Heterogeneous Baylis-Hillman using a polystyrene-bound 4-(N-benzyl-N- methylamino)pyridine as reusable catalyst

Article abstract of DOI:10.1039/b309117a

An insoluble Merrifield type resin having 4-aminopyridine units is a suitable and reusable heterogeneous catalyst for the Baylis-Hillman coupling of aromatic aldehydes and α,β-unsaturated ketones.

Full text of DOI:10.1039/b309117a

Heterogeneous Baylis–Hillman using a polystyrene-bound
4-(N-benzyl-N-methylamino)pyridine as reusable catalyst†
Avelino Corma,* Hermenegildo García* and Antonio Leyva
Instituto de Tecnología Química CSIC-UPV, Avda. de Los Naranjos s/n, 46022, Valencia, Spain.
E-mail: hgarcia@quim.upv.es
Received (in Cambridge, UK) 31st July 2003, Accepted 23rd September 2003
First published as an Advance Article on the web 13th October 2003
An insoluble Merrifield type resin having 4-aminopyridine
units is a suitable and reusable heterogeneous catalyst for the
Baylis–Hillman coupling of aromatic aldehydes and a,b-
unsaturated ketones.
b-hydroxyketone accompanied by minor amounts of the
Michael adduct [eqn. (1)]. The latter compound 2 is a secondary
Among the reactions in which C–C bonds are formed, the
Baylis–Hillman coupling of aromatic or aliphatic aldehydes
with a,b-unsaturated carbonylic compounds is currently attract-
ing much interest due to the mild conditions, the compatibility
with many functional groups and the absence of transition metal
catalyst and residues.1,2 For instance, compared to the Heck,
Suzuki and other palladium catalysed C–C bond forming
reactions,3 the Baylis–Hillman can be promoted using organic
bases in the complete absence of any metal.4,5
(1)
However, all the Baylis–Hillman reactions reported so far use
homogeneous catalysis, therefore making difficult the product
isolation and impeding the reuse of the catalyst. It is worth
commenting that the normal conditions for the Baylis–Hillman
reaction use stoichiometric or overstoichiometric amounts of an
organic amine as a base and, therefore, it would be highly
convenient to recover and reuse the catalyst.
Herein, we report a truly heterogeneous Baylis–Hillman
reaction promoted by 4-(N-benzyl-N-methylamino)pyridine
bound to an insoluble polystyrene scaffold (PAP). We will show
that the catalyst can be reused and eventually reactivated upon
deactivation.
product derived from 18 and only appears at high conversions
when the stoichiometric ratio between 4-nitrobenzaldehyde and
methyl vinyl ketone is 1 to 3, but it is undetectable using a 1 to
1.5 molar ratio. Fig. 2a shows a representative time conversion
plot for this reaction. Firstly, we studied the reaction in the
presence of PAP in several solvents. Table 1 summarizes the
results obtained. As can be seen there, while the reaction does
not work well in protic solvents, high conversions are obtained
in DMF or dichloromethane. This trend is similar to that
observed in homogeneous Baylis–Hillman reactions.8
A general strategy to transform a homogeneous into a
heterogeneous process consists of anchoring a successful
soluble catalyst onto an insoluble support. Polymers have been
widely used as insoluble scaffolds for anchoring catalytically
active species.6
Thus, in view of the fact that nitrogenated nucleophiles are
the most common catalysts for the homogeneous Baylis–
Hillman reaction,4,7 we proceeded to study the activity of a
polymer in which pyridine units (3 mmol g21) are covalently
attached to a Merrifield type resin through an N-benzylamino
group (see ESI†). The structure of the polymer is indicated in
Fig. 1.
As a test reaction to determine the activity of this polymer we
selected the coupling of 4-nitrobenzaldehyde with methyl vinyl
ketone, which is a paradigmatic example of the Baylis–Hillman
reaction.8‡ In all cases the major product was the corresponding
Fig. 2 Time conversion plot for the room temperature Baylis–Hillman
reaction of 4-nitrobenzaldehyde (1 equiv.) and methyl vinyl ketone (3
equiv.) in DMF (5 mL) in the presence of solid catalyst (1 equiv.) (a) and
after filtering the solid at 50% conversion (b).
Table 1 Results for the Baylis–Hillman reaction of 4-nitrobenzaldehyde
(0.5 mmol) and methyl vinyl ketone at 20 °C using PAP as catalyst in
different solvents (5 mL). For the molar ratios see Table
Aldehyde : methyl vinyl
Product
Entry
ketone : catalyst molar ratio Solvent
Time/h
yield (%)
1
2
3
4
5
6
7
8
9
10
11
12
13
1 : 3 : 1
1 : 3 : 1
1 : 3 : 1
1 : 3 : 1
1 : 3 : 1
1 : 3 : 0.2
1 : 3 : 3
1 : 1.5 : 1
DMF
CH2Cl2
CH3CN
MeOH
H2O
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
18
18
18
18
18
72
24
24
48
24
24
24
24
70
22
25
6
4
89
90
75
93
67
59
51
85
1 : 1.5 : 1
1 : 1.5 : 1 (1 reuse)
1 : 1.5 : 1 (2 reuse)
1 : 1.5 : 1 (3 reuse)
1 : 1.5 : 1 (reactivated)
Fig. 1 Polymer-bound 4-(N-benzyl-N-methylamino)pyridine (PAP).
† Electronic supplementary information (ESI) available: procedure for the
synthesis of PAP. See http://www.rsc.org/suppdata/cc/b3/b309117a/
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CHEM. COMMUN., 2003, 2806–2807
This journal is © The Royal Society of Chemistry 2003

