Comparison between polyethylenglycol and imidazolium ionic liquids as solvents for developing a homogeneous and reusable palladium catalytic system for the Suzuki and Sonogashira coupling

Article abstract of DOI:10.1016/j.tet.2005.06.119

The carbapalladacycle complex of 4-hydroxyacetophenone oxime is a highly active palladium catalyst to effect the Suzuki coupling of aryl chlorides and other C-C forming reactions in water. In an attempt to develop a reusable, homogeneous system based on this complex, its stability against prolonged heating in different ionic liquids and polyethylenglycol (PEG) has been studied. It was found that the palladium complex decomposes in water, 1-butyl-1-methylimidazolium hexafluorophosphate and 1-butyl-1-methylimidazolium chloride to form palladium nanoparticles in the first two cases and PdCl ₄^2- in the third case. In contrast, this cyclic palladium complex was stable upon extended heating in 1-butyl-2,3-dimethylimidazolium hexafluorophosphate and in PEG. The activity of this complex for the Suzuki and Sonogashira correlates with the stability of the complex, the activity in PEG being higher than any of the ionic liquids tested. Although the carbapalladacycle complex also decomposes in PEG upon reaction, the resulting Pd nanoparticles (2-5 nm size) are stabilized by PEG acting as ligand. In this way, a reusable, homogeneous system in PEG has been developed that is able to effect the Suzuki and Sonogashira couplings without the need of copper and phosphorous ligands, working at the open air.

Full text of DOI:10.1016/j.tet.2005.06.119

Tetrahedron 61 (2005) 9848–9854
Comparison between polyethylenglycol and imidazolium ionic
liquids as solvents for developing a homogeneous and reusable
palladium catalytic system for the Suzuki and
Sonogashira coupling
*
´
Avelino Corma, Hermenegildo Garcıa and Antonio Leyva
´
´
Instituto de Tecnologıa Quımica CSIC-UPV, Av. De los Naranjos s/n, 46022 Valencia, Spain
Received 21 March 2005; revised 13 June 2005; accepted 28 June 2005
Available online 25 August 2005
Abstract—The carbapalladacycle complex of 4-hydroxyacetophenone oxime is a highly active palladium catalyst to effect the Suzuki
coupling of aryl chlorides and other C–C forming reactions in water. In an attempt to develop a reusable, homogeneous system based on this
complex, its stability against prolonged heating in different ionic liquids and polyethylenglycol (PEG) has been studied. It was found that the
palladium complex decomposes in water, 1-butyl-1-methylimidazolium hexafluorophosphate and 1-butyl-1-methylimidazolium chloride to
form palladium nanoparticles in the first two cases and PdCl24K in the third case. In contrast, this cyclic palladium complex was stable upon
extended heating in 1-butyl-2,3-dimethylimidazolium hexafluorophosphate and in PEG. The activity of this complex for the Suzuki and
Sonogashira correlates with the stability of the complex, the activity in PEG being higher than any of the ionic liquids tested. Although the
carbapalladacycle complex also decomposes in PEG upon reaction, the resulting Pd nanoparticles (2–5 nm size) are stabilized by PEG acting
as ligand. In this way, a reusable, homogeneous system in PEG has been developed that is able to effect the Suzuki and Sonogashira couplings
without the need of copper and phosphorous ligands, working at the open air.
q 2005 Elsevier Ltd. All rights reserved.
1. Introduction
complexes considered highly active homogeneous catalysts
should be surveyed for stability and considered in principle
as suspicious of being precursors of other Pd species that are
really the active catalysts for the C–C coupling. In
particular, our work focus on carbapalladacycle complex
1. Carbapalladacycle complex 1 has been reported by
Imidazolium ionic liquids have been widely used as medium
to perform Pd catalyzed C–C bond reactions.1–6 In
precedents related to this work it has been demonstrated
that some organometallic palladium complexes act as
catalyst precursors rather than being the actual catalyst
since they are transformed under reaction conditions into
different Pd species.5,7–11 The nature of these species
depends on a large extent on the imidazolium substitution
and on the nature of the counter-balancing anion.6,11,12
Thus, using non-coordinating anions, black Pd nanoparti-
cles are formed, while PdCl24K can be stabilized when ClK
is the counter anion of 1,2,3-trialkylimidazolium ionic
liquid.12 On the other hand, using chloride or bromide salts
of 1,3-dialkylimidazolium, a dimeric imidazolidene Pd
complex is formed, which can exhibit some activity for the
Suzuki and Heck coupling reactions (Scheme 1).
