Cooperative catalysis of primary and tertiary amines immobilized on oxide surfaces for one-pot C-C bond forming reactions

Article abstract of DOI:10.1002/anie.200802515

(Chemical Equation Presented) D'you know what amine? Primary and tertiary amines are both immobilized on the same silica-alumina surface by silane-coupling reactions. The resultant silica-alumina-supported double-amines are found to exhibit excellent catalysis for 1,3-dinitroalkane synthesis from various aldehydes with nitromethane. A cooperative catalytic mechanism on the solid surface for this efficient synthesis is proposed.

Full text of DOI:10.1002/anie.200802515

Communications
DOI: 10.1002/anie.200802515
Heterogeneous Catalysis
Cooperative Catalysis of Primary and Tertiary Amines
À
Immobilized on Oxide Surfaces for One-Pot C C Bond
Forming Reactions**
Ken Motokura, Mizuki Tada, and Yasuhiro Iwasawa*
Dedicated to the Catalysis Society of Japan
on the occasion of the 50th anni-
versary
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Chemie
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Table 1: Reaction of benzaldehyde (1) and nitromethane (2) on various
supported and unsupported amines.[a]
The development of multicatalytic functions enables highly
efficient organic syntheses in both homogeneous and hetero-
geneous catalyst systems.[1] Recently, supported catalysts with
chemically designed surfaces have received much attention,
not only as recoverable reagents, but also as multifunctional
surface materials.[2,3] These multifunctional catalysts can
enable one-pot reaction sequences[2] and cooperatively pro-
mote single-reaction steps.[3] There are several reports of
heterogeneous catalysts having multifunctional sites on their
surfaces, which promote organic synthesis.[4,5] Nevertheless,
clear examples of cooperative multifunctional catalysis at
surfaces for carbon–carbon bond-forming reactions are still
required, to understand the synthetic strategy of efficient
multifunctional catalysis at surfaces from fundamental and
industrial points of view.
Tertiary amines act as Lewis and Brønsted bases for the
activation of nucleophiles. Conversely, supported primary
amines efficiently catalyze condensation reactions of carbonyl
compounds, such as nitro-aldol reactions,[6] in which the
primary amines are thought to activate the carbonyl com-
pounds through formation of imine intermediates.[4c,6] These
facts suggest that the immobilization of both tertiary and
primary amines onto the same solid surface can create an
Entry
Catalyst
Conversion Rate of 1
[mmolhÀ1 [b]
]
1[c]
2
SA–NH2–NEt2-A (85/15 NH2/NEt2)
SA–NH2–NEt2-B (60/40 NH2/NEt2)
SA–NH2–NEt2-C (30/70 NH2/NEt2)
SA–NH2–NEt2-D (10/90 NH2/NEt2)
SA–NH2–NEt2-B-cap[d]
SA–NH2 +SA–NEt2
SA–NH2
1.87
1.45
0.62
0.43
0.40
0.13
0.03
0.08
0.31
0.38
0.26
0.08
0.09
<0.01
0.66
0.45
3[c]
4[c]
5
6
7
8
SA–NEt2
9[e]
10[f]
11
SA+n-hexylamine+triethylamine
HCl+n-hexylamine+triethylamine
n-hexylamine+triethylamine
n-hexylamine
triethylamine
SA
12
13
14[e]
15[e,g]
16[e,g]
MgO
CaO
[a] Reaction conditions unless otherwise stated: 1 (5 mmol), 2 (2 mL),
catalyst (-NH2: 0.015 mmol, NEt2: 0.012 mmol), 1008C. [b] Determined
À
efficient heterogeneous catalyst for organic C C bond-
1
by GC and H NMR spectroscopy. [c] 0.027 mmol of total amines was
forming reactions by activation of both nucleophiles and
electrophiles. In an organized ensemble of the immobilized
system, surface acid sites may also contribute to promotion of
the surface reactions. Herein, we report the first example of a
heterogeneous combined tertiary and primary amine catalyst,
immobilized on silica–alumina (SA), with tremendous effi-
ciency for the one-pot synthesis of 1,3-dinitroalkanes.
