Mild palladium-catalysed highly efficient hydrogenation of CN, C-NO2, and CO bonds using H2 of 1 atm in H2O

Article abstract of DOI:10.1039/c8gc03285h

Here we present the first example of a mild and high-efficiency protocol enabling a process in water using 1 atm of H₂ for the efficient and selective hydrogenation of nitriles, nitro compounds, ketones, and aldehydes to yield primary amines and alcohols with satisfactory yields of up to >99%. Several palladium-based nanoparticle catalysts were prepared from K₂PdCl₄ and ligands, and one of them was found to be the best and most suitable for the hydrogenation of CN, C-NO₂, and CO bonds. In addition, the catalyst Pd-NPs can be easily recycled and reused without losing their activity and selectivity. A plausible mechanism for the hydrogenation of a CN bond was also proposed, representing the first example that possesses great potential for sustainable industrial purposes.

Full text of DOI:10.1039/c8gc03285h

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DOI: 10.1039/C8GC03285H
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Mild palladium-catalysed highly efficient hydrogenation of C≡N, C-
NO and C=O bonds using H of 1 atm in H O
2
,
2
2
Received 00th January 20xx,
Accepted 00th January 20xx
Yaxu Liu, Shaopo He, Ziyi Quan, Huizhuo Cai, Yang Zhao, Bo Wanga,b,c*
a
a
a
a
a
DOI: 10.1039/x0xx00000x
2
Presented here is the first example of a mild and high-efficiency protocol enabling a process in water using 1 atm of H for
efficient and selective hydrogenation of nitriles, nitro compounds, ketones, and aldehydes to yield primary amines and
alcohols with satisfactory yields of up to >99%. Several palladium-based nanoparticle catalysts were prepared from K PdCl
www.rsc.org/
2
4
and ligands, and one of them was found to be the best and most suitable for hydrogenation of C≡N, C-NO2, and C=O Bonds.
In addition, the catalyst Pd-NPs can be easily recycled and reused without losing its activity and selectivity. A plausible
mechanism for the hydrogenation of a C≡N bond was also proposed, representing the first example that possesses great
potential for sustainable industrial purposes.
9
10
Rh, and Re for enhanced selectivity and activity, and novel reaction
systems as well. Also, recent works on homogeneous catalysts from
the groups of Milstein using cobalt catalysts and Beller using
manganese catalysts are worth noting.
Introduction
1
1
12
Amines, especially primary amines, are an important class of
compounds in synthetic organic or bioorganic chemistry, and they
are also valuable building blocks for the synthesis of pharmaceuticals,
agrochemicals, fine chemicals, polymers, dyestuffs, and plasticizing
agents due to their straightforward valorization and structural
Compared with homogeneous catalysts, heterogeneous ones are
preferred due to easy recyclability and environmental concerns,
particularly for large-scale or industrial preparations. In this case,
1
3
14
some noble-metal catalysts, such as Ru and Pd, and some non-
1
diversity. Recently, a host of procedures has been reported for
1
5
16
precious ones, such as Ni and Co , were employed. Nevertheless,
high pressure and reaction temperatures were usually involved for
those methods with non-precious metal catalysts compared to those
using noble metal catalysts. Under most conditions, those
procedures promoted by non-precious Ni, and/or Co, or Mn catalysts
and high hydrogen pressures suffer from unavoidable by-product
formations, low product yields or substrate conversions, poor
selectivity, and the need to employ custom high-pressure tolerant
reaction vessels. Therefore, developing novel and recyclable
heterogeneous metal catalysts with excellent selectivity and activity
toward nitriles, which enables reactions to proceed under mild
2
primary amine synthesis, such as the direct amination of alcohols,
reductive amination of carbonyl compounds, elimination of carbonyl
group of amides, hydrogenation of compounds containing C=N
bond(s), reduction of nitro-compounds, and reductive
hydrogenation of nitriles. In addition, nitriles are readily available in
nature, and the reduction of nitriles to primary amines has recently
received considerable attention. Generally, nitriles can be reduced
3
4
1a
5
using hydrosilanes, toxic NH
consideration of sustainability and to meet some principles of green
chemistry, H would be a better choice. Nevertheless, for those
processes using H , a common consequence is the formation of
3 3 2
BH , or molecular hydrogen (H ). For
2
2
2
conditions, particularly in the abundant solvent H O (to the best of
our knowledge, water, as a kind of solvent, is always considered to
be environmentally friendly, renewable, affordable, and non-
undesired secondary- and tertiary amines, as well as other by-
6
products. Solving the problems may rely on improving the existing
7
8
or developing new novel homogeneous catalysts based on Ru, Fe ,
2
hazardous), using molecular hydrogen (H ) at a pressure as low as 1
atm, allowing easy application for hydrogenation of a wide spectrum
of nitriles is highly desirable, which is rather challenging. It would be
preferable for the heterogeneous catalyst to cover broader substrate
scopes and can be extended to other compounds bearing
unsaturated bonds.
a. M.S. Y. Liu, Mr. S. He, Mis. Z. Quan, Mis. H. Cai, Mis. Y. Zhao, and Prof. Dr. B.
