Mechanistic studies of the reduction of nitroarenes by NaBH4 or hydrosilanes catalyzed by supported gold nanoparticles

Article abstract of DOI:10.1021/cs500379u

Herein, we show that mesoporous titania-supported gold nanoparticle assemblies (Au/MTA) catalyze the activation of NaBH₄ and 1,1,3,3-tetramethyl disiloxane (TMDS) compounds, which act as transfer hydrogenation agents for the reduction of nitroarenes to the corresponding anilines in moderate to high yields. On the other hand, nitroalkanes are reduced to the corresponding diazo and hydrazo compounds under the studied conditions. The substantial measured primary kinetic isotope effects found here suggested that B-H bond cleavage occurs in a rate-determining step and [Au]-H active hybrids are formed, which are responsible for the reduction of nitroarenes to the corresponding amines. Formal Hammett-type kinetic analysis of a range of para-X-substituted nitroarenes lends support to this hypothesis. Nitro compounds substituted with electron-withdrawing groups were reduced faster than the corresponding compounds with electron-donating groups. The presence of water enhanced the catalytic activity of Au/MTA in aprotic solvents. Nuclear magnetic resonance studies support the formation of the corresponding hydroxylamines as the only intermediate products. On the basis of the high observed chemoselectivities and the fast and clean reaction processes, these catalytic systems, i.e., Au/MTA-NaBH₄ and Au/MTA-TMDS, show promise for the efficient synthesis of aromatic amines at industrial levels.

Full text of DOI:10.1021/cs500379u

Research Article
pubs.acs.org/acscatalysis
Mechanistic Studies of the Reduction of Nitroarenes by NaBH4 or
Hydrosilanes Catalyzed by Supported Gold Nanoparticles
Stella Fountoulaki,† Vassiliki Daikopoulou,† Petros L. Gkizis,† Ioannis Tamiolakis,‡ Gerasimos S. Armatas,‡
and Ioannis N. Lykakis*,†
†Department of Chemistry, Aristotle University of Thessaloniki, University Campus, 54124 Thessaloniki, Greece
‡Department of Materials Science and Technology, University of Crete, University Campus, 71003 Voutes Heraklion, Crete, Greece
S
* Supporting Information
ABSTRACT: Herein, we show that mesoporous titania-
supported gold nanoparticle assemblies (Au/MTA) catalyze
the activation of NaBH4 and 1,1,3,3-tetramethyl disiloxane
(TMDS) compounds, which act as transfer hydrogenation
agents for the reduction of nitroarenes to the corresponding
anilines in moderate to high yields. On the other hand,
nitroalkanes are reduced to the corresponding diazo and
hydrazo compounds under the studied conditions. The
substantial measured primary kinetic isotope effects found
here suggested that B−H bond cleavage occurs in a rate-
determining step and [Au]−H active hybrids are formed,
which are responsible for the reduction of nitroarenes to the
corresponding amines. Formal Hammett-type kinetic analysis of a range of para-X-substituted nitroarenes lends support to this
hypothesis. Nitro compounds substituted with electron-withdrawing groups were reduced faster than the corresponding
compounds with electron-donating groups. The presence of water enhanced the catalytic activity of Au/MTA in aprotic solvents.
Nuclear magnetic resonance studies support the formation of the corresponding hydroxylamines as the only intermediate
products. On the basis of the high observed chemoselectivities and the fast and clean reaction processes, these catalytic systems,
i.e., Au/MTA-NaBH4 and Au/MTA-TMDS, show promise for the efficient synthesis of aromatic amines at industrial levels.
KEYWORDS: gold nanoparticles, heterogeneous catalysis, nitro compounds, selective reduction, kinetic isotope effects, Hammett kinetics
Recently, we demonstrated mesoporous Au-loaded TiO2
nanoparticle assemblies (Au/MTA) featuring controllable
gold particle size (i.e., ranging from 3 to 10 nm) to be highly
effective catalysts for the chemoselective reduction of nitro-
arenes into amines, using sodium borohydride as a reducing
agent under ambient conditions.13 The results suggested that
Au/MTA associated with 5 nm Au particles is a uniquely active
catalyst for such hydrogenation reactions, providing exception-
ally high selectivity (>99%) and conversion yield (>90%) to the
corresponding aryl amines. Following our interest in novel
applications of supported AuNPs in several organic trans-
formations,14 we turned our focus on the mechanistic studies of
the Au-mediated reduction of nitroarenes in the presence of
borohydrides or hydrosilanes. Previous kinetic isotope effect
studies under hydrogenation of nitroaromatics with Au/TiO2
showed that the rate-determining step in this process is the
dissociation of H2 on gold particles.4d In addition, Cao and co-
workers proposed that the Au/meso-CeO2 catalyzes the
controlled formation of reduced products, such as azoxy, azo,
1. INTRODUCTION
Synthesis of anilines or amines from the corresponding nitro
compounds is an important process in the laboratory and in the
chemical industry because of their versatility in several
biologically active natural products, dyes, and pharmaceuticals.1
The most popular and promising route for the transformation
of nitro groups to amine groups is transition metal-catalyzed
hydrogenation,2 although low chemoselectivities are observed,
especially when other reducible groups are present. Therefore,
the development of an efficient catalytic system for chemo-
selective reduction of nitro compounds is a challenging area. So
far, supported gold nanoparticles (AuNPs),3−5 such as Au/
TiO2,4 have been used successfully for the selective trans-
formation of nitro groups into amines through a direct
hydrogenation process, yet that process requires harsh
reduction conditions, i.e., high temperatures and H2 pressures.