´
Najera and co-workers as a highly active homogeneous
palladium catalyst that is able to promote in water the
Suzuki coupling of aryl chlorides and even the coupling of
electron-withdrawing aryl fluorides.13–18 Considering this
high activity, it would be of interest to convert this Pd
catalyst into a recoverable and reusable catalytic system
(Structure 1).
In the present work, we have considered the carbapallada-
cycle 1 and addressed its stability in different ionic liquids
and polyethylenglycol (PEG). The objective is to determine
In view of these precedents, it is clear that most Pd
Keywords: Sonogashira coupling; Carbapalladacycle complex; Poly-
ethyleneglycol; Imidazolium ionic liquids; Suzuki coupling.
*
Corresponding author. Tel.: C34 963877805; fax: C34 963877809;
e-mail: hgarcia@qim.upv.es
Scheme 1. Formation of [Pd2(m-Br)2Br2(C4C1)im2].
0040–4020/$ - see front matter q 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2005.06.119

A. Corma et al. / Tetrahedron 61 (2005) 9848–9854
9849
Complex 1 exhibits in UV/Vis spectroscopy characteristic
metal-to-ligand charge transfer bands peaking at 350 and
290 nm. Given the transparency of imidazolium ionic
liquids and PEG in the long wavelength regimen of the
optical spectrum,20,21 recording transmission UV/vis spectra
can be a simple, suitable spectroscopic technique to follow
the persistence of the complex. The list of solvents studied
and the result obtained are summarized in Table 1.
Structure 1. Carbapalladacycle 1 derived from 4-hydroxyacetophenone.
the stability of carbapalladacycle 1 in different liquid media
with the target of obtaining a highly active reusable,
homogeneous catalytic system for the Suzuki and Sonoga-
shira coupling. We have compared the performance and
catalytic activity of 1 in imidazolium ionic liquids with that
in polyethyleneglycol and we have found that PEG is a very
convenient medium for these Pd catalyzed reactions,
allowing the reuse of the catalyst without loss of the
catalytic activity. Although complex 1 also decomposes
quickly in PEG in the first use, reusability of the system
derives from the ability of PEG to stabilize Pd nanoparticles
by acting as ligand. PEG has advantages of being a green
solvent, with a complete lack of toxicity, large availability,
low cost and immiscibility with ethyl ether and other
organic solvents.
Table 1. List of solvents studied and summary of the results obtained after
the thermal treatment at 120 8C
Solvent
H2O
Time (h) Stability Product
Evidence
24
72
24
No
No
No
Pd nanoparticles
Visual darkening
UV/vis spectra
TEM
Visual darkening
UV/vis spectra
TEM
(C1C4)
imPF6
Pd nanoparticles
(C1C4)
imCl
Pd chloride
species com-
plexed with imi-
dazolidene
Carbapallada-
cycle 1
UV/vis spectra
HPLC-ESI-MS
(C1C1C4)
imPF6
PEG
72
72
Yes
Yes
UV/vis spectra
HPLC-ESI-MS
UV/vis
Carbapallada-
cycle 1
2. Results and discussion
HPLC-ESI-MS
Firstly, we will comment on the stability of carbapallada-
cycle 1 in imidazolium ionic liquids and PEG and our
attempts to characterize the Pd species derived there from in
each case. Secondly, we will compare the reactivity of
carbapalladacycle 1 in ionic liquids and PEG.
As it can be seen in the Table 1, heating the complex 1 in
water, (C1C4)imPF6 and (C1C4)imCl lead to the gradual
decomposition (hours) of the complex, evidenced by the
disappearance of the absorption bands characteristic of
complex 1. Figure 1 shows some selected optical spectra to
illustrate the UV/Vis monitoring of carbapalladacycle 1
decomposition. The disappearance of complex 1 is
accompanied in two cases by a darkening of the solution.
