PVP-Pd nanoparticles as efficient catalyst for nitroarene reduction under mild conditions in aqueous media

Article abstract of DOI:10.1039/c6gc02710e

The catalytic activity of PVP-Pd nanoparticles synthesized by electrochemical methods was explored in nitroaromatic hydrogenation reaction. In this transformation, the colloidal nanocatalyst proved to have outstanding catalytic activity under sustainable reaction conditions. This mild process efficiently reduced the nitroaromatic group at room temperature, without high pressure of molecular hydrogen and in aqueous medium. Furthermore, several functional groups were tolerated, given the corresponding substituted arylamines in excellent yields and with high TOF. In addition, one-pot reactions and tandem process were explored, in which nitroaromatic hydrogenation reaction was included in the synthesis of modified amines. This methodology was effectively incorporated in tandem reactions and one-pot procedures, achieving N-arylamines functionalized in good isolated yields. Finally, comparison of sustainable chemistry metrics analysis demonstrated that this methodology is a reliable approach to perform the nitro compound hydrogenation process.

Full text of DOI:10.1039/c6gc02710e

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PVP-Pd nanoparticles as efficient catalyst for nitroarene reduction
under mild conditions in aqueous media
Paula M. Uberman,* Carolina S. García, Julieta R. Rodríguez, Sandra E. Martín*.
Received 00th January 20xx,
Accepted 00th January 20xx
The catalytic activity of PVP-Pd nanoparticles synthesized by electrochemical methods was explored in nitroaromatic
hydrogenation reaction. In this transformation, the colloidal nanocatalyst proved to have outstanding catalytic activity under
sustainable reaction conditions. This mild process efficiently reduced the nitroaromatic group at room temperature, without
high pressure of molecular hydrogen and in aqueous medium. Furthermore, several functional groups were tolerated, given
the corresponding substituted arylamines in excellent yields and with high TOF. In addition, one-pot reactions and tandem
process were explored, in which nitroaromatic hydrogenation reaction was included in the synthesis of modified amines.
This methodology was effectively incorporated in tandem reactions and one-pot procedures, achieving N-arylamines
functionalized in good isolated yields. Finally, comparison of sustainable chemistry metrics analysis demonstrated that this
methodology is a reliable approach to perform the nitro compound hydrogenation process.
DOI: 10.1039/x0xx00000x
www.rsc.org/
chemistry principles is to reduce the impact of any chemical
processes on the environment. Accordingly, the use of safer
chemicals and the prevention of primary pollutions are
endorsed.13–15 Sustainable chemistry transformation could be
accomplished by application of this philosophy to the planning
of any process, like solvent selection, avoiding the use of hazard
reagents, or reducing waste generation.16–18
Introduction
The synthesis of highly functionalized amines is an important
goal in modern organic chemistry. Amine functional groups are
ubiquitous among natural and pharmaceutical products, and
key intermediates in the preparation of fine chemical products
like dyes, chemical fibers, pesticides, rubber additives, etc.1
Several methods were developed to synthesize functionalized
amines, such as catalytic amination of aryl halides,2 or reduction
of functional groups like imine, nitrile, etc.3–5 The catalytic
hydrogenation of nitro compounds by noble metal catalyst (Pt,
Pd, Ni, Rh and, more recently, Au) is the most traditional and
widely used method for the industrial production of amines.6–9
The catalytic reduction of nitro compounds is a widespread
methodology; however, it suffers from several drawbacks such
as the use of a large amount of metal catalysts, organic reaction
medium, and expensive or harmful hydride source, or under
high molecular hydrogen pressure. In some cases, harsh
reaction conditions were required (e.g., high temperature),
under which the amine products could be susceptible to
degradation. Moreover, nitro compound hydrogenation is
usually limited in complex structures like pharmaceutical
intermediates, since these compounds typically contain other
sensitive functionalities. All these features restrict the
applicability of procedures, making them non-environmentally
friendly. Thus, development of sustainable or “green”
methodologies represents a challenging task for both catalysis
and organic synthesis progress. 10–12 The concept behind green
Regarding Pd-catalyzed nitroaromatic hydrogenation, there is a
plethora of methods available to perform this reaction, with
both homogeneous and heterogeneous catalysts. However,
fewer examples of homogeneous Pd catalytic systems using
water or alcoholic reaction media at room temperature have
been reported.19–21 Even though homogeneous systems usually
show higher selectivities than heterogeneous, the
homogeneous complexes present the disadvantage of
decomposing in several reaction media, or of incorporating
sophisticated, toxic and expensive ancillary ligands.
In relation to heterogeneous catalyst, in the last decades the
development of nanocatalysts has drawn special attention. This
is due to the high-level activities and selectivities shown by
nanoparticles (NPs),22,23 attributes related to high surface-to-
volume ratio and raised surface energy of the NPs, making their
surface atoms particularly active.24,25 Considering the growing
environmental concern, different Pd NPs catalytic systems were
developed to perform the hydrogenation reaction. There are a
number of reports devoted to performing the reduction of nitro
compounds by employing Pd-heterogeneous nanocatalysts in
aqueous medium26–29 or at room temperature,12,30–34 or a
combination of both.35–38 However, the methodologies are still
far away from employing less amount of reducing agent,
avoiding the use of expensive hydride source like silanes, toxic
a.INFIQC- CONICET- Universidad Nacional de Córdoba. Departamento de Química
Orgánica, Facultad de Ciencias Químicas, UNC. Córdoba, Argentina. X5000HUA.
† Corresponding authors: uberman@fcq.unc.edu.ar; martins@fcq.unc.edu.ar
Electronic Supplementary Information (ESI) available: [details of any supplementary
information available should be included here]. See DOI: 10.1039/x0xx00000x
39–41
hydrazine, or high pressure of molecular hydrogen.
In
general, heterogeneous catalysts are stable and can be easily
re-cycled; nonetheless, these show fewer selectivities than
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those of homogeneous ones, and harsh reaction conditions may DMSO-d6 or acetone-d6. Coupling constants (J) are given in Hz.
