A Study of Graphene-Based Copper Catalysts: Copper(I) Nanoplatelets for Batch and Continuous-Flow Applications

Article abstract of DOI:10.1002/asia.201900781

The use of graphene derivatives as supports improves the properties of heterogeneous catalysts, with graphene oxide (GO) being the most frequently employed. To explore greener possibilities as well as to get some insights into the role of the different gr

Full text of DOI:10.1002/asia.201900781

CHEMISTRY
AN ASIAN JOURNAL
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Accepted Article
Title: A study of graphene-based Cu-catalysts.
Cu(I) nanoplatelets for batch and continuous-flow applications
Authors: Sonia De Angelis, Mario Franco, Alessandra Triminì, Ana
Gonzalez de Prádena, Raquel Sainz, Leonardo Degennaro,
Giuseppe Romanazzi, Claudia Carlucci, Valentina Petrelli,
Alejandro de la Esperanza, Asier Goñi, Rafael Ferritto, José
Luis Aceña, Renzo Luisi, and Belén Cid
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10.1002/asia.201900781
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A study of graphene-based Cu-catalysts.
Cu(I) nanoplatelets for batch and continuous-flow applications
Sonia De Angelis,[a] Mario Franco,[b] Alessandra Triminì,[a,b] Ana González,[b] Raquel Sainz,[c,d]
Leonardo Degennaro,[a] Giuseppe Romanazzi,[e] Claudia Carlucci,[a] Valentina Petrelli,[a,b] Alejandro de
la Esperanza,[b] Asier Goñi,[c] Rafael Ferritto,[c] José Luis Aceña,*[f] Renzo Luisi,*[a] and M. Belén Cid*[b,g]
Abstract: The use of graphene derivatives as supports improves the
properties of heterogeneous catalysts, being graphene oxide (GO) the
most frequently employed. In order to explore greener possibilities as
well as to get some insights into the role of the different graphenic
supports (GO, rGO, carbon black, and graphite nanoplatelets), we
Environmental compliance is a critical concern in modern
industrial settings, and when developing new chemical processes.
Thus, sustainable methods in organic synthesis are nowadays
increasingly needed, with a special focus on the recyclability of
materials and the reduction of waste. In this context,
heterogeneous catalysis may offer several advantages when
compared to homogeneous protocols, namely the ease in
handling the catalysts and the possibility of recovering and
recycling them after use.[1] Moreover, supported catalysts allow
easy access to the benefits of flow chemistry: faster and safer
reactions, cleaner products, quick reaction optimization, easy
scaling-up, and post-synthesis integration steps such as work-up,
and analysis.[2]
prepared, under the same standard conditions,
a variety of
heterogeneous Cu-catalysts and systematically evaluated their
composition and catalytic activity in azide-alkyne cycloadditions as a
model reaction. The use of sustainable graphite nanoplatelets (GNPs)
afforded a Cu(I) stable catalyst with good recyclability properties,
compatible with flow conditions, and able to catalyse other reactions
such as the regio- and stereoselective sulfonylation of alkynes
(addition reaction) and the Meerwein arylation (SET process).
Other limitations associated to homogeneous methods (the
relatively high cost and potential toxicity of transition metal
catalysts, as well as the need of organic ligands) are easily
circumvented when the catalysts are anchored onto a solid
support, and hence new heterogeneous metal-based catalytic
systems are nowadays in great demand. In addition to
mesoporous materials, lately carbon-based materials[3] and
especially some graphene derivatives constitute a very interesting
alternative.[4] This is due to the exclusive properties of graphene,
which include a highly active surface area, outstanding electronic
and mechanical properties and thermal stability that contribute to
the overall catalytic activity.[5] Nevertheless, the vast diversity of
graphene-supported metal catalysts, the variety of methods for
preparing them as well as the different reactions employed to test
the catalytic activity, hamper a rational design to choose the best
support in terms of sustainability, accessibility, efficiency in
catalysis and recyclability for a given process.[6]
The Cu(I)-catalysed azide-alkyne cycloaddition (CuAAC), a
well-known example of click chemistry, is also one of the most
useful transformations in the arsenal of a synthetic organic
chemist and allows accessing 1,2,3-triazole scaffolds in a
straightforward manner.[7] The CuAAC reaction has been
frequently adapted to heterogeneous conditions[8] and is usually
employed as a model reaction to prove the efficiency of new
Introduction
[a]
