Selectivity matters: Graphene oxide-mediated oxidative coupling of benzylamine to N-benzylidine-1-phenylmethanamine under microwave irradiation

Article abstract of DOI:10.1016/j.molcata.2015.05.010

A selective, efficient and benign oxidative coupling of benzylamine under microwave irradiation was achieved at mild reaction conditions in the absence of oxidant using graphene oxide as catalyst. Reaction conditions seem to point to the favoured formation of an imine intermediate which subsequently reacts with benzylamine to provide high selectivities at almost quantitative conversion of starting material to the oxidative coupling product N-benzylidine-1-phenylmethanamine. A plausible reaction mechanism is proposed.

Full text of DOI:10.1016/j.molcata.2015.05.010

Journal of Molecular Catalysis A: Chemical 406 (2015) 19–22
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Journal of Molecular Catalysis A: Chemical
journal homepage: www.elsevier.com/locate/molcata
Selectivity matters: Graphene oxide-mediated oxidative coupling of
benzylamine to N-benzylidine-1-phenylmethanamine under
microwave irradiation
Jose M. Bermudeza,b, J. Angel Menendezc, Ana Arenillasc, Rafael Martinez-Paloud,
Antonio A. Romeroa, Rafael Luquea,∗
a Departamento de Quimica Organica, Universidad de Córdoba, Campus de Rabanales, Edificio Marie Curie, Ctra Nnal IV-A, Km 396, E14014, Córdoba, Spain
b Chemical Engineering Department, Imperial College London, SW7 2AZ, London, United Kingdom
c Instituto Nacional del Carbón-CSIC, Apdo. 73, 33080 Oviedo, Spain
d Instituto Mexicano del Petroleo, Eje Central Lazaro Cardenas 152, 07730, Mexico D.F., Mexico
a r t i c l e i n f o
a b s t r a c t
Article history:
A selective, efficient and benign oxidative coupling of benzylamine under microwave irradiation was
achieved at mild reaction conditions in the absence of oxidant using graphene oxide as catalyst. Reaction
conditions seem to point to the favoured formation of an imine intermediate which subsequently reacts
with benzylamine to provide high selectivities at almost quantitative conversion of starting material to
the oxidative coupling product N-benzylidine-1-phenylmethanamine. A plausible reaction mechanism
is proposed.
Received 23 March 2015
Accepted 14 May 2015
Available online 15 May 2015
Keywords:
Graphene oxide
Oxidative coupling
Benzylamine
Microwaves
© 2015 Elsevier B.V. All rights reserved.
1. Introduction
dopant elements (i.e. N, P, S, halogens) and covalent functionalisa-
tion (i.e. −COR, −SO3H, −SH, −CN, −NHR) [10,11].
Graphene and chemically modified graphenes (CMGs) have
attracted much attention in recent years due to their interesting
physico-chemical properties [1–3]. These materials are expected
to have a significant impact in different fields including chemistry,
physics, biotechnology, engineering and materials science [4–7].
Although the synthesis of these materials was complex in the early
stages of research, advances on the development of CMGs have
granted access to high quality materials with a wide range of prop-
erties.
In particular, the use of these materials in catalytic applica-
tions has been only explored very recently following the seminal
reports by Dreyer et al.,[8] but is currently gaining much interest,
particularly related to the development of functionalised graphene
systems for various catalytic applications [9].
Comparatively, the use of metal-free carbonaceous materials in
synthetic chemistry offers a more promising alternative to highly
valuable products derived from different chemistries [12].
Graphene oxide (GO), a material that can be easily obtained from
the oxidative exfoliation of graphene, can in principle be a good
candidate for catalytic applications [13,14].
This material is a readily available and inexpensive material
that has been proven as catalytically active in oxidation of various
alcohols, alkenes, epoxides, thiols, sulfides and alkynes to produce
alcohols, sulfones and ketones [12–17].
More recently, graphene oxide has been proved to be
catalytically active in the conversion of carbohydrates into 5-
ethoxymethylfurfural via etherification [18].
The main advantages of the use of GO as catalyst are the use of
a simple and inexpensive catalyst, metal-free reactivity and easy
recovery of the GO by filtration from the reaction media. However,
catalytic results reported to date for GO have been obtained under
relatively extreme conditions, especially in terms of catalyst load
(200% wt.) and times of reaction (24 h+) [8,19]. These conditions
have to be improve for future applications of GO as catalyst in the
chemical industry. For this reason, current research efforts of the
group have been focused on the improvement of the catalytic prop-
In this regard, most applications of graphene and CMGs in
catalysis have been mainly focused on their functionalisation via
deposition of metal nanoparticles and/or doping graphene through
∗
Corresponding author. Tel.: +34 957 211050; fax: +34 957 212066.
E-mail address: q62alsor@uco.es (R. Luque).
http://dx.doi.org/10.1016/j.molcata.2015.05.010
1381-1169/© 2015 Elsevier B.V. All rights reserved.