Wang
Key Laboratory of Advanced Materials of Tropical Island Resources
(Hainan University), Ministry of Education
Hainan University
In addition to primary amines, alcohols are also important building
blocks and constitute key intermediates for the synthesis of
No.58 Renmin AVE. Haikou 570228, P.R. China.
E-mail: wangbo@hainu.edu.cn, bo.wang@biotech.kth.se (Prof. B. Wang)
b.
State Key Lab of Marine Resource Utilizations in South China Sea,
Hainan University
16a
pharmaceuticals, agrochemicals, and fine chemicals. Conventional
No.58 Renmin AVE. Haikou 570228, P.R. China.
Institute of Chemical Engineering, College of Materials and Chemical Engineering
Hainan University
methods for the preparation of alcohols usually rely on reducing
c.
4 4
reagents, such as NaBH , LiAlH , boranes, and silanes, to react with
1
6a
ketones or aldehydes. Nevertheless, undesired waste is generated,
which restricts their applications in industry for environmental
No.58 Renmin AVE. Haikou 570228, P.R. China.
Footnotes relating to the title and/or authors should appear here.
†
Electronic Supplementary Information (ESI) available: [details of any supplementary
information available should be included here]. See DOI: 10.1039/x0xx00000x
This journal is © The Royal Society of Chemistry 20xx
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Journal Name
concerns, particularly for industrial-scale preparations. An (Entry 11, Table 1). However, during or after reactions, no product
View Article Online
DOI: 10.1039/C8GC03285H
assortment of smart hydrogenation catalyzing systems has been formation was observed, indicating that no reactions occurred in the
1
4a
17
18
19
20
21
22
developed, such as Pd-, Pt-, Ru-, Rh-, Co-, Mn-, Fe-, and absence of Pd-Ligand or with L6 itself as the possible catalyst. To
2
3
C- based complex catalysts and molecular hydrogen. Although explore the effect of pH on product yields, some reactions were
excellent selectivity and activity of these catalysts toward aldehydes carried out with pH (adjusted with diluted H SO and solution of
2
4
and ketones to form alcohols were displayed, high-pressure and/or NaOH) varying from 1.0 to 11.0, and pH 1.0 proved most suitable for
organic solvents were required in most conditions. Therefore, smooth, mild, and efficient hydrogenation of benzonitrile, as the
discovering new and novel recyclable heterogeneous catalysts yield of the benzylamine (in the form of ammonium salt) was boosted
capable of catalyzing mild transformations using 1 atm of H
2
,
to >99%, an excellent and satisfactory yield very close to an ideal of
particularly for those proceeding in naturally abundant and green 100% (Entry 12, Table 1). Strongly alkaline conditions seemed to
solvent H
2
O, is of great interest.
negatively affect the yields of benzylamine, as when performing
reactions at pH 11.0, the yield decreased to about 5% (Entry 18,
Table 1). When the pH was increased, there was a tendency for the
Results and discussion
Initial evaluations for suitable catalyst(s) and optimized reaction yields of the proposed product benzylamine to gradually decrease
conditions were carried out on a 10-ml scale using benzonitrile as the (Entries 12–18, Table 1). Therefore, all further reactions were carried
model substrate, and all of the reactions proceeded in water. out at pH 1.0. When reduced loading of the catalyst by 50% (0.5mg)
Reaction parameters, such as the catalyst and its loading, including was attempted to achieve a satisfactory yield, a prolonged time of 3
the metal precursor and the ligand (Figure 1), pH of the reaction h was required (Entry 19, Table 1), proving the excellent
medium varying from 1.0 to 11.0, and reaction time were performance of the catalyst Pd-L6 towards benzonitrile, even at 50%
investigated. The results are summarized in Table 1.
loading, which equals 4mol% based on the metal Pd.
