–Alder reaction, Michael addition and protection of
3
ligands. In order to further extend the catalytic activity
through structure modification, a post-synthetic modification
14
alcohols. However, several issues need to be overcome in
(PSM) strategy can be introduced to provide access to porous
order to make thiourea catalysts more practical. First, homo-
geneous thiourea catalysts are difficult to recycle. Another
issue is that thiourea catalysts are known to deactivate
through self-quenching, which is a self-assembly behavior due to
catalyst–catalyst interaction, such as dimerization or oligomeriza-
materials with new or enhanced properties for specialized
4
applications, such as catalysis. PSM is generally achieved
using a pre-installed moiety on the precursor ligand that can
5
be coupled with a reactive species in a heterogeneous fashion.
IRMOF-3 (isoreticular metal–organic framework-3) is a porous
15
tion (Fig. 1). Immobilization of the thiourea functionality would
MOF decorated with primary amine groups, which can be
be ideal to prevent both recycling and self-quenching issues.
6
further modified through a PSM approach. Cohen pioneered
7
the modification of the IRMOF-3 structure moiety, and several
IRMOF-3 have been post-synthetically modified through dif-
8
ferent organic transformations. While tremendous amounts
of MOF materials have been utilized as catalysts, nanosized
9
MOFs received much less attention. Although IRMOF-3 at the
nanoscale has been synthesized, its use in catalysis has not
1
0
been studied yet. The nanomorphology of MOFs strongly
influences or even improves chemical properties of these
School of Materials Science and Engineering, University of Science and
Technology Beijing, 30 Xueyuan Road, Beijing 100083, PR China.
E-mail: gewang@mater.ustb.edu.cn; Fax: +86 10 62327878; Tel: +86 10 62333765
†
Electronic supplementary information (ESI) available: Experimental
procedures, characterization data of the products and NMR spectra of
products. See DOI: 10.1039/c3cy00864a
Fig. 1 Thiourea catalyst and the MOF–thiourea catalyst.
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At the same time, solvation issues of thiourea catalysts can
1
6
also be suppressed. To immobilize the thiourea functionality,
1
7
18
various supports such as mesoporous silica, polymer and
MOF have recently been reported.
19
Merging organocatalysis and MOF heterogeneous catalysis
offers great opportunities to take advantage from both catalytic
processes (Fig. 1). Reactions with excellent catalytic perfor-
mance under extremely mild conditions, easy separation
between the catalyst and substrates and the prevention of self-
quenching can all be achieved using one MOF catalyst.
Recently, post-synthetic modification reactions have been
employed to introduce organocatalytic functional groups into
MOFs, which mimic known Brønsted acid catalysts for cata-
2
0
lytic transfomations. Important organocatalytic molecules,
namely proline, 1,1′-bi-2-naphthol and urea, have been
1
2
1
22
23
Fig. 2 H NMR spectra of digested IRMOF-3. Resonances in the spectra for
unmodified IRMOF-3 (bottom) and modified IRMOF-3: IRMOF-3–thiourea-C6,
4
incorporated into MOF structures as catalysts. Urea and
% modified; IRMOF-3–thiourea-C7, 17% modified; and IRMOF-3–thiourea-C8,
6% modified. All are based on IRMOF-3. Squares and circles represent
signals of modified and 2-aminoterephthalic acid, respectively.
2
4
thiourea containing MOFs
and other hydrogen-bonded
2
2
5
MOFs have been synthesized through different approaches
but rarely employed as catalysts. Despite much progress
in this area, the generation of a thiourea structure motif as
part of the MOF catalyst has attracted much less attention.
Herein, we report a nanoscale MOF–thiourea catalyst that
mimics known organocatalysts – small organic molecules
that accelerate chemical reactions. This approach presents
the first thiourea hydrogen-bonding catalyst synthesized via
post-synthetic modification at the nanoscale. Our idea is to
take some of the concepts from a hydrogen-bonding catalyst
and merge them with the field of metal–organic frameworks,
and boost the catalytic reactivity by taking advantage of the
MOF nanomorphology.
thiourea synthesis and storage, was not observed in our
IRMOF-3–thiourea catalyst according to the NMR spectrum.
The successful synthesis of the IRMOF-3–thiourea catalyst was
also confirmed by electrospray ionization mass spectrometry
(ESI-MS) and FTIR. ESI-MS results showed the expected
molecular ion peak for the modified component in the
IRMOF-3–thiourea molecule. The FTIR study further confirms
the observed CS stretching bands of IRMOF-3–thiourea,
which represent the thiourea network at 1132.5 and 1179.0 cm .
The synthesis of nanoscale IRMOF-3 was achieved using
modified literature procedures. Cubic crystals of IRMOF-3
with good monodispersity and crystallinity were successfully
produced in very high yield (Fig. 3a). Crystal sizes of
about 200–300 nm diameters were observed in the present
synthesis at room temperature. The loading of the thiourea
functionality did not affect the nanomorphology of IRMOF-3
(Fig. 3b). Our successful synthesis of IRMOF-3 was proved by
powder X-ray diffraction (PXRD) studies (Fig. S2†). The PXRD
pattern of nano IRMOF-3 was similar to that of regular IRMOF-3.