View Article Online
be necessary in order to achieve high conversions.42
An Autolab PGSTAT100 (ECO CHEMIE) potentiostat was used for
DOI: 10.1039/C6GC02710E
The use of colloidal NPs as catalysts provides a way to combine the synthesis of PVP-Pd NPs in the galvanostatic mode. PVP-Pd
the main advantages of homogeneous and heterogeneous NPs observation by Transmission Electron Microscopy (TEM)
catalytic systems, setting up a bridge between them.5 In was performed with a JEM-Jeol 1120 microscope operating at
addition, metal colloidal clusters are well dispersed in the 80 kV, at the IFFIVE Research Institute, INTA, Córdoba,
reaction medium, their cluster size may be effectively Argentina (See Figure S1 and S2, Supporting Information). In
controlled, and they are usually weakly stabilized by capping order to characterize NPs by TEM, samples were prepared
agent, leaving their surface exposed and available to participate depositing a drop of colloidal PVP-Pd NPs solution on a formvar-
in the catalysis.43
carbon coated cooper grid and dried at room temperature. The
Recently, we synthesized small-size Pd NPs stabilized by PVP by total content of palladium was determined by Atomic
electrochemical methods.44,45 The use of PVP as stabilizer Absorption in a Perkin Elmer Analyst 600, using ET (electro
allowed NPs to be disperse in aqueous medium. PVP also shows thermal mode with graphite furnace) at the ISIDSA Institute,
several advantages like low toxicity, inexpensiveness and Universidad Nacional de Córdoba, Córdoba, Argentina. Aqueous
thermal stability. The catalytic activity of the electrochemically solutions were prepared from analytical grade chemicals and
obtained nanocatalyst in Suzuki and Heck coupling reactions Milli-Q-Millipore water.
was outstanding for colloidal NPs, and PVP-Pd NPs proved to be
reusable and stable for several months.44,45 Therefore, in the
search of new catalysts with high selectivity in the reduction of
2. Experimental Procedures
nitro compounds and under environmentally friendly reaction
conditions, the catalytic activity of the PVP-Pd NPs
electrochemically synthesized was explored. The selectivity for
2.1. Representative procedure for the nitroaromatic reduction by
PVP-Pd NPs
The following reaction procedure is representative: into a 25 mL
bottom round flask equipped with a magnetic stirrer, p-
the nitro group reduction was examined under several
conditions, employing NaBH4 as safe source of hydrogen.29,36,46
In addition, incorporation of nitro group hydrogenation by PVP-
Pd NPs in one-pot consecutive reactions was also examined.
chloronitrobenzene
1 (0.25 mmol) was dissolved in EtOH (0.5
mL) and 0.90 mL of colloidal dispersion of PVP-Pd NPs was
added. Finally, under vigorous stirring, a solution of 1 mmol of
NaBH4 in H2O (2 mL) was dropped. At this stage, an intense
colour change took place, and effervescence evolution was
observed. After 15 minutes under vigorous stirring, a
decolouration occurred. The reaction was stirred for 1 hour at
room temperature. The mixture was finally diluted with water
and then extracted three times with ethyl acetate (5 mL each).
The reaction mixture was analysed by GC and GC-MS after being
dried with anhydrous Na2SO4. The amine product was
Experimental Section
1. General Methods
All materials were commercially available and used as received.
PdCl2, KNO3, PVP [poly-(N-vinyl-2-pirrolydone), Mw=10,000 Da,
HCl 35 %, p-chloronitrobenzene, o-chloronitrobenzene,
nitrobenzene, p-nitroaniline, p-dinitrobenzene, o-nitrophenol,
m-nitrophenol, methyl m-nitrobenzoate, p-nitroacetanilide, 2-
1
compared with authentic samples by GC, GC-MS and H NMR.
The product was quantified by CG employing benzophenone as
internal standard.
chloro-3-nitropyridine,
5-nitroquinoline,
styrene,
1,1-
Several reactions were analysed by HPLC. In these cases, once
the reaction was completed, MeOH HPLC grade was added until
final dilution of 1:100. Then, 1 mL of this solution was filtered
and analysed in HPLC equipment, using the external standard
method for quantifying the amine products.
diphenylethylene, p-nitroacetophenone, p-chloroaniline, o-
chloroaniline, nitrobenzene, p-aminoaniline, o-aminophenol,
m-aminophenol,
methyl
m-aminobenzoate,
p-
aminoacetanilide,
benzophenone,
p-iodonitrobenzene,
phenylboronic acid, benzaldehyde, di-tert-butyl dicarbonate
((Boc)2O), ethanol 98 %, methanol HPLC grade, NaBH4 (AF
granules) 98%, Pd(AcO)2, BINAP, K3PO4, K2CO3, KI, and Na2SO4
were used without purification. Silica gel (0.063-0.200 mm) was
used in column chromatography. All solvents were analytical
grade and distilled before use.
For competition reactions: when performing a competition
reaction, the same procedure was followed, incorporating
alkene 1,1-diphenylethene
(
14
)
together with p-
chloronitrobenzene , before adding NaBH4.
1
2.2. Representative procedure for one-pot synthesis of 4-amine
biphenyl (16), by consecutive Suzuki-nitro hydrogenation reaction
catalysed by PVP-Pd NPs
GC analyses were performed on a gas chromatograph with a
flame ionization detector, equipped with VF-5 30 m x 0.25 mm
x 0.25 μm column.GC-MS analyses were performed on a GC/MS
QP 5050 spectrometer equipped with a VF-5ms, employing a 30
m x 0.25 mm x 0.33 μm. Ionization was achieved by electronic
For Suzuki cross-coupling reaction: into a 25 mL bottom round
flask equipped with a magnetic stirrer, p-iodonitrobenzene
(0.25 mmol) was dissolved in EtOH (0.5 mL). Then,
phenylboronic acid (0.375 mmol), K3PO4 (1 mmol) and 1 mL of
water were added. Finally, 0.90 mL of colloidal dispersion of
PVP-Pd NPs was added. The reaction was stirred overnight at 50
1
impact (70eV) and detection setup positive mode. H and 13C
NMR spectra were recorded at 400 MHz and 101 MHz
respectively on a Brüker Advance II 400 spectrometer in CDCl3,
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ºC. After this, the mixture was cooled down before proceeding gradient (100:00→70:30), obtaining amine 22 as an orange
View Article Online
DOI: 10.1039/C6GC02710E
with the hydrogenation reaction.
solid.
