Improving catalytic activity by synergic effect between base and acid pairs in hierarchically Porous Chitosan@Titania nanoreactors

Article abstract of DOI:10.1021/ol9029319

(Figure Presented) The beneficial effect of the afunctional character of the chitosan@titania hybrid In heterogeneous catalysis was elucidated: considering a prototypical Henry condensation, Michael addition, and Jasminaldehyde synthesis, the cohabitation of a basic site (NH₂) and an acidic site (Ti) in the same reactor provided clear activity and selectivity enhancements, with respect to the monofunctional acidic titania and basic chitosan counterparts.

Full text of DOI:10.1021/ol9029319

ORGANIC
LETTERS
2
010
Vol. 12, No. 5
48-951
Improving Catalytic Activity by Synergic
Effect between Base and Acid Pairs in
Hierarchically Porous Chitosan@Titania
Nanoreactors
9
,
†,‡
†
Abdelkrim El Kadib,* Karine Molvinger, Mosto Bousmina, and
Daniel Brunel
‡
†,§
Institut Charles Gerhardt, UMR 5253 CNRS/ENSCM/UM2/UM1, 8 rue de l’Ecole
Normale, 34296 Montpellier Cedex 5, France, Institut of Nanomaterials and
Nanotechnology (INANOTECH)-ENSET, AVenue de l’Arm e´ e Royale, Madinat El
Irfane, 10100 Rabat, Morocco, and Instituto de Tecnolog ´ı a Qu ´ı mica UPV-CSIC -
UniVersidad Polit e´ cnica de Valencia, AV. de los Naranjos s/n - 46022 Valencia, Spain
a.elkadib@inanotech.ma
Received December 21, 2009
ABSTRACT
The beneficial effect of the bifunctional character of the chitosan@titania hybrid in heterogeneous catalysis was elucidated: considering a prototypical
Henry condensation, Michael addition, and Jasminaldehyde synthesis, the cohabitation of a basic site (NH ) and an acidic site (Ti) in the same reactor
provided clear activity and selectivity enhancements, with respect to the monofunctional acidic titania and basic chitosan counterparts.
2
The involvement of heterogeneous catalysis in the synthesis
of fine chemicals becomes an exciting area offering envi-
ronmentally more acceptable processes. The advantages of
decrease in the catalytic activity when compared to its
homogeneous counterparts.
3
1
Interestingly, biocatalysis offers some basic lessons for
preparing more efficient synthetic catalysts. Indeed, enzymes
are able to accelerate chemical reactions through cooperative
interactions between precisely positioned reactive groups in
the active site. This inspired researchers to design a large
library of homogeneous bifunctional catalysts. Surprisingly,
few examples describing the synergetic and cooperative
effects in heterogeneous systems were reported, and the
heterogeneous processes, easier way for product recovery
and catalyst recycling, prompted researchers to immobilize
a homogeneous catalytic site on various supports. In addition,
solid catalysts are very suitable for the regulatory issues of
metal contamination in the context of pharmaceutical syn-
2
thesis. Unfortunately, with very few exceptions, the im-
mobilization of an active catalytic site caused a significant
4
-8
subject still represents a real challenge.
†
UMR 5253 CNRS/ENSCM/UM2/UM1.
Institut of Nanomaterials and Nanotechnology (INANOTECH)-ENSET.
Universidad Polit e´ cnica de Valencia.
(2) For reviews, see: (a) Garrett, C. E.; Prasad, K. AdV. Synth. Catal.
2004, 346, 889–900. (b) Konisberger, K.; Chen, G. P.; Wu, R. R.; Girgis,
M. J.; Prasad, K.; Repic, O.; Blacklock, T. J. Org. Process Res. DeV. 2003,
7, 733–742.
‡
§
(
1) (a) Anastas, P. T.; Kirchhoff, M. M. Acc. Chem. Res. 2002, 35, 686–
6
94. (b) Clark, J. H. Green Chem. 1999, 1, 1–8.
(3) Corma, A.; Garcia, H. Top. Catal. 2008, 48, 8–31.
