Reduced graphene oxide supported piperazine in aminocatalysis

Article abstract of DOI:10.1039/c4cc02701a

Reduced graphene oxide (rGO) has been used as a support for piperazine to provide a heterogeneous bifunctional organocatalyst (rGO-NH) that is able to efficiently promote vintage organic transformations such as Knoevenagel, Michael and aldol reactions. The obtained results suggest a significant role of the support in the course of these reactions. This journal is the Partner Organisations 2014.

Full text of DOI:10.1039/c4cc02701a

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Reduced graphene oxide supported piperazine in
aminocatalysis†
Cite this: Chem. Commun., 2014,
50, 6270
Eduardo Rodrigo,a Beatriz Garcıa Alcubilla,a Raquel Sainz,b J. L. Garcıa Fierro,c
´
´
Rafael Ferrittob and M. Belen Cid*a
´
Received 11th April 2014,
Accepted 18th April 2014
DOI: 10.1039/c4cc02701a
www.rsc.org/chemcomm
Reduced graphene oxide (rGO) has been used as a support for
piperazine to provide a heterogeneous bifunctional organocatalyst
(rGO-NH) that is able to efficiently promote vintage organic transforma-
tions such as Knoevenagel, Michael and aldol reactions. The obtained
results suggest a significant role of the support in the course of
these reactions.
The interest shown in graphene and its applications has significantly
increased in the last few years.1 In addition to graphene, other
derivatives such as graphene oxide (GO)2 have been demonstrated to
be capable of promoting some organic reactions. However, the use
Fig. 1 Working hypothesis: piperazine-grafted reduced graphene oxide
(rGO-NH) as the catalyst in organic reactions.
of covalently functionalized structures based on graphene to catalyse ions of a piperazine-grafted reduced graphene oxide material
organic reactions has been scarcely explored and the scope and (rGO-NH) (Fig. 1). The presence of two nitrogen atoms in
variety of reactions analysed are very limited.3
piperazine not only simplifies the anchoring, but also affords
Although supported catalysts have demonstrated high utility a bifunctional catalyst that opens different reactivity pathways
in organic synthesis,4 the surface areas of these heterogeneous like iminium and basic activation (Fig. 1).
materials are normally inactive. It has been proposed that graphene
The preparation of rGO-NH was carried out in three steps:
and its derivatives may function as a Lewis base, stabilizing cationic (a) oxidation of graphite powder using a modified Hummers’
species5 and therefore their electronic properties6 might offer some method9 followed by sonication in order to get the exfoliation of the
advantages compared with other surfaces. Interestingly, the high material; (b) opening of the resulting epoxides with piperazine
catalytic ability of amines,7 recognised as a highly useful tool in through nucleophilic substitution10 and (c) reduction with hydrazine
organic chemistry,8 mainly implies cationic intermediates such as in basic medium11 (Scheme 1).
iminium or ammonium species. As a consequence, we considered
The introduction of piperazine into the support as well as
that the study of the catalytic properties of directly anchored the characterization of the material has been unequivocally
amines on an rGO surface could be of interest, as the support
could help to stabilize those positively charged intermediates
accelerating some processes.
We present herein the preparation, characterization and
effective use of rGO-NH as a catalyst in a variety of organic
reactions, which presumably involve iminium and ammonium
a
´
Department of Organic Chemistry, Universidad Autonoma de Madrid,
Cantoblanco 28049, Madrid, Spain. E-mail: belen.cid@uam.es
b
c
´
Nanoinnova Technologies SL, Parque Cientıfico de Madrid, Calle Faraday, 7,
28049 Madrid, Spain
´
Instituto de Catalisis y Petroleoquimica, CSIC, C/Marie Curie 2, Cantoblanco,
28049 Madrid, Spain
† Electronic supplementary information (ESI) available. See DOI: 10.1039/
Scheme 1 Preparation of rGO-NH from graphite.
c4cc02701a
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Table 1 Knoevenagel reactiona
Scheme 2 Michael addition via base activation.
