Sol-gel immobilized and reusable copper-catalyst for arylation of phenols from aryl bromides

Article abstract of DOI:10.1039/b905205d

A simple β-diamide ligand was immobilized by the sol-gel process on hybrid silica for Cu-mediated O-arylation reactions. Combined with 5% of CuI, the latter can easily be recovered and reused to generate diarylethers under smooth conditions from cheap aryl bromides in an eco-friendly solvent (MIBK). Besides, negligible metal leaching occurred after reaction in solution from the supported catalyst.

Full text of DOI:10.1039/b905205d

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Sol–gel immobilized and reusable copper-catalyst for arylation of phenols
from aryl bromides†
Sofia Benyahya,a Florian Monnier,*a Michel Wong Chi Man,*a Catherine Bied,a Fouad Ouazzanib and
Marc Taillefer*a
Received 13th March 2009, Accepted 30th April 2009
First published as an Advance Article on the web 19th May 2009
DOI: 10.1039/b905205d
A simple b-diamide ligand was immobilized by the sol–
gel process on hybrid silica for Cu-mediated O-arylation
reactions. Combined with 5% of CuI, the latter can easily
be recovered and reused to generate diarylethers under
smooth conditions from cheap aryl bromides in an eco-
friendly solvent (MIBK). Besides, negligible metal leaching
occurred after reaction in solution from the supported
catalyst.
protocol was envisaged for a smoother and greener synthesis of
diaryl ethers. Since its renaissance in its catalytic version, many
Cu-mediated Ullmann systems were designed with a myriad
of original ligands.2 Among them, the class of b-dicarbonyl
derivatives is one the most versatile and efficient.6j,10–13 For
example they have allowed room-temperature C–N Ullmann
coupling,10a,b O-arylation from aryl chlorides,6j C–S coupling12
and also Sonogashira-type coupling.13 We then decided to
heterogenize a simple b-dicarbonyl derivative (in its b-diamide
form) on hybrid silica by a sol–gel process,14 and tested it in
C–O coupling. It is worth noting that it is the first time that a
b-diamide derivative is used as ligand in Ullmann condensations.
Starting from commercially available and cheap materials,
the supported ligand M was obtained in two steps: condensa-
tion of malonyl dichloride with (3-aminopropyl)triethoxysilane,
yielding the bis-silylated precursor P, followed by the sol–gel
hydrolysis of the latter (Scheme 1).15 This b-diamide-based
hybrid silica M was further used in association with CuI
to generate in situ heterogeneous precatalyst CuI/M for
O-arylation of phenols in a green manner.
Since a few decades numerous systems have been developed for
the preparation of diarylethers, which are important backbone
molecules in polymer industries1a,b and life science.1c,2c At the
turn of this century, metal-mediated O-arylation methodologies2
have supplanted traditional organic pathways3 with a much
better functional group tolerance under smoother conditions
reactions. Hartwig et al. and Buchwald et al. have greatly
contributed to novel Pd-catalyzed arylation of phenols,4 but
their systems still suffer from the expensive price of palladium
and ligand sources. In the meantime,5 a catalytic version of Cu-
mediated Ullmann coupling of aryl halides and phenols was
successfully developed and so offered a cheaper alternative to
Pd. Thus, important efforts were invested to provide the most
efficient Cu/Ligand system in terms of softening conditions
reaction and widening functional tolerance.6 Nonetheless and
surprisingly, little interest was devoted to immobilize such
Cu- or Pd-catalytic systems.7 To date, only four reports de-
scribed copper reusable catalytic systems for C–O coupling
that allowed the recycling of active metal,8 nevertheless only
one reported leaching measurements of metal toxic residues in
final products.8d This feature is of high importance for purity
requirements in pharmaceutical industries. Therefore, mild,
simple and low-cost reusable methods are highly desirable to
avoid this toxic and environmentally issue.
Scheme 1 Synthesis of supported ligand M on hybrid silica.
