Hybrid inorganic-organic materials carrying tertiary amine and thiourea residues tethered on mesoporous silica nanoparticles: Synthesis, characterization, and co-operative catalysis

Article abstract of DOI:10.1002/adsc.200800635

Mesoporous silica nanoparticles carrying different loadings of tertiary amine and thiourea residues (residues ratios 53/47, 68/32, and 22/78, respectively) were synthesized by the co-condensation method and fully characterized by CP MAS NMR, powder XRD, S

Full text of DOI:10.1002/adsc.200800635

FULL PAPERS
DOI: 10.1002/adsc.200800635
Hybrid Inorganic-Organic Materials Carrying Tertiary Amine and
Thiourea Residues Tethered on Mesoporous Silica Nanoparticles:
Synthesis, Characterization, and Co-Operative Catalysis
Alessandra Puglisi,a,* Rita Annunziata,a Maurizio Benaglia,a,* Franco Cozzi,a
Antonella Gervasini,b Vittorio Bertacche,c and Maria Chiara Salac
a
ISTM-CNR and Dipartimento di Chimica Organica e Industriale, Universitaꢀ degli Studi di Milano, via Golgi 19, 20133
Milano, Italy
Fax : (+39)-0250-314-159; phone: (+39)-0250-314-171; e-mail: maurizio.benaglia@unimi.it
Dipartimento di Chimica Fisica ed Elettrochimica, Universitaꢀ degli studi di Milano, via Golgi 19, 20133 Milano, Italy
Istituto di Chimica Organica “A. Marchesini” della Facoltaꢀ di Farmacia, Universitaꢀ degli Studi di Milano, via Venezian
b
c
21, 20133 Milano, Italy
Received: October 16, 2008; Revised: December 5, 2008; Published online: January 12, 2009
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/adsc.200800635.
Abstract: Mesoporous silica nanoparticles carrying and with different combinations of monofunctional
different loadings of tertiary amine and thiourea resi- supported and non-supported catalyst, the co-opera-
dues (residues ratios 53/47, 68/32, and 22/78, respec- tivity of the tertiary amine and thiourea residues in
tively) were synthesized by the co-condensation catalyzing the reaction was demonstrated. The use of
method and fully characterized by CP MAS NMR, the bifunctional catalyst was extended to the addi-
powder XRD, SEM, BET, BJH and FT-IR tech- tion of acetylacetone to an activated imine. Catalyst
niques. These materials were tested as bifunctional recycling for a total of three reaction cycles was
catalysts in the conjugate addition of acetylacetone demonstrated without significant erosion of activity.
to 2-nitrostyrene, a reaction that under solvent-free
conditions occurred in quantitative yield. By carrying Keywords: catalyst recycling; co-operative catalysis;
out several experiments with the bifunctional cata- mesoporous materials; organic catalysis; organic-in-
lysts featuring different molar ratios of active sites, organic hybrid composites
Introduction
As a support, mesoporous silica takes advantage both
of the large pore size of the nanoparticles (ꢀ2 nm),
The catalytic efficiency of enzymes largely relies upon that allows easy mass transfer, and of ready function-
co-operative interactions of functional groups synerg- alization with different organic residues.[2] Among the
istically at work in the active site. In the attempt at synthetic protocols investigated to obtain mesoporous
mimicking enzymatic catalysis with simpler molecules, silica-supported catalysts, co-condensation appears su-
the concept of co-operative catalysis has been imple- perior to post-synthetic grafting, especially when, as
mented in the design of artificial catalytic systems, in the case of co-operative catalysis, inorganic-organic
mostly by assembling bifunctional catalysts on differ- hybrid materials carrying different catalytic residues
ent scaffolds. These can be structures of widely differ- must be obtained.[3] In addition, the nature of the co-
ent properties and complexity, ranging from short condensation process, that involves the reaction of a
chains of carbon atoms to organic or inorganic macro- tetralkoxysilane with trialkoxyorganosilanes carrying
scopic materials. The selection of the scaffold, which the different functionalities required for catalysis, can
has the very important task of keeping the catalysts in open access to systems in which the functional group
the correct relative disposition required for co-opera- ratios can be varied at will, allowing an additional
tivity and of providing a favourable reaction environ- tuning of the catalystꢀs properties. This approach can
ment, is crucial to the success of the design.
also benefit extensively from the great number of or-
Recently, a limited number of bifunctional catalysts ganocatalysts that have recently become available
supported on mesoporous silica have been reported.[1] both in the soluble[4] and in the supported form.[5]
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According to a recent review,[1] co-operativity[6] of
bifunctional catalysts supported on mesoporous silica
has been demonstrated so far only by the groups of
Lin[7] and Davis.[8] In particular, Lin and his co-work-
ers synthesized a catalyst featuring secondary amine
and urea residues, and showed that this system pro-
moted the addition of acetone, nitromethane, and tri-
methylsilyl cyanide to 4-nitrobenzaldehyde, possibly
by co-operative activation of the aldehyde carbonyl
by H-bonding with urea and of the nucleophiles by
the secondary amine. Davis and his collaborators re-
ported co-operation of sulfonic acids with thiol
groups in the bisphenol A synthesis and of Brønsted
acids (sulfonic, phosphonic, and carboxylic acids) with
primary amine residues in the aldol reaction.
