Homogeneous RuCl2(PPh3)3-catalyzed regioselective liquid-phase transfer hydrogenation of carbon-carbon double bond in chlorobenzylidene ketones with ethylene glycol as hydrogen donor

Article abstract of DOI:10.1021/op0000327

The regioselective transfer hydrogenation of a carbon-carbon double bond of different chlorobenzylidene ketones is effectuated in ethylene glycol with a very high selectivity in the presence of homogeneous, tris(triphenylphosphine)ruthenium-(II) chloride

Full text of DOI:10.1021/op0000327

Organic Process Research & Development 2000, 4, 571−574
Homogeneous RuCl2(PPh3)3-Catalyzed Regioselective Liquid-Phase Transfer
Hydrogenation of Carbon-Carbon Double Bond in Chlorobenzylidene Ketones
with Ethylene Glycol as Hydrogen Donor
Sudip Mukhopadhyay, Anan Yaghmur, Axel Benichou, and Yoel Sasson*
Casali Institute of Applied Chemistry, Hebrew UniVersity of Jerusalem, 91904, Israel
Abstract:
of double bonds in chlorobenzylidene ketones but that with
some unavoidable dechlorinated product and the reaction
ceased at around 50% conversion level, thus makes the
product separation more tedious. Raney nickel19 can be used
selectively for this purpose, but very high hydrogen pressure
requirements and the presence of an organic sulphur com-
pound make the process somewhat complicated.
We have previously shown the possibility of selective
transfer hydrogenation20 of a carbon-carbon double bond
with complete conversion of the starting chalcones. We now
present the results of kinetic investigation and process
parameter studies of highly selective transfer hydrogenation
of double bonds in halo-substituted benzylidene ketones,
catalyzed by homogeneous RuCl2(PPh3)3 with ethylene
glycol as the hydrogen donor.
The regioselective transfer hydrogenation of a carbon-carbon
double bond of different chlorobenzylidene ketones is effectu-
ated in ethylene glycol with a very high selectivity in the
presence of homogeneous, tris(triphenylphosphine)ruthenium-
(II) chloride catalyst. Different important process parameters
such as temperature, catalyst loading, and reaction period are
studied. The reaction follows a first-order kinetics, and the
energy of activation was found to be 52 kJ/mol.
Introduction
Chemoselective hydrogenations of carbon-carbon double
bond in R,â-unsaturated carbonyl compounds are always a
challenge to the process chemists. Thus, different catalyst
systems1-10 have been investigated by several workers for
the reduction of either the double bond or the carbonyl group.
Pd is the preferred industrial catalyst as it can be recycled
without altering the selectivity and reaction rate. Hydrogen
gas or hydrogen transfer agents such as alcohols,11 li-
monene,12 ethylene glycol13,14 have also been successfully
employed for these type of reactions.
The heterogeneous Pd and hydrogen combination is
always preferred for easy bulk management, minimal ef-
fluents, facile product separation, and longer catalyst life,
and thus it is invariably used in large-scale industrial appli-
cations. Despite of these facts, there are limitations of this
combination especially in the presence of a halo substituents.
Pd is a known hydrodehalogenation15,16 catalyst and thus