We examined the reaction between benzaldehyde (1) and
nitromethane (2) in the presence of various heterogeneous
and homogeneous amines, as shown in Table 1. In almost all
cases, 2-nitrostyrene (3) was obtained as a main product. The
double-amine catalysts (SA–NH2–NEt2-A–D, see Experi-
mental Section) showed high initial conversion rates of 1
compared with other amine catalysts (Table 1, entries 1 and
2). A homogeneous solution containing a mixture of the
primary and tertiary amines (n-hexylamine and triethyl-
amine), in equivalent amounts to NH2 and NEt2 in SA–NH2–
NEt2-B, was much less active than SA-supported heteroge-
neous catalyst (Table 1, entry 11). The low activity was
slightly improved by the addition of SA into the solution
(Table 1, entry 9). The reactions using SA–NH2 and SA–NEt2
with similar amine loadings to those in the SA–NH2–NEt2-B
proceeded at very low conversion rates (Table 1, entries 7 and
8). In the case of a physical mixture of SA–NH2 and SA–NEt2,
used. [d] Catalyst was treated with hexamethyldisilazane. [e] Solid
catalyst (0.034 g). [f] Triethylamine hydrochloride (0.012 mmol) was
used. [g] The main product on MgO and CaO was nitroalcohol.
the reaction was not enhanced by the coexistence of both
amines (Table 1, entry 6). We also examined the perform-
ances of SA–NH2–NEt2 with various ratios of the primary and
tertiary amines (Table 1, entries 1–4). The initial reaction rate
increased with increasing primary amine content, which
suggests that 1 is activated mainly by the primary amine
immobilized at the SA surface.[7] Notably, the performances
of the double-amine immobilized catalysts were much higher
than those for typical solid bases, such as MgO and CaO
(Table 1, entries 15 and 16).
It is noteworthy that 1,3-dinitro-2-phenylpropane (5)
formed at 7% selectivity (after 2 h) along with the main
product 3 and a small amount of nitroalcohol (4) on the
catalyst SA–NH2–NEt2-B (Table 1, entry 2), whereas, with
SA–NH2, 3 formed with > 99% selectivity, although the
conversion rate was low (2–6 h; Table 1, entry 7). The 1,3-
dinitroalkane synthesis may proceed through nitro-aldol
reaction, followed by 1,4-addition of 2 to 3.[8] Recently,
many synthetic methods have been reported, which utilize
1,3-dinitroalkanes as a key building block toward a variety of
functional organic compounds, including biologically active
substances.[9] Because of the synthetic usefulness of 1,3-
dinitroalkanes, a further investigation for optimal reaction
conditions was conducted to develop the SA–NH2–NEt2
catalytic system for 1,3-dinitroalkane synthesis. Remarkably,
the synthesis of 5 with 93% selectivity and 100% conversion
of 1 was achieved after 8 h in the presence of SA–NH2–NEt2-
B (Table 2, entry 2). A sample of SA–NEt2 possessing a full
loading of NEt2 (SA–NEt2-f, NEt2 0.90 mmolgÀ1) showed an
improved catalytic activity (Table 2, entry 7) compared with a
[*] Dr. K. Motokura, Dr. M. Tada, Prof. Dr. Y. Iwasawa
Department of Chemistry, Graduate School of Science
The University of Tokyo
Hongo, Bunkyo-ku, Tokyo 113-0033 (Japan)
Fax: (+81)3-5800-6892
E-mail: iwasawa@chem.s.u-tokyo.ac.jp
[**] This work was supported by the JSPS (19760541) and the Global
COE Program for Chemistry Innovation.
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/anie.200802515.
