Versatile CO-assisted direct reductive amination of 5-hydroxymethylfurfural catalyzed by a supported gold catalyst

Article abstract of DOI:10.1039/c7gc01579h

Reductive amination (RA) constitutes an attractive and practical strategy for discovering protocols capable of converting biomass into valuable N-containing compounds. Described herein is a versatile and sustainable RA of 5-hydroxymethyl-furfural (HMF), an important biomass-derived aldehyde, using abundant and cheaply available CO and water as reductants. A single phase rutile titania supported gold (Au/TiO₂-R) catalyst is shown to efficiently catalyze this CO/H₂O-mediated RA under mild and convenient conditions. With this system, a broad spectrum of primary and secondary amines can be used as suitable substrates and the desired reaction can proceed favourably in a highly chemoselective, efficient and atom-economical fashion. In particular, this protocol can also allow convenient access to bis(hydroxylmethylfurfuryl)-amines, a new group of furan-based monomers with great potential to form functional biopolymers with tunable properties. Moreover, this CO-assisted RA is more efficient (higher TON and TOF) and more eco-friendly (increased resource efficiency) than the previous state-of-the-art technique.

Full text of DOI:10.1039/c7gc01579h

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A Versatile CO-assisted Direct Reductive Amination of 5-
Hydroxymethylfurfural Catalyzed by Supported Gold†
Received 00th January 20xx,
Accepted 00th January 20xx
Ming-Ming Zhu, Lei Tao, Qi Zhang, Jing Dong, Yong-Mei Liu,* He-Yong He, and Yong Cao*
DOI: 10.1039/x0xx00000x
Reductive amination (RA) constitutes an attractive and practical strategy for discovering protocols capable of converting
biomass into valuable N-containing compounds. Described herein is a versatile and sustainable RA of 5-hydroxymethyl-
furfural (HMF), an important biomass-derived aldehyde, using abundant and cheaply available CO and water as reductant.
www.rsc.org/
2 2
A single phase rutile titania supported gold (Au/TiO -R) catalyst is shown to efficiently catalyze this CO/H O-mediated RA
under mild and convenient conditions. With this system, a broad spectrum of primary and secondary amines can be used
as suitable substrates and the desired reaction can proceed favorably in a highly chemoselective, efficient and atom-
economical fashion. In particular, this protocol can also allow convenient access to bis(hydroxylmethylfurfuryl)-amines, a
new group of furan-based monomers with great potential to form functional biopolymers with tunable properties.
Moreover, this CO-assisted RA is more efficient (higher TON and TOF) and more eco-friendly (increased resource efficiency)
than the previous state-of-the-art technique.
benign methods for the synthesis of aminoalkylfurans from readily
available starting materials has long been an active area of
Introduction
1
0
research. In this respect, utilization of bio-based feedstocks like 5-
hydroxymethylfurfural (HMF) derived from abundantly available
Depletion of readily available fossil fuel reserves and global climate
change concerns have prompted efforts to make chemical
production more benign and hence contribute to a more sustain-
11
non-edible lignocellulosic biomass could be an ideal option for
accessing this class of compounds. Indeed, several recent studies
have shown that it is possible to achieve an amino functionalization
1
able future. Compared to other alternative feedstock choices, the
production of chemicals from biorenewable resources, such as
biomass, has attracted increasing interests in recent years due to
the vast potential availability of lignocellulosic materials and the
versatility of adaptating existing technologies that potentially
enable the production of useful chemicals in commercial scales in a
1
4
0b
of HMF by reductive amination (RA) using NaBH
or molecular H2
1
2
as reducing agent. Despite these encouraging results, there are
still major incentives to develop alternative strategies capable of
facilitating more efficient and reliable RA, especially given that
2
fossil-dependent nature of H
is nowadays recognized as being a
2
shorter time frame. Owing to the inherently oxygen-rich nature of
1
3
less sustainable part of the biorefinery concept.
lignocellulosics, significant attention has been directed to processes
for converting bio-based feedstocks into a variety of oxygenates,
Driven by the huge potential of CO as a key intermediate in the
chemical industry, mainly as a C1 building block, there is a
continuous interest in the development of novel transformations
that can expand the utility of the existing methods for CO
valorization. Particularly given that CO is also a steel-work off-gas,
3
4
5
6
such as furfurals, diols, hexitols, ketones and various organic
7
acids, etc. In contrast, transformation of biomass into more value-
added N-containing compounds has remained largely under-
8
developed, despite the huge untapped potential to create novel
1
4
produced in multi-ton quantities, it represents an abundant and
functional molecules with unusual properties which might not be
achievable with the use of conventional fossil-based methods.
Aminofurans, in particular aminoalkylfuran derivatives, are key
structural units in many biologically active natural products and are
also an indispensible class of industrially sought-after compounds
known for their wide range of pharmacological activities (Scheme
9
1
). Therefore, the development of efficient and environmentally
Department of Chemistry, Shanghai Key Laboratory of Molecular Catalysis and
Innovative Materials, Fudan University, Shanghai 200433, P. R. China.
†
Electronic Supplementary Informaꢀon (ESI) available: [details of any
supplementary information available should be included here]. See
DOI: 10.1039/x0xx00000x
Scheme 1. Selected bioactive molecules incorporating aminoalkyl-furan core
structure.