Herein, we report the synthesis and complete char-
acterization of a new bifunctional catalytic system
supported on mesoporous silica featuring tertiary
amine and thiourea functionalities in different ratios.
The co-operativity of the active sites of this system
has been demonstrated in the conjugate addition of
acetylacetone to 2-nitrostyrene, a reaction occurring
in quantitative yield when performed under solvent-
free conditions. The same catalyst was also demon-
strated to be active in the addition of acetylacetone to
N-carbobenzyloxybenzaldimine. Preliminary experi-
ments also showed that catalyst recycling was possi-
ble.
Results and Discussion
Synthesis and Characterization
The design of the bifunctional catalyst was influenced
by Takemotoꢀs discovery that the organocatalyst re-
ported in Figure 1 effectively promoted the conjugate
addition of diethyl malonate to nitrostyrene.[9] The
catalysis was believed to involve deprotonation of
malonate by the tertiary amino group and activation
of the nitroalkene by formation of a double H-bond
between the relatively acidic protons of the thiourea
moiety and the nitro group.[10]
Figure 1. Structures of Takemotoꢀs catalyst, bifunctional cat-
alysts 1–3, their precursors 4 and 5, and monofunctional spe-
cies 6 and 7.
(DTPA, 4) and N-(3,5-bistrifluoromethylphenyl)-N’-
On these bases, the three bi-functional catalysts 1–3 (3-trimethoxysilyl-1-propyl)thiourea (TFPU, 5). Com-
reported in Figure 1 were synthesized by the co-con- pound 4 is commercially available as are 3-trimeth-
densation method.[3,7] We reasoned that the two func-
ACHTUNGTRENoNUGN xysilylpropanamine and 3,5-bis(trifluoromethylphen-
tional groups, the tertiary amine and the thiourea yl) isothiocyanate required for the preparation of
moiety, could be forced in proximity by the silica scaf- compound 5. Monofunctional catalysts 6 and 7 were
fold and could co-operate by simultaneous activation also prepared by the same approach.
of a nucleophile and an electrophile, like in Takemo-
The actual concentrations of the DTPA and TFPU
toꢀs catalyst. In principle, this approach allows an easy functional groups were determined by the previously
preparation of a multifunctional heterogeneous recov- described solid-state 13C cross-polarized magic angle
erable and reusable catalyst, by simple assembly of spinning (CP MAS) and 29Si MAS NMR spectroscop-
different precursors.
ic methods.[7] The total surface concentrations of the
Catalysts 1–3 are identified by the initial molar organic residues (DTPA+TFPU) in catalysts 1–3
ratio of their trialkoxyorganosilane precursors, were determined to be 1.52, 1.44, and 1.16 mmolgÀ1,
namely N,N-dimethyl-3-trimethoxysilylpropanamine respectively. The DTPA/TFPU concentration ratios
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for 1–3 were 53/47, 68/32, and 22/78, respectively, in
fair agreement with the stoichiometric ratios of the monium bromide), employed as templating agent for
trialkoxyorganosilanes employed for their synthesis. fabrication of the silica material, directed the forma-
The presence of the surfactant (cetyltrimethylam-
The structural properties of catalysts 1–3 were in- tion of an ordered pore structure. The surface areas,
vestigated using different techniques. Powder XRD pore volumes, and pore size distributions of catalysts
patterns revealed the complete amorphous character 1–3 were determined by N2 adsorption-desorption iso-
of these materials. This was expected because of the therms. All surfaces exhibited characteristic type IV
very rapid gelation of the mixture containing the pre- BET isotherms consistent with the presence of cylin-
cursors of the final products in the synthesis of the drical meso-scale pores. The step corresponding to ca-
materials. The XRD patterns of catalysts 1–3 were do- pillary condensation in the mesopores appeared in
minated by a very broad band in the 15–258 2q inter- the relative pressures range 0.20–0.35 (Figure 3). A
val, diagnostic of the presence of disordered silica not unique pore population can be detected for the
(see Supporting Information). Amorphous functional- three catalysts; a major population centered at ca.
ized silicas are among the most widely studied and 20 ꢂ and a minor one, with larger pore size and
used organic-inorganic hybrid solids for catalytic ap- broader resolution, at ca. 40 ꢂ. In agreement with the
plications.[2c]
literature studies on similar materials,[3a,7] and by com-
Morphological examination of the sample particles parison with the bare silica (obtained by the same
was performed by collecting images of the surfaces by synthetic route), it could be assumed that the func-
SEM analysis. The images of the surfaces of all the in- tionalized silica materials present a hierarchy of
organic-organic hybrid materials compared with those pores; the major population is associated with smaller
of bare silica display a variety of particle shapes and and well defined mesopores and the minor population
sizes. Figure 2 shows the micrographs of 1, chosen as with wider pore population, mainly housing the or-
an example, at two different magnifications. Rod- ganic functionalities.
shaped particles of different lengths and diameters
The BET surface areas (S.A.) of 1, 2, and 3 are of
(ca. 1 mm in length and 500 nm in diameter) with 658, 712, and 772 m2 gÀ1, respectively. The observed
curved hexagonal-shaped tubular morphology quite differences could be ascribed to the different DTPA/
completely cover irregular polyhedral-shaped grains, TFPU concentration ratios of the functional groups
associated with the silica morphology.
