H. Eckert, A. Studer et al.
4.48 mmol) were added all at once and the reaction was stirred at
500 rpm for additional 2 h at 808C. A white precipitate formed that was
filtered off and washed with copious amounts of water and MeOH. To
remove CTAB, the particles were suspended in MeOH (ꢀ100 mL per
1 g) and HCl (conc., 300 mL per 1 g) was added and the suspension was
heated for another hour at 608C. Filtration and drying of the particles in
high vacuum afforded the mesoporous silica nanoparticles 10 (MSNs) as
white solid (ꢀ3 g).
Typical alkyne/azide click reaction protocol: Azide/alkene-functionalized
MSNs 10 (500 mg, ꢀ0.8 mmolgÀ1, ꢀ0.4 mmol) were treated with CuSO4
(40 mg, 0.25 mmol), sodium ascorbate (60 mg, 0.30 mmol), and sodium
pro-2-yne sulfonic acid 4 (250 mg, 1.76 mmol) overnight at 908C in
EtOH/H2O (2:1, 10 mL). Filtration of the particles and washing with
H2O (50 mL), HCl (2m, 25 mL), MeOH (50 mL), CH2Cl2 (50 mL), and
Et2O (20 mL) afforded the acid-functionalized MSNs 11 (ꢀ500 mg) as
white solid.
Conclusion
We have introduced a conceptually new approach for prepa-
ration of bifunctional acid/base mesoporous silica nanoparti-
cles. Triethoxyalkylsilanes bearing azides, alkenes, or alkoxy-
amines at their termini could be co-condensed with TEOS
to provide mesoporous silica particles containing orthogo-
nally addressable functionalities. Catalytically active acid
and base moieties were readily introduced by late stage or-
thogonal click chemistry. The Cu-catalyzed azide/alkyne cy-
cloaddition, the radical thiol–ene reaction, and the radical
nitroxide exchange reaction turned out to be very efficient
for late stage particle functionalization. Our approach al-
lowed for the preparation of a series of catalysts of the same
type in a short time. This process was very useful for identi-
fying active catalysts.
Typical thiol–ene click reaction protocol: The acid-functionalized MSNs
11 (200 mg, ꢀ0.16 mmol) were treated with AIBN (30 mg, 0.18 mmol),
cysteamine hydrochloride 8 (100 mg, 0.88 mmol), and pyridine (100 mL,
1.24 mmol) in DCE (3 mL) at 908C overnight. The MSNs were filtered
and washed with H2O, MeOH, CH2Cl2, and Et2O (30 mL each) and were
dried at 500 mbar and 408C to afford the bifunctional MSNs 13.
Particles were successfully analyzed by IR spectroscopy,
elemental analysis, SEM, and solid state 1H and 13C CP/
MAS NMR spectroscopy. The results of the present study
Typical method for the preparation of azide/alkoxyamine-functionalized
SiO2 particles: According to a procedure described by Huh et al.,[5a] ce-
tyltrimethylammonium bromide (CTAB, 1.50 g, 4.12 mmol) and NaOH
(5.25 mL, 2m, 10.5 mmol) in H2O (360 mL) were stirred for 30 min at
1
also highlight the utility of H and 13C solid state NMR tech-
niques for the structural analysis of chemically modified sur-
faces of this kind. The orthogonally functionalized materials
were catalytically active in the acid/base-catalyzed Henry re-
action of nitromethane with benzaldehyde to give trans-b-ni-
trostyrene. Importantly, it was shown that the linker length
between the inorganic host material and the two catalytical-
ly active organic functionalities has to be carefully adjusted.
If the linker was too long, inactive hybrid materials resulted,
likely due to acid/base quenching at the particle surface.
Particles containing only the amino functionality showed
lower activities and provided 1,3-dinitro-2-phenylpropane as
a follow up product as a major component. Particles bearing
exclusively sulfonic acid moieties at the surface were inac-
tive. These results clearly revealed that the success of that
particular Henry reaction was based on cooperative acid/
base catalysis.
808C. Subsequently tetraethyl orthosilicate
2
(TEOS) (6.64 mL,
30.0 mmol, 8.0 equiv), the corresponding azide 1 (3.75 mmol, 1.0 equiv),
and the corresponding alkoxyamine 14a–c (3.75 mmol, 1.0 equiv) were
added all at once and the reaction was stirred for additional 2 h at 808C.
