Preparation of L-phenylalaninol with high ee selectivity by catalytic hydrogenation of L-phenylalaninate over Cu/ZnO/Al2O3 catalyst

Article abstract of DOI:10.1039/c2cy20763j

The Cu/ZnO/Al₂O₃ catalyst for hydrogenation of l-phenylalaninate to l-phenylalaninol was prepared by a co-precipitation method, and characterized by XRD, low-temperature N₂ adsorption, H ₂-TPR, N₂O chemisorption and ICP-AES. The results show that the physicochemical properties of the catalyst are greatly affected by the ZnO amount, and that the exposed copper surface area, dispersion of CuO and BET surface area of the Cu/ZnO/Al₂O₃ catalyst (Cu/Zn/Al = 1.0:0.3:1.0) reach the largest. The chemoselectivity of l-phenylalaninol is changed with ZnO amount in the Cu/ZnO/Al₂O₃ catalyst, and when Cu/Zn/Al = 1.0:0.3:1.0, the catalyst exhibits higher catalytic performance and chemoselectivity to l-phenylalaninol. Furthermore, the effect of temperature, pressure, reaction time and the molar ratio of catalyst to ester on the catalytic hydrogenation of l-phenylalaninate were investigated. When the catalytic hydrogenation of l-phenylalaninate was operated at 110 °C and 4 MPa of H₂ for 5 h, the yield of l-phenylalaninol can reach 69.2 %, and its ee selectivity is 99.84 %.

Full text of DOI:10.1039/c2cy20763j

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A table of contents entry:
Preparation of L-phenylalaninol with high ee selectivity by
catalytic hydrogenation of L-phenylalaninate over
Cu/ZnO/Al2O3 catalyst
Chunyou Gao, Xiuzheng Xiao, Dongsen Mao, Guanzhong Lu*
OH
OCH3
O
H2
+ CH3OH
NH2
NH2
Cu/ZnO/Al2O3
Cu/ZnO/Al2O3 (Cu/Zn/Al = 1/0.3/1, mol) catalyzed hydrogenation of L-phenylalaninate by
H2 at 110 °C and 4 MPa for 5 h, 69.2 % yield of L-phenylalaninol with 99.84 % ee value
was obtained.

Catalysis Science & Technology
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ARTICLE TYPE
Preparation of L-phenylalaninol with high ee selectivity by
catalytic hydrogenation of L-phenylalaninate over
Cu/ZnO/Al2O3 catalyst
Chunyou Gao a, Xiuzheng Xiao a, Dongsen Mao a, Guanzhong Lu a,b
*
5
Received (in XXX, XXX) Xth XXXXXXXXX 20XX, Accepted Xth XXXXXXXXX 20XX
DOI: 10.1039/b000000x
The Cu/ZnO/Al2O3 catalyst for hydrogenation of L-phenylalaninate to L-phenylalaninol was prepared by
a co-precipitation method, and characterized by XRD, low-temperature N2 adsorption, H2-TPR, N2O
chemisorption and ICP. The results show that the physicochemical properties of catalysts are greatly
10 affected by the ZnO amount, and the exposed copper surface area, dispersion of CuO and BET surface
area of Cu/ZnO/Al2O3 catalyst with Cu/Zn/Al = 1/0.3/1(mol) reach the largest. The chemoselectivity of L-
phenylalaninol is changed with ZnO amount in the Cu/ZnO/Al2O3 catalyst, and when Cu/Zn/Al =
1/0.3/1(mol) in the Cu/ZnO/Al2O3 catalyst, it exhibits higher catalytic performance and chemoselectivity
to L-phenylalaninol. Furthermore, the effect of temperature, pressure, reaction time and the molar ratio of
15 catalyst to ester on the catalytic hydrogenation of L-phenylalaninate were investigated. The catalytic
hydrogenation of L-phenylalaninate was operated at 110 °C and 4 MPa of H2 for 5 h, the yield of L-
phenylalaninol can reach 69.2 %, and its ee selectivity is 99.84 %.
catalyst for a hydrogenation of esters of certain amino acids to
amino alcohols at 35~100 °C 27. 10 years ago, Nishimura’s
catalyst (mixed Pt/Rh oxide of 45.9%Rh and 19.9%Pt) was
reported to catalyze hydrogenation of amino esters to
50 corresponding amino alcohols at 25 °C under 10 MPa hydrogen
pressure without racemization, while phenyl group was
1. Introduction
The formation of chiral amino alcohols, especially L-
20 phenylalaninol, has become the subject of considerable efforts
because of their importance in asymmetric synthesis, peptide and
pharmaceutical chemistry, resolution of racemic mixtures,
catalytically hydrogenated to cyclohexyl group simultaneously 26
.
synthesis of insecticidal compounds, and so on 1–10
.
Recently, a ruthenium complex was found to catalyze the
hydrogen reduction of optically active esters to the corresponding
55 chiral alcohol without loss of optical purities. A variety of
optically active esters can be reduced to the corresponding
alcohols in excellent yield without loss of their optical purity or
L-phenylalaninol has often been prepared by reducing the
25 corresponding L-phenylalanine or esters. In most cases, the metal
hydrides were used as a reducing agent, which are reactive at low
temperature thereby guaranteeing the integrity of the stereogenic
center. It was reported that, LiAlH4 11–12, LiAlH4-THF 13, BH3
,
14
causing undesirable side reactions, but for amino esters 28
.