S. De Angelis, A. Triminì, Dr. L. Degennaro, Dr. C. Carlucci, V.
Petrelli, Dr. R. Luisi
Department of Pharmacy – Drug Sciences
University of Bari “A. Moro”
FLAME-Lab – Flow Chemistry and Microreactor Technology
Via E. Orabona 4, I-70125 Bari (Italy)
E-mail: renzo.luisi@uniba.it
[b]
M. Franco, A. Triminì, A. González, V. Petrelli, A. de la Esperanza,
Dr. M. B. Cid
Department of Organic Chemistry
Universidad Autónoma de Madrid
Cantoblanco, 28049 Madrid (Spain)
E-mail: belen.cid@uam.es
[c]
[d]
[e]
[f]
Dr. R. Sainz, Dr. A. Goñi, Dr. R. Ferritto
NanoInnova Technologies SL.
Avenida de las Naciones 11, Illescas, 45200 Toledo (Spain)
Dr. R. Sainz
Current address: Instituto de Catálisis y Petroleoquímica, CSIC
C/ Marie Curie 2, 28049 Madrid (Spain)
Dr. G. Romanazzi
DICATECh, Politecnico di Bari
Via E. Orabona 4, Bari 70125 (Italy)
Dr. J. L. Aceña
catalysts. Quite expectedly,
a
seminal example of
a
Departament of Organic and Inorganic Chemistry, Chemical
Research Institute “Andrés M. del Río” (IQAR)
Universidad de Alcalá, IRYCIS
Alcalá de Henares, 28871 Madrid (Spain)
E-mail: jose.acena@uah.es
heterogeneous copper-in-charcoal catalyst was tested in this
reaction.[9] Despite the excellent performance of the catalyst,
some aspects that exemplified the difficulties to understand
composition and reaction mechanisms for this type of materials,
deserve to be mentioned. First, the preparation of the material
required long times of sonication, which is not a straightforward
technique for all laboratories. Moreover, CuO or Cu2O were
initially proposed as the active catalyst, although nine years later
a different species (Cu2(OH)3NO3) was identified as the real
[g]
Dr. M. B. Cid
Institute for Advanced Research in Chemical Sciences (IAdChem)
Universidad Autónoma de Madrid
Cantoblanco, 28049 Madrid (Spain)
Supporting information for this article is given via a link at the end of
the document.
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precatalyst, which is reduced under the reaction conditions to a Results and Discussion
copper(I) acetylide intermediate that is able to catalyse the
reaction.[10] In addition, an impurity identified as Cu2(PO4)OH that
inactivate the CuAAC reaction was also found.
We started our study focusing on the development of graphene-
derived surfaces avoiding the use of GO or rGO as supports. In
this sense, we used graphenit-OX, which is a scarcely oxidized
(ca. 2% oxygen content) low dimensional graphite nanoplatelet
with ca. 2-3 microns size and a few layers thickness.[20] Graphenit-
OX is produced by means of an environmentally friendly protocol,
using a mechanochemical procedure in the absent of any solvent
and displays several advantages compared to other graphene-
derived materials in terms of chemical stability, dispersibility,
Brunauer-Emmett-Teller (BET) surface area (101 m2/g), and bulk
density (0.2 g/mL).[20] With the aim of preparing a homogeneously
dispersed material, we adapted typical conditions found in the
literature for preparing Cu NPs, entailing the use of a Cu(II) salt
and a reducing agent[21] to graphenit-OX. After testing several
combinations of Cu(II) salts and reducing agents under different
concentrations and temperatures, the optimal conditions used
CuCl2 and NaBH4 at 0 °C (Scheme 1). Such a prepared new
material, graphenit-Cu(I) (A), displayed good catalytic activity
(see infra).