Table 2 Knoevenagel–Michael one-pot processa
Entry R2
R1
Product
Time (h) Yield (%)
1
2
3
1a (CO2Et) 2a (Ph)
3aa
21
24
7
24
24
7
21
21
3
16
16
20
83
78
80
88
90
83
86
81
87
85
88
89
1a (CO2Et) 2b ( p-OMe–C6H4–)b 3ab
1a (CO2Et) 2c ( p-NO2–C6H4–) 3ac
4
5
6
1b (COPh) 2a (Ph)
1b (COPh) 2b ( p-OMe–C6H4–) 3bb
1b (COPh) 2c ( p-NO2–C6H4–) 3bc
3ba
7
8
9
10
11
12
1c (CN)
1c (CN)
1c (CN)
1c (CN)
1c (CN)
1c (CN)
2a (Ph)
3ca
2b ( p-OMe–C6H4–) 3cb
2c ( p-NO2–C6H4–)b 3cc
2d (CHQCH–Ph)
2e (CHQCH–CH3) 3ce
2f (CH2–CH–(CH3)2) 3cf
3cd
Equiv. Time Time
MeNO2 (h) (1) (h) (2) Prod (%)
Yield
Entry Nucleophile
Aldehyde
1
2
3
4
5
1a (R2 = CO2Et) 2a (R1 = H)
20
8
24
21
21
21
24
72
48
24
72
4aa 78
13c 1c (CN)
65
68
1a (R2 = CO2Et) 2b (R1 = OMe) 50
1a (R2 = CO2Et) 2c (R1 = NO2) 20
4ab 74
4ac 79
4ca 72
4cb 70
1c (R2 = CN)
1c (R2 = CN)
2a (R1 = H)
20
a
b
2b (R1 = OMe) 50
0.3 mmol of aldehyde was used and 50 mg of rGO-NH was used. We
have observed that those reactions, although to a much smaller extent,
also take place in the absence of the catalyst (see ESI for more details).
a
0.3 mmol of aldehyde was used and 50 mg of rGO-NH was used.
c
3 equiv. of nucleophile and toluene at 80 1C was used.
Knoevenagel–Michael sequence. We observed that rGO-NH
demonstrated using different techniques: X-ray diffraction (XRD), catalysed the Michael addition via formation of 4ac with a
field emission scanning electron microscopy (FE-SEM), energy 71% yield after 8 h of reaction (Scheme 2).
dispersive spectroscopy (EDS) mapping, X-ray photoelectron
spectroscopy (XPS), FT-IR spectroscopy, and thermogravimetric we demonstrated, with some representative examples, that rGO-NH
and elemental analyses.12
was capable of catalysing the one-pot Knoevenagel–Michael process.
Once the viability of both independent processes was established,
Once the material was characterized and we had determined Using nucleophiles 1a and 1c and aldehydes 2a–c in the first step,
that the process for obtaining it was reproducible and scalable and just adding nitromethane for the second step, the sequential
to at least 10 g of rGO-NH, we checked the catalytic ability of the procedure worked efficiently (Table 2).
anchored catalyst. First we decided to exploit the advantages of
After demonstrating the synthetic utility of the rGO-NH, we
the supported catalyst in the classical Knoevenagel condensation, wanted to assess the role of the support on the reactivity of this
which is typically catalysed by amines, mainly secondary ones via new solid catalyst. If the initial hypothesis of the stabilization of
iminium ion activation (Table 1). We were glad to observe that the positively charged intermediates due to the electronic properties5
Knoevenagel reaction afforded high yields with different nucleo- of graphene were operative, we should observe a more significant
philes (1a–c) and a variety of aromatic aldehydes, with both electron effect of the support in reactions that imply iminium ion activa-
donating and electron withdrawing groups (2a–c) (entries 1–9). tion than in those that require enamine activation.
Other types of aldehydes, such as a,b-unsaturated (2d and 2e)
To evaluate this difference we systematically analysed the
and aliphatic aldehydes (2f), also provided high yields effect of the catalyst (rGO-NH) and all the separated compo-
(entries 10–12). Even ketones could also be employed as electro- nents in the Michael addition of nitromethane to enals and the
philes, i.e. 1,4-cyclohexanedione afforded 3cg in a 68% yield aldol reaction of acetone, which presumably occur via iminium
(entry 13). Compound 3cg is an immediate precursor of tetra- ion and enamine activation, respectively (Tables 3 and 4).15
cyanoquinodimethane (TCNQ),13 an electron-acceptor com- We have chosen the Michael addition of enals for this study
pound of high interest in the area of molecular electronics.14 because, if the iminium mechanism was not operating, the
Moreover, we have proven, in the preparation of 3cc, that the 1,2-addition products would be also obtained.16 A comparison
material might be recovered and used without losing efficiency of the efficiency of the reaction and the ratio of products
after at least 3 cycles.