NaBH4 (NaBH4/LiCl, NaBH4/TiCl4, NaBH4/CeCl3, NaBH4-I2-
As is well-known, copper containing catalysts are widely used
60 in a hydrogenation of esters to alcohols, because they allow
30 THF, NaBH4/Cyanuric chloride, NaBH4/I2) 15–20, KBH4-CaCl2
,
21
Zn(BH4)2 22, LiBH4/DCC 23, Lewis base catalysts
have been
24
selective hydrogenation of carbon-oxygen bonds and are
employed for the reduction of L-phenylalanine or esters to obtain
L-phenylalaninol. Even though those reactions can be carried out
at room temperature on a 100-150g scale, the costs and the large
35 amount of waste render this methodology less attractive for
technical application 25. Therefore, another approach of catalytic
hydrogenation is obviously more attractive. However, carboxylic
acids and esters are the least reactive functional groups for the
classical hydrogenation catalysts, and the reaction temperature
40 of > 200 °C is usually needed for efficient transformation, which
29
relatively inactive for carbon-carbon bond hydrogenolysis
.
Among them, Cu/ZnO/Al2O3 catalysts are typical catalysts, and
are employed in synthesis of methanol 30−33, synthesis of N-
34
35
65 ethylethylenediamine
,
gas phase hydrogenolysis
and
hydrogenolysis of glycerol to propylene glycol 36. However, the
effect of ZnO promoter in copper catalysts is a matter of
controversy in the hydrogenation of esters to alcohols. Some
research works suggest that Zn can increase electron density on
70 copper and can store or activate hydrogen 37–39. It was reported
that, in the Cu-ZnO mixed oxide highly active and epitaxial
bound metallic copper platelets can be formed after a reduction of
catalyst 40−42. Kawamura et al. thought that the presence of Zn can
increase the dispersion of Cu particles 43. Despite there are lots of
75 works done on the copper catalysts for a hydrogenation of fat
will cause the racemization of products 26
.
The industrial prospect of amino alcohols is driving the
research of catalysts for the effective hydrogenation of amino
acid or esters for a very long time. From the earliest reports by
45 Ovakimian, Kuna and Levene, Raney nickel was used as the
This journal is © The Royal Society of Chemistry [year]
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Page 3 of 8
Catalysis Science & Technology
esters to alcohols, no detailed research works have been reported
H2-temperature-programmed
reduction
(H2-TPR)
was
on the copper catalyst for hydrogenation of amine acids or esters
to corresponding alcohols.
performed on a flow system equipped with a thermal conductivity
detector (TCD). 50 mg catalyst was used and pretreated at 350 °C
In this paper, we have developed the Cu/ZnO/Al2O3 catalyst 55 for 1 h under N2 flow of 50 mL/min. After it was cooled to room
View Article Online
5
for hydrogenation of methyl L-phenylalaninate to methyl L-
phenylalaninol under mild reaction conditions, in which the
catalyst is very cheap and highly effective. The Cu/ZnO/Al2O3
catalyst was prepared by the co-precipitation method and exhibits
temperature under N2, it was flushed by 10 % H2/N2 of 50
mL/min instead of N2, and TPR of sample was run from room
temperature to 500 °C at 10 °C/min. Effluent gas was dried by
powder KOH and consumption of hydrogen was analyzed by
higher activity and selectivity for methyl L-phenylalaninol 60 TCD. The amount of hydrogen consumption was calibrated by
10 synthesis by L-phenylalaninate hydrogenation, which may be
useful for the commercial application of the catalyst in
hydrogenation of L-phenylalaninate to methyl L-phenylalaninol.
This reaction formula is described as follows:
using known amount of CuO 44, and denoted as X. The amount of
surface metallic copper sites was determined by dissociative N2O
adsorption at 50 °C 44,45, and the experiment procedure was as
follows: the catalyst was first reduced in the TPR procedure
65 described above by 10 % H2/N2 (50 mL/min) at room temperature
to 500 °C. Then the catalyst bed was purged with N2 (50 mL/min)
and cooled to 50 °C, and was oxidized in 2 % N2O/He (50
mL/min) at 50 °C for 0.5 h. Finally, this catalyst was flushed with
N2 to remove the N2O oxidant and cooled to room temperature to
70 start second TPR run. Hydrogen consumption in the second TPR
was denoted as Y. The dispersion of Cu and exposed Cu surface
area were calculated as following equations:
OH
OCH3
H2
O
+ CH3OH
NH2
NH2
Cu/ZnO/Al2O3
15
2. Experimental
All copper atoms were reduced in the first TPR:
2.1. Catalyst preparation
The Cu/ZnO/Al2O3 catalysts were prepared by the co-
precipitation method. The starting materials were
CuO + H2 → Cu + H2O, hydrogen consumption = X
75
Surface copper oxidized by N2O at 50 °C, which is Cu2O, was
reduced in the second TPR:
20 Cu(NO3)2·3H2O, Zn(NO3)2·3H2O, Al(NO3)3·3H2O (A.R.,
Sinopharm Chemical Reagent Ltd.) and solved in de-ionized
water to form 1 mol/L aqueous solution. 10 % ammonia aqueous
solution was added into 1 mol/L Al(NO3)3 solution until pH 8.0,
and 0.5 mol/L Na2CO3 solution was added into a mixed solution
25 of 1 mol/L Cu(NO3)2 and 1 mol/L Zn(NO3)2 until pH 8.0, in
which 10 % ammonia aqueous solution and Na2CO3 solution
were used as a precipitating agent. After two as-prepared
solutions were mixed under stirring, this synthesis solution was
aged for 5 h at 70 °C under stirring in an oil bath, and then it was
30 cooled to room temperature at static condition and kept for 2 h.
