Direct reductive amination of aldehydes with nitroarenes using bio-renewable formic acid as a hydrogen source

Article abstract of DOI:10.1039/c5gc02583d

Reductive amination (RA) is one of the most important transformations in organic chemistry. A versatile and sustainable gas-free RA of aldehydes carried out directly with cheaply available nitroarenes using stoichiometric amounts of non-toxic and entirely renewable formic acid (FA) as the terminal reductant is described herein. A single phase rutile titania supported gold (Au/TiO₂-R) catalyst is shown to catalyse efficiently this FA-based direct RA in neat water under mild reaction conditions. The broad scope, mild and neutral conditions, together with CO₂ and water as environmental harmless byproducts, make this transformation very useful. Moreover, straightforward examples of the direct construction of bioactive heterocyclic compounds containing a benzimidazole motif were achieved through this protocol.

Full text of DOI:10.1039/c5gc02583d

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Direct Reductive Amination of Aldehydes with Nitroarenes Using
Bio-renewable Formic Acid as a Hydrogen Source†
Received 00th January 20xx,
Accepted 00th January 20xx
Qi Zhang, Shu-Shuang Li, Ming-Ming Zhu, Yong-Mei Liu, He-Yong He, and Yong Cao*
Reductive amination (RA) is one of the most important transformations in organic chemistry. Described herein is a
versatile and sustainable gas-free RA of aldehydes directly with cheaply available nitroarenes using stoichiometric amount
of non-toxic and entirely renewable formic acid (FA) in as the terminal reductant. A single phase rutile titania supported
gold (Au/TiO2-R) catalyst is shown to catalyse efficiently this FA-based direct RA in neat water under mild conditions. The
broad scope, mild and neutral conditions, together with CO2 and water as environmental harmless byproducts, makes this
transformation very useful. Moreover, straightforward examples for direct construction of bioactive heterocyclic
compounds containing a benzimidazole motif were achieved through this protocol.
DOI: 10.1039/x0xx00000x
www.rsc.org/
catalytic methods offering more eco-friendly and operationally
simple reaction conditions is highly appreciated.
Introduction
Transfer hydrogenative DRA is obviously a compelling approach
The pursuit of sustainable chemistry has stimulated the developm-
ent of new strategies and technologies to access organic compou-
nds with higher values in a safe, compact and energy-efficient
manner. In this regard, the reduction of imines, which can be
formed in situ by the reaction of carbonyl compounds with amines,
offers an attractive access to higher functionalized amines, the
compounds that are of great interest for industrial applications.1
Although tremendous success has been achieved by the reductive
amination (RA) of aldehydes or ketones with amines,2 the develop-
pment of a novel catalytic system for the direct RA (DRA) from
stable and readily available substrates still remains a major challen-
ge. Considering that nitroarenes are cheap and readily available
organic compounds and the reduction of nitro groups is a common
method in preparing of amines,3 the DRA of carbonyl compounds
with nitroarenes in a domino fashion is an important alternative.
Such a reaction would be especially attractive given the use of
nitroarenes as more straightforward and flexible feedstocks as well
as the step economy as compared to traditional RA procedures.
Despite the evident potential of this particular DRA strategy, only a
few examples in dealing with DRA between nitroarenes and carbon-
yl compounds have appeared.4 Unfortunately, applications of these
procedures are constrained by their limited functional-group tolera-
nce, the need of organic solvents, as well as the potential explosion
hazards posed by the use of molecular hydrogen gas as the reduc-
ing agent. Furthermore, special handling of the air-sensitive or
pyrophoric Pd-based supported catalysts is required in most cases.
