Metal-Organic Framework Derived Metal Oxide Clusters in Porous Aluminosilicates: A Catalyst Design for the Synthesis of Bioactive aza-Heterocycles

Article abstract of DOI:10.1021/acscatal.8b03908

Simple solid-state mixing and calcination of catalytic amounts of metal-organic frameworks (MOFs) in the presence of aluminosilicates allow for the generation of active and robust supported metal oxide nanoparticles that catalyze C-C and C-N bond formatio

Full text of DOI:10.1021/acscatal.8b03908

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Letter
MOF-derived metal oxide clusters in porous aluminosilicates: a
new catalyst design for the synthesis of bioactive aza-heterocycles
Nuria Martin, Michiel Dusselier, Dirk E. De Vos, and Francisco G Cirujano
ACS Catal., Just Accepted Manuscript • DOI: 10.1021/acscatal.8b03908 • Publication Date (Web): 20 Nov 2018
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ACS Catalysis
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MOF-derived metal oxide clusters in porous aluminosilicates: a new
catalyst design for the synthesis of bioactive aza-heterocycles
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Nuria Martín, Michiel Dusselier, Dirk E. De Vos and Francisco G. Cirujano*
Centre for Surface Chemistry and Catalysis, KU Leuven Celestijnenlaan 200F, 3001 Leuven, Belgium.
Supporting Information Placeholder
ABSTRACT: Simple solid-state mixing and calcination of
catalytic amounts of MOFs in the presence of aluminosilicates
allows for the generation of active and robust supported metal
oxide nanoparticles that catalyze C-C and C-N bond formations.
The proposed Cu and Zn containing aluminosilicates outperform
state-of-the-art solid catalysts for the synthesis of various aza-
heterocycles under mild and heterogeneous conditions, exhibiting
the highest TOFs ever reported for cost-efficient and reusable
CuO and ZnO active sites.
Metal acetates
MOF derived clusters
CuOMOF
Y
CuOAcY
Bioactive aza-heterocycles
KEYWORDS: metal oxides, MOFs, organic synthesis, N-
heterocycles, heterogeneous catalysis, aluminosilicates.
New strategies are needed to improve the activity and selectivity
of MOF catalysts in industrial synthesis of organic molecules. In
our group, we have recently designed reusable and heterogeneous
catalytically active metal sites in MOFs as an eco-friendly alterna-
tive to traditional homogeneous organic catalysts.1 Full coordina-
tion of the metal sites and/or poor accessibility of the inner active
sites in the crystal are the main challenges to improve its catalytic
activity in comparison with homogeneous catalysts. Although the
generation of active defects in highly stable frameworks, like
UiO-66 with its normally 8-coordinated Zr4+, partially solves the
problem,1b,c an excessive amount of defects compromises the
stability of the framework, especially for more labile MOFs with
tetrahedrally coordinated Zn2+ or Cu2+ metals.2
Figure 1. Pharmaceutically interesting scaffolds obtained using
well-dispersed MOF derived metal oxides within porous H-USY.
The new general methodology presented here is based on the
solvent-free grounding and co-calcination of catalytic amounts of
MOFs (HKUST-1 or MOF-5) with aluminosilicates (USY or
MCM-41). This solid-state synthesis allows to generate MOF
derived non-precious metal oxide nanoparticles as catalysts in C-
C (alkynylation, alkylation, aldol condensation, hetero-Diels-
Alder) and C-N (amination) bond formations to make propargyl-
amine, (spiro)(ox)indole and quinoline derivatives (Fig. 1, bot-
tom),7 with the highest TOFs ever reported for simple H+/Zn/CuO
active sites. The MOF derived metal oxide MO in the H-USY
zeolite used as support is abbreviated in this work as
“MOMOFYw”, where M is Zn or Cu and w indicates the weight
percentage (A, B, C) of metal in each sample (see Tables S1-S2).
For comparison purposes, zinc or copper acetates as precursors of
metal oxides “MOAcYw” were employed, following a similar
synthetic procedure (see supporting information for details).
