Synthesis of unsaturated secondary amines by direct reductive amination of aliphatic aldehydes with nitroarenes over Au/Al2O3 catalyst in continuous flow mode

Article abstract of DOI:10.1039/c6ra20904a

A series of unsaturated secondary amines was successfully synthesized by direct reductive amination of aliphatic aldehydes with nitroarenes over a 2.5% Au/Al₂O₃ catalyst in a continuous flow reactor using molecular hydrogen as a reducing agent. In most cases, the targeted secondary amines were obtained in good to excellent yields. Interestingly, the hydrogenation of CC group is practically absent in both initial aldehydes and secondary amines under the reaction conditions. It was found that the introduction of electron-donating substituents in the para- and meta-position of nitrobenzenes increased the yield of secondary amine, while in the case of nitrobenzenes with electron-withdrawing substituents or electron-donating substituents in the ortho-position a decrease in the yield of the target product was observed.

Full text of DOI:10.1039/c6ra20904a

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DOI: 10.1039/C6RA20904A
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Synthesis of unsaturated secondary amines by direct reductive
amination of aliphatic aldehydes with nitroarenes over Au/Al2O3
catalyst in a continuous flow mode
Received 00th January 20xx,
Accepted 00th January 20xx
A. L. Nuzhdin,a,* E. A. Artiukha,a,b G. A. Bukhtiyarova,a S.Yu. Zaytsev,c P. E. Plyusnin,b,c Yu. V.
DOI: 10.1039/x0xx00000x
Shubinb,c and V. I. Bukhtiyarova,b
www.rsc.org/
A series of unsaturated secondary amines was successfully synthesized by direct reductive amination of aliphatic
aldehydes with nitroarenes over the 2.5% Au/Al2O3 catalyst in a continuous flow reactor using molecular hydrogen as a
reducing agent. In most cases, the targeted secondary amines were obtained in good to excellent yields. Interestingly, the
hydrogenation of C=C group is practically absent in both initial aldehydes and secondary amines under reaction conditions.
It was found that introduction of electron-donating substituent in the para- and meta-position of the nitrobenzene
increased the yield of secondary amine while in the case of nitrobenzenes with electron-withdrawing substituent or
electron-donating substituent in the ortho-position a decrease in the yield of the target product was observed.
5
(Scheme 1).
Introduction
Various secondary aromatic amines containing alkyl,
hydroxy, alkoxy, halogen, carbonyl and carboxylate groups
have been obtained by the above mentioned reaction in good
to excellent yields2,3 but the number of the works describing
the successful synthesis of secondary amines containing C=C
group is very limited3b,c because the carbon–carbon double
bond is one of the most reactive functions in metal-catalyzed
hydrogenation.4a To our knowledge, there are only two
examples of such synthesis, and in both cases the reaction has
been realized over supported gold catalysts. So, Au/TiO2
catalyst provides the one-pot synthesis of N-(3-vinylbenzyl)-
aniline with a yield of about 83% by reaction between
nitrobenzene and m-vinylbenzaldehyde in a batch reactor
using two-stage procedures.3b Recently, we managed to realize
the synthesis of N-heptyl-3-vinylaniline by direct reductive
amination of n-heptaldehyde with m-nitrostyrene over
Au/Al2O3 catalyst in a continuous flow reactor with a yield of
74%.3c This is a promising approach, since the reaction occurs
in one step within a short time. In addition, the use of three-
phase flow reactor allows an improvement of gas-liquid-solid
interaction and reduction of the side products through a better
control over process variables.5 Herein, we report the results
of successful synthesis of a variety of unsaturated secondary
amines by direct reductive amination of aliphatic aldehydes
with nitroarenes over Au/Al2O3 catalyst in a flow reactor.
Secondary amines are important intermediates in
pharmaceutical and agrochemical industries.1-3 Direct
reductive amination of aldehydes with nitroarenes over metal
catalysts (mainly based on Pd, Au and Pt) where several
cascade reactions are carried out using one vessel under
hydrogenation condition is an attractive method for the
synthesis of secondary aromatic amines. This approach allows
reducing the number of synthetic steps as compared with the
traditional methods and minimizes waste production due to
the use of molecular hydrogen as a reducing agent.2,3 The
process starts with the hydrogenation of nitroarene
corresponding aniline , which reacts with aldehyde
imine and further hydrogenation of
1
2
to the
to form
gives secondary amine
3
4
4
R2
R2
NH2
NO2
CHO
N
NH
R2
H2
2
H2
- H2O
- H2O
R1
R1
R1
R1
1
3
5
4
Scheme 1 Direct reductive amination of aldehydes with
nitroarenes.
a. Boreskov Institute of Catalysis, SB RAS, Lavrentieva Ave. 5, Novosibirsk, 630090,
Russia. E-mail: anuzhdin@catalysis.ru.