1
0.1021/ol9029319  2010 American Chemical Society
Published on Web 02/01/2010

Recently, we have investigated the development of new
porous and structured materials from renewable resources,
particularly from chitin. This area of research has great
(i) the higher surface areas and the macroporous network of
these scaffolds which are important for the diffusion of bulk
molecules to (and from) the active site, (ii) the high
dispersion of titanium nanoparticles, which play a crucial
role in catalysis, and (iii) the robustness of these microspheres
9
importance for the development of cleaner and more efficient
1
0
processes. In this respect, we report herein an interesting
cooperative effect in catalysis using hybrid chitosan@titania
porous materials. The preparation of these nanoreactors
consists first in the gelation of chitosan biopolymer in basic
conditions, which allows shaping chitosan as a hydrocolloid
11
assessed under hydrothermal, acidic, and basic conditions.
The stability of these hybrids is very relevant as the faint
stability of organic polymers generally limits their use as
support.
1
1
microsphere (Figure 1). This swelled polymer was pro-
tracted in titanium alkoxide solution [Ti(Acac) (OiPr)
Ti(OiPr) , or Ti(OBu) ], and then the respectively obtained
M1H, M2H, and M3H chitosan@titania hybrid alcogels
were dried under CO supercritical conditions. Nitrogen
2
2
,
4
4
2
adsorption isotherms demonstrated the macroporous character
of the materials, with a specific surface area ranging from
2
-1 11
3
70 to 480 m g . SEM analysis showed a fibrillar network
Figure 1
.
Chemical structure of chitosan.
of the secondary structure of the biopolymer (Figure 2). TEM
analysis revealed the existence of highly dispersed titanium
1
1
nanoparticles. Both the fibrillar network of the biopolymer
and the presence of amine functions play a pivotal role to
direct the growth and mineralization of titanium precursors
leading to the replication of polysaccharide fibers by highly
dispersed titanium dioxide nanoparticles. Excitingly, these
hybrid materials are imparted with three main advantages:
(4) For reviews, see: (a) Margelefsky, E. L.; Zeidan, R. K.; Davis, M. E.
Chem. Soc. ReV. 2008, 37, 1118–1126. (b) Chechik, V. Annu. Rep. Prog.
Chem., Sect. B 2008, 104, 331–348. (c) Tada, M.; Motokura, K.; Iwasawa,
Y. Top. Catal. 2008, 48, 32–40. (d) Notenstein, J. M.; Katz, A. Chem.sEur.
J. 2006, 12, 3954–3965.
Figure 2
.
Photo and SEM of M1H.
(
5) (a) Climent, M. J.; Corma, A.; Garcia, H.; Guil-Lopez, R.; Iborra,
1
2
S.; Forn e´ s, V. J. Catal. 2001, 197, 385–393. (b) Climent, M. J.; Corma,
A.; Iborra, S.; Velty, A. J. Mol. Catal. A: Chem. 2002, 182-183, 327–
Intrigued by this acid-base cohabitation, we decided to
examine how these hybrid materials could catalyze coop-
eratively different condensation reactions involving carbonyl
3
42. (c) Climent, M. J.; Corma, A.; Forn e´ s, V.; Guil-Lopez, R.; Iborra, S.
AdV. Synth. Catal. 2002, 344, 1090–1096.
6) (a) Hruby, S. L.; Shanks, B. H. J. Catal. 2009, 263, 181–188. (b)
Anan, A.; Quellette, W.; Sharma, K. K.; Asefa, T. Catal. Lett. 2008, 126,
(
activation. It was expected that the presence of both NH
2
1
2
2
42–148. (c) Sharma, K. K.; Asefa, T. Angew. Chem., Int. Ed. 2007, 46,
879–2882. (d) Zeidan, R. K.; Hwang, S.-J.; Davis, M. E. J. Catal. 2007,
47, 379–382. (e) Bass, J. D.; Solovyov, A.; Pascall, A. J.; Katz, A. J. Am.
and titanium clusters in close proximity could cooperatiVely
actiVate the electrophile and nucleophile reactants and
consequently enhance the reaction rates of the desired
organic transformations. Herein we investigate this approach
for specific model reactions (Henry condensation, Michael
addition, jasminal synthesis) and report the proof of concept
of the synergetic effect between the two catalytic site
partners.