Table 1. Conditions optimization for hydrogenation of benzonitrilea
Metal
precursor
Catalyst
(mg)
Entry
Ligand
pH Yield (%)b
1
2
3
4
5
6
7
8
9
K
K
K
K
K
K
K
K
K
2
2
2
2
2
2
2
2
2
PdCl
PdCl
PdCl
PdCl
PdCl
PdCl
PdCl
PdCl
PdCl
4
4
4
4
4
4
4
4
4
L1
L2
L3
L4
L5
L6
L7
L8
L9
L6
—
L6
L6
L6
L6
L6
L6
L6
L6
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
0.5
7.0
7.0
7.0
7.0
7.0
7.0
7.0
7.0
7.0
7.0
7.0
1.0
2.0
3.0
5.0
7.0
9.0
11.0
1.0
9
6
Figure 1. Structures of varied ligands
4
Synthesis and screening of Pd-ligands
15
13
35
20
2
The catalysts were chemically synthesized from the metal
precursor K
of the ligand (0.1 mmol) and HBF
13.8mg, 0.2mmol) dissolved in ultrapure water was added
2
PdCl
4
and varied ligands (Figure 1): To a mixed solution
4
(40%, 1ml), sodium nitrite
(
o
dropwise. The solution was stirred at 0 C for 1 h, toluene of 1ml,
potassium tetrachloropalladate (K PdCl ,0.08mmol), ultrapure water
of 2ml along with the resulted light-yellow solid were mixed and
stirred with a magnetic bar for another 1 hour. NaBH (22.6mg,
.6mmol) dissolved in water (1ml) was dropped at room 11
2
4
5
1
0
—
—
n.d.c
n.d.d
>99
90
55
38
26
12
5
4
0
temperature to the previous solution and incubated at room
temperature for 2 h. After that, the mixed solution was transferred
to a 10 ml centrifuge tube and centrifuged, the aqueous phase was
1
1
1
2
3
4
K
K
K
K
K
K
K
K
2
PdCl
2
PdCl
2
PdCl
2
PdCl
2
PdCl
2
PdCl
2
PdCl
2
PdCl
4
4
4
4
4
4
4
4
separated and washed firstly with diluted H
solution of NaHCO
2 4
SO , and then with
3
each three times, the resulted suspension was 15
centrifuged again, the solid was washed with ethanol and sonicated
for 5 minutes, and centrifuged to remove ethanol, the resulted solid
was dried to provide Pd-ligands. In view of green chemistry, all
reactions using these nine catalysts for hydrogenation were carried
1
1
1
6
7
8
out in water at pH 7.0. After reactions completed, the yields of the 19e
desired product benzylamine were determined to range from 2% -
>99
aUnless otherwise stated, all reactions were carried out under the following
3
5% (Entries 1-9, Table 1). Among the catalysts (Pd-(L1–L9))
conditions: nitrile, 0.05 mmol; H
atm filled in a balloon; reaction time, 1h. Conversions and yields were determined
2
O as the solvent, 10 ml, proceeded at rt, H
2
at 1
evaluated, the one derived from K PdCl and L6 turned out to be the
2
4
b
best, as the desired product was obtained with the yield of 35% by high performance liquid chromatography (HPLC) analysis equipped with a C18
reverse column; c,dn.d., not detected; e Reaction time was 3 h.
(Entry 6, Table 1). We also tried to perform reactions by solely using
the ligand L6 (Entry 10, Table 1) or under catalyst-free conditions
2
| J. Name., 2012, 00, 1-3
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ARTICLE
Characterization of Pd-L6
nm, 4.4 nm, 4.2 nm, 4.9 nm, and 4.1 nm, respectively, falling within
the range of nanoparticle and therefore classified as Palladium
nanoparticles. All of the nanoparticles had some levels of
aggregation; however, the catalyst Pd-L6 was found to be relatively
well dispersed.
