Bifunctional metal organic framework catalysts for multistep reactions: MOF-Cu(BTC)-[Pd] catalyst for one-pot heteroannulation of acetylenic compounds

Article abstract of DOI:10.1002/adsc.201100503

A bifunctional metal organic framework catalyst containing palladium and copper(II) benzene-1,3,5-tricarboxylate - MOF-Cu(BTC)-[Pd] - has been prepared. This catalyst enables the performance of the tandem Sonogashira/click reaction starting from 2-iodoben

Full text of DOI:10.1002/adsc.201100503

FULL PAPERS
DOI: 10.1002/adsc.201100503
Bifunctional Metal Organic Framework Catalysts for Multistep
Reactions: MOF-Cu(BTC)-[Pd] Catalyst for One-Pot
G
Heteroannulation of Acetylenic Compounds
Avelina Arnanz,a Mercedes Pintado-Sierra,b Avelino Corma,c,* Marta Iglesias,a
and Fꢀlix Sꢁnchezb
a
Inst. Ciencia de Materiales de Madrid, CSIC. C/Sor Juana Inꢀs de la Cruz, 3, Cantoblanco 28049 Madrid, Spain
Fax : (+34)-9-1372-0623
Inst. Quꢂmica Orgꢁnica General, CSIC. C/Juan de la Cierva, 3, 28006 Madrid, Spain
b
Fax : (+34)-9-1564-4853
Inst. Tecnologꢂa Quꢂmica, UPV-CSIC. Avda. los Naranjos, s/n, 46022 Valencia, Spain
c
Fax : (+34)-9-6387-7809; e-mail: acorma@itq.upv.es
Received: June 29, 2011; Revised: February 13, 2012; Published online: April 19, 2012
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201100503.
Abstract: A bifunctional metal organic framework doles with good yields under mild reaction condi-
catalyst containing palladium and copper(II) ben- tions.
zene-1,3,5-tricarboxylate – MOF-CuACTHNUTRGNEU(GN BTC)-[Pd] –
has been prepared. This catalyst enables the perfor-
mance of the tandem Sonogashira/click reaction Keywords: bifunctional metal organic frameworks
starting from 2-iodobenzylbromide, sodium azide (MOFs); copper-palladium catalysis; coupling-cycli-
and alkynes to produce 8H-[1,2,3]triazoloACTHUNRTGNEUNG[5,1-a]isoin- zation; isoindoles; tandem recations
Introduction
upon the chosen reaction conditions. For instance,
only a few amine-functionalized frameworks[9] are
Metal organic frameworks (MOFs) are hybrid materi- known, out of the more than 10,000 MOF structures
als with potential interest in gas storage,[1,2] catalysis,[3] reported in the literature.
and separations.[4] However, in spite of the initial en-
The research on catalytic applications of MOFs has
thusiasm, several factors are hampering the further been focused on rigid structures with permanent po-
development of MOF applications in those important rosity to allow accessibility of the reactants to the co-
areas of research. First, the continuous runaway status ordinatively unsaturated metal active sites (CUS).[3f,10]
of MOF chemistry is a strong driving force for per- It is also of much interest to design stable multifunc-
forming proof-of-principle work that still remains in- tional MOF catalysts that can perform multistep reac-
complete. Furthermore, although several series of tions in one pot, avoiding intermediate separation and
MOFs have shown unusual thermal and chemical sta- purification steps. This is not only of interest from the
bility, their use in catalysis and gas separations is still point of view of sustainability, but also reduces invest-
largely limited by the lack of functional and selective ment costs because of process intensification.[11]
sites in most stable MOF frameworks. Practical routes
In the present work we have prepared a bifunctional
to create functional solids include direct synthesis or MOF catalyst starting from Cu3ACHNUTTRGEGNUN(N BTC)2 (BTC=ben-
post-synthetic functionalization,[5] grafting of active zene-1,3,5-tricarboxylate).[12] An additional metal (Pd)
groups on the open metal sites of certain structures,[6] complex has been introduced by reaction of
and encapsulation of active species.[7] One of the cur- Cu
3ACHTUNGTRENNUNG
(BTC)2 with aminopyridine compounds and
2A
rent challenges is the development of stable MOFs PdCl CHTUNGTRNE(NUNG PhCN)2, and the resultant bimetallic Cu-Pd
with functional organic sites,[8] that could be used di- MOF is able to act as a multifunctional catalyst in
rectly or after post-synthesis modifications. However, a one-pot cascade reaction starting from 2-iodobenzyl
the incorporation of ligands, including additional bromide, to afford 8H-[1,2,3]triazoloACTHNUGTRNEUNG[5,1-a]isoindoles.
functional moieties, is not trivial since such groups
may directly coordinate to the metal ions depending
Adv. Synth. Catal. 2012, 354, 1347 – 1355
ꢃ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
1347

Avelina Arnanz et al.
FULL PAPERS
Results and Discussion
Synthesis and Characterization of Catalysts
The structure of Cu3ACHTUNTGRENUNG(BTC)2 is constituted by a cluster
of two metal atoms with a paddle-wheel shape that
has a square planar coordination.[13] BTC acts as
a trigonal planar ligand connecting the diatomic
metal clusters[13b] which define nanocages. The
CuBTC structure consists of two types of “cages” and
two types of “windows” are separating these cages.