(53/47, 68/32, and 22/78 for 1, 2, and 3, respectively).
Figure 2. SEM iamges of a sample of bi-functional catalyst 1 at two different magnifications of 5,000ꢃ and 10,000ꢃ.
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Figure 3. N2-adsorption-desorption isotherms of the bifunctional catalysts: a) 1; b) 3; and c) 2 (left) with corresponding pore
size BJH distribution curves (right).
Table 1. Main morphological properties of the bifunctional the presence of the functional groups on the surface
catalysts.
of the nanoparticles and to determine their relative
concentration.[11] Comparison of the FTIR spectra
(Figure 4) of bifunctional catalyst 1 and monofunc-
tional material 7, both containing the thiourea resi-
due, (Figure 1) allowed us to assign the signal at
1555 cmÀ1 to the C=S double bond stretching of this
Catalyst N2 uptake
[cm3 gÀ1
S.A.
Pore
Pore
size[a]
[ꢂ]
(BET)
volume
(STP)]
[m2 gÀ1]
[cm3 gÀ1]
1
2
3
151
163
177
658
712
772
0.344
0.594
0.420
22 (42)
24 (37)
21 (42)
group, the signal at 1388 cmÀ1 to the Ar N bond
À
stretching, and the signal at 1282 cmÀ1 to the C F
À
[a]
bond stretching; together with other signals at 847,
700, and 682 cmÀ1 the latter signal was considered di-
agnostic of the meta substitution pattern on the aro-
Pore size of major and (minor) population.
Because of the modest porosity offered by the three matic ring. As expected, all of these signals were
catalysts (Table 1, 4th column), the measured high sur- absent in the spectrum of the dimethylamino-func-
face area values should be mainly due to the small tionalized material 6 (Figure 1). Due to the lack of
siliceous particles.
functional groups providing significant IR signals in
Further characterization of these hybrid materials compound 6, comparison of the spectra of the latter
was obtained by Fourier transform infrared (FT-IR) with those of compounds 1 and 7 was carried out
spectroscopy. This technique was used both to assess using a “five points” second derivative function
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Figure 4. Comparison between the FT-IR spectra of monofunctional (6,7) and of bifunctional (1) materials.
(Figure 5),[12] with the aim of emphasizing differences signals at 847, 700, 682 cmÀ1, assigned to the
between the spectra. By this comparison it was possi- (CF3)2Ar-N part of the thiourea residue, observed on
ble to demonstrate that materials 1 and 6 shared sig- passing from 2 to 1 to 3, was also evident (Figure 6,
nals at 1482 and 1418 cmÀ1, which did not appear in 7, b).[13]
and that hence can be ascribable to the dimethylami-
no residue.
It is also interesting to note how the second deriva- Catalytic Activity
tive spectrum of bifunctional catalyst 1 showed the
combination of the signals at 1482 and 1474 cmÀ1, in- To determine whether the bifunctional catalysts 1–3
dividually present in the spectrum of mono-functional could act through co-operative catalysis, they were
6 and 7, respectively.
employed in the conjugate addition of acetylacetone
Remarkably, the FT-IR spectra of bifunctional 1–3 to 2-nitrostyrene to afford 3-[1-(1-phenyl-2-nitroeth-
showed relative signal intensities in agreement with yl)]-2,4-pentanedione 8 [Eq. (1)].[14] It must be noted
the different loading of functional groups (Figure 6, a,
1900–1250 cmÀ1 region; Figure 6, b 1000–650 cmÀ1
region). For instance, with respect to what observed
in the spectrum of catalyst 1 (DTPA:TFPU ratio
53:47) the signals at 1282 cmÀ1 (due to C F bond
À
stretching) and at 1555 cmÀ1 (C=S stretching) in-
creased in the spectrum of catalyst 3 (DTPA:TFPU
ratio 22:78) and decreased in that of 2 (DTPA:TFPU
ratio 68:32). Accordingly, the signal at 1417 cmÀ1 (as-
signed to the residue of DTPA, see above) was stron- that conjugate addition reactions have never before
ger in the spectrum of compound 2 and weaker in been reported for organic catalysts supported on mes-
that of 3 (Figure 6, a). The increased intensity of the oporous silica nanoparticles.[15]
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Figure 5. Second derivative (five points) spectra of materials 1, 6, and 7.
Figure 6. Comparison between FT-IR spectra of compounda 1–3 (a 1900–1250 cmÀ1 region; b 1000–650 cmÀ1 region).