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Table 2: Performances of the amine-immobilized catalysts for 1,3-dinitroalkane (5) synthesis.[a]
entries 7, 8, and 10). It should be
noted that 4-carboxybenzaldehyde
also reacted with 2 in the presence
of the SA–NH2–NEt2-B catalyst,
affording a 65% yield of the cor-
responding 1,3-dinitroalkane prod-
uct (Scheme 1). This reaction
scarcely proceeded with sodium
methoxide as a base, as a result of
neutralization by the carboxylic
acid group. To our knowledge,
this is the first report of a catalytic
addition reaction of a nitroalkane
to an aldehyde with a strong acidic
group.
Entry
Catalyst
Yield of 3
Yield of 4
Yield of 5
[%][b]
[%][b]
[%][b]
1[c]
2
SA–NH2–NEt2-A (85/15 NH2/NEt2)
SA–NH2–NEt2-B (60/40 NH2/NEt2)
SA–NH2–NEt2-C (30/70 NH2/NEt2)
SA–NH2–NEt2-D (10/90 NH2/NEt2)
SA–NH2-f
SA–NH2
SA–NEt2-f
SA–NEt2
6
3
2
4
4
90
93
77
64
39
29
30
8
3[c]
4[c]
5
13
18
<1
<1
30
7
1
60
71
2
6
7
8
68
Usually, the direct synthesis of
from 1 and 2 requires high
reaction temperatures around
[a] Reaction conditions unless otherwise stated: 1 (1 mmol), 2 (2 mL), catalyst (-NH2: 0.044 mmol,
-NEt2: 0.036 mmol), 1008C, 8 h. [b] Determined by 1H NMR spectroscopy, based on 1. [c] 0.08 mmol of
total amine groups was used.
5
SA–NEt2 of a similar amine NEt2 loading to that in SA–NH2–
NEt2-B (Table 2, entry 8); however, the yield of 5 was only
30%. The SA–NH2 and SA–NH2-f were also less active and
unselective (Table 2, entries 5 and 6) for the synthesis of 5.
The generality of the SA–NH2–NEt2-B-catalyzed 1,3-
dinitroalkane synthesis was examined with the use of various
aldehyde substrates (Table 3). Electron-donating groups in
the para-position of benzaldehyde enhanced the reactivity of
the aldehyde with 2, and the corresponding 1,3-dinitroalkanes
formed in excellent yields (Table 3, entries 2–4, 91–93%).
Conversely, low product selectivities were detected for
benzaldehydes with electron-withdrawing groups (Table 3,
entries 5 and 6). This reaction also proceeded successfully
with piperonal, 3,4-dimethoxybenzaldeyde, and the hetero-
aromatic aldehyde 2-thiophenecarboxyaldehyde (Table 3,
Scheme 1. Reaction of 2 with 4-carboxybenzaldehyde.
100–1208C.[8] It is noteworthy that the SA–NH2–NEt2-A
catalyst efficiently promoted the reaction of 2 with 1 at 508C,
giving an 82% yield of 5 (Scheme 2), whereas, in the MgO-
promoted reaction at 508C, the yield of 5 was just 5%. The
supported double-amine catalyst provides an economical
reaction process to synthesize nitro compounds with ther-
mally unstable groups.
Table 3: 1,3-dinitroalkane synthesis from various aldehydes.[a]
Entry
Aldehyde
t [h]
Conversion [%][b]
Yield [%][b]
1
2
3
4
5
6
X=H
X=Me
X=OMe
X=OH
X=Cl
8
5
5
5
8
8
>99
99
99
>99
98
95
93
93
91
91
Scheme 2. Comparison of 1,3-dinitroalkane synthesis catalyzed by SA–
NH2–NEt2-A or MgO under mild reaction conditions.