In addition, the reduction of nitroarenes in the presence of
AuNPs and several reducing agents such as CO/H2O,6
HCOONH4,7 alcohols,8 NaBH4,9 hydrosilanes,10 hydrazine,11
and ammonia borane12 has been studied. In a similar context,
the activation of NaBH4 by gold nanoparticles was mainly
investigated in the chemoselective reduction of 4-nitrophenol
to 4-aminophenol.9
Received: March 21, 2014
Revised: June 26, 2014
Published: August 25, 2014
© 2014 American Chemical Society
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and amine compounds, in the presence of 2-propanol under
specific reaction conditions.8a Herein, we report a detailed
mechanistic route for the AuNP-catalyzed reduction of
nitroarenes in the presence of sodium borohydride or
hydrosilane reductants. The catalytic results are interpreted
on the basis of kinetic isotope effects (KIEs) and Hammett-
type kinetic analysis, as well as on the product characterization
by liquid chromatography−mass spectrometry (LC−MS) and
nuclear magnetic resonance (NMR) spectroscopy.
nonlocal density functional (NLDFT) method on the basis of
the adsorption data. Transmission electron microscopy (TEM)
analysis was conducted using a JEOL JEM-2100 electron
microscope (operating at an accelerating voltage of 200 kV).
Elemental microprobe analysis was conducted on a JEOL JSM-
6390LV scanning electron microscope (SEM) equipped with
an Oxford INCA PantaFET-x3 energy dispersive X-ray
spectroscopy (EDS) detector. Data were acquired at an
accelerating voltage of 20 kV with an accumulation time of
60 s.
2. EXPERIMENTAL DETAILS
2.4. Catalytic Reactions. Supported gold catalyst Au/
MTA or Au/TiO2 (1 mol % Au) was placed in a 5 mL glass
reactor, followed by the addition of ethanol (1 mL), nitro
compound (0.1 mmol), and NaBH4 (0.4−0.6 mmol) or TMDS
(0.25 mmol), and the reaction mixture was stirred at room
temperature for a selected time. The reaction was monitored by
thin layer chromatography (TLC), and after completion, the
slurry was filtered under pressure through a short pad of Celite
and silica to withhold the catalyst with the aid of ethanol or
methanol (∼5 mL). The filtrate was evaporated under vacuum
to afford the corresponding products in pure form. Product
2.1. General. The aromatic nitro compounds used as
substrates were of high purity and commercially available from
Aldrich. Primary nitroalkanes were synthesized via oxidation of
the corresponding amines according to the literature procedure
using excess m-CPBA.15 Brij-58 surfactant [HO-
(CH2CH2O)20C16H33; Mn ∼ 1124], titanium tetrachloride
(99.9%), anatase TiO2 (99.8%), HAuCl4, and absolute ethanol
(99.8%) were purchased from Sigma-Aldrich. Titanium(IV)
isopropoxide (>98%) was purchased from Merck. TiO2
nanoparticles (P25) were purchased from Degussa AG.
1
analysis was conducted by H NMR and 13C NMR spectros-
2.2. Preparation of Catalysts. Catalysts Au/TiO2, Au/
Al2O3, and Au/ZnO (∼1 wt % in Au) used in this study are
commercially available. The titania-supported gold catalysts
Au/MTA were synthesized by the deposition−precipitation
method over mesoporous TiO2 nanoparticle assemblies
(MTA),16 according to the method described previously.13
Briefly, an aqueous solution of Au(en)3Cl3 (5 mL) correspond-
ing to the desired gold loading was adjusted to pH 10 with a 1
M NaOH solution. Subsequently, 100 mg of MTA was
dispersed into the gold solution with vigorous stirring for 1 h,
and the resulting powder was recovered by filtration, washed
with water, and dried at 40 °C under vacuum. Reduction of
gold species on the surface of MTA was conducted by
suspending (for 30 min at 25 °C) 100 mg of Au/MTA in 1.5
mL of a 0.3 M NaBH4 ethanolic solution. The purple-colored
solid was then recovered by filtration, washed with water and
ethanol, and dried in a vacuum oven at 80 °C. A series of Au/
MTA(x) catalysts with various Au loadings (x = 0.5, 1, and 2 wt
%) were prepared by varying the amount of Au in the reaction
mixture. For comparative studies, the Au/TiO2 (P25) material
was prepared via a procedure similar to that used for Au/MTA,
but depositing 2 wt % gold on commercially available TiO2
nanoparticles (Degussa P25).
