Imidazole based solid-supported catalysts for the benzoin condensation

Article abstract of DOI:10.1016/j.tetlet.2005.08.141

New polymer-supported imidazolium salts have been synthesised, and their utility as pre-catalysts in the benzoin reaction has been demonstrated.

Full text of DOI:10.1016/j.tetlet.2005.08.141

Tetrahedron
Letters
Tetrahedron Letters 46 (2005) 7337–7339
Imidazole based solid-supported catalysts for the
benzoin condensation
John M. D. Storey* and Craig Williamson
Department of Chemistry, University of Aberdeen, Meston Building, Meston Walk, Old Aberdeen AB24 3UE, UK
Received 8 June 2005; revised 28 July 2005; accepted 25 August 2005
Available online 13 September 2005
Abstract—New polymer-supported imidazolium salts have been synthesised, and their utility as pre-catalysts in the benzoin reaction
has been demonstrated.
ꢀ 2005 Elsevier Ltd. All rights reserved.
N-Heterocyclic carbenes have received much attention
recently for the catalysis of organic reactions due to
their ability to form acyl-anion equivalents.1 This fea-
ture has been successfully exploited in numerous cata-
lytic reactions. Notable examples include the Stetter
reaction,2 the acylation/trans-esterification of alcohols,3
and the synthesis of c-butyrolactones.4 Our interest in
their use focuses upon the benzoin condensation.
long reaction times, often leading to catalyst decomposi-
tion under the basic conditions required.
Imidazole derived heterocycles have also been used as
active catalysts in the benzoin condensation for some
time,8 although they have been mainly overlooked due
to their comparatively low C2 acidity. A number of
recent reports however, have described efficient imidazole
based carbene catalysts with the advantage of trivial
catalyst synthesis, and increased stability over other
heterocyclic systems.9
The benzoin condensation provides a convenient and
powerful method for the formation of C–C bonds from
aldehyde starting materials (Scheme 1). In its traditional
form, only aromatic aldehydes or glyoxals could be cou-
pled using cyanide anion as a catalyst.5 Several nucleo-
philic carbenes derived from heterocyclic systems
including triazoles6 and thiazoles7 have also found
application as catalysts, which has increased the scope
of the reaction allowing aliphatic aldehydes to be cou-
pled. Unfortunately, these systems generally rely on high
catalyst loadings (10–30 mol %), and frequently need
Despite these developments, cyanide anion still remains
a serious contender for practical synthesis of symmetri-
cal acyloins, as evidenced by recent reports.10 Indeed,
the development of novel cyanide ion catalytic systems
has recently been reported.11 It became apparent that
there was a need for an efficient catalytic system, which
would ease handling, and reduce reaction times to
minutes rather than hours or days. In addition, easy
removal of the catalyst from the reaction mixture was
a desirable design feature.
O
O
We describe here the synthesis and use of three easily
prepared polymer-bound imidazolium salt carbene pre-
cursors, and their subsequent application in the benzoin
condensation of a range of aromatic aldehydes. The use
of a polymer support appeared to be an attractive propo-
sition, since we believed that this should alleviate the
handling problems associated with free salts of imidaz-
oles, which tend to form viscous room temperature ionic
liquids.
catalyst
2 X
R
R
H
R
a; R = H
b; R = Cl
c; R = tBu
d; R = MeO
e; R = 2-naphthyl
OH
1
2
Scheme 1.
Keywords: Benzoin condensation; Solid-supported imidazolium
catalysts.
*
Previously there have been numerous examples of immo-
bilisation of imidazolium derived carbene-containing
Corresponding author. Tel.: +44 01224 272926; fax: +44 01224
272921; e-mail: j.storey@abdn.ac.uk
0040-4039/$ - see front matter ꢀ 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2005.08.141