Hydrogenation of p-nitrobiphenyl: to the previous reaction
mixture, EtOH (0.5 mL) and 2 mmol of NaBH4 in H2O (4 mL) were
dropped. After 45 minutes under vigorous stirring, a
2.5 Catalyst reuse experiment in nitroaromatic hydrogenations by
PVP-Pd NPs
decolouration occurred. The reaction was stirred for 2 h at room In order to perform the reuse test of PVP-Pd nanocatalyst, after
temperature. Finally, the mixture was diluted with water and carried out the hydrogenation reaction following the procedure
then extracted three times with ethyl acetate (5 mL each). The previously described in Section 2.1 with 0.2 mol % of Pd, the
reaction mixture was analysed by GC and GC-MS after being same reaction mixture was used by addition of fresh amounts
dried with anhydrous Na2SO4. The amine product was of reactants. The experiment was performed five times by
1
compared with authentic samples by GC, GC-MS and H NMR. consecutive addition of a new batch of p-chloronitrobenzene (
1
,
The 4-aminebiphenyl
(
16
)
was isolated by column 0.25 mmol), NaBH4 (1 mmol), EtOH (0.5 mL) and water (2 mL).
chromatography on silica gel eluting with pentane:ethyl acetate The reaction mixture was stirred at room temperature for 1 h.
gradient (100:00→70:30), obtained as a yellow solid.
After this time, the reaction was monitored by CG analyses and
no p-chloronitrobenzene ( ) was observed in the reaction
mixture after each catalytic cycle.
1
2.3. Representative procedure for the synthesis of N-protected
arylamines with benzaldehyde (17) or di-tert-butyl dicarbonate
(18)
Results and Discussions
After the hydrogenation protocol was performed over p-
chloronitrobenzene
1 (section 1.2), 0.75 mmol of benzaldehyde
The PVP-Pd NPs were electrochemically synthesized as
previously described, and used without further purification.44,45
This electrochemical methodology allowed to obtain Pd NPs of
mean diameter lower than 10 nm. Taking into account our
previous reports on the catalytic activity of the PVP-Pd NPs, we
decided to evaluate the nitroaromatic reduction in a mixture of
EtOH:H2O as solvent. The benchmark substrate, 4-
(
17) or di-tert-butyl dicarbonate (18) were added to the
mixture. The reaction was stirred for 3 h at room temperature.
The mixture was finally diluted with water and then extracted
three times with ethyl acetate (5 mL each). The reaction mixture
was analysed by GC and GC-MS after being dried with
anhydrous Na2SO4. The N-protect amine product was compared
with authentic samples by GC, GC-MS and H NMR. Imine
product 19 was purified by sublimation in
microdistillation system at 70 °C, obtained as a white solid. N-
Boc protect amine 20 was isolated by column chromatography
on silica gel eluting with pentane:ethyl acetate gradient
(100:00→70:30), obtained as a pale-yellow solid.
1
cloronitrobenzene (1), was chosen as a model for the
a Büchi
hydrogenation process (eq. 1),47 since the presence of chlorine
substituent allowed evaluating the selectivity of the process.
The reducing agent selected was NaBH4 as it is easy to handle
and involves
a safe source of hydrogen under low
concentrations.29,36,46
2.4 Representative procedure for the synthesis of N2-(4-chloro
phenyl)pyridine-2,3-diamine (22)
Catalytic amination of 2-chloro-3-nitropyridine: in a Schlenk
tube, p-chloroaniline 2 (0.25 mmol), 2-chloro-3-nitropyridine 23
(0.25 mmol), K2CO3 (1mmol), Pd(AcO)2 (2 mol%), BINAP (2
mol%), KI (3 mol%), and toluene (1 mL) were placed together
with a magnetic stirrer. The reaction was stirred for 24 h at 110
ºC in an oil bath. To elaborate the reaction, the mixture was
diluted with water, and then extracted three times with ethyl
acetate (5 mL each). The reaction mixture was analysed by GC
and GC-MS, after being dried with anhydrous Na2SO4. Nitro
Several reactions conditions were evaluated in the optimization
process of this catalytic system, like: time, amount of reducing
agent and catalyst loading. These assays were conducted at
room temperature, under vigorous stirring for 1 hour in a
mixture of EtOH:H2O (1:6). The yields of aniline
2 and
conversions for the reactions are presented in Scheme 1. In
every case, GC and GC-MS were used to evaluate the reactions,
in order to quantify yield of amine 2, and detect formation of
side products.
compound 21 was isolated by crystallization from
a
water:acetone 5:1 mixture as a brown solid compound.
Catalytic hydrogenation of N-(4-chlorophenyl)-3-nitropyridin-
2-amine (21) by PVP-Pd NPs: into a 25 mL bottom round flask
equipped with a magnetic stirrer, nitro 21 (0.25 mmol) was
dissolved in EtOH (0.5 mL) and 0.90 mL of colloidal dispersion of
PVP-Pd NPs was added. After that, a solution of 2 mmol of
NaBH4 in H2O (4 mL) was dropped. After 45 minutes under
vigorous stirring, a decolouration occurred. The reaction was
stirred for 2.5 h at room temperature. The mixture was finally
diluted with water and then extracted three times with ethyl
acetate (5 mL each). To isolate amine product 22, column
chromatography on silica gel eluting with pentane:ethyl acetate
When the reaction was conducted in the presence of 1.5
equivalents of NaBH4 but without PVP-Pd NPs, substrate
1 was
fully recovered from the reaction media after 1 hour (Scheme
1). Moreover, the hydrogenation proceeded smoothly with the
addition of 0.05 mol % of Pd (Scheme 1). As a general trend, the
yield of amine
NaBH4 was increased. In these cases good conversions were
observed. However, aside from amine , other side products
2 was raised as the amount of PVP-Pd NPs and
2
were identified and isolated from the reaction mixture. This
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could be interpreted considering the mechanism proposed for of low Pd loading and low NaBH4 addition allowed obtaining
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this reaction (Scheme 2).48
azoxy
3 in 47 % of yield and 88 % of selectivity (Scheme 1). The
DOI: 10.1039/C6GC02710E
preparation of azoxy compounds like
3
finds important
applications in dye and pigment production.50 These azoxy
adducts were usually prepared by hydrogenation of nitro
compounds; yet, in general, special reaction conditions and
catalysts are needed.50 In the present study, azoxy
3 was
obtained in moderate yield but with good selectivity just by
changing the ratio between catalyst and reducing agent
(Scheme 1).
%amine 2
% azoxy 3
% Conversion 1
98
100
94
93
100
80
60
40
20
0
Likewise, full conversion of substrate
1 was achieved when 3
74
53
65
equivalents of NaBH4 were combined with 0.05 mol % Pd
(Scheme 1). This particularly low catalyst loading is a
remarkable characteristic of these Pd nanocatalysts.
