Poly(ethylene glycol) as reaction medium for mild Mizoroki-Heck reaction in a ball-mill

Article abstract of DOI:10.1039/c2cc36286d

Phosphine-free palladium-catalyzed Mizoroki-Heck reaction was performed using ball-milling in polyethylene glycol under mild conditions. Good to excellent yields of coupling products were obtained. This activation technique also allowed the concomitant fo

Full text of DOI:10.1039/c2cc36286d

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Poly(ethylene glycol) as reaction medium for mild Mizoroki-Heck
reaction in a ball-mill
Valérie Declerck,a,b Evelina Colacino,a Xavier Bantreil,a Jean Martineza and Frédéric Lamatya*
Received (in XXX, XXX) Xth XXXXXXXXX 20XX, Accepted Xth XXXXXXXXX 20XX
5
DOI: 10.1039/b000000x
Phosphine-free palladium-catalyzed Mizoroki-Heck reaction
was performed using ball-milling in polyethylene glycol under
mild conditions. Good to excellent yields of coupling products
were obtained. This activation technique also allowed the
10 concomitant formation of round shape Pd/PEG nanoparticles
that were characterized by TEM analysis.
Table 1 Optimization of ballꢀmilling MizorokiꢀHeck reactiona
Pd(OAc)2 (5 mol%)
K2CO3 (3 equiv)
HCO2Na (0.2 equiv)
Ph
t
t
Ph
I
CO2 Bu
CO2 Bu
PEG
Ball-mill, 30 Hz, 1h
Grinding, dry mixing or ballꢀmilling have proved their efficiency
as unconventional techniques in the field of organic chemistry in
solid state.1 These techniques have been applied to a large number
15 of organic transformations, but with limited use in the case of CꢀC
bond formation, to aldol and Knoevenagel condensations, Michael
additions, BaylisꢀHillman and Wittig reactions, and asymmetric
alkylation of Schiff bases.2 Transition metalꢀcatalyzed coupling
reactions, especially with palladium, are very efficient and well
20 developed CꢀC bond formation reactions.3 Such reactions
performed in a ballꢀmill have been limited to a small number of
examples of transformations, mainly the SuzukiꢀMiyaura4 and
MizorokiꢀHeck5 cross couplings.
Entry PEG
Acrylate (equiv) Additive Yield (%)b
1
2
PEGꢀ3400ꢀOH
PEGꢀ3400ꢀOH
1.2
1.2
1.2
1.2
1.2
5
NaCl
0.4
67
2
88
0
100
46
27
74
0
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
3c PEGꢀ3400ꢀOH
4
PEGꢀ2000ꢀOH
5d PEGꢀ2000ꢀOH
6
7
8
9
10
PEGꢀ2000ꢀOH
MeOꢀPEGꢀ2000ꢀOMe
MeOꢀPEGꢀ2000ꢀOH
PEGꢀ1100ꢀOH
ꢀ
5
5
5
1.2
a
50
Reaction conditions: phenyl iodide (0.1 mmol), tertꢀbutyl acrylate,
Pd(OAc)2 (5 mol%), HCO2Na (0.2 equiv), K2CO3 (3 equiv), PEG (110
b
mg). Yield were determined by 1H NMR using CH2Br2 as an internal
standard. c Na2CO3 was used instead of K2CO3. d 1 mol% Pd(OAc)2.
In the last years we have developed a metalꢀbased catalytic system
25 using solid PEGs [poly(ethylene glycols)] as solvent and
stabilizing/precipitating agent to separate the organic product from
the metallic catalytic system.6 We questioned whether the use of
solid PEG would be adapted to the development of a useful
catalytic system to perform Pdꢀcatalyzed reactions in a ballꢀmill.