Therefore, the development of new efficient, mild and general
in this regard, in which the use of a reductant other than H2 allows
for reductions under ambient conditions, thus advantageously no
special high-pressure equipment is needed.5 This is of special intere-
st to organic synthesis as well as fine chemical production in batch
processes. Until recently, studies on transfer hydrogenative reduc-
tions have been mostly concentrated on the use of homogeneous
catalysis, with reductants ranging from Hantzsch esters2g, isopro-
panol5d and silanes5g to formic acid (FA)5h. FA is currently produced
industrially by hydrolysis of methyl formate and also easily accessi-
ble via CO2 hydrogenation.6 Particularly given that it is one of the
major by-products formed in biomass processing, its high energy
density, non-toxicity and excellent stability, FA represents an eco-
nomic, safe and easy-to-handle liquid hydrogen carrier for renew-
able energy storage.7 In this context, the DRA of nitroarenes using
green and versatile FA is exceedingly attractive, as it would repre-
sent a mild, one-step construction of higher amines from a mixture
of cheaply available compounds, which is of intense current interest
with regard to sustainable use of both renewable and non-
renewable natural resources. Even more appealing is the use of
stoichiometric amounts of FA for this reaction sequence, which
signifies a more atom-efficient utilization of the raw materials.
Despite these envisioned benefits, the implementation of such a
truly convenient and green approach for DRA of carbonyl compou-
nds with nitroarenes remains elusive, largely due to the lack of
efficient catalyst capable of suitably activating FA under transfer
hydrogenative conditions as well as the perceived problems of the
formation of multiple products.
In recent years, catalysts based on supported gold nanoparticles
(NPs) have emerged as new promising nitro reduction materials
owing to their high intrinsic selectivity toward the formation of the
desired amino compounds.8 This was initiated by Corma's discovery
that TiO2 supported gold NPs can deliver an exceptionally high level
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
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of selectivity control for the hydrogenation of nitroarenes in the appreciablelevels of DRA selectivity was achieved, thus furnishing
presence of other reducible functional groups.8a As a part of our the desired 3 in a yield of 76% (Table 1, entry 2).
effort in this area, we demonstrated the remarkable abilities of CO/
8c
H2O8b, HCOONH4 or HCOOH8d as alternative reducing agents for Table 1. The direct RA of benzaldehyde and nitrobenzene to N-benzyl-
Au-catalyzed nitro-to-amine reductions under ambient conditions. aniline. a
Meanwhile, from our continuing study on supported Au catalysis,
we have discovered that ZrO2 supported Au NPs can efficiently
catalyze the dehydrogenation of FA at temperatures as low as 25
oC.9 Given the prominent efficiency of the gold system for low tem-
Yield[b] [%]
perature FA activation, we became interested in exploring the Au-
FA-based reduction strategy for DRA with nitroarenes. Herein we
wish to report that chemoselective transfer hydrogenative DRA of
aldehydes with nitroarene derivatives can be carried out efficien-
tly in neat water in the presence of a single phase rutile titania
supported gold catalyst using FA as the hydrogen donor, and good
to excellent yields have been obtained for a range of substrates.
The present procedure possesses the following noteworthy featur-
es: (i) use of a robust and reusable heterogeneous catalyst, (ii) use
of entirely renewable and stoichiometric amount of FA as the
terminal reductant, (iii) use of water as a solvent and ease of phase-
separation of water-insoluble products in the work-up procedure,10
(iv) use of readily available starting materials, and (v) formation of
CO2 and water as environmental harmless byproducts.