As mentioned before, we believed that the tertiary temperature, 24 h) carried out in the presence of 10
amine and thiourea groups could act co-operatively mol% of the catalyst (based on the total surface con-
on the nucleophile donor and on the electrophile ac- centrations of the organic residues)[16] were consistent
ceptor, respectively, facilitating the process, as depict- with this hypothesis.
ed in Scheme 1. The results obtained by studying the
As can be seen from the data reported in Table 2,
reaction of Eq. (1) (1.6 mol equiv. of acetylacetone, bifunctional catalyst 1, featuring a 53/47 loading of
1.0 mol equiv. of 2-nitrostyrene, diethyl ether, room basic and acid sites, promoted the reaction in 80%
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As expected on the basis of the proposed activation
mechanism, catalysts containing only a thiourea group
such as 5 and 7 were not effective (entry 6 and 7).
However, when the supported monofunctional thiour-
ea material 7 was used in combination with non-sup-
ported tertiary amine 4 (entry 8) or with triethylamine
(TEA, entry 9) good yields were obtained (71 and
75%, respectively). These were higher than those ob-
served in the presence of only tertiary amines (en-
tries 4 and 5), a fact that again points to an active role
for the thiourea residue. Interestingly, a physical mix-
ture of equimolar amounts of the monofunctional de-
rivatives 6 and 7 was less effective than the bifunc-
tional catalyst 1 (entry 10), showing that the proximity
of the two active sites on the surface, a peculiar fea-
ture of the bifunctional catalyst, pays off in terms of
co-operativity. Remarkably, the activity of bifunction-
al 1 can be replicated only by operating under homo-
geneous reaction conditions with an equimolar mix-
ture of 4 and 5 (entry 11).
Scheme 1. Co-operative activation of nucleophile donor and
electrophile acceptor by bifunctional catalyst 1–3.
Table 2. Synthesis of adduct 8 in the presence of different
catalyst species.
With the aim of further demonstrating the true co-
operativity between tertiary amine and thiourea resi-
dues in our bifunctional catalysts, it was decided to
check whether the observed enhancement in the yield
of adduct 8 observed on passing from the supported
tertiary amine catalyst 6 (entry 5) to the bifunctional
catalysts 1–3 (entries 1–3) was not due to a more fa-
vourable modulation of surface properties induced by
the thiourea residue.[1,6,7] In principle, it could be hy-
pothesized that the thiourea residue, for instance by
creating a lipophilic environment around the tertiary
amine site,[6e] makes this site more accessible to the
hydrophobic reagents of Eq. (1) and thus enhances
the yield of this reaction. With this goal in mind, the
bifunctional material 9 (Figure 7), featuring a stoi-
chiometric 1/1 ratio of the tertiary amine residue and
Entry
Catalyst
Amine/thiourea ratio
Yield [%]
1
2
3
4
5
6
7
8
1
2
3
4
6
5
7
53/47
68/32
22/78
1/0
1/0
0/1
0/1
1/1
1/1
1/1
80
54
56
25
43
0
0
4+7
TEA+7
6+7
4+5
71
75
53
82
9
10
11
1/1
yield (entry 1). Varying the ratios of the supported of a tertiary amide group structurally related to the
tertiary amine and thiourea functions to 68/32 or 22/ thiourea moiety of 1–3, was synthesized and tested as
78, as in catalysts 2 and 3, respectively, led to lower
yields (ca. 55%, entries 2 and 3). In this respect, the
behaviour of our catalysts differed from that of
Linꢀs[7] and Davisꢀ catalysts,[8a] for which the best cata-
lytic activity was observed with unbalanced mixtures
of active sites.
In the presence of either non-supported (entry 4)
or supported (entry 5) tertiary amine catalysts 4 and 6
the reaction proceeded in lower yields (25 and 43%,
respectively), an indication of the active role played
by the thiourea group in the catalytic process. The
better yield observed with the supported catalyst 6 in-
stead of non-supported 4 could suggest that also the
relatively acidic silanol protons present on the surface
of the support can activate to some extent the nitroal-
kene.[6a–d] However, the fact that when a thiourea resi-
due is present on the catalysts better yields are ob-
tained (entries 1–3), indicates that this residue is a
stronger activator than the silanol groups.
Figure 7. Structure of bifunctional material 9.
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catalyst in the reaction of Eq. (1) under the condi- reaction was performed for three hours at room tem-
tions of entry 1, Table 2. perature without solvent in the presence of 10 mol%
We were pleased to find that, from this reaction, of the catalyst (entry 1, Table 4), the reaction mixture
adduct 8 was isolated in 43% yield, a value identical was simply rinsed with diethyl ether (100 mL/30 mg of
to that observed in the reaction promoted by the catalyst), and the catalyst was recovered by filtration,
monofunctionalized amine catalyst 6. We believe that dried under vacuum under different conditions (see
together with the previous findings (Table 2), this Table 4), and recycled. The results are collected in
result could be taken as a strong indication of co-op- Table 4.
erativity for bifunctional catalysts 1–3.
The effect of the solvent on the efficiency of the re-
action was then investigated in the case of bifunction-
Table 4. Recycling experiments with catalyst 1.
al catalyst 1. The results (Table 3) showed that the
Entry Catalyst regeneration con- Cycles Time
Yield
[%]
ditions
[h]
Table 3. Synthesis of adduct 8 in the presence of catalyst 1
in different solvents.