30 As a model reaction, the MizorokiꢀHeck arylation7 of tertꢀbutyl
acrylate to produce cinnamate was chosen. A mixture of PhI, tertꢀ
butyl acrylate, PEG, Pd(OAc)2 and an inorganic base was reacted
in a high energy stainless steel vibratory ball mill for 1h at 30 Hz
together with additives in some cases. Under traditional heating
35 and microwave irradiation, PEG has already been shown to reduce
Pd(OAc)2 to Pd(0).8,6d However, under ballꢀmilling conditions, it
was found necessary to add sodium formate as reducing agent for
the activation of Pd(OAc)2 (67 % yield). This was the best from a
practical point of view, as sodium formate is easy to handle, as
40 well as from the results obtained with reducing agents such as H2
(28%) or NaBH4 (59 %). At the end of the reaction, the mixture
was dissolved in a small amount of CH2Cl2 and precipitated in
ether, filtered, evaporated and analyzed by 1H NMR using CH2Br2
as an internal standard. Integration of the signal corresponding to
45 the H of the ester group of tertꢀbutylcinnamate measured against
the unique signal of the standard (CH2Br2) provided the yield of
the product. Results are presented in Table 1.
55 It was shown previously that solid additive like sodium chloride
could be valuable for the MizorokiꢀHeck arylation reaction.5 In our
study, when PEGꢀ3400ꢀOH was used, adding NaCl was found
detrimental to the reaction and barely any conversion was
observed whilst 67% yield was obtained in the absence of NaCl
60 (entries 1ꢀ2). Attempt to change the inorganic base by switching
from K2CO3 to Na2CO3 (entry 3) resulted in a lower conversion
most probably because the PEGꢀK+ interaction is stronger than the
corresponding PEGꢀNa+ thus enhancing the base activity. When
triethylamine was used, substrates also remained unchanged. We
65 realized that during the course of the reaction, it appeared that
PEG melted due to the slight heating of the ballꢀmill.9 As the
viscosity of the PEG used might have an influence on the reaction,
we turned our attention to shorter polymers having a lower melting
point. As a result, the yield increased by 20% by using PEGꢀ2000ꢀ
70 OH (entry 4). While reducing catalyst loading to 1 mol% resulted
in no conversion (entry 5), increasing the quantity of acrylate from
1.2 to 5 equivalents resulted in total conversion (entry 6). The
exact excess amount of acrylate needed for completion of the
reaction was not studied in detail. Several PEGs were then tested
75 under these conditions. The use of monoꢀ and diꢀmethylated PEGꢀ
2000 was detrimental as the yields dropped down (entries 7ꢀ8).
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Finally, shorter PEGꢀ1100ꢀOH gave a 74% yield (entry 9). It is
worth noting that due to the stabilizing effect of oxygen atoms in
This was confirmed by our previous work, using convection6g or
microwave heating.6d Furthermore, when a long chain PEG (PEGꢀ
PEG, no phosphine ligand was necessary for the catalysis. In the 45 2000ꢀOH or PEGꢀ4000ꢀOH) in the presence of Pd(OAc)2 but no
absence of PEG, no reaction occurred (entry 10). In addition,
MizorokiꢀHeck coupling generally requires elevated temperatures,
unfriendly
substrate was stirred a temperature of 80ꢀ120°C, nanoparticles of 5
nm were observed.8 When using PEGꢀ400ꢀOH, phenantroline as
reducing agent was necessary to observe formation of 2ꢀ6 nm
particles.12 However, under vibrating ballꢀmilling conditions, since
5
Table 2 Exemplification of the ballꢀmilling MizorokiꢀHeck reactiona
50
100 nm
200 nm
a)
b)
Pd(OAc)2 (5 mol%)
K2CO3 (3 equiv)
HCO2Na (0.2 equiv)
Ar
t
t
Ar
X
CO2 Bu
CO2 Bu
PEG-2000-OH
Ball-mill, 30 Hz, 1h
Entry
ArX
PhI
Additive
ꢀ
Yield (%)b
1
2
3
4
5
6
7
8
9
100
73
62
68
100
35
100
29
0
c)
d)
100 nm
4ꢀMeOꢀC6H4ꢀI
4ꢀNCꢀC6H4ꢀI
4ꢀBrꢀC6H4ꢀI
4ꢀOHCꢀC6H4ꢀI
4ꢀNO2ꢀC6H4ꢀI
3ꢀFꢀC6H4ꢀI
2ꢀMeꢀC6H4ꢀI
PhBr
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
100 nm
10
11
12
PhBr
PhCl
PhCl
NaI
ꢀ
NaI
0
0
0
e)
200 nm
100 nm
100 nm
f)
100 nm
a
Reaction conditions: phenyl iodide (0.1 mmol), tertꢀbutyl acrylate (0.5
10 mol), Pd(OAc)2 (5 mol%), HCO2Na (0.2 equiv), K2CO3 (3 equiv), PEGꢀ
2000ꢀOH (110 mg). b Yield were determined by 1H NMR using CH2Br2 as
an internal standard.