T
[oC]
t
Conv.b
[%]
Entry
Catalysts
[h]
3
4
4
6
1
9
2
5
26
18
2
6
0
0
0
0
0
0
0
0
1
-
1
2
Au/ZrO2
Au/TiO2-P25
Au/TiO2-R
Au/TiO2-A
Au/TiO2-R
Au/CeO2
80
80
80
80
90
80
80
80
80
80
80
80
100
60
25
80
80
80
3
3
>99
>99
>99
>99
98
70
76
97
78
94
3
3
4
3
13
2
5c
20
3
6
89
27 15 47
68 10 22
7
Au/Al2O3
Au/C
3
>99
4
Results and discussion
8
3
1
1
1
2
-
2
2
-
We began our research by examining the DRA of benzaldehyde
(2) with equimolar amount of nitrobenzene (1) as a benchmark
system. In the first stage of our work, the experiments were carried
out in neat water at a metal loading of 1 mol%, by using 4
equivalents of FA and temperatures of 80 oC. We initially
investigated a zirconia supported gold catalyst system comprising
small Au NPs (approx. 1.8 nm) deposited on ZrO2 (Au/ZrO2), which
has been previously identified as a very efficient catalyst for low
temperature dehydro- genation of FA.9 However, we found that this
catalyst was not selec- tive for the formation of desired secondary
amine, N-benzylaniline (3). After 3 h of reaction, only ca. 70% of 1
can be converted into 3 (Table 1, entry 1). It is worth noting that
benzyl alcohol, one of the most unwanted by-products for metal-
catalyzed DRA reactions, was not observed in this case. Careful
analysis of the reaction products showed the formation of 26 % of
aniline (5) and 4% of imine inter- mediate N-
benzylidenebenzylamine (4) as the byproducts. Running the
reaction for extended periods did not produce an increase of the 3
formation (Table S1). Catalysts favouring the crucial imine
formation and its subsequent reduction would be highly beneficial.
We therefore examined a series of gold deposited on other mineral
supports such as Al2O3, CeO2, and activated carbon. The preparation
procedure for these catalysts and relevant characterization data are
provided in the Supporting Information. These catalysts, however,
can only deliver the desired 3 with an even lower selectivity in the
range of 1-68% (Table 1, entries 6-8). Interestingly, when applying a
commercial biphasic nanocrystalline titania (Evonik P25) supported
9
Pd/TiO2-R
Pt/TiO2-R
Ir/TiO2-R
Ru/TiO2-R
Au/TiO2-R
Au/TiO2-R
Au/TiO2-R
Au/TiO2-R
Au/TiO2-R
Au/TiO2-R
3
6
10
11
12
13
14
15d
16e
17f
18g
3
n.r.
n.r.
n.r.
>99
>99
>99
>99
91
-
3
-
-
-
-
3
-
-
-
-
1.5
6
92
95
94
96
8
4
5
1
0
1
1
3
0
0
0
0
0
28
16
3
3
24 33 34
3
>99
2
3
2
a Nitrobenzene (1 mmol), benzaldehyde (1 mmol), FA (4 mmol), H2O (5
mL), metal (1 mol%), N2 (1 atm). n.r. = no reaction. b Conversions (Conv.)
based on nitrobenzene, Conv. and yields determined by GC using n-
c
dodecane as the internal standard. Nitrobenzene (20 mmol), benzal-
dehyde (20 mmol), FA (80 mmol), water (10 mL), Au (0.05 mol%). d Au (4
mol%). Under air atmosphere. FA (3 mmol). g FA (6 mmol), 65% yield
e
f
of N-benzyl-N-phenylformamide was obtained.