1
2
3
4
5
6
7
8
1
2
3
2
3
2
3
4
3
100
75
55
100
67
100
93
Vacuum, 4 h at 258C
Vacuum, 4 h at 258C
Vacuum, 4 h at 908C
Vacuum, 4 h at 908C
Vacuum, 4 h at 1508C
Vacuum, 4 h at 1508C
Vacuum, 4 h at 1508C
24
24
24
24
3
Solvent
Time [h]
Yield [%]
Et2O
24
24
24
24
24
24
24
3
80
80
56
45
30
10
100
100
68
CH2Cl2
Toluene
MeCN
DME
Dioxane
Neat
3
3
91
These data showed that the catalyst regeneration
Neat
Neat
procedure played a fundamental role in determining
the activity of the recovered material. After drying
the catalyst under vacuum at 258C for 4 h, a yellow
powder was recovered, whereas a freshly prepared
1
use of dichloromethane allowed us to obtain the same catalyst sample was perfectly white.[17] When em-
yield observed in diethyl ether (80%), while other sol- ployed in a second reaction (entry 2, Table 4) this re-
vents were less effective. However, when the reaction covered material showed to be less active, affording
was carried out in the absence of solvent a quantita- the product in 75% yield after 24 h (first cycle: 100%
tive yield was observed. Furthermore, it was shown yield after 3 h, entry 1, Table 4). The catalyst activity
that, under these conditions, the reaction time could further decreased in a third cycle (entry 3). By regen-
be drastically reduced from 24 to 3 h.
eration of the catalyst at higher temperature (4 h
We next demonstrated that the catalyst really oper- under vacuum at 908C) better results were obtained
ates under heterogeneous conditions. A mixture of in the second reaction (100% yield after 24 h, entry 4)
acetylacetone, 2-nitrostyrene, and catalyst
1 (10 but once again a decrease in the yield was observed
mol%) was stirred at room temperature until a yield in the third cycle (67% yield, entry 5). Finally reliable
of 35% was obtained, as monitored by NMR analysis. catalyst regeneration conditions were identified; by
The mixture was then diluted with diethyl ether, the drying the recovered catalyst under vacuum at 1508C
catalyst was filtered off and the volatile materials for 4 h[18] its activity was preserved and also in a
were evaporated. To the obtained residue, containing second cycle the product was obtained in 100% yield
2-nitrostyrene and product 8, acetylacetone was in just 3 h reaction time (entry 6).[19] The yield still re-
added to restore the initial reagent ratio, and the mix- mained very high (93% and 91%) in a third and
ture was allowed to stir at room temperature for addi- fourth cycle, clearly assessing the recyclability of the
1
tional 18 h. H NMR analysis showed no further for- properly regenerated catalyst 1 (entries 7 and 8).
mation of product 8. This result showed that the catal-
Finally, the use of catalyst 1 in another reaction was
ysis was indeed heterogeneous and that the siliceous investigated. On the basis of the recognized ability of
material did not suffer from any leaching of catalyti- thiourea-based organocatalysts to activate N-carboxy-
cally active organic residues into the reaction environ-
ment.
alkylimines toward nucleophilic attack,[9b] the N-car-
ACHTUNGTRENNUNG
bobenzyloxy (Cbz) imine of benzaldehyde was react-
The excellent results obtained in the absence of sol- ed with acetylacetone in the presence of 10 mol%[16]
vent led us to preliminarily investigate the issue of re- of catalyst 1 in toluene at room temperature for 18 h
cyclability of catalyst 1 since recovery and recycling is to afford product 10 in 83% isolated yield [Eq.
the major goal of catalyst supporting.[5] After a first (2)].[20]
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lybdate tetrahydrate (27 g) in water (469 mL) and concen-
trated sulfuric acid (31 mL). Flash chromatography was per-
formed on Fluka silica gel 60.
NMR Spectroscopy
Solid state NMR spectra were obtained at 125.62 (13C) and
at 99.36 (29Si) MHz on a Bruker Avance 500 spectrometer,
equipped with a 4 mm magic angle spinning (MAS) broad-
band probe (spinning rate nR up to 15 kHz). The MAS spec-
tra were recorded on solid samples, (typically 0.15 g); each
sample was packed into a 4 mm MAS rotor (50 mL sample
volume) spinning at 13 kHz and at a temperature of 330 K.
Direct polarization (DP) and variable amplitude cross polar-
ization (CP) methods were used for 29Si and 13C, respective-
ly. 250 scans and a delay of 300.0 s have been used for the
acquisition of 29Si NMR spectra, and 10,000 scans and a
delay of 2.0 s for that of 13C NMR spectra. These measure-
ments provided quantitative evidence for functionalization
of the materials with the organic moieties and confirmed
their structure. The assignments of 29Si resonances followed
Linꢀs report;[7] the assignments of 13C resonances were based
on comparison with the corresponding unbound compounds.
The spectra are reported in the Supporting Information.
From these spectra T2, T3, Q2, Q3, and Q4 values were ob-
tained. These data are collected in Table 5.
