Polyionic polymers - heterogeneous media for metal nanoparticles as catalyst in Suzuki-Miyaura and Heck-Mizoroki reactions under flow conditions

Article abstract of DOI:10.3762/bjoc.5.21

The preparation of monolithic polyionic supports which serve as efficient heterogeneous supports for palladium(0) nanoparticles is described. These functionalized polymers were incorporated inside a flow reactor and employed in Suzuki-Miyaura and Heck cro

Full text of DOI:10.3762/bjoc.5.21

Polyionic polymers – heterogeneous media for metal
nanoparticles as catalyst in Suzuki–Miyaura and
Heck–Mizoroki reactions under flow conditions
Klaas Mennecke and Andreas Kirschning*
Full Research Paper
Open Access
Address:
Beilstein Journal of Organic Chemistry 2009, 5, No. 21.
Institut für Organische Chemie and Zentrum für Biomolekulare
Wirkstoffe (BMWZ), Leibniz Universität Hannover, Schneiderberg 1B,
D-30167 Hannover, Germany
doi:10.3762/bjoc.5.21
Received: 28 March 2009
Accepted: 28 April 2009
Published: 08 May 2009
Email:
Andreas Kirschning* - andreas.kirschning@oci.uni-hannover.de
Guest Editor: A. Kirschning
* Corresponding author
© 2009 Mennecke and Kirschning; licensee Beilstein-Institut.
License and terms: see end of document.
Keywords:
Heck–Mizoroki reaction; heterogeneous catalysis; ion exchange resin;
microreactor; monolith; palladium; Suzuki–Miyaura reaction
Abstract
The preparation of monolithic polyionic supports which serve as efficient heterogeneous supports for palladium(0) nanoparticles is
described. These functionalized polymers were incorporated inside a flow reactor and employed in Suzuki–Miyaura and Heck cross
couplings under continuous flow conditions.
Introduction
Functionalized solid supports like polymers loaded with homo- In continuation of our efforts in developing immobilization
geneous catalysts are well established in organic synthesis concepts for reagents and catalysts including transition metals
[1-4]. Simple purification of the products and easy recyclability on solid phases inside monolithic flow reactors [9-18] we
of the catalysts are major advantages of heterogenization of describe the preparation of palladium nanoparticles loaded on
transition metals. A major hurdle for industrial applications of polyionic polymers and their use under continuous flow condi-
heterogenized homogeneous metal catalyst is associated with tions in various C-C-cross-coupling reactions [19-22].
keeping metal leaching down to a minimum. Immobilization
Results and Discussion
can be regarded as one enabling technique in organic chemistry
[5,6] that in conjunction with continuous flow processes creates Preparation of the catalyst
an ideal setup for an automated solution-phase synthesis. Recently, we reported on the preparation of a monolithic poly-
Furthermore, this combination of enabling techniques has great meric material incorporated inside megaporous glass shaped
potential in the production of fine chemicals [7,8].
Raschig-rings [11-18,23,24]. The polymeric phase was created
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Beilstein Journal of Organic Chemistry 2009, 5, No. 21.
tion of the resin inside a porous glass has the advantage that the
resin can only swell inside the glass while the glass monolith
provides a stable rod-like shape inside the microreactor. The
Merrifield-type resin was aminated to yield polyionic support 1.
This polymer serves as an anchor to leave the metal species
(sodium tetrachloropalladate; Na2PdCl4) in close proximity to
the ammonium group by means of ion exchange (Scheme 1). In
the following, the active Pd particle is generated upon reduc-
tion with a solution of sodium borohydride. A particular benefit
of the resulting solid support is the stabilization of the gener-
ated nanoparticles by the polymer-bound ammonium species
[23-29]. These functionalized composite Raschig-rings are
incorporated inside the flow microreactor which has a dead
volume of about 1–2 mL (Figure 1) [30]. We could show that
the palladium clusters are composed of palladium nanoparticles.
Particle sizes highly depend on the monomer composition of the
Scheme 1: Preparation of Pd(0) nanoparticles inside flow reactors.
by radical precipitation polymerization of styrene, vinylbenzyl polyionic support [4-vinylbenzyl chloride (VBC), divinylben-
chloride and divinylbenzene as monomers and consists of very zene (DVB), styrene]. Depending on the particle diameter a
small bead-like particles (0.2–2 µm) which are connected large impact on their catalytic performance (batch vs. flow;
through polymeric bridges. As a result an extended monolithic conventional vs. microwave heating) was noted [24]. In this
polymeric phase inside a glass monolith is created. Incorpora- context these materials have clear advantages over Pd(0) on
Figure 1: Top: Reactor (1–2 mL dead volume) with functionalized Raschig-rings; bottom: TEM-micrographs of Pd(0) nanoparticles on optimized
polyionic gel (left and central) and Raschig-rings (right).
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Beilstein Journal of Organic Chemistry 2009, 5, No. 21.
charcoal because the latter cannot be further optimized with min did not result in improved results, so that we commonly
respect to the mode of application [31-33]. In the present study, operated the system as a closed loop reactor in the following.
our highly optimized composite material was chosen (5.3%
DVB crosslinker and a 1:1 mixture of VBC/styrene) doped with Under these optimized conditions several examples of