Chem. Soc. 2006, 128, 3737–3747. (f) Zeidan, R. K.; Hwang, S.-J.; Davis,
M. E. Angew. Chem., Int. Ed. 2006, 45, 6332–6335. (g) McKittrick, M. W.;
Jones, C. W. J. Am. Chem. Soc. 2004, 126, 3052–3053. (h) Hicks, J. C.;
Dabestani, R.; Buchanan, A. C.; Jones, C. W. Chem. Mater. 2006, 18, 5022–
5
032.
(
7) (a) Motokura, K.; Tada, M.; Iwasawa, Y. J. Am. Chem. Soc. 2009,
1
31, 7944. (b) Solin, N.; Lu, H.; Schnai, C.; Terasaki, O. Catal. Commun
2
009, 10, 1386–1389. (c) Puglisi, A.; Annunziata, R.; Nenaglia, M.; Cozzi,
F.; Gervasini, A.; Bertacche, V.; Sala, M. C. AdV. Synth. Catal. 2009, 351,
First, Henry condensation of nitromethane with 4-meth-
oxybenzaldehyde as a prototype was investigated because it
illustrates the paradoxical statement that initiated the present
219–229. (d) Motokura, K.; Tomita, M.; Tada, M.; Iwasawa, Y. Chem.sEur.
J. 2008, 14, 4017–4027. (e) Motokura, K.; Tada, M.; Iwasawa, Y. Chem.
Asian J. 2008, 3, 1230–1236. (f) Motokura, K.; Tada, M.; Iwasawa, Y.
J. Am. Chem. Soc. 2007, 129, 9540–9541. (g) Huh, S.; Chen, H. T.; Wiench,
J. Z.; Pruski, M.; Lin, V. S.-Y. Angew. Chem., Int. Ed. 2005, 44, 1826–
13
work (Table 1). The catalytic performances using the
1
830. (h) Huh, S.; Chen, H.-T.; Wiench, J. W.; Pruski, M.; Lin, V. S-Y.
J. Am. Chem. Soc. 2004, 126, 1010–1011.
8) For an elegant work describing an in situ generation of a spatially
various porous chitosan@titania among different catalysts
are shown in Table 1. Actually, chitosan@titania micro-
spheres were found to be the more active catalysts (entries
4-6). With chitosan alone, featuring a similar texture, the
reaction proceeded smoothly, and a quantitative yield was
(
grafted bifunctional site, see: (a) Margelefsky, E. L.; Bendjeriou, A.; Zeidan,
R. K.; Dufaud, V.; Davis, M. E. J. Am. Chem. Soc. 2008, 130, 13442–
1
3449. For the positioning of two distinct functional groups in the channels,
see: (b) Alauzun, J.; Mehdi, A.; Reye, C.; Corriu, R. J. P. J. Am. Chem.
Soc. 2006, 128, 8718–8719. (c) Mouawia, R.; Mehdi, A.; Reye, C.; Corriu,
R. J. P. J. Mater. Chem. 2008, 18, 4193–4203.
(12) An interesting topic is recently introduced by Stephan by designing
homogenous noncoordinated Lewis pairs (known as F. L. P.: Frustrated
Lewis Pairs). These bifunctional pairs exhibit an unusual reactivity. See
for review: Stephan, D. W Org. Biomol. Chem. 2008, 6, 1535–1539.
(13) (a) Ma, K.; You, J. Chem.sEur. J. 2007, 13, 1863–1871. (b)
Palomo, C.; Oiarbide, M; Laso, A. Angew. Chem., Int. Ed. 2005, 44, 3881–
3884. (c) Risgaard, T.; Gothelf, K. V.; Jorgensen, K. A. Org. Biomol. Chem.
2003, 1, 153–156. (d) Ooi, T.; Doda, K.; Maruoka, K. J. Am. Chem. Soc.
2003, 125, 2054–2055.