Graphene oxide (GO) as well as reduced graphene oxide
(rGO) surfaces have also been recently used as supports of Cu
nanoparticles (Cu NPs)[11] to catalyse click reactions[12] as well as
several other processes.[13] However, it is worth mentioning that
the preparation of GO implies oxidation of graphite under harsh
and hazardous conditions posing problems for scalability.
Furthermore, different conditions were employed in each case for
anchoring the Cu NPs on the graphenic surface, and the resulting
materials displayed a variety of properties regarding composition,
distribution on the surface and oxidation state of copper. The
conditions in the click reaction were also quite different, which
hampers the comparison between materials in terms of catalytic
activity (See SI for a more detailed information). Graphene itself,
prepared by exfoliation of graphite using surfactants and
ultrasound, has also been used as support to provide an efficient
Cu(II)-material.[14]
It is thus manifest that a good understanding of the effect of
each support, as well as the consequences of all the above-
mentioned parameters, is essential in the development of
catalytic processes in terms of activity, leaching and reuse.
According to the existing information, it is difficult to predict the
necessary conditions in the formation of the material to control
factors such as the oxidation state of the metal after using a
certain deposition method. Therefore, systematic comparative
studies would be required to rationally choose a type of support
as well as the preparation conditions that allow a rationally
designed graphene metal/metal oxide material with tailor-made
properties and optimal catalytic activity.[6] Moreover, when using
graphene derivatives as solid supports, it would be desirable to
avoid materials such as GO or rGO and address the research
towards the development of more sustainable, general, scalable
and economical heterocatalysts.
Scheme 1. Synthesis of graphenit-Cu(I) A.
Characterization of graphenit-Cu(I) (A) was performed using
different analytical techniques detailed in the Supporting
Information. For instance, the scanning electron microscopy
(SEM) analysis showed that the Cu particles were
homogeneously dispersed, and not significantly concentrated on
small surface areas (Figure 1a).
In this context, graphite nanoplatelets (GNPs) might represent
a practical solution, since they are usually obtained from sources
other than GO, and therefore they constitute a greener and
cheaper alternative for the deposition and growth of metal
nanoparticles.[15]
Based on our previous experience on graphene-supported
organocatalysts[16] and flow chemistry,[17] we present herein the
preparation of different heterogeneous graphene-based Cu-
catalysts under the simplest standard reaction conditions, as well
as a systematic comparison in terms of composition, catalytic
activity and recyclability by using a classical click process as a
test reaction. We found that the material based on graphite
a)
b)
Figure 1. SEM and XRD of material A.
nanoplatelets presented interesting properties such as
a
surprising stability for Cu(I) species and recyclability and we also
analysed the scope and limitations of this catalyst under batch
and continuous flow conditions.[18],[19] Moreover, we have
validated its utility as catalyst in some other valuable reactions
scarcely explored in a heterogeneous version such as the
sulfonylation of alkynes and the Meerwein arylation.
Graphenit-Cu(I) shows similar structural characteristics
compared to the starting graphenit-OX. The X-ray diffraction
(XRD) pattern showed characteristic peaks for Cu2O (36.5° and
42.3°)[22] and graphene nanoplatelets (26.2°, 43.8°, 54.6°, 77.6°).
The crystallite size (Lc) estimated from the peak width of the (111)
Bragg reflection using the Scherrer’s equation was 20 nm (Figure
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1b). We should point out that the crystallite size measured here is
not the particle size, as our catalyst is polycrystalline. Energy-
Scheme 2. Preparation of graphenic Cu materials A-F.
dispersed X-ray spectroscopy (EDX) analysis and IR spectrum
confirmed the presence of Cu (see the Supporting Information).
