Catalytic carbonylation of α-(6-methoxyl-2-naphthyl)ethanol to methyl esters of naproxen using PdCl2-CuCl2-PPh3-acid catalyst system

Article abstract of DOI:10.1016/S0022-328X(97)00757-2

α-(6-Methoxyl-2-naphthyl)ethanol was carbonylated into methyl ester of α-(6-methoxyl-2-naphthyl)propionic acid (Naproxen) in up to 100% yield and 100% selectivity using PdCl₂-CuCl₂-PPh₃-p-Ts catalyst system without any halogen promoter or other extreme condition.

Full text of DOI:10.1016/S0022-328X(97)00757-2

Journal of Organometallic Chemistry 556 (1998) 239–242
Priority communication
Catalytic carbonylation of h-(6-methoxyl-2-naphthyl)ethanol to methyl
esters of naproxen using PdCl –CuCl –PPh –acid catalyst system
2
2
3
Hongying Zhou, Jing Cheng, Shijie Lu, Hongxiang Fu *, Hanqing Wang
Lanzhou Institute of Chemical Physics, Chinese Academy of Sciences, Lanzhou, 730000, China
Received 6 October 1997; received in revised form 18 November 1997
Abstract
h-(6-Methoxyl-2-naphthyl)ethanol was carbonylated into methyl ester of h-(6-methoxyl-2-naphthyl)propionic acid (Naproxen)
in up to 100% yield and 100% selectivity using PdCl –CuCl –PPh –p-Ts catalyst system without any halogen promoter or other
2
2
3
extreme condition. © 1998 Elsevier Science S.A. All rights reserved.
Keywords: Carbonylation; h-(6-Methoxyl-2-naphthyl)ethanol; Methyl esters of Naproxen; PdCl –CuCl –PPh –acid catalyst
2
2
3
system
The transition metal complex catalyzed carbonyla-
also carbonylated to Ibuprofen using the same cata-
lytic system [9,10]. But both carbonylation reactions
of the alcohols took place in hydrogen chloride media
which is seriously corrosive for the autoclave and
may deactivate the catalyst. The carbonylation of
tert-butyl alcohol to esters of iso-valeric acid using
tion of olefins with carbon monoxide and alcohol is
of great interest for the synthesis of industrially valu-
able carboxylic esters such as linear fatty acid esters
and 2-aryl-propionic acid esters [1–3]. The carbonyla-
tion reaction of vinyl aromatics leads itself to the
synthesis of intermediates towards nonsteroidal antiin-
fammatory agents which are functionalized 2-aryl-pro-
pionic acids [4–7], but the satisfactory yields have not
been obtained. In some cases, it is difficult to obtain
olefins from corresponding alcohol or other com-
pounds. Therefore, in place of the olefins, it is desir-
able to use the corresponding hydroxylic compounds
as substrates for carbonylation. The study of car-
bonylation of alcohols to acids have been reported
Pd–PPh –p-Ts catalyst system was reported in our
3
previous papers [13–15].
In this work the catalytic system obtained in situ
from PdCl , CuCl , PPh , and p-toluenesulfonic acid
2
2
3
(p-Ts) promotes a highly selective formation of
methyl esters of Naproxen from h-(6-methoxyl-2-
naphthyl)ethanol, carbon monoxide and methanol in
1,4-dioxane without any halogen, and the results of
the carbonylation of h-(6-methoxyl-2-naphthyl)ethanol
and other similar alcohols to various esters catalyzed
by this catalyst system are presented in this paper.
The reaction of carbonylation of the h-(6-methoxyl-
[
8–12], such as h-(6-methoxyl-2-naphthyl)ethanol was
carbonylated to Naproxen using Pd(PPh ) /HCl cata-
3
2
lytic system [8], and 1-(4%-isobutylphenyl)ethanol was
2
-naphthyl)ethanol to methyl ester of Naproxen is
shown in Eq. (1), and the side reaction in Eq. (2) and
Eq (3).
*
Corresponding author.
0
022-328X/98/$19.00 © 1998 Elsevier Science S.A. All rights reserved.
PII S0022-328X(97)00757-2