(
9) (a) Valentin, R.; Molvinger, K.; Quignard, F.; Brunel, D. New
J. Chem. 2003, 27, 1690–1692. (b) Molvinger, K.; Quignard, F.; Brunel,
D.; Boissiere, M.; Devoisselle, J. M. Chem. Mater. 2004, 16, 3367–3372.
(
c) El Kadib, A.; Molvinger, K.; Guimon, C.; Quignard, F.; Brunel, D.
Chem. Mater. 2008, 20, 2198–2204.
10) (a) Guibal, E. Prog. Polym. Sci. 2005, 30, 71–109. (b) Macquarrie,
D. J.; Hardy, J. J. E. Ind. Eng. Chem. Res. 2005, 44, 8499–8520.
11) See Supporting Information for details.
(
(
Org. Lett., Vol. 12, No. 5, 2010
949

achieved only after 24 h of reaction (entries 2 and 3). Lower
yield was obtained with inorganic titanium dioxide (entry
Table 1. Henry Reaction of Nitromethane with
7). This reveals the higher activity of the base catalysts versus
a
4
-Methoxybenzaldehyde
acid solids and the crucial role played by the amino groups
in these bifunctional chitosan@titania materials. The pre-
dominance of nitrostyrene 1 versus nitroalcohol 2 (entries
2
-6) suggests that the condensation occurs by an imine
formation mechanism as primary amines supported silica that
6
b
b
entry
cat.
t (h)
% convn
1 (%)
2 (%)
produced preferentially nitrostyrene, by contrast of sup-
ported tertiary amine that switched the selectivity to nitroal-
cohol. In the latter case, the reaction proceeds via an ion
1
2
3
4
5
6
7
8
9
0
----
M0
M0
M1H
M2H
M3H
TiO2
NEt3
24
3
24
3
3
3
24
5
5
24
24
24
24
0
15
68
98
90
95
7
55
90
13
16
0
---
95
95
97
93
95
100
29
92
81
94
---
---
5
5
3
7
5
0
71
8
19
6
6
b
pair mechanism. Katz et al. showed a dramatic effect of
6e
outer sphere acidity on the selectivity in the Henry reaction.
In a hydrophilic primary amine-tethered silica, considered
as bifunctional acid-base material, the surface silanols (Si-
OH) are shown to accelerate the formation of imine and
iminium, both of which are intermediate in nitrostyrene
c
Et-NH2
Ph-NH2
Ti(OiPr)4
Et3N/Ti(OiPr)4
Et-NH2/Ti(OiPr)4
6
e
formation. In our case, the higher reactivity of the hybrid
chitosan@titania (compared to the monofunctional chitosan)
can be explained by an assistance of titanium Lewis acid
during the imine formation.
1
11
12
---
---
13
0
---
a
The results obtained with homogeneous bases correlate
with the strength of the base and with the proposed
Conditions are as follows: T ) 80 °C. 4-Methoxybenzaldehyde (1
b
mmol), catalyst (0.05 mmol), nitromethane (8 mL). Determined by GC
c
(
dodecane as external standard). TiO2 was obtained by calcination of the
mechanism (entries 8-10). When Ti(OiPr)
4
was used as
hybrid M1H (see Supporting Information).
catalyst, the yield did not exceed 16% (entry 11). Addition-
ally, the efficiency of either triethylamine or ethylamine was
inhibited in the presence of a stoichiometric amount of
titanium tetraisopropoxide, and neither nitrostyrene nor
nitroalcohol were found in the solution (entries 12 and 13).
This trend probably results from a neutralization effect
between the Lewis base and Lewis acid in homogeneous
media. When heterogeneous chitosan and homogeneous
The Michael addition of ethyl cyanoacetate with 2 equiv
of methyl vinyl ketone demonstrates clearly the higher
activity (and selectivity) of our hybrid microspheres (Table
2
).
Quantitative yields were obtained after only 30 min at
room temperature (entries 2-4). With native chitosan M0,
a moderate 41% yield was reached after an extended time
of 1 h. The poor yield obtained with the nonporous xerogel
M1Hxero (entry 5) highlights the role of the macroporosity
that facilitates the diffusion of the reactant to the active sites
and the scavenging of the products (and water byproduct)
from the reactor, enhancing thus the kinetics of the reaction.