solvent and inert atmosphere. In our study, the use of PEG in a
15 vibratory ballꢀmill allowed the reaction to proceed in air under
mild conditions.
g)
h)
200 nm
The scope of the reaction was first explored by varying the olefin
part. Unfortunately, the reaction was efficient only with tertꢀbutyl
20 acrylate. Either no reaction was observed or a very poor yield was
obtained with acrylonitrile (0%), acrylamide (0%), methyl
methacrylate (5%) or styrene (13%). The aromatic partner was
then evaluated (Table 2). Different substituents could be used on
the aryl moiety.10 Electronꢀdonating as well as withdrawing groups
25 were well tolerated in para position as pꢀMeO, pꢀCN, pꢀBr gave
satisfactory yields (entries 2ꢀ4) and pꢀCHO was converted
quantitatively (entry 5). Surprisingly, pꢀNO2 substitution resulted
in poor yield (entry 6) . This is maybe due to a physicoꢀchemical
characteristic of the starting 4ꢀiodo nitrobenzene than an electronic
30 effect of the substituent. A fluorine atom in meta position allowed
quantitative conversion (entry 7). However, having a methyl group
in ortho position reduced the yield to 29% (entry 8). Finally, the
influence of the halide leaving group (I vs. Br, Cl) was explored.
Only the iodine atom was reactive enough to provide the expected
35 product, even when sodium iodide was added to the reaction
mixture (entries 9ꢀ12).
i)
j)
200 nm
55
Figure 1. TEM images of PEG/Pd nanoparticles obtained after Mizorokiꢀ
Heck reaction (left column) and without substrates (right column) in
different PEG: aꢀb) PEGꢀ1100ꢀOH; cꢀd) PEGꢀ2000ꢀOH; eꢀf) PEGꢀ3400ꢀ
OH; gꢀh) MeOꢀPEGꢀ2000ꢀOH; iꢀj) MeOꢀPEGꢀ2000ꢀOMe.
60 the reaction temperature was mild,9 an external reducing agent
such as sodium formate was required for activation of Pd(OAc)2.
According to these results, we questioned whether formation of
nanoparticles would also occur in the ball mill during the course of
the reaction, knowing that physical and chemical properties would
65 depend on the size and shape of the particles. Transition Electron
Microscopy (TEM) analysis of the precipitates obtained after
reactions reported in table 1 with various PEGs was performed
(Figure 1, left column). In order to compare, experiments were run
It has already been demonstrated that palladium salts in the
presence of polyethylene glycol are transformed in nanoparticles
40 under classical activation. Because the order of the reduction
potentials of the polyol and noble metals is not favorable at rt, this
method requires high temperatures to reduce the noble metals.11
2
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2
a) S. L. James, C. J. Adams, C. Bolm, D. Braga, P. Collier, T. Friscic,
F. Grepioni, K. D. M. Harris, G. Hyett, W. Jones, A. Krebs, J. Mack,
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under the same reaction conditions but in the absence of phenyl
iodide and tertꢀbutyl acrylate (Figure 1, right column). In all cases,
light yellow Pd(OAc)2 was transformed into a deep brown solid,
indicating formation of Pd/PEG nanoparticles. TEM analysis
confirmed this experimental assumption (Figure 1). To our
knowledge, this represents the first example of generation of
Pd/polymer nanoparticles using a ballꢀmill.13 In the absence of
substrates, the reaction led to significant particle aggregation,
regardless of the PEG used. When substrates were present, the
60
65
5
3
4
10 aggregation was less important and nice roundꢀshape nanoparticles
could be obtained. The size of nanoparticles is directly connected
to the size of the polymer. Indeed, average size of the
nanoparticles observed was 6ꢀ8 nm, 8ꢀ11 nm and 7ꢀ13 nm with
PEGꢀ1100ꢀOH, PEGꢀ2000ꢀOH and PEGꢀ3400ꢀOH, respectively
15 (Figure 1 a, c and e). In addition, with PEGꢀ3400ꢀOH, particles
were found to be slightly more elliptical than with other polymers.