Experimental
Chemicals
b. Novosibirsk State University, Pirogova Str. 2, Novosibirsk, 630090 Russia.
c. Nikolaev Institute of Inorganic Chemistry, SB RAS, Lavrentieva Ave. 3, Novosibirsk,
630090 Russia.
Hydrogen tetrachloroaurate HAuCl4aq (49.47 wt% Au) was
purchased from Aurat (Russia) and used without further
Electronic Supplementary Information (ESI) available: Characterization of the
catalyst samples, GC chromatograms, NMR data. See DOI: 10.1039/x0xx00000x
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purification. Nitrobenzene (99%), o-nitrotoluene (99+%), m- The investigation of the catalytic properties was performed
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nitrotoluene
(99%),
p-nitrotoluene
(99%),
p- using commercially available continuouDsOflI:o1w0.1d03e9v/iCc6eRAH2-0C9u0b4eA
chloronitrobenzene (99%), p-bromonitrobenzene (99%), p- ProTM (Thalesnano, Hungary).5a A scheme of the catalytic setup
nitrophenol (99%), p-nitroacetophenone (97%), 4-nitrophenyl is shown in Fig. 1. The liquid feed was introduced into the
acetate (97%), m-nitrostyrene (97%), undecylenic aldehyde reactor by an HPLC pump in up-flow mode after mixing with
(97%), n-heptaldehyde (95%), 3-methylcrotonaldehyde (97%), the hydrogen flow, generated by a built-in electrolytic cell. The
n-decane (99+%) from Acros Organics, as well as p- packed bed cartridge-like reactors CatCart®30 or CatCart®70
ethylnitrobenzene from Aldrich (95%), were used as supplied. with an inner diameter of 4 mm and length of 30 mm or 70
Toluene (99.5%) from “ECOS” (Russia) was employed as mm were used.
solvent.
Before the experiment, the cartridge containing the
catalyst (0.200 g for CatCart®30 or 0.550 g for CatCart®70) was
installed in a heater unit, and the mixture of toluene with
hydrogen was fed to the reactor with the rate of 0.5 mL min-1
until the required reaction parameters (temperature, pressure,
flow rates of hydrogen) were reached. Afterwards, the inlet
was switched to the flask with the substrate’s solution and this
moment was chosen as the starting point of the reaction. The
solutions of nitroarene (0.025 M) and aldehyde (0.030 M or
0.0375 M) in toluene were used in the experiments with n-
decane as the internal standard. In the standard experiment,
the reaction was carried out at 50 bars of hydrogen pressure,
0.5 mL min-1 liquid feed rate, 60 mL min-1 hydrogen flow rate,
Catalyst preparation
The γ-Al2O3 support (BET specific surface area: 162 m2 g-1, total
pore volume: 0.69 mL g-1, mean pore diameter: 18.6 nm) was
prepared by extrusion of a paste, obtained by mixing of 18 g of
aluminum oxide (Puralox TH 100/150, Sasol), 42 g of aluminum
hydroxide (Disperal 20, Sasol) and 40 mL of 0.5 wt% aqueous
solution of nitric acid for peptization of alumina. The cylindrical
Al2O3 granules of 1.5 mm in diameter thus obtained were dried
at 110
h. Then they were crushed and sieved to obtain support grains
of 250–500 m in diameter. The method for preparing the
C overnight and calcined in a flow of air at 550 C for 4

Au/Al2O3 catalyst was similar to those described previously:6
20 mL of 0.02 M HAuCl4 solution was adjusted to pH 7 with 0.5
M NaOH. The solution was added with stirring to 1.0 g of Al2O3
suspended in 60 mL of distilled H2O at 70 °C. After stirring for 2
h, the solid was filtered, washed by 50 mL of distilled water at
room temperature, dried at 100 °C overnight, and calcined in
air at 350 °C for 1 h.
and the temperature was changed in the range of 50–100 C.