When apparent darkening of the solution occurs, the
resulting transmission optical spectrum was compatible
either with that of the neutral acetophenone oxime ligand
when water was used as solvent or with protonated oxime
ligand in the case of (C1C4)imPF6. These optical spectra
suggest that decomplexation of the carbapalladacycle has
occurred and the acetophenone oxime ligand has been
formed. TEM images of the black solution after heating
carbapalladacycle 1 in water or (C1C4)imPF6 (Fig. 2) show
2.1. Stability of carbapalladacycle complex in ionic
liquids and PEG
Imidazolium ionic liquids appear as promising green media
for the purpose of developing a homogeneous, reusable
catalytic system since they exhibit solubility for a wide
range of organic compounds that latter can be separated
from the ionic liquid by liquid–liquid extraction using some
conventional immiscible organic solvents such as ethyl
ether and hexane. Also solid PEG becomes liquid at
temperatures higher than 40 8C, exhibits high chemical
stability to a wide range of reagents and a high solubility for
many organic compounds as well as inorganic salts. Since
PEG is immiscible with hexane, ethyl ether and even cold
methanol, substrates and reaction products can be recovered
by liquid–liquid extraction in hot. The condition to have a
reusable homogeneous catalytic system is, as in the case of
ionic liquids, that the catalytic species should remain
unextracted and active in PEG.
A previous point concerning reusability is the stability of the
complex under the reaction conditions, particularly know-
ing that most carbapalladacyles decompose under reaction
conditions to give various Pd species that are finally
converted into Pd particles.7,19 Aimed at studying the
stability of complex 1 and the influence of the nature of the
ionic liquid on its stability, we submitted 1 to prolonged
heating in different imidazolium ionic liquids and PEG and
followed the evolution of the system by UV/vis spec-
troscopy. The heating temperature corresponds to that
commonly used in Pd catalyzed reactions.
Figure 1. UV/vis spectra recorded in CH3CN of: (a) complex 1 in
(C1C4)imPF6 after 2 h of thermal treatment; (b) complex 1 in (C1C4)imPF6
after 72 h of thermal treatment; (c) complex 1 in (C1C4)imCl after 24 h of
thermal treatment; (d) complex 1 in water after 24 h of thermal treatment;
(e) acetophenone oxime treated with a 10% v/v HCl; (f) acetophenone
oxime.

9850
A. Corma et al. / Tetrahedron 61 (2005) 9848–9854
6000 Da) does not produce the decomposition of the
complex. Figure 3 shows the optical spectra recorded at
different heating times showing that the bands of complex 1
at 350 and 290 nm do not decay even after 3 days of heating
at 120 8C. The above results suggest that nucleophilic
counter anions and the acidity of the H at 2-position of the
imidazolium are two factors that eventually produce
carbapalladacycle complex instability.
Stability of carbapalladacycle 1 in (C1C1C4)imPF6 after the
thermal treatment was also confirmed by HPLC-ESI-MS, in
where peaks at m/z 297, 338 and 594, containing the
characteristic Pd isotopic distribution, were recorded. These
peaks can be attributed, respectively, to the carbapallada-
cycle ligated to one (297 Da) and two (338 Da) CH3CN and
the corresponding dimer of the mono CH3CN complex
(594 Da). CH3CN is the solvent used in HPLC analyses and
the MS spectra would indicate the occurrence of a CH3CN
by ClK exchange in complex 1. It is appropriate to comment
here that control experiments by HPLC-ESI-MS in the case
of water and (C1C4)imPF6 treatment did not allow to detect
any Pd peak, suggesting that in those cases in where
darkening of the solution occurs, no organometallic
complex is present. Importantly, for (C1C4)imCl and
(C1C1C4)imPF6 in where no darkening of the solution
upon thermal treatment was observed, TEM images show
that the ionic liquid is free from Pd nanoparticles.
Scheme 2 summarizes the results of our thermal stability
study. It is clear that the solvent is not an innocent medium
and leads to the decomposition of complex 1. Water and
Figure 2. TEM images of Pd nanoparticles formed upon heating a solution
of carbapalladacycle 1 in (C1C4)imPF6. The scale bar of parts (a) and (b)
correspond to 500 and 100 nm, respectively.
the presence of palladium nanoparticles (2–5 nm, Table 1).
The possibility of having in addition imidazolium carbene
complexes as reported in other cases cannot be disregarded
from our data although no evidences from electrospray
ionization HPLC-MS (HPLC-ESI-MS) could be obtained
(see below).
In contrast to the evolution of complex 1 in water and
(C1C4)imPF6, decomposition of complex 1 in (C1C4)imCl
also occurs as evidenced by UV/vis spectroscopy but in this
case no darkening of the solution was observed, therefore,
formation of Pd metal particles does not seem to occur in
(C1C4)imCl. Using HPLC-ESI-MS we have been able to get
evidence of the presence of Pd species being compatible
with PdCl2 associated to imidazolidene carbene. It has to be
noted that MS is very useful and safe spectroscopic
technique to determine the elemental composition of Pd
species, since the natural isotopic distribution constitutes a
fingerprint revealing the presence of Pd. This is also the case
of Cl and, therefore, the structure of PdCl2 associated to
imidazolidene carbene is firmly supported by MS.
