Asymmetric hydrogenation of 3-chloro-1-phenylpropan-1-one catalyzed by ruthenium complexes

Article abstract of DOI:10.1134/S1070363215040271

Abstract A ruthenium complex modified with (1S,2S)-1,2-diphenyl-1,2-ethanediamine efficiently catalyzes asymmetric hydrogenation of 3-chloro-1-phenylpropan-1-one in the presence of potassium hydroxide solution in isopropyl alcohol, specific optical rotation of the synthesized products reaching -24.6°. Effects of the reaction time, hydrogen pressure, and the alkali concentration on the reaction course have been elucidated.

Full text of DOI:10.1134/S1070363215040271

ISSN 1070-3632, Russian Journal of General Chemistry, 2015, Vol. 85, No. 4, pp. 922–925. © Pleiades Publishing, Ltd., 2015.
Asymmetric Hydrogenation
of 3-Chloro-1-phenylpropan-1-one Catalyzed
by Ruthenium Complexes1
Yanmei Liua, Yulei Taia,b, Ruqi Guana, Guoku Chaoa,
Caiping Yea, Haihua Lia, Xiaoyan Lia, and Yajuan Zhaoa
a College of Chemistry and Materials Engineering, Wenzhou University, Wenzhou, 325027 China
e-mail: taiyulei@163.com; zyj@wzu.edu.cn
b Wenzhou University Oujiang College, Wenzhou University, Wenzhou, 325027 China
Received April 1, 2014
Abstract—A ruthenium complex modified with (1S,2S)-1,2-diphenyl-1,2-ethanediamine efficiently catalyzes
asymmetric hydrogenation of 3-chloro-1-phenylpropan-1-one in the presence of potassium hydroxide solution
in isopropyl alcohol, specific optical rotation of the synthesized products reaching –24.6°. Effects of the
reaction time, hydrogen pressure, and the alkali concentration on the reaction course have been elucidated.
Keywords: asymmetric hydrogenation, ketone; ruthenium catalysts
DOI: 10.1134/S1070363215040271
Hydrogenation of carbonyl compounds has recently
attracted much interest due to promising applications
of the products in the field of medicine [1]. Asym-
metric hydrogenation of simple ketones provides an
efficient approach to prepare chiral (optically active)
secondary alcohols, important organic synthesis inter-
mediates [2].
Although many highly selective chiral catalysts
have been successfully used for ketones hydrogena-
tion, their industrial applications have been compli-
cated by requirement to remove traces of the toxic
metals from the product [9]. In order to overcome the
problem, catalytic asymmetric reactions catalyzed by
heterogeneous catalysts have been recently inves-
tigated, heterogeneous catalysts allowing for better
reaction control and being easier separated off and
recycled [10].
Catalytic asymmetric hydrogenation is among
industrially used reactions due to its simplicity and
material efficiency [3]. In particular, asymmetric
hydrogenation of simple ketones occurring under mild
conditions to yield chiral alcohols has received a
portion of attention [4]. A number of transition-metal
complexes have revealed catalytic activity towards
hydrogenation of ketones; however, only rhodium and
iridium complexes have efficiently catalyzed asym-
metric hydrogenation with pronounced enantioselectivity
[5]. A recent report has also demonstrated the potential
of ruthenium complexes [6]; on top of the promising
catalytic promising, ruthenium compounds are better
available and cheaper than rhodium or iridium ones.
Several chiral triarylphosphine ligands have been
successfully applied in asymmetric hydrogenation pro-
cesses [7, 8].
Herein, we report on preliminary studies on
asymmetric hydrogenation of 3-chloro-1-phenylpropan-
1-one catalyzed with γ-Al2O3-loaded DPEN-modified
Ru/TPP complex [TPP standing for triphenylphosphine
and DPEN standing for (1S,2S)-1,2-diphenyl-1,2-ethane-
diamine] [11].
O
Cl
Ru/γ-Al2O3
DPEN, KOH, i-C3H7OH
OH
Cl
OH
Cl
or
1 The text was submitted by the authors in English.
922

