Henry reaction catalyzed by aminopropylated nanosilica

Article abstract of DOI:10.1246/cl.2009.790

The Henry reaction was catalyzed by 0.01 equiv of aminopropylated nanosilica particles (nano-NAP) in refiuxing nitroalkanes to provide nitrostyrenes in good yields. The catalyst could be recycled up to three times in 76% average yield. Copyright

Full text of DOI:10.1246/cl.2009.790

790
Chemistry Letters Vol.38, No.8 (2009)
Henry Reaction Catalyzed by Aminopropylated Nanosilica
Hisahiro Hagiwara,ꢀ1 Masayoshi Sekifuji,1 Norio Tsubokawa,2 Takashi Hoshi,2 and Toshio Suzuki2
1Graduate School of Science and Technology, Niigata University, 8050 2-Nocho, Ikarashi, Niigata 950-2181
2Faculty of Engineering, Niigata University, 8050 2-Nocho, Ikarashi, Niigata 950-2181
(Received May 22, 2009; CL-090506; E-mail: hagiwara@gs.niigata-u.ac.jp)
The Henry reaction was catalyzed by 0.01 equiv of amino-
CHO
NO2
Nano-NAP
Solvent
propylated nanosilica particles (nano-NAP) in refluxing nitro-
alkanes to provide nitrostyrenes in good yields. The catalyst
could be recycled up to three times in 76% average yield.
+
CH3NO2
Scheme 1. Henry reaction of benzaldehyde catalyzed by nano-
NAP.
Immobilization of an organocatalytic residue on a solid sup-
port imparts stability and recyclability to the original homogene-
ous organocatalyst. Silica gel with grafted organic residues on
the surface has played an important role as a heterogeneous or-
ganocatalyst in synthetic organic chemistry.1 We have success-
fully utilized amorphous aminopropylated silica of micrometer
particle size (NAP) as sustainable catalysts for 1,4-conjugate ad-
ditions of naked aldehydes,2 aldol condensation,3 transesterifica-
tions,4 Michael reactions,5 hydropyran synthesis by three com-
ponent condensations,6 Knoevenagel reactions,7 and subsequent
Mislow–Evans rearrangements8 in environmentally benign reac-
tion media such as water or ionic liquids.
Table 1. Optimization of reaction conditions
Run
Catalyst
Solvent
Time/h Yield/%
1a
2a
3a
4a
5a
6a
None
NAP
CH3NO2
CH3NO2
CH3NO2
CH3NO2
CH3NO2
CH3NO2
20
5
2
12
20
12
3
31
0
95
4
Nano-NAP
Nano-NAP
Nano-silica
n-Octylamine
n-Octylamine +
Nano-silica
Nano-NAP
81
7a
8b
CH3NO2
12
60
[bmim]PF6
2
0
Currently, catalysts of nanometer particle size attract con-
siderable attention because they have the advantages of both
homogeneous and heterogeneous catalysts. Their fine size and
miscibility in solvent are expected to enhance catalytic activity.
However, due to the strong interactions between nanoparticles,
they usually are present in micromolar concentrations in solvent,
while at higher concentrations they aggregate to form a gel. In
order to prevent aggregation and to increase the concentration
of the nanoparticles in solution, modification of the surface is re-
quired. Thus, we have newly developed an efficient solvent-free
protocol for grafting aminopropyl residues on nanosilica parti-
cles having an average size of 12 nm (Figure 1). In this process,
a solution of 3-aminopropyltriethoxysilane in ethanol is sprayed
directly onto silica nanoparticles.9 This protocol is environmen-
tally benign and favorable for large-scale preparation. One of the
characteristic features of such aminopropylated nanosilica parti-
cles (nano-NAP) compared to amorphous silica is the higher
graft density of the organic residue due to its large surface
area.
aReaction was carried out under reflux of nitromethane with
0.01 equiv of catalyst. Product was isolated by medium pres-
sure LC after decantation followed by evaporation of nitro-
methane. bReaction was carried out with 0.05 equiv of
nano-NAP and 1.2 equiv of nitromethane at 85 ꢁC under mi-
crowave heating.
Michael acceptor and building blocks in the synthesis of phar-
maceutical products.12
Nano-NAP disperses homogeneously into nitromethane
without forming a gel even at concentrations of 1.4 M. Opti-
mized reaction conditions for the Henry reaction were investi-
gated by examining the reaction of benzaldehyde and nitro-
methane (Scheme 1), and the results are shown in Table 1.
The reaction was dependent on reaction temperature and time,
probably due to initial formation of iminium cation. At the re-
fluxing temperature of nitromethane, the reaction went to com-
pletion after 12 h (Table 1, Runs 3 and 4). A catalyst loading
of 0.01 equiv of nano-NAP was sufficient to produce a 95% yield
of nitrostyrene (Table 1, Run 4). The ionic liquid [bmim]PF6 was
not suitable as a recyclable and activating reaction medium even
under microwave irradiation at 85 ꢁC, even though nano-NAP
was miscible under the reaction conditions (Table 1, Run 8).
The optimized reaction conditions (Table 1, Run 4) were
general to a variety of arylaldehydes as shown in Scheme 2
and Table 2. Aldehydes bearing not only electron-withdrawing
(Table 2, Runs 2 and 3) but also electron-donating substituents
(Table 2, Runs 4 and 5) provided nitrostyrenes in good yields.
The reaction conditions are so mild that base- or acid-sensitive
protecting groups such as OAc or OTBDMS groups remained in-
tact (Table 2, Runs 6 and 7), which is favorable for use with
multifunctional substrates such as in natural product synthesis.
Moreover, nitroethane provided nitrostyrene when 0.1 equiv of
As part of our efforts to develop heterogeneously immobi-
lized organocatalysts, we investigated the catalytic activity of
nano-NAP as an immobilized organocatalyst for the Henry reac-
tion.10,11 This reaction is one of the most powerful procedures for
the production of ꢀ,ꢁ-unsaturated nitro compounds, which are
important substrates as dienophiles of Diels–Alder reaction or
O
SiO2
Si
NH2
O
OEt
12 nm
Figure 1. Nano-NAP: aminopropylated nano-silica.
Copyright Ó 2009 The Chemical Society of Japan