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1
5
inexpensive source for large-scale chemical synthesis. We recently Table 1. Catalytic Reductive Amination of HMF with Aniline over Different
a
introduced an Au-CO/H
2
O reduction system where the transient Catalysts.
Au -H formed by the CO-induced H O reduction is believed to be
the key active species for a H -free reduction. This system per-
0
2
2
formed well in chemoselective reduction of substituted nitro and
carbonyl compounds as well as semireduction of alkynes under very
1
6
mild conditions. Following publication of our work, examples of
CO-assisted reduction or deoxygenation by other type of transition
b
Entry
Catalysts
Au/TiO -P25
Conv.
%]
Yield [%]
1
7
[
3a
4a
5
metal-based catalysts were also reported. Our continuing interest
in finding new application of this Au-CO/H O reduction system led
1
2
2
96
89
81
43
15
46
0
0
2
Au/TiO
Au/TiO
2
-A
us to investigate the possibilities offered by CO/H
obtain aminoalkylfurans from HMF.
2
O-assisted RA to
c
3
2
-A
95
>99
>99
>99
>99
>99
84
79
>99
>99
97
87
98
53
25
4
16
0
0
0
4
Au/TiO
Au/TiO
Au/TiO
Au/TiO
Au/TiO
2
-R
-R
-R
-R
-R
d
5
2
2
2
2
0
0
Results and discussion
e
6
3
0
Our initial investigations focused on using aniline (2a) as the
aminating reagent for direct RA of HMF showed that the suitable
choice of an underlying support material stands out as one of the
most important parameters that determine the conversion of
substrate and desired product selectivity over various gold-based
catalysts. A promising lead result was observed when using
f
7
0
13
0
g
8
2
9
Au/CeO
Au/ZrO
Au/Al O
2
31
54
74
66
76
70
0
10
2
79
0
1
1
1
2
2
3
78
0
2
commercial titania P25 supported gold catalyst (Au/TiO -P25, Figure
Au/SiO
2
68
1
0
S1 and S4), furnishing 81% of the desired amination product upon
13
HAuCl
4
76
0
0
o
reaction under 20 bar CO for 2.5 hours at 60 C (Table 1, entry 1). In
0
1
4
Au colloid
70
0
0
this case, 15% imine (4a) remained unreduced. Further
a
investigation revealed, however, that the use of phase pure anatase
Reaction conditions: 1 (0.5 mmol), 2a (0.5 mmol), catalysts (Au 0.5 mol%),
o
b
2
2
TiO as the supporting material was much less successful, providing MeOH-H O (1:1 v/v, 3 mL), CO (20 bar), 60 C, 2.5 h. GC-MS yields using
c
d
e
o
f
the expected RA product in only very moderate yields, even after an anisole as internal standard. 4 h. 60 bar CO, 1 h. 25 C, 22 h. 20 bar H2,
g
extended reaction time of 4 h under identical conditions (Table 1, 1.5 h. 10 mmol 1, 10 mmol 2a, MeOH:H O (1:1 v/v, 10 mL) Au/TiO -R (Au
2
2
entries 2 and 3). Nevertheless, to our delight, the related catalyst 0.05 mol%), 60 bar CO, 15 h.
compris- ing gold deposited on single phase rutile TiO (Au/TiO -R)
2
2
turned out to be much more efficient, furnishing the desired
aminated product in a near-quantitative yield under similar
conditions (Table 1, entry 4).
o
after approximately 2.5 h at 60 C, with 4a being the sole transient
intermediate. During the whole reaction process, the carbonyl
group of HMF remains unreduced, which highlights the robustness
and effectiveness of our protocol (Scheme 2). This is striking,
1
8
This is remarkable given that, on the themes described herein,
there had previously been no studies that could utilize only considering that a competitive reduction of the carbonyl group into
the corresponding alcohol is in fact an issue that has long plagued
equimolar amount of aminating reagent to accomplish the intended
1
0b,12a,18c,f
reaction.
Of yet further interest is that in this particular
1
00
case the specific activity based on HMF conversion is up to 79.2 mol
-1
-1
molAu h , which is over 2 times more active than the previously
1
2a
established homogeneous Ru-based catalytic systems.
quent study revealed that a binary solution system comprising 1:1
volumic ratio of methanol/H O was the optimal solvent for this
catalyst (Table S1). Control experiments lacking Au/TiO -R
catalyst, CO, or H O provided none of the desired adduct (Table S2).
Subse-
8
0
2
1
9
60
2
HMF (1)
Corresponding imine (4a)
Corresponding amine(3a)
2
Addi-tional investigation into the various reaction parameters
revealed that both CO pressure and temperature have a profound
influence on the reaction outcome. The reaction time can be greatly
shortened from 2.5 to 1 h as the PCO was raised from 20 to 60 bar
4
0
0
0
2
(
Table 1, entries 4 and 5). Of particular note is that, at a tempera-
o
ture as low as 25 C, the reaction can also proceed efficiently
without affecting 3a yield (Table 1, entry 6).