20
J.M. Bermudez et al. / Journal of Molecular Catalysis A: Chemical 406 (2015) 19–22
erties of GO in terms of versatile transformations to be performed as
well as to switch to milder and benign conditions including the use
of microwave irradiation and continuous flow processes combined
with benign reagents (e.g. hydrogen peroxide as oxidant, water and
ethanol as solvents).
Imines are important and versatile intermediates for the syn-
thesis of a broad variety of nitrogen-containing compounds with
significant application in biological and pharmaceutical fields
[20–26]. For this reason, their synthesis is attracting high interest in
recent years [25,27–29]. Traditionally, imines have been prepared
by condensation of carbonyl compounds with amines in the pres-
ence acid catalysts, but these procedures present disadvantages
including high reaction temperature, prolonged reaction times and
require costly dehydrating reagents [22]. The direct coupling of
amines to imines represents an alternative strategy of increasing
interest [20,22,25,27,28,30].
Reactions were performed controlling temperature (150–200 ◦C).
Different times of reaction were also studied (30 and 60 min).
The reaction mixture was composed by acetonitrile (2 mL), ben-
zylamine (0.2 mL), H2O2 (0.3 mL, 50% v/v aqueous solution) and
a weighted amount of GO as catalyst. The influence of the pres-
ence of the oxidant species (H2O2) was determined by carrying
out some test without H2O2. The influence of a previous sonica-
tion pre-treatment to improve the exfoliation of the GO layers was
also studied by including a test with 15 min of pre-treatment of the
reaction mixtures. An additional test with a reduced GO was car-
ried out to as blank run. Table 1 summarises the conditions of the
experiments.
After the experiments, the reacting mixtures were filtered
off and the filtrate was analysed by means of
a GC and
GC/MS Agilent 6890N fitted with capillary column HP-5
a
(30 m × 0.32 mm × 0.25 ␮m) and a flame ionisation detector (FID).
Main advances in this field have been focused in the catalytic
oxidation of secondary amines into imines [31], but much lower
attention has been paid to the synthesis of imines from primary
amines because it generally leads to other nitrogen containing com-
pounds, normally nitriles [21,26]. However, increasing efforts are
being made with the aim of developing the catalytic oxidation of
the primary amines to the corresponding imines [21,26–28,32].
Most of these efforts have been focused in the development of
metal-based catalytic processes. Nevertheless, the high prices and
low availability of most of these metals (V, Ru) make it necessary
to find alternative catalysts. Carbon materials, and more precisely
graphene-based materials could constitute an attractive alternative
[33].
In recent years, organic chemistry has been virtually rewritten
using microwaves as non-conventional heating source. A signifi-
cant body of work has shown considerable reduction in reaction
times and improved yields and selectivity of obtained products by
means of microwaves [34–36]. However, there is a lack of studies of
the microwave-assisted oxidative coupling of benzylamine beyond
the mechanistic study of Atanassova et al., where very high catalyst
loadings were used [37].
3. Results and discussion