Chemistry Letters Vol.38, No.8 (2009)
791
Table 3. Recyclability of nano-NAP in the reaction with benz-
aldehyde
CHO
NO2
Nano-NAP
+
R'-CH2NO2
R'
R
R
Cycle
Time/h
Yield/%
R = H, Cl, NO2, OMe, OH,
OAc, OTBS
R' = H, Me
1
12
12
16
95
81
52
2a
3a
Scheme 2. Henry reaction of arylaldehyde catalyzed by nano-
NAP.
aReaction was carried out with recovered nano-NAP
under reflux of nitromethane.
Table 2. Nano-NAP-catalyzed Henry reaction with a variety of
aldehydesa
In summary, we found that aminopropylated nanosilica
particles—nano-NAP—catalyze the Henry reaction for various
combinations of arylaldehydes and nitroalkanes to afford a vari-
ety of substituted nitrostyrenes. The reaction conditions are mild
enough to ensure that acid- or base-sensitive substituents of the
substrates remain intact. Nano-NAP could be recycled up to
three times in 76% average yield. Miscibility of nano-NAP in
solution due to its hyperfine structure might be useful as a pseu-
do-heterogeneous catalyst.
Run
R
R0
Time/h
Yield/%
1
2
3
4
5
6
7b,c
8b
H
Cl
NO2
OMe
OH
OAc
OTBS
H
H
H
H
H
H
H
H
Me
12
12
10
13
11
12
24
24
95
86
81
91
89
95
44
89
References and Notes
aReaction was carried out with 0.01 equiv of nano-NAP
1
For recent representative reviews, see: a) M. Tada, Y.
Iwasawa, Chem. Commun. 2006, 2833. b) A. Corma, H.
Garcia, Adv. Synth. Catal. 2006, 348, 1391.
H. Hagiwara, T. Sayuri, T. Okabe, T. Hoshi, T. Suzuki, H.
Suzuki, K. Shimizu, Y. Kitayama, Green Chem. 2002, 4,
461.
under reflux of nitromethane. b0.1 equiv of nano-NAP
was used. Starting aldehyde was recovered in 56% yield.
c
2
nano-NAP was used (Table 2, Run 8). The reaction of 4-tert-
(butyldimethylsiloxy)benzaldehyde also required 0.1 equiv of
nano-NAP due to the low reactivity of the aldehyde (Table 2,
Run 7). The reactions of aliphatic aldehydes such as citronellal,
decanal, or hydrocinnamaldehyde resulted in recovery of the
starting materials, which exemplifies the chemoselective nature
of the present protocol.
3
4
5
6
7
8
9
H. Hagiwara, J. Hamaya, T. Hoshi, C. Yokoyama, Tetra-
hedron Lett. 2005, 46, 393.
H. Hagiwara, A. Koseki, K. Isobe, K. Shimizu, T. Hoshi, T.
Suzuki, Synlett 2004, 2188.
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The initial content of silanol groups in the nanosilica was
1.37 mmol gꢂ1 as determined by volumetric measurements8 em-
ploying trimethylaluminium. The loading of amino residues on
nano-NAP was 0.28 mmol gꢂ1 as determined by elemental anal-
ysis, which indicates that more than 40% of the silanol groups on