The performance of the catalyst was evaluated by averaging
the 2 samples taken at 30–33 min and 33–36 min after the
start of the experiment. The novel batch of catalyst was used
in each experiment.
The reaction products were analyzed by gas
chromatography (Agilent 6890N instrument with a 19091S-416
HP 5-MS capillary column 60.0 m × 320 μm × 0.25 μm). The
conversion of aldehydes was calculated using n-decane as the
internal standard. Yields of N-containing products were
calculated using GC data as the ratio of the product
concentration to the sum of the concentrations of all products
containing nitrogen (complete conversion of nitroarenes was
observed in all experiments). The identification of the reaction
products were performed by GC–MS on an Agilent 7000B
Triple Quad System. In some cases the main reaction product
was purified by silica gel column chromatography and
Catalyst characterization
The transmission electron microscopy (TEM) studies were
carried out using
a JEM-2010 (JEOL, Japan) electron
microscope with a lattice resolution of 0.14 nm and a 200 kV
accelerating voltage. The mean diameters of gold particles for
each catalyst sample were determined by counting of 250–300
particles in TEM images taken with a medium magnification.
XRD patterns of Au/γ-Al2O3 samples were recorded on a
Shimadzu XRD-7000 diffractometer using CuKα radiation (λ =
0.15418 nm) and Ni filter on the reflected beam. The gold
content in the samples was measured by Atomic absorption
spectroscopy on Hitachi Z-8000 instrument. The simultaneous
TG–DSC–MS measurement was performed in an apparatus
consisting of a STA 449 F1 Jupiter thermal analyzer and a QMS
403D Aëolos quadrupole mass spectrometer (NETZSCH,
Germany). The measurements were made in a "synthetic air"
flow (80 vol.% Ar and 20 vol.% O2) in the temperature range of
30–800 °C using the heating rate of 10 °C min-1, the gas flow
rate of 25 mL min-1 and open Al2O3 crucibles. The sample
weight is 25 mg. Textural characteristics were determined
from adsorption–desorption isotherms of nitrogen measured
at 77 K by using an automatic volumetric device ASAP 2400
(Micrometritics).
1
characterized by H and 13C NMR spectroscopy (NMR spectra
can be found in ESI†).
Catalyst regeneration
After the reaction was finished, a flow of pure toluene (0.5 mL
min-1) was fed into the reactor instead of a reaction mixture,
and the catalyst sample was washed for 30 min, and then
completely dumped out from the reactor. To remove toluene
the sample was placed in the vacuum heat chamber at room
Typical procedure for reductive amination of aldehydes with
nitroarenes over Au/Al2O3 catalyst
Fig. 1. Scheme of the H-Cube Pro™ set-up.
2 | J. Name., 2012, 00, 1-3
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temperature, evacuated to 5 mbar, slowly heated up to 80 °C
and dried at this temperature for 3 hours. Subsequently, the
spent catalyst was heated in an air oven from room
temperature to 330 °C at a heating rate of 1 °C min-1 and then
maintained at this temperature for 20 hours.7
Results and discussion
Au/Al2O3 catalyst containing 2.5 wt% Au with the mean Au
particle diameter equal to 3.4 nm (Fig. 2) used herein was
prepared in accordance with the so-called “deposition-
precipitation” method.6 The catalyst has been studied in the
reductive amination of unsaturated aliphatic aldehydes such as
undecylenic aldehyde and 3-methylcrotonaldehyde with
various nitroarenes (Tables 1 and 2) as well as in the reaction
between m-nitrostyrene and n-heptaldehyde (Table 3). It
should be noted that the complete conversion of nitroarenes
was observed in all experiments. Simultaneously with the main
Fig. 2. TEM data of the as-prepared Au/Al2O3 catalyst.
process aldehydes
2 could produce the corresponding alcohols
Table 1 Direct reductive amination of aldehydes with nitroarenes over Au/Al2O3 catalyst (Scheme 1)a
Entry Nitroarene,
Aldehyde, 2
Main product
2:1
Т, °С Conversion
Yield, %b
others
1
of 2, %
3
4
5
NO2
CHO
HN
1
1.2
80
80
n.d.c
n.d.
6
2
90 (88)
90
1d+1e
NO2
HN
2
CHO
1.2
4
n.d.