We chose the Ullmann-type coupling of bromobenzene with
3,5-dimethylphenol as the model reaction with Cs2CO3 as base
(Scheme 2).
In a previous report we have successfully developed a sol–gel
immobilized bipyridyl-based ligand for O-arylation of phenols.8d
Though its efficiency, non-environmentally friendly DMF was
used as solvent9a and KI was needed to facilitate coupling from
aryl bromides at 120 ◦C. Thus a more efficient and sustainable
aInstitut Charles Gerhardt Montpellier UMR 5253
Scheme 2 Optimisation of reaction conditions for synthesis of 1.
CNRS-UM2-ENSCM-UM1, Architectures Mole´culaires et Mate´riaux
Nanostructure´s, ENSCMontpellier 8, rue de l’Ecole Normale, 34296,
Montpellier, France. E-mail: florian.monnier@enscm.fr,
marc.taillefer@enscm.fr, michel.wong-chi-man@enscm.fr
We have screened several experimental conditions with dif-
ferent combinations of ligands, solvents, and looked after the
influences of amount of catalytic system, reaction concentration,
and temperature (Table 1).
bLCOA, FST Fe`s. BP 2202, 30 000, Fe`s, Morocco
† Electronic supplementary information (ESI) available: Spectroscopic
data. See DOI: 10.1039/b905205d
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Table 1 Study on the reaction conditions for synthesis of 1
Table 2 Coupling of various aryl bromides with 3,5-dimethylphenol
Entry CuI (%) Ligand (%)
T/◦C
Solvent/mL
Yield (%)a
Entry
R1
Reuse
Product
Yield (%)a
1
2
3
4
5
6
7
8
9
10
10
10
10
10
10
10
10
10
5
0
90
90
DMF (1)
DMF (1)
DMF (2)
DMF (2)
DMF (2)
DMSO (2)
DMF (1)
MIBK (2)
MIBK (1)
MIBK (1)
MIBK (1)
MIBK (1)
Traces
Traces
Traces
Traces
46
47
70
1
2
3
4
5
6
4-H
1
2
3
4
5
6
99
75
77
90
98
95
10 (M)
0
4-OMe
4-Me
4-CN
Hb
1
2
3
4
5
110
110
110
110
110
110
110
110
110
110
10 (M)
5 (M)
5 (M)
5 (M)
5 (M)
5 (M)
5 (M)
5 (P)
5 (M)
4-NO2
a Isolated yields after flash chromatography. b Reaction performed from
2-bromopyridine.
52
99
99
10
11
12
5
5
99 (0)b
99 (99)b
a GC-MS Yields determined with 1,3-dimethoxybenzene as internal
standard. b In brackets, GC-MS Yield values after one recycling of the
catalytic system.
Scheme 3 Coupling of various aryl bromides with 3,5-dimethylphenol.
First of all, we tested the coupling reaction at 90 ◦C in DMF
with 10% of CuI with or without material M (10%). No coupling
product 1 was observed (entries 1–2), even after heating up
to 110 ◦C (entries 3–4). Surprisingly, we have observed that
decreasing the amount of ligand M from 10% to 5% allowed
moderate yield in 2 mL of DMF (a similar result was obtained
in DMSO, entry 6) and more interestingly a better yield was
obtained (70%) in more concentrated media (1 mL of DMF,
entry 7). At this stage, we envisaged to replace DMF by MIBK
(methylisobutylketone),9 a solvent with low toxic potential
which is highly used on an industrial scale due to its easy
elimination. Interestingly under the same reaction conditions
as in entry 7 but with MIBK as solvent, 1 was obtained
quantitatively (entry 9) and this yield can be reproduced with an
even lower amount (5%) of CuI (entry 10). To summarise, the
best conditions with the ligand immobilized on hybrid silica M,
were determined as the following: CuI (5 mol%), M (5 mol%)
Cs2CO3 (1.5 equiv.) in 1 mL of MIBK at 110 ◦C during 22 h.
The next point was to test the recyclability of the hybrid
CuI/M in comparison with the CuI/P system (entries 11–12).
