Bimetallic Oriented (Au/Cu2O) vs. Monometallic 1.1.1 Au (0) or 2.0.0 Cu2O Graphene-Supported Nanoplatelets as Very Efficient Catalysts for Michael and Henry Additions

Article abstract of DOI:10.1002/ejoc.201801443

Michael and Henry addition reactions have been investigated using mono (Au and Cu₂O) and bimetallic nanoplatelets (Au/Cu₂O) grafted onto few-layers graphene (fl-G) films as heterogeneous catalysts by comparison with homogeneous NaOH and K₂CO₃ ones. In the presence of the heterogeneous catalysts, these reactions occurred in the absence of any extrinsic (NaOH and K₂CO₃) base with turnover numbers (TONs) at least four orders of magnitude higher. While the homogeneous catalysts provided TONs close to the unity for Au/Cu₂O/fl-G this was of the order of 10⁷. These reactions also occurred with a very good selectivity to the targeted products. These performances are in line with the basicity of these catalysts demonstrated from CO₂ chemisorption measurements. The effect of the nanosize and the interaction of the nanoparticles with the graphene are also important to achieve this high activity.

Full text of DOI:10.1002/ejoc.201801443

A Journal of
Accepted Article
Title: Bimetallic Oriented (A￿ ꢀ￿ uꢁ￿ ꢀ￿ CO ) versꢀs monometallic
1.1.1 A￿ ꢀ￿ (0) or C.0.0 ꢁ￿ ꢀ￿ CO Graphene sꢀpported Nano-
platelets as very efficient ꢁatalysts for Michael and Henry
Additions
Authors: Andrada Simion, Natalia ꢁandꢀ, Simona M. ꢁoman, Ana
Primo, Ivan Esteve-Adell, Véroniqꢀe Michelet, Vasile I.
Parvꢀlescꢀ, and Hermenegildo Garcia
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to this Accepted Article as a resꢀlt of editing. Readers shoꢀld obtain
the VoR from the joꢀrnal website shown below when it is pꢀblished
to ensꢀre accꢀracy of information. The aꢀthors are responsible for the
content of this Accepted Article.
To be cited as: Eur. J. Org. Chem. 10.100Cuejoc.C01801443
Link to VoR: http:uudx.doi.orgu10.100Cuejoc.C01801443
Supported by

European Journal of Organic Chemistry
10.1002/ejoc.201801443
FULL PAPER
Bimetallic Oriented (A ͞u ͞/ C ͞u ͞ O ) versus monometallic 1.1.1 A ͞u ͞ (0)
2
or 2.0.0 C O Graphene supported Nano-platelets as very
͞u ͞
2
efficient Catalysts for Michael and Henry Additions
[
a]
[a]
[a]
[b]
[b]
Andrada Simion, Natalia Candu, Simona M. Coman, Ana Primo, Ivan Esteve-Adell, Véronique
[
c]*
[a]*
[b]*
Michelet, Vasile I. Parvulescu, Hermenegildo Garcia
Abstract: Michael and Henry addition reactions have been
investigated using mono (A and C O) and bimetallic nanoplatelets
/C O) grafted onto few-layers graphene (fl-G) films as
heterogeneous catalysts by comparison with homogeneous NaOH
and K CO ones. In the presence of the heterogeneous catalysts
these reactions occurred in the absence of any extrinsic (NaOH and
CO ) base with turnover numbers (TONs) at least four orders of
magnitude higher. While the homogeneous catalysts provided TONs
oxide has also reported to promote the Michael addition of
malonates [8]. The use of metal complexes and organocatalysts
has allowed expanding the scope of this reaction for the
synthesis of complex molecules [9].
͞
͞
͞u ͞
2
(A ͞u ͞ ͞u ͞
2
2
3
Besides these, heterogeneous catalysts exhibiting acid and
base properties have also been investigated in this reaction [10].
In this context, among many other types of heterogeneous
catalysts, the last two decades have seen an impressive number
of examples showing the activity, and especially the selectivity of
gold and copper in many catalytic reactions. For the particular
case of the Michael addition the reported studies indicated that
the selectivity can be controlled by tuning the oxidation state of
Au from 0 to (I) and (III) [11]. Au support, consisting of an
organic functionalized material or an oxide, should play the role
controlling the charge density on the Au nanoparticles [12]. Au
nanoparticles may exhibit an even more complex behavior. They
can generate and stabilize electron–rich carbenes on their
surface, after an electronic transfer to the anti–bonding valence
orbitals of the C-O group of substrates [13]. Thus, beyond gold-
catalyzed Michael additions, this constitutes an example of how
gold nanoparticles modify the electronic density of unsaturated
bonds [14]. The interaction of copper with organic functionalities
of a support [15] or with the support itself [16] is producing quite
similar effects in this reaction.