nanoparticles (7–10 nm in size and a palladium content of 0.03 successful cross coupling reactions were achieved that are listed
weight% Pd on polyionic polymer).
in Table 1. We included combinations of electron rich and elec-
tron deficient aryl bromides with functionalized boronic acids
and yields of coupling products were commonly good to excel-
Suzuki–Miyaura cross coupling reactions
In our earlier work we showed that these materials are well lent. Aryl chlorides did not react with catalyst 3 under flow
suited for transfer hydrogenations under flow conditions [23, conditions.
24]. Recently, the Suzuki–Miyaura reaction and other palla-
dium catalyzed reactions have emerged as industrially very To fully explore the potential of polyionic gel 3 its reusability
desirable processes and miniflow fixed bed reactors loaded with was investigated next. The Suzuki reaction of 4-bromotoluene
Pd(0) nanoparticles should be well suited to perform these C-C (6) with phenylboronic acid (10) served as model reaction.
coupling reactions [34]. A particular challenge for utilizing the After each reaction the continuous flow reactor was regener-
Suzuki–Miyaura reaction in flow devices is the quest for truly ated by pumping a solution of DMF/water (10:1, 40 mL)
homogeneous reaction conditions in order to prevent clogging through the reactor before the next run was initiated (Figure 2).
of the irregular microchannels. We chose the coupling of The palladium particles inside the flow reactor showed excel-
4′-bromoacetophenone and phenylboronic acid as model reac- lent stability without loss of activity after the tenth run. Palla-
tion for optimizing the process and found that 85% conversion dium leaching was determined to be about 0.7 ppm for each
could be achieved within 10 min at 95 °C in DMF/water 10/1 run. This very low value for leaching corresponds to the
with 2.5 mol% of catalyst 3 using CsF as base. The reaction was leaching determined for transfer hydrogenations with this cata-
performed in a cyclic mode with a flow rate of 2 mL/min. lytic flow system using cyclohexene as hydrogen source and
Single pass experiments with flow rates between 0.1 and 1 mL/ solvent [23,24].
Table 1: Suzuki–Miyaura reactions catalyzed by Pd nanoparticles 3 inside flow reactors.
aryl bromide
boronic acid
product
time [h]
yield [%]a
4
5
6
7
8
9
4
4
4
10
10
10
10
10
10
11
12
13
14
15
16
17
18
19
20
21
22
1
85
85
60
75
99
86
81
89
99
5.5
5.5
3.5
4.5
24
1
2.5
2
aIsolated yield of pure product.
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Beilstein Journal of Organic Chemistry 2009, 5, No. 21.
Table 2: Heck–Mizoroki reactions catalyzed by Pd nanoparticles 3
inside flow reactors.
Figure 2: Repeated Suzuki reaction of 4-bromotoluene (6) with
phenylboronic acid (10) under flow conditions. Deviations may result
from work up as only isolated yields are presented.
Heck–Mizoroki reactions
One other very important cross coupling reaction that bears
industrial relevance is the Heck–Mizoroki reaction. We were
able to perform C-C coupling reaction under flow conditions
with aryl iodides 23–28 using catalyst 3 (Table 2). Optimiza-
tion of the conditions for our monolithic flow reactor was
conducted with 4′-iodoacetophenone (23) and styrene (29) as
coupling partners. With n-butylamine as base and 2.5 mol%
catalyst 3 in DMF at 120 °C and a flow rate of 2 mL/min it was
possible to achieve full conversion with complete E-selectivity
within 30 min. Formation of by-products resulting from homo-
coupling was not observed. When 4′-iodoacetophenone (23)
was exchanged with 4′-bromoacetophenone coupling with
styrene yielded Heck-product 30 in only 35%.
aryl iodide
product
time [h]
yield [%]a
23
24
25
26
27
28
30
31
32
33
34
35
0.5
24
19
3
99
99
93
77
99
99
24
4
aIsolated yield of pure product.
In order to generalize the reaction protocol different aryl iodides
were coupled with styrene. In all cases, the C-C coupling
products were formed within 0.5 to 24 h in very good yield with
excellent stereocontrol (see Table 2). Palladium leaching was
determined to be 0.04% for each run based on the catalyst used
initially, which is an exceptionally low value in view of the fact
that DMF a well coordinating solvent is employed [35].
Even commercially available and widely employed catalysts
that are based on encapsulated Pd particles such as PdEnCat
[35] show a similarly low degree of leaching in DMF to our Pd
nanoparticles [36]. With reference to the fundamental work by
Reetz and de Vries the ionic environment on the polymer phase
that is located in very close vicinity to the palladium nano-
particles has very likely to be made responsible for the stabiliza-
tion of the nanoparticles which results in low degree of leaching
[25-29].
Figure 3: Repeated Heck–Mizoroki reaction of 4′-iodoacetophenone
(23) with styrene (29) under flow conditions.
reservoirs for Pd nanoclusters that are released into solution at
very low concentrations. With respect to transfer hydrogena-
tions using precatalyst 3 we recently conducted a thorough
study on the principal question whether 3 serves as a Pd reser-
voir [23]. As was first demonstrated by Reetz [25-28] and de
Vries [29] these clusters exert pronounced catalytic activity in
solution at very low concentrations. This view is further
supported by the fact that the catalytic species operating in the
It has to be noted that like many other heterogenized Pd sources
[15,16,36-41] these polyionic gels very likely also serve as
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Beilstein Journal of Organic Chemistry 2009, 5, No. 21.
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