Ambient-Temperature Synthesis of Primary Amines via Reductive Amination of Carbonyl Compounds

Article abstract of DOI:10.1021/acscatal.0c01872

Efficient synthesis of primary amines via low-temperature reductive amination of carbonyl compounds using NH3 and H2 as the nitrogen and hydrogen resources is highly desired and challenging in the chemistry community. Herein, we employed naturally occurring phytic acid as a renewable precursor to fabricate titanium phosphate (TiP)-supported Ru nanocatalysts with different reduction degrees of RuO2 (Ru/TiP-x, x represents the reduction temperature) by combining ball milling and molten-salt processes. Very interestingly, the obtained Ru/TiP-100 had good catalytic performance for the reductive amination of carbonyl compounds at ambient temperature, resulting from the synergistic cooperation of the support (TiP) and the Ru/RuO2 with a suitable proportion of Ru0 (52%). Various carbonyl compounds could be efficiently converted into the corresponding primary amines with high yields. More importantly, the conversion of other substrates with reducible groups could also be achieved at ambient temperature. Detailed investigations indicated that the partially reduced Ru and the support (TiP) were indispensable. The high activity and selectivity of Ru/TiP-100 catalyst originates from the relatively high acidity and the suitable electron density of metallic Ru0.

Full text of DOI:10.1021/acscatal.0c01872

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Article
Ambient-Temperature Synthesis of Primary Amines
via Reductive Amination of Carbonyl Compounds
Chao Xie, Jinliang Song, Manli Hua, Yue Hu, Xin Huang, Haoran Wu, Guanying Yang, and Buxing Han
ACS Catal., Just Accepted Manuscript • DOI: 10.1021/acscatal.0c01872 • Publication Date (Web): 16 Jun 2020
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Ambient-Temperature Synthesis of Primary Amines
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via Reductive Amination of Carbonyl Compounds
Chao Xie,†,‡ Jinliang Song,*,†,§ Manli Hua,†,‡ Yue Hu,†,‡ Xin Huang,†,‡ Haoran Wu,†,‡ Guanying
Yang,†,§ and Buxing Han*,†,‡,§
†Beijing National Laboratory for Molecular Science, CAS Key Laboratory of Colloid and
Interface and Thermodynamics, CAS Research/Education Center for Excellence in Molecular
Sciences, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190, China.
‡School of Chemistry and Chemical Engineering, University of Chinese Academy of Sciences,
Beijing 100049, China.
§Physical Science Laboratory, Huairou National Comprehensive Science Center, Beijing 101400,
China.
KEYWORDS: Reductive amination, Ambient temperature, Primary amines, Carbonyl
compounds, Supported metal catalysts
ABSTRACT: Efficient synthesis of primary amines via low-temperature reductive amination of
carbonyl compounds using NH3 and H2 as the nitrogen and hydrogen resources is highly desired
and challenging in chemistry community. Herein, we employed naturally occurring phytic acid
as a renewable precursor to fabricate titanium phosphate (TiP)-supported Ru nanocatalysts with
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different reduction degrees of RuO2 (Ru/TiP-x, x represents the reduction temperature) by
combining ball milling and molten-salt processes. Very interestingly, the obtained Ru/TiP-100
had good catalytic performance for the reductive amination of carbonyl compounds at ambient
temperature, resulting from the synergistic cooperation of the support (TiP) and the Ru/RuO2
with suitable proportion of Ru0 (52%). Various carbonyl compounds could be efficiently
converted into the corresponding primary amines with high yields. More importantly, the
conversion of other substrates with reducible groups could also be achieved at ambient
temperature. Detail investigations indicated that the partially reduced Ru and the support (TiP)
were indispensable. The high activity and selectivity of Ru/TiP-100 catalyst is originated from
the relative high acidity and the suitable electron density of metallic Ru0.
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1. INTRODUCTION
Primary amines are very important compounds and are widely applied to produce fine chemicals,
agrochemicals, pharmaceuticals, and functionalized materials, etc.1-3 Synthesis of primary
amines is of central importance,4-8 and several synthetic methods have been developed, including
reductive amination of carbonyl compounds,9-12 N-alkylation of ammonia with haloalkanes13 or
alcohols,14-16 and reduction of specific nitrogen sources (e.g., oxime ethers,17 amides,18 nitriles,19
and nitro compounds20). Among these methods, reductive amination of carbonyl compounds
employing ammonia (NH3) and H2 as the nitrogen resource and reductant is the most attractive
route because carbonyl compounds, NH3 and H2 are all inexpensive and widely available raw
materials. Moreover, the reductive amination of carbonyl compounds can proceed at relatively
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mild conditions and water is the main byproduct. This makes reductive amination of carbonyl
compounds an atom-effective and environmental-friendly approach to produce primary amines.