With the aim to further improve the catalytic efficiency, we exa-
gold catalyst (Au/TiO2-P25, Au mean particle size ~ 2.2 nm), which mined an additional set of Au catalysts comprising gold NPs with
has been widely studied and proven to be highly effective for a identical average particle size (ca. 2 nm, see details in the Suppor-
variety of organic transformations including chemoselective nitro ting Information) supported on TiO2 with different polymorphic
reduction8b-c, alkyne semihydrogenaion11 and nitrile hydration12
,
structures. Much to our delight, when gold was deposited on single-
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phase rutile TiO2, the selectivity for 3 increased significantly. In con- unexpected, as the imine formation is thought to be greatly retard-
trast to the sample in which gold is loaded on single phase anatase ed upon the presence of a large excess of water.2f-g
(Au/TiO2-A), an excellent yield of 3 (97%) was obtained at 80 oC
after 3 h when using a Au/TiO2-R sample (Table 1, entry 3). These
results further confirm that the support material plays a key role in
the selectivity of this reaction. At this juncture, it should be
mentioned that the reaction with only various TiO2 supports or
unsupported Au NPs alone did not proceed at all (Table S2). Note
that Au/TiO2-R successfully promoted the DRA reaction even at
room temperature (entry 15), conditions under which other
supported metals, such as Pd, Pt, Ir and Ru, are totally inefficient
(entries 9-12). Remarkably, the Au loading could be decreased to
0.05 mol% without affecting the conversion (entry 5). Thus, in a
gram-scale reaction of 1 and 2 (20 mmol scale up) for 20 h, 94%
yield of 3 was obtained. In this case, no traces of N-formyl deriva-
tive (<0.5%), an unwanted by-product that usually formed in appre-
ciable levels with traditional FA-based protocols under mild conditi-
ons, are observed during the reaction. Furthermore, the recovered
Au/TiO2-R can also be reused at least five times without loss of
Figure 1. Reaction profile for N-benzylaniline formation from nitrobenzene
activity on this scale (Figure S1). The transmission electron micro-
and benzaldehyde. (■) conversion of nitrobenzene, (●) yield of N-benzyl-
scopy (TEM), X-ray photoelectron spectroscopy (XPS) and X-ray
aniline, (▲) yield of aniline, (▼) yield of N-benzylidenebenzylamine. Reacti-
diffraction (XRD) measurements revealed almost no change in the
on conditions: nitrobenzene (1 mmol), benzaldehyde (1 mmol), FA (4 mmol),
dispersion of the Au or metallic state of Au before and after reuse
water (5 mL), Au/TiO2-R (Au: 1 mol%), N2 (1 atm), 80oC.
(Figures S2-4). Moreover, by filtering off the Au/TiO2-R catalyst after
conducting the DRA reaction for 1 h, we observed no additional
To examine the DRA reaction performed with Au/TiO2-R in detail,
product during the next 2 h under the above conditions (Scheme
a kinetic experiment for the reaction of 1 with 2 was monitored by
S1), indicating that the heterogeneous reaction involves minimal
utilizing continuous sampling by gas chromatography. As can be se-
catalyst leaching and mechanisms entailing homogeneous reactions
en in Figure 1, 5 and 4 was initially formed followed by the formati-
are not likely operating.
on of 3. During the whole reaction process, the carbonyl group of
Significantly more interesting is the observation that this catalytic
benzaldehyde remains unaffected and the level of selectivity for 4
system can also afford near quantitative formation of 3 in an air
never exceed 20%. Furthermore, it was confirmed in separate exp-
atmosphere (Table 1, entry 16), thus offering a clear and compelling
eriments that the direct and complete conversion of 1 to 5 in the
advantages over existing methods to establish a more convenient
presence of 3 equiv. of FA occurred rapidly in the first 15 min, while
and viable FA-based DRA process. Encouraged by these promising
the hydrogenation of 4 readily proceeded to give 3 in 98% yield in 3
results, a more detailed study of the proposed process has been
h in the presence of 1 equiv. of FA as a hydrogen donor (Tables S4
carried out with the Au/TiO2-R catalyst. We confirmed in control ex-
and S6). These results indicate that the direct synthesis of 3 would
periments that the reaction did not proceed in the absence of a cat-
proceed through a series of consecutive steps in a cascade mode, in
alyst and the reaction practically did not occur when H2 was applied
which the initial step must be the transfer hydrogenation (TH) of 1
instead of FA as a reductant (Table S3). Meanwhile, analysis of the
to aniline. Then the aniline readily reacts with a starting carbonyl
headspace gases at the end of a typical reaction (Table 1, entry 3)