Besides Michael addition, the Henry reaction is other classic
carbon–carbon bond formation reaction, consisting in the
addition of a nucleophilic anion derived from nitroalkane to an
electrophilic aldehyde or ketone [17]. Typically, it utilizes only a
catalytic amount of a homogeneous catalyst that could be alkali
metal hydroxides, alkoxides, carbonates, triflates, compounds of
fluoride anion or nonionic organic amines [18]. Other
homogeneous catalysts utilized in this reaction are metal
complexes [19]. Base-heterogeneous catalysts as Mg-Al
hydrotalcite have been used as well [20].
K
2
3
7
2
close to the unity for A ͞u ͞/ C ͞u ͞ O/fl-G this was of the order of 10 .
These reactions also occurred with a very good selectivity to the
targeted products. These performances are in line with the basicity
of these catalysts demonstrated from CO
2
chemisorption
measurements. The effect of the nano-size and the interaction of the
nano-particles with the graphene are also important to achieve this
high activity.
Introduction
Michael addition, as originally defined, [1] is the addition of an
enolate of a ketoneor aldehyde or a doubly stabilized carbon
nucleophile [2] to an α,β-unsaturated carbonyl compound at the
β carbon. Thus, this reaction consists on the nucleophilic
1,4-addition of a carbanion or another nucleophile to an α,β-
unsaturated carbonyl compound [3]. This reaction is catalyzed
by both acid [4] and base [5] catalysts. More recently, the
homogeneous catalysts utilized in this reaction were enlarged by
using metal complexes [6] and organocatalysts [7]. Organic
superbase, 1,1,3,3-tetramethylguanidine funcionalized graphene
[
[
a]
b]
A. Simion, Dr. N. Candu, Prof. S.M. Coman, Prof. V.I. Parvulescu
Department of Organic Chemistry, Biochemistry and Catalysis
University of Bucharest
Beside catalytic activity, the use of Cu-complexes bearing
various ligands has allowed also to gaindia- and
stereoselectivity in the Henry reaction [21].
However, the literature referring to heterogeneous catalysts
with Cu for the Michael reaction is scarce and refers either to
immobilized Cu(II) complexes [22] or to MOF systems
incorporating Cu [23]. For Au as catalyst, in our best knowledge
there is no other precedent in this reaction.
4-12 Regina ElisabetaBlv., 030016, Bucharest, Romania
E-mail: vasile.parvulescu@chimie.unibuc.ro
Dr. A.Primo, Dr. I. Esteve-Adell, Prof. H. Garcia
Instituto Universitario de TecnologiaQuimica Consejo Superior de
Investigaciones Científicas
Universidad Politecnica de Valencia
Avda. de los Naranjos s/n, Valencia 46022, Spain
E-mail: hgarcia@qim.upv.es
[
c]
Prof. V. Michelet
Institut de Chimie de Nice, UMR 7272 CNRS, Parc Valrose, Faculté
des Sciences
University Côte d’Azur
Graphene, an allotrope of carbon, has been considered as an
excellent suitable catalytic support due to its high carrier
mobility, high electrical and thermal conductivity, high surface
06100 Nice, France
2
E-mail: veronique.michelet@unice.fr
area (theoretical value of 2630 m /g), unique two-dimensional
(
2D) honeycomb lattice, high electron mobility, strong metal-
This article is protected by copyright. All rights reserved.

European Journal of Organic Chemistry
10.1002/ejoc.201801443
FULL PAPER
support interactions and easy surface functionalization [24-25].
In addition, doping graphene-nanosheets with heteroatoms
became an attractive method of tuning its electronic and
catalytic properties [26].