Various catalysts, especially supported metals, have been developed for the synthesis of
primary amines via reductive amination of carbonyl compounds.21-28 For example, Ni@SiO2
(using NH3 and 2 MPa H2)21 and Ni/Al2O3 (using aqueous ammonia and 1 MPa H2)22 can
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catalyze reductive amination of carbonyl compounds at 120 and 80 C, respectively. MOF-
derived cobalt nanoparticles could efficiently catalyze the formation of primary amines via
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reductive amination using NH3 and 4 MPa H2 at 120 C.23 Moreover, reductive amination of
aldehydes/ketones could be carried out with aqueous NH3 and 2 MPa H2 over partially reduced
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Ru/ZrO2 at 65-125 C,24 and Ru/Nb2O5 could promote the reductive amination of carbonyl
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compounds using NH3 at 90 C and 4 MPa H2.25 It was also found that Pd0/enzymatic multiple
relay catalytic system showed good performance for the reductive amination of carbonyl
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compounds using HCO2NH4 at 80 C.26 Additionally, primary amines could be generated from
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reductive amination of carbonyl compounds over Cu/ZrO2 at 250 C,27 Pt-MoOx/TiO2 at 100
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oC,28 and Rh/Al2O3 at 80 C,29 etc. However, most of these processes require high reaction
temperature, and one great challenge in this area is to develop robust and efficient catalytic
systems that can perform reductive amination of carbonyl compounds at ambient temperature.
Herein, we developed a series of titanium phosphate-supported Ru nanocatalysts (denoted
as Ru/TiP-x, and x represents the reduction temperature), which employed naturally occurring
phytic acid as a renewable precursor. These Ru catalysts with different reduction degree of RuO2
were then systematically investigated for the reductive amination of carbonyl compounds to
produce primary amines using NH3 and H2 as the nitrogen and hydrogen resources. It was found
that the Ru/TiP-100 with a reduction degree of RuO2 of around 52% showed the highest activity
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and selectivity at ambient temperature, resulting from the desirable electron density of the
metallic Ru and the strong acidity of the titanium phosphate. The fact that this catalytic reaction
can be performed at ambient temperature with Ru-TiP-100 represents a major breakthrough in
this area. The synergistic cooperation between the active metal species and the support resulted
in its high activity; and the wide applicability of this catalyst to other substrates with other
reducible groups further confirms its great potential.
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2. METHODS
2.1. Materials. Ruthenium(III) chloride (99%), titanium(IV) n-butoxide (99%),
cyclohexanone (99%), cycloheptanone (99%), 2-pentanone (99%), 4-methyl-2-pentanone (99%),
3-pentanone (99%), 2-octanone (99%), 2-nonanone (99%), 4-phenyl-2-butanone (99%),
valeraldehyde (98.5%), n-octanal (98%), 3-phenylpropionaldehyde (95%), furfural (98%),
benzaldehyde (98%), 4-fluorobenzaldehyde (99%), 4-chlorobenzaldehyde (98%), 4-
bromobenzaldehyde (99%), p-anisaldehyde (99%), 3,4-dimethoxybenzaldehyde (99%), 4-tert-
butylbenzaldehyde (96%), 4-acetamidobenzaldehyde (98%) and methyl 4-formylbenzoate (99%)
were provided by J&K Scientific Ltd. Potassium nitrate (99+%), androsterone (97%) and
titanium(IV) oxide (98%) were obtained from Acros. Phytic acid (70+% aqueous solution),
methanol and acetone were purchased from Sinopharm Chemical Reagent Beijing Co. Ltd.
Cyclopentanone (99.5%), acetophenone (99%) and zirconium dioxide (99%) were purchased
from Alfa Aesar. Butyraldehyde (99%), citronellal (96%), 3-pyridinecarboxaldehyde (98%), 5-
hydroxymethylfurfural (98%) and Ru/C (5 wt%) were purchased from Innochem. 4-Formyl-
trans-stilbene (98%) was purchased from TCI.
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2.2. Preparation of RuO2/TiP and TiP. In a typical procedure for preparing RuO2/TiP,
phytic acid (1 mmol) and tetrabutyl titanate (3 mmol) were completely mixed with potassium
nitrate (15 g) by ball milling in a polyurethane tank (50 ml) with zirconia balls (3 mm×10 g and
8 mm×50 g) for 10 h, and the milling speed was 300 r min-1. After the above process, the milling
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tank was placed into an oven (80 C) for 12 h to evaporate the generated n-butyl alcohol. Then,
ruthenium trichloride (RuCl3, 1 mmol) was added, and the mixture was milled for another 24 h.
After the mixture was further dried at 80 °C in a vacuum oven to remove the small amount of
water and n-butyl alcohol, it was further milled for 6 h to ensure that RuCl3 was dispersed
uniformly. After that, the obtained solid was calcined in air at 400 °C for 2 h (5 °C min-1).
Finally, the product was thoroughly washed with hot deionized water to remove KNO3. The only
difference for the preparation of TiP was that the step for the addition of RuCl3 was omitted.
2.3. Preparation of Ru/TiP-x. RuO2/TiP was loaded into the reactor with methanol. After
sealing, 2 MPa H2 was charged and the reactor was put into a constant temperature air bath at
desired temperature for 2 h. Finally, Ru/TiP-x, where x represented the reduction temperature,
was recovered by centrifugation, and washed with methanol and ethyl ether (5 × 10 mL), then
finally dried at 60 oC under vacuum.