83 (8)[c]
48 (36)[c]
The initial rate of SA–NH2–NEt2-catalyzed reaction of 1
and 2 is also much higher than those for SA–NH2, SA–NEt2,
and the mixture of SA–NH2 and SA–NEt2 (Table 1). These
results suggest a cooperative catalysis of the neighboring
primary and tertiary amine groups on the SA surface. After
treatment of the SA–NH2–NEt2-B with 1, new signals in solid-
state 13C magic-angle spinning (MAS) NMR spectrum
X=NO2
7
8
5
5
97
99
89
88
9
5
8
99
94
89
80
=
appeared at d = 159 ppm (Figure 1a, b’: N CH), d = 135–
10
120 ppm (Figure 1a, a’: phenyl), and d = 63 ppm (Figure 1a,
c’: N-CH2), indicating the formation of a benzyl imine
intermediate by dehydration.[6b,10,11] To examine the interac-
tion between the immobilized amines and the substrates in
[a] Reaction conditions: aldehyde (1 mmol), 2 (2 mL), SA–NH2–NEt2-B
(0.1 g, NH2: 0.044 mmol, NEt2: 0.036 mmol), 1008C. [b] Determined by
1H NMR spectroscopy, based on aldehyde. [c] Yield of nitroalcohol.
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molecular motion of the tertiary amines in SA–NH2–
NEt2-B is restricted by interaction with the substrates,[12]
probably by formation of a reaction intermediate (pri-
mary amine–aldehyde(imine intermediate), nitrome-
thane–tertiary amine) (Scheme 3b).
The cooperative catalysis of primary and tertiary
amines was enhanced by acid addition (Table 1, entries 9
and 10 cf. entry 11). In addition, the activity of SA–NH2–
NEt2-B was significantly decreased by the capping of
surface OH groups with hexamethyldisilazane (Table 1,
entry 5).[13] These results suggest that the surface acid site
on SA enhances the SA–NH2–NEt2-catalyzed nitro-aldol
reaction. The supported catalyst showed higher perform-
ances than those for the homogeneous amine–acid
mixture (Table 1, entry 2 cf. entries 9 and 10) because
undesired acid–base neutralization is suppressed at the
immobilized surfaces.[4b,e,5]
À
Si OH groups on a primary-amine-immobilized SiO2
surface promote two steps in the nitro-aldol reaction:
a) imine formation from the primary amine and the
aldehyde, and b) the addition of the nitroalkane to the
resultant imine.[4c] We also prepared a SiO2-supported
double amine catalyst, which gave similar results to SA–
NH2–NEt2, suggesting that, not only strong acid sites (Si-
O(H+)-Al), but also weak acid sites (Si-OH) contribute
to the nitro-aldol reaction.[14] However, amine immobi-
lization occurred at higher rate and to a higher degree on
SA than on SiO2 (nitrogen content; SA–NH2–NEt2-B:
1.10 wt%, SiO2–NH2–NEt2: 0.52 wt%). As a result, the
activity of the SiO2-supported catalyst based on weight
was half that for the SA–NH2–NEt2.
Figure 1. a) Solid-state 13C CP/MAS NMR spectrum (6 kHz) for SA–NH2–
NEt2-B treated with benzaldehyde, and atom-labeling scheme. b) Depend-
ence of the normalized intensity of variable-contact-time 13C CP/MAS NMR
spectra at dꢀ9.5 ppm on contact time: A) fresh SA–NH2–NEt2-B (+), and
*
B) SA–NH2–NEt2-B treated with benzaldehyde in nitromethane solution ( ).
The arrows indicate the change from before (A) to after (B) the treatment of
SA–NH2–NEt2 with substrates.