On the other side, graphene supported metal nanoparticles
(
MNPs) have already shown very active and selective properties
for various organic transformations such as: oxidations [27],
reductions [28-29] or coupling reactions [30-32]. In this context,
we recently demonstrated that coupling reactions can be
efficiently catalyzed by MNPs strongly grafted on few- and
multilayer defective graphenes prepared by pyrolysis of natural
-
2+
4
polysaccharides containing metal salts (ie. AuCl or Cu as
source of metal ions) [33]. Furthermore, the pyrolysis of thin
films of alginate can provide fl-G (fl meaning few layers
structures; G meaning defective graphene) of few nanometers
thickness [34-35]. Under pyrolysis at 900ºC in inert atmosphere
copper is orientated onto the graphene as (1.1.1) C
after exposure to air spontaneously render to oriented (2.0.0)
copper (I) oxide nanoplatelets (C O/fl-G). Under the same
conditions, onto the few layers of graphene, Au generates
1.1.1) oriented Au nanoplatelets (A /fl-G), where the lateral
͞u ͞/ fl-G which
͞u ͞
2
3
+
(
͞u ͞
sides correspond to (0.0.1) oriented planes [9].
In order to prove the versatility of the graphene supported MNPs
in coupling reactions in this study we extended the investigation
of these materials from the monometallic to bimetallic A
2
͞u ͞/ C ͞u ͞ O
2
Figure 1. TEM image of the A u͞ ͞/ C ͞u ͞ O/fl-G catalyst.
/
fl-G films looking for a synergistic effect in two important C-C
coupling reactions, namely Michael and Henry additions [36].
Henry reaction is a ’’nitroaldol condensation’’ and one of the
most atom-economical C-C coupling processes [37-38]. Under
classical conditions, both reactions require basic or acidic
catalysts in the presence of organic solvents, and long reaction
times, which may lead to environmentally hazardous residues
and undesirable by-products [39-43].
The considered Henry addition is the coupling of benzaldehyde
with nitromethane to nitroaldol. Michael addition was
investigated in water, while the Henry addition in both protic
(
isopropyl alcohol, IPA) and aprotic solvents (heptane).
Results and Discussion
2
Monometallic C ͞u ͞ O/fl-G and A ͞u ͞/ fl-G catalysts were exhaustively
characterized as described in our previous works [31, 33]. Briefly,
in accordance to TEM images combined with the analysis of the
diffraction patterns of back scattered electrons, the oriented
C
͞
u
͞
2
O/fl-G are constituted from Cu
exhibit a preferential (2.0.0) facet orientation [33] while A
catalysts display preferential (1.1.1) facet orientation
2
O
nano-platelets which
Scheme 1. Michael addition of acetoacetates with MVK (1) and Henry reaction
of benzaldehyde with nitromethane (2).
͞u ͞/ fl-G
a
irrespective the Au loading and the thickness of G [31]. To
illustrate the materials used as catalysts in the present study that
are also coincident with those previously reported [31], Figure 1
Comparative behavior of A
catalysts in Michael addition
2 2
͞u ͞/ fl-G, C ͞u ͞ O/fl-G and A ͞u ͞/ C ͞u ͞ O/fl-G films as
presents
a
transmission electron microscopy image of
A
͞
u
͞
/C O/fl-G.
͞
u
͞
2
Table 1 compiles results in the presence of C
͞
͞
O/fl-G, A
͞
u
͞
/fl-G
2
Catalytic performance of these oriented nanoplatelets on
graphene were checked in two reactions controlled by
completely different mechanisms, such as Michael (Scheme 1,
Eq. 1) or Henry additions (Scheme1, Eq. 2). For the Michael
addition, the experiments were carried out considering methyl
acetoacetate (MeAcOAc) and ethyl acetoacetate (EtAcOAc) as
activated methylene substrates and methyl vinyl ketone (MVK)
as Michael acceptor.
and A ͞u ͞/ C ͞u ͞ O/fl-G catalysts. With acetoacetates as Michael
2
donors the reaction may proceed in two steps (Scheme 1, Table
1), where the first step leads to the formation of mono adduct
MA1 which can be subsequently deprotonated affording the
addition of another MVK molecule with the formation, in the
second step, of the MA2 product. The catalytic results show that
the performances in this reaction are controlled by the nature of
the catalyst and of the Michael donor. Prior controls using fl-G
This article is protected by copyright. All rights reserved.

European Journal of Organic Chemistry
10.1002/ejoc.201801443
FULL PAPER
as catalyst showed the failure of this material to promote either
the Michael or the Henry reaction. These preliminary blank
controls clearly established that the presence of metal
nanoparticlesis required to obtain catalytically active materials.
Working with MeAcOAc the homogeneous NaOH base catalyst
total. This behavior can be related to the different basic
properties of A
or A /fl-G films.