Figure 3. (a) UV/vis spectra of carbapalladacycle 1 dissolved in
(C1C1C4)imPF6 recorded in CH3CN after heating at 120 8C for (a) 2 h;
(b) 8 h; (c) 24 h; (d) 48 h; (e) 72 h. (b) UV/vis spectra of carbapalladacycle
1 dissolved in PEG recorded in CH3CN after heating at 120 8C for (a) 2 h;
(b) 8 h; (c) 24 h; (d) 48 h; (e) 72 h.
The evolution of complex 1 in (C1C1C4)imPF6 and PEG was
also different as the previous liquids. Thus, heating for
prolonged periods in (C1C1C4)imPF6 and PEG (MW average

A. Corma et al. / Tetrahedron 61 (2005) 9848–9854
9851
some activity for the Suzuki coupling, either the complex or
atomic Pd species or Pd nanoparticles at early stages are
more active catalysts to promote the Suzuki coupling than
aged Pd nanoparticles.
In view of this encouraging catalytic performance in
aqueous medium, we attempted the same reaction in
(C1C4)imPF6 and (C1C1C4)imPF6 using CsAcO as base
without observing any product formation (Table 2). Fur-
thermore, even using highly reactive iodobenzene as
substrate, the corresponding biphenyl was only observed
in trace amounts (Table 2). In contrast to this, the use of
PEG as solvent and complex 1 as catalyst leads to the
corresponding 4-methylbiphenyl with almost complete
selectivity and high mass balance, thus showing the superior
performance of PEG compared to the series of imidazolium
ionic liquids tested.
Scheme 2. Thermal stability of carbapalladacycle 1 in H2O, imidazolium
ionic liquids and PEG.
imidazolium H-2 protons are sufficiently acidic to attack the
complex 1 and eventually Pd nanoparticles are formed,
unless Pd2C ions are intercepted by ClK or other complex-
ing anion. In this regard (C1C1C4)imPF6 is an inert medium.
PEG is also an inert medium for 1. It has to be remarked,
however, that in the presence of reactants under real
reaction conditions even in inert PEG, decomposition of
complex 1 takes place, probably during the reductive
elimination of the catalytic cycle (vide infra).
These promising results using PEG as solvent for Pd C–C
coupling reactions were expanded for the Sonogashira
cross-coupling between phenylacetylene and substituted
halobenzenes. The media studied and the results obtained
are summarized in Table 3.
As it can be seen there, using the organometallic complex 1
as catalyst in ionic liquids results, in general, in low to
moderate yields depending on whether more active iodo-or
a less reactive bromo-benzenes are used as starting
materials. If the palladacycle complex 1 is firstly decom-
posed and, then, the resulting Pd nanoparticles used
subsequently for the Sonogashira coupling, worst results
are generally obtained. This again indicates that carbapalla-
dacycle 1 or Pd species at early stages of the formation of
nanoparticles are more active than the aged Pd nanoparticles
themselves. In agreement with this, it is worth commenting
from Table 3 that (C1C1C4)imPF6, in where we have
previously demonstrated the stability of carbapalladacycle
1, results in significant higher yield than that of
(C1C4)imPF6 for the Sonogashira coupling, again in line
with the higher activity of the complex 1 compared to aged
Pd nanoparticles. In any case, the overall conclusion of the
catalytic tests is that imidazolium ionic liquids, particularly
those unsubstituted at position C-2, are not suitable as
2.2. Comparison of the catalytic activity of species
derived from carbapalladacycle 1 in ionic liquids and
PEG
To provide a valid comparison of the catalytic activity of
species derived from complex 1 in water, ionic liquids and
PEG, we initially studied the Suzuki coupling of 4-chlor-
oacetophenone and phenylboronic acid. Using complex 1 as
precursor in water under the reaction conditions previously
reported in the literature,16,17 the expected substituted
biphenyl was formed in very high yields. If, instead of a
fresh sample of complex 1 in water, the resulting black
colloidal suspension obtained after previous thermal
decomposition of complex 1 in water is used as catalyst,
then also the 4-acetylbiphenyl product is formed but with
significantly lower yields (Table 2). This must indicate that,
although Pd nanoparticles derived from complex 1 show
Table 2. Results for the Suzuki coupling of aryl halides with phenylboronic acids in different media
Solvent
Waterb
X
R1
R2
H
Base
Yield (%)a
Mass balance (%)
Cl
COCH3
K2CO3
78 (8)
62 (2)c
!5
!5
O99
O99
O99
—
30
80
(C4C1)imPF6
(C4C1C1)imPF6
PEG
I
H
CH3
CsOAc
a In brackets yield of 4,40-bisacetylbiphenyl.