2.4. Preparation of Ru/TiO2, and Ru/ZrO2. The synthesis of Ru/ZrO2 and Ru/TiO2 are of
similar procedures and here we use Ru/ZrO2 as an example. In a typical procedure for preparing
Ru/ZrO2 (Ru 5 wt%), ZrO2 (0.5 g) was initially dispersed into an aqueous solution of RuCl3
under stirring and kept overnight. The solvent was slowly evaporated at 60 °C by the rotary
evaporation. Then, the solid was further dried at 80 °C for 12 h under vacuum, and subsequently
calcined at 300 °C for 2 h (5 °C min-1). Finally, the obtained sample was reduced at 150 oC under
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hydrogen flow for 2 h. Ru/TiO2 was also prepared according to this route by changing the
support from ZrO2 to TiO2.
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2.5. Typical procedures for the reductive amination of carbonyl compounds. In a
typical experiment, the desired carbonyl compound and catalyst were charged into a stainless
steel reactor with Teflon coating (14 mL inner volume). After the reactor was sealed, it was
purged with 0.2 MPa NH3 for three times to remove air residual. After that, the NH3 was charged
into the reactor to reach a desired pressure. Then, the reactor was further pressurized with H2.
Then the reactor was put into a constant temperature air bath at desired temperature, and the
magnetic stirrer was started. After a certain reaction time, the reactor was placed into ice water
and the gases in the reactor was released slowly through a cold trap containing methanol to
absorb the trace amounts of reactant and product. After depressurization, methanol in the cold
trap and internal standard n-butanol (cyclohexanol for the case with butyraldehyde as the
substrate) were added into the reactor. The reaction mixture was then analyzed quantitatively by
GC (Agilent 6820) equipped with a flame-ionized detector, and identification of the products
was done by GC-MS (Shimadzu QP2010).
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2.6. Reusability of the Ru/TiP-100. To examine the reusability of Ru/TiP-100, the catalyst
was recovered by centrifugation and washed with methanol and ethyl ether (5 × 10 mL). After
drying under vacuum at 60 °C for 12 h, the recovered catalyst was reused for the next cycle.
2.7. Characterization. The scanning electron microscopy (SEM) measurements were
performed on a Hitachi S-4800 scanning electron microscope operated at 15 kV. The
transmission electron microscopy (TEM) images were obtained using a TEM JEOL-1011 and
TEM JEOL-2100. Powder X-ray diffraction (XRD) patterns were collected on a Rigaku D/max-
2500 X-ray diffractometer using Cu Kα radiation (λ = 0.154 nm). Fourier transform infrared
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(FT-IR) spectra were recorded using a Bruker Tensor 27 spectrometer and the samples were
prepared by the KBr pellet method. The N2 adsorption-desorption isotherm was determined using
the Micromeritics ASAP 2020 msystem. X-ray photoelectron spectroscopy (XPS) measurements
were carried out on a ESCAL Lab 220i-XL specrometer. The content of Ru in the RuO2/TiP was
determined by inductively coupled plasma atomic emission spectroscopy (ICP-AES VISTA-
MPX). 31P MAS NMR measurements were carried out on Bruker AVIII 500WB. H2-TPR, NH3-
TPD and CO2-TPD were performed on Micromeritics’ AutoChem 2950 HP Chemisorption
Analyzer. AFM was performed on Dimension FASTSCANBIO. CO-DRIFT spectra were
collected on Bruker Tensor II spectroscope equipped with a MCT detector. The sample was
degassed at 300 °C for 2 h and then cooled to 25 °C in a Ar flow (10 mL min-1). Taking this as
the background, the sample was exposed to a 0.4% CO/Ar flow, and then purged in an Ar flow
(10 mL min-1) to remove physically adsorbed CO. IR spectra of chemisorbed CO were recorded
at 25 °C.
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3. RESULTS AND DISCUSSION
3.1. Preparation and Characterization of the RuO2/TiP. Titanium phosphate supported
RuO2 material (RuO2/TiP) was synthesized using naturally occurring phytic acid as the
renewable precursor through the combination of ball milling and molten-salt processes (Figure
S1), which were widely employed in the synthesis of nanomaterials.30-32 Power X-ray diffraction
(XRD) patterns (Figure 1A) showed that the prepared RuO2/TiP had low crystallinity with no
characteristic peaks of RuO2 species, indicating that the RuO2 species were highly dispersed
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without aggregation. In the P MAS NMR spectra, P signal for RuO2/TiP became broadened
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with a slight shift compared with that of phytic acid (Figure 1B), indicating the presence of
strong interaction between Ti4+ and the phosphate groups. Moreover, in FT-IR spectrum of
RuO2/TiP (Figure S2A), a sharp band around 1050 cm-1 corresponding to Ti-O-P stretching
vibrations was found, while this band was absent for TiO2, suggesting the presense of Ti-O-P
networks in RuO2/TiP.33,34 Additionally, Brunauer-Emmett-Teller (BET) surface area of
RuO2/TiP was 225.3 m2/g as calculated form the N2 adsorption-desorption isotherm (Figure
S2B).
