Pd(0) supported onto monolithic polymers containing IL-like moieties. Continuous flow catalysis for the Heck reaction in near-critical EtOH

Article abstract of DOI:10.1039/b603224a

Long-term stable Pd(0) catalysts can be easily supported onto polymeric monoliths containing methyl-imidazole moieties and the corresponding reactors based on these materials can be applied for the continuous Heck reaction in near-critical EtOH. The Royal Society of Chemistry 2006.

Full text of DOI:10.1039/b603224a

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Pd(0) supported onto monolithic polymers containing IL-like moieties.
Continuous flow catalysis for the Heck reaction in near-critical EtOH{
Naima Karbass, Victor Sans, Eduardo Garcia-Verdugo,* M. Isabel Burguete and Santiago V. Luis*
Received (in Cambridge, UK) 3rd March 2006, Accepted 30th May 2006
First published as an Advance Article on the web 14th June 2006
DOI: 10.1039/b603224a
Long-term stable Pd(0) catalysts can be easily supported onto
polymeric monoliths containing methyl–imidazole moieties and
the corresponding reactors based on these materials can be
applied for the continuous Heck reaction in near-critical EtOH.
The Heck reaction is a versatile tool for C–C bond formation by
vinylation of aryl halides.1 The current challenge for palladium
catalyzed coupling reactions is the development of high perfor-
mance along with sustainable and environmentally benign reaction
conditions. In this regard, a specific target is to develop a
phosphine-free recyclable heterogeneous catalytic system to avoid
the use of expensive and air-sensitive basic phosphines.
Most of the Pd-supported catalysts used for Heck reaction are
defined as ‘‘Trojan horses’’ because they are only the reservoirs of
Scheme 1
the ‘‘soluble’’ active species generated under the reaction condi-
tions.2 Therefore, the long term stability of the immobilised
were used as catalysts for the Heck reaction between iodobenzene 5
and methyl acrylate 6a using 0.02 mol% Pd and DMF as solvent.
catalyst would be related to the ability of the support to release
Both catalysts showed a high efficiency for the Heck coupling
reaction. Quantitative yields for the trans-methyl cinnamate were
obtained after 3 h. Fig. 1 shows that the kinetic profiles for both
resins (3 and 4) are quite similar. In both cases, an induction period
is observed. This suggests that the reaction proceeds with a similar
mechanistic pathway for both catalysts. A hot filtration test
confirmed the leaching of palladium species for both resins. The
reaction proceeded in the filtrate with even higher reaction rates
than those observed in the presence of the Pd-supported solids. It
seems reasonable to assume that resins 3 and 4 act as pre-catalysts
releasing active palladium species into the solution.2
and catch the active species in order to regenerate the catalyst for a
new Heck reaction cycle.
Here we report on the combined use of Pd(0) catalysts supported
onto monolithic polymers containing imidazolium ionic liquid-like
(ILs) fragments and supercritical fluids. The surface of our mono-
lithic polymers contain imidazolium IL-like subunits that enable
the immobilisation and improve the stability of Pd(0) particles
leading to stable and active Pd(0) catalysts for the Heck reaction.
Recently ILs have been used to immobilise catalytic metal
complexes3 or to stabilise metal nanoparticles.4 In a similar way,
the surface of our monoliths modified by imidazolium IL-like
moieties can be used for the immobilisation of palladium. Also, the
monolithic materials have an additional advantage in their
potential for development of flow-through reactor systems.5
In preliminary studies, we and others have prepared several
methylimidazolium salts supported onto polystyrene resins.6,7
These fragments allow the immobilisation of palladium in two
different ways (Scheme 1): i) acid conditions: polymer 1 is treated
with Pd(OAc)2–HCl in THF to give a red polymer 2, which is
further reduced with NaBH4–EtOH, leading to polymer 3
containing supported Pd(0); ii) basic conditions: polymer 1 is
treated with a solution of Pd(OAc)2–Na2CO3 in DMF to afford the
corresponding Pd–NHC complexes 4.6 Pd-supported resins 3and 4
Asignificantdifferencewasfoundwhentheresinswerereusedfor
new cycles (see Table 1). The conversion observed for 4,preparedas
aPd–NHCcomplex,fallsdramaticallyafterthethirduse.However,
polymer 3 could be reused up to 6 times without any decrease in its
catalyticactivity.Thissuggeststhatinthepolymer3theIL-likeunits
canplayanimportantroleeitherininducingaslowerPdreleaseorin
Dept. of Inorganic and Organic Chemistry, A.U. for Advanced Organic
Materials, University Jaume I/CSIC, E-12071, Castello´n, Spain.