2.3. Physical Characterization. Small-angle X-ray scatter-
ing (SAXS) measurements were performed on a JJ X-ray
system (Denmark) equipped with a Rigaku Helium-3 detector
and a Cu (λ = 1.54098 Å) rotating anode operated at 40 kV and
40 mA. The sample-to-detector distance and the center of beam
were precisely determined by calibration with the Ag-behenate
(d001 = 58.38 Å) standard. The average size of spherically
shaped TiO2 particles was determined from the scattering data,
using the Guinier approximation: I(q) = A exp(q2Rg2/3), where
I is the scattering intensity and Rg is the radius of gyration.
Nitrogen adsorption and desorption isotherms were measured
at −196 °C using a Quantachrome NOVA 3200e volumetric
analyzer. Before analysis, the samples were degassed at 130 °C
under vacuum (<10−5 Torr) for 12 h to remove the moisture.
The specific surface area was calculated using the Brunauer−
Emmett−Teller (BET) method on the adsorption data in the
relative pressure (P/Po) range of 0.05−0.22. The total pore
volumes were derived from the adsorbed volume at P/Po =
0.95, and the pore size distributions were calculated by the
copy (Bruker AM 300 and Agilent AM 500). Identification of
the products was realized by comparing the NMR spectral data
with those of the commercially available pure substances. Mass
spectra were determined on an LC−MS-2010 EV instrument
(Shimadzu) under electrospray ionization (ESI) conditions.
Reusability testing of the catalyst was conducted in the case of
the Au/MTA(2) sample through the hydrogenation of 4-
nitrotoluene. A 2 mL mixture of the feeding solution (0.2 mmol
of 4-nitrotoluene and 1 mmol of NaBH4) together with 20 mg
of the catalyst (1 mol % Au) was placed into a vial. Each
catalytic reaction was stopped after 2 h, and the catalyst was
collected by filtration, washed with ethanol, and dried in an
oven at 100 °C for 12 h. Then the recovered catalyst was used
for the next catalytic run without any reactivation.
3. RESULTS AND DISCUSSION
3.1. Morphology and Structural Properties of AuNP
Catalysts. In this work, we employed commercially available
Au/TiO2, Au/Al2O3, and Au/ZnO nanoparticles and meso-
porous Au-loaded TiO2 nanoparticle assemblies (Au/MTA) as
catalysts for the reduction of various nitro compounds. All
commercial catalysts have a Au loading of 1 wt % and possess
an average gold crystallite size of ∼2−3 nm. To prepare the
mesoporous Au/MTA(x) with various loadings of gold (x =
0.5, 1, and 2 wt %), a surfactant-assisted aggregated assembly of
titanium compounds [Ti(OPr)4 and TiCl4] was used. Gold
nanoparticles were deposited by the deposition−precipitation
method.13 The products obtained after cautious removal of the
surfactants consist of a continuous network of tightly
interconnected gold and anatase TiO2 nanoparticles and exhibit
a large internal surface area (approximately 110−120 m2 g−1)
and a narrow pore size distribution (approximately 7.5−7.6
nm), according to the small-angle X-ray scattering (SAXS),
transmission electron microscopy (TEM), and N2 physisorp-
tion measurements; these results are reported elsewhere
(Figure S1 of the Supporting Information).13 On the basis of
TEM analysis, we found that the average Au particle size is
strongly related to the gold loading as determined by elemental
microprobe analysis (EDS) and continuously increased from
3.2 to 4.4 nm and from 4.4 to 5.2 nm while the gold loading
was increased from 0.5 to 1% and from 1 to 2%, respectively
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[named Au/MTA(0.5), Au/MTA(1), and Au/MTA(2),
respectively (Table T1 of the Supporting Information)]. The
average size of titania particles estimated using the Guinier
approximation on the low-q range of X-ray scattering data was
found to be ∼10 nm.