Conclusions
In conclusion, mesoporous silica nanoparticles carry-
ing different loadings of tertiary amine and thiourea
residues (residues ratios 53/47, 68/32, and 22/78, re-
spectively) were synthesized by the co-condensation
methods and fully characterized by CP MAS NMR,
powder XRD, SEM, BET, BJH and FT-IR tech-
niques. These materials were tested as bifunctional
catalysts in the conjugate addition of acetylacetone to
2-nitrostyrene, a reaction that under solvent-free con-
ditions occurred in quantitative yield. By carrying out
several experiments with the bifunctional catalysts
featuring different molar ratios of active sites, and
with different combinations of monofunctional sup-
ported and non-supported catalyst, the co-operativity
of the tertiary amine and thiourea residues in catalyz-
ing the reaction was demonstrated. The use of the bi-
functional catalyst was extended to the addition of
acetylacetone to N-Cbz-benzaldimine. Catalyst recy-
cling for a total of three reaction cycles was also dem-
onstrated. Work is in progress toward the synthesis of
bifunctional materials featuring enantiomerically pure
organocatalysts in order to exploit catalyst co-opera-
tivity in the context of stereoselective synthesis.
N2 Physisorption
Surface area and porosity were determined by collecting N2
adsorption/desorption isotherms at À1968C using a Carlo
Erba Sorptomatic 1900 series instrument. Prior to the analy-
sis, the samples (ca. 0.1 g) were outgassed at 908C for 3 h,
after this temperature remained constant. Specific surface
area was calculated via the BET model at relative pressure
of P/Po =0.05–0.35, assuming the molecular N2 diameter in
the adsorbed state as 16 ꢂ2. The total pore volume was esti-
mated from the uptake of nitrogen at a relative pressure of
P/Po =0.99. Pore size distribution was obtained from the de-
sorption branch of the isotherm using the Barrett–Joyner–
Halenda (BJH) model equation.[21]
Experimental Section
General
Scanning Electron Microscopy
All commercially available reagents including dry solvents
were used as received. Organic extracts were dried over
sodium sulfate, filtered, and concentrated under vacuum
using a rotatory evaporator. Non-volatile materials were
dried under high vacuum. Reactions were monitored by
thin-layer chromatography on pre-coated Merck silica gel 60
F254 plates and visualized either by UV or by staining with
a solution of cerium sulfate (1 g) and ammonium heptamo-
Scanning electron micrographs (SEM) were obtained by a
JEOL JSM-5500 LV operating at 20 kV.
Fourier Transform Infrared (FT-IR) Spectroscopy
FT-IR spectroscopy was used to determine the vibrational
frequencies of surface functional groups.[11] Spectra were ac-
quired on
a Spectrum One FTIR Spectrophotometer
Table 5. Relative concentrations of Tn and Qn silicon groups (in %), surface coverage (SC, in %), molecular concentrations
of organic functionalities (MC, in mmolgÀ1), molecular formulas (MF), DTPA:TFPU molar ratios (MR), and DTPA/TFPU
concentrations (in mmolgÀ1) derived from solid state 13C CP MAS- and 29Si MAS-NMR data.
Catalyst
T2
T3
Q2
Q3
Q4
SC
MC
MF[a]
MR
Concentration
1
2
3
6
5
4
8
7
7
6
6
6
37
35
40
43
47
43
25
23
19
1.52
1.44
1.16
N
(H2O)
(ORG)14
53:47
68:32
22:78
0.80/0.72
0.98/0.46
0.26/0.90
[a]
ORG indicates the organic functional groups. For the definitions of T2, T3, Q2, Q3, and Q4 see refs.[3a,7]
Adv. Synth. Catal. 2009, 351, 219 – 229
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227

Alessandra Puglisi et al.
FULL PAPERS
(Perkin–Elmer) in the range 4000–450 cmÀ1 (transmittance
mode). FT-IR grade KBr was ground for 5 min and dried at
1258C. KBr was then mixed with silicate in an agate mortar
for 1 min at 0.33% (w/w) concentration. Spectra were re-
corded selecting a scan number of 300 and 4 cmÀ1 resolu-
tion. The background of pure KBr was separately recorded
using the same conditions and automatically subtracted
from sample spectra.
yield: 43 mg (83% yield). The product was identical by
1H NMR to an authentic sample of compound 10.[20]
Supporting Information
Powder XRD determination of material 1; synthesis of thio-
urea 5; NMR spectra of bifunctional catalysts are available
as Supporting Information.
Synthesis of the Catalysts
The procedure reported by Lin et al.[7] was followed. The
preparation of catalyst 1 is representative of the procedure.
A solution of cetyltrimethylammonium bromide (365 mg,
1 mmol) in water (88 mL) and 2M NaOH (1.3 mL) was me-
chanically stirred at 550 rpm at 808C for 30 min. The stirring
speed was decreased to 200 rpm and tetraethoxysilane
Acknowledgements
Financial support by MIUR–PRIN (Nuovi metodi catalitici
stereoselettivi e sintesi stereoselettiva di molecole funzionali)
is gratefully acknowledged.