E-mail: luiss@qio.uji.es; eduardo.garcia-verdugo@qio.uji.es;
Fax: +34 964 728714; Tel: +34 964 728751
{ During manuscript preparation B. Karimi and D. Enders have reported
on the use of silica-supported ILs for this reaction (Org. Lett., DOI:
10.1021/ol060129z). Some of their results are strongly coherent with the
mechanistic considerations of the present work.
Fig. 1 Yield of trans-methylcinnamate 7a using different catalytic
systems at 90 uC in DMF.
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was monitored by the disappearance of the CH2–Cl group using
Table 1 Stability study for supported Pd catalysts 3 and 4
Yield (%)
bothFT-IRRamanspectrometryanda colorimetric method based
on the NBP test.10,11 A 95% conversion of the chloride groups was
achieved aftera 5 h reaction. Longer reaction timesdid notimprove
the conversion degree. It is possible that a small percentage C–Cl
groups are located in non-accessible highly cross-linked regions.
The reaction, under acidic conditions, of Pd(OAc)2 with the IL-
like units on the monolith yielded the corresponding Pd2+
supported complexes. The monolithic reactor was then attached
to the system shown in Fig. 2 and hot pressurised ethanol (200 uC,
8 MPa) was pumped through the monolith over 4 h. Ethanol
reduced Pd2+ to Pd(0) with the formation of Pd(0) particles on the
surfaces of the monoliths. SEM and electron probe microanalysis
revealed the presence of well dispersed Pd metal particles. It is of
note that the final Pd(0) loading of the catalyst (0.21 meq Pd g21
polymer) was kept much lower than the methyl–imidazolium
content (3.07 meg g21 polymer ca. 15 : 1 NHC : Pd ratio) to
favour the ‘‘catching’’ effect of the IL-like moieties.
Entry Polymer Run 1 Run 2 Run 3 Run 4 Run 5 Run 6
1
2
a
3a
4b
99
99
99
99
99
20
99
12
99
—
99
—
0.9 meq Pd g21 approx. ratio NHC/Pd 1.1. 0.4 meq Pd g21
.
b
approx. ratio NHC/Pd 2.2.
improving the release–catch mechanism. In order to test the ability
ofourfunctionalmaterialstocapturefromthesolutionthecatalytic
Pdspecies,amodelHeckreactionwasperformedusing0.02%molof
Pd(OAc)2 in the presence of resin 1. The reaction was completed
after 60 min at 90 uC. The presence of resin 1 slightly decreased the
reaction rate with respect to the ‘‘ligand free’’ catalysed reaction.
Polymer 1, which became black (resin 8), was filtered off from the
reaction medium, thoroughly washed and used as a catalyst for the
modelreaction.Thereactionwenttocompletionafter2.5h.Thus,it
seems that IL-like moieties in resin 1 can capture and stabilise
catalytically active soluble palladium species, which are generated
during the reaction. PVP-polymers and ammonium salts have
shownrelatedsequestrationandstabilisationeffectsforPdspecies.8
Our results show the practical advantages of the heterogeneous
system 3, whose higher stability enables the achievement of high
TON values by using the resin in consecutive cycles (30000 for 3 vs.
11000 for 4). A continuous flow system is a simpler way to perform
consecutive cycles because reaction and filtration operations are
carried out simultaneously. Thus, consecutives cycles can be
performed in a less time consuming mode. Simple process
intensification and space–time yield are best achieved in this way.
Encouraged by the promising initial results, a continuous flow
reactor system was developed (see Fig. 2). For the continuous set-
up, catalysts were prepared as monolithic polymers containing
imidazolium IL-like units. Monoliths are macroporous materials
with a well defined structure of continuous channels and confined
spaces allowing the development of flow-through reactor sys-
tems.5,9 Functionalisation of the matrix was introduced by
solventless reaction of benzyl chloride groups with methylimida-
zole at 90 uC. The introduction of the imidazolium IL-like moieties
The reaction of iodobenzene 5 with methyl acrylate 6a was
examined in a continuous flow system (Fig. 2) using DMF as the
solvent. A solution of 5 and 6a (0.67 mol L21 of 5 in DMF, molar
ratio 5 : 6a : Et3N of 1 : 1.1 : 2) was pumped at flow rates of
50 mLmin21 through the monolithic reactor. Aliquots were
analyzed for the methylcinnamate content (7a) at regular time
intervals. The reaction proceeds continuously with 100% yield for
7a at 200 uC and 8 MPa. In the flow system a small amount of the
substrate is actually forced into intimate contact with an ‘‘excess’’
of catalyst favouring higher conversions. Thus, a total conversion
of 5 can be achieved with residence times as short as 3–4 min, using
a monolithic mini-reactor with a free-volume of ca. 230 mL.