As expected, an increase in the amount of catalyst and reducing
agent gradually led to the disappearance of intermediate
53
47
46
37
20
10
5
1
0
0 0
0
0.05
(1.5)
0.05
(3)
0.1
(1.5)
0.1
(3)
0.1
(4)
products, raising the selectivity for amine
2 (Scheme 1).
(1.5)
% mol Pd
(eq. NaBH4)
Accordingly, 94 % of yield of amine could be reached after 1
2
hour with a combination of 0.1 mol% of PVP-Pd NPs and 4
equivalents of NaBH4. Finally, when catalyst loading or NaBH4
amount were further increased, the dehalogenated product
aniline was detected.
Therefore, the catalytic system PVP-Pd NPs/NaBH4 proved to be
highly efficient under sustainable reaction conditions (aqueous
medium, short reaction time, room temperature and moderate
excess of reducing agent compared to other Pd NPs
systems).29,51 It also proceeded with an excellent conversion
under low catalyst loading conditions. This is a notable feature
since usually higher amounts of Pd are required to perform this
kind of transformation.
Scheme 1. Selectivity and conversion observed in the reduction of 4-
cloronitrobenzene (1).
It is generally accepted that the hydrogenation process follows
a multistep mechanism that involves several intermediates
(Scheme 2). The direct hydrogenation path involving the nitroso
(
III) and hydroxylamine (IV) derivatives (Scheme 2), are usually
observed with Pd catalyst.47,48 However, in the present work
only traces of nitroso intermediate (III) was detected by GC-MS
analysis. Conversely, the major by-product was azoxy (VI), and
to a lesser extent, azo (VII) intermediate. Thus, the
condensation route was preferentially followed (Scheme 2). It
was proposed that under some reaction conditions the
condensation path could be favored, as in the reactions
performed under low concentration of H2 or nitroaromatic
compound.49 Both Turáková, et. al. and Gelder, et. al. suggested
that the formation of azoxy (VI) came from the condensation of
two molecules of chemisorbed species Ar-N-O-H (II, Scheme 1),
which are accumulated over the catalyst surface.48,49
Furthermore, azoxy compound was obtained almost exclusively
when the reaction was performed with 0.05 mol% of PVP-Pd
NPs and 1.5 equivalents of NaBH4 (Scheme 1). The combination
Furthermore, when the reaction was performed in a higher
scale using 1 mmol of p-chloronitrobenzene (
1), the amine 2
was achieved in 92 % of yield with 93 % of selectivity.
To establish a reactivity order for the catalytic system PVP-Pd
NPs/NaBH4, this nanocatalyst was compared with some
selected examples of p-chloronitrobenzene (1) hydrogenation
(Table 1). The selection criteria was based on methodologies
that use solvents recommended in guidelines elaborated by
16
CHEM21 consortium project
.
Both colloidal and supported
nanocatalysts were analyzed, in combination with different
reducing agents like H2, siloxanes and NaBH4.
Scheme 2. General mechanism for the nitroaromatic hydrogenation.
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Table 1: Selected Pd catalyst for hydrogenations of p-chloronitrobenzene (1).a
Table 2: Nitroaromatic hydrogenation by PVP-Pd NPs and NaBH4 in
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aqueous medium.a
DOI: 10.1039/C6GC02710E
Pd
Catal. load. Reaction
Temp Time
TOF b
(min-1)ref
[H]
catalyst
(% mol)
medium
(ºC)
(min)
NaBH4
(3 eq.)
33
PVP-Pd NPs
0.05
EtOH: H2O
r. t.
60
This work
2 (94 %)b TOF: 16 min-1
Octyne- Pd
NPs
H2
(8 atm)
H2
(1 atm)
H2
(90 %)c
0.04
0.20
0.06
0.5
THF
EtOH
30
r. t.
r. t.
r. t.
80
1560
60
1 52
8 53
Pd@Fe3O4
Pd/C
(NF)
AcOEt
AcOEt
H2O
120
120
120
60
13 54
2 55
(10 atm)
H2
5 (97 %)b TOF: 16 min-1
4 (76 %)c TOF: 13 min-1
Pd-Si (foam)
Ps-Pd-MgO
Pd-SS
(1 atm)
PMHS
(4 eq.)
NaBH4
(3 eq.)
2.0
0.5 27
1 29
2.0
MeOH:H2O
50
7 (99 %)b TOF: 17 min-1
6 (93 %)c TOF: 16 min-1
8 (92%c) TOF: 15 min-1
10 (100 %)c TOF: 17 min-1
The data collected in Table 1 shows that the electrochemically
prepared PVP-Pd NPs had a great catalytic activity in the
nitroaromatic hydrogenation, exhibiting high TOF values
compared to those of heterogeneous and colloidal catalysts.
Besides these catalytic systems, very high TOF values under
sustainable conditions were obtained by Göksu et. al.
employing an heterogeneous catalyst consisted in Pd NPs
supported over AlO(OH). The system proceed with TOF values
close to 900 min-1 for several nitro compounds. 36 However, in
this heterogeneous catalytic system the reaction with p-
8 (75 %c)d, e TOF: 13 min-1
11 (100 %)c TOF: 17 min-1
chloronitrobenzene (1) was not informed.
To further evaluate the scope of this methodology, several
nitroaromatic substrates were hydrogenated under the
optimized reaction conditions (Table 2). In general, all
nitroaromatic compounds were efficiently reduced with high
TOF values and excellent yields.
Both electron-donating and electron-withdrawing groups were
tolerated, in different positions o-, m- and p- (Table 2). Chlorine
substituent in o- or p- position was not reduced under the
conditions employed. However, some steric hindrance was
13 (92 %)b TOF: 61 min-1
12 (75 %)c TOF: 25 min-1
(15 min)
(30 min)
a Reaction conditions: 0.25 mmol of ArNO2, 1 mmol de NaBH4, 0.1 mol % PVP-Pd
NPs, a mixture EtOH: H2O 1:6 (final volume 3.5 mL), room temperature, 1 hour.
b
The reaction mixture was extracted with ethyl acetate and quantified by GC
analysis with benzophenone as internal standard. The reaction mixture was
diluted with MeOH and quantified by HPLC analysis using external standard
method. d 1.5 mmoles of NaBH4 were used (6 equivalents). e 13 % of p-nitroaniline
(9) was quantified.
observed with chloro in o-position, since amine
in 79 % of yield (Table 2). Aniline ( ) was obtained in excellent
yield by reduction of nitrobenzene. Amines bearing amide or
ester groups, and respectively, were efficiently obtained
with high selectivity for nitro group hydrogenation (Table 2).