0
20
40
60
80
100
120
140
One scenario that deserves special mention is the beneficial
Time (min)
2
selectivity control of this Au-CO/H O-driven RA system capable of Figure 1. Reaction profile for aminoalkylfuran formation from HMF and
delivering the expected reaction product in an almost exclusive aniline. Reaction conditions: HMF (1) (0.5 mmol), aniline (2a) (0.5 mmol),
o
manner. As revealed in Figure 1, the conversion of HMF with MeOH-H O (1:1 v/v, 3 mL), Au/TiO -R (Au: 0.5 mol%), CO (20 bar), 60 C.
2
2
2
Au/TiO -R proceeds smoothly and reaches complete conversion
2
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transformation of 4a to 3a. We also tested other gold-based
0
precursors or materials such as HAuCl
particle size, ca. 50 nm, Figure S3), but all of them gave no 3a (Table
, entries 13 and 14). Herein it is important to point out that we did
4
and bulk Au colloid (mean
1
not observe any formation of humins when HAuCl
reaction, despite the notoriously unstable nature of HMF,
presumably due the presence of only minimal amount of HAuCl
4
was used in the
21
4
which can hardly influence the pH value of the reaction medium. It
is also revealed that neither the Pt, Pd, nor Ru catalysts were
effective for this reaction (Table S3). Taken together, these results
show that the combination of CO and Au NPs strongly associated
Scheme 2. Synthesis of aminoalkylfurans via direct RA of HMF with amines
assisted by CO.
2
with rutile TiO is essential for achieving a high catalytic activity for
2
0
traditional RA systems, thus leaving ample opportunities for
functional group manipulation via CO-assisted reductive chemistry.
This point is nicely illustrated by the fact that, when the reaction
selective RA of HMF and 2a into 3a under mild conditions.
A leaching test was performed to evaluate the potential
durability and to exclude the possible contribution of leached Au
2
was comparatively carried out by replacing CO with H under other-
2
species. When Au/TiO -R was removed from the reaction mixture
wise identical conditions, 2,5-bis-(hydroxylmethyl)furan (BHMF) (5)
is formed at appreciable levels even at low HMF conversion levels,
albeit with a much higher 3a formation rate (Figure S5; Table 1,
entry 7)
after 1 h, no extra products were detected by continuing this
reaction for another 1.5 h (Figure S6). The remaining solution was
checked by inductively coupled plasma-atomic emission spectro-
scopy (ICP-AES), and indeed there was no leaching of Au (see
Supporting Information). In addition, reusability tests confirmed
2
As a further illustration of the efficacy of this Au-CO/H O-
mediated RA catalysis, the use of lower Au loadings (S/C = 2000)
proved to be equally effective in the model reaction with aniline
2
that Au/TiO -R could be recovered and reused up to five times
without any appreciable loss of activity (Figure S7). The X-ray
diffraction (XRD) analysis displayed that both the fresh and used
(
Table 1, entry 8). Thus, in a gram-scale reaction of 1 and 2a (10
mmol scale up) for 15 h, 98% yield of 3a was obtained. Under the
2
Au/TiO -R catalysts showed the similar crystal phase, with no
aforementioned optimized conditions, some of the common
obvious distinguishing Au features being identified in these two
samples, suggesting that the Au particle sizes were quite small
2 2 2 3 2
supporting materials, such as CeO , ZrO , Al O and SiO (Table 1,
entries 9-12; Figure S1 and S2) can deliver appreciable conversion
of 1, despite their lack of sufficient capability to facilitate eventual
2 2
Figure 2. (a) and (b) TEM images and particle distribution of fresh and used Au/TiO -R; (c) and (d) XRD and XPS of fresh and used Au/TiO -R.
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0
.72% Au/TiO -R
biphasic P25 and anatase TiO supported Au. Taken together, these
2
2
0
.73% Au/TiO -P25
results unambiguously demonstrate that the present Au-catalyzed
2
0
.86% Au/CeO2
CO/H
water-gas-shift/4a-reduction pathway (Scheme S1) in which the
O-mediated 4a reduction may proceed via a sequential
2
0.68% Au/TiO -A
2
0
0
.76% Au/ZrO2
generation of transient Au -H species formed by CO-induced H
activation is the central step.
O
2
1.05% Au/Al O
2 3
0
.64% Au/SiO2
The preceding results highlight the distinct capability of Au/TiO2-
R in enabling a facile CO-assisted RA synthesis of 3a from 1 and 2a
via intermediacy of 4a，apparently due to an unusual and extra-
ordinary metal-support synergy that can markedly suppress the
undesired pathways and favor product formation under above-
mentioned conditions. At this point it is important to note that, in
1
7c
17d
the two related precedents to this work, Rh/C and Co Rh /C
2
2
5
0
100
150
200
250
300
350
400
were shown to be efficient catalysts for reductive transformation of
a set of carbonyl compounds by using carbon monoxide as a
deoxygenative agent. However, either a high CO pressure (50 bar)
and/or extended reaction times at elevated temperatures (up to 20
o
Temperature ( C)
Figure 3. CO/H
2
O-TPSR over various supported Au catalysts, Conditions: 100
o
-1
mg sample, 1% CO-3% H
2
O-He (20 mL·min-1), 5 C·min .