2d+4e
NO2
HN
7
7
3
4
5
1.5
1.5
1.5
80
90
100
67
79
86
16
11
13
7
4
2
77
85
85
n.d.
n.d.
n.d.
CHO
7
NO2
HN
6
7
8
1.5
1.5
1.2
80
90
90
83
91
98
7
4
10
2
0.5
0.3
91
96 (95)
90
n.d.
n.d.
n.d.
CHO
7
a
Catalyst (Au/Al2O3) = 200 mg, reactor CatCart®30 (30 mm × 4 mm), concentration of
1
= 0.025 mol L-1, solvent = toluene,
pressure = 50 bar, hydrogen flow rate = 60 mL min-1, flow rate of liquid = 0.5 mL min-1, reaction time = 30–36 min. b GC yield. The
values in parentheses are the yields of the isolated products. c n.d. = Not detected. d Secondary amine with reduced C=C group. e
Tertiary amine.
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in a side reaction3c therefore an excess of the aldehyde to an increase of the imine formation rate through the reaction with
nitroarene was used. Interestingly, the hydrogenation of C=C group aldehyde. At the same time, anilines with electron-withdrawing
is practically absent in both initial aldehydes and secondary amines substituent display weaker nucleophilic properties that lead to a
5 (Table 1) which has been confirmed by GC–MS and NMR data decrease in the rate of imine formation. Additionally, the position
(ESI†). So, the yield of secondary amines with reduced C=C group of the substituent in nitrobenzene has a strong influence on the
did not exceed 2% in the reactions between 3- reaction. It was found that the yield of secondary amines in the
methylcrotonaldehyde and nitrobenzenes. Meanwhile, in the case reaction between undecylenic aldehyde and nitrotoluene isomers
of undecylenic aldehyde the formation of such products was not decreased in the following order: p-nitrotoluene > m-nitrotoluene
detected at all. It was found that the unsaturated secondary amines >> o-nitrotoluene (Table 2, entries 2, 10 and 11). It is explained by a
5 could be produced with the high yields under flow conditions. The decrease of the nucleophilic properties of the corresponding
reactions of nitrobenzene and p-nitrotoluene with 3- methylanilines due to the steric hindrance created by a methyl
methylcrotonaldehyde gave the targeted products with the yield of substituent in meta- and ortho-position of the benzene ring.8
90% (Table 1, entries 1 and 2).The adjustment of the reaction
In contrast to the above-mentioned results, the significant
temperature and reagents ratio allowed improving the yield of amounts of products with reduced C=C group were formed in the
secondary amine 5 up to 96% in the reaction of undecylenic reaction between m-nitrostyrene and n-heptaldehyde over
aldehyde and p-nitrotoluene (Table 1, entries 6–8).
Au/Al2O3 catalyst (Table 3). Decreasing the reaction temperature
The effect of the substituent nature and its position in led to a decrease in the formation of the C–C double bond
nitroarenes on reductive amination of aldehydes was studied on reduction products, but at the same time, significant amounts of m-
the example of reaction between undecylenic aldehyde and vinylaniline 3a and imine 4a were formed at lower temperatures.
different nitroarenes (Table 2). It was found that introduction of To increase the yield of the target product 5a the contact time was
electron-donating substituent (–CH3, –CH2CH3, –OH) in the para- increased by reducing the liquid flow rate from 0.5 to 0.35 mL min-1
position of the nitrobenzene increased the yield of secondary amine and increasing the catalyst loading from 200 mg to 550 mg at 50 °C
while in the case of nitrobenzenes with electron-withdrawing and 50 bars of H2 (Table 3, entries 1–3). As a result, the yield of 5a
substituent (–Cl, –C(O)CH3, –Br) the decrease in the yield of the increased from 65% to 82%. Meanwhile, the change in hydrogen
target product was observed. This can be explained by the fact that pressure from 20 to 50 bars showed no significant effect on the
nucleophilic properties of anilines formed during the reaction grow yield of secondary amine (Table 3, entries 3–6).
with the introduction of electron-donating substituent8 resulting in
Table 2 Reductive amination of undecylenic aldehyde with nitroarenes over Au/Al2O3 catalysta
Entry
R
Conversion of
aldehyde,%
Yield, %b
secondary amine
primary amine
imine
4
0.5
1
n.d.
2
3
12
9
8
7
others
n.d.c
n.d.
n.d.
1
1
2
3
H
79
91
91
87
93
81
70
80
77
75
96
11
4
4
n.d.
n.d.