Diamine , a key product in polymer preparations, could be
prepared by monohydrogenation of p-nitroaniline ( ) or
dehydrogenation of dinitrobenzene, both in good yields (Table
2). For the complete reduction of p-dinitrobenzene, 6
equivalents of NaBH4 were needed in order to obtain the fully
4 was obtained
c
5
6
7
8
Likewise, heteroaromatic amines 12 and 13 were also obtained
in good yields employing this methodology (Table 2). These
kinds of compound are important synthetic intermediates, and
they are difficult to obtain by other methodologies.33 In these
examples, the reactions should not exceed the 30 minutes,
since longer exposition to the reaction medium leads to
decomposition of products, lowering the mass balance of the
reaction.
9
hydrogenated product
of reducing agent was used, a mixture of p-nitroaniline (
diamine products was achieved.
8
in 75 % of yield. When a lower excess
9
) and
8
Several nitro compounds like nitrophenols are environmental
pollutants, usually remediated by hydrogenation process.56 In
these cases, they were successfully converted to the
corresponding amines 10 and 11 in short reaction times (Table
2).
The chemoselectivity of hydrogenation reaction over other
susceptible functionalities, like alkenes and ketones, was also
examined. The selectivity for nitro hydrogenation against the
keto group reduction was corroborated using p-
nitroacetophenone as a substrate. Several reaction conditions
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were tested; yet, the keto group was unfortunately always were performed to evaluate the cross-coupVliienwgArtpiclreoOcnelisnes
DOI: 10.1039/C6GC02710E
hydrogenated before the nitro group, even under 0º C and with between p-iodonitrobenzene (15) and phenylboronic acid, in
lower excess of reducing agent. In general, the nitro group could which time and temperature were optimized. Under the best
be selectively reduced over the keto group when reducing condition (50 ºC, overnight), p-nitrobiphenyl was obtained with
agents like hydrazine,20 silicon derivatives39 or H2 were 83 % of isolated yield. Then, one-pot reaction was examined to
used.34,38,37
obtain amine 16 directly from p-iodonitrobenzene (15). Thus,
The selectivity over alkene functionalities was evaluated in after performing Suzuki cross-coupling reaction, the mixture
competitive reactions. For these experiments, p- was cooled down and a water solution of 8 equivalents of NaBH4
chloronitrobenzene (1) and the corresponding alkene were was added. The reaction was kept at room temperature for 2
mixed with PVP-Pd NPs catalyst and NaBH4 (Scheme 3).
hours. Accordingly, p-aminobiphenyl (16) was obtained in 79 %
of isolated yield by this one-pot consecutive protocol.
It was important to evaluate the directly amino group
protection after the catalytic hydrogenation in a tandem
process. The synthesis of N-protected arylamines is a key step
in the chemistry of amino compounds since, even though
amines are important chemical products, their major drawback
involves inherent reactivity. Thus, they often require protection
to participate in multistep synthesis.57 In general, there are a
number of method to perform these protection reactions. The
most used methods involve reactions in organic media or
anhydrous conditions.58,59 In order to avoid purification steps or
change the reaction media, after performing the hydrogenation
Scheme 3: Competitive reaction between nitroaromatic compound (1) and alkene (14)
for hydrogenation process by NaBH4 and PVP-Pd NPs.
With a hindered alkene, like 1,1-diphenylethylene (14, Scheme
3), the reaction proceeded efficiently over the nitro group giving
protocol with p-chloronitrobenzene (1), 3 equivalents of
benzaldehyde (17) or di-tert-butyl dicarbonate (18) were added
to the reaction media (Scheme 5).
amine
2 in 84 % of yield, leaving alkene 14 unchanged. By
contrast, an opposite behavior was observed in the presence of
mono substituted alkene styrene, since both alkene and nitro
compound
basis that the interactions of the alkene
1
were partially reduced. This could be explained on
system with the NPs

surface were efficiently blocked by steric hindrance in the
alkene 14, avoiding the coordination and later hydrogenation of
the double bond. Hence, PVP-Pd NPs were able to discriminate
between the nitro groups from the bulky alkene system. When
styrene was explored, due to its smaller size, the alkene
coordinates efficiently to the catalyst surface, leading to
reduction of both functional groups.47
Once the scope of the reaction was established, it was
important to investigate the synthetic applicability of this green
protocol in a tandem process. Hence, we analyzed the
incorporation of nitro group hydrogenation by PVP-Pd NPs in
one-pot consecutive reactions.
Scheme 5: One-pot strategy to obtain N-protected arylamines with benzaldehyde (17)
or di-tert-butyl dicarbonate (18).
First,
a
Suzuki cross-coupling reaction/nitroaromatic The reactions were stirred for 3 hours until ethyl acetate was
hydrogenation reaction sequence was examined (Scheme 4), as added to extract the reaction mixture. As a result, amines
an example of consecutive one-pot reactions catalyzed by PVP- derivatives 19 and 20 were obtained in good isolated yield for
Pd NPs.
this one-pot procedure in a EtOH:H2O mixture (Scheme 5).
Therefore, without any purification or isolation steps, amine
2
was directly protected by only adding the protecting agent to
the reaction mixture of the hydrogenation protocol.
The hydrogenation protocol was also employed to obtain 2,3-
diaminopyridines 22 (Scheme 6). The great significance of this
kind of functionalized 2,3-diaminopyridines lies in their use as
precursors for the synthesis of ligands and biologically active
molecules.60–62 Some hydrogenation protocols for reduction
nitro compounds like 21 were developed, since they were
involved in API’s production. These methodologies currently are
protected by basic patents.63 Taking into account the synthetic
Scheme 4: One-pot Suzuki/Hydrogenation reaction sequence catalyzed by PVP-Pd NPs
to synthesize biphenyl amine 16.
This one-pot procedure was accomplished considering the
previously reported optimized conditions for the Suzuki cross-
coupling reaction.45 For that, a number of control experiments
relevance
of
the
2,3-diaminopyridines
derivatives,
hydrogenation reaction by PVP-Pd NPs was chosen to perform
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synthesis of amine 22, and also to evaluate the sustainability of for values lowers than 70 %.17 Thus, in both cases for the yield
View Article Online
DOI: 10.1039/C6GC02710E
the process.
parameter were assigned an amber flag, and a green flag for the
reaction selectivity.