o
h at 160 C) was required to obtain high yields of the desired
(Figure 2c). The transmission electron microscopy (TEM) and X-ray
secondary or tertiary amines. Thus, the most distinctive aspect of
photoelectron spectroscopy (XPS) measurements further confirmed
the stable crystalline and electronic structure of Au (Figure 2a, 2b
and 2d). These results account for the remarkable durability of
the present Au/TiO -R catalyst system is that effective CO-mediated
2
direct RA can be readily achieved by using substantially milder
conditions compared with prior-art methods. Notably, the specific
Au/TiO
2
-R in the recycling test.
activity based on carbonyl conversion using Au/TiO -R catalyst is up
2
-1
-1
to 79.2 mol molAu
9 %), which is over 19 and 24 times more active than the
previously reported Rh/C and Co Rh /C catalytic systems.
h (corresponding to HMF conversion level ~
Having demonstrated the suitability of the present CO/H
2
O-
9
mediated approach for a practical and efficient HMF amination, we
sought to further elucidate the fundamental aspects underlying the
2
2
We next set out to expand the substrate scope of this Au-
Au-CO/H
a separate set of experiments that the direct conversion of HMF
and 2a to 4a in inert N atmosphere occurred at a much faster rate
than the reduction of 4a to 3a under otherwise identical conditions
Tables S4 and S5). These results indicate that the direct synthesis
2
O-driven phenomenon. In this respect, it was confirmed in
CO/H O-mediated RA process. As revealed in Table 2, various
2
structurally diverse anilines, regardless of the presence of electron-
withdrawing or donating functional groups, could be mono-
alkylated with HMF to give the corresponding secondary amines in
2
(
o
good to excellent yields at 60 C. It is important to note that this
of 3a would proceed through a series of consecutive steps in a
procedure tolerates the presence of halogens (3g-3k), thereby
permitting further transformations of the present HMF-derived
aminoarylfuran product using crosscoupling technologies. Addi-
tionally, a variety of nitrogen heterocycles that are frequently found
cascade mode, in which the rate-determining step must be the
CO/H
R in promoting this CO/H
by comparing the direct condensation of HMF with aniline as well
as the direct reduction of 4a with CO/H O for Au NPs deposited on
2
O-mediated reduction of 4a to 3a. The critical role of Au/TiO
2
-
2
O-mediated RA process is further clarified
23
in medicinally active agents, including a pyridine, and a pyrazole,
2
could be applied with this RA process and furnishing corresponding
amino-alkylfurans (3l, 3m) in 85-90% yields. Moreover, it was found
that aliphatic amines could also be effectively converted into their
corresponding secondary aminoalkylfurans with excellent selectivity
different supports (Tables S4 and S5), wherein it is revealed that all
relevant reactions, in particular the direct reduction of 4a with
CO/H
than that over other catalysts.
Essentially, these observations demonstrate the critical role of
Au/TiO -R in promoting the crucial imine reduction step for an
efficient CO/H O-mediated RA process. To gain an insight into the
origin of the enhanced CO-assisted direct RA activity achieved by
using rutile TiO as support, temperature-programmed surface
2
reaction (TPSR) in the presence of CO and H O (CO/H O-TPSR) has
2 2
O (Table S5) over Au/TiO -R occurred with much higher rates
(
3n, 3o), showcasing the generality of the current CO/H O-based
2
methodology for direct HMF amination. Contrastingly, previously
reported dichlorobis(2,9-dimethyl-1,10-phenanthroline) rutheni-
um(II) (Ru(DMP) Cl complex system is found to be totally inactive
2
2
2
2
for this substrate, owing to a strong coordination of the primary
12a
2
alkylamine groups to Ru(II) complex.
2
2
2
To further evaluate the potential of this Au-CO/H O-mediated RA
2
been investigated for Au deposited on several different supports.
Based on the results from Figure 3, the lower performance
reactions, we turned our attention toward tertiary amine formation
via direct amination of HMF with secondary amines, which are
challenging aminating agents compared with primary amines using
RA strategy because of the difficulty associated with the in-situ
formation and rapid hydrogenation of the relevant imine intermedi-
observed with Au/TiO
2
-A, Au/CeO
2
, Au/ZrO
2
, Au/Al
2
O
3
, and Au/SiO
2
2
0
can be rationalized by the fact that the rate of transient Au -H or H
formation catalyzed by these catalysts is significantly lower than
that over Au/TiO -R sample. This scenario is further reinforced by
the observation that the low temperature H production rate over
Au/TiO -R also occurred with much higher rate than those over
20b
2
ates. To the best of our knowledge, a heterogeneous catalytic
2
system capable of delivering RA with only equivalent amounts of
20b,24
2
secondary amines as aminating agents has so far been elusive.
4
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Table 2. Au-catalyzed Direct Reductive Amination of HMF with primary
a,b
amines
OH
OH
OH
OH
OH
O
O
HN
O
NH
COMe
O
O
NH
OMe
Scheme 3. CO-assisted one-pot synthesis of BHMFAs.