The precipitate was filtrated, and washed with de-ionized water
and ethanol until the filtrate is neutral. After dried in air at 120 °C
for 24 h, the catalysts were calcined at 450 °C for 4 h, and
pressed and crushed to 0.45–0.85 mm (20–40 mesh). The resulted
35 Cu/ZnO/Al2O3 catalysts with different Zn amounts were termed
as C0, C1, C3, C4, C5 and C7, respectively. The compositions of
Cu/ZnO/Al2O3 catalysts are listed in Table 1.
Cu2O + H2 → 2Cu + H2O, hydrogen consumption = Y
The dispersion of Cu (DCu) and exposed Cu surface area (SCu)
were calculated as follows:
80
DCu = (2 × Y/X) × 100 %
SCu = 2 × Y × NAV/(X × MCu × 1.4 × 1019) = 1353 × Y/X
(m2Cu/gCu)
Where NAV = Avogadro’s constant, MCu = relative atomic mass
(63.456 g/mol), 1.4 × 1019 comes from that an equal abundance of
85 an average copper surface atom area of 0.0711 nm2 (equivalent to
1.4 × 1019 copper atoms per square meter).
2.3. Testing of catalyst performance
The performance of catalyst for methyl L-phenylalaninate
hydrogenation was tested in 0.5 L stainless steel autoclave under
90 stirring at a speed of 500 rpm. Prior to the catalytic activity
measurement, 1 g (20−40 mesh) catalyst in the stainless steel
autoclave was reduced in H2 (> 99.999 %) of 1 MPa at 250 °C for
4 h, then the autoclave was cooled to room temperature under H2
and methyl L-phenylalaninate diluted in ethanol (> 99.999 %)
95 was introduced. The typical reaction condition is at 80 °C and 3
MPa of H2 for 5 h, and the mass ratio of catalyst/L-
phenylalaninate (Cat./L-p) is 1. Reactants and products were
analyzed by High Performance Liquid Chromatograph (HPLC)
equipped with an ultraviolet detector and fitted with a column
100 (eclipse XDB-C18, 150 × 4.6 mm, 5 μm column P/N 993967-
902). The operated conditions of HPLC were that, mobile phase
was 0.05 mol/L ammonium acetate (pH = 5)/methanol (30/70) of
0.6 mL/min, detection wavelength of 254 nm, injection volume of
6 μL, and column temperature of 20 °C. The conversion of
105 methyl phenylalaninate (X) and chemoselectivity to methyl L-
2.2. Catalyst characterization
The compositions of Cu, Zn and Al in the Cu/ZnO/Al2O3
40 catalysts were analyzed by inductively coupled plasma-atomic
emission spectroscopy (ICP, Optical Emission Spectrometer,
optima 7000 DV). The surface areas of catalysts were measured
by a N2 adsorption at −196 °C on a Micrometrics ASAP 2020
apparatus and calculated by the Brumauer-Emmett-Teller (BET)
45 method.
The powder X-ray diffraction (XRD) patterns of catalysts were
recorded on
a
PANalytical PW 3040/60 X’Pert PRO
diffractometer with Ni-filtered CuKα radiation and operated at 40
kV and 40 mA. The average crystallite sizes of catalysts were
50 calculated based on the diffraction peak broadening by the
Scherrer equation.
2
| Journal Name, [year], [vol], 00–00
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Catalysis Science & Technology
Page 4 of 8
phenylalaninol (S) was calculated respectively as follows:
observed. For the reduced C7 catalyst with Zn/Cu = 0.7 (mol), the
diffraction peaks of ZnO can be obviously observed. The
crystallite size of Cu0 is decreased conversely with an increase in
X (%) = (molar amount of L-phenylalaninate converted/total
molar amount of L-phenylalaninate in the feed) × 100
50 the Zn amount. This is attributed to the separation of ZnO and
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CuO phases in the Cu/ZnO/Al2O3 catalyst when the Zn amount is
S (%) = (molar amount of L-phenylalaninol formed/total molar
amount of L-phenylalaninate in the feed) × 100
higher (Fig.1A).
5
Yield of L-phenylalaninol (%) = X × S
b
b
a
A
a
a
b
3. Results and Discussion
b b
a
b
a
a
b
b
C7
C5
3.1. Textural and structural properties of catalysts
C4
C3
In preparation of Cu/ZnO/Al2O3 catalysts, the molar
10 compositions of Cu, Zn and Al in synthesis solutions and
prepared copper-based catalysts are listed in Table 1. It can be
seen that the compositions of Cu, Zn and Al in Cu/ZnO/Al2O3
catalysts are similar to those in synthesis solutions.
C1
Table 1. The molar compositions of Cu, Zn and Al in Cu/ZnO/Al2O3
15 catalysts
C0
In solid catalyst a
10
20
30
40
50
60
70
In synthesis gel
Catalyst
Cu
Zn
0
Al
Cu
Zn
0
Al
1
2 Theta (degree)
C0
C1
C3
C4
C5
C7
1
1
1
1
1
1
1
1
1
1
1
1
1.07 (49.9)b
1.08 (47.3)
1.03 (41.2)
1.03 (38.8)
1.07 (37.6)
1.05 (34.4)
0.1
0.3
0.4
0.5
0.7
0.10
0.32
0.44
0.55
0.73
1
c
B
a
1
c
a
a
c
a
a
1
a
C7
C5
C4
1
1
a) It was analyzed by ICP; b) The value in brackets is Cu amount (wt.%) in
the catalyst.