ASYMMETRIC HYDROGENATION OF 3-CHLORO-1-PHENYLPROPAN-1-ONE
OP, %
923
Conversion, %
T, °C
Time, min
Fig. 1. The reaction conversion and the product optical
purity as function of temperature. Hydrogen pressure
1.2 MPa; reaction time 180 min; RuCl3 : DPEN : ketone 1 :
1 : 100 (mol/mol/mol).
Fig. 2. The reaction kinetics at different hydrogen pressures.
T 60°C; RuCl3 : DPEN : ketone 1 : 1 : 100 (mol/mol/mol).
In detail, we have examined effects of the reaction
time, hydrogen pressure, and alkali concentration on
the yield and specific optical rotation of the products.
were as follows: T 60°C, hydrogen pressure 1.2 MPa,
the reaction time 90–180 min. Under those conditions,
the substrate conversion was of 100%, and the product
optical purity was of 98%.
Effect of temperature on the reaction conversion
and the product specific rotation is shown in Fig. 1. As
seen from the data, the prepared Ru/TPP/DPEN/γ-
Al2O3 catalyst revealed good activity towards 3-chloro-
1-phenylpropan-1-one enantioselective hydrogenation
into 3-chloro-1-phenylpropan-1-ol under mild temperature
and moderate hydrogen pressure of 1.2 MPa. The
substrate conversion increased with the reaction
temperature to reach a maximum of 97% at 80°C.
Optical purity of the product decreased upon heating;
however, remaining moderately high up to 60°C.
The effect of potassium hydroxide concentration,
other conditions being the same (hydrogen pressure
1.2 MPa, T 60°C, reaction time 90 min, and Ru :
DPEN : ketone ratio 1 : 1 : 100 mol/mol/mol) on the
reaction conversion and the product optical purity are
documented in Fig. 4. The results indicated that the
reasonably high yield of the pure enantiomer required
the presence of certain amount of the alkali in
isopropanol medium. In particular, fairly low yield of a
mixture of enantiomers was found in the absence of
KOH; both the reaction conversion and the optical
purity of the product went up with the alkali concentra-
tion increasing in the range of 0.02–0.08 mol/L, and
further increase of the alkali amount resulted in
somewhat decreased product yield of lower optical purity.
We further studied the effect of hydrogen pressure
on the reaction course and the product properties. The
reaction was accelerated with hydrogen pressure
increasing up to 1.2 MPa; however, further increase of
hydrogen pressure to 1.4 MPa somewhat slowed the
hydrogenation down (Fig. 2). The effect is better
documented in Fig. 3 displaying the reaction outcome
after 180 min. Interestingly, the optical purity of the
product increased with the conversion as hydrogen
pressure increased to 1.2 MPa, whereas decrease of the
conversion at hydrogen pressure of 1.4 MPa was
accompanied with steep decrease of the optical purity.
Hence, the reaction conditions optimized in terms of
reaction time, hydrogen pressure, and temperature
To conclude, a Ru/TPP complex modified with
DPEN and applied on γ-Al2O3 support has revealed
excellent catalytic activity towards conversion of 3-
chloro-1-phenylpropan-1-one into the corresponding
alcohol. All the altered reaction conditions (reaction
time, temperature, hydrogen pressure, and alkali
concentration) should be chosen properly in order to
attain the high product yield and the high optical
purity. In detail, the best conditions have been optimized
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 85 No. 4 2015

924
Conversion, %
YANMEI LIU et al.
OP, %
Conversion, %
OP, %
0
c(KOH), mol/L
P, MPa
Fig. 3. The reaction conversion and the product optical
purity as function of hydrogen pressure. T 60°C; reaction
Fig. 4. The reaction conversion and the product optical
purity as function of KOH concentration. T 60°C; hydrogen
pressure 1.2 MPa; reaction time 90 min; RuCl3 : DPEN :
ketone 1 : 1 : 100 (mol/mol/mol).
time 180 min; RuCl3
(mol/mol/mol).
:
DPEN : ketone 1 : 1 : 100
1
as follows: T 60°C; hydrogen pressure 1.2 MPa, KOH
concentration 0.08 mol/L, and reaction time 90 min.
Further work is being run to elucidate the reaction
mechanism and broadening the range of substrates of
the reported asymmetric hydrogenation process.
3-Chloro-1-phenylpropan-1-ol. H NMR spectrum
(500 MHz, CDCl3, TMS), δH, ppm: 7.371 d (3J1 4.5 Hz,
4H), 7.307 m (3J1 4.0 Hz, 1H), 4.951 m (1H), 3.721–
3.770 m (1H), 3.543–3.588 m (1H), 2.209–2.278 m,
(1H), 2.063–2. 129 m (1H), 1.884 s (1H); 13C NMR
spectrum, δC, ppm: 143.943, 128.916, 128.176,
126.011, 71.599, 41.950, 41.697. GC-MS (EI, 70 eV)
170 (MH+).
EXPERIMENTAL
3-Chloro-1-phenylpropan-1-one, (1S,2S)-diphenyl-
1,2-ethylenediamine, (1R,2R)-diphenyl-1,2-ethylenedi-
amine, and isopropanol were used as received from the
supplier.
The reaction conversion was determined from gas
chromatography–mass spectrometry data. Specific
rotation of the product was determined by polarimetry
and reflected the optical purity (OP) of the product:
The ruthenium complex catalyst Ru/TPP/γ-Al2O3
was prepared as described elsewhere [11].
[α]exp
× 100%.
OP =
The hydrogenation reaction was performed in a 50 mL
stainless steel autoclave equipped with a magnetic
stirring bar. The prepared catalyst, the substrate 3-
chloro-1-phenylpropan-1-one (0.2 g, 1.2 mmol), and
required amounts of DPEN modifier and KOH were
dissolved in 15 mL of isopropyl alcohol. The solution
was placed into the autoclave; the latter was fed with
hydrogen up to the desired pressure and incubated at
the experiment temperature. After suction filtration of
the solids and evaporation off the solvent on a rotary
evaporator, the product was purified by recrystal-
lization from cyclohexane to form white solid powder.
[α]theor
ACKNOWLEDGMENTS
This work was partly supported by the Fund of
Science & Technological Project of Zhejiang, China
(grant no. 2009C33059), Discipline Construction Project
of Wenzhou University (no. 316406125020301), and
Zhejiang Provincial Top Key Discipline of New Materials
and Process Engineering (20110949).
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 85 No. 4 2015

ASYMMETRIC HYDROGENATION OF 3-CHLORO-1-PHENYLPROPAN-1-ONE
925
Catal. Lett., 2008, no. 120, p. 307.
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