Alternatively, it is possible to thermally decompose these bulk
MOFs into high performance carbons3 or metal catalysts.4 With
the aim of decreasing the cost of such MOF derived catalysts,
lower amounts of MOF are proposed here as precursor of metal
oxide catalytic species on inexpensive and robust aluminosilicates
(~1 wt.% MOF with respect to the aluminosilicate). The excellent
dispersion of the metal-oxo clusters in the MOF precursor (spaced
by the organic linker in the extended framework) and the very low
MOF loading, produce well-dispersed nanoparticles after thermal
decomposition of the linker with respect to the use of discrete
molecular species, such as acetate salts or preformed metal nano-
particles in a porous zeolite support (Fig. 1, top).5 Despite the
widespread use of supported metal oxide nanoparticles in the
synthesis of bulk chemicals and petrochemicals (selective oxida-
tions, NH3 and MeOH synthesis, etc.), their application in the
production of fine chemicals and pharmaceuticals has been large-
ly overlooked, due to their smaller production scale.6 However, it
is necessary to develop alternative strategies to selectively modify
important bio-active scaffolds in a clean and efficient manner,
avoiding the waste generated during the steps of purification of
pharmaceutically interesting compounds.
On the one hand, X-ray diffraction (XRD) patterns of the
CuOMOFYC and ZnOMOFYC catalysts, which contain the higher
metal loading, indicate that the zeolite structure is maintained
o
after its co-calcination with the MOF (at 550 C in air for 4 h).
Diffraction peaks of the MOF precursor vanish; new peaks appear
corresponding to the CuO or ZnO phases around 2θ ~ 30-40
degrees (see Fig. 2a). N2 physisorption suggests some decrease of
the H-USY porosity due to MOF derived metal oxide species
since the microporous volume (obtained by t-plot) of the starting
zeolite decreases from 0.28 cm3g-1 to 0.25 cm3g-1 after calcining
the MOFs in the presence of the H-USY support, as well as its
surface area (see Fig. 2b and Table S3). Temperature
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Page 2 of 6
a)
a)
1
2
*
ZnO
* *
*
CuO
*
3
4
ZnOMOFYC us.
ZnOMOFYC
CuOMOFYC us.
CuOMOFYC
5
6
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8
1
15
10
5
15
10
5
H-USY
H-USY
10 20 30 40 50 60
10 20 30 40 50 60
2 (degree)
2 (degree)
b)
H-USY
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400
300
200
100
0
CuOMOF
Y
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CuOMOFYused
CuOMOFYusedcalc.
0
0
1
A
B
C
1
A
B
C
Y
Ac
Y
Y
Y
Y
Ac
2
Y
Ac
20
CBV7
00
CBV4
calc.
iO
S
MOF
MOF
MOF
MOF
MOF
Calcination
H-USY
MCM4
CuO
CuO
CuO
CuO
CuO
CuO
AlMCM4
ZnOMOF
Y
Calcination
ZnOMOFYused
ZnOMOFYusedcalc.
b)
0.0 0.2 0.4 0.6 0.8 1.0 0.0 0.2 0.4 0.6 0.8 1.0
P/P0 P/P0
Cu-O
Cu-Cu
c)
strong
MCM-41
Al-MCM-41
H-USY
weak
2
CuOMOFYA
CuOMOFYA
CuOMOF
80
60
40
20
0
80
60
40
20
0
ZnOMOFYA
CuO
CuBTC
Cu2O
Cu foil
0
2
4
6
8
150 300 450 600 750
T/ oC
Binding distance (Å)
Figure 2. (a) XRD, (b) N2 physisorption, (c) NH3-TPD (left) and
XAS (right) of the MOF derived metal oxide on H-USY support.
1
A
B
Y
C
B
C
Y
Ac
1
A
Y
Y
2
Y
Ac
Y
Ac
00
calc.