C3
C1
The XRD patterns of the Cu/ZnO/Al2O3 catalysts are shown in
20 Fig.1. It can be seen that, there are no diffraction peaks of Al2O3,
which shows that Al2O3 in the Cu/ZnO/Al2O3 catalysts is
amorphous or high-dispersed in both fresh and reduced
Cu/ZnO/Al2O3 catalysts. In the XRD patterns (Fig. 1A) of fresh
catalysts, the characteristic diffraction peaks of CuO can be
25 observed at 2θ = 35.56, 38.77, 48.66, 53.74, 58.29, 61.53, 66.07
and 68.19° (PDF 48-1548). For the reduced catalysts, the peaks
of CuO disappear and the peaks of metallic copper can be
observed at 2θ = 43.24 and 50.33° (PDF 04-0836) (Fig. 1B),
indicating that CuO has been reduced to Cu0. Similar XRD
30 results have been reported by Y.H. Feng et al. for Cu/ZnO/MOx
(MOX = Al2O3, TiO2, and ZrO2) catalysts [35]. In the XRD patterns
of both fresh and reduced catalysts, the characteristic peaks of
ZnO appear at 2θ = 31.71, 33.95, 36.26, 47.72, 56.71 and 62.83°
(PDF 36-1451) when the ZnO amount reaches Zn/Cu = 0.7 (mol),
35 which show that ZnO in Cu/ZnO/Al2O3 catalysts cannot be
reduced under this reduction condition. When Zn/Cu < 0.7 (mol)
in the catalyst, such as the C5 catalyst, no diffraction peaks of
ZnO can be observed, which should be ascribed to its high
dispersion in the catalyst.
C0
10
20
30
40
50
60
70
2 Theta (degree)
55 Fig.1. XRD patterns of (A) fresh and (B) reduced Cu/ZnO/Al2O3 and
Cu/Al2O3 catalysts. (a―ZnO; b―CuO; c―Cu0 )
The BET surface areas of Cu/ZnO/Al2O3 catalysts derived
from nitrogen physisorption are listed in Table 2. The results
show that with an increase in the ZnO amount, BET surface areas
60 of catalysts firstly increase and then decrease. The minimum
surface area was obtained for C5 and C7, which is 77 m2/g, and
C3 exhibits the maximum surface area of 160 m2/g.
The metallic copper surface area (SCu) of catalyst was
investigated by means of the reactive N2O adsorption technique,
65 and the results are shown in Table 2. We can find that the
variation trend of metallic copper surface area with an increase in
the ZnO amount is similar to that of BET surface area. The
minimum surface area of metallic copper was obtained for C5
and C7, which is 34~37 m2/gcat, and C3 has the maximum surface
70 area of metallic copper (113 m2/gcat). It is well-known, the value
of metallic copper surface area reflects the dispersion of Cu in the
catalyst 46, that is to say, the smaller the metallic coppers surface
area and the lower the dispersion of Cu is. Therefore the C3
possesses the highest dispersion of Cu (DCu) and the C5 and C7
75 possess the lowest dispersion of Cu, which is agreed with the data
40
The average crystallite size of Cu0 in the reduced catalyst was
calculated based on the XRD patterns by the Scherrer equation
and their results are shown in Table 2. We can find that the
crystallite size of Cu0 is varied with the ZnO amount. When the
Zn/Cu < 0.7 (mol) in the catalyst, the average crystallite size of
45 Cu0 in the reduced catalyst is decreased with an increase in the Zn
amount, in which the diffraction peaks of ZnO cannot be
This journal is © The Royal Society of Chemistry [year]
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Page 5 of 8
Catalysis Science & Technology
shown in Table 2.
50 interaction between Cu and ZnO weakened, resulting in
decreasing the dispersion of CuO in the Cu/ZnO/Al2O3 catalyst
Table 2. BET surface areas (SBET), metallic copper surface areas (SCu),
dispersions of Cu (DCu) and Cu crystallite sizes (d) of Cu/ZnO/Al2O3
catalysts.
46
and the presence of β peak due to the reduction of bulk CuO
.
Among the Cu/ZnO/Al2O3 catalysts, the C3 catalyst (Cu/Zn/Al =
View Article Online
1/0.3/1, mol) shows the lowest temperature of reduction peak.
55 The smaller the CuO particles and the lower the reduction
temperature should be 52. It is in good agreement with the highest
surface area of Cu (SCu) and surface dispersion of Cu (Dcu, Table
2).
SBET
SCu
SCu
DCu
(%)
d
Catalyst
(m2/g)
(m2/gCu
)
(m2/gCat
)
(nm) a
C0
C1
C3
C4
C5
C7
112
150
160
149
77
189
197
275
233
97.4
100
93.3
93.2
113
27.7
29.1
40.7
34.5
14.4
14.8
16.8
7.37
6.93
4.72
3.52
6.55
The TPR results above prove that ZnO can promote the
60 dispersion of copper oxide and enhance the reducibility of the
copper phase; the low temperature peak (α peak) is attributed to
the reduction of highly dispersed CuO strongly interacting with
ZnO, and the peak at higher temperature (β peak) is due to the
90.4
36.6
34.4
77
5
a) It is the Cu average crystallite size in reduced catalyst and calculated
based on XRD patterns by Scherrer equation.
reduction of bulk CuO 46
.
According to the above results, we can see that the Cu
dispersion is correlated with the loading amount of ZnO in
α
β
C7
C5
10 Cu/ZnO/Al2O3 catalyst. The interaction between ZnO promoter
and Cu can increase the Cu dispersion, while ZnO has occupied
the Cu sites on the catalyst surface, resulting in the decrease of
the effective surface area of Cu. Therefore, we may surmise that
when the loading amount of ZnO is lower (Zn/Cu ≤ 0.3, mol), the
15 interaction between ZnO and Cu is stronger to make the Cu
dispersion increase, and when the loading amount of ZnO is
higher (Zn/Cu ≥ 0.3, mol), much more ZnO has occupied the Cu
sites to make the effective surface area of Cu decrease.