3.2. Evaluation of the Catalytic Reactions. To optimize
the reaction conditions, the reduction of 4-nitro toluene (1)
using different hydrides, solvents, and supported gold catalysts
was initially investigated (Table 1). Specifically, the supported
Figure S2 of the Supporting Information). To elucidate if the
protic solvent is necessary for this catalytic process, the
reduction of 1 also occurred in EtOAc, THF, and CH3CN
upon addition of small amounts of water (5, 9, and 18 μL). A
substantial enhancement of the nitroarene consumption was
observed in the presence of 18 μL (1 mmol) of water, forming
the corresponding aniline 1a in good to high yields (Figure S3
of the Supporting Information). This result suggests that a
protic solvent is necessary for the efficient reduction of
nitroarenes under the reaction conditions described above, by
means of a possible protonation process of the nitro group
and/or the possible enhancement of the borohydride reagent
solubility; even further mechanistic studies are required.
To compare the catalytic activity of Au/TiO2 with that of
mesoporous Au/MTA assemblies, we studied the reduction of
1 with Au/MTA(x) (x = 0.5, 1, and 2) catalysts in the presence
of NaBH4 and ethanol as solvents. For the purpose of
comparison, we also prepared Au/TiO2 (P25) catalyst by
precipitating 2 wt % gold on Degussa P25 (∼26 nm particle
size, 53 m2 g−1) nanoparticles and evaluated their catalytic
performance under similar reaction conditions (Figure S2 of
the Supporting Information). The evolution of the hydro-
genation products (Table 1, entries 12−14) indicated that Au/
MTA(x) materials, although they afforded excellent selectivity
(>99%) of 1, in 1 h, possess moderate-to-high yield
(approximately 49−99%) to the corresponding amine (1a),
which is highly related to the Au loading amount and particle
size. Among them, the Au-MTA(2) catalyst associated with 5
nm AuNPs showed the best catalytic activity in terms of
conversion (Table T1 of the Supporting Information). Of
particular note was the fact that 1 was completely reduced by
Au/MTA(2) within 1 h, yielding 1a as the only product; no
detectable amounts of azoxy- and azobenzene derivatives were
observed in the reaction mixture based on NMR spectroscopy.
These findings are in good agreement with previous studies,
which suggest that gold particles in the range of 3−5 nm are
more active for Ar-NO2 reduction.13 Control experiments
showed no obvious transformation of 1 in the absence of
catalyst or in the presence of gold-free TiO2 (MTA) support,
confirming that gold particles are essential for hydrogenation
reactions.
Table 1. Evaluation of Supported Au Catalysts, Hydride
Compounds, and Solvents in the Catalytic Reduction of 4-
Nitrotoluene (1) into 4-Toluidine (1a)
hydrogen source
time (h)/yield
a
b
c
entry
catalyst
solvent
(equiv)
(%)
1
Au/TiO2
Au/TiO2
Au/TiO2
Au/TiO2
Au/TiO2
Au/TiO2
Au/TiO2
DCM
THF
NaBH4 (6)
NaBH4 (6)
NaBH4 (6)
NaBH4 (6)
NaBH4 (6)
NaBH4 (6)
NaBH4 (4)
NaBH4 (4)
NaH (20)
2/5
2
2/43
2/4
3
EtOAc
CH3CN
MeOH
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
4
2/41
1/96
5
d
6
1/>99 (97)
7
4/52
8
no catalyst
Au/TiO2
4/no reaction
e
9
4/no reaction
e
10
11
12
13
14
Au/TiO2
LiBH4 (6)
BH3THF (6)
NaBH4 (6)
NaBH4 (6)
NaBH4 (6)
4/no reaction
e
Au/TiO2
4/no reaction
Au/MTA(0.5)
Au/MTA(1)
Au/MTA(2)
1/49
1/98
d
1/>99 (98)
a
b
Twenty milligrams of each catalyst was used (1 mol %). Hydride
c
fold excess of millimoles based on starting material. Relative yield of
d
1a determined by 1H NMR. Values in parentheses correspond to the
e
isolated yield. THF (dry) was also used as a solvent.