2
40
H. Zhou et al. / Journal of Organometallic Chemistry 556 (1998) 239–242
This reaction was strongly influenced by the amount
tion of h-(6-methoxyl-2-naphthyl)ethanol was investi-
gated and the results were listed in Table 2. Under these
conditions high yield was obtained only when the palla-
dium chloride is used as precursors in combination with
of p-Ts, the results are listed in Table 1. Under the
reported experimental conditions high yield and selectiv-
ity are obtained when p-Ts/Pd (mol/mol)=13.1. These
results suggest that the starting h-(6-methoxyl-2-naph-
thyl)ethanol undergoes a reversible reaction in Eq. (2),
that is, in the presence of certain amounts of p-Ts,
h-(6-methoxyl-2-naphthyl)ethanol is dehydrated to 2-
vinyl-6-methoxynaphthalene which is carbonylated to the
esters of Naproxen by PdCl –CuCl –PPh .
six equivalents of PPh , and mild yield was obtained using
3
Pd/C as precursors. When the amount of PPh was
3
reduced at half, the yield and selectivity were also reduced
nearly at half. This result showed that molar ratio of P
to Pd must surpass 3, otherwise poor yields were obtained.
The reaction in Eq. (1) is also influenced by the
nature of the solvents and the results are listed in Table
3. It can be seen from Table 3 that the highest yields of
methyl esters of Naproxen were obtained when the
solvents with suitable polarization were used, such as
2
2
3
Various palladium compounds are widely used as
carbonylation catalysts. When the dioxane was used as
solvent and the molar ratio of p-Ts to Pd was 13.1, the
effect of the Pd(II) catalyst precursors on the carbonyla-
Table 1
The effect of the amount of p-Ts on carbonylation of h-(6-methoxyl-2-naphthyl)ethanol
No.
p-Ts/Pd (mol/mol)
Conversion of alcohol (mol%)
Yield (mol%)a
Ester Ether
Selectivity to ester (%)
Olefin
1
2
3
4
7.5
9.9
13.1
15.0
ꢀ100
96.3
ꢀ100
ꢀ100
66.7
77.0
ꢀ100
78.6
17.9
4.8
0
15.4
14.5
0
66.7
80.0
ꢀ100
78.6
5.2
16.4
Reaction conditions: PdCl , 0.08 mmol; CuCl , 0.185 mmol; PPh , 0.50 mmol; pressure, 6.0 MPa; temp. 100°C; reaction time, 24 h;
2
2
3
h-(6-methoxyl-2-naphthyl) ethanol, 0.80 g; methanol, 0.5 ml; 1,4-dioxane, 6.0 ml.
a
Yield based on the starting alcohol.
Table 2
Carbonylation of h-(6-methoxyl-2-naphthyl)ethanol using different palladium precursors
No.
Catalyst precursor (0.08 mmol)
Conversion of alcohol (mol%)
Yield (mol%)
Selectivity to ester (%)
Ester
Ether
Olefin
1
2
3
4
5
PdCl2
ꢀ100
ꢀ100
95.7
ꢀ100
0
0
0
5.0
7.6
12.6
39.2
ꢀ100
95.0
89.6
84.6
50.8
a
Pd (dba)2
95.0
3
Pd(OAc)2
85.0 3.1
69.1
45.9 5.2
Pd/C
81.7
90.3
0
b
PdCl2
Reaction conditions are the same as in Table 1, except that p-Ts/Pd=13.1 and catalyst precursor varied.
a
dba: dibenzylideneacetone.
b
PPh , 0.25 mmol.
3