C4
C3
C1
C0
264
207
3.2. The reduction properties of catalysts
50
100
150
200
250
300
350
Temperature (oC)
20 The H2-TPR technique was used to investigate the reduction
behaviour of the Cu/ZnO/Al2O3 catalysts, and the results are
shown in Fig. 2. The results show that the reduction profiles of all
samples with different ZnO amounts exhibit a broad peak of H2
consumption at 200–320 °C, in which the reduced peaks for C0,
25 C5 and C7 can be disassembled to α and β peaks.
65
Fig. 2. H2-TPR profiles of the Cu/ZnO/Al2O3 catalysts.
3.3. Catalytic performance of Cu/ZnO/Al2O3
3.3.1. Effect of the Zn content
The effect of ZnO content on the catalytic performance of the
70 Cu/ZnO/Al2O3 catalyst for hydrogenation of methyl L-
phenylalaninate was investigated at 80 °C and 3 MPa of H2 for 5
h and the results are shown in Fig. 3. The results show that the
Cu/ZnO/Al2O3 and Cu/Al2O3 catalysts exhibit a high activity, that
is, ~100% conversion of L-phenylalaninate can be obtained at
75 this reaction condition. However, the yield of desired product
(methyl L-phenylalaninol) is different for the different catalysts
and strongly related to the ZnO content in the Cu/ZnO/Al2O3
catalyst, because of the ZnO content affecting the Cu surface area
and Cu dispersion. The results in Fig.3 show that, the methyl L-
80 phenylalaninol chemoselectivity (CS-nol) over the Cu/Al2O3
catalyst is 10.7 %, and after adding ZnO in the Cu/Al2O3 catalyst,
CS-nol is increased obviously. When Zn/Al = 0.3(mol), that is
using the C3 catalyst, the maximal CS-nol (42.4 %) can be
obtained, and further increasing the ZnO content in the
85 Cu/ZnO/Al2O3 catalyst, CS-nol is instead decreased.
It is well-known, ZnO and Al2O3 cannot be reduced at below
500 °C, and the presence of ZnO can promote the reduction of
CuO by hydrogen spillover 47; the α and β peaks are ascribed to
the reduction of two kinds of Cu species or CuO with two kinds
30 of sizes. In the former the reduction peak at lower temperature is
corresponding to Cu2+ → Cu+ and the peak at higher temperature
is corresponding to Cu+ → Cu0, and in the latter the reduction of
two peaks are corresponding to Cu2+ → Cu0, in which the peak at
lower temperature is due to the reduction of high dispersed CuO
35 and the peak at higher temperature is due to the reduction of bulk
CuO 48−50. In the TPR curve of C0 (CuO/Al2O3), there are two
peaks and the α peak area is obviously unequal to that of β peak,
so that it can be conclude that the α peak is ascribed to the
reduction of high dispersed CuO on the catalyst surface and the β
40 peak is ascribed to the reduction of bulk CuO in the catalyst.
After adding ZnO with lower loading (as C1, C3 and C4 samples),
the two peaks in the TPR curve of C0 are overlapped, which
indicates that the presence of ZnO makes CuO homogeneously
As shown in Table 2, the Cu surface area of the Cu/ZnO/Al2O3
catalyst is increased with the BET surface area, and the Cu
dispersion is increased with the Cu surface area. Based on the
BET surface area, Cu surface area and Cu dispersion of the
90 Cu/ZnO/Al2O3 catalyst, we can find that CS-nol is increased with
the Cu dispersion that is enhanced by increasing Cu surface area.
disperse by forming the solid solution of Cu-Zn-O 49 that can be
51
45 reduced at markedly lower temperatures compared to CuO
.
Therefore, the reduction peak temperature in C1, C3 and C4
catalysts are lower than that of β peak in the C0 catalyst. With a
further increase in the ZnO loading, the ZnO phase was formed in
Cu/ZnO/Al2O3 catalyst (as the XRD spectra of C7 in Fig.1), the
4
| Journal Name, [year], [vol], 00–00
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Catalysis Science & Technology
Page 6 of 8
60
120
100
80
60
40
20
0
A
C5
C7
C1
C3
C4
C0
55
50
45
40
View Article Online
Conversion (%)
Selectivety (%)
Cat./L-p=1
3 MPa of H2
42.4%
5h
14.6%
35
60
80
100
120
140
160
10
6
10.7%
Reaction temperature (oC)
0.0
0.2
0.4
0.6
0.8
60
50
40
30
20
10
0
Molar ratio of Zn/Cu
B
Fig. 3. The effect of Zn/Cu in Cu/ZnO/Al2O3 (Cat./L-p = 1/1) on the
conversion and chemoselectivity of methyl L-phenylalaninol for the
catalytic hydrogenation of methyl L-phenylalaninate at 70 °C and 3 MPa
5 of H2 for 5 h.
Cat./L-p=1
3 MPa of H2
110 oC
3.3.2. Effects of reaction conditions
Based on the results above, among the prepared Cu/ZnO/Al2O3
catalysts, the C3 catalyst is an optimized catalyst for methyl L-
phenylalaninate hydrogenation to methyl L-phenylalaninol.
10 Therefore the C3 catalyst was used as a model catalyst to
investigate the effect of the reaction condition, such as the
reaction temperature, time, pressure and the Cat./L-p mass ratio
on the yield of methyl L-phenylalaninol (that is the
chemoselectivity to methyl L-phenylalaninol in 100% conversion
15 of methyl L-phenylalaninate).