A reaction mechanism for the 1,3-dinitroalkane
synthesis on the SA–NH2–NEt2 including the effect of the
acid support is illustrated in Scheme 3 (for full version, see
Supporting Information, Figure S1): a) the aldehyde is acti-
vated by a surface acid site and reacts with an amino group to
form an imine intermediate,[6] b) the a-proton of 2 is
abstracted by a tertiary amine group, accompanied by the
the nitro-aldol reaction, variable-contact-time 13C cross-
polarization (CP)/MAS NMR spectra of SA–NH2–NEt2-B
were measured, before and after the interaction with both
nitromethane and benzaldehyde (see Supporting Informa-
tion, Figure 2S). Variable-contact-time 13C CP/MAS NMR
spectroscopy is a technique used to determine the molecular
motion of solid materials.[12] As CP is a measure of the
efficiency of magnetization transfer by the dipolar coupling
1
1
from H to 13C, it is most efficient for static H–13C dipolar
interactions. As a result, the less-mobile carbon groups
exhibit a faster CP rate, and the NMR signal intensity
becomes stronger with relatively short CP contact times. This
signal intensity becomes weak with prolonged contact time, as
a result of attenuation of the transferred magnetization.
Conversely, the signal intensity of a molecule with high
mobility is strong with relatively long contact times.[12] The
13C NMR signal of SA–NH2–NEt2-B at d ꢀ 9.5 ppm is due
mainly to the terminal carbon atoms of the immobilized
tertiary amine group (h), whose molecular motion is strongly
affected by interactions of the substrate with the tertiary
amine. Comparison of the normalized intensities of NMR
signals around d = 9.5 ppm with contact times revealed that
signals for the catalyst SA–NH2–NEt2-B when interacting
with substrates showed relatively higher intensity with the
shorter contact times (ꢁ 0.5 ms) and lower intensity with
longer contact times (ꢂ 2.0 ms) than those for the parent SA–
NH2–NEt2-B (Figure 1b). These results indicate that the
Scheme 3. A proposed cooperative reaction mechanism. See text for
details.
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nucleophilic attack of the deprotonated 2 on the imine,
which is also assisted by surface acid site, resulting in the
product 3, before, c) another molecule of 2 is activated by
the tertiary amine group and the Michael reaction with 3
occurs to give the desired product 5.[15] Nitrostyrene (3)
might also be activated by surface acid sites.[16]
In a separate experiment, the Michael reaction of 2
with 3, affording 5, was examined with a range of amine
catalysts. SA–NH2–NEt2-B and SA–NEt2-f both showed
high activities, but SA–NH2-f was found to be much less
active(Scheme 4), providing further indication that the
Michael addition is promoted by tertiary amine groups. In
addition, SA–NEt2-f showed double the activity of
homogeneous triethylamine (Scheme 4).
Full-coverage SA–NH2-f was active for the condensa-
tion reaction to afford 3, whereas the full-coverage SA–
NEt2-f gave nitroalcohol 4 by aldol reaction (Table 2).
This formation of 4 and the subsequent dehydration of 4
Figure 2. Solid-state 13C CP/MAS NMR spectra (4 kHz) and atom-labeling
scheme: A) SA–NEt2-f, B) SA–NH2-f, C) SA–NH2–NEt2-B, and D) SA–NH2–
NEt2-A.
affording the catalyst SA–NH2–NEt2. The amine groups in SA–NEt2,
SA–NH2, and SA–NH2–NEt2 were characterized by solid-state 13C
CP/MAS NMR spectroscopy (Figure 2); the NMR signals derived
from primary and tertiary amines in SA–NH2–NEt2 showed no
significant changes compared to those for SA–NH2 and SA–NEt2.
Received: May 29, 2008
Revised: July 25, 2008
Published online: September 2, 2008
À
Keywords: C C coupling · cooperative effects · immobilization ·
nitroalkanes · supported catalysts
.