Indeed although the latter gave similar high yield (entry 11)
for the first run, no reaction occurred for the second run with
this homogeneous system. On the other hand, we observed the
same reactivity for the generation of 1 after one reuse of the
immobilised CuI/M system. Moreover it is noteworthy that we
were able to elaborate an easy-handling protocol for recycling
our CuI/M system by separating and filtering the crude solution
in air without any other precaution, which constitutes a very
simple pathway as a recycling procedure.
Based on these results, we have performed several series of
reactions to test the versatility of our reusable system for the
coupling of various aryl bromides with 3,5-dimethylphenol. In
each series, 5% of CuI and M were charged only in the first
experiment, all the other runs worked with the same reusable
catalytic system. Table 2 relates the substituent effect on the aryl
bromides under optimized reaction conditions found previously
for the coupling from bromobenzene (Scheme 3).
After the first run affording 1 in quantitative yield, we
demonstrated that re-using the same supported ligand M gave
the corresponding products 2–6 in good to excellent yields
(Entries 2–6). Besides, this reusable catalytic system is efficient
even with electron-donating and electron-withdrawing groups
on the aryl bromides.
In a second time, we studied the substituent effect on the
phenols for the coupling with bromobenzene (Scheme 4). Results
presented in Table 3 showed moderate (Entry 2) to excellent
yields, and revealed the excellent reusability of CuI/M system
even after 6 runs.
Scheme 4 Coupling of various phenols with bromobenzene.
Table 3 Coupling of various phenols with bromobenzene
Entry
R2
Reuse
Product
Yield (%)a
1
2
3
4
5
6
4-H
4-Cl
4-OMe
4-Me
2-Me
4-tBu
7
8
87
65
92
95
92
99
1
2
3
4
5
9
10
11
12
a Isolated yields in % after flash chromatography.
Finally, we have measured amounts of copper leaching in the
crude solution phases containing diarylethers. For this study, we
wanted first to compare copper leaching after synthesis of 1 both
with homogeneous precursor ligand P and supported ligand M
(similar conditions as for entry 1 of Table 2, respectively with 5%
of P and M). The results clearly indicated that the immobilized
system based on supported ligand M is a powerful and efficient
chelate of Cu atom (Table 4). This latter allows a minimal
leaching of copper in the crude mixture after coupling reaction
(<30 ppm, entry 1), on the other hand the non-supported system
CuI/P releases a much higher amount of copper in the crude
mixture which is not acceptable for a toxic reason.16 (1400 ppm,
entry 1 of Table 4).
In a second set of results, we have measured the copper
leaching at different stages of recycling protocol as followed
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Table 4 Coupling of phenols with bromobenzene
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Entry
Ligand
Yield of 1
Copper leachinga
1
2
P
M
97
98
1400 ppm
< 30 ppm
a Measured by elementary analysis on the crude mixture.
7 For reviews on heterogeneous Pd-catalysts for cross-coupling reac-
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in Table 2. For entries 1, 2, 4 and 6 of Table 2, we have obtained
a copper leaching of only 20 ppm in all cases. These important
observations could explain the high and stable reactivity of our
supported system even after more than 5 cycles by the fact that
copper is strongly encapsulated into the hybrid silica matrix
of M.
In summary, we have synthesized an easy-handling supported
ligand from commercially cheap materials. This ligand M in as-
sociation with a catalytic amount of CuI allows the O-arylation
of phenols from cheap aryl bromides under smooth conditions
with a simple recyclable protocol under air atmosphere. The use
of MIBK, an industrial solvent with low toxic potential, and the
very low amount of copper leaching, provide a real improvement
for a green and sustainable route to diarylethers via Cu-mediated
Ullmann condensation.
Acknowledgements
The authors thank CNRS for financial support, and CNRST of
Morocco for PhD grant for S. B.
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This journal is
The Royal Society of Chemistry 2009
Green Chem., 2009, 11, 1121–1123 | 1123
©