Large cages are interconnected by 9 ꢄ windows of
a square cross-section. The large cages are also con-
nected to tetrahedral-shaped pockets of ca. 6 ꢄ size
through triangular-shaped windows of ca. 4.6 ꢄ. At
this point, the activity of the catalyst depends on (i)
the availability of significant numbers of accessible
sites whitin the open MOF crystal structure, (ii) rever-
sible coordination in organic linkers with the metal
atom and iii) the influence of the electrostatic field in
Figure 1. PXRD of CuBTC, L1-CuBTC and L2-CuBTC.
the cavity by the partially charged framework. Trimer- copper ions has occurred (Scheme 1). The XRD pat-
ic copper(II) octahedral clusters of CuBTC possess tern of the resultant material is similar to that of Cu3
terminal water molecules, and their lability allows
ACHTUNGRTENUN(NG BTC)2 in d-spacing and line shape, demonstrating
their replacement by other groups after vacuum treat- that chemical functionalization can be achieved with-
ment at 393 K for 2 h, without changes of the struc- out a loss of structural integrity (see Figure 1), but
ture (Scheme 1).
Treatment
with some slight variations of the Bragg intensities.
The presence of ligands is detected by FT-IR spec-
of
the
dark-violet
anhydrate
ACHTUNGTRENNUNG[Cu3ACHTUNGTRENNUNG(BTC)2]n with 4-substituted pyridines (L1, L2) in troscopy working in transmission mode with KBr pel-
dry toluene (at reflux temperature) followed by wash- lets. The IR spectra of the self-supported L1-CuBTC
ing with dichloromethane, gave green derivatives. As and L2-CuBTC dehydrated at 393 K for 2 h under
has been described for re-adsorption of molecules vacuum confirm the grafting (Figure 2 and Figure 3).
such as acetone, THF, ethanol, acetonitrile, benzalde- Figure 2 shows the spectra of the starting CuBTC
hyde, and amines,[14] the addition of 4-substituted pyr- compound compared with the samples after NH2 pyri-
idines gives rise to new compounds that restore the dine grafting. The n(NH) and n(CH) stretching re-
original color indicating that coordination to the gions indicate the presence of 4-aminopyridine (see
Scheme 1. Functionalization of Cu3ACHTNUGRTENUNG(BTC)2 with palladium complexes.
1348
asc.wiley-vch.de
ꢃ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2012, 354, 1347 – 1355

Bifunctional Metal Organic Framework Catalysts for Multistep Reactions: MOF-CuACTHNUTRGNEUGN(BTC)-[Pd] Catalyst
Figure 2. FT-IR spectra of L1-CuBTC.
Figure 4. FT-IR spectra of L1-CuBTC derivatives.
Figure 5. FT-IR spectra of L2-CuBTC derivatives.
Figure 3. FT-IR spectra of L2-CuBTC.
reference spectrum of 4-aminopyridine). Furthermore, that can react with transition metal complexes to give
the frequencies of the imino group of the L2 ligand a new hybrid MOF-transition metal complex. Indeed,
appears at 1718 cmÀ1 as shown in Figure 3. It is worth reaction of Cu
(BTC) with PdCl
E
À
noting that the observed aliphatic C H stretching vi- heterogenized Pd-MOF (CuBTC-Pd). The IR spectra,
brations (2800–3000 cmÀ1) are shifted to larger values, in Figure 4 and Figure 5, show the changes due to the
as observed when the molecule is coordinated to introduction of the palladium. Furthermore, there is
a Lewis acid center,[15] clearly demonstrating the se- no apparent loss of crystallinity in X-ray diffraction
lective L2 grafting onto copper(II) CUSs in the cages patterns and no supplementary Bragg peaks appear
of the MOF.
after the metal complex formation, but the intensities
Elemental analysis indicates that the amine content of the peaks of CuBTC change confirming the intro-
is between one and two molecules per trimer of duction of the complex into the pores (Figure 6). The
copper octahedra for the NH2Py-CuBTC and L2- analytical results by inductively coupled plasma MS
CuBTC solids, respectively, which is in agreement give 2.67wt% (for PyNH2-derivative) and 0.68 wt%
with an effective grafting on the CUS.
(for L2-complex) Pd metal-containing CuBTC materi-
The current successful concept of pyridine deriva- als, that also support the successful formation of the
tives grafting onto CUSs has a very important conse- Pd complex.
quence since allows us to have a new hybrid ligand
Adv. Synth. Catal. 2012, 354, 1347 – 1355
ꢃ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
1349

Avelina Arnanz et al.
FULL PAPERS
clic carbene Pd-Cu complex catalyzes the tandem
click/Sonogashira reaction of 1-(bromomethyl)-4-io-
dobenzene, NaN3, and ethynylbenzene in a single
flask.[32] In this case 1-(4-iodobenzyl)-4-phenyl-1H-
1,2,3-triazole was the main product.
According to the above, it appeared to us that an
MOF catalyst containing Cu and Pd sites in the same
structure could be an adequate bifunctional heteroge-
À
neous catalyst for combining a Sonogashira C C cou-
pling with an intramolecular cycloaddition “click” re-
action, to prepare in one-pot a series of triazoloACHTUNGTRENNUNG[5,1-
a]isoindoles. Isoindoline derivatives are interesting
because of their diverse biological activities and clini-
cal applications. The core ring structure is present in
many heterocycles that have been shown to produce
a wide array of biological effects:[33] NMDA receptor
antagonism, modulation of estrogen and dopamine D3
and D4 receptors, inhibition of selective serotonin re-
uptake and antibacterial activity. Similarly, the 1,2,3-
triazole nucleus is a structural motif found in a large
number of compounds exhibiting anti-HIV, antimicro-
bial and antibacterial activities.[34] Fused triazoles
have also found widespread[35] use as antiallergic
Figure 6. PXRD: CuBTC; L-CuBTC; L-CuBTC-[Pd].
