, 2006, 16(2), 107–109
80
100
80
Acids
Conversion
Acids yield
60
40
60
40
20
0
1-Phenylethanol
Styrene
20
Styrene yield
0
1
2
3
4
5
20 40 60 80 100 120 140 160 180 200 220 240
P/MPa
t/min
Figure 1 Effect of pressure on the indicators of 1-phenylethanol car-
bonylation in the Pd(OAc)2/TsOH/NBu4Br. T = 110 °C, 2 h.
Figure 2 Carbonylation of 1-phenylethanol in the system 0.5% Pd(OAc)2/
20% TsOH/NBu4Br/heptane. T = 110 °C, P = 5 MPa.
The carbonylation of 1-phenylethanol was studied in detail,
since one of the products (hydratropic acid 1) is a structural
fragment of ibuprofen and its analogues.13–15 The reaction gives
hydrocinnamic acid 2 as a by-product. Furthermore, styrene
and traces of ethylbenzene were found in the reaction mass.
To ascertain Koch chemistry is not involved we carried out
a blank run without a Pd catalyst. No carbonylation occurred.
Styrene was the sole product formed in 45% yield, based on
GLC data.
The reaction requires an acidic promoter. Experiments showed
that HCl, HBr and TsOH were equally efficient. In the presence
of these compounds, complete conversion of phenylethanol was
reached for 2 h with 85–90% selectivity for the acids. The yield
of compounds 1 + 2 in the presence of trichloroacetic acid was
8%, and the reaction did almost not occur in the presence of
formic acid. Thus, a high acidity of the medium is a prerequisite
for the reaction to be successful, whereas the nature of the
anion is not important. This is reasonable because the system
contains an excess of bromide ions.
passes through a maximum. In this series of experiments, hexane
was added to the reaction mixture to prevent the possible
polymerisation of styrene and to determine its amount more
accurately. As a result, the reaction rate was somewhat lower
(Figure 2).
Based on the relationships obtained, it can be assumed that
styrene, which results from the dehydration of 1-phenylethanol,
is the true substrate of the carbonylation. Insertion of the olefin
into the Pd–H bond gives a branched (3) or linear (4) alkylpal-
ladium complex. Subsequent insertion of CO gives the corre-
sponding acyl complexes. Hydrolysis of the latter gives acids 1
and 2. The selectivity of the olefin insertion stage is presumably
determined by the CO pressure. As the carbon monoxide
pressure is increased and hence its concentration in the solution
increases, CO molecules compete more successfully for sites in
the ligand sphere of Pd. As a result, the catalytic complex
becomes more compact, which favours the formation of com-
pound 3, and hence 1, in agreement with experimental and
published data.15
We tested some other molten salts as reaction media. Only
trace amounts of carboxylic acids were obtained in NBu4Cl,
[BMIM][Cl], [BMIM][BF4] and [BMIM][PF6] with Pd(OAc)2
as a catalyst precursor. Remarkably, 1-phenylethanol conversion of
14% or less was reached in Cl–-containing molten salts, while the
substrate was completely converted in molten salts with complex
anions. Styrene was the major product in all of the runs.
The high yields of the acids can be obtained at a CO pressure
of 2 MPa or above. A decrease in the pressure affects the con-
version of the alcohol only slightly, but the selectivity of car-
bonylation decreases abruptly. On the contrary, the yield of
styrene increases, and styrene becomes the main reaction
product at CO pressures lower than 0.7 MPa (Figure 1). Likewise,
the regioselectivity depends considerably on the CO pressure.
A pressure decrease increases the selectivity with respect to
branched acid 1. The 1:2 ratio is 0.25 at a pressure of 0.5 MPa
and increases almost linearly with an increase in pressure to
reach 1.05 at 5 MPa. Similar dependences were obtained in a
study on the 1-(4-isobutylphenyl)ethanol carbonylation in the
presence of a traditional Pd-phosphine catalyst.15
If, for some reasons, carbonylation is hindered (for example,
the CO pressure is insufficient), styrene becomes the main
product. Furthermore, the reaction mixture contained traces of
ethylbenzene, which was obviously formed by the hydrogena-
tion of styrene (Figure 3).
Further evidence for the proposed consecutive scheme is the
fact that styrene can be converted into corresponding acids under
the reaction conditions giving the same regioselectivity.11,12
In the absence of phosphine ligands, palladium is retained in
the system as suspended nanoparticles stabilised by NBu4Br.8,10
Presumably, nanoparticles do not show catalytic activity but
COOH
Ph CH Me
1
i, CO
ii, H2O
Pd(OAc)2
CO, H2O TsOH/NBu4Br
PdLn
HPdLn
Ph CH Me
The time dependence of the reaction mixture composition
has a shape typical of consecutive reactions. The styrene content
3
HPdLn
Table 1 Carbonylation of alcohols in the 0.5% Pd(OAc)2/20% TsOH/
NBu4Br catalytic system. T = 110 °C, P = 5 MPa, 2 h.
OH
Ph CH Me
Ph
H+
Conversion
(%)
Yield (%)
(GLC)
– H2O
Alcohol
Product
PhCH CH2
CO, H2O
PhCH2CH2PdLn
MeOH
EtOH
73
32
MeCOOH
65
19
9
66
87
43.5
44
6
4
EtCOOH
EtCOOEt
i, CO
ii, H2O
BunOH
PhCH2OH
PhCH(OH)Me
73
98
100
BunCOOBun
PhEt
PhCH2COOH
PhCH(Me)COOH 1
PhCH2CH2COOH 2
cyclo-C6H11COOH
c-C6H11C(O)OC6H11-c
PhCH2CH2COOH
L = TsO, CO, Br
Figure 3 Conversion scheme.
2
cyclo-C6H11OH
13
5
108 Mendeleev Commun. 2006
Eliseev, Oleg L.