3
a, 99%
3b, 72%c
3c, 99%
Given the superb efficiency observed for Au/TiO -R toward HMF
2
OH
amination, we were thus prompted to check whether this CO/H O-
NH
O
NH
NH
2
driven Au catalysis would also allow the direct synthesis of bis-
(hydroxylmethylfurfuryl)amines (BHMFAs) from HMF by reacting
primary amines with two equivalents of HMF. Owing to their
attractive malleability and self-healing ability, BHMFAs has recently
been advocated as a new group of furan-based monomers that hold
great potential to form functional biopolymers with tunable
3
d, 62%
3e, 99%
3f, 99%
OH
OH
OH
OH
O
O
NH
F
O
NH
Cl
O
NH
Br
g, 98%c
3h, 91%c
3i, 78%c
3
OH
OH
N
NH
O
NH
O
HN
25
properties. We have performed a straightforward process that
Cl
Cl
subjects two equivalents of HMF to several typical primary amines
by adopting the above-mentioned RA procedure. The results
presented in Scheme 3 show that it is possible to achieve yield up to
j, 60%c
3k, 85%c
3l, 86%c
3
OH
OH
OH
N
N
O
HN
O
HN
O
NH
9
3% through this simple CO/H O-based procedure. In a precedent
2
study, Zhang and co-workers have demonstrated that a high yield
(ca. 90%) of BHMFAs can be attained from HMF and a number of
primary amines via a homogeneous ruthenium-catalyzed RA using
m, 89%c
n, 92%d, e
3o, 68%d, e
3
3
a
Reaction conditions: 1 (0.5 mmol), 2 (0.5 mmol), Au/ TiO
2
-R (Au 0.5mol%),
o
b
MeOH-H
2
O (1:1 v/v, 3 mL), CO (20 bar), at 60 C for 2.5 h. GC yields using
25
c
d
o
e
H as the hydrogen source. In addition to the lower process
2
anisole as the internal standard. 18 h. At 70 C for 8 h. Bi-N-alkylation
productivity, this homogeneous catalytic RA system necessitated
the addition of HMF in excess of that required to ensure the desired
reaction process as proceeded.
products were detected.
Table 3. Au-catalyzed Direct Reductive Amination of HMF with secondary
a,b
amines
Conclusions
In conclusion, we have successfully developed a facile and
2
environment-friendly CO/H O-driven RA approach that can
provide an effective means to access an array of aminoalkyl-
based furans, a valuable structure in medicinal and materials
chemistry, directly from biogenic HMF under very mild
conditions. This RA method, using only equimolar amount of
amines as aminating reagent and a robust and reusable gold
O
OH
OH
OH
OH
O
N
O
N
O
N
O
N
3r, 95%
3s, 87%d
catalyst with inexpensive and abundantly available CO and H O
2
3
p, 89% c
3q, 91% c
as the appealing reductant under mild conditions, would be
OH
OH
O
OH
useful for further applications in the synthesis of new bio-
based amines and is currently in progress.
O
N
N
O
N
OMe
3
t, 86%
3u, 97%
3v, 98%
a
Reaction conditions: 1 (0.5 mmol), 2 (0.5 mmol), Au/TiO
2
-R (Au 0.5 mol%),
o
b
Experiments
MeOH-H
2
O (1:1 v/v, 3 mL), CO (20 bar), at 60 C for 6 h. GC yields using
c
d
anisole as the internal standard. 5 h. 20 h.
General procedure for direct reductive amination of HMF with
amines: A mixture of HMF (0.5 mmol), amines (0.5 mmol),
To our delight, with the current heterogeneous Au-catalyzed RA supported metal catalysts (metal 0.5 mol%), anisole (0.5 mmol,
system, sec-benzylic amines as well as secondary anilines gave internal standard), methanol (1.5 mL) and water (1.5 mL) were
excellent yields for direct amination of HMF under mild conditions charged into a 25 mL Hastelloy-C high pressure Parr reactor. After
(
3t-3v). Remarkably, secondary aliphatic secondary amines also the reactor was sealed, the remaining air was purged by flushing
proved to be excellent aminating agents (3p, 3q). Under the present with CO five times. The reactor was pressured to 20 bar CO and
o
catalyst system, sterically more hindered heterocyclic amine can then heated to 60 C. The mixture of substrates and catalyst were
also be used as the aminating agent, and up to 95% (3r) and 87% stirred at a rate of 800 rpm for given reaction time. After
(
3s) yield were achieved when morpholine and tetrahydroquinoline completion of the reaction, the liquid products were separated by
were used as the aminating agents.
centrifugation and then analyzed on a Agilent 7820A gas
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chromatograph equipped with a capillary column HP-INNO Wax (30 1% CO-He through a water bubbler with a flow rate of 70 mL·min .
m × 0.32 mm × 0.25 µm) and flame ionization detector (FID) In each experiment, the catalyst was stabilized in 1% CO-3% H O-He
2
o
o
o
-1
detector. The identification of the products was performed by using for 20 min at 50 C before being heated up to 400 C at 5 C·min .
a GC-MS spectrometer. After that, the crude product was purified The effluent gas was analyzed by an on-line mass spectrometry.
by column chromatography [silica gel (300-400 mesh); petroleum
o
ether (60~90 C)/ethyl acetate mixture] to afford the pure product.
1
13
Acknowledgements
All the products were identified by H-NMR and C-NMR and the
spectra obtained were compared with the standard spectra (See
Supporting Information).