Catalytic Results
Since the introduction of copper salts-catalyzed 1,3-di- agents and potent glycosidase inhibitors amongst
polar cycloadditions of organic azides and alkynes,[16] others. Although a variety of approaches to isoindo-
a plethora of methods have flourished around this re- lines and triazoles has been described, there are few
action.[17] Enormous efforts have been devoted in papers reporting the synthesis of isoindoline fused
order to maximize the general efficiency of the pro- with triazoles (as building block or a perhaps novel
cess adapted to the multiple and manifold applica- pharmacophore).[36]
tions of the resulting 1,2,3-triazoles, and to reduce the
After synthesizing bimetallic CuBTC-Pd MOFs we
amounts of copper in solution. In this sense, heteroge- observed that they could be stored in air for months
neous catalysts offer several advantages over the ho- without observable decomposition. This result encour-
mogeneous counterparts, such as easy recovery, easy aged us to examine their catalytic properties for the
recycling, and enhanced stability.[18]
tandem transformation combining two reactions typi-
Charcoal,[19] zeolites,[20] montmorillonite,[21] NHC- cally catalyzed by Pd and Cu precatalysts. Then we
modified silica,[22] polystyrene,[23] chitosan[24] or have carried out the liquid phase multicomponent re-
MOFs[25] are some of the supports used with copper action outlined in Scheme 2 as a test to study selectiv-
for the heterogeneous version of the title click reac- ity and activity of the Cu
ACHTUNGERTN(NUNG BTC)-L-[Pd] MOF and the
tion. On the other hand, metal-catalyzed carbon- results are summarized in Table 1.
carbon bond forming reactions have dominated ho-
In order to establish the optimal reaction condi-
mogeneous catalysis over the last decade.[26] One of tions, after initial tests with preformed 1-(azidometh-
the most widely used catalytic reactions is the Sono- yl)-2-iodobenzene (Table 1, entries 1 and 2), we start-
gashira coupling of aryl halides with acetylenes, which
is catalyzed by a Pd/Cu system.[27] Solid catalysts
based on supported, Pd-free gold system[28] or immo-
bilized catalytic systems (Sil-Cu/Pd) that are active
and can be recycled,[29] have been reported for Sono-
[30]
À
gashira C C coupling reactions. Gruber et al. have
shown the synthesis of 2-phenylindole in a one-pot
process by reacting 2-iodoaniline with phenylacety-
lene in the presence of 1 mol% Pd(II)/C and 1 mol%
CuI at 1208C using DMF/H2O (1:1) as solvent. The
authors also reported the excellent activity of a bimet-
allic heterogeneous (Pd-Cu) catalyst based on Pd and
Cu complexes entrapped into NaY zeolite for the syn-
thesis of 2-phenylindole.[31] It has also been demon-
strated that the homogeneous bimetallic N-heterocy- Scheme 2.
1350
asc.wiley-vch.de
ꢃ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2012, 354, 1347 – 1355

Bifunctional Metal Organic Framework Catalysts for Multistep Reactions: MOF-CuACTHNUTRGNEUGN(BTC)-[Pd] Catalyst
Table 1. MOF-copper-palladium-catalysed cycloadditions of azides with phenylacetylene affording triazoloCAHTUNGTRENNNUG
Entry
Base
Cat.[a]
Conditions[b]
4
5
b) r.t. 3 h;
c) 1008C, 15 h
b) r.t. 48 h;
c) r.t., 48 h
a) r.t. 72 h;
b), c) r.t. 30 h
a), b), c) 508C, 24 h
a), b) r.t. 72 h,
c) 508C, 24 h
1
2
3
1.1
4.4
2.2
NEt3[c] (4 equiv.)
NEt3[c] (4 equiv.)
NEt3[c] (4 equiv.)
10% (L1)
5% (L1)
3% (L1)
56
100
–
73
91.7
15.5
8.3
84.5
100
4
5
2
2
CsF (3 equiv.)
CsF (3 equiv.)
3% (L1)
1% (L2)
97
59
26.8
94.8
73.2
5.2
6
7
8
9
10
11
12
13
2
2
2
2
2
2
1.2
1.2
CsF (3 equiv.)
1% (L2)
3% (L1)
3% (L1)
3% (L1)
5% (L1)
5% (L1)
5% (L1)
5% (L2)
508C, 24 h
100
100
traces
57
85
98
47
9
–
98
100
95.1
100
68.7
53
91
–
2
traces
4.9
traces
31.3
K2CO3 (2 equiv.)
K2CO3 (2 equiv.)
K2CO3 (2 equiv.)
K2CO3 (2 equiv.)
K2CO3 (2 equiv.)
K2CO3 (2 equiv.)
K2CO3 (2 equiv.)
a) 508C, b) 1008C, 8 h
a), b), c) r.t., 24 h
a), b), c) 508C, 4 h
a), b), c) 508C, 4 h
508C, 10 h
a), b), c) 508C, 4 h
a), b), c) 508C, 4 h
20
100
[a]
[b]
[c]
[d]
Based on Pd.