gold catalyst (1 wt % in Au) was placed in a 5 mL glass reactor,
followed by the addition of ethanol (1 mL), substrate (0.1
mmol), and hydride compound, and the reaction mixture was
vigorously stirred for the appropriate time. To our delight, Au/
TiO2 in the presence of NaBH4 and ethanol as solvent provide
fast, quantitative, and clean reduction without the requirement
of any chromatographic purification of product 1a (Table 1,
entry 6). The amount of NaBH4 (4−6-fold molar excess, based
on the nitroarene concentration) used in our experiments is
significantly smaller than that in previous studies employing
similar reductions; they used a 50−650-fold molar excess of
NaBH4.9 Therefore, our protocol is highly appealing for
practical applications. In addition, after completion of 1, as
evidenced by thin layer chromatography (TLC), the slurry was
filtered through a short pad of Celite and silica to withhold the
catalyst with the aid of ethanol or methanol (∼5 mL). Then,
the filtrate was evaporated under reduced pressure to give pure
4-toluidine 1a (97% yield) as a brown solid. It is worth noting
that in the presence of NaH, LiBH4, or BH3-THF hydrides, no
conversion of nitro compound 1 was observed (Table 1, entries
9−11). Even if THF was used as a reaction solvent, no
reduction product was observed after prolonged reaction times
(results not shown). In addition, Au/Al2O3 was found to
catalyze the reduction of 1 to 1a in good yield (91% yield, 1 h),
while Au/ZnO is a less efficient catalyst (5% yield, 1 h) (see
To determine if the examined catalysts might also be
applicable for the chemoselective reduction of nitro compounds
in the presence of different hydrogen donor molecules, such as
dimethylphenylhydrosilane (DMPS), triethylhydrosilane
(TES), and 1,1,3,3-tetramethyldisiloxane (TMDS), we per-
formed the reduction of 4-nitroanisol (2) catalyzed by Au/TiO2
and Au/MTA(2). All the reactions were conducted in a 5 mL
glass reactor at ambient temperature, using a variety of organic
solvents. As shown in Table 2, the reduction occurs faster over
both catalysts in ethanol and THF with 2.5 equiv of TMDS,
giving the corresponding amine 2a in >98% yield in up to 30
min (Table 2, entries 2, 8, and 9). Even in water, the reduction
of 2 proceeds fast enough to afford 2a in 42% yield, as
1
determined by H NMR (after aqueous phase extraction with
ethyl acetate). To the best of our knowledge, only one study
that examined the reduction of nitroarenes in the presence of
hydrosilanes using magnetically separable gold nanoparticles
Au/Fe3O4 as catalyst appeared recently in the literature;10 even
longer reaction times were required.
3.3. Chemoselective Reduction of Nitro Compounds
with NaBH4 or TMDS Catalyzed by Mesoporous Au/MTA
Assemblies. To study the limitation of this practical
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Table 2. Evaluation of Hydrosilanes and Solvents in the
Reduction of 4-Nitroanisole (2) into 4-Anisidine (2a)
Catalyzed by Au/TiO2 or Au/MTA(2)
Table 3. Chemoselective Reduction of Nitro Compounds
(8−18) with NaBH4 and TMDS Catalyzed by Mesoporous
a
Au/MTA(2) Material
hydrogen source
a
b
c
entry
catalyst
solvent
(equiv)
yield (%)
1
Au/TiO2
Au/TiO2
Au/TiO2
Au/TiO2
Au/TiO2
Au/TiO2
Au/TiO2
Au/TiO2
DCM
THF
TMDS (2.5)
TMDS (2.5)
TMDS (2.5)
TMDS (2.5)
TMDS (2.5)
TMDS (2.5)
TMDS (2.5)
TMDS (2.5)
TMDS (2.5)
TMDS (2.5)
TMDS (2)
64
2
98
3
EtOAc
CH3CN
toluene
MeOH
H2O
60
4
67
5
66
6
97
7
42
8
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
>99
>99
9
Au/MTA(2)
no catalyst
10
11
12
13
no reaction
Au/MTA(2)
Au/MTA(2)
Au/MTA(2)
90
94
85
PDMS (5)
TES (5)
a
With regard to catalysts, 20 mg of each catalyst was used (1 mol %).
b
Hydrosilane fold excess in millimoles based on starting material.
c
1
Yields of 2a as determined by H NMR after 30 min.
chemoselective reduction process, a series of nitroarenes (3−
18) were examined (Table 3), under the conditions described
above. Notably, Au/TiO2 and Au/MTA(2) gave similar
activities (see Tables 1 and 2); the latter was used for these
catalytic reductions, using NaBH4 and TMDS (values in
parentheses) as the hydrogen donor molecules. In all cases, the
corresponding substituted anilines were formed, with excellent
yields (>90%) and selectivity (>99%). Inert-atmosphere
conditions are preferable, as under open air, minor amounts
of azoxyarenes can be occasionally seen via a gold-catalyzed
aerobic oxidation of the produced anilines.17 As shown in Table
3, among the two reducing agents, TMDS affords faster
reaction rates (the reactions were complete in up to 1 h),
judging from the TLC analysis.