Indeed the CO
different concentrations of basic sites and CO
temperatures (Table 2). These results correspond to values
2 2
͞u ͞/ C ͞u ͞ O /fl-G in comparison to those of C ͞u ͞ O /fl-G
͞u ͞
2
chemisorption on these catalysts results in
desorption
2
(
Table 1, entry 1) provides a very high conversion but with a
relatively low selectivity to MA1 (~12.7%). In the absence of
base, on A /fl-G and C O/fl-G films (entries 2 and 3) the
resulted after the substraction of the CO
by the graphene support [44].
2
directly chemisorbed
͞u
͞
͞u ͞
2
conversion is lower compared to the homogeneous catalyst, but
the achieved selectivity in MA1 is very high. Under the same
Table 2. CO chemisorption results.
2
conditions, bimetallic A
to a high conversion comparable with that produced by the
monometallic /fl-G, O/fl-G but with much higher
2
͞u ͞/ C ͞u ͞ O/fl-G films (entry 4) as catalyst, led
Temperature at Maximum
Sample
Adsorbed
(mmoles/g) x 10
CO
2
-3
(°C)
A
͞
u
͞
C
͞
͞
a
selectivity in MA1 compared to all the individual catalysts.
Replacing the Michael donor with ethyl acetoacetate (EtAcOAc),
led to an increase of the conversion for all the catalysts. Under
these conditions the differences between the homogeneous
catalyst (NaOH) and the heterogeneous graphenes are very
small.
A
͞
͞
346
292
2.78
2.20
0.94
6.29
3.99
C ͞u ͞
2
3
50
252
47
2
A ͞u ͞/ C ͞u ͞ O/fl-G
3
Table 1. Catalytic performances of A
2 2
͞u ͞/ fl-G, C ͞u ͞ O/fl-G and A ͞u ͞/ C ͞u ͞ O/fl-G
films in the Michael addition of acetoacetates donors with MVK acceptor.
The concentration of the basic sites decreased in the order
[
a]
[b]
[b]
Michael
donor
Base
Graphene
Catalyst
C
S
S
(%)
A
͞
͞
͞
͞
O/fl-G > C
͞
2
͞ O/fl-G >A
͞
͞
(%)
(%)
MA1
MA1
o
sites, appreciated from the CO
order A /C O/fl-G >A
͞
͞
͞
͞
͞
͞
͞
͞
line with the catalytic data included in the Table 1 supporting the
role of the basicity in this reaction.
1
2
3
4
5
6
7
8
9
MeAcOAc
MeAcOAc
MeAcOAc
MeAcOAc
MeAcOAc
MeAcOAc
EtAcOAc
EtAcOAc
EtAcOAc
NaOH
no
no
100
12.7
75.7
77.4
72.8
100
87.3
24.3
22.6
27.2
0
A
͞
͞
32.4
31.1
85.8
5.8
Table 3. Time evolution of the conversion and selectivity to MA1 and MA2 for
no
C ͞u ͞
2
A
͞
͞
2
͞u ͞/ C ͞u ͞ O/fl-G in the Michael addition of MeAcOAc donor
no
A
͞
͞
͞u ͞
2
[
a]
[b]
[b]
Time
Catalyst
C
S
S
TON
no
Au(0.52wt%)/fl-G
(h)
(%)
(%)
(%)
MA1
MA 2
NaOH
no
no
100
10.2
45.7
63.1
100
89.8
54.3
36.9
0
5
5
7
A
͞
͞
97.0
92.3
98.8
1
A
͞
͞
14.3
12.8
68.9
2.3
92.6
93.5
88.4
100.0
28.8
85.2
86.6
81.6
22.4
75.7
77.4
72.8
12.7
7.4
1.27x10
5
no
C
͞
͞
2
C
͞
6.5
0.41x10
no
A
͞
͞
͞
͞
3
A
͞
͞
͞
11.6
0
1.43x10
4
Au/fl-G
1.74
1
0
1
EtAcOAc
EtAcOAc
no
no
Au/fl-G
fl-G
8.3
0
100
0
0
0
5
NaOH
84.9
21.7
19.4
73.4
100
71.2
14.8
13.4
18.4
77.6
24.3
23.6
17.2
87.3
7.07
1
6
A
͞
-
-
-
-
-
-
-
-
9
Reaction conditions: Michael donor: 1 mmol: Michael acceptor: 1.5 mmoles,
2
7
C ͞u ͞
2
Catalyst: 0.12 mmoles NaOH or 1 piece of 1×1 cm of C
͞
͞
O /fl-G on quartz
0.20 mg of Cu total), or one piece of 1 × 1 cm plate of A /fl-G film (0.24
O/fl-G (0.32 mg
O deionized, temperature:
RT; time 18h. Note: [a]-Conversion refers to Michael donor transformation.
b]-selectivity to MA1 and MA2. Conversion and selectivities were
determined by GC-MS.