Sodium azide: 1.1 equiv.
No water was added.
The alkyne homocoupling observed in all cases is formed at the beginning of the reaction due to the excess added. Satis-
factory spectroscopic (1H NMR, and mass) data were obtained for 4.
ed with 1-(azidomethyl)-2-iodobenzene, 2, and phe- temperature. The scope of the reaction was studied
nylacetylene as model substrates to test the one-pot by varying the terminal alkyne and it has been found
Sonogashira coupling/click cyclization reaction, under that the reaction is applicable to both aromatic and
different reaction conditions. While a low effect of
the added base was observed (see Table 1), it was
Table 2. Domino Sonogashira coupling/click cyclization for
the synthesis of triazolo
[5,1-a]isoindoles.[a]
ACHTUNGTRENNUNG
seen that the reaction temperature plays a key role.
For instance, when the reaction is performed at room
temperature no transformation was obtained and at
temperatures higher than 508C, the intermolecular
click reaction to form 5 was preferred to Sonogashira
coupling, thus, in an experiment at 1008C the unde-
sired compound 5 was the main product and was iso-
lated in 90% yield (see Scheme 2 and entry 8 in
Table 1). However, the reaction could be carried out
in a one-pot two steps sequence that is, first we obtain
the azide, 2, and then the alkyne is added at a temper-
ature below 508C, and the Sonogashira coupling
product 3 is formed which evolves into the desired
final product 4 by intramolecular cycloaddition. When
dimethoxyethane was used as solvent, the reaction
was slower and four days were required for complete
conversion, yielding a mixture of 65% intramolecular
(4) and 35% intermolecular (5) cycloaddition prod-
ucts.
Entry Alkyne
Time [h] Conv. [%]
Sel. [%]
4
5
1
2
3
4
5
6
2
100
100
36
99
traces
3
99
traces
traces
–
28
72
72
48
24
99
50
100
89
25
11
94
66
34[b]
–
7
<10
100[c]
[a]
Cat. 5 mol% (based on Pd), K2CO3, 2 equiv., NaN3: 1.1
equiv. DMF, alkyne, 2 equiv.
We obtained also:
[b]
The possibility of performing a real tandem Sono-
gashira/click reaction was also studied starting from 2-
iodobenzyl bromide, sodium azide, and different alk-
ACHTUNGTRENNUNGynes. Taking into account the results in Table 1, the
following reaction conditions were chosen: 2 equiv. of
potassium carbonate, 5 mol% of catalyst, and 508C
[c]
Desilylation took place under our reaction conditions.
Adv. Synth. Catal. 2012, 354, 1347 – 1355
ꢃ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
1351

Avelina Arnanz et al.
FULL PAPERS
aliphatic acetylenes (Table 2). The acetylenic compo-
nents could also carry various substituents like
methyl, methoxy, or trimethylsilyl, without affecting
the heteroannulation. p-Tolylacetylene (Table 2,
entry 2) reacted with 1-(azidomethyl)-2-iodobenzene
(formed in situ) to afford the corresponding product 4
in 99% yield. An electron-donating OMe substituent
on the aryl ring, gives only 36% yield after 28 h
(Table 2, entry 3). Simple aliphatic terminal alkynes
were also transformed to triazoloACTHNUTRGNEUNG[5,1-a]isoindole
products but with low yields after 3 days reaction
(25% conversion). Ethynylcyclohexane gives the
product with moderate yield (Table 2, entry 4). Fur-
thermore, the reactions of alkyl-substituted terminal
alkynes bearing a free hydroxy functional group led
to the formation of triazoloACTHNUGRTNEUNG[5,1-a]isoindoles in 66%
yield (94% conversion) (Table 2, entry 6). The yields
were generally found to be good except in the case of
trimethylsilylacetylene (entry 7) that only yields
traces of the desilylated product.
Figure 7. PXRD of L1-CuBTC-Pd after recycling.
In order to study the recyclability of the bimetallic
MOF-system, a filtering test was carried out. After
4 h (85% conversion), 50% of the solution (solvent: containing the catalyst, the conversion of the sub-
DMF) was separated from the catalyst by filtration or strate continues. The filtering experiment indicates
centrifugation and the reaction was followed by GC/ that with the bimetallic MOF we are dealing with
MS in the remaining suspension containing the solid a heterogeneous catalytic system. However, the recy-
catalyst, and in the filtrate. In the filtrate, the reaction clability of this system is limited and starting from 2-
does not proceed further, whereas in the suspension iodobenzyl bromide the activity decays in the second
cycle and practically disappears in the third cycle. If
the starting material is 1-(azidomethyl)-2-iodoben-
zene, activity is maintained for at least two cycles
Table 3. Recycling experiments with L1-CuBTC-Pd.[a]
without loss of activity or selectivity (Table 3). This
Cycle Starting product Time [h] Conv. [%]
Sel. [%]
fact is related to the gradual destruction of the struc-
ture as can be seen by PXRD analysis (Figure 7).
Therefore, and in order to further demonstrate the
existence of an heterogeneous catalytic process, addi-
tional experiments have been carried out (see
Table 4)
4
5
1
2
2
30
100
96
99 traces
90 10
1
2
4
2
85
100
100 traces
91
9
Firstly, it was observed that the reaction does not
occur using the Cu3BTC2 MOF without Pd (Table 4,
entry 1), or with only a soluble palladium complex
[a]
Cat. 5 mol% based on Pd; base=K2CO3, 3%; alkyne=
phenylacetylene, T: 508C.