obtained with different materials could give us a qualitative
After verifying the efficiency of the nucleophilic secondary idea of the stabilizing role of the support.
amine in a reaction that most likely occurs via iminium ion
We initially demonstrated that rGO-NH was able to catalyse the
activation, we decided to explore the Michael addition of Michael reaction with both aromatic and aliphatic enals affording
nitromethane to 3ca, obtained in the Knoevenagel condensa- the 1,4 adduct as the main products (entries 1 and 2). We even
tion (Table 1, entry 7), because it would offer the opportunity used p-chlorocinnamaldehyde (2h) (Table 3, entry 3), because
to go a bit further and explore the synthetic possibilities of adduct 6h is an immediate precursor of Baclofen (see structure
this bifunctional heterogeneous catalyst using both abilities in Table 3), a drug used to treat, among other afflictions, muscle
(presumably iminium and basic activation) in a one-pot process spasms caused by multiple sclerosis or spinal cord disease.17
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Table 3 Michael addition of nitromethane to enals via iminium activation
and piperazine afforded comparable results to rGO-NH in terms
of yield; only a slightly different ratio of aldol 7b to enone 8b was
observed (compare entries 3 and 5). The combination of rGO
and piperazine as catalysts (entry 6) afforded similar results to
piperazine. These results seem to indicate a null effect of the
support in this reaction.
Piperazine has been successfully anchored to an rGO surface.
The resulting heterogeneous bifunctional and recyclable catalyst
has been characterized and effectively applied to a variety of organic
transformations such as Knoevenagel, Michael and aldol reactions,
which follow different activation pathways. The synthetic utility of
the new catalyst has been demonstrated via the preparation of
several intermediates of interest such as precursors of baclofen and
TCNQ. The comparison of the catalytic activity of the new material
rGO-NH with some precursors suggests an effect of the surface
stabilizing positively charged intermediates. The search for new
aminocatalytic systems, combining different amines and graphene-
type supports to explore the effect of the electronic properties
of the surface on their catalytic activity, is currently being
conducted in our lab.
Time Conv. Ratio Yield
Entry Aldehydea
Catalyst
(h)
(%)
5/6
6 (%)
1
2
3
4
5
6
7
2d (R = Ph)
2e (R = Me)
rGO-NHe
rGO-NHe
72
72
48
72
72
77 27/73 45
n.d. 8/92 58
55 21/79 71f
2h (R = p-Cl–C6H4–) rGO-NHe
2e (R = Ph)
2e (R = Ph)
2e (R = Ph)
2e (R = Ph)
rGOb
0
—
—
Piperazinec
56 86/14 n.d.
60 56/44 16
rGO/piperazined 72
GO-NHe
72
495 51/49 37
a
b
c
0.3 mmol of aldehyde was used. 50 mg of rGO was used. 5 mol%
d
e
was used. 50 mg of rGO and 5 mol% of piperazine were used. 50 mg
f
was used. Based on the recovered starting material.
Table 4 Aldol condensation
We thank the Spanish Government (CTQ-2012-35957) and
CAM (AVANCAT CS2009/PPQ-1634) for financial support.
E.R. thanks the Spanish Ministry for a predoctoral fellowship
(FPU/AP-2010-0807). R.S. thanks the Spanish Ministry of Science
for a postdoctoral contract (PTQ-11-04601). We thank Manuel
Time Conv. Ratio Yield Yield
Entry Aldehyde
Catalyst
rGO-NH
(h)
(%)
7 : 8
7 (%) 8 (%)
´
Lopez Granados and Rafael Mariscal for useful discussions
1
2
3
4
5
6
2a (R = H)
72
48
72
72
490 53 : 47 39
87 83 : 17 77a
45 31 : 69 15a
37
a
´
about FT-IR interpretation and M Jose de la Mata for her help
2c (R = NO2) rGO-NH
2b (R = OMe) rGO-NH
2b (R = OMe) rGO
15a
47a
—
with thermogravimetric analyses.
0
n.r.
—
2b (R = OMe) Piperazine 72
2b (R = OMe) rGO + Pip 72
49 6 : 94 n.d.
37 4 : 96 n.d.
56a
61a
Notes and references
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a
Based on the recovered starting material.
Using cinnamaldehyde (2e) as the enal we carried out several
comparative experiments.12 We proved that the support rGO
was unsuccessful as a catalyst (entry 4). In contrast, free
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