Besides, the continuous flow set-up improved the stability of the
system. No noticeable changes to activity were observed in both
product yield and selectivity after 745 min (ca. 162 bed-volumes) of
continuous use under the same conditions.
Some efforts have been reported to develop continuous flow
systems for palladium catalysed C–C bond formation.12 All of
them, however, require conventional organic solvents to be used
either for the reaction or for the extraction processes. In the search
for more environmentally friendly protocols the use of supercritical
fluids was considered. Initial runs were performed using scCO2 as
the reaction solvent. Although product formation was detected, the
low product/reactants solubility in scCO2 led to reactor blockage.
Hot pressurised ethanol can be a good alternative solvent.
Ethanol is not only benign, easily available and relatively cheap,
but is also a solvent whose properties are easily adjustable with P
and T. Supercritical ethanol provides a less corrosive solvent and
with more accessible critical parameters (Tc = 516 K, Pc = 6.4 MPa,
rc = 0.276 g?cm21) than scH2O. Therefore, it can be seen as a non-
corrosive, low pressure scH2O. One can also expect a pronounced
enhancement in the solubility compared with CO2 due to the
hydrogen-bonding ability of the former. Therefore, the use of
ethanol as a reaction medium of tuneable density and polarity was
evaluated. The optimisation of the conditions was systematically
investigated by varying temperature, pressure and flow rate.
Table 2 gathers some of the results achieved using near-critical
ethanol. In general, temperatures higher than 150 uC were required
to achieve significant yields of trans-methylcinnamate (entries 1–5,
Table 2). The reaction did not take place in ethanol at atmospheric
pressure and 90 uC. Conversion of 5 into 7a reached 85% at 200 uC
Fig. 2 Schematic diagram for the continuous flow reactor system. P-01,
reagents feed pump (flow rate = 0.01–5 mL min21, maximum allowed
pressure (Pmax) = 40 MPa); P-02, ethanol feed pump (flow rate =
0.25–1 mL min21, Pmax = 40 MPa); MX-01, Mixer Gilson; R-01,
monolithic microreactor (1/4 in AISI 316 tubing 15 cm, heat supplied by a
band heater (Watlow, 240 V, 200 W, NTB25X6UA3, 47 02 DM)); BPR-
01, back pressure regulator (Jasco BP-1580-81 Pmax = 42 MPa, Cv , 0.01).
3096 | Chem. Commun., 2006, 3095–3097
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nature of the solvent and support, temperature and the presence of
reducing agents have a dramatic effect not only in the activity of
the catalysts but also on the extent of the palladium leaching.2 The
presence of IL-like moieties in the polymer seem to help to stabilise
the Pd(0) reducing the leaching.
Table 2 Pressure and temperature dependence for the continuous
flow Heck reaction using hot pressurised ethanol
Residence
Entry mL min21 P/MPa T/uCb % Yield timec/min TOFd
1a
2
3
4
5
6
7
8
a
—
50
50
50
50
100
100
100
atm.
8
8
8
8
20
15
8
90
100
125
150
200
200
200
200
2
4
5
11
85
83
67
62
—
—
1.5
In summary, we have developed a highly stable and efficient
Pd(0) catalyst supported onto polymeric monoliths containing IL-
like units. This catalyst shows a good activity and stability under
continuous flow conditions. The reaction does not require the use
of inert atmosphere as is typical for these processes. The presence
of IL-like units seems to play an important role in the capture and
stabilisation of the active Pd species. The catalytic materials
presented here allow the substitution of classical solvents such as
DMF by more benign solvents like near-critical ethanol.
3.96
3.76
3.54
2.98
1.49
1.49
1.49
1.8
4.0
31.0
60.5
48.8
45.8
b
c
Run under batch conditions. Wall temperature. Residence
time = (VR?rEtOH/Reactor)/(FR?rEtOH/STP) where VR = reactor volume/
.
cm3, rEtOH
rEtOH
= EtOH density at process T and P/g cm23
Reactor
= EtOH density at standard T and P/g cm23. FR
=
Reactor
d
flow rate/cm3 min21
.
TOF calculated as (g 7a/g Pd)?h21
.