b TBAB (0.5 equiv) were added, reaction time: 2 h (see Section 3).
c After thermal Pd reduction.

9852
A. Corma et al. / Tetrahedron 61 (2005) 9848–9854
Table 3. Results for the Sonogashira coupling of different aryl halides with phenylacetylene in different media
Solvent
X
Solvent/substrate ratio
(wt)
Yield (%)
By-products (%)a
Mass balance (%)b
(C4C1)imPF6
5
5
5
50
5
50
5
50
5
57
17
!5
0
38
52
6
5
2
—
—
—
1
2
—
3
90
O99
72
O99
74
79
27
38
79
I
Br
Br
Br
(C4C1C1)imPF6
(C4C1)imCl
PEG
2
2
50
50
5
50
50
5
88
O99c
0
12
—
2
20 (84)
50
75
40
(80)
70
Br
Brd
Cl
5
3
45c
0
—
—
18
2
50
50
0
(75)
40
25c
a Acetophenone and 4,40-bisacetylbiphenyl.
b Extracted with ethyl ether (3 ml!7) at room temperature. In brackets the mass balance value when the products are extracted by stirring the PEG mixture in
hot ether for 4 h.
c 1508C.
d Bromoanisole.
solvents for C–C coupling reactions using carbapallada-
cycle complex 1.
extracts, while Pd is under the analytical detection limit in
the extracts from PEG.
In this regard, PEG as solvent showed a better performance
that any of the imidazolium ionic liquid studied (see
Tables 2 and 3). Thus, using a solvent-to-substrate ratio of
50 and performing the liquid–liquid extraction in hot to
recover the reaction products, good mass balances and
product yields were obtained starting from 4-bromoaceto-
phenone. Moreover, the system could be reused five times
without any decrease in the selectivity of the process.
Concerning the relative activity of complex 1 in PEG and
water (where complex 1 exhibits the highest initial activity)
it has been previously established the positive influence of
the solvent polarity on the performance of carbapallada-
cycle 1. According to this, carbapalladacycle 1 is initially
more active in water, but in water decomposition and
formation of Pd black lead to an extensive deactivation that
make impossible the reusability of the system. Decompo-
sition of complex 1 under real reaction conditions (in the
presence of substrates) also occurs in PEG in the first use of
the complex 1 as revealed by TEM. However, the known
ability of PEG to act as a ligand plays a positive role
stabilizing the Pd nanoparticles and permitting their reuse,
although with lower intrinsic activity than in the first run in
water. Importantly, TEM images of Pd nanoparticles in PEG
after the first and fifth use of complex 1 show no change in
the particle size (Fig. 4).
Since it is known the higher reactivity of electron
withdrawing halobenzenes for the C–C cross-coupling
reactions, the benchmark to really assess the activity of a
Pd catalyst should be either for chloro- and bromo-
benzenes substituted by electron donor groups. Table 3
contains also data of the activity of carbapalladacycle 1 in
PEG using 4-bromoanisole and 4-chloroacetophenone, for
which moderate product yields were obtained. It is worth to
comment than no conversion at all was observed for the
same substrates in any of the imidazolium ionic liquids
studied and, thus, PEG is more suitable solvent as those
imidazolium ionic liquids tested.
The main advantage of PEG as solvent for the Sonogashira
coupling compared to previous literature reports23,24 is that
to achieve good yields of Sonogashira coupling products is
not necessary to use noxious copper(I) compounds and
expensive phosphorous ligands. Also, the fact that the
reaction is carried out in PEG at the open air instead of
under inert atmosphere (mainly due to the oxidability of the
phosphorus the ligands) is an additional advantage of this
process using PEG.