This indicates the high similarity of both crystalline structures.
XRD patterns showed that the thiourea modified IRMOF-3 material
possessed the same reflections as unmodified IRMOF-3.
−1
The synthesis of the IRMOF-3–thiourea catalyst started from
the literature known IRMOF-3. Reacting pre-synthesized IRMOF-3
with 3,5-bis(trifluoromethyl)phenyl isothiocyanate under basic
conditions provided the desired IRMOF-3–thiourea catalyst
(Scheme 1). Scheme 1 illustrates the orientation of the supported
3
,5-bis(trifluoromethyl)phenylthiourea after DFT energy mini-
mization. The thiourea group occupies a large portion of the
pore structure, allowing the entry and exit of substrate
molecules due to its flexibility. The loading of a thiourea
moiety can be controlled by reaction conditions and then
analyzed using nuclear magnetic resonance (NMR) spectro-
scopy (Fig. 2). NMR studies provided the different loading
ratios of catalysts C6, C7 and C8, which correspond to 4%,
1
7% and 26% thiourea incorporation, respectively. Further-
more, solvent incorporation, which is a common problem in
Scheme
1
Post-synthetic
modification
of
IRMOF-3
with
3,5-bis(trifluoromethyl)phenyl isothiocyanate.
Fig. 3 SEM images of nanoscale IRMOF-3 (a) and IRMOF-3–thiourea (b).
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The thiourea-containing IRMOF-3 was examined by thermal
gravimetric analysis (TGA) to confirm the thermal and struc-
tural stability of the heterogeneous thiourea catalyst. The nano
MOF catalyst showed good thermal stability similar to
IRMOF-3. A weight loss at ~344 °C and decomposition temper-
ature around 386 °C were observed according to the TG analysis,
very low reactivity (Table 1, entry 6). 3,5-Bis(trifluoromethyl)-
phenylthiourea (C7) showed much improved reactivity com-
pared to its urea counterpart (C5) (Table 1, entries 7 and 8).
At 17% loading, nanosized IRMOF-3–thiourea C7 showed
better performance than its bulk partner, which suggested a
higher utilization rate of the MOF surface and pore (Table 1,
entries 8 and 9). A higher thiourea loading (26%) on the
IRMOF-3–thiourea catalyst C8 gave a comparable yield, with
the turnover numbers (TON) up to 490 (Table 1, entry 10).
The aforementioned conditions were successfully applied to
a range of acetalization and Morita–Baylis–Hillman reactions
(Table 2). Halogenated aromatic rings, such as F and Br, were
tolerated (Table 2, entries 1–2). Ethene diol 2b can also act as
an alcohol nucleophile (Table 2, entry 3). 9-Anthraldehyde (1e)
gave almost no desired product based on the crude NMR
analysis, which demonstrates reagent size selectivity for such
a heterogeneous MOF thiourea catalyst (Table 2, entry 4). This
2
6
which agree with the literature data.
We initiated our investigation by evaluating the acetalization
reaction of benzaldehyde (1a) at room temperature. Strong
Brønsted acids are known to promote the acetalization of
benzaldehyde (Table 1, entry 2). An organocatalyst offers a great
advantage in promoting the same reactivity under much milder
conditions. Homogeneous thiourea catalysts for acetalization
27
have been reported. Schreiner's catalyst was able to induce
the formation of benzaldehyde acetal (3a) (Table 1, entry 4). A
similar thiourea catalyst with two carboxylate groups was also
evaluated, which gives a good yield of acetal (Table 1, entry 3).
Acetal formation can be promoted by certain MOF structures,
2
8
29
such as Cu (BTC) (BTC = 1,3,5-benzenetricarboxylate), FeBTC
3
2
3
0
and In(III) MOFs under various conditions. However, IRMOF-3
shows almost no reactivity at room temperature for 12 h
Table 2 IRMOF-3–thiourea catalyzed acetalization and Morita–Baylis–
Hillman reactionsa
(Table 1, entry 5). It can be concluded that the thiourea moiety
is responsible for acetalization reactivity. The phenyl substituted
IRMOF-3–thiourea catalyst (C4) at the nanoscale showed
Table 1 Acetalization promoted by various catalystsa
Entry
1
Substrate
Nu
Product
Yield
92%
EtOH
2
3
EtOH
91%
96%
4
EtOH
<5%
b
c
Entry
Catalyst
Loading
Yield
TON
b
1
2
3
4
5
6
7
8
9
—
pTsOH
Thiourea (C1)
Thiourea (C2)
—
0%
0
10
81
89
0.6
75
320
480
410
490
5
73%
81%
10 mol%
1 mol%
1 mol%
10 mol%
0.2 mol%
0.2 mol%
0.2 mol%
0.2 mol%
0.2 mol%
99%
81%
89%
6%
15%
64%
96%
82%
98%
b
IRMOF-3 (C3)
6
IRMOF-3–thiourea (C4)
IRMOF-3–urea (C5)
IRMOF-3–thiourea (C7)
Bulk C7
a
Reaction conditions. For acetalization (entries 1–4): the same
conditions as in Table 1. For Morita–Baylis–Hillman reaction (entries 5
b
10
IRMOF-3–thiourea (C8)
and 6): benzaldehyde (0.1 mmol), 2-cyclopenten-1-one (2.0 mmol),
1,4-diazabicyclo[2.2.2]octane (0.5 mmol). IRMOF-3–thiourea catalyst
(C8) (2 mol%) were stirred at 4 °C for 24 h. The product was purified
by column chromatography on silica gel and the yield was based on
the isolated product.