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Figure 1. Characterization of the synthesized RuO2/TiP. (A) Powder XRD pattern, (B) 31P MAS
NMR spectra, (C,E) TEM image, (D) SEM images and (F) the size distribution of RuO2 particles
in the prepared RuO2/TiP.
Transmission electron microscopy (TEM) and scanning electron microscopy (SEM) images
clearly showed that the synthesized RuO2/TiP had a two-dimensional structure (Figures 1C and
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1D), and the thickness of RuO2/TiP nanosheets was around 2 nm as measured by AFM (Figure
S3). Meanwhile, RuO2 nanoparticles dispersed uniformly in the RuO2/TiP (Figure 1E) with the
particle sizes centered at 2 nm (Figure 1F), which was consistent with the results of XRD (Figure
1A). Elemental distribution mappings (Figure S4) indicated that Ti, O, P and Ru were dispersed
uniformly in RuO2/TiP. Additionally, H2-TPR (Figure S5) demonstrated that the RuO2/TiP could
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be reduced from 60 C, and the advantage of such low temperatures is that the reduction degree
of RuO2 can be easily controlled, and the reduction process does not affect the size distribution
of Ru species or the structure of the catalysts.
3.2. Activity of various catalysts. Ru-based catalysts are generally known to favor the
formation of primary amines by the reductive amination of carbonyl compounds, thus various
Ru-based catalysts were initially screened for the reductive amination of cyclohexanone to
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cyclohexylamine as a model reaction at 30 C (Table 1). In the absence of any catalysts, no
cyclohexylamine was detected (Table 1, entry 1). The synthesized RuO2/TiP with 3.35 wt% Ru
(from ICP-AES) was found inactive for the formation of cyclohexylamine (Table 1, entry 2). In
contrast, cyclohexylamine was generated over Ru/TiP-80 (Table 1, entry 3), indicating the key
role of metallic Ru in this catalytic reaction. It has been reported that the reduction degree of
RuO2 in the Ru/ZrO2 catalysts could greatly affect their activity and selectivity of reductive
amination.24 Therefore, we carried out the reduction of the obtained RuO2/TiP at different
temperature and time to control the reduction degree of RuO2, which shows key influences to the
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catalytic activity (Figures 2A and 2B) as discussed in the following section. At 30 C, the
Ru/TiP-100 with a RuO2 reduction degree of 52% (Table 1, entry 4) showed better performance
than Ru/TiP-80 (44% reduction degree, Table 1, entry 3), and the yield of cyclohexylamine
could reach 97% over the Ru/TiP-100 with a complete conversion of cyclohexanone. When the
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reaction was conducted at 30 C over Ru/TiP-150 (55% reduction degree), the cyclohexylamine
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yield slightly decreased with more cyclohexanol generated (Table 1, entry 5). Negligible
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cyclohexylamine was detected when the reaction was carried out at 30 C with Ru/TiP-150-30h
(67% reduction degree, Table 1, entry 6), and higher reaction temperature (80 oC) was needed to
achieve a good yield of cyclohexylamine (91%) with a reaction time of 6 h (Table 1, entry 7). In
comparison, we examined the activity of Ru/TiO2 (with a RuO2 reduction degree of 53%) and
the reported Ru/ZrO2-150 (with a RuO2 reduction degree of 49%) under our reaction conditions
(Table 1, entries 8 and 9), but poor performance was achieved. Ru/ZrO2-150 was efficient but
only at higher reaction temperature (95 oC),24 suggesting that the support material was also a key
factor for the performance of the catalysts. Additionally, commercial Ru/C catalyst (Table 1,
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entries 10 and 11) also required high temperature (80 C) and longer reaction time (24 h) to
achieve a relative high yield of cyclohexylamine (82%) with the formation of more cyclohexanol
(about 16%). The above results indicated that the Ru/TiP-100 was the only effecient catalyst at
ambient temperture for the conversion of cyclohexanone to cyclohexylamine.
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Table 1. Activity of various catalysts for reductive amination of cyclohexanone.a
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OH
NH
NH2
O
H
N
N
D
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8
9
+
NH3
+
+
+
+ H2
+
A
B
C
E
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Yield (%)
C
Entry
Catalyst
Conversion (%)
A
B
D
E
1
2
3
4
Blank
85
83
0
0
0
0
2
2
4
1
9
0
0
0
81
80
0
0
0
33
0
54
58
73
0
0
0
0
0
0
0
0
0
0
0
0
0
0
RuO2/TiP
Ru/TiP-80
Ru/TiP-100
Ru/TiP-150
Ru/TiP-150-30h
Ru/TiP-150-30h
Ru/TiO2
Ru/ZrO2
Ru/C
Ru/C
>99
>99
>99
71
>99
93
90
90
>99
10
97
96
<1
91
<1
<1
0
83
<1
0
34
0
36
27
14
2
5
6b
7c
8d
9e
10
11f
82
16
aReaction conditions: cyclohexanone, 1 mmol; methanol, 2 mL; H2, 1.4 MPa; NH3, 0.6 MPa;
catalyst, 0.2 mol%; 30 oC; 6 h. The Ru loading in RuO2/TiP-x, Ru/TiO2, Ru/ZrO2, and Ru/C was
3.35, 4.86, 5.04, and 5 wt%, respectively. The reduction time for RuO2/TiP was 30 h. The
b
c
o
d
reaction was conducted at 80 C. The reduction degree of RuO2 in Ru/TiO2 was controlled at
53%. eThe catalyst was prepared based on reference 24. fThe reaction was conducted at 80 oC for
24 h.