could not be used for the selective double bond hydrogena-
tion of halo-substituted R,â-unsaturated ketones. Thus, efforts
have been made to use Rh catalyst17,18 for the hydrogenation
Results and Discussion
In a typical reaction (Scheme 1), 2.5 g (10 mmol) of
4-ClC6H4CHdCHCOC6H5 (1a), 0.15 g (0.156 mmol) of
RuCl2(PPh3)3, and ethylene glycol (total reaction volume,
25 mL) were charged to a glass reactor fitted with a
condenser and a six-bladed turbine stirrer. The reaction
mixture was heated for 4 h at 150 °C.
After the stipulated time, depending on reaction condi-
tions, 4-ClC6H4CH2CH2COC6H5 was found to be the sole
product. The reaction profile is given in Figure 1.
Excellent selectivity to the double bond transfer hydro-
genation was obtained using various substrates, as shown in
Table 1. No hydro-dehalogenated products were observed
throughout the reaction period with any of those different
starting materials except 1c and 1d. In the case of 1c, 30%
hydro-dechlorination and 17% alcohol were obtained as
byproducts, whereas for 1d, only 18% debrominated product
has been found.
(1) Zhang, L. Q.; Winterbottom, J. M.; Boyes, A. P.; Rayamahasay, S. J. Chem.
Technol. Biotechnol. 1998, 72(3), 264.
(2) Satagopan, V.; Chandalia, S. B. J. Chem. Technol. Biotechnol. 1994, 59(3),
257.
(3) Rylander, P. N. Catalytic Hydrogenation in Organic Synthesis; Academic
Press: New York, 1979.
(4) Brown, H. C.; Krishnamurthy, S. Tetrahedron 1979, 35, 567.
(5) Wigfield, D. C. Tetrahedron 1979, 35, 449.
(6) Collman, J. P.; Finke, R. G.; Matlok, P. L.; Wahren, R.; Komoto, R. G.;
Brauman, J. I. J. Am. Chem. Soc. 1978, 100, 1119.
(7) Chikashita, H.; Miyazaki, M.; Itoh, K. Synthesis 1984, 308.
(8) Yoneda, F.; Kuroda, K.; Tanaka, K. J. Chem. Soc., Chem. Commun. 1984,
10, 1.
(9) Alba, A.; Aramendia, M. A.; Borau, V.; Garcia-Raso, A.; Jimenez, C.;
Marinas, J. M. Can. J. Chem. 1984, 62, 917.
(10) Ravasio, N.; Antenori, M.; Gargano, M. Tetrahedron Lett. 1996, 3529.
(11) Sasson, Y.; Blum, J. J. Org. Chem. 1975, 40, 1887.
(12) von Holleben, M. L. A.; Zucolotto, M.; Zini, C. A.; Oliveria, E. R.
Tetrahedron 1994, 50, 973.
After the reaction time, water was added to the reaction
mixture, and the compound was extracted in dichlo-
romethane. The organic layer was passed through a silica
gel column to remove the catalyst, and then the desired
product was isolated by simply evaporating the organic
solvent.
(15) Wiener, H.; Blum, J.; Sasson, Y. J. Org. Chem. 1991, 56, 6145.
(16) Bar, R.; Sasson, Y.; Blum, J. J. Mol. Catal. 1982, 16, 175.
(17) Cabello, J. A.; Campelo, J. M.; Garcia, A.; Luna, D.; Marinas, J. M. J.
Catal. 1985, 94, 1.
(18) Cabello, J. A.; Campelo, J. M.; Garcia, A.; Luna, D.; Marinas, J. M. J.
Org. Chem. 1986, 51, 1786.
(19) Wolfgang, K.; Heinz, Z. U.S. Patent 4,940,819, 1990; Chem. Abstr. 1990,
113, 40152.
(20) Sasson, Y.; Cohen, M.; Blum, J. Synthesis 1973, 359.
(13) Sasson, Y.; Blum, J. Tetrahedron Lett. 1971, 2167.
(14) Sasson, Y.; Blum, J.; Dunkelblum, E. Tetrahedron Lett. 1973, 3199.
10.1021/op0000327 CCC: $19.00 © 2000 American Chemical Society and The Royal Society of Chemistry
Published on Web 08/23/2000
Vol. 4, No. 6, 2000 / Organic Process Research & Development
•
571