The favourable influence of using a high PEG to substrate
ratio can be understood by the need to solubilize completely
CsOAc that is the base being used in the process. The ability
of PEG to complex large alkali metal ions leading to
solubilization of the base is well known.22 Concerning the
reusability, chemical analyses of the extracted solutions
indicate the absence of CsC either in ionic liquid or PEG as
reaction solvents. However, chemical analyses reveal the
presence of significant amounts of Pd in the ionic liquid
In conclusion, we have established that organometallic
carbapalladacycle 1 undergoes extensive decomposition in
ionic liquids depending on the substitution and nature of the

A. Corma et al. / Tetrahedron 61 (2005) 9848–9854
9853
sources and were used without further purification. Gas
chromatographic analyses were performed on a HP 5890
instrument equipped with a 25 m capillary column of 5%
phenylmethylsilicone. GC/MS analyses were performed on
an Agilent 5973N spectrometer equipped with the same
column as the GC and operated under the same conditions.
ESI-HPLC-MS analyses were performed in an Agilent 1100
equipment with a parallel UV diode array detector using as
mobile phase CH3CN–H2O (50/50 v/v, flow: 0.7 ml minK1
and diammonium hydrogenphosphate as buffer. 1H and 13
)
C
NMR were recorded in a 300 MHz Bruker Avance
instrument using CDCl3, DMSO-d6 or CD3OD as solvents
and TMS as internal standard. UV/vis spectra were recorded
on a Shimadzu spectrophotometer using CH3CN as solvent.
The Pd and Cs content of the extracts was determined by
concentrating the solvent under reduced pressure, dissolving
the residue in a mixture 1:1 of concentrated HCl/HNO3
(2.5 mg in ca. 3 ml), diluting the strongly acidic solution in
water and measuring by quantitative atomic absorption
spectroscopy. Transmission electron microscopy were per-
formed in a Philips equipment after dispersing the sample in
CH2Cl2 and allowing to evaporate the halogenated solvent.
3.1.1. Procedure for the synthesis of 4-hydroxyaceto-
phenone oxime. 4-Hydroxy-acetophenone (3 g, 0.022 mol)
was added to a solution of hydroxylamine hydrochloride
(5.13 g, 0.074 mol) and sodium acetate (10.26 g, 0.125 mol)
in water (26 ml). The solution was stirred at reflux
temperature for 1 h. After that time, diethyl ether was
added several times for extraction. The organic phases were
dried and the solvent evaporated under vacuum. To the
obtained residue, hexane was added and 1-(4-hydroxyphe-
nyl)ethanone oxime started to precipitate as a white solid
(3.25 g, 0.0215 mol, 98%). Mp: 146–147 8C. IR(KBr, cmK1):
3324, 1642, 1603, 1514, 1444, 1316, 1240, 1176, 940, 825,
589. 1H NMR dH (ppm, 300 MHz, CD3OD): 7.49 (2H, d, JZ
5 Hz), 6.77 (2H, d, JZ5 Hz), 2.18 (3H, s). 13C NMR dC (ppm,
300 MHz, CD3OD): 159.9, 156.7, 130.2, 128.9, 116.5, 12.55.
MS (FAB): m/z 151. Anal. Calcd for C8H9NO2 (151.15): C,
63.5; H, 5.95; N, 9.26. Found: C, 63.19; H, 6.22; N, 9.35.
Figure 4. TEM images recorded from a solution containing originally
carbapalladacycle 1 in PEG after one (top) or five (bottom) uses as catalyst
for the Sonogashira coupling of 4-chloroacetophenone and phenylacetyl-
ene. The scale bar of the figures corresponds to 100 nm.
counter ion. In one case, using (C1C1C4)imPF6, no thermal
decomposition was observed. However, even in (C1C1C4)-
imPF6, the catalytic activity is low probably due to a poor
CsAcO solubility. This low catalytic activity of (C1C1C4)-
imPF6 makes the development of a homogeneous and
reusable catalytic system for Pd C–C coupling reaction
based on complex 1 in imidazolium ionic liquids
unpractical. In contrast to the behaviour of ionic liquids,
PEG appears as a promising green medium to perform Pd
catalyzed reactions. The decomposition of organometallic
Pd complex 1 in PEG does not occurs upon prolonged
heating, but it occurs under real reaction conditions.
However, Pd nanoparticles appears to become stabilized
by PEG and, in addition, the CsAcO is fairly soluble in PEG.
In this way, a reusable and recoverable, homogeneous Pd
system based on PEG had been demonstrated. This has been
particularly interesting for the Sonogashira coupling in
where no copper salts and P ligands are used.