The influence of the reaction temperature on the yield of
methyl L-phenylalaninol was investigated at 70 ~ 150 °C and 3
MPa of H2 for 5 h and Cat./L-p = 1, and the results are shown in
Fig. 4A. The results show that the yield of methyl L-
20 phenylalaninol is increased with the reaction temperature, but
when the reaction temperature is more than 110 °C, the increase
of yield is unobvious. Therefore, the appropriate reaction
temperature is 110 °C.
2
4
6
8
Reaction time (h)
80
60
40
20
0
C
Cat./L-p=1
110 oC
5h
0
1
2
3
4
5
Reaction pressure (MPa)
The influence of the reaction time on the yield of L-
25 phenylalaninol at 110 °C and 3 MPa of H2 and Cat./L-p = 1 are
shown in Fig. 4B. It shows that with an increase in the reaction
time from 3 to 5 h, the yield of methyl L-phenylalaninol is
increased, and after 5 h, it is decreased. As the conversion of
methyl L-phenylalaninate is ~100 %, the chemoselectivity to by-
30 products is increased with the reaction time after 5 h. Therefore
the appropriate reaction time is 5 h when the reaction is operated
at 110 °C.
The effect of the hydrogen pressure on the catalytic
hydrogenation of L-phenylalanate was studied at 110 °C and
35 Cat./L-p = 1 for 5 h, and the results are shown in Fig. 4C. It is
observed that the yield of methyl L-phenylalaninol is increased
with the H2 pressure, and when the H2 pressure is more than 4
MPa, the yield almost remain constant. Hence the appropriate
reaction pressure is 4 MPa.
70
D
60
50
40
30
20
10
0
110 oC
4 MPa of H2
5h
0.0
0.5
1.0
1.5
2.0
2.5
Cat./L-p (mass)
50 Fig. 4. Influence of reaction conditions on the yield of methyl L-
phenylalaninol over the C3 catalyst: (A) temperature, (B) time, (C)
pressure and (D) Cat./L-p. (Reaction condition: (A) Cat./L-p = 1, at 3
MPa of H2 for 5 h, (B) Cat./L-p = 1, at 110 °C and 3 MPa of H2; (C)
Cat./L-p = 1, at 110 °C for 5 h, and (D) at 110 °C and 4 MPa of H2 for 5h).
40
Fig. 4D shows the effect of the catalyst content (Cat./L-p) on
the yield of methyl L-phenylalaninol. We can see that, when
Cat./L-p is less than 1/1.5, the yield of methyl L-phenylalaninol is
increased with increasing the catalyst amount; when Cat./L-p is
more than 1/1.5, the yield of methyl L-phenylalaninol is hardly
55
Based on the results mentioned above, the more optimal
reaction conditions for the selective hydrogenation of methyl L-
phenylalaninate to methyl L-phenylalaninol over the
45 changed with the catalyst amount.
This journal is © The Royal Society of Chemistry [year]
Journal Name, [year], [vol], 00–00 | 5

Page 7 of 8
Catalysis Science & Technology
Cu/ZnO/Al2O3 catalyst can be determined, which are 110 °C, 4
MPa of H2, 5 h and Cat./L-p = 1/1.5. At this reaction condition,
the yield of methyl L-phenylalaninol can reach 69.2 %. The e.e.
of methyl L-phenylalaninate to methyl L-phenylalaninol are
shown in Table 3. It can be seen that, the C3 catalyst exhibits the
highest yield (69.2 %) and the largest reaction rate (1.16
value of the product is 99.84 % obtained by HPLC (with the 20 mmol/gcat·h), because of C3 possessing the most active sites per
View Article Online
5
separation column of Chiralcel OD, 250 × 4.6 mm) after the
gram catalyst. For TOF, Cu/ZnO/Al2O3 is higher than Cu/Al2O3
chiral amine of methyl phenylalaninol was protected by benzyl
chloroformate
indicating that the presence of Zn enhances the catalytic activity
of Cu sites. However, TOF of C7 is higher than that of C3, which
gives us enlightenment that the higher effective active sites can
53
.
The 1H NMR spectrum of methyl L-
phenylalaninol was obtained on a Bruker AVANCE-III 500.
1HNMR(CDCl3): 7.16~7.29 (5H, m, Ph-H), 3.41~3.66 (2H, m, - 25 be designed and prepared by highly loading Zn to modify Cu
10 CH2-O-), 3 3.15~3.20 (1H, m, CHNH2), 2.51~2.82 (2H, m, CH2
Ph).
sites, to form more surface defects of metallic Cu (such as step,
kink, edge and so on), because these defect Cu sites exhibit only
catalytic activity. And the higher effective Cu/ZnO/Al2O3 catalyst
can be prepared by increasing the Cu surface area of
30 Cu/ZnO/Al2O3, because the larger the surface area of Cu, the
more the active sites of Cu is and higher its catalytic activity is.
3.3.3. Turn over frequency of catalyst for hydrogenation of
methyl L-phenylalaninate
15 Turn over frequencies (TOFs) for product 54 and average reaction
rates of Cu/ZnO/Al2O3 catalysts for the selective hydrogenation
Table 3. TOFs, reaction rates and product yields for hydrogenation of methyl L-phenylalaninate over Cu/ZnO/Al2O3 catalysts a.