The oxidative coupling of benzylamine was selected as key
process to investigate the influence of graphene oxide in the
selectivity to products, particularly related to the main products
of oxidative coupling: N-benzylidine-1-phenylmethanamine and
N-benzylacetamide. Blank runs, in the absence of catalyst and oxi-
dant (labelled as a and b), gave no conversion in the systems even
at high temperatures (>200 ◦C). However, the simple addition of an
oxidant (hydrogen peroxide) to reaction mixture in the absence of
catalyst provided quantitative conversion of benzylamine (Fig. 1,
run c).
An interesting 40–45% selectivity to N-benzylacetamide was
observed, together with a very low selectivity to the oxida-
tive coupling product (N-benzylidine-1-phenylmethanamine).
Benzaldehyde, benzonitrile, the corresponding oxime (Y) and
benzamide were also detected in moderate quantities in the
catalyst-free reaction under the investigated conditions. Following
previous literature reports on mechanistic insights on the reaction,
we envisaged graphene oxide (GO) as a potentially interesting can-
didate to achieve a selective conversion to the oxidative coupling
product as opposed to the formation of N-benzylacetamide. These
reports speculated about the formation of an N-oxide intermediate
on oxidative active sites followed by conversion to benzaldehyde
that reacts with benzylamine (Fig. 2) [37].
In this work, we report a simple approach to microwave-
assisted selective oxidative coupling of benzylamine catalysed by
GO in which we show significant improvements compared to both
uncatalysed and metal-catalysed protocols. A plausible reaction
mechanism is also proposed to provide molecular insights into the
oxidative coupling.
Results under optimised conditions are shown in Figs. 1 and 3
(runs d–h) as compared to the blank runs. All experiments provided
high conversions (in the range of 85–99%), with the exception of the
GO experiment in the absence of oxidant (run e) for which conver-
sion remained under 50%. These findings pointed out that oxidant
species are required to achieve high conversions if low loadings of
catalyst are used. At increasing GO loadings (experiments f and g),
the conversion remains high even in the absence of oxidant (run f).
2. Experimental
2.1. Preparation of graphene oxide (GO) and reduced GO (rGO)
GO was kindly donated by the company NanoInnova (Madrid,
Spain) and its synthesis can be briefly described as follows:
graphene oxide was synthesized by using a modified Hummers’
method [38]. Briefly graphite powder (<150 ␮m Sigma–Aldrich)
was chemically oxidized in a solution containing NaNO3, H2SO4
and KMnO4. Reduced GO was also kindly provided by NanoInnova,
with a surface area of around 100 m2 g−1 and different structural
features as compared to GO [39]. Full details, including characteri-
zation of the materials, can be seen at the website of the company
http://www.nanoinnova.com/Product
2.2. Catalytic tests
A series of experiments under different conditions was per-
formed in order to study the catalytic properties of the GO provided
by NanoInnova. The tests were performed under microwave heat-
ing in a pressure-controlled CEM-discover microwave reaction.
Fig. 1. Conversions achieved in the oxidative coupling of benzylamine (runs c–h).