This work was supported by National Natural Science
Foundation of China (21473035, 91545108, 91645201),
Science & Technology Commission of Shanghai Municipality
Procedure for large-scale direct reductive amination of HMF with
aniline: A mixture of HMF (10 mmol), aniline (10 mmol), supported
metal catalysts (metal 0.05 mol%), anisole (10 mmol, internal
standard), methanol (5 mL) and water (5 mL) were charged into a
(
16ZR- 1440400), SINOPEC (X514005) and the Open project of
State Key Laboratory of Chemical Engineering (SKL-ChE-
5C02).
1
100 mL Hastelloy-C high pressure Parr reactor and stirred at a rate
of 800 rpm under 60 bar CO for 15 h. The mixture of substrates and Notes and references
catalyst were heated to the desired temperature in less than 15
minutes. After completion of the reaction, the liquid products were
separated by centrifugation. The conversion and yield were
determined by Agilent 7820A gas chromatograph equipped with a
HP-INNOWax column (30 m × 0.32 mm × 0.25 μm) and a flame
ionization detector (FID).
1
(a) J. J. Bozell and M. K. Patel, Feedstocks for the Future:
Renewables for the Production of Chemicals and Materials,
ACS Symposium Series, Washington, D. C., 2006. (b) A. D.
Sagar and S. Kartha, Annu Rev Environ Resour, 2007, 32, 131-
167. (c) J. H. Clark, R. Luque and A. S. Matharu, Annu Rev
Chem Biomol Eng, 2012, 3, 183-207. (d) J. C. Bergstrom and A.
Randall, Resource Economic: An Economic Approach to
Natural Resource and Environmental Policy, 4th end, EE
Press, UK, 2016.
Physicochemical characterization: The metal loading of the
catalysts was measured by inductively coupled plasma atomic
emission spectroscopy (ICP-AES) using a Thermo Electron IRIS
Intrepid II XSP spectrometer. The BET specific surface areas of the
prepared catalysts were determined by adsorption-desorption of
2
(a) A. Corma, S. Iborra and A. Veltly, Chem. Rev., 2007, 107
2
,
411-2502. (b) T. P. Vispute, H. Zhang, A. Sanna, R. Xiao and
G. W. Huber, Science, 2010, 330, 1222–1227. (c) M. Besson,
P. Gallezot and C. Pinel, Chem. Rev., 2014, 114, 1827-1870.
(a) Y. Nokagawa, M. Tamura and K. Tomishige, ACS Catal.,
nitrogen at liquid nitrogen temperature, using Micromeritics TriStar
3
4
o
2
2
013,
016,
3
, 2655-2668. (b) X. Li, P. Jia and T. Wang, ACS Catal.,
3
000 equipment. Sample degassing was carried out at 300 C prior
6
, 7621-7640.
to acquiring the adsorption isotherm. The crystal structures of
various catalysts were characterized with powder X-ray diffraction
(a) N. Perret, A. Grigoropoulos, M. Zanella, T. D. Manning, J.
B. Claridge and M. J. Rosseinsky, ChemSusChem 2016,
21-531. (b) B. Xiao, M. Zheng, X. Li, J. Pang, R. Sun, H. Wang,
X. Pang, A. Wang, X. Wang and T. Zhang, Green Chem. 2016,
, 2175-2184.
9
,
(XRD) on a Bruker D8 Advance X-ray diffractometer using the Ni-
5
filtered Cu Kα radiation source at 40 kV and 40 mA. The field
emission scanning electron microscopy (FESEM) measurements
were carried out on a Nova NanoSem 450 field-emission scanning
electron microscope, operated at 3 kV and using a TLD detector.
TEM images for various noble metal catalysts were taken with a
JEM 2011 electron microscope operating at 200 kV. Before being
transferred into the TEM chamber, the samples dispersed with
ethanol were deposited onto a carbon-coated copper grid and then
quickly moved into the vacuum evaporator. The size distribution of
the metal nanoparticles was determined by measuring about 120
random particles on the images. High-angle annular dark-field
scanning transmission electron microscopy (HAADF-STEM) images
were obtained on a Tecnai G2 F20 S-Twin electron microscope,
operated at 200 kV and using a HAADF detector. The XPS
measurements were performed with a Perkin Elmer PHI 5000C
spectrophotometer with Mg Κα radiation (1253.6 eV). The samples
were pressed into a pellet and transferred to a test chamber. The
spectra were collected with an analyzer pass energy of 23.5 eV and
1
8
5
6
(a) J. Gobers, S. Van de Vyver, K. Carpentier, K. de Blochouse,
P. Jacobs and B. Sels, Chem Commun., 2010, 46, 3577-3579.
(
b) J. Pang, A. Wang, M. Zheng, Y. Zhang, Y. Huang, X. Chen
and T. Zhang, Green Chem., 2012, 14, 614-617. (c) G. Liang, L.
He, H. Cheng, W. Li, X. Li, C. Zhang, Y. Yu and F. Zhao, J.
Catal., 2014, 309, 468-476.
(a) J. Ohyama, R. Kanao, A. Esaki and A. Satsuma, Chem.
Commun., 2014, 50, 5633-5636. (b) G. S. Zhang, M. M. Zhu, Q.
Zhang, Y. M. Liu, H. Y. He and Y. Cao, Green Chem., 2016, 18,
155-2164. (c) Z. Xu, P. Yan, H. Li, K. Liu, X. Liu, S. Jia and Z. C.