Table 3. Comparison of methodologies for reduction of nitro compound 21 by green
metrics toolkit.17
Reaction Conditions: This work
Scheme 6: Synthesis of 2,3-diaminopyridine 22 by sequential Pd-catalyzed reactions.
Green parameters
Crit.
The synthetic path proposed for amine 22 consisted in three
steps (Scheme 6). First, hydrogenation protocol was used to
Yield
Sel.
AEa
RMEb
Solv.
H&Sc
Elem.c
obtain amine
synthesized by a Pd-catalyzed amination of 2-chloro-3-
nitropyridine (23) with amine in toluene, employing a mixture
2 (Scheme 6). Then, nitropyridine 21 was
76
39
Reaction Conditions: Kamal, et. al.
2
Pd(OAc)2:BINAP as catalyst. Nitropyridine 21 was obtained in 75
% of isolated yield after 24 hours. Unfortunately, when
amination reaction was performed in the presence of PVP-Pd
NPs as catalyst, no conversion of 2-chloro-3-nitropyridine (23
)
was observed.
Green parameters
Crit.
Reduction of nitropyridine 21 was performed under the
previously optimized condition for hydrogenation reaction with
PVP-Pd NPs. In this particular case, 8 equivalents of NaBH4 and
2 hours of reaction were needed in order to obtain better yields
Yield
Sel.
AEa
RMEb
Solv.
H&Sc
Elem.c
46
20
of 22
.
a- AE = (molecular weight product/total molecular weight of reactants)*100. b-
RME = (mass of isolated product/total mass reactants)*100. c- ref.17 .
With the aim of determining whether the hydrogenation
protocol by PVP-Pd NPs is a convenient tool in this synthetic
path (providing improvements in term of sustainability), some
considerations about the “greenness” of the reaction were
examined. For that, some key parameter were evaluated (Table
3). Moreover, our protocol was compared with one of the few
reports available for the synthesis of amine 22. The procedure
reported by Kamal, et. al., in which stoichiometric excess of
SnCl2 was used as a reducing agent in MeOH under reflux for 2
hours (Table 3).60
The “green metrics” analyzed in Table 3 were proposed by
McElrond, et. al.17 as an unified “green metrics toolkit” which
facilitates monitoring, measuring, comparing and evaluating
new methodologies in terms of their “green credentials”.17 This
toolkit was classified into a number of levels that move from the
discovery of a process towards commercialization of a product,
and in each stage, some key parameters were analyzed. The
analysis of these parameters allows scoring greenness with a
flag system: green flag for “preferred”, amber flag for
“acceptable/some issues” and red flag denotes “undesirable”.17
In the present study the first stage of the toolkit, the discovery
level or “zero pass”, was chosen to perform the analysis.
Under the two protocols, amine 22 was obtained with high
selectivity and in good isolated yields (73 % and 85 %, Table 3).
The McElrond et al. toolkit establish that yields and selectivities
higher than 89 % are assigned with a green flag; an amber flag
corresponds to values between 89 % and 70 %; and a red flag
Nevertheless, when the Atom Economy parameter (AE) was
calculated, a significant difference was observed. The AE is a
useful parameter since it measured the reaction efficiency by
the number of atoms in the reactants which appear in the final
product. To determine AE parameter, the molecular weight of
the product and all reactants was taken into account.64 In that
sense, the methodology using SnCl2 as a stoichiometric reducing
agent had a considerably lower value of AE, because of the large
amounts of heavy metal tin (Table 3). Complementary to the AE
parameter was defined the Reaction Mass Efficiency (RME)
parameter. It provides a fuller picture of the utilization of
reactants, since incorporates yield and stoichiometry of the
reaction. For calculation of RME values, the ratio between mass
of isolated product and the total mass of reactants was
performed.17,64 Similarly to the observed with AE, RME value
was higher for the catalytic hydrogenation reaction by PVP-Pd
NPs (Table 3). In addition, the use of tin reagent in the Kamal
methodology also had an impact on other parameters like
Health and Safety (H&S) and Critical Elements considerations.
The H&S parameters is employed to determine if the reactants
used in the synthesis had a severe hazard statement, based on
the globally harmonized system of classification and labelling of
chemicals (GHS).65 Accordingly to the McElrond et al. toolkit,
some Hazard statements (H-statement) results in the
production of a red flag.17 Since SnCl2 has environmental
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implications and high toxicity, a red flag and three amber flags This reusing outcome of the PVP-Pd NPs clearly pVoieinwtAsrtioclue tOntlhinee
DOI: 10.1039/C6GC02710E
were assigned in agreement with its H-statements. In the robust nature of this nanocatalyst.
catalytic hydrogenation, H-statements for NaBH4 lead to one In order to analyses the possible modification of the catalyst
red flag and one amber flag assignation (Table 3). In addition, during the reaction the TEM micrograph of PVP-Pd NPs before
an element was defined by the EU to be critical if it is of high and after one catalytic cycle was performed. For that,
economic value coupled with a high risk of supply.66 This nanocatalyst was separate from the reaction mixture
considerations were evaluated in both hydrogenation reactions performing a physical separation of NPs by centrifugation.
with the Critical Element parameter (Table 3).17 A red flag was Considering that, the physical manipulation of the NPs might
given to the Kamal methodology, since Sn have a high risk to generate changes in size or morphology of the nanocatalyst,
depletion within the next 5-50 years. In the case of catalytic and in order to compare NPs being process in the same way, the
hydrogenation methodology an amber flag was generated, due original colloidal dispersion of PVP-Pd NPs was centrifuged
Pd and B are considered more available in the next 50-500.17 before the TEM achievement (Figures S1 and S2, Supporting
Solvent choice was also examined, and in both cases a green flag information). The comparison between NPs mean diameter
was given, since MeOH and a water: EtOH mixture are reveal that the original small size PVP-Pd NPs (7 ± 5) nm clump
recommend.17
to larger aggregates after the catalytic cycle, providing NPs with
Metrics analysis demonstrated that our process provided a mean diameter of (20 ± 10) nm with high dispersion in size
improvements in terms of sustainability for be used in organic (Figures S1 y S2, Supporting information). Despite of the
synthesis; and confirmed that replacing stoichiometric coalescence of small size NPs by action of the chemical reaction,
hydrogenation method by catalytic hydrogenation with PVP-Pd the bigger NPs were still active as catalysts, as was
NPs is appropriate for the synthesis of compounds like 22
.