3.3. Effect of H2/NH3 Ratio on the Reaction Activity and Selectivity. H2/NH3 ratio is
another key factor in determining the selectivity of cyclohexylamine over Ru/TiP-100 catalyst
(Figure 2C), and the best H2/NH3 ratio was found to be 7/3. Lowering or rising H2/NH3 ratio was
found to suppress the subsequent conversion of the formed Schiff base to the desired primary
amine. In another aspect, more cyclohexanol would be generated from the direct hydrogenation
of cyclohexanone with excess H2.
3.4. Reusability of Ru/TiP-100. As important properties of a heterogeneous catalyst, the
reusability and the heterogeneous nature of Ru/TiP-100 were evaluated as these are the crucial.
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Ru/TiP-100 could be recycled for at least 5 times without decline of the catalytic activity and
product selectivity (Figure 2B). Moreover, no obvious change was observed between the virgin
and recovered Ru/TiP-100 as characterized by SEM, TEM and XPS (Figure S6), further
confirms the high stability of Ru/TiP-100. Additionally, the yield of cyclohexylamine plateaued
after Ru/TiP-100 was removed from the reaction system after 3 h (Figure S7), and no Ru species
were detected by ICP examination. These results firmly verified the heterogeneous nature of
Ru/TiP-100.
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Figure 2. (A) Effect of reduction temperature for RuO2/TiP, (B) Reduction degree of RuO2/TiP
in Ru/TiP-x detected by XPS, (C) Effect of NH3 pressure, and (D) Reusability of Ru/TiP-100.
o
Reaction conditions: cyclohexanone, 1 mmol; methanol, 2 mL; 30 C; 6 h; Ru/TiP-100, 0.2
mol%; Total pressure of NH3 and H2 was 2 MPa, and 1.4 MPa H2 and 0.6 MPa NH3 in D.
3.5. Scope of the substrates. Encouraged by the good performance of Ru/TiP-100 for the
reductive amination of cyclohexanone, the reductive amination of other ketones was explored
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over Ru/TiP-100 (Table 2). In our catalytic system, all examined alkyl ketones (Table 2, entries
1-8) could be efficiently converted into the corresponding primary amines with good yields at 30
oC. Although the reactivity of aryl ketone (acetophenone) was very poor at 30 oC because of the
electronic and steric effect of phenyl group (Table 2, entry 9), a satisfactory yield (93%) of the
desired product could be achieved (Table 2, entry 10) by increasing the temperature (80 oC) and
lowering the H2 pressure (0.4 MPa H2 in a total pressure of 1 MPa).
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Table 2. Reductive amination of various ketones over Ru/TiP-100.a
Entry
1
Ketone
Product
Time (h)
10
Yield (%)
92
O
NH2
O
NH2
2
3
6
97
95
O
NH2
10
O
NH2
NH2
NH2
NH2
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10
96
97
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94
O
O
O
O
NH2
8
15
24
24
98
<1
93
O
O
NH2
NH2
9
10b
aReaction conditions: ketone, 1 mmol; methanol, 2 mL; H2, 1.4 MPa; NH3, 0.6 MPa;
o
b
o
Ru/TiP-100 (the Ru loading was 3.35 wt% Ru), 0.2 mol%; 30 C. 80 C; NH3, 0.6 MPa;
H2, 0.4 MPa.
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In comparison with ketones, the reductive amination of aldehydes to primary amines with
high selectivity is more challenging because of their higher reactivity. To our delight, Ru/TiP-
100 even showed high activity and selectivity for reductive amination of various aldehydes with
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a suitable NH3/H2 ratio (1.7 MPa H2 and 0.3 MPa NH3 at a total pressure of 2 MPa) at 30 C
(Table 3), and the corresponding primary amines could be generated with high selectivity. In
addition, it was demonstrated that Ru/TiP-100 showed much better performance under lower
reaction temperature (30 oC) and H2 pressure (< 2 MPa) than the typical reported catalysts (Table
S1). These results further indicated the good performance of Ru/TiP-100 for the reductive
amination of various carbonyl compounds.
Table 3. Reductive amination of various aldehydes over Ru/TiP-100.a
Entry
Aldehyde
Product
Time (h) Yield (%)
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2
3
15
15
15
96
94
96
NH2
O
NH2
O
NH2
O
NH2
O
4
5
6
7
24
24
15
20
92
91
96
97
O
O
NH2
O
NH2
O
N
O
N
NH2
aReaction conditions: aldehyde, 1 mmol; methanol, 2 mL; H2, 1.7 MPa; NH3, 0.3 MPa; Ru/TiP-
100 (the Ru loading was 3.35 wt% Ru), 0.2 mol%; 30 oC.