20
CBV7
iO
S
MOF
MOF
MOF
MOF
MOF
MCM4
CuO
CuO
CuO
CBV4
CuO
CuO
CuO
AlMCM4
Figure 3. Catalytic performance of CuO containing aluminosili-
cates and MOFs in the synthesis of propargylamine 1 (a) and
quinoline 2 (b). Left: MOF derived CuO on different supports.
Right: MOF (blue) vs. Cu(OAc)2 (red) derived CuO at increasing
metal loadings (A < B < C) on H-USY (see Table S1).
programmed NH3 desorption (NH3-TPD) experiments show the
higher strength of the acid sites in the H-USY support with re-
spect to those in the acid mesoporous silica H-MCM-41(Al). The
incorporation of MOF derived metal oxide slightly decreases the
number of acid sites (H+) and affects their strength distribution
(see left part of Fig. 2c). Finally, X-ray Absorption Spectroscopy
(XAS) indicates that the Cu active sites are in the form of CuO
(see right part of Fig. 2c).
The higher TOFs obtained using the H-USY zeolite with strong
acidity (CBV 720) as support of the CuO active sites with respect
to lower Si/Al ratio (from 15 to 2.5, named as CBV 400 in Fig. 3)
alludes to the fact that the acidity of the support favors the A3
reaction (see left part of Fig. 4).10 An important role of the acidity
is to promote a very high dispersion of the CuO clusters, maybe
due to some re-protonation of the MOF linkers (during the cata-
lyst preparation in the presence of acidic supports) and relocation
of the Cu2+ cations partially compensated by the oxide anions of
the CuO clusters and zeolite. The catalytic activity of the bifunc-
tional CuO/H+ sites on the microporous H-USY zeolite or meso-
porous H-MCM-41(Al) is higher than that obtained when using
non-acidic mesoporous or amorphous silica supports (see Fig. 3a).
The same trend is observed for reactions where the acidity of the
support plays a major role, such as the Friedländer condensation
of 2-aminobenzophenone with acetylacetone (see Fig. 3b and Fig.
S7).11 In this case, the TOFs obtained with copper oxide contain-
ing MCM-41 catalyst, bulk Cu3(BTC)2 or pure CuO derived from
this MOF (by calcining it in bulk) are far below from those ob-
tained when CuO is dispersed via co-calcination in acid supports
such as H-USY or H-MCM-41(Al). For both reactions, the use of
the CuBTC as precursor of CuO active species instead of tradi-
tional Cu(OAc)2 remarkably improves the catalytic activity of the
copper containing zeolite.
The supported CuOMOFY metal oxide samples were employed as
catalysts in C-C (alkynylation) and C-N (amination) bond forming
reactions involving a multicomponent reaction between alkyne,
aldehyde and amine groups, a green process for the synthesis of
bio-active propargylamines.8 Copper catalysts have been tradi-
tionally employed due to their low cost and toxicity, especially
when immobilized in a solid support.9 The CuOMOFYA proposed
here (having only 0.9 wt.% Cu) compares very favorably to litera-
ture data of benchmark copper oxide or Cu-MOFs,9a,b copper on
mesoporous silica,9c,d or copper nanoparticles on zeolite NaY (see
Table S5).9e Other amines, such as morpholine and pyrrolidine,
also produce the corresponding propargylamines 1a-c in good
yields using the novel CuOMOFYA catalytic system (see Table S9).
In our hands, the turnover frequency (TOF) of the well-dispersed
copper active sites in CuOMOFY, is one order of magnitude higher
than those present in bulk copper oxide derived from the MOF
(CuOMOF) and starting Cu-MOF material (see Fig. 3a). Moreover,
using the calcined MOF instead of the intact one facilitates the
regeneration of the spent CuOMOFY catalyst after reaction, by a
simple thermal treatment in order to remove the reactants that
otherwise remain adsorbed in the microporous zeolite for subse-
quent reuses (see Fig. 2b and Fig. S4-S6). On the contrary, the
limited thermal stability of MOF powders only allows regenera-
tion by washing, which is associated with large volumes of organ-
ic solvents and compromises the stability of the MOF.