a
Reaction conditions: benzaldehyde (1.0 mmol), dry ethanol (4.0 mmol)
and 0.2 mol% (based on thiourea) organocatalyst at room temperature
b
for 12 h. MOF catalysts are used in nanoscale unless otherwise noted.
c
Determined by GC-MS.
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observation indicates that acetalization occurs mostly inside
the MOF porous tunnel, since substrates that are bigger than
the size of the pore will have limited access to catalytic
sites inside the MOF tunnel. To further extend the utility of
our new IRMOF-3–thiourea catalyst, Morita–Baylis–Hillman
reactions of benzaldehyde (1a) and 2H-cinnamaldehyde (1f)
were evaluated with 2-cyclohexen-1-one (5) as the nucleophile
and 1,4-diazabicyclo[2.2.2]octane as the base. An enhanced
yield was obtained with only 2 mol% catalyst loading, which
is significantly lower than the loading in the previous report
catalyst. Morita–Baylis–Hillman reaction undergoes a similar
reaction mechanism except that 2-cyclopenten-1-one (5) acts as
a nucleophile in the presence of a base promoter. Multiple
experiments were run under various catalyst loadings, and the
rates were extracted from the slopes of the curves using
ReactIR. These rates were averaged and plotted as depicted in
Fig. 4. From this graph, it is clear that there is a linear relation-
ship between the amount of the catalyst in the acetalization
reaction and its rate. This indicated first order reaction kinetics
with respect to the catalyst.
3
1
(Table 2, entries 5 and 6). A controlled experiment showed
that there was no reactivity in the absence of the catalyst.
The stability of IRMOF-3–thiourea was tested by performing
repeated reaction cycles under the same reaction conditions.
IRMOF-3 is known to be sensitive to weak acid and base, and
the loss of framework integrity has been observed in certain
cases. However, IRMOF-3–thiourea served as an efficient and
stable hydrogen-bonding catalyst under mild organocatalytic
conditions. The strong covalent bond between the thiourea
moiety and the amino group on IRMOF-3 ensures the stability
of the catalytic functional groups, which maintains over 95%
yield after five cycles. The supernatant liquid of the ethanol
suspension showed no reactivity towards the acetalization
of the benzaldehyde substrate, which indicates no leakage of
the IRMOF-3–thiourea catalyst. The X-ray powder diffraction
patterns and FTIR spectra of the IRMOF-3–thiourea catalyst
after five times reuse were also indistinguishable from those
of the fresh catalyst (Fig. S2†).
Our current mechanistic proposal for the MOF–thiourea cat-
alyzed acetalization of aldehydes begins with the coordination
of the catalyst with the carbonyl group to form TS2 (Fig. 4).
Binding and activation are the driving forces for the coordina-
tion, as well as the secondary π–π interaction between the two
aromatic groups in TS2. The second step is the nucleophilic
attack of two alcohols through an ion-pair intermediate, which
leads to benzaldehyde acetal and water binding (TS3). The
dehydration of water through ligand exchange regenerates the
Conclusions
In conclusion, a simple and rapid one-step approach to
achieve thiourea functionalized IRMOF-3 via post-synthetic
modification was developed. The structure and nano-
morphology of IRMOF-3–thiourea were retained after post-
synthetic modification. The new nanoscale IRMOF-3–thiourea
showed high activity and selectivity in acetalization and
Morita–Baylis–Hillman reactions. The catalyst did not suffer
from a leaching problem during catalysis and could be
recycled several times without loss of activity or selectivity.
This heterogeneous thiourea incorporation strategy overcomes
32
self-aggregation and solvation issues that existed in
homogeneous thiourea catalyst. Future studies including the
incorporation of a chiral thiourea moiety are underway.
a
Acknowledgements
We thank the Innovative Foundation from China National
Petroleum Corporation (grant no. 2012D-5006-0504) and the
National Natural Science Foundation of China (grant no. 51073023)
for financial support.
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