More importantly, the aryl aldehydes with reduction-sensitive substituents, including
halogen (Table 4, entries 1-3), methoxy (Table 4, entries 4-5), acetamido (Table 4, entry 6), ester
(Table 4, entry 7), nitrile (Table 4, entry 8), and ethylene (Table 4, entries 9-10) groups, could all
be converted into the desired primary amines at high yields, and those reducible groups remained
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intact. In addition, 5-hydroxymethylfurfural (a biomass platform molecule) and androsterone (a
bio-active molecule) could also be transformed into the corresponding primary amines with high
yields of 93% and 92%, respectively (Table 4, entries 11 and 12). These results further
highlighted the unique advantage of applying ambient temperature reaction condition with those
substrates that possess h reduction-sensitive substituents.
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Table 4. Reductive Amination of Various Challenging Substrates over Ru/TiP-100.a
Entry
Aldehyde
Product
Time (h)
Yield (%)
NH2
NH2
NH2
NH2
O
1
2
3
4
24
24
24
15
92
90
86
92
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O
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Br
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NH2
O
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91
84
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O
NH2
O
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NH2
O
O
O
O
7
8
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83
93
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NH2
O
NC
NC
9
15
24
89
O
NH2
NH2
O
10
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O
NH2
O
O
HO
HO
11
24
24
93
5
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7
8
O
NH2
12b
92c
HO
HO
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aReaction conditions: ketone, 1 mmol; methanol, 2 mL; H2, 1.4 MPa; NH3, 0.6 MPa; Ru/TiP-
100 (the Ru loading was 3.35 wt% Ru), 0.2 mol%; 30 oC.bH2, 1.4 MPa; NH3, 0.6 MPa. cIsolated
yields, and the isolation method was based on reference 21.
3.6. Reasons for the High Activity of the Ru/TiP-100. As discussed above, Ru/TiP-100
showed much better activity and selectivity than Ru/C and Ru/TiO2 (Table 1). As examined by
XPS, the binding energy of Ru 3d (for Ru0, 280.94 eV) in Ru/TiP-100 was much lower than
those in Ru/TiO2 and Ru/C (Figure S8), indicating that the Ru0 in Ru/TiP-100 was more
negatively charged, which favors the formation of active H on the metallic Ru for the
hydrogenation steps (Figure S9). Furthermore, in situ CO-DRIFT measurements were performed
to determine the electronic property of the Ru species in Ru/TiP-100 and Ru/TiO2. As shown in
Figure 3, the band of the CO that was adsorbed on the metallic Ru (Ru-CO) of Ru/TiP-100
showed an obvious red shift in comparison to the one that was adsorbed on the metallic Ru in
Ru/TiO2. The red shift of the CO adsorption band strongly suggested the increased electron
density of the metallic Ru in Ru/TiP-100 compared with that in Ru/TiO2, which was consistent
with the XPS results (Figure S8). These results indicated that TiP was a better electron-donating
support than TiO2, which was probably caused by the higher basicity of TiP than TiO2 as the
basic support was generally recognized to favor the transfer of electron from support to the
supported metals.25,35,36 Based on the results of CO2-TPD (Figure S10), Ru/TiP-100 indeed
possesses much larger amount of basic sites with higher strength than Ru/TiO2. Therefore, it
could be concluded that the metallic Ru mainly interacted with the basic sites in the Ru/TiP-100,
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and thus, the electron density of metallic Ru in Ru/TiP-100 was higher than that in Ru/TiO2. This
phenomenon was probably caused by the electronic metal-support interaction (EMSI) between
the Ru species and basic sites of the TiP support in the Ru/TiP-100.37-41 The results above
elucidated the key role of the TiP support as the electron donor to significantly increase the
electron density of Ru species (both metallic Ru and RuO2), which facilitates the activation of H2
in the hydrogenation steps (Figure S9).
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Figure 3. In situ DRIFT spectra of CO adsorbed on Ru/TiP-100 and Ru/TiO2.