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DOI: 10.1039/C8GC03285H
High-resolution transmission electron microscopy (HRTEM)
images of all the catalyst Pd-(L1-L9) are presented in Figure 2 to
observe their morphology clearly. The HRTEM analysis showed that
the catalysts Pd-(L1–L5), and Pd-(L7–L9) were not well dispersed
nanoparticles, as the average diameters of the Pd-(L1–L9)
nanoparticles were measured as 4.8 nm, 5.2 nm, 5.1 nm, 4.5 nm, 5.1
2-3 3-4 4-5 5-6 6-7 7-8
2-3 3-4 4-5 5-6 6-7 7-8
2-3 3-4 4-5 5-6 6-7 7-8
Pd-L1
Pd-L2
Pd-L3
2-3 3-4 4-5 5-6 6-7
3-4 4-5 5-6 6-7 7-8
2-3 3-4 4-5 5-6 6-7 7-8
2
0 nm
Pd-L4
Pd-L5
Pd-L6
2-2.52.5-33-3.53.5-44-4.5
2-3 3-4 4-5 5-6 6-7 7-8
2-3 3-4 4-5 5-6 6-7
Pd-L7
Pd-L9
Pd-L8
Figure 2. High resolution TEM patterns of Pd-complexes
As already stated, among the catalysts tested, Pd-L6 performed
the best during hydrogenation of benzonitrile. As a result, Pd-L6 was
further characterized by X-ray diffraction (XRD), elemental analysis
1
11
(
EA), inductively coupled plasma-optical emission spectrometer (ICP-
1
OES), H NMR, and X-ray photoelectron spectroscopy (XPS). The XRD
pattern of Pd-L6 shown in Figure 3 indicates that the broad
diffraction peak at 25° could be indexed to the existence of carbon
elements; and the peaks at 40.0°, 46.5°, 67.9°, 81.8°, and 86.3°
exhibit diffraction lines (hkl) corresponding to the crystal planes at
(111), (200), (220), (311), and (222), respectively, indicating the
existence of the Pd in Pd-L6.
3
11
2
00
2
20
2
22
1
0
20
30
40
50
60
70
80
90
2
Theta (degree)
Figure 3. XRD pattern of heterogeneous catalyst Pd-L6.
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ARTICLE
Journal Name
1
of diazonium salt at 8.01–8.86 ppm, the H NMR solid spectrum of
View Article Online
DOI: 10.1039/C8GC03285H
K PdCl4
Pd-L6 showed a broad peak at 4.20 ppm (Figure S5), indicating that
2
Pd 3d
Pd-L6
the chemical-shift change took place. The peak broadening (Figure
S5) would possibly be due to fast spin-spin relaxation of atoms close
to a metal core while performing solid state NMR through magic-
2
5
angle spinning. This evidence suggests that the formed diazonium
salt from L6 generated new palladium-nitrogen (Metal-N) bonds, and
the deduced structure of Pd-L6 is shown in Figure 5.
2
Hydrogenation of C≡N, C-NO , and C=O bonds
The selectivity of Pd-L6 with time towards the model substrate
benzonitrile under varied pH conditions was also evaluated at a
loading of 4mol%, and the results are listed in Figure S1 and Figure
S2. Results indicate that the selectivity of Pd-L6 was pH tolerant,
although there was an obvious loss in its catalytic activity under
strongly alkaline conditions (Figure S1).
355
350
345
340
335
330
325
Binding Energy (eV)
After optimizing the conditions, an array of nitriles listed in Table
2
were subjected to the same reaction conditions, and the results are
Figure 4. The XPS analyses of Pd-L6 and K PdCl
2
4
summarized in Table 2. All of the reactions proceeded smoothly
under the conditions mentioned above, and the majority of these
products were obtained in yields of up to 99% with satisfactory
chemoselectivity (Entries 1–4,7-11, 13–16, Table 2), which was a
great enhancement by comparison with the existing protocols listed
in the introduction section. No obvious effects of substituent(s)
In order to further characterize the chemical state of catalyst, Pd-
L6 mixed with K PdCl was subjected to XPS analyses. The result was
shown in Figure 4. The XPS result proves the presence of palladium,
oxygen, carbon and nitrogen in Pd-L6. The spectra of K PdCl (in black)
2
4
2
4
(either electron-donating, or electron-withdrawn) on product yields
revealed peaks at 343.28 and 338.08 eV were assigned to the Pd 3d3/2
and 3d5/2 respectively. In the spectra of Pd-L6 (in red), the peak of Pd
were observed, as most of the desired products were provided with
close to full yields. However, steric hinderance seemed to make
some slight negative effects on the yields of product. For those
aromatic substrates with unsaturated substituent(s), such as C≡N on
the aromatic ring, although most of them could be converted with
ideal conversions (>99%), diamine products were usually provided
3d5/2 shown at 334.68 eV, which correlated well with the peak of Pd
2
4
(
0) referencing the publication by J. Dupont, and therefore, the
presence of Pd (0) in Pd-L6 is proved.
NO2
NH
(Entry 6, Table 2) to a lesser extent. Furthermore, HPLC analysis
showed that a small portion of the converted substrates was actually
mono-reduced (only one C≡N group on the ring was successfully
HN
2
converted to C-NH , the other C≡N bond kept unchanged).