7
42
23
8
85
96
95
99
98
86
46
56
82
46
92
p-CH3
p-CH2CH3
p-OH
p-OH
p-OC(O)CH3
p-Cl
p-C(O)CH3
p-Br
о-CH3
4
5d
6
n.d.
4e
7
n.d.
12e
2e
n.d.
n.d.
8f
9
10
11
47
8
m-CH3
0.5
Catalyst (Au/Al2O3) = 200 mg, concentration of nitroarene and undecylenic aldehyde: 0.025 mol L-1 and 0.0375 mol L-1,
a
b
c
d
respectively, pressure = 50 bar, T=90 °C, reaction time = 30–36 min. GC yield. n.d. = Not detected. Concentration of
undecylenic aldehyde = 0.030 mol L-1. e Secondary amine with reduced R group. f T=80 °C.
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Table 3 The effect of reaction parameters on the products distribution in the reaction between m-nitrostyrene and n-
heptaldehyde over Au/Al2O3 catalysta
C6H13
N
C6H13
N
C6H13
NH
C6H13
NH
NO2
NH2
NH2
H2
CHO
+
+
+
+
+
+
C6H13
Au/Al2O3
5a
7
4a
6
8
3a
Entry
P, bar
Flow rate of liquid phase,
mL min-1
Yield, %b
3a
24
17
3
3
6
4a
7
5
1
1
2
2
1
5a
6
1
1
1
1
1
1
2
7
8
3
3
13
12
8
1c
2
3
4
5
50
50
50
40
30
20
20
0.50
0.50
0.35
0.35
0.35
0.35
0.35
65
74
82
83
83
83
76
0.3
0.2
0.3
0.2
0.2
0.2
0.4
6
7
4
7
17
7d
a Catalyst (Au/Al2O3) = 550 mg, reactor CatCart®70 (70 mm × 4 mm), concentration of m-nitrostyrene and n-heptaldehyde: 0.025
mol L-1 and 0.0375 mol L-1, respectively, T=50 °C, reaction time = 30–36 min. GC yield. Catalyst loading = 200 mg, reactor
b
c
CatCart®30 (30 mm × 4 mm). d T=60 °C.
The one-pot synthesis of unsaturated secondary amines in reduction of double bond.
A similar reaction between
the batch reactor by direct reductive amination of aldehydes nitrobenzene and m-vinylbenzaldehyde over Au/TiO2 catalyst
with nitroarenes is the difficult task, because the several type was realized previously in a batch reactor but the reaction
of reactions should be performed at the same condition and should be carried out for a long time by using two-stage
reaction time should be properly adjusted to avoid the
procedure with different conditions to achieve a high yield of
secondary amine.3b Firstly, the hydrogenation of the
nitroaromatic compound was performed at 120 C under H2
100
pressure until 95-98% conversion level, and then the reactor
was depressurized and left at the same temperature until
completion of the cascade process. In our case, the reaction
occurs in one step within a short time. Therefore, continuous
flow processes are more efficient than standard batch
protocols for synthesis of unsaturated secondary amines by
direct reductive amination of aldehydes with nitroarenes over
supported gold catalysts.
80
The time-dependent investigation of Au/Al2O3 catalyst in
reductive amination of undecylenic aldehyde with p-
nitrotoluene showed a decrease in secondary amine yield from
96% to 88% after 154 minutes on-stream (Fig. 3). To elucidate
the impact of the different factors on the catalyst deactivation
we compared the gold content, the mean particle size of gold
nanoparticles, textural properties, and the carbon deposits
content in the as-prepared and spent Au/Al2O3 catalysts using
atomic absorption spectroscopy, TEM, low-temperature
nitrogen adsorption and TG–DSC–MS analysis, respectively.
The characteristics of the as-prepared and spent catalyst are
provided in the Table 4.
as-prepared
regenerated
60
30
60
90
120
150
Time-on-stream, min
Fig. 3 The time dependence of secondary amine yield in the
reaction between p-nitrotoluene (0.025 M) and undecylenic
aldehyde (0.0375 M) over the as-prepared and regenerated
Au/Al2O3 catalysts at 90 C and 50 bar H2.
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Fig. 4 TG–DSC–MS data for the as-prepared Au/Al2O3 catalyst.
Fig. 5 TG–DSC–MS data for the spent Au/Al2O3 catalyst.