In another aspect, the reduction temperature of RuO2/TiP showed strong impact on the
reaction activity and product distribution (Figure 2A). Clearly, higher reduction temperature
would lead to an increased reduction degree of RuO2 to metallic Ru0 in RuO2/TiP, as confirmed
by XPS (Figure 2B and Figure 4). It is widely acknowledged that the metallic Ru sites can
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facilitate the hydrogenation steps (Figure S9), and thus, Ru/TiP-100 showed much better
performance than RuO2/TiP (without metallic Ru0) and Ru/TiP-80. However, with excess
metallic Ru0 in the catalyst (e.g., Ru/TiP-150), the selectivity of the desired primary amines
would decrease, and with extended reduction time, the desired product is not even formed (e.g.,
Ru/TiP-150-30h). It is commonly accepted that the different electronic state of the Ru species
plays a crucial role on the catalytic behaviour of the Ru/TiP-x. As determined by XPS (Figure 4),
the binding energy of Ru 3d became lower with the increasing reduction temperature, suggesting
the formation of more negatively charged Ru0 (higher electron density) at higher reduction
temperature.42,43 The higher electron density of Ru0 was beneficial for the formation of the active
H on Ru for hydrogenation of imines and Schiff bases (Figure S9). However, when the electron
density of Ru0 is overly high, strong adsorption of imines and Schiff bases occurs, especially at
30 oC, owing to the strong eletrophilicity of imines and Schiff base.44-47 This results in the lower
ability of their subsequent hydrogenation to form the desired primary amines, which could be the
main reason that Ru/TiP-150-30h needed higher reaction temperature (80 oC, Table 1, entry 7) to
desorb the imines and Schiff bases and to release the active hydrogenation sites, so that a good
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yield of primary amines can be achieved at 80 C. The above results imply that the catalytic
performance of Ru/TiP-x was significantly affected by its proportion of metallic Ru and RuO2, to
reach an optimised electron density of Ru0 for activation of H2 and desorption of intermediates
(imines and Schiff bases). Therefore, Ru/TiP-100 showed the best performance among the
Ru/TiP-x owing to its suitable amount of Ru0 (around 52%).
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Figure 4. XPS spectra of Ru 3d in RuO2/TiP and Ru/TiP-x.
Additionally, it should be pointed out that the acidity of Ru/TiP-100 (from the NH3-TPD
results in Figure S11) was much higher than those of Ru/TiO2 and the reported Ru/ZrO2.24
Higher acidity was beneficial to the activation of the C=N groups in the in situ generated imines
and Schiff bases via the interaction between the acidic sites and the N atom of the corresponding
C=N bonds (Figure S12),48,49 thus aided the reaction to occurr at low temperature.
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The results above indicated that the combination of the support TiP and the Ru species
(Ru0/RuO2) with suitable Ru0 proportion contributed to the good performance of Ru/TiP-100.
First, TiP could significantly increase the electron density of Ru0 in Ru/TiP-100 via EMSI effect
(Figure 3), which was beneficial to the activation of H2 in the hydrogention step (Figure S9) in
the catalytic cycle. Meanwhile, the strong acidic property of TiP results in the high acidity of
Ru/TiP-100 (Figure S11), and higher acidity could activate the C=N bonds in the in situ
generated imines and Schiff bases for their subsequent conversion to the desired products.49
Therefore, TiP was a better support than TiO2 and ZrO2. Secondly, the suitable reduction degree
of RuO2 could ensure the ample Ru0 for H2 activation and control the electron density of Ru0 to a
suitable degree for the desorption of intermediates (imines and Schiff bases), which both affected
the catalytic performance. Therefore, RuO2 of suitable amount played a key role in tuning the
electron density of Ru0. On the basis of the above discussion, both the support material and the
Ru species affected the catalytic activity significantly, and in Ru/TiP-100, TiP (strong acidity
and EMSI effect) and Ru0/RuO2 with suitable Ru0 proportion cooperated nicely to promote the
reductive amination at ambient temperature.
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3.7 Mechanism Discussion. To investigate the mechanism of the catalytic reaction
mechanism, the dependence of product distribution on time was studied in detail by employing
reductive amination of cyclohexanone as an example. As shown in Figure 5, most of
cyclohexanone were rapidly consumed in 1 h to form imine and Schiff base. No
cyclohexylamine (the desired product) was detected in the first hour because the formed
cyclohexylamine from imine hydrogenation could easily react with cyclohexanone to generate
Schiff base. Cyclohexylamine began to form when most of cyclohexanone was converted after
1.5 h. Finally, cyclohexylamine was generated from the conversion of both imine and Schiff
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base. In the reaction process, nearly no cyclohexanol was detected because the imine formed
much more quickly, which resulted in the rapid conversion of cyclohexanone with NH3, and thus
decreased the direct hydrogenation of cyclohexanone to a large extent. Moreover, control
experiments using Schiff base as the reactant over Ru/TiP-100 (Figure S13) indicated that the
primary amine was yielded in the presence of NH3, while the secondary amine was formed
without NH3. These results further clearly explained the absense of secondary amine in the entire
reaction process. Additionally, when using aldehydes as the substrates, the formed imines would
be converted into imidazolines (a potential by-product, Figure S14) at a very low yield.
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Figure 5. Time-Yield plots. Reaction conditions: cyclohexanone, 1 mmol; methanol, 2 mL; 30
oC; Ru/TiP-100 (the Ru loading was 3.35 wt% Ru), 0.2 mol%; 1.4 MPa H2 and 0.6 MPa NH3.
On the basis of the above discussion and some reported knowledges,23-25,50 a reasonable
mechanism was proposed for the reductive amination of carbonyl compounds to primary amines
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using NH3 and H2 over Ru/TiP-100 (Figure 6). Initially, imines were rapidly generated from the
condensation of carbonyl group and NH3 even in the absence of any catalysts. Subsequently, the
formed imines were hydrogenated over Ru/TiP-100 to produce primary amines (desired
products), which could rapidly react with the unreacted carbonyl compounds to form Schiff
bases. Finally, in the presence of NH3, the generated Schiff bases were further converted into the
desired primary amines over Ru/TiP-100.