3.1.2. Procedure for the synthesis of the oxime
carbapalladacycle 1. To a solution of Li2PdCl4
(524.1 mg, 2 mmol) in methanol (4 ml), a methanolic
solution (2 ml) of 4-hydroxyacetophenone oxime (302 mg,
2 mmol) and sodium acetate (0.164 g, 2 mmol) was added.
The mixture was stirred at room temperature for 72 h. The
mixture was filtered and after adding water (5 ml), the
cyclopalladated complex (1) starts to precipitate as a yellow
solid (75%). Mp: O250 8C. IR (KBr, cmK1): 3429, 1627,
1584, 1472, 1430, 1375, 1326, 1260, 1211, 1037, 873, 799,
1
608. H NMR dH (ppm, 300 MHz, DMSO-d6): 10.38 (1H,
s), 9.88 (1H, s), 9.77 (1H, s) 9.63 (1H, s), 7.3 (2H, s), 7.15
(2H, d, JZ8 Hz), 6.5 (2H, d, JZ8 Hz), 2.23 (6H, s). 13C
NMR dC (ppm, 300 MHz, DMSO-d6): 167.5, 157.3, 154.7,
133.1, 128.3, 122.1, 111.8, 11.6. MS (FAB): m/z 584. Anal.
Calcd for C16H16N2O4Pd2Cl2 (584.04): C, 32.87; H, 2.74;
N, 4.79. Found: C, 32.12; H, 2.87; N, 4.59.
3. Experimental
3.2. Study of the stability of the carbapalladacycle oxime
complex in the different solvents
3.1. General
Reagents and solvents were obtained from commercial
The carbapalladacycle complex 1 (14.6 mg, 0.05 mmol) and

9854
A. Corma et al. / Tetrahedron 61 (2005) 9848–9854
the corresponding solvent (1 g) were magnetically stirred in
a pre-heated oil bath at 120 8C. The course of the reaction
was periodically followed by stopping the stirring and
taking aliquots (100 ml) that were diluted in CH3CN (ca.
2 ml) and monitored by UV spectroscopy.
times). The combined ether extract was filtered and the
solvent removed under reduced pressure. The crude was
weighed and analysed by GC using nitrobenzene as external
1
standard, GC–MS and H and 13C NMR.
3.3. Typical procedure for Sonogashira reactions
Acknowledgements
The carbapalladacycle complex 1 (14.6 mg, 0.05 mmol,
5 mol%) was placed in a screw capped vial and
4-bromoacetophenone (199 mg, 1 mmol), phenylacetylene
(124, 1.2 equiv), cesium acetate (230 mg, 1.2 equiv) and the
corresponding solvent (1 g, solvent/aryl halide weight
ratioZ5) were added. When the solvent-to-reactive weight
ratio was 50 the amount of reagents and catalyst was divided
by 5 and 2 g of solvent were used. The resulting mixture was
placed in a preheated oil bath at 120 8C under magnetic
stirring. After 24 h, the reaction was cooled for 1 min and
the resulting mixture extracted with diethyl ether (2 ml!7
times). The combined ether extract was filtered and the
solvent removed under reduced pressure. The crude was
weighed and analysed by GC using nitrobenzene as external
Financial support by the Spanish Ministry of Science and
Technology (MAT2003-01226) and Generalidad Valencia
(grupos 03-020) is gratefully acknowledged. A.L. thanks the
Spanish Ministry of Education for a postgraduate
scholarship.
References and notes
1. Keim, W.; Korth, W.; Wasserscheid, P. Preparation of ionic
liquids for catalysts. WO Patent 0016902, 2000.
2. Sheldon, R. Chem. Commun. 2001, 2399–2407.
3. Dupont, J.; de Souza, R. F.; Suarez, P. A. Z. Chem. Rev. 2002,
102, 3667–3691.
1
standard, GC–MS and H and 13C NMR.
3.4. Recovery and reuse of the catalyst in PEG
4. Wasserscheid, P. Ionic Liq. Synth. 2003, 213–257.
5. Welton, T. Coord. Chem. Rev. 2004, 248, 2459–2477.
6. Welton, T.; Smith, P. J. Adv. Organomet. Chem. 2004, 51,
251–284.