Scheme 1. Transfer hydrogenation reaction using ethylene glycol
Scheme 2. Intermediate ketal formation and subsequent breaking to product
Table 1. a
starting
material
major
product
entry
t/h
conversion
selectivity
1
2
3
4
5
1a
1b
1c
1d
1e
4
6
8
5
7
2a
2b
2c
2d
2e
100
100
100
100
100
100
97
53
82
99
a Reaction conditions: starting ketone, 10 mmol, RuCl2 (PPh3)3 catalyst, 0.156
mmol, ethyleneglycol, 25 mL, temperature, 150 °C, 900 rpm stirring speed
Figure 2. Concentration profile for the transfer hydrogenation
of 4-ClC6H4CHdCHCOCH3. Reaction conditions: substrate,
10 mmol; catalyst, 0.156 mmol; temperature, 150 °C; ethylene
glycol (total reaction volume), 25 mL.
concentration of starting ketone and catalyst. A pseudo-first-
order rate law was observed for fixed catalyst loading. The
rate law can be expressed as follows:
-dCA/dt ) kCketoneCcat
-dCA/dt ) kobsCketone
,
where kobs ) kCcat
or
-ln(1 - XA) ) kobs
t
Figure 1. Reaction profile for the transfer hydrogenation of
4-ClC6H4CHdCHCOC6H5. Reaction conditions: substrate, 10
mmol; catalyst, 0.156 mmol; temperature, 150 °C; ethylene
glycol (total reaction volume), 25 mL.
where XA is the fractional conversion of 1a. The average
kobs value was 2.25 × 10-2 min-1 (see also Experimental
Section), and the energy of activation, Eact was found to be
52 kJ/mol.
Temperature was found to influence both substrate
conversion and product selectivity. Performing the reaction
at higher temperatures led to a faster rate of reaction, as
expected. However, the selectivity decreased marginally with
temperature (Figure 3). This is due to the other hydrogen
transfer reactions at different functional groups under the
reaction conditions, leading to some dehalogenation and
alcohol formation.
An entirely different profile was obtained when the
starting material was 4-ClC6H4CHdCHCOCH3. The reaction
then proceeds via an intermediate ketal (Scheme 2). To our
surprise it transformed with time to the desired product with
98% selectivity. The concentration profile is shown in Figure
2.
4-ClC6H4CHdCHCOC6H5 (1a) was chosen as a model
substrate for the kinetics and different process parameter
studies. The reaction rate was found to be a function of the
572
•
Vol. 4, No. 6, 2000 / Organic Process Research & Development