the nanosilica were functionalized with aminopropyl residues.
The original nanosilica could not catalyze the reaction, resulting
in the recovery of the starting aldehyde (Table 1, Run 5). These
results show that the aminopropyl residues on the nano-NAP are
active as the catalytic site. Although n-octylamine also catalyzed
the reaction in a similar manner (Table 1, Run 6), the yield was
slightly lower. According to TLC analysis, this is probably due
to the formation of aldimine. Although by-products were ob-
tained when a mixture of n-octylamine and nanosilica was em-
ployed as the catalyst (Table 1, Run 7), the spatial proximity
of the basic amine and acidic silanol on the nanosilica surface
might be effective for realizing acid and base bicatalytic syner-
gy, which attracts and activates both the aldehyde and nitro-
methane.1a,11c The turnover number of the nano-NAP catalyst
was 110 in the reaction of benzaldehyde and nitromethane.
NAP (0.01 equiv) could be reused up to three times in 76%
average yield for the reaction of benzaldehyde in refluxing nitro-
methane (Table 3). The catalyst was isolated after the reaction by
precipitation with n-hexane followed by weak and brief centrifu-
gation followed by evacuation. Loss of reactivity in the third cy-
cle might be due to loss of nano-NAP particles during isolation.
Performing the reaction on a larger scale or using a more power-
ful centrifuge may prevent loss of the catalyst during work.
10 During the course of our study, a Henry reaction catalyzed
by nano-NAP, was reported. C. A. Bradley, B. D. Yuhas,
M. J. McMurdo, T. D. Tilley, Chem. Mater. 2009, 21, 174.
11 For recent representative examples catalyzed by amorphous
or mesoporous aminopropylated silica, see: a) S. Huh, H.-T.
Chen, J. W. Wiench, M. Pruski, V. S.-Y. Lin, J. Am. Chem.
Soc. 2004, 126, 1010. b) S. Huh, H.-T. Chen, J. W. Wiench,
M. Pruski, V. S.-Y. Lin, Angew. Chem., Int. Ed. 2005, 44,
1826. c) K. Motokura, M. Tomita, M. Tada, Y. Iwasawa,
Chem.—Eur. J. 2008, 14, 4017. d) T. M. Suzuki, T.
Nakamura, K. Fukumoto, M. Yamamoto, Y. Akimoto, K.
Yano, J. Mol. Catal. A: Chem. 2008, 280, 224.
12 For example: a) S. K. Srivastava, S. M. Husbands, M. D.
Aceto, C. N. Miller, J. R. Traynor, J. W. Lewis, J. Med.
Chem. 2002, 45, 537. b) S. V. Ley, D. J. Dixon, R. T.
Guy, F. Rodriguez, T. D. Sheppard, Org. Biomol. Chem.
2005, 3, 4095. c) D. Enders, M. R. Huttl, J. Runsink,
¨
G. Raabe, B. Wendt, Angew. Chem., Int. Ed. 2007, 46,
467.
Published on the web (Advance View) June 27, 2009; doi:10.1246/cl.2009.790