7338
J. M. D. Storey, C. Williamson / Tetrahedron Letters 46 (2005) 7337–7339
Cl
N
N
O
O
O
3
4
N
N
N
N
O
Cl
Cl
4
5
Figure 1. Solid-supported imidazolium catalysts.
catalysts onto polymers, although these all tend to be
based on metal centred catalysts using one or more car-
bene ligands as a covalent linker.12 However, it would
appear that this communication represents the first
attempt to immobilise imidazolylidenes onto a solid
phase to act as catalysts, in the absence of a metal.
respectively. All quaternisations were performed in
refluxing toluene with a 10-fold excess of modifying
agent. After filtration to isolate the supported salts, and
washing with toluene, the catalysts were stored under vac-
uum (15 mmHg) at 25 ꢁC to remove all residual solvent.
The loading of the resins was determined by averaging
Three different, commercially available, functionalised
polystyrene beads were modified to produce quaternary
salts (Fig. 1). Imidazole carbamate resin was quaternised
with (2-chloroethyl)benzene to give 3. [(4-Chloromethyl)-
5-phenyl] pentylstyrene and chlorinated Wang resin were
quaternised with N-methylimidazole to give salts 4 and 5,
three microanalyses for each. For 3, the loading was
found to be 0.62 mmol/g,
4 had a loading of
0.89 mmol/g and 5 had a loading of 1.32 mmol/g.
The activity of these solid-supported catalysts was then
investigated for the condensation of a range of substi-
Table 1. Yield of benzoins using solid-supported catalysisa
Entry
Catalyst
Amount of catalyst (mol %)
Reactant
Time
Isolated yield (%)
a
b
c
d
e
f
g
h
i
j
k
l
m
n
o
p
q
r
3
3
3
3
1.25
0.5
0.5
0.5
0.5
1.0
0.7
0.3
0.09
0.7
0.7
3.5
0.7
0.7
0.7
1.0
1.4
0.7
1a
1a
1b
1c
1d
1a
1a
1a
1a
1b
1c
1d
1e
1a
1a
1a
1a
1a
5 min
60 min
10 min
5 h
37
66
39
20
7
3
48 h
4b
10 min
5 min
5 min
30 min
10 min
15 min
90 min
30 min
25 h
77
54
35
30
30
29
41
56
62
34
72
57
0
4b
4b
4b
4b
4b
4b
4b
4c
4d
40 h
15 min
1 h
5
4e
Unmodified beads
48 h
a Typical procedure for benzoin condensation: A two-necked flask was charged with the catalyst, THF (50 cm3), and the appropriate aldehyde. The
reaction mixture was heated to reflux with vigorous stirring, and base (0.5 cm3 50% aq NaOH) was added in one portion via a syringe. When the
reaction mixture solidified, the solvent was removed, and the resulting solid dissolved in water, and extracted with DCM (3·50 cm3). The combined
organic extracts were filtered to remove the catalyst, dried (MgSO4) and the solvent was removed at reduced pressure. The residue was purified by
flash chromatography on silica gel (hexane/EtOAc) followed by recrystallisation from EtOH. Benzoins were characterised by comparison with the
literature data.
b THF as solvent.
c Acetonitrile as solvent.
d Methanol as solvent.
e NaH as base, where NaH was used as base, it was first washed with dry petrol, and suspended in dry THF. The polymer-supported pre-catalyst and
aldehyde were then added to the suspension at room temperature. If heat was required it was applied after all components had been combined. After
reaction, the beads were filtered and washed with MeOH. Removal of solvent from the filtrate produced a residue, which was washed with water
before purification.

J. M. D. Storey, C. Williamson / Tetrahedron Letters 46 (2005) 7337–7339
7339
tuted aromatic aldehydes (Table 1). In most cases, the
reaction times were short, with moderate to good yields,
which follow the previously observed trend of electron-
deficient aldehydes reacting more rapidly than electron-
rich aldehydes in benzoin condensation reactions.
Regeneration of the catalyst after each cycle was also
possible simply by treatment with acid. This was demon-
strated using catalyst 4, which was used in three succes-
sive benzoin condensations, albeit with approximately
10% lower yield in each cycle. We believe that this is
the first reported re-use of an imidazole based catalyst
in benzoin reactions.
Entry i clearly shows that less than 0.1 mol % of catalyst
is needed for reasonable conversion to the benzoin prod-
uct after just 30 min.
In summary, the first polymer-supported imidazolium
salt pre-catalysts have been reported and their utility
for the benzoin reaction has been demonstrated. More-
over, these catalysts are easy to handle, can be used at
lower catalyst loading than previously reported non-
polymer-supported catalysts, reaction times are cut from
many hours or days to minutes, and they can be regen-
erated for re-use.
Solvent effects were briefly investigated (entries g, n and
o). THF proved to be a far superior solvent with respect
to the rate of benzoin formation of those tested. The rela-
tive swelling of polystyrene could explain this, since
methanol and acetonitrile do not swell the polystyrene
to the same degree as THF.13 Greater swelling assists
diffusion of reactants and products to and from the
active sites within the beads.14
Acknowledgments
Since diffusion is a relevant factor in solid-phase cataly-
sis, the limit of the catalysts with regard to substrate size
was also investigated. 2-Naphthaldehyde 1e was rapidly
coupled in moderate yield (entry m), thus indicating sub-
strates are not limited to monocyclic aldehydes.
We gratefully thank EPSRC for financial support. In
addition, we would like to thank the EPSRC National
Mass Spectrometry Centre at the University of Wales,
Swansea, for providing accurate mass measurements.
References and notes
Variation of the base required for formation of the car-
bene was also investigated. As previously described,9
excess aqueous NaOH is effective in deprotonating imi-
dazolium salts, however NaOH has a tendency to cause
the benzoins formed in the reaction to precipitate as
their sodium salts, which solidifies the reaction medium
and tends to retard any further reaction. Triethylamine
is a commonly employed base for benzoin reactions,
but was shown to be completely inactive in this case.
The 1H NMR spectrum of structurally similar, non-teth-
ered salt 6 (Scheme 2) in the presence of excess triethyl-
amine, showed no evidence of C2 deprotonation after a
prolonged time, even at temperatures close to that of
refluxing THF, confirming that Et3N is insufficiently
basic to initiate this reaction.
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Entry r indicates that the polymer is not responsible for
the catalytic activity, since as expected none of the ben-
zoin product was produced during this reaction, and
starting material was recovered in near quantitative yield.
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Ph
Ph
Ph
Br
N
N
N
N
Et3N
N
N
NaH
6
Scheme 2.