Table 2 Results for the room temperature Baylis–Hillman reaction of
aldehydes : methyl vinyl ketone : PAP (1 : 1.5 : 1 molar ratio) in DMF (5
mL)
To demonstrate that the Baylis–Hillman coupling catalysed
by the pyridine polymer is really a heterogeneous process, an
experiment was carried out in DMF in which the catalyst was
filtered at 50% conversion and the resulting clear solution
surveyed for additional conversion in the absence of the solid.
Fig. 2b shows that no further increase in the conversion level
occurs after filtration of the catalyst, thus indicating that the
solution does not contain any catalytically active species that
could have been leached from the solid to the solution.
Besides the solvent and the reactant ratio, another parameter
that was also studied was the substrate to catalyst molar ratio,
which varied from 0.33 to 5 mol of 4-nitrobenzaldehyde to mol
of pyridine units in PAP. As expected, the initial rate decreases
upon increase of this ratio, but conversions higher than 90%
were also achieved at long times for high ratios (5 mol/mol).
This indicates the slow deactivation of PAP and this subject is
related to the recycling of the catalyst.
Substrate
Time/days
Product yield (%)
1
81
3
82a
63
10
Thus, one aspect of relevance in heterogeneous catalysis is
the recycle of the catalyst and its reactivation upon extensive
reuse. After having performed one reaction under the conditions
indicated in Table 1, the catalyst was recovered by filtration,
washed with an aliquot of fresh DMF and CH2Cl2, dried in the
open air and reused for a consecutive run under the reaction
conditions. As expected, the activity of the used catalyst
decreased gradually upon successive reuses (Table 1, entries
10–12), the product yield in the fourth run being slightly above
50%. We speculated that the main cause of deactivation could
be the covalent attachment of methyl vinyl ketone or any a,b-
unsaturated ketone to the pyridine nitrogen of the polymer [eqn.
(2)]. Fig. 3 shows an expansion of the aromatic region of the IR
spectrum of the catalyst before and after extensive deactivation.
This Figure shows that reuse of the catalyst causes the
appearance of several bands from 1750 to 1650 cm21
attributable to the presence of several types of carbonyl groups
in the deactivated polymer. In order to regain the initial activity,
the deactivated catalyst was submitted to treatment with acid or
base. While no activity recovery occurs upon contacting the
polymer with acid, a reactivation higher than 95% of the initial
activity was accomplished by stirring a suspension of the
polymer in 2 M NaOH at 60 °C for 1 h. In accordance, the IR of
the original PAP was restored. Eqn. (2) shows a reasonable
proposal to rationalize the reactivation of the catalyst upon base
treatment.
3
41
10
6
25
26
a Corresponding to the normal Baylis–Hillman product (10%) plus the
subsequent Michael addition product (72%).
To demonstrate the applicability of PAP as a heterogeneous
catalyst for the Baylis–Hillman coupling, other aldehydes were
tested as reactants. Table 2 shows the results achieved in DMF.
High chemical yields were also obtained for other aromatic
aldehydes and the polymeric catalyst was recovered and
reused.
In summary, herein we have demonstrated that an insoluble
polymer having aminopyridine groups covalently bonded is a
recoverable and reusable heterogeneous catalyst for the Baylis–
Hillman coupling of aromatic aldehydes and a,b-unsaturated
ketones.
Financial support by the Spanish D.G.E.S. (MAT2000-
1768-C02-01) is gratefully acknowledged. A.L. thanks the
Spanish Ministry of Education for a post-graduate scholar-
ship.
Notes and references
(2)
‡ Reaction procedure: 4-nitrobenzaldehyde (75.6 mg, 0.5 mmol), methyl
vinyl ketone (from 1 to 3 equiv.) and polymer (for ratios see Tables, 6 mmol
N/g) were placed in a vessel. Then, DMF (5 mL) was added and the
suspension was magnetically stirred. The course of the reaction was
monitored by taking periodically aliquots from the solution and analyzing
them by GC. When no further conversion was observed, the suspension was
filtered under vacuum and the solid was washed with DMF (30 mL) and
CH2Cl2 (30 mL) and dried in the open air. All the products were
characterised by GC-MS, 1H and 13C NMR.
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Fig. 3 Part of the IR spectrum of fresh PAP (a) and after its fourth reuse
(b).
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