J.M. Bermudez et al. / Journal of Molecular Catalysis A: Chemical 406 (2015) 19–22
21
Table 1
Experimental conditions of the tests performed.
Run
Conditions
GO (mg)
H2O2
Temperature (◦C)
Time (min)
Sonication
a
b
c
d
e
f
Blank (absence of oxidant)
Blank (absence of oxidant and high temperature)
Blank (presence of oxidant)
0
0
0
50
50
100
100
50
No
No
Yes
Yes
No
No
Yes
Yes
150
200
150
150
150
150
150
150
60
60
60
60
60
30
30
60
No
No
No
No
No
No
No
No
GO experiment
GO experiment in the absence of oxidant
Experiment doubling catalyst loading in the absence of oxidant
Experiment doubling catalyst loading in the presence of oxidant
Experiment with reduced graphene oxide
g
h
absence of oxidant after a few minutes of microwave irradiation
(see entry f, Figs. 1 and 3). Reducing the time of reaction (from 30
to 15 min) did have a detrimental effect on the conversion of the
systems, decreasing to ca. 60% under the investigated conditions.
These findings demonstrate the unique potential of GO as oxidising
catalyst per-se, especially for the oxidative coupling mechanism,
which was found to be strongly favoured by the presence of GO.
The presence of oxidant has a negative effect in terms of selectiv-
ity over the process even when GO is present, since the selectivity
to the oxidative coupling product slightly decreased upon oxidant
addition while the selectivities to other products (mainly benzalde-
hyde) increased, as clearly observed from results of runs d (presence
of H2O2) and e (absence of H2O2) and between runs g (presence of
H2O2) and f (absence of H2O2).
This can be explained due to the reaction mechanisms proposed
by Atanassova et al. (Fig. 2). When the process is carried out using
clays as catalysts (such as K-10 montmorillonites), the reaction took
place through two different mechanisms, favouring the formation
of benzaldehyde as intermediate product. The addition of H2O2 in
these experiments seems to promote the same chemistries. How-
ever, the use of GO as catalyst in absence of H2O2 may promote the
alternative pathway.
Based on this observation, a mechanism for imine formation
via graphene oxide (GO) catalysed oxidative coupling is pro-
posed in Fig. 4. In this mechanism, the carboxyl groups in the
surface if the GO give rise to a reaction intermediate. This inter-
mediate, in combination with the surface ether groups, gives
rise to the hydroxylamine intermediate. This intermediate subse-
quently dehydrates to produce an unstable imine which undergoes
transamination with another unreacted benzylamine molecule
to form N-benzylidine-1-phenylmethanamine. Depending on the
reaction conditions, the process can switch to both previously
Fig. 2. Mechanism for the self-coupling of benzylamine over K-10 montmorillonites
(from Atanassova et al.) [37].
The effect of the addition of GO in the conversion of the systems can
be also inferred from results observed when reduced GO was used
as catalyst (run h). In this run, the conversion was slightly reduced
(85% instead of 95%) as compared to reactions with GO.
In any case, the relevant findings of this work relate to
the remarkable changes in selectivity observed for the differ-
ent reactions as depicted in Fig. 3. The addition of GO favoured
the formation of the oxidative coupling product (N-benzylidine-
1-phenylmethanamine) at the expense of N-benzylacetamide
(reaction c-blank with oxidant vs reactions d–f). Interestingly, a
complete selectivity to the target oxidative coupling product could
be obtained at 94% conversion for the GO catalysed process in the
Fig. 3. Selectivity distribution in the oxidative coupling of benzylamine (runs c–h).

22
J.M. Bermudez et al. / Journal of Molecular Catalysis A: Chemical 406 (2015) 19–22
under mild conditions, with additional possibilities in the selec-
tive oxidations of alcohols, alkenes and alkynes currently under
investigation in our laboratories that will be reported in due course.
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promote the conversion of the formed N-oxide intermediate to
the unstable imine that reacts with benzylamine to generate the
oxidative coupling product N-benzylidine-1-phenylmethanamine.
The use of reduced GO as catalyst (entry h) provided a range
of products, with the target N-benzylidine-1-phenylmethanamine
also obtained as major compound. These were relatively similar
as compared to the analogous process with GO but with reduced
selectivity to the oxidative coupling product, which may indicate
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The synergy between GO and microwave irradiation has been
demonstrated for the selective production of N-benzylidine-1-
phenylmethanamine from the oxidative coupling of benzylamine.
Relatively low catalyst loadings (typically 0.1 g) were able to pro-
vide almost quantitative yields of imine in the absence of any
oxidant as compared to significantly reduced selectivities observed
in the presence of oxidant even using similar catalyst loadings,
favouring the benzaldehyde formation. The reported results illus-
trate the potential of GO to selectively promote oxidative processes