As seen in Table 3, p-dinitrobenzene (4) was completely
reduced to the corresponding diamine (4a) in 1 h in 94%
isolated yield using NaBH4 and in 98% yield in 0.5 h using
TMDS. Chloro- and bromo-substituted nitroarenes (5 and 6,
respectively) were also reduced without undergoing any
dehalogenation (Table 3, entries 3 and 4, respectively). Also,
carboxylic, carboxylate, and cyano functionalities in 8, 9, and 13
nitroarenes remain intact under these conditions, indicating
highly chemoselective reduction. However, in the case of
carbonyl-substituted nitroarenes, such as 4-nitroacetophenone
(10) and 4-nitrobenzaldehyde (11), the corresponding
hydroxyl aryl amines [10b and 11b, , respectively (see the
Supporting Information)] were isolated as the only product
when NaBH4 was used as the reducing agent. On the other
hand, the presence of TMDS (2.5 equiv) does not affect the
carbonyl groups of the nitroarenes, giving the correspoding
carbonyl-substituted anilines (10a and 11a) as the only
products (Table 3, entries 8 and 9, respectively). In the
reduction of 15, the benzyl-protected moiety remains intact,
under the reaction conditions presented here (Table 3, entry
13), using either NaBH4 or TMDS as the reducing agent. Also,
the reduction of 6-nitro-1H-indazole (16) and 6-nitro-
isobenzofuran-1(3H)-one (17) gave the corresponding amines
a
b
Twenty milligrams of Au/MTA(2) was used (1 mol %). Hydride
c
fold excess on a molar basis of the starting material. The
corresponding hydroxyl aryl amines 10b and 11b were formed (see
the Supporting Information). The values in parentheses correspond to
the times/yields of the reduction in the presence of TMDS.
without further transformation of the pyrazole and lactone
rings. These results clearly support the high chemoselectivity of
the present Au/MTA-NaBH4 and Au/MTA-TMDS catalytic
systems, with the latter being the more efficient one.
Because of the extended network of interconnected gold and
TiO2 nanoparticles, the Au/MTA(2) catalyst can be easily
separated from the reaction mixture by simple filtration and can
be reused for the next catalytic run. The stability of the Au/
MTA was examined in repeated catalytic experiments. As
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shown in Figure S4 of the Supporting Information, the catalyst
can be used at least six times without a significant loss of its
catalytic activity and selectivity.
For this reason, 0.2 mmol of 5, 1 mol % Au/MTA(2), and 0.2
mmol of NaBH4 (or NaBD4) were stirred in ethanol (1 mL),
and a 100 μL aliquot of the mixture was taken at 0.5, 1.5, 3, and
5 min time intervals. The mixture was filtered through a short
pad of Celite and silica (to withhold the catalyst) and washed
with ethanol (∼1 mL). Then the filtrate was evaporated under
reduced pressure, and the corresponding consumptions of 5
were determined by integrating the appropriate proton signals
To further probe the feasibility of the present catalytic
systems in a small-scale synthesis, 3-nitrostyrene (18) was
reduced under the experimental conditions described above
using Au/MTA(2) catalyst and TMDS as the hydrogen donor
molecule (Table 3, entry 16). In this case, 3-aminostyrene
(18a) was observed as the only product, through the formation
of the corresponding unsaturated hydroxylamine 18b (Figure
S16 of the Supporting Information). Because no reduction of
the CC bond was observed, the high chemoselectivity of the
catalyst by means of preferential hydrogen transfer reduction
can be inferred. Unlike in the case of TMDS, in the presence of
NaBH4, further reduction of the C−C double bond was
1
in H NMR spectra. Each reaction was repeated at least five
times, and the average values are depicted in Figures S5−S7 of
the Supporting Information.
On the basis of this analysis, a plot of ln(x) versus time
yielded a straight line with a slope equal to a pseudo-first-order
reaction rate constant (k), eq 1. Assuming that the rate constant
of the reduction using NaBH4 is equal to kH, while that
obtained using NaBD4 is kD, a kH/kD ratio of 1.60 0.05 is
determined, which is proportional to the primary KIE (Figure
S7 of the Supporting Information). The substantial primary
isotope effects found here suggest that B−H(D) bond cleavage
occurs in a slow step, while at a same time a [Au]−H(D) bond
is formed.20 A substantial KIE was also measured in a previous
hydrogenation study, suggesting dissociation of H2 (vs D2) on a
gold surface is the rate-determining step in a bimetallic Au@Pt/
TiO2 system-catalyzed hydrogenation of nitro aromatic
compounds.4d A similar KIE (kH/kD = 1.54) was observed in
the transfer hydrogenation of nitroarenes in the presence of
CO/H2O6b upon switching the solvent from H2O to D2O;
however, this observation does not necessarily provide solid
evidence with regard to the rate-determining step of the
reduction. To evaluate the influence of the heterogeneous
nature of the catalyst in the measurement of KIEs, we
performed the same kinetics using Au/Al2O3 and Au/TiO2
(commercially available). Similar values for both kinetics were
measured: kH/kD = 1.79, and kH/kD = 1.71, respectively
(Figures S5 and S6 of the Supporting Information,
respectively). This result indicates that the heterogeneous
support of the catalyst plays an insignificant role in the
transition state of the reduction process. Therefore, we propose
that the in situ-formed gold hydrides ([Au]−H) are responsible
for the reduction of nitroarenes.