Faujasite zeolites were also described as acid catalysts in the
Friedel-Crafts alkylation at the C-3 of the electron rich indole,
using alcohols or electron deficient alkenes such as
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ACS Catalysis
er Zn MOF loadings, or the use of Zn(OAc)2 precursor, pure or
calcined MOF, results in the decrease of TOFZn and TONZn by 1-2
orders of magnitude (see Figure 5 and Table S10).
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a)
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60
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60
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20
0
Figure 4. Proposed mechanism for the synthesis of propargyla-
mines 1 and substituted indoles 3 using the bifunctional MO/H+
CuOMOFY and ZnOMOFY heterogeneous catalysts.
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β-nitrostyrene.1d, 12 For the last reaction, we have observed that
commercial H-USY zeolite with Si/Al =15 shows a higher initial
reaction rate (r0 = 0.40 h-1) with respect to lower Si/Al = 2.5, i.e.
weaker acid sites, r0 = 0.28 h-1, (see CBV720 and CBV400 in Fig.
S8 and Table S7). With CuOMOFYA, the initial reaction rate in-
creases twofold with respect to the pure Faujasite acid support and
the TOFCu is two orders of magnitude higher with respect to
CuBTC: 104 vs. 5 h-1 (see Fig. S8 and Table S7).1a, 13 Those find-
ings indicate that the novel method of creating CuO active sites in
acidic supports could be unique and generic for different catalytic
reactions. To broaden the scope of this concept, we have also
employed zinc MOFs as precursor of inexpensive and non-toxic
ZnO acid-base sites on H-USY. This bifunctional system is an
optimal catalyst for the Michael addition of indole to β-
nitrostyrene (see right part of Fig. 4). The catalytic activity of the
Zn sites is boosted when they are dispersed on the HY porous
zeolite, especially for low metal loadings (1.4 wt.%), obtaining a
TOFZn of 204 with respect to the 104 mol of indole converted per
mol of copper sites and per hour in the CuOMOFYA. Moreover, the
ZnOMOFYA MOF derived heterogeneous catalytic approach re-
markably outperform reported homogeneous Zn(OAc)2 cata-
lysts.14 The acid sites associated to Al in the H-USY or H-MCM-
41(Al) supports (see NH3-TPD in Fig. 2c), cooperatively interact
with the supported and well-dispersed (~1 wt.%) CuO or ZnO
nanoparticles and promote the nitro, carbonyl and alkyne activa-
tions involved in the C-C and C-N couplings shown in Figure 4.
1
1
A
B
C
Y
C
A
B
Y
Ac
Y
Y
Y
Ac
Y
Ac
2
00
CBV4
20
CBV7
calc.
iO
S
MOF
MOF
MOF
MOF
MOF
MCM4
ZnO
ZnO
ZnO
ZnO
ZnO
ZnO
AlMCM4
b)
5
60
40
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60
40
20
0
A
B
C
Y
1
1
B
Y
Ac
C
Y
Y
A
2
Y
Ac
Y
20
CBV7
00
iO
calc.
S
Ac
MOF
MOF
MOF
MOF
MOF
MCM4
ZnO
ZnO
ZnO
CBV4
ZnO
ZnO
ZnO
AlMCM4
Figure 5. Catalytic performance of ZnO containing aluminosili-
cates and MOFs in the synthesis of substituted oxindoles 4 (a) or
spirooxindoles 5 (b). Left: MOF derived ZnO on different sup-
ports. Right: MOF (blue) vs. Zn(OAc)2 (red) derived ZnO at
increasing metal loadings (A < B < C) on H-USY (see Table S2).