The white precipitate formed was filtered off and washed with copious
amounts of water and MeOH. To remove CTAB, the particles were sus-
pended in MeOH (ꢀ100 mL per 1 g) and HCl (conc., 300 mL per 1 g)
was added and the suspension was heated for another hour at 608C. Fil-
tration and drying of the particles in high vacuum afforded the mesopo-
rous silica nanoparticles 15a–c (MSNs) as white solid (ꢀ2.5 g).
Typical alkyne/azide click reaction protocol: Azide/alkene-functionalized
MSNs 15a–c (500 mg, ꢀ0.8 mmolgÀ1, ꢀ0.4 mmol) were reacted with
CuSO4 (40 mg, 0.25 mmol), sodium ascorbate (60 mg, 0.30 mmol), and
sodium pro-2-yne sulfonic acid 4 (250 mg, 1.76 mmol) overnight at 908C
in EtOH/H2O (2:1, 10 mL). Filtration and washing with H2O (50 mL),
HCl (2m, 25 mL), MeOH (50 mL), CH2Cl2 (50 mL), as well as Et2O
(20 mL) afforded the acid-functionalized MSNs 17a–c (ꢀ500 mg) as
white solid.
Since the applied orthogonal click reactions are very
robust processes, other functionalities than organic acids
and bases can be introduced at the surface of such prefunc-
tionalized silica particles. For example, various ligands for
transition metals should be readily covalently bound to the
particle surface through this strategy. This will allow for the
preparation of bifunctional catalysts in which one function-
ality might be an organocatalyst and the other functionality
could be a transition-metal-based catalyst acting in concert.
Moreover, cooperative catalysis at the surface with two dif-
ferent metals should be possible using this concept; studies
along this line are underway.
Typical nitroxide exchange reaction protocol: The acid-functionalized
particles (200 mg, ꢀ0.8 mmolgÀ1, ꢀ0.16 mmol) were suspended in DCE
(5 mL) and 4-amino-TEMPO 17 (100 mg, 0.584 mmol) was added. The
reaction mixture was heated for 24 h at 1258C. The nanoparticles were
filtered and washed with H2O, MeOH, CH2Cl2, and Et2O (30 mL each)
and were dried at 500 mbar and 408C to afford the bifunctional MSNs
18a–c.
General procedure for the Henry reaction: The bifunctional MSNs (30 or
50 mg) were suspended in MeNO2 (1 mL) and benzaldehyde (100 mL,
0.984 mmol) was added dropwise. The reaction was stirred at 908C. The
conversion was controlled by GC and the reaction was quenched by fil-
tration if no further conversion could be detected.
NMR spectroscopy: The solid-state NMR measurements were carried
out on Bruker spectrometers equipped with 2.5 and 4 mm single and
double resonance NMR probes. The resonance frequencies were
500 MHz for 1H at 11.7 T, 75.433 MHz for 13C at 7.04 T and 99.325 MHz
for 29Si at 11.7 T. Chemical shifts are reported relative to TMS, using ada-
mantane (d=1.78 ppm), adamantane (d=38.56 ppm for the methylene
resonance) and tetrakis(trimethylsilyl)silane (TTMSS) (d=À9.8 ppm,
Experimental Section
General method for preparation azide/alkene-functionalized SiO2 parti-
cles: According to a procedure published by Huh et al.,[5a] cetyltrimethy-
lammonium bromide (CTAB, 2.00 g, 5.49 mmol) and NaOH (7 mL, 2m,
14 mmol) in H2O (480 mL) were stirred for 30 min at 808C. Tetraethoxy-
silane 2 (TEOS) (9.94 mL, 44.8 mmol), (5-azidopentyl)triethoxysilane 1
(1.23 g, 4.48 mmol), and 7-octenyltrimethoxysilane 6 (1.12 mL, 1.04 g,
1
main peak), respectively, as secondary references. H MAS-NMR spectra
were recorded using rotor synchronized Hahn spin echo experiments
with evolution times of 3–6 rotor periods at a spinning frequency of
30 kHz. The 908 pulse length was 3.9 ms. FIDs (256–512) were accumulat-
ed using a recycle delay of 5 s. The 13C{1H} CP/MAS and 29Si{1H} CP/
16696
ꢂ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2012, 18, 16689 – 16697