(TEOS, 1.82 mL, 8.16 mmol), compound
4 (0.121 mL,
0.525 mmol), and compound 5 (237 mg, 0.525 mmol; see the
Supporting Information for its synthesis) were rapidly added
in this order. After 2 min stirring at 200 rpm a precipitate
was formed. Stirring at 500–600 rpm was continued for 2.0 h
at 808C and the mixture was filtered while still hot. The
solid was washed with water (150 mL) and MeOH
(150 mL), and dried under high vacuum for 3 h to afford a
white material (794 mg). This was then treated with a solu-
tion of concentrated HCl (0.6 mL) in MeOH (80 mL) under
mechanical stirring for 2.5 h at 608C in order to remove the
surfactant. The cooled mixture was filtered and the solid
washed again with water and MeOH (100 mL each). The
white solid was dried under high vacuum for 3 h at 908C, to
afford a final yield of 576 mg of compound 1. Other sup-
ported catalysts were prepared by identical procedures in
similar yields. See text for their characterization.
References
[1] For an excellent recent review see: E. L. Margelefsky,
R. K. Zeidan, M. E. Davis, Chem. Soc. Rev. 2008, 37,
1118–1126.
[2] For reviews on mesoporous materials and application
to catalysis see: a) A. Corma, Chem. Rev. 1997, 97,
2373–2419; b) J. H. Clark, D. J. Macquarrie, Chem.
Commun. 1998, 853–860; c) A. P. Wight, M. E. Davis,
Chem. Rev. 2002, 102, 3589–3614; d) M. H. Valken-
berg, W. F. Hçlderich, Catal. Rev. 2002, 44, 321–374;
e) F. Hoffmann, M. Cornelius, J. Morell, M. Frçba,
Angew. Chem. 2006, 118, 3290–3328; Angew. Chem.
Int. Ed. 2006, 45, 3216–3251; f) Y. Wan, D. Zhao,
Chem. Rev. 2007, 107, 2821–2860.
[3] For description of the co-condensation method see:
a) S. Huh, J. W. Wiench, J.-C. Yoo, M. Pruski, V. S.-Y.
Lin, Chem. Mater. 2003, 15, 4247–4256; b) S. Huh,
J. W. Wiench, B. J. Trewyn, M. Pruski, V. S.-Y. Lin,
Chem. Commun. 2003, 2364–2365; c) R. Kumar, H.-T.
Chen, J. L. V. Escoto, V. S.-Y. Lin, M. Pruski, Chem.
Mater. 2006, 18, 4319–4327. For a comparison between
co-condensation and post-synthetic grafting methods
see: d) M. H. Lim, A. Stein, Chem. Mater. 1999, 11,
3285–3295; e) P. D. Vaz, C. D. Nunes, M. Vasconcellos-
Dias, M. M. Nolasco, P. J. A. Ribeiro-Claro, M. J. Cal-
horda, Chem. Eur. J. 2007, 13, 7874–7882.
Synthesis of 3-[1-(1-Phenyl-2-nitroethyl)]-2,4-
pentanedione (8)
To
a homogeneous mixture of 2-nitrostyrene (64 mg,
0.43 mmol) and acetylacetone (0.070 mL, 0.68 mmol), cata-
lyst 1 (28 mg, 10 mol%) was added and the mixture was
magnetically stirred at room temperature for 3 h. Diethyl
ether (10 mL) was then added and the suspension was fil-
tered under vacuum on a Durapore ꢄ 0.1 mm membrane
filter (Millipore). The catalyst was washed with diethyl ether
(total volume 100 mL), dried under vacuum at 908C, and re-
covered in >90% yield. The filtrate was concentrated under
vacuum to afford the product; yield: 107 mg (100%). This
[4] a) A. Berkessel, H. Groger, Asymmetric Organocataly-
sis: From Biomimetic Concepts to Applications in
Asymmetric Synthesis, Wiley-VCH, Weinheim, 2005;
b) A. Dondoni, A. Massi, Angew. Chem. 2008, 120,
4716–4739; Angew. Chem. Int. Ed. 2008, 47, 4638–
4660.
1
was identical by H NMR to an authentic sample of com-
pound 8.[14]
[5] For reviews on supported organic catalysts see: a) A.
Puglisi, F. Cozzi, M. Benaglia, Chem. Rev. 2003, 103,
3401–3430; b) F. Cozzi, Adv. Synth. Catal. 2006, 348,
1267–1290; c) M. Benaglia, New J. Chem. 2006, 30,
1525–1533.
[6] Reactions in which the silanol residues of the silica sur-
face participate to the catalytic activity of a mono-func-
tional catalyst supported on the same surface are not
considered as occurring under co-operative catalysis.
For examples, see: a) J. D. Bass, A. Soloyvov, A. J. Pas-
call, A. Katz, J. Am. Chem. Soc. 2006, 128, 3737–3747;
Synthesis of 3-[N-
(Carbobenzyloxy)aminophenylmethyl]-2,4-
pentanedione (10)
To a solution of N-carbobenzyloxybenzaldimine (36 mg,
0.15 mmol) and acetylacetone (0.031 mL, 0.30 mmol) in dry
toluene (2 mL) catalyst 1 (10 mg, 10 mol%) was added and
the mixture was stirred at room temperature for 18 h. The
reaction was then worked up as described above to afford
the product after purification by flash chromatography with
a 9:1 and then 7:3 hexanes:ethyl acetate mixture as eluants;
228
asc.wiley-vch.de
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Adv. Synth. Catal. 2009, 351, 219 – 229

Hybrid Inorganic-Organic Materials Carrying Tertiary Amine and Thiourea Residues
FULL PAPERS
b) J. M. Notenstein, A. Katz, Chem. Eur. J. 2006, 12,
3954–3965; c) K. K. Sharma, T. Asefa, Angew. Chem.