Scheme 4. The amine-catalyzed Michael reaction of 2 and 3.
to form 3 are considered as a minor reaction pathway (see
Supporting Information, Scheme S1(a) and (b)). Nucleo-
philic attack of 2 on benzaldehydes with electron-withdrawing
groups at the para-position might easily occur without the
formation of imine intermediates, resulting in lower selectiv-
ity to 1,3-dinitrocompounds in favor of nitroalcohol forma-
tion (Table 3).[17]
[1] a) H. Grꢀger, Chem. Eur. J. 2001, 7, 5246; b) M. Kanai, N. Kato,
E. Ichikawa, M. Shibasaki, Pure Appl. Chem. 2005, 77, 2047; c) S.
Kanemasa, K. Ito, Eur. J. Org. Chem. 2004, 4741; d) J. A. Ma, D.
Cahard, Angew. Chem. 2004, 116, 4666 – 4683; Angew. Chem.
Int. Ed. Engl. 2004, 43, 4566 – 4583; e) Y. Wang, H. Li, Y. Q.
Wang, Y. Liu, B. M. Foxman, L. Deng, J. Am. Chem. Soc. 2007,
129, 6364.
[2] a) B. M. Choudary, N. S. Chowdari, S. Madhi, M. L. Kantam, J.
Org. Chem. 2003, 68, 1736; b) K. Motokura, N. Fujita, K. Mori,
T. Mizugaki, K. Ebitani, K. Jitsukawa, K. Kaneda, Chem. Eur. J.
2006, 12, 8228; c) G. Torres, C. R. Apesteguꢁa, J. I. Di Cosimo,
Appl. Catal. A 2007, 317, 161.
[3] a) P. Barbaro, C. Bianchini, V. D. Santo, A. Meli, S. Moneti, R.
Psaro, A. Scaffidi, L. Sordelli, F. Vizza, J. Am. Chem. Soc. 2006,
128, 7065; b) A. Dahan, M. Portnoy, J. Am. Chem. Soc. 2007, 129,
5860.
[4] a) S. Huh, H. T. Chen, J. W. Wiench, M. Pruski, V. S.-Y. Lin,
Angew. Chem. 2005, 117, 1860; Angew. Chem. Int. Ed. 2005, 44,
1826; b) R. K. Zeidan, S.-J. Hwang, M. E. Davis, Angew. Chem.
2006, 118, 6480; Angew. Chem. Int. Ed. 2006, 45, 6332; c) J. D.
Bass, A. Solovyov, A. J. Pascall, A. Katz, J. Am. Chem. Soc. 2006,
128, 3737; d) T. Takahashi, T. Watahiki, S. Kitazume, H. Yasuda,
T. Sakakura, Chem. Commun. 2006, 1664; e) R. K. Zeidan, M. E.
Davis, J. Catal. 2007, 247, 379.
In summary, a silica–alumina-supported double-amine
catalyst (SA–NH2–NEt2) was found to be highly active for the
production of 1,3-dinitroalkanes, whereas the supported
single amines and the corresponding amines in solution
exhibited almost no significant activity in this reaction. The
SA–NH2–NEt2 catalyst has two notable properties, owing to
the multifunctional catalyst surface: a) acceleration of a single
reaction by cooperative catalysis and b) promotion of one-pot
reaction sequences. The design of more precisely controlled
surface structures and further extensions to a variety of
organic syntheses are currently under investigation.
Experimental Section
Silica–alumina-supported double-amine catalysts (SA–NH2–NEt2-A–
D) were prepared by treatment of amorphous aluminosilicate (SA)
with a toluene solution involving given amounts (1.7 mmol of total
amine) of 3-aminopropyltriethoxysilane and 3-(diethylamino)propyl-
trimethoxysilane under reflux. The solid was removed by filtration,
washed with dichloromethane, and dried under reduced pressure,
[5] a) K. Motokura, M. Tada, Y. Iwasawa, J. Am. Chem. Soc. 2007,
129, 9540; b) K. Motokura, M. Tomita, M. Tada, Y. Iwasawa,
Chem. Eur. J. 2008, 14, 4017.
[6] a) X. Wang, K. S. K. Lin, J. C. C. Chan, S. Cheng, J. Phys. Chem.