Substrates with sensitive group(s) have been shown to affect product
yields, which were lower compared to substrates bearing non-
sensitive substituent(s) (Entries 5, 12, Table 2), regardless of position.
NO2
However, when aliphatic nitrile was employed under the same
conditions, both the substrate conversions and the yields of the
desired product were poor. For instance, when using butyronitrile as
the substrate, the conversion was 62%, same as its yield (62%) (Entry
17, Table 2), and the above results showed that a lower yield resulted
when using aliphatic nitriles compared to aromatic substrates. A
prolonged time of 6 h was also tested to check whether there were
some improvements in both product yields and substrate
conversions, but no better outcomes were observed. It should be
noted that when a substrate bears a halogen on an aromatic ring,
either at the p-, or m-, or o- position, the afforded product typically
NO2
NH
NN H2
NH2 aN
O
2
l
4
L6
C
d
P
Pd-NPs
/
H
B
2
F
4
K
N2 BF4
N2 BF4
HN
O2N
Pd Pd
Pd-L6
Figure 5. Structures of unbound (black) and Pd-bound L6 (blue).
1
The H NMR spectrum of the diazonium salt derived from L6
Figure S4) showed that the ligand L6, 4-nitrobenzene-1,2-diamine,
was transformed into a diazonium salt (blue compound, red box in
Figure 5). Elemental analysis of Pd-L6 showed that all three N atoms
in a molecule of L6 remained, and an average of two metal atoms of
palladium was found for each ligand, indicating that the ratio (mol)
2
6
exhibited the halogen atom substituted by a hydrogen atom
Entries 1, 8, Table 2). However, this is not applicable for all, as when
we use substrates possessing an F atom on the aromatic ring (Entries
, 10, Table 2), the resulting product kept fluorine at its original
position.
Encouraged by the Pd-NPs(Pd nanoparticles)-catalyzed, highly
(
(
2
of N: Pd: aromatic ring (from the ligand L6) is about 3: 2: 1,
1
respectively. In terms of the H NMR spectrum of the chemical shift efficient synthesis of primary amines starting from nitriles with
excellent chemoselectivity, we intended to expand the possible
4
| J. Name., 2012, 00, 1-3
This journal is © The Royal Society of Chemistry 20xx

Page 5 of 8
Green Chemistry
Journal Name
ARTICLE
substrate scope of this procedure to nitro compounds for primary conversions and yields of product could almost reachV1ie0w0A%rtic(ElenOtnrliienes
amines as well. Therefore, eight nitro-aromatic substrates were 5,8, Table 3). As to those compounds with hDaOloI:g1e0n.1s0o3n9/tCh8eGaCr0o3m28a5tiHc
tested, and the results are listed in Table 3. As expected, all of the ring, similar to nitriles, the dehalogenation process was inevitable,
reactions proceeded well within 2h, with ideal conversions very close which would occur upon initiation of the hydrogenation of nitro-
to 100%, and the products were provided in yields of up to 99% compounds, as the halogen atoms contained in the starting material
(Entries 1–8, Table 3) with excellent selectivity. During or after the were replaced by hydrogen (Entries 3, 4, Table 3). For those
reaction, we did not detect any formation of by-products, indicating substrates with fluorine on the aromatic ring, the desired products
that the catalyst Pd-NPs, along with the developed procedure are were afforded as expected, and F was retained in the product,
versatile, and particularly applicable to the hydrogenation of nitro- doubling reaction time (for R=Br, and Cl, Entries 1,8, Table 2) to 6.0h
compounds to obtain primary amines. Furthermore, the effects of will lead to a satisfied yield when fluorine substituted aromatic nitrile
substituent(s) on yields or conversions were investigated, and it was was used, for instance, 4-fluorobenzonitrile (Entry 2, Table 2), this
very difficult to draw a conclusion as we did not find any differences may possibly due to less reactive activity of fluorine, similar results
1
6a
between the conversions and the yields because during the whole were also illustrated in Beller’s work. The excellent performance
course of reaction, almost all of the substrates were successfully of Pd-NPs toward both nitriles and nitro-compounds promoted us to
converted to the desired products, and there were basically no by- further explore the possible substrate scope and the applications of
products formed. Note that when sensitive-group-bearing substrates the catalyst Pd-NPs in reduction of other unsaturated bond-
were employed, different from nitriles whose product yields were containing compounds, particularly for C=O compounds.
less than their conversions (Entry 5, Table 2) and both substrate
a
Table 2. Hydrogenation of nitriles assisted by Pd-NPs
Time
h)
Conv.
Yield
Time
(h)
Conv.