The Cu content in graphenit-Cu(I) was examined by inductively
coupled plasma mass spectrometry (ICP-MS) giving a 7 wt% of
Cu.
Then, we turned our attention to the preparation of the
different materials B-F following the same protocol employed for
material A, starting from copper salts and different supports such
as GO, rGO and carbon black (Scheme 2). We also studied the
different properties (% Cu, oxidation state, SEM and crystallite
size) observing that all of them were very dependent on the
support (Table 1). Material B was prepared from GO and
displayed a higher content of copper compared to material A
(entry 1), but consisted of a mixture of Cu(I) and Cu(0) particles
(entry 2). In contrast, material C was obtained using hydrazine as
reducing agent, which caused a full reduction of copper to Cu(0)
(entry 3). Two more materials were prepared from rGO (material
D) and carbon black (material E) (entries 4 and 5). Cu
nanoparticles (F) were also prepared in the absence of support.
Similarly to graphenit-Cu(I), SEM images of material B also
showed a good and homogeneous distribution of copper (Figure
2). However, in materials C-E, areas with accumulation of
particles and areas with little copper were observed. Material C
seems the less homogeneous material, probably due to the use
of hydrazine as reducing agent.
a)
b)
The catalytic activity of each material (A-F) in the CuAAC
reaction was analysed under several reaction conditions (Table
1). We performed all the click reactions between azide 1a and
phenylacetylene 2a using equimolecular amounts of the reagents
in THF as solvent at 80oC. It is worth mentioning that some
problems of reproducibility arose when using different sources of
the azide. A recent report indicated the presence of long-chain
alkyl amines as impurities that may affect the catalytic behaviour
of Cu NPs.[23] Therefore, the catalytic activity of the materials in
Table 1 was assessed employing azide 1a previously purified by
column chromatography.
c)
d)
Figure 2. SEM images of: a) material B; b) material C; c) material D; d) material
E.
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After some experimentation using material A, we established
that 0.8-1.0 mol % was the optimal catalyst loading (see the
Supporting Information). In a preliminary assessment of the
catalytic activity of all materials, we employed the same weight of
material regardless of their Cu ratio, by using a 0.4 M solution and
by analysing conversions after 6 h. Thus, the reaction catalysed
by materials A and B proceeded in high yields (entries 1-2), but
rather disappointing catalytic performances were observed
instead in the click reaction with the rest of materials C-E (entries
3-5) or the non-supported Cu NPs (F) (entry 6). When we
readjusted the amount of catalyst according to the Cu amount of
each material (0.8 mol %), we found that material A provided
higher conversions than B
material B (entries 1 and 2, last columns). Nevertheless, after
some more experiments we observed that this surprising result
was a consequence of an erratic behavior of material B. We
speculated that it could be due to the irregular distribution of both
Cu(I) (more active) and Cu(0) (less active) on different samples
taken for each experiment. This unreliable performance did not
occur with material A as only Cu(I) was present. The conversion
for the rest of materials was slightly affected (entries 3 and 6, last
columns). We also determined that the reaction did not work in
the absence of catalysts, neither using Cu2O nor graphenit-OX
separately (Table 1, entries 7-9) or together (entry 10) pointing
out the synergistic effect between Cu2O and the support. These
results agree with the theory that graphene derivatives are more
than innocent supports and that the electronic interactions
between the conducting surface and the metal increase the
efficiency of a given catalytic process.[24]
Table 1. Properties and comparison of catalytic activity of graphenic Cu
materials A-F.
Therefore, following the same preparation method, only
graphenit-Cu(I) (A) keeps Cu(I) as a stable and sole oxidation
state, showing a homogeneous copper distribution and results.
Moreover, it is prepared starting from a green and cheaper
material.
Using 1 mol % catalyst loading, and 2-methyltetrahydrofuran
(2-MeTHF) as a greener solvent because of its environmental
compliance,[25] the scope of the CuAAC reaction was explored,
employing different azides and alkynes. Thus, substituted
triazoles 3a-g were obtained in good to excellent yields (Scheme
3).