2
(
͞u ͞
2
mg of Au total) or one piece of 1 × 1 cm plate of A
Au/Cu of 3/1), 5mg Au(0.52 wt %)/fl-G, 8 mL H
͞
͞
͞
8
A
͞
2
9
[
10
11
A
͞
32.4
31.1
85.8
100
1
8
However, for NaOH, and A
increase corresponded to a further decrease of the selectivity to
MA1 (Table 1, entries 5, 6 and 7). Interestingly, the increase of
͞
͞
͞
O/fl-G films this
C ͞u ͞
2
1
2
3
A
͞
the conversion for the bimetallic A
2
͞u ͞/ C ͞u ͞ O /fl-G films catalyst did
1
not affect the selectivity in MA1, which on the contrary becomes
This article is protected by copyright. All rights reserved.

European Journal of Organic Chemistry
10.1002/ejoc.201801443
FULL PAPER
although the conversions were smaller, in terms of activity, these
catalysts presented much higher TONs. They increased till the
order of 10 . Importantly, an increase of the temperature from
RT to 50ºC led to a further increase of the TON with one order of
magnitude. The reaction by-product in these reactions was
1
1
1
1
4
5
6
7
A
͞
u
͞
/fl-G
O/fl-G
/C O/fl-G
NaOH
44.4
42.5
89.9
100
74.5
75.7
71.5
7.0
24.5
24.3
18.5
93.0
-
-
-
-
30
4
C
͞u
͞
2
A
͞u
͞
͞u ͞
2
benzoic acid. For C
further oxidized to benzoic acid which becomes the major by-
product. Non-orientated Au/G and Cu O/G catalysts showed
2
͞u ͞ O/fl-G, in addition, benzaldehyde was
Reaction conditions: Michael donor: 1 mmol: Methylacetoacetate (MeAcOAc),
Michael acceptor: 1.5 mmoles, Catalyst: 0.12 mmoles NaOH or 1 piece of
2
even higher TONs than the corresponding orientated catalysts
that might be an evidence of an increased activity of the smaller
particles.
A
͞u
͞
/fl-G C
temperature: RT; Note: [a]-Conversion refers to Michael donor transformation.
b]-selectivity to MA1 and MA2. Conversion and selectivities were determined
2 2 2
͞u ͞ O/fl-G, A ͞u ͞/ C ͞u ͞ O/fl-G or 5 mg Au/fl-G, solvent: 8 mL H O deionized,
[
by GC-MS.
Table 4. Catalytic efficiency of C
͞
͞
O/fl-G, A
͞
͞
͞
͞
͞
͞
catalysts in the Henry reaction.
In order to better understand the kinetics of the Michael addition
we measured the conversion and the selectivity in the Michael
addition of MeAcOAc donor with MVK acceptor using NaOH,
[
a]
[b]
Solvent
Catalyst
C
(
S
(%)
TON
%)
and the A
͞
u
͞
/fl-G, C
͞
u
͞
O/fl-G,
A
͞
͞
͞
͞
O/fl-G film catalysts at
[c]
1
2
3
4
5
6
7
8
9
1
1
no
K
A
A
A
2
CO
/fl-G
/fl-G
/fl-G
3
59.8
91.8
0
0.15
0
different reaction times. The results are listed in Table 3. With
NaOH as catalyst the conversion becomes total after 5h. Further
increase of the reaction time till 30h corresponded to a
continuous deplete in the selectivity to MA1 in the favor to MA2
no
͞
͞
0
[
[
d]
d]
4
5
6
IPA
͞
͞
11.1
64.7
33.6
0
32.0
46.2
54.0
0
4.6x10
2.7x10
4.4x10
0
(
93% selectivity), which is a typical behavior for a strong basic
medium leading to a second addition. In terms of conversion, the
monometallic A /fl-G and C O/fl-G film catalysts provided much
smaller conversions and better selectivities to MA1. Surprisingly
was the behavior of the A /C O/fl-G film which allowed indeed
IPA
͞u ͞
[e]
IPA
Au(0.15wt %)/G
͞
u
͞
͞u ͞
2
no
C
C
C
C
͞
͞
O/fl-G
͞u ͞ ͞u ͞
2
very good conversions but also selectivity to MA1 even after 30h.