Apart from propargylamines and indoles, oxindoles are interesting
compounds that exhibit antitumor activity by inhibiting tyrosine
kinase receptors, as occurs with the C-3 substituted indolin-2-one
Sunitinib.15 This type of substituted oxindoles are currently pre-
pared using harsh conditions and/or toxic reagents, i.e. KF/Al2O3
or piperidine, piperazine, NaOH in ethanol under reflux.16 When
using the 1.2 wt.% loaded ZnOMOFYA it is possible to obtain the
3-benzyliden-2-oxindole 4 in high yields (90%) after only two
hours of aldol condensation of benzaldehyde with oxindole, prov-
ing the good performance of these novel Zn containing zeolites in
C-C bond forming Michael additions (see Fig. 4) and aldol con-
densations (see Fig. 5a). Other aliphatic aldehydes such as
heptanaldehyde or the biomass derived furfural were successfully
employed to functionalize the oxindole substrate (see Table S9).
The use of H-MCM-41(Al) acid mesoporous support increases the
Zn TOFs with respect to the use of microporous H-USY
(CBV720) zeolite, non-acidic MCM-41 or amorphous silica. This
indicates the importance of H+/ZnO acid-base sites, as well as a
good dispersion and accessibility to the active sites.17 Finally, the
aldol condensation/oxa-Diels-Alder reaction of isatin (1H-indole-
2,3-dione) with an hetero diene such as an α,β-unsaturated ketone,
was also studied in order to obtain pharmaceutically interesting
spirooxoindoles.18 A clear improvement in the final turnover
number (TONZn) or moles of isatin converted to 5 per mol of Zn
is obtained with the lowest loaded sample ZnOMOFYA (see Fig.
5b). As observed previously for the Cu containing catalysts, high-
In conclusion, the methodology proposed allows for the eco-
efficient solid-state synthesis of metal containing porous catalysts,
producing more mechanically and chemically resistant materials
in comparison with the starting MOFs, with a very low metal
content (below 2 wt.%). No solvent is employed during the pro-
cedure; thus the solid-to-solid (MOF-zeolite) co-calcination syn-
thesis can be easily scaled up without requiring filtration or wash-
ing steps. The solids were used as active and stable heterogeneous
catalysts for a range of C-C (compounds 1-5) and C-N (com-
pounds 1 and 2) bond formations in N-heterocyclic scaffolds,
resulting in substituted propargylamines (1), quinolines (2), in-
doles (3), oxoindoles (4) and spirooxoindoles (5), outperforming
state-of-the-art Cu and Zn supported catalysts and MOF bench-
marks. The higher availability of this metal oxide sites when they
are dispersed within the porous matrix with respect to bulk metal-
oxide or metal-organic framework, results in a better activity
(TOFs up to two orders of magnitude higher) and reusability (by
simple calcination), compared to the pure MOF.
ASSOCIATED CONTENT
Supporting Information
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Page 4 of 6
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Wang, S.; Liu, J.; Jiang, J. S.; Yamauchi, Y.; Hu, M. Hollow car-
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The Supporting Information is available free of charge on the
ACS Publications website.
Kinetic experiments, characterization of the catalysts and reaction
products.
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AUTHOR INFORMATION
Corresponding Author
*E-mail: francisco.garcia@kuleuven.be
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sis and Reactivity of Propargylamines in Organic Chemistry.
Chem. Rev. 2017, 117, 14091-14200; (b) Zindo, F. T.; Joubert, J.;
Malan, S. F. Propargylamine as functional moiety in the design of
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The authors declare no competing financial interests.
ACKNOWLEDGMENT
F.G.C. and N.M. acknowledge the European Commission-
Horizon 2020 for funding through Marie Sklodowska Curie Indi-
vidual Fellowships under the grant agreements numbers: 750391
(SINMOF) and 792943 (ZEOCO2). The XAS experiments were
performed on beamline BM26A at the European Synchrotron
Radiation Facility (ESRF), Grenoble, France. We are grateful to
D. Banerjee at the ESRF for providing assistance in using beam-
line and also to Cristina Almansa for performing the TEM analy-
sis of the samples at the research technical services of the Univer-
sity of Alicante in Spain.
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SYNOPSIS TOC “Co-calcining MOFs with aluminosilicate hosts as a new path to uniquely active metal-oxide catalysts for
eco-friendly C-C and C-N bond formations in N-heterocyclic scaffolds”
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