Entry
Material, copper % Cu[b]
oxidation states[a]
3a (%), 0.4 M,
3a (%), 0.8 M,
6 h[c,d]
3 h (1 h)[d,e,f]
3 mg
0.8 mol %
Cu[e]
1
2
3
4
5
6
Graphenit-Cu(I)(A)
7
84
84
100 (64)
17 (traces)
24 (traces)
28 (6)
Cu (I)
GO-Cu (B)
Cu(I), Cu(0)
10.2
10.8
6.6
7.2
–
93-100
21
54-100
GO-Cu (C),
Cu(0)
–
–
–
–
rGO-Cu (D)
Cu(I), Cu(0)
41
CB-Cu (E)
Cu(I)
46
37 (9)
Cu NPs (F)
25
26 (traces)
Cu(I), Cu(0)
7
–
–
–
–
–
–
–
–
–
–
–
–
–
Traces (–)
11 (–)
8
Cu2O
9
Graphenit-OX
Traces (–)
Traces (–)
Scheme 3. Synthesis of triazoles 3 from azides 1 and alkynes 2.
10
Graphenit-OX
Cu2O
The recyclability of the catalyst was also considered. For
practical reasons, and to reduce the loss of catalyst between
different cycles, a 2 mol % loading was employed. As reported in
Table 2, the catalyst was tested for up to 5 cycles, evaluating
complete NMR conversion. For each catalytic cycle, the catalyst
was recovered by centrifugation, rinsed with solvent, and further
re-suspended for a new catalytic cycle. As dispersion methods,
both ultrasounds (US) and vortex were used and compared. As
can be seen in Table 2, yields were high and comparable in both
cases, but the final amount of Cu was found slightly higher with
[a] Established by XRD. [b] Established by TXRF. [c] The reaction was
performed at a 0.43 mmol scale of azide 0.43 M using 3 mg of each catalyst.
[d] Conversion calculated by 1H NMR analysis. [e] Using 0.8 mol% of catalyst
calculated according to the amount of Cu of each material. [f] The reaction
was performed at a 0.86 mmol scale of azide 0.86 M.
The effectiveness of material
A increased with the
concentration. Interestingly, we observed the opposite effect for
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the use of vortex. According to SEM analysis, neither structural
changes nor change in oxidation state were observed in material
A after recycling.
After assessing the performance of the catalyst under batch
conditions and its excellent recyclability, the possibility to use this
material for performing reactions under continuous flow
conditions was considered. Because of the beneficial features of
flow chemistry, the use of flow processing in synthetic chemistry
is becoming
process.[25b]
a paradigm when developing a sustainable
Table 2. Recyclability study in the formation of triazole 3a using US and
vortex.
Scheme 4. Flow conditions for CuAAC reaction.
Once demonstrated the higher overall performance compared
to the other supports, and the recyclability of graphenit-Cu(I) in
the CuAAC reactions under batch and continuous flow conditions,
we were keen to test the material in other types of reactions
implying different mechanistic pathways. First, given the synthetic
versatility of sulfones and our interest in their chemistry, including
that of vinyl sulfones,[26] we decided to apply this material to the
synthesis of 2-substituted vinyl sulfones. With this aim, we
adapted the protocol developed by Taniguchi for the regio- and
stereoselective copper-catalysed sulfonylation of alkynes using
sodium sulfinates under acidic conditions.[27] The heterogeneous
version of this transformation required optimal conditions
achieved after performing a systematic study to analyze the effect
of solvent, temperature, nature of the acid and reaction time
(Table 3, see also the Supporting Information).
Cycle
1
2
3
4
5
%wt Cu[c]
5.94±0.18
US[a]
(% yield)[b]
99
99
97
96
96
Vortex[a]
(% yield)[b]
99
97
97
95
95
6.40±0.14
[a] The sample was dispersed for 2 minutes using sonication, and 5 minutes
using vortex. [b] Determined by 1H NMR using mesitylene as internal
standard. [c] Cu content after 5 runs. Measurements are referred to four
independent samples and were determined by graphite furnace atomic
absorption spectroscopy (GFAAS) after all samples were dissolved in an
aqueous mixture of HNO3/HCl (1/3 ratio) using microwave irradiation.