Table 4. Experiments to test the heterogeneity.[a]
Entry
Catalyts
Time [h]
Conv. [%]
Sel. [%][c]
4
5
1
2
3
4
5
6
7
8
9
5%CuBTC
16
16
3
3
3
3
16
2
traces
traces
91
68
31
29
traces
33
–
–
–
–
5% Pd
A
5%CuBTC/5% Pd
A
99
99
99
99
–
traces
traces
traces
traces
–
5%CuBTC/2.5% Pd
5%CuBTC/0.5% Pd
5%CuBTC/0.1% Pd
filtrate (from reaction)
filtrate (from reaction)/5%CuBTC
5%CuBTC-Pd
G
E
A
99
99
traces
traces
2
100
[a]
K2CO3, 2 equiv.; alkyne=phenylacetylene, 2 equiv.; T: 508C.
1352
asc.wiley-vch.de
ꢃ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2012, 354, 1347 – 1355

Bifunctional Metal Organic Framework Catalysts for Multistep Reactions: MOF-CuACTHNUTRGNEUGN(BTC)-[Pd] Catalyst
200 cmÀ1) in KBr pellets. DRUV was obtained from a Shi-
madzu UV-2401 PC. 1H NMR and 13C NMR spectra were
recorded on Varian XR300 and Bruker 200 spectrometers.
Powder X-ray diffraction (PXRD) measurements were per-
formed with a Bruker D8 diffractometer in the q-q mode
using nickel-filtered Cu Ka1,2 (l=1.5418 ꢄ) radiation. The
best counting statistics were achieved by using a scanning
step of 0.028 taken between 5 and 308 Bragg angles in an ex-
posure time of 0.5 s per step. GC analysis was carried but
with an Agilent Technologies 6890N gas ghromatograph
equipped with a 5973 quadrupole mass selective detector
(Agilent Technologies) and with a KONIK HRGC 40000B
chromatograph equipped with an FID detector. An HP-5ms
fused-silica capillary column (30 mꢆ0.25 mm i.d., 0.25 mi-
crons film thickness of 5% phenylmethylpolyxilosane) was
employed.
such as Pd
Cu3BTC2 and PdACHTUNGTRENNUNG
ACHTUNGTRENNUNG
alyst, it was found that the reaction occurs and the
final yield depends on the concentration of the Pd
complex (Table 4, entries 3–6). We have described
previously that, after the hot filtration test, the reac-
tion with the filtrate does not proceed further. Since
we cannot discard the presence of palladium in solu-
tion we performed an experiment by adding Cu3BTC2
to the filtrate and found that the reactions proceed
but their rates are notably lower than the reaction
with the parent CuBTC-Pd catalysts (Table 3, en-
tries 7 and 8). These last experiments indicate that
some leaching of Pd occurs and that the leached Pd
can also react together with the remaining CuBTC to
give the final product. However, most of the reaction
still comes from the, heterogeneous bifunctional cata-
lyst.
Preparation of L-CuBTC
0.5 g of blue-turquoise [Cu3ACTHNUGTRENNUG(BTC)2AHCUTNGTREN(NUGN H2O)3]n was dehydrated
at 393 K under vacuum to obtain a dark-violet solid. A solu-
tion of 4-aminopyridine (50 mg, 0.53 mmol) or (E)-2-(tert-
butyl)-4-methyl-6-[(pyridin-4-ylimino)methyl]phenol (50 mg,
0.19 mmol) was added to a suspension in toluene (15 mL) of
the dehydrated material, the mixture was heated at 908C for
12 h, filtered, washed with CH2Cl2 and dried at 373 K/
1 mmHg for 3 h. Elemental analysis for L1-CuACTHNUTRGNEUG(N BTC): C
35.33, H 3.72, N 1.54%. Elemental analysis for L2-CuACHTUNGTRENNUNG(BTC):
C 35.30, H 2.65, N 0.40%.
Conclusions
The presence of copper(II) CUSs in copper(II)-1,3,5-
benzenetricarboxylate CuBTC has been found to pro-
vide an intrinsic chelating property with electron-rich
functional groups, leading to the formation of the
thermally stable pyridine species grafted on the sur-
face. This feature offers a powerful way to selectively
functionalize the unsaturated sites in CuBTC. This Preparation of L-CuBTC-[Pd]
methodology has been used to prepare a pyridine-Pd-
A solution of PdCl2ACHTNUGTRNE(UGN PhCN)2 (20 mg, 0.05 mmol) in CH2Cl2
grafted CuBTC bifunctional catalyst that exhibits
good activities for the one-pot Sonogashira/click reac-
tions of 2-iodobenzyl bromide, NaN3, and alkynes.
This reaction relies on carbon-carbon bond formation
followed by cycloaddition of azide to the internal al-
kynes (generated in situ) under appropriate reaction
conditions. A small leaching of Pd occurs that, togeth-
er with CuBTC, can be responsible for the formation
of a relatively smaller amount of product. The present
approach ensures the development of newly function-
alized materials through the immobilization of organ-
ic molecules and the formation of transition metal
complexes, for preparing multifunctional MOF cata-
lysts. In this case, it will be a key factor to preserve
the stability of the catalyst.