The formation of ketal under the reaction conditions when
there is a methyl group adjacent to the carbonyl functional
group could be supported by our previous work reported
elsewhere.21 The fact that there was no ketal formation, when
the phenyl group was adjacent to the carbonyl group instead
of the methyl group, might be explained by the steric
hindrance decreasing the probability for ethylene glycol to
access the carbonyl function.
Conclusions
Ethylene glycol can be directly utilized as a hydrogen-
transfer agent for the regio-specific double bond hydrogena-
tion of chlorobenzylidene ketones in the presence of RuCl2-
(PPh3)3 catalyst at 150 °C with a very high selectivity. The
separation process becomes much easier and convenient due
to high selectivity and complete conversions unlike reported
processes.
Experimental Section
Materials and Instrumentation. GC and GC-MS analy-
ses were performed using a HP-5890 gas chromatography
with a 50% diphenyl-50% dimethylpolysiloxane packed
column (25 m/0.53 mm). Starting ketones22 and the catalyst23
were synthesized at laboratory without any difficulties. Other
chemicals were purchased from commercial firms (>99%
pure) and used without further purification. Starting material
and products were characterized by MS data.
Figure 3. Effect of temperature on conversion and selectivity.
Reaction conditions: substrate, 10 mmol; catalyst, 0.156 mmol;
temperature, 150 °C; time, 4 h; ethylene glycol (total reaciton
volume), 25 mL.
General Procedure for Transfer Hydrogenation. In a
100 mL glass reactor were charged 2.5 g (10 mmol) of
4-ClC6H4CHdCHCOC6H5 (1a), 0.15 g (0.156 mmol) of tris-
(triphenylphosphine) ruthenium(II) chloride catalyst, and
ethylene glycol (total reaction volume 25 mL). The reactor
was heated to 150 °C, and the mixture was stirred (900 rpm)
at 150 °C for 4 h. Reaction progress was monitored by GC.
After the stipulated time the mixture was cooled, and 50 mL
of water was added to it. The product was then extracted
with 40 mL of CH2Cl2. Solvent evaporation afforded 2.2 g
of double bond hydrogenated product. In a view to do some
scale up works, the same reaction was performed in a 10
times batch with substrate 1a, and a substrate-to-catalyst ratio
of 1:100 at 150 °C for 6 h. A 98% selectivity to the desired
product has been achieved.
Experimental Procedure for Kinetic Studies. To a glass
reactor fitted with a condenser and six-bladed turbine stirrer
were charged 2.5 g (10 mmol) of 4-ClC6H4CHdCHCOC6H5
(1a), 0.15 g (0.156 mmol) of RuCl2(PPh3)3, and ethylene
glycol (total reaction volume 25 mL). The reaction mixture
was heated at 150 °C. Reaction progress was monitored by
GC. The following parameters were studied: (i) initial
substrate concentration, (three experiments at 10%w/v, kobs
) 2.24 × 10-2 min-1, r2 ) 0.97 for 5 observations; 20%w/
v, kobs ) 2.77 × 10-2 min-1, r2 )0.99 for five observations;
and 30%w/v, kobs ) 2.83 × 10-2 min-1, r2 ) 0.98 for five
observations); (ii) catalyst loading (four experiments using
Figure 4. Effect of catalyst loading on the rate and selectivity;
reaction conditions: substrate, 10 mmol; temperature, 150 °C;
time, 4 h; ethylene glycol (total reaction volume), 25 mL.
Conversely, increasing the catalyst loading increased the
rate of reaction, but the selectivity towards the desired
product decreased after a specific catalyst loading (Figure
4). Optimum selectivity was obtained when catalyst loading
was between 0.156 and 0.2 mmol.
Performing the reaction with homogeneous bis(triphenyl-
phosphine) palladium(II) chloride (0.11 g, 0.156 mmol) cata-
lyst led to only 18% selectivity to the desired saturated
ketone. The major product was hydro-dehalogenated product.
Use of other hydrogenating agents such as hydrogen gas even
at room temperature, formate at 100 °C, with the same cata-
lyst but instead of ethylene glycol, did not give any encour-
aging results. When the reaction was performed with propan-
2-ol at 150 °C, only 41% selectivity to the desired product
was achieved in 4 h, and the rest was hydro-dechlorination.
(21) Albin, P.; Blum, J.; Dunkelblum, E.; Sasson, Y. J. Org. Chem. 1975, 40,
2402.
(22) Vogel’s Textbook of Practical Organic Chemistry, 5th ed.; Longman
Scientific & Technical: Harrow, England, 1989.
(23) Stephenson, T. A.; Wilkinson, G. J. Inorg. Nucl. Chem. 1966, 945.
Vol. 4, No. 6, 2000 / Organic Process Research & Development
•
573

0.4% w/v RuCl2 (PPh3)3, kobs ) 0.8 × 10-2 min-1, r2 )
0.9838 for nine observations; 0.6% w/v RuCl2 (PPh3)3, kobs
) 2.25 × 10-2 min-1, r2 ) 0.982 for six observations; 0.8%
w/v mol % RuCl2(PPh3)3, kobs ) 3.08 × 10-2 min-1, r2 )
0.98 for five observations; and 1.0% w/v RuCl2(PPh3)3, kobs
) 3.88 × 10-2 min-1, r2 ) 0.998 for four observations);
(iii) reaction temperature (four experiments at 140 °C, kobs
) 1.53 × 10-2 min-1, r2 ) 0.996 for eight observations;
150 °C, kobs ) 2.25 × 10-2 min-1, r2 ) 0.97 for six
observations; 160 °C, kobs ) 3.5 × 10-2 min-1, r2 ) 0.97
for five observations; and 170 °C, kobs ) 4.2 × 10-2 min-1,
r2 ) 0.94 for five observations).
Received for review March 22, 2000.
OP0000327
574
•
Vol. 4, No. 6, 2000 / Organic Process Research & Development