Yield
Entry
R-C≡N
R-CH
2
NH
2
Entry
10
R-C≡N
2 2
R-CH NH
b
c
b
c
(
(%)
(%)
(%)
(%)
1
2
3
4
R = Br
R = F
3.0
6.0
3.0
3.0
>99
>99
>99
>99
99
99
99
99
R = F
8.0
3.0
3.0
3.0
>99
>99
>99
>99
99
99
89
99
N
11
R = OCH
3
R = CH
3
12
R = NH
2
R
N
R
R = OCH
3
13
R = CH
R = CH
3
N
5
6
R = NH
2
3.0
8.0
>99
>99
85
95
14
15
3
3.0
3.0
>99
>99
99
99
R
R = CN
R = OCH
3
N
7
R = CF
3
1.5
>99
99
16
3.0
3.0
99
62
99
62
N
d
8
9
R = Cl
R = H
3.0
3.0
>99
>99
99
99
17
a
2 2
Unless otherwise stated, all of the reactions were carried out under conditions: nitrile, 0.05 mmol; H O as the solvent, 10 ml proceeded at rt, H of 1 atm filled in a
balloon; b,c Conversions and yields were determined by high performance liquid chromatography (HPLC) analysis equipped with a C18 reverse column; d Conversions
and yields were determined by GC analysis.
In addition to hydrogenation of nitriles and nitro-group high-pressure capabal reaction vessels are often necessary; and c)
compounds for primary amines, the hydrogenation/reduction of the use of unrecyclable homogeneous complex noble metal catalysis
substrates containing C=O bond(s) to prepare products possessing C- and associated high costs. Therefore, the preparation of alcohols
2
OH bond(s), especially those using H and proceeding under normal from ketones/aldehydes under mild conditions has recently received
atmospheric pressure (1 atm), is rather challenging in both academia considerable attention, particularly for the consideration of green
and industry. Similar to the synthesis of primary amines via and sustainable industrial applications. An array of aldehydes was
hydrogenation of nitriles and nitro-compounds, the clean and thus evaluated, and the results are summarized in Table 4.
efficient preparation of alcohols starting from aldehydes/ketones is
still suffering from: a) employing stoichiometric metal hydride, which
is usually accompanied by undesired by-product and waste salt
formations; b) unsafe high pressure when using H
2
, and again custom
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Table 3. Hydrogenation of nitro-aromatic substratesa
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DOI: 10.1039/C8GC03285H
All reactions were proceeded well, and all of the aldehydes listed
in Table 4 could provide ideal conversions of >99%. During or after
reactions, we did not observe any detectable formations of by-
products, as all products provided excellent yields of 99% (Entries 1–
15, Table 4). It seems that electron-donating or -withdrawn
substituent(s) on aromatic rings do not have any negative or positive
effect on substrate conversions or the yields of products (Entries 1–
Time
h)
Conv.
(%)
Yield
(%)
Entry
Ar-NO
2
Ar-NH
2
b
c
(
1
2
R = H
R = F
1.5
2.0
2.0
2.0
2.0
2.0
2.0
1.5
>99
>99
>99
>99
>99
>99
>99
>99
R = H
R = F
R = H
R = H
99
99
99
99
99
99
99
99
5
, 7, Table 4) within 2h, whereas when substrates possess a hydroxy
3
R = Cl
R = Br
R = OH
group , a prolonged time was required to achieve a satisfactory yield
of 99%, a tendency that is also exhibited by sterically hindered
substrates (Entries 8, 13, 14, Table 4). Similar to nitriles and nitro
compounds, dehalogenation occurred simultaneously upon
initiation of the dehydrogenation process for substrates bearing a
chloride or bromide atom on the aromatic ring, resulting in
dehalogenated aromatic alcohols (Entries 3,4, Table 4). However,
when the halogen was fluorine, the corresponding product was
provided with the yield of 99% when the reaction was performed
4
5
R = OH
6
R = CH
3
R = CH
3
7
R = OCH
3
R = OCH
3
8
R = NH
2
R = NH
2
a
Unless otherwise stated, all reactions were carried out under the following
O, proceeded at rt, H of 1
(Entry 1, Table 4) under the same reaction conditions.
conditions: nitro compound, 0.05 mmol, 10 ml H
2
2
atm filled in a balloon; b,c Conversions and yields were determined by high-
performance liquid chromatography (HPLC) analysis equipped with a C18
reverse column.
Table 4. Reductive hydrogenation of aldehydesa
Entry
Conv.
Product
Time
(h)
Yield
(%)
Entry
Conv.