(5 mL) was added to a suspension of 200 mg of L1-CuBTC
or L2-CuBTC in CH2Cl2 (10 mL). The mixture was heated
at reflux for 4 h, cooled to room temperature, filtered,
washed with CH2Cl2 for removing any non-reacted Pd com-
plex and dried at 353 K under vacuum. Elemental analysis
for L1-CuACTHNUTRGNEUG(N BTC)-[Pd]: C 34.67, H 2.95, N 1.78, Pd, 2.68%.
Elemental analysis for L2-CuACTHNUTRGNEUGN(BTC)-[Pd]: C 35.84, H 2.60, N
0.55, Pd 0.68%.
Catalytic Experiments
The general reaction procedure for the cascade reaction was
as follows: a mixture of 2-iodobenzyl bromide (10 mg,
0.034 mmol), sodium azide (2.3 mg, 0.035 mmol) MOF-L-
Cu[Pd] catalyst (0.007 mmol Pd), K2CO3 (10 mg,
0.072 mmol) in water (0.2 mL) and the respective acetylene
(0.067 mmol) was stirred in DMF (1.5 mL) under an atmos-
phere of argon at 323 K. Aliquots were taken during the
course of the reaction and analyzed by GC using tetrade-
cane as external standard. DMF was filtered and the filtrate
evaporated under reduced pressure and the residue was ex-
tracted with ethyl acetate. The combined organic layers
were dried with Na2SO4, filtered and the solvent removed
under vacuum. The residue was purified by chromatography
on silica gel to obtain the desired product 4. The reaction
Experimental Section
General Methods
A
3A
3A
CHTUNGTRENNUNG(BTC)2 (Basoliteꢅ C 300 produced by BASF] was sup-
plied by Aldrich (BET=1500–2100 m2 gÀ1). Elemental C, H,
N analyses were determined with a Lecco apparatus. Metal
contents were analyzed by plasma ICP Perkin–Elmer
OPTIMA 2100 DV. FT-IR spectra were recorded with
1
product was confirmed by means of H and mass spectrosco-
py analysis of the isolated product. For the filtration tests,
part of the reaction suspension was withdrawn at a certain
conversion at the reaction temperature, the catalyst was sep-
a
Bruker IFS 66v/S spectrophotometer (range 4000–
Adv. Synth. Catal. 2012, 354, 1347 – 1355
ꢃ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
1353

Avelina Arnanz et al.
FULL PAPERS
arated, and the supernatant was allowed to react further in
a separate vial.
[12] a) Z. Wang, G. Chen, K. Ding, Chem. Rev. 2009, 109,
322–359; b) M. C. Bernini, F. Gꢁndara, M. Iglesias, N.
Snejko, E. Gutiꢀrrez-Puebla, E. V. Brusau, G. E.
Narda, M. A. Monge, Chem. Eur. J. 2009, 15, 4896–
4905; c) F. Gꢁndara, B. Gꢈmez-Lor, E. Gutiꢀrrez-
Puebla, M. Iglesias, M. A. Monge, D. M. Proserpio, N.
Snejko, Chem. Mater. 2008, 20, 72–78; d) F. X. Llabrꢀs
i Xamena, A. Abad, A. Corma, H. Garcꢂa, J. Catal.
2007, 250, 294–298; e) F. X. Llabrꢀs i Xamena, O. Casa-
nova, R. Galliasso Tailleur, H. Garcꢂa, A. Corma, J.
Catal. 2008, 255, 220–227.
Acknowledgements
We thank the MICINN of Spain (Projects: Consolider-Ingen-
io 2010, CSD-0050-MULTICAT, MAT2011-29020-C02-02)
for financial support.
[13] a) K. Park, Z. Ni, A. P. Cote, J.-T. Choi, J. Uribe-
Romo, H. K. Chae, R. Huang, M. O Keeffe, O. M.
Yaghi, Proc. Natl. Acad. Sci. USA 2006, 103, 10186–
10189; b) I. A. Baburin, S. Leoni, G. Seifert, J. Phys.
Chem. B 2008, 112, 9437–9443.
[14] a) S. S.-Y. Chui, S. M.-F. Lo, J. P. H. Charmant, A. G.
Orpen, I. D. Williams, Science 1999, 283, 1148; b) K.
Schlichte, T. Kratzke, S. Kaskel, Microporous Mesopo-
rous Mater. 2004, 73, 81–88.
[15] a) K. Krishnan, R. A. Plane, Inorg. Chem. 1996, 35,
852–860; b) D. A. Young, T. B. Freedman, E. D. Lipp,
L. A. Nafie, J. Am. Chem. Soc. 1986, 108, 7255–7263.
[16] a) R. Huisgen, G. Szeimies, L. Moebius, Chem. Ber.
1965, 98, 4014–4021; b) R. Huisgen, Pure Appl. Chem.
1989, 61, 613–628.
[17] a) V. D. Bock, H. Hiemstra, J. H. van Maarseveen, Eur.
J. Org. Chem. 2006, 51–68; b) M. Meldal, C. W. Tornøe,
Chem. Rev. 2008, 108, 2952–3015; c) P. Appukkuttan,
E. Van der Eycken, Eur. J. Org. Chem. 2008, 1133–
1155; d) C. O. Kappe, E. Van der Eycken, Chem. Soc.
Rev. 2010, 39, 1280–1290.