B 2005, 109, 1763; b) G. Sartori, F. Bigi, R. Maggi, R. Sartorio,
D. J. Macquarrie, M. Lenarda, L. Storaro, S. Coluccia, G. Martra,
9234 www.angewandte.org
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Chemie
J. Catal. 2004, 222, 410; c) G. Demicheli, R. Maggi, A.
Mazzacani, P. Righi, G. Sartori, F. Bigi, Tetrahedron Lett. 2001,
42, 2401.
[13] The performance of SA–NH2–NEt2-B-cap (Table 1, entry 5) was
higher than that for the homogeneous amine mixture (Table 1,
entry 11) because a part of silanol groups still remained, as
suggested by IR spectroscopy.
[7] Because imine-intermediate formation from 1 and primary
amines is generally very fast, the rate determining step in the
nitro-aldol reaction is the addition of 2 to the imine intermediate
including proton abstraction from 2 by the tertiary amine.
[8] For other reports on synthetic procedures incorporating 1,3-
dinitroalkanes, see: a) A. Ferro, M. C. Rezende, S. Sepulveda-
boza, M. Reyes-Parada, B. K. Cassels, J. Chem. Res. 2001, 7, 294;
b) R. Ballini, G. Bosica, D. Fiorini, A. Palmieri, Synthesis 2004,
1938; c) T. Hara, S. Kanai, K. Mori, T. Mizugaki, K. Ebitani, K.
Jitsukawa, K. Kaneda, J. Org. Chem. 2006, 71, 7455.
[9] a) R. Ballini, L. Barboni, D. Fiorini, G. Giarlo, A. Palmieri,
Chem. Commun. 2005, 2633; b) R. Ballini, L. Barboni, D.
Fiorini, G. Giarlo, A. Palmieri, Green Chem. 2005, 7, 828; c) R.
Ballini, L. Barboni, C. Femoni, G. Giarlo, A. Palmieri, Tetrahe-
dron Lett. 2006, 47, 2295; d) D. Y. Park, K. Y. Lee, J. N. Kim,
Tetrahedron Lett. 2007, 48, 1633.
[14] Strong acid sites on SA (Si-O(H+)-Al) effectively activate the
acceptor substrates. However, they also show a buffering effect
on the basic amines. We envisage this effect is the reason for the
similar catalytic activity for SA and SiO2 supports.
[15] After collecting the solid catalyst by filtration, the reaction did
not occur in the filtrate under similar reaction conditions,
indicating an absence of homogeneous contributions. The
catalyst was reusable, but the catalytic activity decreased; for
example, in the nitroaldol reaction of 1 and 2, 93% yield after
2 h, however when the catalyst is reused the yield is 86% after
5 h. The primary-amine-immobilized catalyst was reusable with
similar reaction conditions,[5] indicating that the tertiary amine
groups are less stable than primary amines at such high
temperatures. Nevertheless, the significance of the immobilized
double-amine catalyst is not reduced, owing to tremendous
performances for the one-pot bifunctional catalysis.
[10] R. Sayah, K. Glegoła, E. Framery, V. Dufaud, Adv. Synth. Catal.
2007, 349, 373.
[11] I. L. Lagadic, Microporous Mesoporous Mater. 2006, 95, 226.
[12] a) S. K. Sahoo, D. W. Kim, J. Kumar, A. Blumstein, A. L. Cholli,
Macromolecules 2003, 36, 2777; b) H.-M. Kao, T.-T. Hung,
G. T. K. Fey, Maclomolecule 2007, 40, 8673.
[16] C. Palomo, S. Vera, A. Mielgo, E. Gꢂmez-Bengoa, Angew.
Chem. 2006, 118, 6130; Angew. Chem. Int. Ed. 2006, 45, 5984.
[17] Electron-withdrawing groups would also prevent the dehydra-
tion reaction of nitroalcohols.
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www.angewandte.org
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