We would like to acknowledge the Spanish Ministerio de Ciencia
y Tecnolog´ıa (CTQ 2005-08016) and Bancaixa-UJI (P1B2004-13)
for financial support. E. G.-V. and V. S. also thank MEC for
personal financial support (Ramo´n y Cajal and PPQ programs).
and 8 MPa leading to a 100% selectivity for the trans isomer.
Temperatures higher than 250 uC led to transesterification of
methyl cinnamate to the corresponding ethyl cinnamate. The
reaction also showed some pressure dependence. An increase in
pressure is reflected in slight improvements in productivity (entries
6–8, Table 2).
Notes and references
1 (a) F. Alonso, I. P. Beletskaya and M. Yus, Tetrahedron, 2005, 61,
11771; (b) I. J. S. Fairlamb, Tetrahedron, 2005, 61, 9647.
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Commun., 2001, 2399.
Thereactionwasperformedat200uCand8MPaandusingdiffer-
ent flow rates to evaluate the effect of the residence time (Fig. 3). As
expected,anincreaseintheflowrate(from50to500mLmin21)ledto
a decrease in the yield of 7a (from 85% to 16%), which is consistent
with a reduction in the residence time in the reactor.13 On the other
hand, in the continuous flow system in hot pressurised EtOH the
Heck reaction did not show any significant induction period.
Again a stable performance for 420 min (ca. of 91 bed-volumes)
was observed for the Heck reaction in near critical EtOH (200 uC
and 8 MPa). After this experiment, the same mini-reactor was used
for the Heck reaction between iodobezene 5 and acrylonitrile 6b.
The reaction was studied for 480 min (ca. 104 bed-volume) leading
to 66% yield and 70 : 30 trans–cis selectivity. 14 These results are in
agreement with the different reactivities of 6a and 6b. An
additional test with this reactor for the reaction between 5 and
6a gave the same results as before.
4 J. Dupont, G. S. Fonseca, A. P. Umpierre, P. F. P. Fichtner and
S. R. Teixeira, J. Am. Chem. Soc., 2002, 124, 4228.
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A. Puzary and V. Sans, Tetrahedron Lett., 2006, 47, 2311.
8 (a) M. T. Reetz, R. Breinbauer and K. Wannlnger, Tetrahedron Lett.,
1996,37,4499;(b)M.T.ReetzandE.Westermann,Angew.Chem.,Int.Ed.,
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R. Gallina, A. Biffis, M. Zecca and B. Corain, J. Catal., 2005, 234, 1.
9 These materials were prepared as mini-reactors by polymerisation of
4-chlorovinylbenzene and divinylbenzene (40 : 60 w/wt 4-ClVB:DVB)
using toluene and dodecanol as porogenic agents in a stainless steel
column (15 cm 6 J inch) at 70 uC. The mean pore diameter of the
monolith was ca. 1.0 mm with a surface area of 8.5 m2 g21. See: (a)
J. A. Tripp, F. Svec and J. M. J. Frechet, J. Comb. Chem., 2001, 3, 216;
(b) B. Altava, M. I. Burguete, J. M. Fraile, J. I. Garc´ıa, S. V. Luis,
J. A. Mayoral and M. J. Vicent, Angew. Chem., Int. Ed., 2000, 39, 1503.
10 The NBP test is a sensitive colorimetric method developed by our group
for qualitative analysis of the presence of chlorine in chloromethylated
polymers, either in gel type (Merrifield) or monolithic resins
(Macroporous). See: F. Galindo, B. Altava, M. I. Burguete,
R. Gavara and S. V. Luis, J. Comb. Chem., 2004, 6, 859.
Metal analysis by ICP-MS of the solution aliquots obtained
showed levels of leached total metals ,1 ppm. It is known that the
11 B. Altava, M. I. Burguete, E. Garc´ıa-Verdugo, S. V. Luis and
M. J. Vicent, Tetrahedron, 2001, 57, 8675.
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13 Residence time was calculated according to standard literature:
O. Levenspiel, Chemical Reaction Engineering, 1999, 3rd edn, Wiley,
New York.
Fig. 3 % Yield 7a vs. flow rate for the continuous Heck reaction between
5 and 6a in ethanol at 200 uC and 8 MPa, 0.67 mol L21 of 5. Kinetics data
showing a pseudo first order rate Kobs = 10.8 6 1023 s21 (38.9 h21).
14 Trans : cis ratio was determined by GC and confirmed by NMR.
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Chem. Commun., 2006, 3095–3097 | 3097