demonstrated by the successful recycling. The morphology of
An important feature of any catalytic system is their ability of the NPs appear not to be modified, and always look like a
reutilization. Thus, recyclability test for this catalytic system was “blackberry”. Probably, this particular structure leave expose
evaluated. Due to the high stability of the PVP-Pd NPs in enough surface available to efficiently perform the catalytic
water,44,45 separated them from the aqueous reaction media is reaction.
a difficult task. Any attempt to separate the nanocatalyst from
reaction media by centrifugation, precipitation or organic
extraction eventually lead to a dramatic drop of the catalytic
Conclusion
activity. Thus, for reuse experiments, repeated runs on the
same batch were performed; reusing the aqueous reaction
mixture with the PVP-Pd nanocatalyst. The benchmark
The electrochemically prepared PVP-Pd NPs exhibited an
outstanding catalytic activity on hydrogenation process for
nitroaromatic reduction, in addition to the already proved
homeopathic activity in coupling reactions for C-C bond
formation.44,45
substrate p-chloronitrobenzene (
experiments. Once the reduction was completed, a new batch
of nitrocompound , NaBH4 and mixture of EtOH:H2O was
1) was employed in these
1
Anilines were obtained in very good or excellent yields and with
high TOF values, even better than those with reported colloidal
and supported Pd nanocatalysts. Several functional groups
were tolerated under the reaction conditions employed, such as
chlorine, ester, amide, amine, hydroxyl, hindered alkenes and
heterocyclic compounds. Moreover, selectivity could be
modulated, obtaining the azoxy derivative in moderate yield by
only changing the ratio between Pd and reducing agent.
Furthermore, this green protocol was compatible to one-pot
process for the synthesis of amines derivatives, and applicable
to the synthesis of complex molecules in consecutive reactions,
key synthones in preparation of biologically active compounds.
Most importantly, the methodology developed was simple, fast
and easily handled, via which the use of harmful solvents or
reagents was avoided. Reducing agent NaBH4 was employed
under relative low excess, and the reactions were performed in
aqueous medium, under mild reactions conditions. Recyclability
test of the reaction mixture showed that PVP-Pd NPs maintain
their outstanding catalytic activity even after five reuse cycle.
reintroduced. The yield, selectivity and conversion of five
successive runs are showed in Scheme 7.
99
98
98
98
97
96
100
90
80
70
60
50
40
30
20
10
0
95
94
94
92
91
91
90
90
88
1º CYCLE
Yield 2 (%)
2º CYCLE
3º CYCLE
4º CYCLE
5º CYCLE
Selectivity 2 (%)
Conversion 1 (%)
Scheme 7: Recyclability test for the PVP-Pd NPs in the hydrogenation of p-
chloronitrobenzene (1) with NaBH4.
The PVP-Pd NPs exhibited a great catalytic activity after five
cycles of hydrogenation reaction, without any significant loss of
activity/selectivity in aqueous medium. This is another factor to
assigned high “greenness” to the PVP-Pd NPs catalytic system.
Acknowledgements
We acknowledge research support from the CONICET, FONCYT
and SECYT-UNC. C.S.G. gratefully acknowledges CONICET for
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35 J. Feng, S. Handa, F. Gallou, B. H. Lipshutz, Angew. Chem. Int.
DOI: 10.1039/C6GC02710E
36 H. Göksu, New J. Chem. 2015, 39, 8498.
37 N. Zhang, Y.-J. Xu, Chem. Mater. 2013, 25, 1979.
38 Y. Fang, E. Wang, Nanoscale 2013, 5, 1843..
39 F. Li, B. Frett, H. Li, Synlett 2014, 25, 1403.
40 V. Yadav, S. Gupta, R. Kumar, G. Singh, R. Lagarkha, Synth.
Commun. 2012, 42, 213.
41 L. Guo, J. Bai, C. Li, Q. Meng, H. Liang, W. Sun, H. Li, H. Liu,
Appl. Surf. Sci. 2013, 283, 107.
fellowships. We thanks to Dr. G. I. Lacconi and Dr. L. A. Peréz for
their support in electrochemical experiments in the laboratory
of electrochemistry of Dr. G. I. Lacconi in INFIQC-CONICET,
Córdoba (Argentina).
View Article Online
Ed. 2016, 55, 1.
Notes and references
1
2
Z. Rappoport, The chemistry of anilines; Wiley, 2007.
C. Thomas, M. Wu, K. L. Billingsley, J. Org. Chem. 2016, 81
330.
,
42 V. Polshettiwar, R. S. Varma, Green Chem. 2010, 12, 743.
43 T. Tsukuda, H. Tsunoyama, H. Sakurai, Chem. - An Asian J.
3
4
5
S. Semwal, J. Choudhury, J. ACS Catal. 2016,
6, 2424.
2011,
44 P. M. Uberman, L. A. Pérez, S. E. Martín, G. I. Lacconi,. RSC Adv.
2014, , 12330.
6, 736.
T. C. Nugent, M. El-Shazly, Adv. Synth. Catal. 2010, 352, 753.
S. Elangovan, C. Topf, S. Fischer, H. Jiao, A. Spannenberg, W.
Baumann, R. Ludwig, K. Junge, M. Beller, M. J. Am. Chem. Soc.
2016, 138, 8809.
4
45 P. M. Uberman, L. A. Pérez; G. I. Lacconi, S. E. Martín, J. Mol.
Catal. A Chem. 2012, 363-364, 245.
6
S. Byun, Y. Song, B. M. Kim, ACS Appl. Mater. Interfaces 2016,
46 H. K. Kadam, S. G. Tilve, RSC Adv. 2015, 5, 83391.
8
, 14637.
47 H.-U. Blaser, H. Steiner, M. Studer, ChemCatChem 2009,
1
4
,
,
7
8
P. Serna, A. Corma, ACS Catal. 2015, 5, 7114.
210.
R. V. Jagadeesh, A.-E. Surkus, H. Junge, M.-M. Pohl, J. Radnik,
J. Rabeah, H. Huan, V. Schunemann, A. Bruckner, M. Beller,
Science, 2013, 342, 1073.
M. M. Dell’Anna, V. Gallo, P. Mastrorilli, G. Romanazzi,
Molecules 2010, 15, 3311.
48 E. A. Gelder, S. D. Jackson, C. M. Lok, Chem. Commun. 2005,
522.
49 M. Turáková, T. Salmi, K. Eränen, J. Wärnå, D. Y. Murzin, M.
Králik, Appl. Catal. A Gen. 2015, 499, 66.