1
observed by H NMR. On the basis of the high chemo-
selectivities, and the fast and clean reaction proceses, we
propose that the Au/MTA(2)-TMDS catalytic system can be
used for various hydrogenation reactions, including amine
synthesis.
It is interesting to note here that reduction of 1-nitroalkanes
19 and 20 gave the corresponding azoalkanes (19d and 20d,
respectively) as the only products, in the presence of a 10-fold
molar excess of NaBH4 or a 5-fold molar excess of TMDS,
within 180 and 20 min, respectively (Figure 1). However, after
Figure 1. Reduction of nitroalkanes (19−21) with NaBH4 and TMDS
(values in parentheses) catalyzed by mesoporous Au/MTA(2)
material.
a prolonged reaction time (12 h), the corresponding hydrazo
compounds were observed in significant amounts, accompanied
by a small amount of alkyl amines 19a and 20a (results not
shown). On the other hand, nitro cycloheptane (21)
transformed into the corresponding hydrazo compound 21e
(Figure 1). Similar results were obtained when NaBH4 was
used as the reducing agent, although a prolonged reaction time
is required.18 These results are in contrast with previous studies
that report on the reduction of nitro compounds with Au/TiO2
and hydrazine hydrate. In that case, the corresponding alkyl
amines were observed as the only products.11
3.4. Mechanistic Studies. To rationalize a possible
mechanistic pathway for the present gold-catalyzed reduction
of nitroarenes, we investigated the primary kinetic isotope
effects (KIEs) of the reduction of 4-chloronitrobenzene (5)
using NaBH4 and NaBD4 as reducing agents. In general, KIEs
are a powerful tool for probing the transition state (TS) and
provide valuable information about the extent of bond breaking
and bond making of a reaction.19 We also report here a
Hammett-type kinetic study for the reduction of a diverse set of
para-X-substituted nitroarenes and discuss the mechanistic
possibilities.
After KIE studies, a formal kinetic analysis of a series of X-
substituted nitroarenes [X = MeO (2), H (3), Cl (5), COOMe
(9), and CN (13)] was performed (Figure 2). Considering that
the concentration of gold hydride species remains constant at
initial times (t < 3 min) and assuming a pseudo-first-order
dependence of the reaction rate on the nitroarene concen-
tration, eq 1 can be applied.
ln(x) = −kt
(1)
where k is the rate constant and x is the consumption of the X-
substituted nitroarene at reaction time t.
According to eq 1, a plot of ln(x) versus time should provide
a linear curve with a slope equal to the rate constant kx. It is
worth noting that the kinetic activity of 2, 3, 5, 9, and 13
nitroarenes is remarkably affected by the nature of the X
substituent group, in which the reduction proceeds faster as the
electron-withdrawing ability of the substituent group improves.
For example, the reduction of 9, 13, and 5 (4-COOMe, 3-CN,
and 4-Cl, respectively) proceeds faster than the corresponding
reduction of nitrobenzene 3 (X = H) (Figure 2) in the presence
of either NaBH4 or TMDS, as indicated by the relative rate
constant ratios (Figures S8 and S9 of the Supporting
Information). On the other hand, nitroarene 2 (MeO-)
The KIEs were determined by monitoring the consumption
1
of 5 (x) in the presence of NaBH4 or NaBD4 using H NMR.
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azoxyarene (5c) is reduced to the corresponding hydrazoarene
(5d) within 1 h, while after a prolonged reaction time (6 h), 5d
is transformed into the corresponding azo compound (5e) via a
possible gold-catalyzed aerobic oxidation process (Scheme 1).15
Scheme 1. Proposed Mechanism for the Reduction of
Nitroarenes Using NaBH4 or TMDS Catalyzed by Gold
Nanoparticles
Also, 4-chloronitrosobenzene was also reduced under the same
reaction conditions, giving a mixture of amine 5a and
hydrazoarene 5e, at 30 min, with the former as the major
product.
Figure 2. Kinetic analysis of the Au/MTA(2)-catalyzed reduction of
para-X-substituted nitroarenes [X = MeO (2), H (3), Cl (5), COOMe
(9), and CN (13)] using NaBH4 (A) and TMDS (B). The reductions
with TMDS occurred at 0 °C.