Yield of methyl
L-phenylalaninol (%)
Number of active
Average rate
Catalyst
TOF (h–1) b
sites (×1020/gcat
)
(mmol/gcat·h) c
C0
C1
C3
C4
C5
C7
12.8
53.2
69.2
61.9
31.0
45.3
13.1
13.0
15.8
12.7
5.12
4.82
0.099
0.413
0.441
0.491
0.610
0.947
0.21
0.89
1.16
1.04
0.52
0.76
a)
Reaction conditions: 1.5 g methyl L-phenylalaninate, 1.0 g Cu/ZnO/Al2O3 catalyst (Cat./L-p = 1/1.5), 110 °C, 4 MPa of H2, 5 h. b) Turn over frequencies
for methyl L-phenylalaninol formed, mol product per Cu per hour at 110 °C 54
.
c) The average reaction rate for 5 h.
35 4. Conclusions
Notes and references
a Research Institute of Applied Catalysis, School of Chemical and
Environmental Engineering, Shanghai Institute of Technology, Shanghai
200235, P. R. China. Fax:(+86)-21-64253824, E-mail:
In summary, the Cu/ZnO/Al2O3 catalyst that shows the highest
catalytic activity and e.e. selectivity to product for hydrogenolysis
of methyl L-phenylalaninate to methyl L-phenylalaninol, was
designed and prepared by a co-precipitation method. The metallic
40 copper plays the role of active site for hydrogenation reactions,
and ZnO can promote the dispersion of copper (oxide) and
enhance the reducibility of the copper oxide phase. The
appropriate molar ratio of Zn/Cu should be ~0.3.
The Cu/ZnO/Al2O3 catalyst with a Cu/Zn/Al molar ratio of
45 1/0.3/1 shows the highest activity and e.e. selectivity to methyl L-
phenylalaninol. Over this catalyst, methyl L-phenylalaninate was
hydrogenated at 110 °C and 4 MPa of H2 for 5 h, the yield of
methyl L-phenylalaninol can reach 69.2 %, and its e.e. = 99.84 %.
Since the Cu/ZnO/Al2O3 catalysts is very cheap and prepared
50 easily for the selective hydrogenation, further investigation
65 gzhlu@ecust.edu.cn.
b Key Laboratory for Advanced Materials and Research Institute of
Industrial catalysis, East China University of Science and Technology,
Shanghai 200237, P. R. China.
1
2
3
E. J. Corey, S. Shibata and R. K. Bakashi, J. Org. Chem., 1988, 53,
2861.
C. B. Li, J. Zhang, P. Y. Zhao and M. Lu, J. Tianjin Univ., 2004,
37(10), 923.
S. J. Lv, R. Jiang, H. Y. Zhou, Y. Zheng and H. X. Fu, Chin. J. Mol.
Catal., 1995, 9(5), 358.
70
75 4 J. M. Andres, Y. Martin, R. Pedrosa and A. P. Encabo, Tetrahedron,
1997, 53, 3787.
5
6
D. Pini and A. Mastantuono, Tetrahedron: Asymmetry, 1994, 5, 1875.
G. J. Lee, T. H. Kim, J. N. Kim, Tetrahedron: Asymmetry, 2002, 13,
9.
regarding the catalytic reaction mechanism and improvement of 80 7 M. Kawai, Y. Omori and H. Yamamura, Tetrahedron: Asymmetry,
1992, 3, 1019.
the chemoselectivity are in progress and will be reported in due
course.
8
J. R. Luly, J. J. Plattner, H. Stein, N. Yi, J. Soderquist, P. A. Marcotte,
H. D. Kleinert, T. J. Perun, Biochem. Biophys. Res. Commun., 1987,
143, 44.
Acknowledgements
85 9 J. M. Cassal, A. Fuerst, Helv. Chim. Acta, 1976, 59, 1917.
10 C. F. Stanfield, J. E. Parker and P. Kanellis, J. Org. Chem., 1981, 46,
4799.
11 D. A. Dickman and A. I. Meyers, Org. Synth., 2001, 7, 530.
12 Q. Hua, J. Z. Lin and Q. Jiang, Chin. Chem. Reag., 1993, 15, 123.
90 13 B. Bai, X. Y. Li, Y. Li and H. J. Zhu, Bioorg. Med. Chem. Lett., 2011,
21, 2302.
55 We would like to acknowledge the financial support from the
National Basic Research Program of China (2010CB732300), and
the “Shu Guang” Project (10GG23) and Leading Academic
Discipline Project (J51503) of Shanghai Municipal Education
Commission and Shanghai Education Development Foundation,
60 and The School to Introduce Talents Project (YJ2011-46).
14 Z. X. Shen, Y. H. Li, H. B. Qin and Y. W. Zhang, Chin. Chem. Reag.,
2004, 15, 23.
6
| Journal Name, [year], [vol], 00–00
This journal is © The Royal Society of Chemistry [year]

Catalysis Science & Technology
Page 8 of 8
15 H. H. He, D. C. Gong and P. Wei, Chin. Chem. Reag., 2005, 27(2), 40 34 H. F. Wang, L. G. Chen, G. Y. Bai, D. Z. Luan, Y. Li, X. L. Yan, Y.
115.
C. Zhang and J. D. Xing, Catal. Commun., 2007, 8, 145.
35 Y. H. Feng, H. B. Yin, A. L. Wang, L. Q. Shen, L. B. Yu and T. S.
Jiang, Chem. Eng. J., 2011, 168, 403.
16 C. H. Zhang, N. F. Yang and L. W. Yang, Chin. J. Org. Chem., 2004,
24, 343.
5 17 C. F. Gan, R. Feng, J. C. Fan and J. G. Cui, Chin. Chem. World, 2007,
9, 538.