In terms of selectivity, the three hybrid microspheres M1H,
M2H, and M3H gave a good selectivity for 5-carboethoxy-
4
Ti(OiPr) were used, no reaction was observed suggesting
thus the poisoning of amine functions by homogeneous
titanium Lewis acid. On the other hand, no significant
improvement was observed by the simultaneous introduction
of the two heterogeneous catalysts (chitosan and titanium
1
4
dioxide).
To rule out the possible role played by chitosan@titania
as a reservoir for homogeneous catalyst based on highly
active titania nanoparticles, leaching experiments were
carried out. The reaction of the three materials (M1H, M2H,
M3H) was performed until half conversion was observed
5
-cyano-2,8-nonanedione 4. By contrast, in the case of
chitosan, longer reaction time improved neither the yield nor
the selectivity. After 5 h, the conversion did not exceed 50%,
and the selectivity for the product 4 remained 58%. This
demonstrates the beneficial effect of the electrophilic activa-
tion of the carbonyl group by titanium nanoparticles.
Similarly, a significant enhancement of catalytic activity
gained by supporting organic amines in silica-alumina
(
1 h, ∼ 49% of conversion). The material beads were
removed from the solution while the reaction mixture was
still hot. No further conversion was observed upon heating
for 4 h (see Supporting Information). Furthermore, no metal
was detected in the solution by ICPMS analysis. This
supports the heterogeneous nature of the reaction.
7
d,e
(Si-O-Al) was recently reported.
This unusual activity
was also rationalized by the dual acid-base character of the
These interesting results prompted us to assess the catalytic
behavior of chitosan@titania hybrid materials in other
reactions involving electrophilic and nucleophilic activations.
designed materials which makes them more reactive than
7
d,e
the classical amine supported silica catalysts.
An important challenge in organic synthesis is how to force
a reaction to result in enrichment with one targeted product.
For instance, jasminaldehyde (-2-pentyl-3-phenyl-2-propenal,
(
14) For sequential one-pot reactions using two separated acidic and
basic catalysts, known as site isolation concept, see for instance: (a) Voit,
B. Angew. Chem., Int. Ed. 2006, 45, 4238–4240. (b) Helms, B.; Guillaudeu,
S. J.; Xie, Y.; McMurdo, M.; Hawker, C. J.; Frechet, J. M. J. Angew. Chem.,
Int. Ed. 2005, 44, 6384–6387. (c) Motokura, K.; Nishimura, D.; Mori, K.;
Mizugaki, K.; Ebitani, K.; Kaneda, K. J. Am. Chem. Soc. 2004, 126, 5662.
5), an important perfumery chemical, is industrially prepared
through the condensation of 1-heptanal and benzaldehyde
in the presence of alkali as catalyst (sodium or potassium
hydroxide). However, one of the drawbacks of this route is
(
3
d) Gelman, F.; Blum, J.; Avnir, D. Angew. Chem., Int. Ed. 2001, 40, 3647–
649.
950
Org. Lett., Vol. 12, No. 5, 2010

a
Table 2. Michael Addition of Ethyl Cyanoacetate with 2 Equiv
of Methyl Vinyl Ketone
Table 3. (E/Z)-2-Pentyl-3-phenyl-2-propenal Synthesis
a
convn
heptanal
(%)
b
temp
(°C)
c
c
b
entry
cat.
M0
M1H
M2H
M3H
t (h)
5 (%)
6 (%)
entry
cat.
t (h)
% convn
3 (%)
4 (%)
1
2
3
4
5
a
6
4
4
4
24
80
80
80
80
120
92
98
85
89
87
48
86
81
79
53
50
11
9
12
19
1
2
3
4
5
6
a
M0
1
41
78
70
70
17
35
43
3
21
13
71
64
57
97
79
87
29
36
M1H
M2H
M3H
0.5
0.5
0.5
1
d
c
TiO2
M1Hxero
c
TiO2
3
Conditions are as follows: heptanal (1 mmol), benzaldehyde (5 mmol),
b
catalyst (0.05 mmol), toluene (10 mL). Determined by GC (dodecane as
external reference). Mixture of both E and Z isomers. Obtained by
calcination of M1H hybrid (see Supporting Information).