Surprisingly, when PEGꢀ2000ꢀOH was monoꢀ or diꢀmethylated,
the particle size changed to 7ꢀ13 nm and 5ꢀ7 nm, respectively
(Figure 1 g and i).
20 Formation of palladium nanoparticles in PEG after a Mizorokiꢀ
Heck reaction activated by microwave irradiation and TEM
analysis had already been reported. In PEGꢀ400ꢀOH, which is a
liquid polymer, particles of 5ꢀ8 nm were obtained.14 In PEGꢀ3400ꢀ
OH, following benzazepine synthesis, TEM analysis of the
25 catalytic system revealed aggregated particles of 5ꢀ7 nm.6d The
particle aspect was quite different from those shown in figure 1
(left column). Thus, the activation method seems to have a strong
influence on the size and aggregation state of the nanoparticles.
70
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Conclusions
30 We reported herein a solventꢀfree/phosphineꢀfree palladiumꢀ
catalyzed MizorokiꢀHeck procedure in a ball mill. Under mild
conditions, quantitative yields were obtained using the appropriate
polymer PEGꢀ2000ꢀOH, with a correct tolerance toward functional
groups on the aryl moiety. Nanoparticles formed during these
35 reactions were characterized by TEM and were found sizeꢀ
dependent on the PEG used. In addition, activation using ballꢀ
milling yielded nanoparticles different from those obtained
previously under convection or microwave heating.
95
10 Typical procedure for the ballꢀmill MizorokiꢀHeck reaction: in a 10
mL stainless steel ballꢀmill reactor were added Pd(OAc)2 (1.1 mg,
0.005 mmol), K2CO3 (41.4 mg, 0.3 mmol), HCO2Na (1.4 mg, 0.02
mmol) and PEGꢀ2000ꢀOH (110 mg). Phenyl iodide (11.2 ꢁL, 0.1
mmol), tertꢀbutyl acrylate (73.2 ꢁL, 0.5 mmol) and two stainless steel
balls with a 7 mm diameter were then added. The mixture was then
submitted to high speed vibration milling for 1h at 30 Hz on a Retsch
MM200. A minimum of CH2Cl2 was then added and the mixture was
precipitated in Et2O (150 mL) for 4h at ꢀ20°C. The solution was
filtered and the filtrate concentrated in vacuo. After addition of 20 ꢁL
of CH2Br2 as internal standard, 1H NMR analysis allowed
measurement of a quantative yield.
11 F. Bonet, C. Guéry, D. Guyomard, R. Herrera Urbina, K. Tekaiaꢀ
Elhsissen and J. M. Tarascon, Int. J. Inorg. Mater., 1999, 1, 47ꢀ51.
12 U. R. Pillai and E. SahleꢀDemessie, J. Mol. Catal. A: Chem., 2004,
222, 153ꢀ158.
13 A. L. Garay, A. Pichon and S. L. James, Chem. Soc. Rev., 2007, 36,
846ꢀ855.
100
105
110
Acknowledgement
40 We are grateful to the “Service Commun de Microscopie
Electronique et Analytique” of the University Montpellier 2 for
TEM analysis and fruitful discussions.
Notes and references
a Institut des Biomolécules Max Mousseron (IBMM), CNRSꢀUniversités
45 Montpellier 1 et 2, Place Eugène Bataillon, 34095 Montpellier Cedex 5,
France. Fax: +33 (0) 4 67 14 48 66; Eꢀmail: frederic.lamaty@univꢀ
montp2.fr
115 14 Z. Du, W. Zhou, L. Bai, F. Wang and J.ꢀX. Wang, Synlett, 2011, 369ꢀ
372.
b Present address: Laboratoire de Synthèse Organique et Méthodologie,
ICMMO (UMR 8182ꢀCNRS), Université Paris−Sud 11, 15 rue Georges
50 Clemenceau, 91405 Orsay cedex, France.
*This article is part of the ChemComm 'Mechanochemistry' web themed
issue.
55
1
K. Tanaka and F. Toda, Chem. Rev., 2000, 100, 1025ꢀ1074.
This journal is © The Royal Society of Chemistry [year]
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