2
Zhang, ACS Catal., 2016, 6, 3784-3788. (d) W. P. Wu, Y. J. Xu,
R. Zhu, M. S. Cui, X. L. Li, J. Deng and Y. Fu, ChemSusChem,
016, , 1209-1215.
(a) X. Wan, C. Zhou, J. Chen, W. Deng, Q. Zhang, Y. Yang and
Y. Wang, ACS Catal., 2014, , 2175-2185. (b) C. Chan-Thaw, L.
E. Chinchilla, S. Campisi, G. A. Botton, L. Prati, N. Dimitratos,
A. Villa, ChemSusChem, 2015, , 4189-4194. (c) S. M. A. H.
2
9
7
8
4
8
Sissiki, A. S. Touchy, K. Kon, T. Toyao and K. Shimizu,
ChemCatChem, 2017, 10.1002/cctc.201700099
(a) X. L. Du, L. He, S. Zhao, Y. M. Liu, Y. Cao, H. Y. He and K. N.
Fan, Angew. Chem. Int. Ed., 2011, 50, 7815-7819. (b) Z. Chen,
H. Zeng, H. Gong, H. Wang and C. J. Li, Chem. Sci., 2015, 6,
4174-4178. (c) M. Chatterjee, T. Ishizaka and H. Kawanami,
Green Chem., 2016, 18, 487-496. (d) V. Froidevaux, C. Negrell,
S. Caillol, J. P. Pascault and B. Boutevin, Chem. Rev., 2016,
o
an electron takeoff angle of 45 . The vacuum in the test chamber
−9
was maintained below 10 Torr. The binding energies scale was
calibrated taking, as a reference, the adventitious C 1s peak at
2
84.6 eV. CO/H
750 instrument equipped with a mass spectrometer (OmniStar TM,
O-He) obtained by flowing
2
O-TPSR were run in a Micromeritics ChemiSorb
2
116, 14181-14224. (e) L. Tao, Z. J. Wang, T. H. Yan, Y. M. Liu,
H. Y. He and Y. Cao, ACS Catal., 2017, 7, 959-964. (f) G. Liang,
QMS 200). The gas mixture (1% CO-3% H
2
6
| Green Chem., 2012, 00, 1-3
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ARTICLE
A. Wang, L. Li, G. Xu, N. Yan and T. Zhang, Angew. Chem. Int.
Ed., 2017, 56, 3050-3054.
(a) B. J. Price, J. W. Clitherow and J. Bradshaw, US Pat., 4 128
Surkus, K. Junge and M. Beller, ChemCatChem, 2015, 7, 62-
64. (c) S. Lu, J. Peng, J. Wu, C. Li, X. Cao and H. Gu, Chem.
Commun., 2016, 52, 760-763. (d) Q. Zhang, S. S. Li, M. M. Zhu,
Y. M. Liu, H. Y. He, Y. Cao, Green Chem., 2016, 18, 2507-2513.
(e) B. Zhang, X. W. Guo, H. Liang, H. Ge, X. Gu, S. Chen, H.
9
6
1
3
58, 1978. (b) J. Copper and D. V. Lee, US Pat., 4 347 191,
982. (c) D. E. Bays, J. W. Clitherow and D. B. Judd, US Pat., 4
99 294, 1983. (d) J. W. Clitherow, US Pat., 4 497 961, 1985.
Yang and Y. Qin, ACS Catal., 2016, 6, 6560-6566.
(
e) L. De Vincentiis, US Pat., 4 634 701, 1987. (f) L. H. 21 K. I. Galkin, E. A. Krivodaeva, L. V. Romashov, S. S. Zalesskiy,
Schlager, US Pat., 5 017 586, 1991. (g) K. S. K. Murthy, G.
Weeratunga, B. K. Radatus and K. P. S. Sidhu, US Pat., 5 750
V. V. Kachala, J. V. Burykina and V. P. Ananikov, Angew.
Chem. Int. Ed. 2016, 55, 8338-8342.
22 N. Yi, R. Si, H. Saltsburg, and M. Flytzani-Stephanopoulos,
7
0 (a) N. Elming and N. C. Kaas, Acta Chem. Scand., 1956, 10
14, 1998.
1
1
,
Energy Environ. Sci., 2010,
3, 831-837.
603-1605. (b) A. Cukalovic and C. V. Stevens, Green Chem., 23 E. Vitaku, D. T. Smith and J. T. Njardarson, J. Med. Chem.,
1
2
Chem., 2011, 3, 3101-3102. (d) Z. L. Xu, P. Xing and B. Jiang, 24 (a) A. Robichaud and A. N. Ajjou, Tetrahedron Lett., 2006, 47,
010, 12, 1201-1206. (c) M. Mascal and S. Dutta, Green
2014, 57, 10257-10274.
Org. Lett., 2017, 19, 1028-1031.
3633-3636. (b) M. D. Bhor, M. J. Bhanushali, N. S. Nandurkar
and B. M. Bhanage, Tetrahedron Lett., 2008, 49, 965-969. (c)
A. Pagnoux-Ozherelyeva, N. Pannetier, M. D. Mbaye, S.
1 (a) Y. Román-Leshkov, J. N. Chheda and J. A. Dumesic,
Science, 2006, 312, 1933-1937. (b) H. Zhao, J. E. Holladay, H.