Conditions are as follows: ethyl cyanoacetate (1 mmol), methyl vinyl
ketone (2.2 mmol), catalyst (0.05 mmol), toluene (5 mL). Determined by
GC (dodecane as external standard). See Supporting Information.
c
d
b
c
stability and reusability. With this aim, successive condensa-
tions of methylvinylketone with ethyl cyanoacetate (Table
the formation of an undesired 2-pentyl-2-nonenal 6 from the
self-condensation of heptanal. Efforts were then directed to
enhance the selectivity to jasminaldehyde by using various
1
) using M1H catalyst were performed. The recovered
5a
15
nanoreactor M1H was successively used for five successive
runs, and the obtained results showed consistent activity with
an average yield of 72% even though extended reaction time
was required (see Supporting Information).
catalysts: HY and ꢀ-zeolites, aluminosilicates, magnesium
1
6
5a,c
organosilicates, and amorphous aluminophosphates,
among others. Corma et al. demonstrated the utility of
acid-base bifunctional solid catalysts for jasminaldehyde
5
a-c
In conclusion, a new class of cooperative acid-base
bifunctional hybrid materials was reported. The templating
effect of chitosan allowed the control of mineral growth of
nanotitania inside the macrochannels of the swelling biopoly-
mer. The supercritical drying improves the textural properties
of these materials, thus leading to high surface area nanore-
actors. The macrochannels, the naturally spaced amino
functions borne by chitosan and the nanosized titanium
dioxide, provide a synergetic means of an efficient approach
of the reactants to the active sites. The remarkable set of
reactions affected by bifunctional catalyst including the
higher activity in Henry and Michael addition and the
selectivity in jasminaldehyde synthesis attest the cooperative
acid-base attainable in chitosan@titania hybrid materials.
Other hybrid materials based on chitosan@inorganic oxides
and their applications in fine chemical synthesis are under
investigation.
synthesis.
The weak acidic site induces an electrophilic
activation of the carbonyl group of benzaldehyde, which
favors the attack of the enolate heptanal intermediate formed
1
7
by interaction with the basic sites.
Having these materials in hands, we explored the catalytic
condensation of heptanal and benzaldehyde by the hybrid
chitosan@titania microspheres (M1H, M2H, and M3H),
native chitosan M0, and nanotitania (Table 3). Chitosan@
titania hybrids (M1H, M2H, and M3H) perform a quantita-
tive conversion of heptanal in relatively short reaction time
(
entries 2-4). By contrast, native chitosan (entry 1) and
nanotitania (entry 5) required a longer reaction time to reach
nearly the same conversion level. The bifunctional chitosan@
titania catalysts provided in addition the highest selectivity
in jasminaldehyde. The undesirable 2-pentyl-2-nonenal 6 did
not exceed 12% using these hybrid materials (entries 2-4)
witnessing thus on their bifunctional character.
The most crucial issue that should be considered for
practical application of heterogeneous systems is the catalyst
Acknowledgment. A. E. K. thanks Carnot foundation and
INANOTECH for financial support.
(
15) Climent, M. J.; Corma, A.; Guil-Lopez, R.; Iborra, S.; Primo, J. J.
Catal. 1998, 175, 70.
16) Sharma, S. K.; Patel, H. A.; Jasra, R. J. Mol. Catal. A: Chem. 2008,
80, 61.
17) In homogenous base-catalyzed condensation of alkanals with
Supporting Information Available: Experimental pro-
cedures and textural and structural characterization of
catalysts M1H, M2H, and M3H. This material is available
free of charge via the Internet at http://pubs.acs.org.
(
2
(
benzaldehyde, the selectivity to R-alkylcinnamaldehydes can be increased
by adding a small amount of an acid. Kuiterman, A.; Castelijns, A. M. C. F.;
Dielemans, H. J. A.; Green, R. European Patent 0771780 A1, 1997.
OL9029319
Org. Lett., Vol. 12, No. 5, 2010
951