(%)
Product
Time
(h)
Yield
(%)
ArCHO
ArCHO
b
c
b
c
(%)
1
2
3
4
5
6
7
8
R = F
>99
>99
>99
>99
>99
>99
>99
>99
>99
R = F
2.0
2.0
2.0
2.0
2.0
3.0
2.0
3.0
2.0
99
99
99
99
99
99
99
99
99
10
11
12
R = OCH
R = OH
3
>99
>99
>99
R = OCH
3
1.5
3.0
2.0
99
99
99
R = OCH
R = Cl
R = Br
3
R = OCH
R = H
3
R = OH
R = CH
3
R = CH
3
R = H
R = CH
3
R = CH
R = CH
3
2
13
>99
3.5
99
R = CHO
OH
R = CF
3
R = CF
3
1
4
>99
>99
3.0
2.0
99
99
R = OH
R = OH
9
R = CH(CH
3
)
2
R = CH(CH
3
)
2
15
a
2 2
Unless otherwise stated, all of the reactions were carried out under the following conditions: aldehyde, 0.05 mmol; H O, 10 ml; proceeding at rt, H of 1 atm filled
in a balloon. b,c Conversions and yields were determined by high-performance liquid chromatography (HPLC) analysis equipped with a C18 column of reverse-phase.
The great success in mild- and high-efficiency hydrogenation of reduction of ketones should be somehow more difficult than
nitriles, nitro compounds, and aldehydes in H
primary amines and alcohols made us excited, and we expected to hydrogenation of ketones to form the corresponding alcohols using
further explore the possible substrate scope of the procedure to (1 atm). Nevertheless, in most conditions, heated conditions were
2
O to form an array of aldehydes. Recently, there have been several examples for the
H
2
other compounds. Ketones are a strong option due to their required, and this is usually accompanied by the formation of
availability. Generally, for ketones, the activation energy for reaction undesired by-products, low substrate conversions, and poor yields of
initiation is higher than that of aldehydes, and theoretically, the products. To the best of our knowledge, the selective reduction of
6
| J. Name., 2012, 00, 1-3
This journal is © The Royal Society of Chemistry 20xx

Page 7 of 8
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ARTICLE
ketones for alcohols using molecular hydrogen under normal process occurred, and the desired alcohol was provided with the
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DOI: 10.1039/C8GC03285H
yield of 99% (Entries 7, 11, Table 5). Regardless of electron-
atmospheric pressure, especially those proceeding in the solvent H
2
O
and at rt, has not been well-studied. A list of ketones, including withdrawn or electron-donating groups present on the aromatic ring,
aromatic and aliphatic ketones, were thus subjected to the same there were no obvious effects observed during or after the reactions.
conditions for aldehydes, and the results are summarized in Table 5. Note that there were no side reactions detected, as all of the
To our delight, almost all of the substrates were fully (> 99%) corresponding products were obtained with yields of 99%. In
converted to form the related products with ideal yields (99%, addition, turn over frequency (TOF) and turn over numbers are very
2
7
Entries 1–15, Table 5). Similarly, for those substrates bearing a important parameters for heterogeneous catalysts. For Pd-NPs, the
halogen atom (F is excluded) on the aromatic ring, the resulting number of active atoms (4.3160%) was determined by chemisorption
products were dehalogenated alcohols (Entries 2, 3, Table 5), and for analysis of hydrogen, and the calculation value of TOF and TON is
substrates with an F atom on aromatic ring, no dehalogenation calculated in Table S2, Table S3, Table S4, and Table S5.
Table 5. Hydrogenation of ketones to the formation of alcoholsa
Conv.
b
Time
(h)
Yield
(%)
Conv.
(%)
Time
(h)
Yield
(%)
Entry
RC(O)CH
3
Product
Entry
RC(O)CH
3
Product
c
b
c
(
%)
1
2
3
4
5
R = OCH
R = Cl
3
>99
>99
>99
>99
>99
R = OCH
R = H
3
3.0
2.0
2.0
3.0
3.0
99
99
99
99
99
10
11
12
13
R = OCH
R = F
3
>99
>99
>99
>99
R = OCH
3
3.0
3.0
3.0
3.0
99
99
99
99
R = F
R = Br
R = H
R = OH
R = OH
R = CH
3
R = CH
3
R = CH
3
R = CH
3
R = C
2
H
5
2 5
R = C H
1
1
4
5
>99
>99
2.0
3.0
99
99
R
=
6
7
>99
R = CH(CH
3
)
2
3.0
99
CH(CH
3 2
)
R = F
>99
>99
R = F
2.0
3.0
99
99
d
8
9
93
4.0
93
a
Unless otherwise stated, all of the reactions were carried out under conditions: ketone, 0.05 mmol, H
2
O as the solvent, 10 ml, proceeded at rt, H
2
of 1 atm
b,c
filled in a balloon; Conventions and yields were determined by high-performance liquid chromatography (HPLC) analysis equipped with a C18 reverse
column; Conversions and yields were determined by GC analysis.