[18] a) J. A. Anderson, Fernꢁndez Garcꢂa, Supported metals
in catalysis, Imperial College Press, London, 2005;
b) K. Kaneda, K. Ebitani, T. Mizugaki, K. Mori, Bull.
Chem. Soc. Jpn. 2006, 79, 981–991.
[19] a) B. H. Lipshutz, B. R. Taft, Angew. Chem. 2006, 118,
8415–8418; Angew. Chem. Int. Ed. 2006, 45, 8235–8238;
b) C.-T. Lee, S. Huang, B. H. Lipshutz, Adv. Synth.
Catal. 2009, 351, 3139–3142.
[20] a) S. Chassaing, A. S. S. Sido, A. Alix, M. Kumarraja, P.
Pale, J. Sommer, Chem. Eur. J. 2008, 14, 6713–6721;
b) S. Chassaing, A. Alix, T. Boningari, K. S. S. Sido, M.
Keller, P. Kuhn, B. Louis, J. Sommer, P. Pale, Synthesis
2010, 1557–1567.
[21] I. Jlalia, H. Elamari, F. Meganem, J. Herscovici, C.
Girard, Tetrahedron Lett. 2008, 49, 6756–6758.
[22] P. Li, L. Wang, Y. Zhang, Tetrahedron 2008, 64, 10825–
10830.
References
[1] a) G. Fꢀrey, Chem. Soc. Rev. 2008, 37, 191; b) J. R.
Long, O. M. Yaghi, Chem. Soc. Rev. 2009, 38, 1213–
1214.
[2] L. J. Murray, M. Dinca, J. R. Long, Chem. Soc. Rev.
2009, 38, 1294–1314.
[3] a) O. M. Yaghi, M. OꢇKeeffe, N. W. Ockwig, H. K.
Chae, M. Eddaoudi, J. Kim, Nature 2003 423, 705–714;
b) O. M. Yaghi, Nature Mater. 2007, 6, 92; c) D. Farrus-
seng, S. Aguado, C. Pinel, Angew. Chem. Int. Ed. 2009
48 7502–7513; d) A. Corma, H. Garcꢂa, F. X. L.
Xamena, Chem. Rev. 2010 110, 4606–4655; e) J. Y. Lee,
O. K. Farha, J. Oberts, K. A. Scheidt, S. T. Nguyen, J. T.
Hupp, Chem. Soc. Rev. 2009, 38, 1450–1459.
[4] a) J. R. Li, R. J. Kuppler, H. C. Zhou, Chem. Soc. Rev.
2009, 38, 1477–1504; b) C. Gucuyener, J. van den
Bergh, J. Gascon, F. Kapteijn, J. Am. Chem. Soc. 2010
132, 17704–17706.
[5] Z. Q. Wang, S. M. Cohen, Chem. Soc. Rev. 2009, 38,
1315–1329.
[6] Y. K. Hwang, D. Y. Hong, J. S. Chang, S. H. Jhung,
Y. K. Seo, J. Kim, A. Vimont, M. Daturi, C. Serre, G.
Fꢀrey, Angew. Chem. 2008, 120, 4212–4216; Angew.
Chem. Int. Ed. 2008, 47, 4144–4148.
[7] J. Juan-AlcaÇiz, E. V. Ramos-Fernꢁndez, U. Lafont, J.
Gascon, F. Kapteijn, J. Catal. 2010, 269, 229–241.
[8] S. Hasegawa, S. Horike, R. Matsuda, S. Furukawa, K.
Mochizuki, Y. Kinoshita, S. Kitagawa, J. Am. Chem.
Soc. 2007, 129, 2607–2614.
[9] a) J. Gascon, U. Aktay, M. D. Hernꢁndez-Alonso,
G. P. M. van Klink, F. J. Kapteijn, J. Catal. 2009, 261,
75–83; b) S. Couck, J. F. M. Denayer, G. V. Baron, T.
Remy, J. Gascon, F. Kapteijn, J. Am. Chem. Soc. 2009,
131, 6326–6327; c) M. Savonnet, D. Bazer-Bachi, N.
Bats, J. Pꢀrez-Pellitero, E. Jeanneau, V. Lecocq, C.
Pinel, D. Farrusseng, J. Am. Chem. Soc. 2010, 132,
4518–4519; d) T. Ahnfeldt, N. Guillou, D. Gunzelmann,
I. Margiolaki, T. Loiseau, G. Fꢀrey, J. Senker, N. Stock,
Angew. Chem. 2009, 121, 5265–5268; Angew. Chem.
Int. Ed. 2009, 48, 5163–5166.
[10] a) S. Kitagawa, R. Kitaura, S. Noro, Angew. Chem.
2004, 116, 2388–2430; Angew. Chem. Int. Ed. 43, 2004,
43, 2334–2375; b) U. Mueller, M. Schubert, F. Teich, H.
Puetter, K. Schierle-Arndt, J. Pastr, J. Mater. Chem.
2006, 16, 626–636; c) J. S. Seo, D. Whang, H. Lee, S. I.
Jun, J. Oh, Y. J. Jeon, K. Kim, Nature 2000, 404, 982–
986.
[23] U. Sirion, Y. J. Bae, B. S. Lee, D. Y. Chi, Synlett 2008,
2326–2330.
[24] M. Chtchigrovsky, A. Primo, P. Gonzalez, K. Molving-
er, M. Robitzer, F. Quignard, F. Taran, Angew. Chem.