compound to form the corresponding imine, which is presumably
showed the mere presence of CO2. These results indicate that the
the rate-determining step of the overall process, followed by a final
present Au-mediated DRA catalysis is entirely a transfer hydrogena-
transfer hydrogenation to afford the corresponding secondary
tion process. A further indication that our process does not proceed
amine. To gain a deeper insight into the origin of the enhanced DRA
via in situ generation of H2 by FA decomposition came from the
performance achieved by using single-phase TiO2-R as support, the
observation that the sole FA decomposition did not occur to any
direct condensation of benzaldehyde with aniline in neat water as
practical degree in the absence of 1 and 2 (Table S3). Subsequent
well as the direct reduction of 1 with FA and direct RA of aniline and
investigation focused on the amount of FA revealed that a 4 equiva-
2 with FA has been investigated for Au NPs deposited on different
lents of FA was enough to obtain the optimal reaction activity. When
supports (Tables S4-5 and S7). It is revealed that all relevant
the reaction was conducted with three equivalents of FA, the conv-
reactions, in particular the direct condensation of benzaldehyde
ersion decreased and formation of more byproducts was observed
with aniline (Table S5) over Au/TiO2-R occurred with much higher
(entry 17). In contrast, significant formation of unwanted N-formyl
rates than that over other catalysts. To clarify the essential role of
derivatives resulting from a further formylation of 3 as the interme-
Au/TiO2-R in promoting the crucial direct condensation of benzalde-
diate was observed when 6 equiv. of FA were employed (Table 1,
hyde with aniline, we characterized the various supports by using
entry 18). The most interesting aspect, however, is that water was
NH3- and CO2-temperature-programmed desorption (NH3/CO2-TPD).
found to be the best solvent to promote the DRA efficiently, and
It is revealed in Figure S5 that TiO2-R shows a much lower abun-
lower yields were obtained inorganic solvents (Table S2). This is
dance of surface acidic and basic sites relative to other supports. It
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is therefore reasonable to conclude that an optimal cooperation examples, alphatic aldehydes (Table 2, entries 8-10) can also
between Au and TiO2-R, in which rutile TiO2 affords mild acid/base converted with aniline to form higher amines in high yields, albeit
sites and Au furnishes suitable TH activity, is essential to facilitate with a prolonged reaction time.
the desired DRA reaction in a domino fashion.13
The generality of this methodology has been extended to various
Building upon these results, we set out to examine the scope and substituted aromatic nitroarenes and benzaldehyde to produce
limitation of this Au-FA-mediated DRA reaction. We started by stud- corresponding secondary amines under mild reaction conditions.
ying the effect of substituents on the aromatic ring of the benzalde- Table 3 compiles the conversion and selectivity results obtained in
hyde substrate. As revealed in Table 2, various aldehydes were red- the reductive amination of benzaldehyde and different nitro- comp-
uctively aminated with nitrobenzene in the presence of 4 equiv. of ounds. The electronic effect on the aromatic ring was not
FA. The aldehydes used for this study included aromatic and alipha- significant; nitrobenzene substituted with electron-donating or -
tic examples. Irrespective of the electronic nature of the substitu- withdrawing groups could undergo reductive coupling to the
ent, aromatic aldehydes reacted smoothly to give the desired seco- corresponding sec- onddary amines with high yields (Table 3,
ndary amine products in excellent yields (Table 2, entries 2-6). For
entries 2-12). For instance,
Table 2. Catalytic synthesis of secondary amines from nitrobenzene and
different aldehydes. a
Table 3. Catalytic synthesis of secondary amines from benzaldehyde
and different nitroarenes. a
Entry
1
Aldehydes
T [h]
3
Conv. [%]b
>99
Yield [%]b
97 (94)
Entry
1
Nitroarenes
T [h]
3
Conv. [%] b
>99
Yield [%] b
97 (94)
2
3
3
4
>99
>99
96 (93)
97 (93)
2
3
4
5
6
4
4
5
4
5
>99
>99
>99
>99
>99
98 (95)
94 (92)
96 (92)
95 (90)
94 (91)
NO2
4
9
>99
95 (91)
5
6
6
5
>99
>99
95 (92)
94 (91)
7
8
9
5
8
9
>99
>99
>99
93 (90)
85 (82)
87 (85)
7
8
5
>99
98
94 (90)
86 (82)
10
10
11
>99
83 (80)
9
9
5
>99
>99
93 (90)
92 (88)
a Nitrobenzene (1 mmol), aldehyde (1 mmol), FA (4 mmol) , H2O (5 mL),
Au/TiO2-R (Au: 1 mol%), N2 (1 atm), 80oC.b Conv. and yields determined
by GC using n-dodecane as the internal standard. Numbers in
parentheses indicate yields of isolated products.