However, the calculation of the TONs after 5h showed a
different order in activity than that presented in the Table 3.
Heptane
IPA
͞
͞
O/fl-G
0
0
0
[
d]
4
5
͞
͞
O/fl-G
7.9
74.5
89.3
0
30.2
60.4
0.3
0
1.2x10
1.2x10
A
͞
u
͞
/C
͞
u
͞
2
O/fl-G exhibits an almost seven times higher TON order
/fl-G and C O/fl-G film catalysts almost five
IPA
͞
͞
O/fl-G
than NaOH while A
͞
u
͞
͞u ͞
2
[
f]
5
0
1
IPA
Cu
2
O(1 wt%)/G
8.9 x10
times. These values confirm, like in other coupling reactions the
extremely high activity of the orientated metal nanoparticles [31,
no
A
A
A
͞
͞
͞
O/fl-G
O/fl-G
O/fl-G
0
33].Unoriented supported Au/fl-G nanoparticle catalysts were
6
7
much less active compared to A /fl-G (five order difference in
activity). However, in terms of TONs the activity of these
nanoparticles is comparable to that of NaOH, namely, still high.
12
Heptane
IPA
͞
͞
͞
90.9
97.4
0.1
96.7
9.4x10
13
͞
͞u ͞
2
1.0x10
Reaction conditions: 10 mmoles MeNO
2
, 0.5 mmoles benzaldehyde, 24h,
Comparative behavior of A
Henry addition
2 2
͞u ͞/ fl-G, C ͞u ͞ O/fl-G and A ͞u ͞/ C ͞u ͞ O/fl-G films in the
50º C, 3mL solvent; catalyst: [a]conversion for benzaldehyde; [b]-selectivity
2
2 3
to nitroaldol. [c] 2 mmoles of K CO ; [d] RT; catalyst: 1 piece of 1×1 cm of
2
2
C ͞u ͞ O /fl-G on quartz (0.20 mg of Cu total), or one piece of 1 × 1 cm plate of
2
A
͞
͞
2
͞u ͞/ C ͞u ͞ O
The Henry addition (Scheme1, Eq. 2) has been investigated in
the presence of the same A /fl-G, C O/fl-G and A /C O/fl-G
/
͞
͞
͞
͞
͞u ͞ ͞u ͞
2
wt%)/G; Conversion and selectivities were determined by GC-MS.
Difference to 100% in selectivity is for benzoic acid.
film catalysts. This reaction is generally catalyzed by many
organic bases, including carbonates, bicarbonates, alkali metal
hydroxides, alkoxides, and organic nitrogen bases with the
disadvantage of the difficulty in separation of various by-
products [45]. Under basic conditions nitroalkanes are able to
However, like for the Michael addition the bicomponent
A ͞u ͞/ C ͞u ͞ O/fl-G films led to the best performances. Very high
2
TONs and selectivities were achieved with this catalyst. Under
the optimal reaction conditions of 50ºC for 24 h, they afforded an
as high conversion of benzaldehyde as 97.4 % and a selectivity
of 96.7 % in favor of nitroaldol.
deprotonate the nitroaldol leading to
a nitronate anion
intermediate [46] which further reacts with aldehydes yielding β-
nitroalcohols [47]. Table 4 summarizes the catalytic results on
the investigated catalysts.
Very important to notice, the catalysts were recycled five times
with almost no changes in the catalytic behavior.
As Table 4 shows, using 2 mmoles of K
inorganic base, the reaction took place with
2
CO
3
as a weak
moderate
a
The role of the solvent in this reaction is very important. In an
aprotic solvent such as heptane the conversions were either
zero or the reaction was directed to benzaldehyde. It is assumed
conversion, but with a relatively high selectivity to the nitroaldol
product. TON value calculated under these conditions was of
2
0.15. On the contrary, in the presence of A ͞u ͞/ fl-G and C ͞u ͞ O/fl-G,
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European Journal of Organic Chemistry
10.1002/ejoc.201801443
FULL PAPER
that the measured basicity is the combined effect of the very
small particle size of these films and the generated interaction
between these and the graphene support.
The behavior of these catalysts in both Michael and Henry
reactions should be associate to their properties as Lewis base.