The comparison of characteristics of the as-prepared and in air atmosphere. The DTG curve of the as-prepared catalyst
spent catalysts allows us to conclude that Au content, Au exhibit the broad peak with a maximum at ~100 C, which is
particle size, and textural properties of Au/Al2O3 catalyst have related to removal of adsorbed water (the loss of the sample
not been changed notably after reaction (Table 4). In order to weight in the 30–200 C range is 1.4%) (Fig. 4). Additionally,
evaluate the contents of carbonaceous deposits, TG–DSC–MS the weight loss of about 1.6% is observed in the 200–550



C
analysis of the as-prepared and spent catalysts was performed range, probably due to elimination of hydroxyl groups from
the alumina surface or water removal from micropores.
Table 4 Physico-chemical characteristics of the as-prepared,
spent and regenerated Au/Al2O3 catalyst.
TG–DSC–MS results for spent Au/Al2O3 catalyst are
presented in Fig. 5. Before TG–DSC–MS analysis the sample
was washed with toluene for 30 minutes (0.5 mL min-1) and
placed in the vacuum heat chamber at room temperature,
As-prepared Spent Regenerated
Content of Au, wt%
Mean Au particle
2.5±0.1
3.4±1.4
2.4±0.1
3.3±1.3
2.5±0.1
3.3±1.2
evacuated to 5 mbar and then slowly heated up to 80 C with
diameter, nm
Content of carbon
the subsequent drying at this temperature for 3 hours. The
DTG curve of spent catalyst exhibited two weight loss regions:
-
4.5
-
deposits, wt%
the first (30–150
water (the weight loss in this temperature range is 1%) and the
second (200–550 C) could be explained by combustion of
hydrogen-enriched carbonaceous species on the catalyst
C) was caused by the removal of adsorbed
BET surface area, m2 g-1
Total pore volume, cm3 g-1
Mean pore diameter, nm
142
0.63
17.8
139
0.60
17.6
143
0.66
18.1

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substituent in the ortho-position a decrease in the yield of the
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target product was observed.
Acknowledgements
The authors thank M. V. Shashkov for his help in carrying out
this work. The work was performed with the support of
Federal Agency of Scientific Organization (V.45.3.7).
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surface, that was confirmed by the exothermic peak on DSC
curve and carbon dioxide and water peaks on MS curves in this
region. According to TG curve the weight loss in the
,
,
temperature region 200–550 C was 6.1% and thus estimated
amount of carbon deposits in spent Au/Al2O3 catalyst was
approximately 4.5 wt%.
Thus, the formation of carbon-based deposits is the main
reason for the Au/Al2O3 catalyst deactivation. This observation
agrees with our previous results of the investigation of
reductive amination of n-heptaldehyde with nitrobenzene over
Au/Al2O3 catalyst in a continuous flow reactor.3c
It was shown that the activity of the spent Au/Al2O3
catalyst could be recovered completely after the oxidative
treatment in air at 330 °C for 20 h (Fig. 3) which results in the
removal of carbonaceous deposits accumulated on the catalyst
surface. According to TG–DSC–MS data the regenerated
catalyst did not contain carbon deposits and TG, DTG, DSC and
MS curves of the regenerated Au/Al2O3 catalyst are similar to
the corresponding curves of the as-prepared catalyst (Fig. 4
and ESI†). Importantly, no increase of gold particle size was
detected after regeneration procedure which has been
confirmed by TEM (Fig 6) and XRD data (ESI†). The textural
properties for the regenerated catalyst also did not deviate
significantly from those characterizing the as-prepared sample
(Table 4).
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Conclusions
The direct reductive amination of unsaturated aliphatic
aldehydes with various nitrobenzenes over Au/Al2O3 catalyst
using molecular hydrogen as a reducing agent was performed
in a continuous flow mode. In most cases, the unsaturated
secondary amines were obtained in good to excellent yields,
the hydrogenation of C=C group is practically absent. It was
found that introduction of electron-donating substituent in the
para- and meta-position of the nitrobenzene increased the
yield of secondary amine while in the case of nitrobenzenes
with electron-withdrawing substituent or electron-donating
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DOI: 10.1039/C6RA20904A
Unsaturated secondary amines were successfully synthesized by reductive amination of aldehydes with
nitroarenes over Au/Al2O3 catalyst in a flow reactor