Starting from phenyl acetylene 2a and sodium phenylsulfinate
4a as model reagents, we evaluated several mixtures of solvents,
to eventually find that ultrasound dispersion of graphenit-Cu(I) in
a 1:1 DMSO/AcOH mixture effectively promoted the reaction to
produce the E-vinyl sulfone 5a, although a conspicuous leaching
of the metal catalyst was observed (entry 1). This inconvenience
was overcome by using Amberlyst-15 as solid acid (200
mg/mmol) with just a slight decrease of yield (entry 2). We also
studied other mixtures of solvents. For instance, adding a small
amount of water allowed us to reduce the reaction time without
much detriment in yield (entry 3). Next, dispersion for 3 min in a
In order to perform the CuAAC reaction under continuous flow
conditions, an Omnifit® cartridge of 700 µL volume was filled with
homogenous powder made of 100 mg of graphenit-Cu(I) (A)
blended with celite or silica. The best conditions were found when
a 2-MeTHF solution of azide 1a and alkyne 2a was introduced
into the cartridge by a syringe pump using 233 µL/min as flow rate
(Scheme 4). Under these conditions, steady-state and full
conversion were observed after 20 min as ascertained by 1H NMR
monitoring. Interestingly, the flow set up could be run up to 5 h
without observing any decrease of yield.
The optimized conditions were further applied for the
continuous flow synthesis of several substituted triazoles 3a, 3c,
3e,f as reported in Scheme 3. Nicely, the catalytic continuous flow
system performs well in producing triazoles in modest to excellent
yields.
o
vortex mixer and increasing the temperature to 100 C was also
tested (entries 4-5), but the highest yield was achieved by using
an 80:20 mixture of DMSO and EtOH as solvent, without
observing catalyst leaching. Thus, after 4 h the E-vinyl sulfone 5a
was obtained in a reasonable 62% yield minimizing the formation
of the undesired ketosulfone 6a (entry 6). Longer reaction times
were not effective (entry 7), and control experiments in the
absence of the Cu catalyst or in the absence of the acid (entry 8)
indicated that the process did not occur.
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Table 3. Optimization study in the formation of sulfone 5a.
Entry
Solvent
Acid
Temp
(º C)
Time
(h)
Suspension
method[a]
Yield (%)[b]
5a
6a
1
2
DMSO
DMSO
AcOH
80
80
24
24
US
US
53
45
–
Amberlyst
15
5
3
4
5
6
7
8
DMSO/
H2O[c]
Amberlyst
15
80
2
US
32
8
DMSO/
H2O[c]
Amberlyst
15
100
100
100
100
100
2
vortex
vortex
vortex
vortex
vortex
41
trac
es
DMSO/
H2O[c]
Amberlyst
15
4
45
4.5
2.5
4.5
Scheme 5. Scope of graphenit-Cu(I)-catalysed regio- and stereoselective
sulfonylation of alkynes.
DMSO/
EtOH[c]
Amberlyst
15
4
62
DMSO/
EtOH[c
Amberlyst
15
24
2
45
Finally, we selected the Meerwein arylation as a model of a
three-component reaction.[28] In this transformation, an aryl group
and a halogen atom are coupled to an alkene, through the
intermediacy of aryl radicals formed from an in situ generated
arenediazonium salt. To the best of our knowledge, a single
example of heterogeneous Meerwein arylation on benzoquinone
has been reported, entailing aniline activation and graphite-
supported copper oxide nanoparticles as catalyst.[29] In our case,
we accomplished a representative example that involved coupling
aniline and methyl acrylate in the presence of NaNO2 and HBr to
DMSO/
EtOH[c
none
traces
[a] The sample was dispersed for 3 min using either sonication or vortex. [b]
Determined by 1H NMR using mesitylene as internal standard. [c] 80:20 ratio.
render α-bromoester
demonstrating the ability of graphenit-Cu(I) to participate in SET
processes (Scheme 6).