General procedure for the Michael addition.
To a solution of β-ketoesters as Michael donor (1 mmol of methyl
acetoacetate or ethyl acetoacetate) in 8 mL of solvent (deionized H O)
was added MVK as Michael acceptor (1.5 mmoles, 0.105 g), base (0.12
2
2
1
0
mmoles, NaOH) if required and one piece of 1 × 1 cm plate of C
͞
u
͞
2
O/fl-G
on quartz (0.24 mg of Cu total), one piece of 1 × 1 cm plate of A /fl-G
O /fl-G films as catalysts.
In Cu
2
O oxide Cu (I) exhibits a d configuration [48] and basicity
2
͞u ͞
2
-
is associated to the presence of surface O species. Au has
2
film or one piece of 1 × 1 cm plate of A ͞u ͞/ C ͞u ͞
2
1
0
also a d configuration and this property affords an increase of
the basicity of the supported metal nanoparticles with direct
catalytic effect [49]. On this basis the behaviour of the individual
The resulting mixture was left stirring at room temperature for 5-30 h. The
reaction mixture was then filtered, extracted with ethyl acetate (3 x 10
mL) and the combined organic layer was dried over Na
concentrated.
2 4
SO , filtered and
2
Cu O and Au/graphene catalysts as bases is well justified
according to the literature.
The increase of the activity of bicomponent Cu O-Au/graphene
2
Product analysis
catalyst should be the result of the direct interaction of Au with
Cu O. Recent studies of Glorius et al.[49]. using gold deposited
on CeO -ZrO -mixed oxides have shown that the density of acid
sites was decreased, whereas the density of basic site was
increased by modification with Au. A similar effect can results
Irrespective of reaction procedure, after reaction the catalyst was
collected by filtration or was manually removed, and the reaction
products were analyzed and identified by GC-MS (THERMO Electron
Corporation instrument), Trace GC Ultra and DSQ, Trace GOLD with a
TG-5SilMS column (30 m × 0.25 mm × 0.25 mm).
2
2
2
2
after the interaction with Cu O. This effect is more evident for the
experiment described in entry 12.
GS-MSanalysis of the reaction products using Methyl acetoacetate
corresponded to: MA1: Methyl 2-acetyl-5-oxohexanoate: GC-MS,
(m/z):186 (M , 2), 155 (12), 154 (12), 144 (100), 143 (18), 139 (25), 129
Such a model is also supported by the results from Table 4
presenting the effect of the solvent. Heptane is not able to
surpress the acidity induced by the two active species. On the
contrary, IPA has two contributions in this reaction: i) to act as a
solvent for the investigated substrates, and ii) to block any
residual Lewis acidity. This effect is more evident for the
+
(15), 116 (40), 112 (56), 111 (57), 101 (21), 97 (17), 87 (64), 84 (64), 69
+
(
(
17), 58 (20), 55 (29).MA2: GC-MS, (m/z): 256 (M , 1), 238 (20), 196
24), 186 (87), 182 (15), 181 (66), 179 (87), 167 (48), 165 (22), 164 (42),
154 (88), 153 (63), 143 (43), 139 (82), 137 (33), 136 (40), 129 (90), 125
(
(
33), 123 (73), 116 (47), 111 (100), 109 (56), 97 (63), 95 (32), 93 (65), 91
23), 85 (18), 84 (12), 79 (14), 71 (32), 55 (25).
catalysts containing Cu
and TONs of 10 .
2
O which reached conversions of 97.4%
7
and for Ethyl acetoacetate to: MA1: Ethyl 2-acetyl-5-oxohexanoate: GC-
+
MS, (m/z): 200 (M , 2), 158 (100), 139 (29), 130 (30), 112 (59), 111 (69),
+
Conclusions
101 (55), 84 (71), 73 (33), 55(17). MA2: GC-MS, (m/z): 270 (M , 1),
2
(
1
52(18), 209 (24), 200 (100), 181 (98), 179 (88), 167 (52), 165 (32), 164
30), 157 (39), 154 (55), 153(25), 143(76), 139 (91), 137 (29), 136 (31),
25 (29), 123 (60), 121 (54), 115 (16), 111 (90), 109 (52), 97 (43), 95
27), 93 (51), 71 (16), 55 (14).