10
11
12
4
6
>99
>99
91 (87)
95 (92)
instance, mixing nitrobenzene with 4-methylbenzadlehyde, or 4-
chlorobenzaldehyde, in water at 80 oC for 4-5 h resulted in the
formation of the corresponding secondary amines in 98 and 96%
yields, respectively (Table 2, entries 2 and 4) and no dehalogenation
of the chloride group is observed. Substituted 4-hydroxy and 4-
methoxy-benzaldehydes also gave the corresponding products in
high yields (Table 2, entries 5 and 6). Notably, all the aromatic alde-
hydes generated the corresponding secondary amines as the prima-
ry products. Heteroaromatic aldehyde, furfural (Table 2, entry 7)
also underwent the DRA with nitrobenzene smoothly and gave the
corresponding secondary amine in good yield. As more challenging
a Nitro compound (1 mmol), benzaldehyde (1 mmol), FA (4 mmol), H2O
(5 mL), Au/TiO2-R (Au: 1 mol%), N2 (1 atm), 80oC. Conv. and yields
b
determined by GC using n-dodecane as the internal standard. Numbers
in parentheses indicate yields of isolated products.
coupling of benzaldehyde with p-methyl-nitrobenzene (Table 3,
entry 2) or 1-fluoro-4-nitrobenzene (Table 3, entry 5) gave desired
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secondary amines in excellent yields with 96 and 95%, respectively. chromatograph equipped with a HP-FFAP column (30 m × 0.25 mm)
Of note is that the reducible function groups such as alkene and ke- and a flame ionization detector (FID). After completing the reaction,
tone group were remained intact during the reduction of nitrobe- the resulting mixture was allowed to cool to room temperature. The
nzene (Table 3, entries 10 and 11). In the transformation of methyl- catalyst was collected by filtration. The filtrate was extracted with
nitrobenzene, the lower rate of o- and m-methyl relative to p- dichloromethane and washed with brine solution. The organic
analogues indicated a steric effect (Table 3, entries 2-4). Again, no phase was collected, dried with anhydrous Na2SO4, and
dehalogenation of the fluorine or chloride group is observed. concentrated by rotary-evaporation. The residue was purified by
Notably, all these results showed the high efficiency of the Au/TiO2- silica flash column chromatography with PE: EA as the eluent.
R-catalyzed RA of nitro compounds and benzaldehyde mixtures to
generate desired secondary amines.
Procedure for a gram-scale DRA of benzaldehyde with nitrobenze-
Last, we investigated the potential of this method to generate N- ne: Nitrobenzene (20 mmol), benzaldehyde (20 mmol), FA (80
heterocycles containing a benzimidazole motif, which are prevale- mmol, was added by peristaltic pump over the course of 15 h),
nt in natural products and pharmaceutical agents and are important water (10 mL), n-dodecane (5 mmol, as the internal standard) and
synthetic targets for drug discovery and development.14 We antici- the Au/TiO2-R catalyst (Au: 0.05 mol %) were placed into a three-
pated that the o-dinitroarene substrate could be employed to furn- necked round-bottom flask (150 mL capacity) fitted with a reflux
ish the desired N-heterocyclc ring construction. Gratifyingly, treat- condenser. The resulting mixture was vigorously stirred (1000 rpm)
ment of equimolar amount of o-dinitroarene (1.0 g, 6 mmol, 7) and at 90 °C under N2 atmosphere (1 atm) for 20 h. The conversion and
benzaldehyde (0.63 g, 6 mmol) with 6 equiv. of FA in the presence product selectivity were determined by Agilent 7820A gas chroma-
o
of 0.5 mol% Au/TiO2-R in water under 120 C for 6 h provided the tograph equipped with a HP-FFAP column (30 m × 0.25 mm) and a
2-phenylbenzimidazole product (8) in 87% isolated yield (Scheme 1). flame ionization detector (FID).