7 in a reasonable 50% yield, thus
Under optimized conditions (Table 3, entry 4), an array of
representative 2-aryl vinyl sulfones 5 was prepared in moderate
to good yields, varying the substitution at both the sulfinate and
alkyne moieties (Scheme 5). In all cases a single regioisomer was
detected, and the products were isolated as pure E geometrical
isomers. The substitution pattern at the aryl ring of alkynes 2a-d
included electron-donating or withdrawing groups without
substantial variation in the chemical yield.
Scheme 6. Meerwein arylation reaction catalysed by graphenit Cu(I).
Conclusions
The lack of systematic studies that help understanding the role of
different graphene supports on the properties and catalytic
performances of these materials pushed us to prepare, under the
same deposition conditions, a variety of Cu-based catalysts using
GO, rGO, carbon black, and graphite nanoplatelets. We analysed
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Flow procedure for 1,2,3-triazole synthesis: 100 mg of graphenit-Cu (I)
was blended with silica powder to load a 700 µL volume Omnifit cartridge.
The solution of azide and acetylene 0.1 M in 2-MeTHF was pumped
through the cartridge by a syringe pump, with 233 µL/min as flow rate: full
NMR conversion was observed after 20 min. The cartridge was housed on
a Syrris FRX Volcano at 90 °C. When the steady state conditions were
reached (after 20 min), the solution dispensed had the maximum NMR
conversion. The residue was purified by flash column chromatography
(hexane:EtOAc, 6:4) to afford the corresponding 1,2,3-triazole.
the oxidation state, crystal size, dispersion and catalytic
behaviour using the CuAAC reaction as a model. All materials
except graphenit-Cu(I) were obtained as a mixture of Cu(I) and
Cu(0) species. We found that GO-Cu and graphenit-Cu(I) were
homogeneously dispersed and catalysed click processes in an
efficient manner. Nevertheless, only graphenit-Cu(I), which can
be easily prepared from a more sustainable and economical
starting material, provided reproducible results, maintaining Cu(I)
as unique oxidation state, even after being employed as catalyst
in air several times. 2-MeTHF can be used as a greener
alternative to traditional solvents, the reaction even works in a 1
mol % catalyst loading under batch conditions, and the catalyst
can be recycled at least 5 times. Moreover, it could be employed
under continuous flow conditions and a cartridge-based packed
bed reactor has been developed and tested for continuous flow
synthesis. The flow reactor could be run up to 5 hours without
clogging, assuring a productivity of >300 mg/h of triazole 3a. The
use of graphenit-Cu(I) has also been successfully expanded to
other types of transformations involving both carbon-carbon and
carbon-heteroatom bond forming processes, namely the
sulfonylation of aryl alkynes, and the Meerwein arylation of methyl
acrylate. Further uses of this catalyst are underway in our
laboratories and will be reported in due course.
General reaction procedure for the preparation of vinyl sulfones: In a
vial the sulfonate 4 (1.5 equiv), Amberlyst 15 (140 mg) and graphenit-Cu
(I) (5%) were dissolved in DMSO:EtOH 1:1. The vial was sealed and
suspended in a Vortex system for 3 min at room temperature. The alkyne
2 (1 equiv) was added and the reaction was kept under continuous stirring
at 100 °C. After 24 h the reaction crude was filtered through HPLC filters.
The organic phase was dried over Na2SO4, and the solvent was removed
under reduced pressure yielding the desired products 5a-5q.
Meerwein arylation procedure: A sealed vial equipped with a magnet
was charged with graphenit-Cu (I) (12.3 mg, 4.4 mol %), 0.8 mL of acetone
and 0.3 mL of MeOH and the mixture was sonicated for 3 min. In a second
vial, aniline (1.15 mmol, 105 μL) and HBr (0.3 mL of a 47% solution) were
mixed with 0.6 mL of MeOH and 0.8 mL of acetone and cooled below 5 °C.