In summary, we have developed
procedure for Michael and Henry addition reactions using
bimetallic nanoplatelets grafted onto few-layers graphene
a simple and efficient
(
A
͞
u
͞
/C
absence of any extrinsic base. Moreover, films of A
fl-G also exhibit a high catalytic activity to promote the Michael
͞
u
͞
2
O/fl-G films as catalyst. These reactions occurred in the
General procedure for the Henry reaction.
͞
͞
and C ͞u ͞ O
2
/
All reagents were purchased from Sigma-Aldrich and used as received
without further purification. To a glass sealed vial containing a magnetic
stir bar with 3 mL of solvent (Isopropyl alcohol dried (IPA) or heptane)
was added benzaldehyde (0.5 mmoles), nitromethane (10 mmoles) and
catalyst. Resulting mixture was left stirring for 24h at room temperature
addition of acyclic active methylene and methine compounds to
α, β-conjugated ketone or the Henry reaction of nitroalkane to β-
nitroaldols. Noteworthy, by comparison to homogeneous NaOH
or K CO , in the presence of the heterogeneous catalysts these
2 3
reactions occurred with TONs at least four orders of magnitude
higher. While the homogeneous catalysts provided TONs close
to the unity for A
oriented supported nanoparticles Au/fl-G catalysts were much
less active compared to A /fl-G. However, in terms of TONs the
0
or 50 C.The reaction mixture was then filtered, concentrated and silylated.
The products were analyzed and identified by using GC-MS (THERMO
Electron Corporation instrument) and a Bruker Advance III UltraShield
7
͞
u
͞
/C
͞
u
͞
O/fl-G this was of the order of 10 . Un-
1
5
00 MHz spectrometer, operating at 500,13 MHz for H NMR, 125,77
13
1
MHz for C NMR. For H NMR were reported downfield from CDCl
3
(δ:
͞
͞
13
7.26ppm) and for C NMR chemical shifts were reported in the scale
activity of these nanoparticles is comparable to that of NaOH,
namely, still high. These performances are in line with the
relative to the solvent of CDCl
reference.
3
(δ: 77.0 ppm) used as an internal
2
basicity of these catalysts demonstrated from CO chemisorption
measurements. The effect of the nano-size and the interaction of
the nano-particles with the graphene is also important to achieve
these properties.
The recovered products were silylated (50 μL pyridine, 100 μL BSTFA
(N,O-bis(trimethylsilyl) trifluoroacetamide) and TMCS
trimethylchlorosilane) silane agent), and analyzed by GC-MS. The
identification of the products was made using a GC-MS (THERMO
Electron Corporation instrument), Trace GC Ultra and DSQ, Trace
GOLD: TG-5SilMS column with the following characteristic: 30m
x0.25mm x 0.25um working with a temperature program (50 °C (2 min) to
(
Experimental Section
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European Journal of Organic Chemistry
10.1002/ejoc.201801443
FULL PAPER
2
50 °C at 10 °C/min (Hold 10.00 min) for a total run time of 32 min) at a
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.63-4.51 (m, 2H, CHHNO
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͞
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/fl-G and C
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͞
u
͞
2
O//fl-G catalysts were prepared according to previous
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quartz plate (2 × 2 cm ) by casting 300 µl of filtered solution spinning at
2
4
,000 rpm. for 1 min. Subsequently, films were immersed into a 1 mM
aqueous solution of NaAuCl (Aldrich) during 1 min to adsorb Au on Cu-
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4
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o
-1
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European Journal of Organic Chemistry
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Entry for the Table of Contents
FULL PAPER
Michael
reactions have been investigated
using mono (A /fl-G and C O/fl-G)
and bimetallic nanoplatelets
/C O/fl-G) grafted onto few-
layers graphene films as
heterogeneous catalysts. These
reactions occurred in the absence of
any extrinsic base with TONs at
least four orders of magnitude
higher.
and
Henry
addition
Graphene, Coupling reactions
Andrada Simion, Natalia Candu,
Simona M. Coman, Ana Primo, Ivan
͞u
͞
͞u ͞
2
*
Esteve-Adell, Véronique Michelet,
(A ͞u ͞ ͞u ͞
2
*
Vasile I. Parvulescu, Hermenegildo
*
Garcia
Page No. – Page No.
Bimetallic Oriented (A
versus monometallic 1.1.1 A
.0.0 C O Graphene supported
͞
͞
͞
͞
O )
͞u ͞
(0) or
2
͞u ͞
2
Nano-platelets as very efficient
Catalysts for Michael and Henry
Additions
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