d
H2
A possible mechanism (taking nitrile as the example) is proposed
in Scheme 1 to address the excellent performance and high catalytic
S4
Pd H
activity of Pd-NPs on reduction of an array of nitriles, nitro-
compounds, aldehydes, and ketones based on the reaction facts and
recent publications. In a molecule of Pd-NPs 1, amines were the
Pd
N
N
H
R
H R
2
H
1
17
S3
S5
ligands to accelerate the reaction, since amine-bound hydrogen
atoms become acidic. First, molecular hydrogen was absorbed by the
catalytic Pd-NPs and transferred to protonate the nitrogen atoms in
ligands (S1) to become the intermediate 2, which then coordinated
with the nitrogen atom in nitrile and activated it to from the
intermediate 3 (S2). Following was the hydrogen transfer from metal
Pd to the carbon to form an imine C1 and back to the catalyst Pd-NPs
1. Next is the coordination of the imine C1 with the intermediate 2
to form another intermediate 4 (S5), which was activated and
protonated to finally generate the product primary amine (S6) and
restore the catalyst Pd-NPs 1.
R
NH
R
R
N
H
H
C1
Pd
H
Pd
N
R
H
N
4
N
R
3
H
H
H
H
S2
S6
N
NH2
Pd H
Pd
N
H
1
R
N
H
R
Substrate
nitrile
H
R
2
R
Product
amine
S1
H2
Conclusions
Scheme 1. The proposed mechanism for Pd-NPs catalyzed
hydrogenation of nitrile.
In conclusion, we have presented a highly active palladium-based
nanocatalyst (Pd-NPs) with excellent selectivity and stability in high-
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 7

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ARTICLE
Journal Name
efficiency and selective hydrogenation of C≡N, C-NO2, and C=O
including aldehydes and ketones) bonds, making the hydrogenation
of nitriles, nitro-compounds, aldehydes, and ketones to form primary
amines and alcohols extremely easy, even in naturally abundant
Wendt; A. Spannenberg; H. Jiao; C. Bornschein; M. Beller, Chem. Eur.
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D.
Srimani;
Y.
Ben-David;
D.
2 2
green solvent H O at rt using H of 1 atm. Most of the corresponding
8
products provided good to excellent yields of up to > 99%, although
dehalogenation occurred when using substrates bearing halogen (F
is excluded) on the aromatic ring. Pd-NPs and its developed
methodologies are applicable for a wide range of nitriles, nitro-
compounds, aldehydes, and ketones, particularly for clean synthesis
of primary amines and alcohols. In addition, the heterogeneous Pd-
NPs could be easily recycled and reused at least 10 times without
losing its major selectivity and activity, and the HRTEM images of the
recovered catalyst after 10 catalytic cycles revealed that no obvious
1
4
H. Junge; S. Bachmann; M. Scalone; C. Topf; K. Junge; M. Beller, Catal. Sci.
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9
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measured (Figure S6, S7). Therefore, Pd-Nps is believed to possess
great potential in sustainable industrial applications, and a possible 12 S. Elangovan; C. Topf; S. Fischer; H. Jiao; A. Spannenberg; W. Baumann; R.
Ludwig; K. Junge; M. Beller, J. Am. Chem. Soc. 2016, 138, 8809-8814.
and plausible mechanism for the hydrogenation of nitriles has also
1
3 S. Muratsugu; S. Kityakarn; F. Wang; N. Ishiguro; T. Kamachi; K. Yoshizawa;
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been proposed. Furthermore, during reactions, we also found that
Pd-NPs showed extremely high hydrogenation activity towards C=C
bonds to form C-C with satisfactory selectivity. Further investigations
on the hydrogenation of compounds bearing C=C and C≡C bonds are
underway.
1
1
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Financial Support from the National Natural Science
Foundation of China (21868011 and 21502036), the National
Key R&D Program of China (2017YFC1103800), and the
Innovative Research Team Project of Hainan Natural Science
Foundation (2016CXTD006) is gratefully acknowledged. We
thank LetPub (www.letpub.com) for its linguistic assistance
during the preparation of this manuscript.
17
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