9
50 Z. Liu, Y. Huang, Q. Xiao, H. Zhu, Green Chem. 2016, 18, 817.
51 J. Sun, Y. Fu, G. He, X. Sun, X. Wang, Catal. Sci. Technol. 2014,
10 K. J. Datta, A. K. Rathi, M. B. Gawande, V. Ranc, G. Zoppellaro,
R. S. Varma, R. Zboril, ChemCatChem 2016, , 2298.
11 A. K.Rathi, M. B. Gawande, V. Ranc, J. Pechoušek, M. Petr, K.
8
4
, 1742.
52 N. Arai, N. Onodera, A. Dekita, J. Hori, T. Ohkuma, Tetrahedron
Lett. 2015, 56, 3913.
Čépe, R. S. Varma, R. Zbořil, Catal. Sci. Technol. 2016, 6, 152.
12 R. B. Nasir Baig, R. S. Varma, ACS Sustain. Chem. Eng. 2014, 2,
53 A. J. Amali, R. K. Rana, Green Chem. 2009, 11, 1781.
54 M. Takasaki, Y. Motoyama, K. Higashi, S. H. Yoon, I. Mochida,
H. Nagashima, Org. Lett. 2008, 10, 1601.
2155.
13 P. T. Anastas, J. B. Zimmerman, Chem 2016, 1, 10–12.
14 F. Roschangar, R. A. Sheldon, C. H. Senanayake, Green Chem.
2015, 17, 752.
55 O. Verho, K. P. J. Gustafson, A. Nagendiran, C. Tai,
ChemCatChem 2014, 6, 3153
15 R. A. Sheldon, Chem. Commun. 2008, 29, 3352.
16 D. Prat, A. Wells, J. Hayler, H. Sneddon, C. R. Mcelroy, S. Abou-
Shehada, P. J. Dunn, Green Chem. 2016, 18, 288.
17 C. R. McElroy, A. Constantinou, L. C. Jones, L. Summerton, J.
H. Clark, Green Chem. 2015, 17, 3111.
56 Y . C. Chang, D. H. Chen, J. Hazard. Mater. 2009, 165, 66
57 S. M. Kelly, B. H. Lipshutz, Org. Lett. 2014, 16, 98.
58 U. Ragnarsson, L. Grehn, RSC Adv. 2013,
59 T. R. Van den Ancker, G. W. Cave, C. L. Raston, Green Chem.
2006, , 50.
3, 18691.
8
18 E. S. Beach, Z. Cui, P. T. Anastas, Energy Environ. Sci. 2009, 2,
60 A.Kamal, S. M. Ali Hussaini, V. Lakshma Nayak, M. Shaheer
Malik, M. Lakshmi Sucharitha, T. B. Shaik, M. Ashraf, C. Bagul,
Bioorg. Med. Chem. 2014, 22, 6755.
1038.
19 P. K. Verma, M. Bala, K. Thakur, U. Sharma, N. Kumar, B. Singh,
Catal. Letters 2014, 144, 1258.
61 C. I. Fincham, A. Bressan, M. Paris, C. Rossi, D. Fattori, Expert
Opin. Ther. Patents 2009, 17, 919.
20 A. Kumar, K. Purkait, S. K. Dey, A. Sarkar, A. Mukherjee, RSC
Adv. 2014, 4, 35233.
62 D. Feng, J. M. Wai, S. D. Kuduk, C. Ng, K. L. Murphy, R. W.
Ransom, D. Reiss, R. S. L. Chang, C. M. Harrell, T. Macneil, C.
Tang, T. Prueksaritanont, R. M. Freidinger, D. J. Pettibone, M.
G; Bock, Bioorg. Med. Chem. Lett. 2005, 15, 2385.
63 D. L. Kuo, M. Eyer, J. P. Roduit, A. Wellig, United States Patent:
Process for preparing imidazopyridine derivatives, US
5498715 A, 1996.
21 R. J. Rahaim, R. E. Maleczka, Org. Lett. 2005,
22 S. Nishimura, K. Ebitani, ChemCatChem 2016,
23 S. B. Kalidindi, B. R. Jagirdar, ChemSusChem 2012,
7
, 5087.
, 2303.
, 65.
8
5
24 Y. Dai, Y. Wang, B. Liu, Y. Yang, Small 2015, 11, 268.
25 R. Narayanan, M. A. El-Sayed, J. Phys. Chem. B 2005, 109
,
12663.
26 Z. Dong, X. Le, C. Dong, W. Zhang, X. Li, J. Ma, Appl. Catal. B
Environ. 2015, 162, 372.
64 A. Jordan, A. Haiß, M. Spulak, Y. Karpichev, K. Kümmerer, N.
Gathergood, Green Chem. 2016, 18, 4374.
27 D. Damodara, R. Arundhathi, T. V. Ramesh Babu, M. K. Legan,
65 United Nations. Economic Commission for Europe.
Secretariat. Globally harmonized system of classification and
labelling of chemicals (GHS) 2015, 6 Edition, UNECE.
66 European Commission. Report on critical raw materials for the
EU, Report of the Ad hoc Working Group on defining critical
raw materials 2014 (http://ec.europa.eu/ enterprise/
policies/raw-materials/files/docs/crm-report-on-critical-raw-
materials_en.pdf).
H. J. Kumpaty, P. R. Likhar, RSC Adv. 2014, 4, 22567.
28 M. Oba, K. Kojima, M. Endo, H. Sano, K. Nishiyama, Green
Chem. Lett. Rev. 2013, , 233.
6
29 K. Shil, D. Sharma, N. R. Guha, P. Das, Tetrahedron Lett. 2012,
53, 4858.
30 E. Kim, H. S. Jeong, B. M. Kim, Catal. Commun. 2014, 45, 25.
31 J. Zhou, Z. Dong, H. Yang, Z. Shi, X. Zhou, R. Li, Appl. Surf. Sci.
2013, 279, 360.
32 F. Zhang, J. Jin, X. Zhong, S. Li, J. Niu, R. Li, J. Ma, Green Chem.
2011, 13, 1238.
33 A. J. Kasparian, C. Savarin, A. M. Allgeier, S. D. Walker, J. Org.
Chem. 2011, 76, 9841.
34 F. Chang, H. Kim, B. Lee, S. Park, J. Park, Tetrahedron Lett.
2010, 51, 4250.
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Table of Contents:
Towards an efficient, mild and sustainable approach for nitroarene hydrogenation by Pd
nanoparticles in aqueous medium.