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Figure 6. A proposed mechanism for the reductive amination of carbonyl compounds to primary
amines using NH3 and H2 over Ru/TiP-100.
4. CONCLUSIONS
In conclusion, various primary amines were successfully synthesized from the reductive
amination of carbonyl compounds using NH3 and H2 as the nitrogen and hydrogen resources
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over Ru nanocatalysts on titanium phosphate at ambient temperature. The properties of both Ru
species (Ru/RuO2) and the support materials had strong impacts on the reaction activity and
selectivity, and Ru/TiP-100 provided the best performance owing to the combination of TiP and
Ru/RuO2 with suitable proportion of Ru0 (52%). Detailed study indicated that the moderating
effect of RuO2 and the electronic metal-support interaction resulted in the suitable electron
density of Ru species, which could balance the activation of H2 for the hydrogenation steps and
the desorption of intermediates (imines and Schiff bases). Meanwhile, the relative higher acidity
of Ru/TiP-100 could promote the conversion of C=N group in the in situ generated imines and
Schiff bases into the desired primary amines. We believe that the prepared Ru/TiP-100 has the
great potential for the production of primary amines via ambient-temperature reductive
amination of carbonyl compounds.
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ASSOCIATED CONTENT
AUTHOR INFORMATION
Corresponding Authors
Jinliang Song-Beijing National Laboratory for Molecular Sciences, CAS Key Laboratory of
Colloid, Interface and Chemical Thermo-dynamics, Institute of chemistry, Chinese Academy of
Sciences, Beijing 100190, China, Email: songjl@iccas.ac.cn
Buxing Han-Beijing National Laboratory for Molecular Sciences, CAS Key Laboratory of
Colloid, Interface and Chemical Thermo-dynamics, Institute of chemistry, Chinese Academy of
Sciences, Beijing100190, China, Email: hanbx@iccas.ac.cn
Authors
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Chao Xie-Beijing National Laboratory for Molecular Sciences, CAS Key Laboratory of Colloid,
Interface and Chemical Thermo-dynamics, Institute of chemistry, Chinese Academy of Sciences,
Beijing 100190, China
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Manli Hua-Beijing National Laboratory for Molecular Sciences, CAS Key Laboratory of Colloid,
Interface and Chemical Thermo-dynamics, Institute of chemistry, Chinese Academy of Sciences,
Beijing 100190, China
Yue Hu-Beijing National Laboratory for Molecular Sciences, CAS Key Laboratory of Colloid,
Interface and Chemical Thermo-dynamics, Institute of chemistry, Chinese Academy of Sciences,
Beijing 100190, China
Xin Huang-Beijing National Laboratory for Molecular Sciences, CAS Key Laboratory of Colloid,
Interface and Chemical Thermo-dynamics, Institute of chemistry, Chinese Academy of Sciences,
Beijing 100190, China
Haoran Wu-Beijing National Laboratory for Molecular Sciences, CAS Key Laboratory of
Colloid, Interface and Chemical Thermo-dynamics, Institute of chemistry, Chinese Academy of
Sciences, Beijing 100190, China
Guanying Yang-Beijing National Laboratory for Molecular Sciences, CAS Key Laboratory of
Colloid, Interface and Chemical Thermo-dynamics, Institute of chemistry, Chinese Academy of
Sciences, Beijing 100190, China
Notes
The authors declare no competing financial interest.
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Supporting Information. The Supporting Information is available free of charge on the ACS
Publications website.
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The process for the preparation of RuO2/TiP, characterization of the synthesized RuO2/TiP
employing various techniques (i.e., FT-IR spectrum, and N2 adsorption-desorption isotherms),
AFM and EDS mapping images of the prepared RuO2/TiP, H2-TPR profiles of RuO2/TiP, TEM
image, SEM image and XPS spectra of Ru 3d for the recovered Ru/TiP-100, time-yield plots for
reductive amination of cyclohexanone, XPS spectra of Ru 3d in Ru/C, Ru/TiO2 and Ru/TiP-100,
the hydrogenation steps in the reaction process, CO2-TPD profile and basic sites quantity of
Ru/TiP-100 and Ru/TiO2, NH3-TPD profile and acidic sites quantity of RuO2/TiP, Ru/TiP-100
and Ru/TiO2, comparison of Ru/TiP-100 with state-of-the-art catalysts, the activation of C=N
groups in the in situ generated imines and Schiff bases, control experiments using Schiff base as
the reactant, and GC-MS spectra of imidazoline, and the GC chromatograms.
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ACKNOWLEDGMENT
The authors thank the National Natural Science Foundation of China (21673249, 21733011),
National Key Research and Development Program of China (2017YFA0403103), Beijing
Municipal Science & Technology Commission (Z181100004218004), the Chinese Academy of
Sciences (QYZDY-SSW-SLH013), and the Youth Innovation Promotion Association of CAS
(2017043).
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