The carbapalladacycle complex (2.9 mg, 0.01 mmol,
5 mol%).) was placed in a round-bottomed flask and
4-bromoacetophenone (39.8 mg, 0.2 mmol), phenylacety-
lene (26.4 ml, 24.8 mg, 1.2 equiv), cesium acetate (76.8 mg,
2 equiv) and PEG (3.6 g) were added. The mixture was
placed in a preheated oil bath at 120 8C and magnetically
stirred for 24 h. Then, the reaction was cooled for 1 min and
the resulting mixture extracted with diethyl ether (5 ml!7
times). The combined ether extract was filtered and the
solvent removed under reduced pressure. The crude was
weighed and analysed by GC using nitrobenzene as external
standard, GC–MS and 1H and 13C NMR. The solid mixture
was dried under vacuum pump (10K1 torr) for 5 min and
reused in a next run.
7. Xu, L.; Chen, W.; Xiao, J. Organometallics 2000, 19, 1123.
¨
8. Herrmann, W. A.; Bohm, V. P. W. J. Organomet. Chem. 1999,
572, 141.
9. Herrmann, W. A.; Bohm, V. P. W. Chem. Eur. J. 2000, 6,
1017.
¨
10. Herrmann, W. A. Angew. Chem., Int. Ed. 2002, 41, 1291.
11. Dupont, J.; Spencer, J. Angew. Chem., Int. Ed. 2004, 43,
5296–5297.
12. Hamill, N.; Hardacre, C.; McMath, S. E. J. Green Chem. 2002,
4, 139.
13. Botella, L.; Najera, C. Angew. Chem., Int. Ed. 2002, 41,
179–181.
3.5. Typical procedure for Suzuki reactions
14. Alonso, D. A.; Najera, C.; Pacheco, M. C. J. Org. Chem. 2002,
67, 5588–5594.
The carbapalladacycle complex 1 (5.8 mg, 0.02 mmol,
5 mol%).) was placed in a screw capped vial and
4-chloroacetophenone (52 ml, 62 mg, 0.4 mmol) or iodo-
benzene (56 ml, 102 mg, 0.5 mmol), phenylboronic acid
(61 mg, 0.5 mmol, 1.25 equiv) or 4-tolylboronic acid
(81.6 mg, 0.6 mmol), potassium carbonate (69 mg,
0.5 mmol, 1.25 equiv) or cesium acetate (115 mg,
0.6 mmol) and bidistilled water (2 ml, dissolving TBAB
(64.5 mg, 0.2 mmol, 0.5 equiv)) or ionic liquids (400 mg) or
PEG (400 mg) were added. The mixture was placed in a
preheated oil bath at 120 8C and magnetically stirred. Water
as solvent. After 2 h, the reaction was cooled, diluted in
bidistilled water (3 ml) and extracted with ethyl acetate (3!
10 ml). The organic phases were dried using magnesium
sulfate, filtered and concentrated under reduced pressure.
The resulting crude was analysed by GC and GC–MS using
nitrobenzene as external standard. Ionic liquids or PEG as
solvents. After 24 h, the reaction was cooled for 1 min and
the resulting mixture extracted with diethyl ether (2 ml!7
15. Alonso, D. A.; Najera, C.; Pacheco, M. C. Tetrahedron Lett.
2002, 43, 9365–9368.
16. Alonso, D. A.; Najera, C.; Pacheco, M. C. Adv. Synth. Catal.
2003, 345, 1146–1158.
17. Najera, C.; Gil-Molto, J.; Karlstroem, S.; Falvello, L. R. Org.
Lett. 2003, 5, 1451–1454.
18. Baleizao, C.; Corma, A.; Garcia, H.; Leyva, A. J. Org. Chem.
2004, 69, 439–446.
19. Cassol, C. C.; Umpierre, A. P.; Machado, G.; Wolke, S. I.;
Dupont, J. J. Am. Chem. Soc. 2005, 127, 3298–3299.
20. Paul, A.; Mandal, P. K.; Samanta, A. Chem. Phys. Lett. 2005,
402, 375–379.
21. Alvaro, M.; Ferrer, B.; Garcia, H.; Narayana, M. Chem. Phys.
Lett. 2002, 362, 435–440.
22. Santaniello, E.; Manzocchi, A.; Sozzani, P. Tetrahedron Lett.
1979, 19, 4581–4582.
23. Tucker, C. E.; De Vries, J. G. Top. Catal. 2002, 19, 111–118.
24. Herrmann, W. A.; Ofele, K.; von Preysing, D.; Schneider,
S. K. J. Organomet. Chem. 2003, 687, 229–248.