H. Zhou et al. / Journal of Organometallic Chemistry 556 (1998) 239–242
241
Table 3
Catalytic carbonylation of h-(6-methoxyl-2-naphthyl)ethanol in different solvents
No.
Solvent (5 ml)
Conversion of alcohol (mol%)
Yield (mol%)
Ester Ether
Selectivity to ester (%)
Olefin
12.6
1
2
3
4
5
6
7
Benzene
Toluene
1,4-dioxane
THF
Anisole
ꢀ100
ꢀ100
ꢀ100
ꢀ100
ꢀ100
ꢀ100
89.0
64.5
86.8
ꢀ100
65.5
ꢀ100
ꢀ100
77.6
22.9
13.2
0
11.2
0
64.5
86.8
ꢀ100
65.5
ꢀ100
ꢀ100
87.2
0
23.3
0
0
11.4
Dimethoxyethane
0
4.5
Dioxanea
Reaction conditions are the same as in Table 1, except that p-Ts/Pd=13.1 and solvent varied.
a
Ethanol was used instead of methanol.
Scheme 1. Carbonylation of two kinds of alcohols in dioxane, namely h-phenyl ethanol and tert-butyl alcohol.
1
,4-dioxane, 1,2-dimethoxyethane and anisole, which
kinds of alcohols in dioxane: h-phenyl ethanol and
tert-butyl alcohol. The results are listed in Scheme 1
(reaction conditions were the same as in Table 1, except
that p-Ts/Pd=13.1, yields are calculated based on the
starting alcohols). It can be seen from Scheme 1 that
the reaction activity of h-phenyl ethanol is lower than
that of h-(6-methoxyl-2-naphthyl) ethanol. A possible
explanation is that h-phenyl ethanol easily undergo
etherification, and the ether is too stable to produce
styrene. In addition, two isomers of the product (b/n=
13.4) were obtained when h-phenyl ethanol was car-
bonylated by this catalyst. This result is just the same as
the carbonylation of styrene using PdCl –CuCl –PPh
give nearly 100% yields of ester. But the yields of ester
were not as high when the solvent’s polarization was
too large and too small. For example, when the ethanol
was used instead of methanol, the yield of ester was
only 77.6% because of the smaller polarization of
ethanol. This phenomena can be explained by the fact
that the first step of this catalytic reaction is the dehy-
dration of h-(6-methoxyl-2-naphthyl)ethanol to 2-vinyl-
6-methoxynaphthalene, then 2-vinyl-6-methoxynaph-
thalene is carbonylated to the esters of Naproxen. In
the first step, the larger polarization of solvent is more
favorable to the dehydration. But in the second step,
the smaller polarization of solvent is more favorable to
the hydroesterification [9]. Therefore, the solvents with
suitable polarization are required for this catalytic reac-
tion.
2
2
3
catalyst system [9]. tert-Butyl alcohol can be also car-
bonylated by this kind of catalyst and poor yield of
ester was obtained. The main product is methyl 2,2-
dimethylpropionate.
Other tertiary and secondary alcohols were also car-
bonylated by PdCl –CuCl –PPh –p-Ts catalytic sys-
tem. We have investigated the carbonylation of two
In conclusion, esters of Naproxen can be obtained in
good yields with excellent regiochemical selectivity by
the carbonylation of h-(6-methoxyl-2-naphthyl)ethanol
2
2
3

2
42
H. Zhou et al. / Journal of Organometallic Chemistry 556 (1998) 239–242
NY, 1982, pp. 101–223.
3] M. Beller, B. Cornils, C.D. Frohning, C.W. Kohlpaintner, J.
Mol. Catal. A. Chem. 104 (1995) 17.
4] H. Alper, J.B. Woell, B. Despeyroux, D.J.H. Smith, J. Chem.
Soc. Chem. Commun. (1983) 1270.
with palladium chloride, copper chloride and p-toluene-
sulfonic acid in the presence of triphenylphosphine
ligand. Other similar alcohols can also be carbonylated
by the same catalytic system.
[
[
[
[
5] H. Alper, D. Leonard, Tetrahedron Lett. 26 (1985) 5639.
6] M. Mlekuz, F. Joo, H. Alper, Organometallics 6 (1987) 1591.
Acknowledgements
[7] H. Alper, N. Hamel, J. Am. Chem. Soc. 112 (1990) 2803.
[
[
8] Mitsubishi Petrochemical Co. Ltd, JP 59-95239, 1984.
9] V. Elango, M.A. Murphy, K.G. Davenport, European Patent,
We are grateful to the Chinese National Natural
Sciences Fund Council for financial support.
2
84310, 1988.
[
[
[
10] J.N. Armor, Appl. Catal. 78 (1991) 141.
11] G. Gavinatio, L. Tonilo, J. Mol. Catal. 78 (1993) 131.
12] V. Elango, K.G. Davenport, M.A. Murphy, European Patent,
400892, 1989.
13] Hongying Zhou, Shijie Lu, Hongxiang Fu, J. Mol. Catal. A
Chem. 116 (1997) 329.
References
[
[
1] H.M. Colquhoun, D.J. Thompson, M.V. Twigg, Carbonylation:
Direct Synthesis of Carbonyl Compounds, Plenum Press, New
York, 1991.
[14] Hongying Zhou, Shijie Lu, Hongxiang Fu, Chin. J. Catal. 17
(1996) 311.
[
2] I. Tkatchenko, in: G. Wilkinson (Ed.), Comprehensive
Organometallic Chemistry, vol. 8, Pergamon Press, Elmsford,
[15] Hongying Zhou, Hongxiang Fu, Jing Chen, J. Mol. Catal. Chin.
10 (1996) 407.
.