According to the observations described above, we propose a
general mechanistic pathway for the AuNP-catalyzed reduction
of nitroarenes. First, a B−H (or Si−H) bond cleavage occurs in
a rate-determining step to give the [Au]−H species (Scheme
1).20 Such species are responsible for the rapid reduction of
nitroarenes into the corresponding hydroxylamines, a mecha-
nistic pathway that does not follow the classical direct route
(nitroarene → nitrosoarene → aryl hydroxylamine → aniline)
but possibly skips the nitrosoarene intermediate. This pathway
found support from the KIE studies in which a significant
normal primary isotope effect was observed. Also, catalytic
experiments conducted in CD3OD suggested the formation of
the corresponding hydroxylamines as the only intermediate
products. The presence of water (protonation pathway) seems
to play a crucial role in the reaction rate, while the nature of the
heterogeneous support plays an insignificant role under our
reaction conditions. On the basis of the kinetic profiles,
nitroarenes bearing electron-withdrawing substituents were
reduced faster than those with electron-donating groups, results
that found support from the Hammett-type kinetic analysis (ρ
≈ 0.55, and ρ ≈ 0.95). Finally, hydroxylamines are reduced
under the conditions described here in a second slow step into
the corresponding amines.
containing an electron-donating group was reduced with a
slower reaction rate (Figure 2); kH/kMeO = 0.7−0.6 as
determined using NaBH4 and TMDS. In addition to these
results, a Hammett-type correlation in the competition of para-
X-substituted nitroarenes [X = CH3O (2), Cl (5), and COOMe
(9)] versus nitrobenzene (3), for the reductions with NaBH4
and TMDS, gave positive slopes: ρ ≈ 0.55, and R2 = 0.9997
(using σ+ values); ρ ≈ 0.95, and R2 = 0.9989 (using σ values)
(Figures S10 and S11 of the Supporting Information). These
results indicate the development of a negative charge (or
hydride transfer) in the transition state, which is better
stabilized by electron-withdrawing substituents.
It is worth noting that, using an equimolar amount of NaBH4
(based on millimoles of nitroarene), hydroxylamines 2a, 3a, 5b,
9a, and 13b were formed as the major products, even after a
prolonged reaction time (1 h), in CD3OD as the reaction
solvent (Figures S12−S15 of the Supporting Information). The
evolution of the reaction was monitored by NMR spectroscopy
directly after filtration of the reaction mixture through a small
pad of Celite and silica. In these reactions, 0.2 mmol of
nitroarenes, 1 mol % Au/MTA(2), and 0.2 mmol of NaBH4 (or
0.3 mmol of TMDS) were stirred in CD3OD (1 mL), and a 100
μL aliquot of the mixture was taken at appropriate time
intervals. No significant amount of the corresponding azoxy-,
4. CONCLUSIONS
Herein, we report a detailed study of the reduction of
nitroarenes into the corresponding amines, catalyzed by
AuNPs loaded on mesoporous TiO2 (Au/MTA). On the
basis of product analysis, nitroarenes are cleanly reduced to the
1
azo-, or hydrazobenzenes was detected by H NMR spectros-
copy. In addition, under our experimental conditions,
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moderate to high yields. Under similar conditions, nitroalkanes
are reduced to the corresponding diazo and hydrazo
compounds. According to the substantial measured kinetic
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H(D) bond formation have been suggested to occur in a rate-
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through the formation of hydroxylamines as the only or major
intermediate. Hammett-type kinetics supports the observation
of a negative charge in the transition state of the reaction. On
the basis of the high chemoselectivities and the fast and clean
reaction processes, both catalytic systems Au/MTA-NaBH4 and
Au/MTA-TMDS can be used for various hydrogenation
reactions, including fine synthesis of amine.
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ASSOCIATED CONTENT
■
S
* Supporting Information
1
Kinetic profiles of the reductions, Hammett-type kinetics, H
and 13C NMR data, and NMR spectra of the amines and
hydroxylamines. This material is available free of charge via the
Internet at http://pubs.acs.org.
AUTHOR INFORMATION
Corresponding Author
*Telephone: +30-2310-997871. Fax: +30-2310-997679. E-mail:
lykakis@chem.auth.gr.
■
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
Financial support by the European Union and the Greek
Ministry of Education (ERC-09, MESOPOROUS-NPs, and
ARISTEIA-2691) and the Aristotle University of Thessaloniki
Research Committee (KA 89309) is kindly acknowledged. We
thank Dr. E. Evgenidou for obtaining the LC−MS data.
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(12) Vasilikogiannaki, E.; Gryparis, C.; Kotzabasaki, V.; Lykakis, I. N.;
Stratakis, M. Adv. Synth. Catal. 2013, 355, 907.
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