2009, 121, 6030–6034; Angew. Chem. Int. Ed. 2009, 48,
5916–5920.
[25] I. Luz, F. X. Llabres i Xamena, A. Corma, J. Catal.
2010, 276, 134–140.
[26] F. Diederich, A. De Meijere, Metal-Catalyzed Cross-
Coupling Reactions, Wiley-VCH, Weinheim, 2004.
[27] R. Chinchilla, C. Nꢁjera, Chem. Rev. 2007, 107, 874–
922.
[11] M. J. Climent, A. Corma, S. Iborra, Chem. Rev. 2011,
111, 1072–1133.
1354
asc.wiley-vch.de
ꢃ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2012, 354, 1347 – 1355

Bifunctional Metal Organic Framework Catalysts for Multistep Reactions: MOF-CuACTHNUTRGNEUGN(BTC)-[Pd] Catalyst
[28] A. Corma, R. Juarez, M. Boronat, F. Sanchez, M. Igle-
sias, H. Garcꢂa, Chem. Commun. 2011, 47, 1446–1448.
[29] T. Posset, J. Guenther, J. Pope, T. Oesera, J. Blꢉmel,
Chem. Commun. 2011, 47, 2059–2061.
[34] a) R. Alvarez, S. Velazquez, F. San, S. Aquaro, C. De-
Clercq, C.-F. Perno, A. Karlsson, J. Balzarini, M. J. Ca-
marasa, J. Med. Chem. 1994, 37, 4185–4194; b) M. J.
Genin, D. A. Allwine, D. J. Anderson, M. R. Barba-
chyn, D. E. Emmert, S. A. Garmon, D. R. Graber,
K. C. Grega, J. B. Hester, D. K. Hutchinson, J. Morris,
R. J. Reischer, C. W. Ford, G. E. Zurenko, J. C. Hamel,
R. D. Schaadt, D. Stapert, B. H. Yagi, J. Med. Chem.
2000, 43, 953–970; c) M. Kume, T. Kubota, Y. Kimura,
H. Nakashimizu, K. Motokawa, M. J. Nakano, Antibiot-
ics 1993, 46, 177–192; d) W.-Q. Fan, A. R. Katritzky, in:
Comprehensive Heterocyclic Chemistry II, (Eds.:A. R.
Katritzky, C. W. Rees, E. F. V.Scriven), Elsevier Sci-
ence, Oxford, 1996, Vol. 4, pp 1–126.
[35] a) V. S. Georgiev, B. Loev, R. Mack, J. Musser, US
Patent 4,276,292, 1981; Chem. Abstr. 1981, 95, 132905v;
b) K. Tatsuta, Y. Ikeda, S. Miura, J. Antibiot. 1996, 49,
836–838; c) G. Roma, M. Dibraccio, G. Grossi, F. Mat-
tioli, M. Ghia, Eur. J. Med. Chem. 2000, 35, 1021–1035;
d) T. M. Krꢉlle, C. De La Fuente, L. Pickering, R. T.
Aplin, K. E. Tsitsanou, S. E. Zographos, N. G. Oikono-
makos, R. J. Nash, R. C. Griffiths, G. W. Fleet, Tetrahe-
dron: Asymmetry 1997, 8, 3807–3820; e) F. Couty, F.
Durrat, D. Prim, Tetrahedron Lett. 2004, 45, 3725–3728.
[36] C. Chowdhury, S. B. Mandalb, B. Achari, Tetrahedron
Lett. 2005, 46, 8531–8534.
[30] M. Gruber, S. Chouzier, K. Koehler, L. Djakovitch,
Appl. Catal. A, 2004, 265, 161–169.
[31] S. Chouzier, M. Gruber, L. Djakovitch, J. Mol. Catal.
A: Chem. 2004, 212, 43–46.
[32] S. Gu, D. Xu, W. Chen, Dalton Trans. 2011, 40, 1576.
[33] a) A. Alanine, S. Burner, B. Buettelmann, N. M. Heitz,
G. Jaeschke, E. Pinard, R. Wyler, Eur. Pat. Appl.
EP1090917, 2001; Chem. Abstr. 2001, 134, 280719b;
b) S. S. Bhagwat, L. M. Gayo, B. Stein, Q. Chao, A.
Gangloff, J. Mckie, K. Rice, PCT Int. Appl. WO
0055137, 2000; Chem. Abstr. 2000, 133, 252323d;
c) C. N. Johnson, G. Stemp, PCT Int. Appl. WO
0021950, 2000; Chem. Abstr. 2000, 132, 279110y;
d) H. B. Broughton, J. J. Kulagowski, P. D. Leeson,
I. M. Mawer, PCT Int. Appl. WO 9421628, 1994;
Chem. Abstr. 1995, 122, 9863d; e) K. J. Kapples, G. M
Shutske, J. Heterocycl. Chem. 1997, 34, 1335–1338;
f) M. Yamada, S. Hamamoto, K. Hayashi, K. Takaoka,
H Matsukura, M. Yotsuji, K. Onezawa, K. Ojima, T.
Takamatsu, K. Taya, H. Yamamoto, T. Kiyoto, H. Kot-
subo, PCT Int. Appl. WO 9921849, 1999; Chem. Abstr.
1999, 130, 311706u.
Adv. Synth. Catal. 2012, 354, 1347 – 1355
ꢃ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
1355