2007, 119, 2937–2940; Angew. Chem. Int. Ed. 2007, 46,
2879–2882. See also: d) K. Motokura, M. Tomita, M.
Tada, Y. Iwasawa, Chem. Eur. J. 2008, 14, 4017–4027.
By the same token, reactions in which the catalytic ac-
tivity of a mono-functional supported catalyst is tuned
by the presence of a neighboring organic residue affect-
ing the polarity around the catalytic sites but not in-
volved in the catalytic cycle are also not considered ex-
amples of co-operative catalysis: e) S. Huh, H. T. Chen,
J. W. Wiench, M. Pruski, V. S.-Y. Lin, J. Am. Chem.
Soc. 2004, 126, 1010–1011.
[10] For a review on hydrogen-bond mediated organocataly-
sis see: X. Yu, W. Wang, Chem. Asian J. 2008, 3, 516–
532.
[11] M. Longhi, V. Bertacche, C. L. Bianchi, L. Formaro,
Chem. Mater. 2006, 18, 4130–4136.
[12] M. R. Fetterman, Opt. Lett. 2005, 30, 2311–2313.
[13] These results together with recent findings in our labo-
ratories indicated that FT-IR could be used as a routine
method for the preliminary structural investigation of
this type of materials. The use of this technique can be
very convenient for checking the structural integrity of
a recovered supported catalyst to be use in recycling
experiments.
[7] S. Huh, H.-T. Chen, J. W. Wiench, M. Pruski, V. S.-Y.
Lin, Angew. Chem. 2005, 117, 1860–1864; Angew.
Chem. Int. Ed. 2005, 44, 1826–1830. For a very recent
contribution see also: K. Motokura, M. Tada, Y. Iwasa-
wa Angew. Chem. Int. Ed. 2008, 47, 9230–9235.
[8] a) R. K. Zeidan, V. Dufaud, M. E. Davis, J. Catal. 2006,
239, 299–306; b) R. K. Zeidan, S.-J. Hwang, M. E.
Davis, Angew. Chem. 2006, 118, 6480–6483; Angew.
Chem. Int. Ed. 2006, 45, 6332–6335; c) R. K. Zeidan,
M. E. Davis, J. Catal. 2007, 247, 379–382. For the syn-
thesis and catalytic activity of a mesoporous siliceous
material carrying a sulfonic acid and a thiol group teth-
ered to the surface through a single chain see: E. L.
Margelefsky, R. K. Zeidan, V. Dufaud, M. E. Davis, J.
Am. Chem. Soc. 2007, 129, 13691–13697.
[9] a) T. Okino, Y. Hoashi, Y. Takemoto, J. Am. Chem.
Soc. 2003, 125, 12672–12673. For a recent review on
this and related reactions, see: b) S. J. Connon, Chem.
Commun. 2008, 2499–2510. For recent examples of the
use of non-supported bi-functional tertiary amine/thio-
urea catalysts see: c) J. M. Andres, R. Manzano, R. Pe-
drosa, Chem. Eur. J. 2008, 14, 56116–55119; d) L.-Q.
Lu, Y.-J. Cao, X.-P. Liu, J. An, C.-J. Yao, Z.-H. Ming,
W.-J. Xiao, J. Am. Chem. Soc. 2008, 130, 6946–6948;
e) S. E. Reisman, A. G. Doyle, E. N. Jacobsen, J. Am.
Chem. Soc. 2008, 130, 7198–7199.
[14] J. Wang, H. Li, W. Duan, L. Zu, W. Wang, Org. Lett.
2005, 7, 4713–4716.
[15] It has been recently shown that a silica-supported
sodium sulfonate can promote the conjugate addition
of indoles to unsaturated ketones only in the presence
of ionic liquids: Y. Gu, C. Ogawa, S. Kobayashi, Org.
Lett. 2007, 9, 175–178.
[16] In other words, this means that when catalyst 1 was
used the catalyst loading was approximately 5 mol%
each for the tertiary amine and the thiourea residues.
[17] Neither the use of larger amount of extracting diethyl
ether, nor the use of other solvents (dioxane, methanol,
dichloromethane) both at room and at high tempera-
ture allowed the isolation of white materials.
[18] After drying the supported catalyst at 1508C for 4 h
under vacuum the material appeared to be not yellow
anymore but a light grey powder.
[19] The integrity of catalyst 1 was clearly demonstrated by
TGA analysis that showed no traces of degradation of
the supported catalyst until 2008C.
[20] A. L. Tillmann, J. Ye, D. J. Dixon, Chem. Commun.
2006, 1191–1193.
[21] E. P. Barrett, L. G. Joyner, P. Halenda, J. Am. Chem.
Soc. 1951, 73, 373.
Adv. Synth. Catal. 2009, 351, 219 – 229
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229