This appears to us to be the most efficient way for accessing this
type of compound, regarding cost, effectiveness, practicability and Recovery and reuse of Au/TiO2-R: The reused catalyst was
scalability. It is also worth noting that for the reaction illustrated in recovered by filtering the solid Au/TiO2-R catalyst from liquid phase
Scheme 1, the work-up simply involves a facile filtration of the after the reaction. The recovered catalyst was washed with ethanol
catalyst followed by direct separation of the organic phase of the fil- for several times. The catalyst was then dried under vacuum at
trate, due to the low solubility of benzimidazole in aqueous solution. room temperature overnight before the next recycle run.
Procedure for the synthesis of 2-phenylbenzimidazole: o-dinitro-
benzene (1.00 g, 6 mmol), benzaldehyde (0.63g, 6 mmol), FA (36
mmol), water (10 mL), n-dodecane (2mmol, as the internal
standard) and the Au/TiO2-R catalyst (Au: 0.5 mol %) were charged
Scheme 1. Gold-catalyzed one-pot reductive amination for the synthesis of
into a 50 mL Hastelloy-C high pressure Parr reactor and stirred at a
benzimidazole.
rate of 1000 rpm at 120 oC under air atmosphere for 6h. The
mixture was stirred for 15 min at room temperature before adding
Au/TiO2-R. The conversion and product selectivity were determined
Conclusions
by Agile- nt 7820A gas chromatograph equipped with a HP-FFAP
In summary, we have developed a new catalytic system for
column (30 m × 0.25 mm) and a flame ionization detector (FID).
DRA in water by using easily handled TiO2 supported gold NPs
After complet- ing the reaction, the mixture was allowed to cool to
as catalyst with renewable FA as a hydrogen source. This mild
room temper- ature. The catalyst was collected by filtration. The
and operationally easy amination employs cheaply available
filtrate was extra- cted with dichloromethane and washed with
nitroarenes and aldehydes, exhibits a broad substrate scope,
brine solution. The organic phase was collected, dried with
and liberates CO2 as the only byproduct. By saving energy and
anhydrous Na2SO4, and concentrated by rotary-evaporation. The
additional steps, our process illustrates the general potential
residue was purified by silica flash column chromatography with PE:
for conducting gas-free reductive condensation reactions in a
EA as the eluent.
less costly, simpler and greener manner.
Acknowledgements
Experiments
Financial support by National Natural Science Foundation of
General procedure for DRA of aldehydes with nitroarenes:
China (21273044, 21473035), the Research Fund for the Doct-
nitroarene (1 mmol), aldehyde (1 mmol), FA (4 mmol), water (5 mL),
oral Program of Higher Education (2012007000011), Science &
n-dodecane (1 mmol, as the internal standard) and the Au/TiO2-R
Technology Commission of Shanghai Municipality (08DZ2270-
catalyst (Au: 1 mol %) were placed into a three-necked round-
500, 12ZR1401500) and Hui-Chun Chin and Tsung-Dao Lee
bottom flask (50 mL capacity) fitted with a reflux condenser. The
Chinese Undergraduate Research Endowment (CURE) (13036)
resulting mixture was vigorously stirred (1000 rpm) at 80 °C under
is kindly acknowledged.
N2 atmosphere (1 atm) for given reaction time. The conversion and
product selectivity were determined by Agilent 7820A gas
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DOI: 10.1039/C5GC02583D
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6 | Green Chem., 2012, 00, 1-3
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