18 Z. X. Wang and Y. Q. Fu, J. Luoyang Normal Univ., 2007, 5, 69.
19 F. Massimo, P. Andrea and T. Maurizio, Tetrahedron Lett., 1999, 40,
4395.
36 Z. M. Zhou, X. Li, T. Y. Zeng, W. B. Hong, Z. M. Cheng and W. K.
View Article Online
45
Yuan, Chin. J. Chem. Eng., 2010, 18(3), 384.
37 F. T. van de Scheur, B. van der Linden, M. C. M. Hazeleger, J. G.
Nazloomian and L. H. Staal, Appl. Catal. A, 1994, 111, 63.
38 P. Claus, M. Lucas, B. Lücke, T. Berndt and P. Birke, Appl. Catal. A,
1991, 79, 1.
10 20 D. C. Gong, P. Wei, H. H. He, H. Zhou and P. K. Ouyang, Chin. Fine
Chem., 2005, 22(5), 384.
50 39 J. C. Frost, Nature, 1988, 334, 577.
21 Y. Z. Li, C. X. Guo, X. Y. Lu, L. C. Shen and H. M. Huang, J. Jilin
Univ. (Sci. Ed.)., 1998, (1), 85.
40 D. S. Brands, E. K. Poels and A. Bliek, Stud. Surf. Sci. Catal., 1996,
101, 1085.
22 S. Narasimhan, S. Madhavan and K. G. Prasad, J. Org. Chem., 1995,
41 D. S. Brands, E. K. Poels, T. A. Krieger, O. V. Makarova, C. Weber,
S. Veer and A. Bliek, Catal. Lett., 1996, 36, 175.
15
60, 5314.
23 J. M. Herbert, A. T. Hewson and J. E. Peace, Synth. Commun., 1998,
55 42 T. M. Yurieva, L. M. Plyasova, O. V. Makarova and T. A. Krieger, J.
Mol. Catal. A, 1996, 113, 455.
28, 823.
24 T. Kashiwagi, S. Kotani, M. Sugiura and M. Nakajima, Tetrahedron,
2011, 67, 531.
43 Y. Kawamura, K. Yamamoto, N. Ogura, T. Katsumata and A.
Igarashi, J. Power Sources, 2005, 150, 20.
20 25 A. Abiko and S. Masamune, Tetrahedron Lett., 1992, 33, 5517.
26 M. Studer, S. Burkhardt and H. U. Blaser, Adv. Synth. Catal., 2001,
343, 802.
27 G. Ovakimim, M. Kuna, P.A. Levene, J. Biol. Chem., 1940, 135, 91.
28 W. Kuriyama, Y. Ino, O. Ogata, N. Sayo and T. Saito, Adv. Synth.
44 Z. L. Yuan, L. N. Wang, J. H. Wang, S. X. Xia, P. Chen, Z. Y. Hou
60
and X. M. Zheng, Appl. Catal. B, 2011, 101, 431.
45 C. J. G. Van Der Grift, A. F. H. Wielers, B. P. J. Jogh, J. V. Beunum,
M. De Boer, M. V. Helder and J. W. Geus, J. Catal., 1991, 131, 178.
46 X. M. Guo, D. S. Mao, G. Z. Lu, S. Wang and G. S. Wu, J. Catal.,
2010, 271, 178.
65 47 I. M. Cabrera, M. L. Granados and J. L. G. Fierro, J. Catal., 2002,
210, 273.
48 M. F. Luo, P. Fang, M. He and Y. L. Xie, J. Mol. Catal. A, 2005, 239,
243.
49 Z. Li, H. Y. Zheng and K. C. Xie, Chin. J. Catal., 2008, 29(5), 431.
70 50 G. Z. Lu and R. Wang, Chin. J. Catal., 1991, 12, 83.
51 F. Arena, K. Barbera, G. Italiano, G. Bonura, L. Spadaro and F.
Frusteri, J. Catal., 2007, 249, 185.
52 Y. P. Zhang, J. H. Fei, Y. M. Yu and X. M. Zheng, Energy Convers.
Manage., 2006, 47, 3360.
25
30
35
Catal., 2010, 352, 92.
29 D. S. Brands, E. K. Poels, A. Bliek, Appl. Catal. A, 1999, 184, 279.
30 V. D. Kumari, M. Subrahmanyam, A. Ratnamala, D. Venugopal, B.
Srinivas, M. V. P. Sharma, S. S. Madhavendra, B. Bikshapathi, K.
Venkateswarlu, T. Krishnudu, K. B. S. Prasad and K. V. Raghavan,
Catal. Commun., 2002, 3, 417.
31 U. Costantino, F. Marmottini, M. Sisani, T. Montanari, G. Ramis, G.
Busca, M. Turco and G. Bagnasco, Solid State Ionics, 2005, 176,
2917.
32 A. Indarto, D. R. Yang, J. Palgunadi, J. W. Choi, H. Lee and H. K.
Song, Chem. Eng. Prog., 2008, 47, 780.
33 M. Behrens, D. Brennecke, F. Girgsdies, S. Kiβner, A. Trunschke, N.
Nasrudin, S. Zakaria, N. F. Idris, S. B. A. Hamid, B. Kniep, R.
Fischer, W. Busser, M. Muhler and R. Schlögl, Appl. Catal. A, 2011,
392, 93.
75 53 J. Clariana, S. G. Granda, V. Gotor, A. G. Fernandez, A. Luna, M. M.
Manas and A. Vallribera, Tetrahedron: Asymmetry, 2007, 48, 8323.
54 S. X. Xia, R. F. Nie, X. Y. Lu, L. N. Wang, P. Chen, Z. Y. Hou, J.
Catal., 2012, 296, 1.
80
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