Brown and Z. C. Zhang, Science, 2007, 316, 1597-1600. (c) J.
B. Binder, R. T. Raines, J. Am. Chem. Soc., 2009, 131, 1979-
Gaillard and J.-L. Renaud, Angew. Chem. Int. Ed., 2012, 51
4976-4980. (d) D. B. Bagal, R. A. Watile, M. V. Khedkar, K. P.
,
1
985. (d) R. J. van Putten, J. C. van der Waal, E. de Jong, C. B.
Rasrendra, H. J. Heeres and J. G. de Vries, Chem. Rev., 2013,
13, 1499-1597.
2 (a) Z. Xu, P. Yan, W. Xu, S. Jia, Z. Xia, B. Chung and Z. C. Zhang,
RSC Adv., 2014, , 59083-59087. (b) G. Chieffi, M. Braun and
D. Esposito, ChemSusChem, 2015, , 3590-3594.
Dhake and B. M. Bhanage, Catal. Sci. Technol., 2012, 2, 354-
358.
1
25 Z. Xu, P. Yan, K. Liu, L. Wan, W. Xu, H. Li, X. Liu and Z. C.
9
1
1
Zhang, ChemSusChem, 2016,
, 1255-1258.
4
8
3 (a) L. Deng, J. Li, D. M. Lai, Y. Fu and Q. X. Guo, Angew. Chem.
Int. Ed., 2009, 48, 6529-6532. (b) J. Li, L. Liu, Y. Liu, M. Li, Y.
Zhu, H. Liu, Y. Kou, J. Zhang, Y. Han, D. Ma, Energy Environ.
Sci., 2014, 7, 393-398. (c) G. H. Wang, X. Deng, D. Gu, K. Chen,
H. Tüysüz, B. Spliethoff, H. J. Bongard, C. Weidenthaler, W.
Schmidt and F. Schüth, Angew. Chem. Int. Ed., 2016, 55
1
,
,
1101-11105.
4 B. P. Bhardwaj, Steel and Iron Handbook; NPCS, Delhi, 2014.
5 A. Ambrosi, S. E. Denmark, Angew. Chem. Int. Ed., 2016, 55
1
1
1
2164-12189.
1
6 (a) L. He, L. C. Wang, H. Sun, J. Ni, Y. Cao, H. Y. He and K. N.
Fan, Angew. Chem. Int. Ed., 2009, 48, 9538-9541. (b) L. He, F.
J. Yu, X. B. Lou, Y. Cao, H. Y. He and K. N. Fan, Chem.
Commun., 2010, 46, 1553-1555. (c) S. S. Li, X. Liu, Y. M. Liu, H.
Y. He and K. N. Fan, Y. Cao, Chem. Commun., 2014, 50, 5626-
5
628.
1
7 (a) Y. Mikami, A. Noujima, T. Mitsudome, T. Mizugaki, K.
Jitsukawa and K. Kaneda, Chem. Lett., 2010, 39, 223-225. (b)
Y. Mikami, A. Noujima, T. Mitsudome, T. Mizugaki, K.
Jitsukawa and K. Kaneda, Tetrahedron Lett., 2010, 51, 5466-
5468. (c) N. Z. Yagafarov, D. L. Usanov, A. P. Moskovets, N. D.
Kagramanov, V. I. Maleev and D. Chusov, ChemCatChem,
2
2
015,
015,
7
, 2590-2593. (d) J. W. Park and Y. K. Chung, ACS Catal.,
5, 4846-4850.
1
8 (a)R. P. Tripathi, S. S. Verma, J. Pandey and V. K. Tiwari,
Current Organic Chem, 2008, 12, 1093-1115. (b) B. S. Takale,
S. Tao, X. Yu, X. Feng, T. Jin, M. Bao and Y. Yamamoto,
Tetrahedron, 2015, 71, 7154-7158. (c) Q. Lei, Y. Wei, D.
Talwar, C. Wang, D. Xue and J. Xiao, Chem. Eur. J., 2013, 19,
021-4029. (d) J. Bariwal and E. Van der Eycken, Chem. Soc.
4
Rev., 2013, 42, 9283-9303. (e) R. Kumar, E. Gravel, A. Hagège,
H. Li, D. Verma, I. N. N. Namnoothiri and E. Doris,
ChemCatChem, 2013, 5, 3571-3575. (f) R. Ma, Y. B. Zhou, L. N.
He, Catal. Today, 2016, 274, 35-39. (g) R. J. Maya, S. Poulose,
J. John and R. L. Varma, Adv. Synth. Catal., 2017, 359, 1177-
1
1
184. (h) P. Zhou and Z. Zhang, ChemSusChem, 2017, 10,
892-1897.
1
2
9 It appears that the water-immiscibility of toluene and
hexane is responsible for the observed inferior performance,
although a detailed understanding of the specific solvent
effect require a further study in this respect.
0 (a) T. Gross, A. M. Seayad, M. Ahmad and M. Beller, Org.
Lett., 2002, 4, 2055-2058. (b) S. Pisiewicz, T. Stemmler, A. E.
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