Then, a solution of NaNO2 (18.8 mg / 0.6 mL) was added and the mixture
was stirred for 30 min, whereupon methyl acrylate (2.3 mmol, 195 μL) was
added dropwise. The mixture was heated to 37 °C and the dispersion
containing the catalyst, previously sonicated, was added to the reaction
mixture which was stirred vigorously for 90 min. The catalyst was removed
by filtration, washed with EtOAc and the filtrates were concentrated under
reduced pressure. The crude was redissolved in EtOAc, and sequentially
washed with NaOH, dilute HCl and a sat. NaCl solution. Finally, it was
dried over anhydrous MgSO4 and the solvent was evaporated. The crude
reaction was further purified by column chromatography (20:1
cyclohexane: EtOAc) to afford 140 mg of 7 (50% yield).
Experimental Section
Preparation of graphenit-Cu(I) (A): A suspension of 1.75 g of graphenit-
OX in deionized H2O (175 mL) was sonicated for 1 h. Then, CuCl2 (381
mg, 2.83 mmol) was added and the mixture was vigorously stirred at room
temperature for 16 h. After that, the mixture was cooled down to 0 °C and
a solution of NaBH4 (227 mg, 6.00 mmol) in deionized H2O (175 mL) was
added dropwise over 30 min. After stirring at room temperature for 24 h,
the material was filtered, washed with deionized water (4 x 50 mL) and
acetone (3 x 50 mL), and dried under vacuum for 4 h to afford 1.98 g of
graphenit-Cu(I).
Acknowledgements
We acknowledge Fondo di Sviluppo e Coesione 2007-2013 –
APQ Ricerca Regione Puglia “Programma regionale a sostegno
della specializzazione intelligente e della sostenibilità sociale ed
ambientale - FutureInResearch” (TBFPTF6_CC) and the Spanish
Government (CTQ-2012-35957, CTQ2016-78779-R) for financial
support. We also thanks Dr. Angel Lozano for suggesting the use
of vortex.
Characterization of graphenit-Cu(I) (A): Graphenit-Cu(I) (A) was
characterized using different analytical techniques. First the scanning
electron microscopy (SEM) of graphenit-Cu(I) showed that the Cu particles
were homogeneously dispersed, and not significantly concentrated on
small surface areas. Figure S1 shows structural characteristics of
graphenit-Cu(I) compared to the starting graphenit-OX. The energy-
dispersed X-ray spectroscopy (EDX) analysis also confirmed the presence
of Cu (Figure S2). The IR spectrum seems to reveal the presence of Cu(I)
because it is possible to see two new peaks at 550 and 583 cm-1 that can
be matched with the Cu-O vibration. Moreover, the 1576 and 1473 cm-1
peaks can indicate the displacement of the C=C bond due to the interaction
with Cu2O (Figure S3). The Cu content in graphenit-Cu(I) was examined
by inductively coupled plasma mass spectrometry (ICP-MS) giving a
concentration of 7 wt% of Cu.
Keywords: graphene • copper • nanoparticles • heterogeneous
catalysis • click chemistry
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Entry for the Table of Contents
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Sonia De Angelis, Mario Franco,
Alessandra Triminì, Ana González,
Raquel Sainz, Leonardo Degennaro,
Giuseppe Romanazzi, Claudia Carlucci,
Valentina Petrelli, Alejandro de la
Esperanza, Asier Goñi, Rafael Ferritto,
José Luis Aceña,* Renzo Luisi* and M.
Belén Cid*
An efficient and green recyclable heterogeneous graphene-based Cu-catalyst has
been applied in batch and continuous-flow click reactions, sulfonylations and
Meerwein arylation
Page No. – Page No.
A study of graphene-based Cu-
catalysts. Cu(I) nanoplatelets for
batch and continuous-flow
applications
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