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Chemistry Letters Vol.38, No.9 (2009)
Nano-silica PAMAM Dendrimer as a Novel Catalyst for Knoevenagel Reactions
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 June 23, 2009; CL-090592; E-mail: hagiwara@gs.niigata-u.ac.jp)
A nano-silica dendrimer, poly(amidoamine)-grafted nano-
O
O
silica (nano-PAMAM), catalyzed the Knoevenagel reaction of
aryl and aliphatic aldehydes with various active methylene com-
pounds at room temperature in good yields. The reaction condi-
tions were mild enough that base-sensitive AcO or acid-sensitive
THPO groups remained intact in the products. The catalyst was
recycled up to 4 times in 78% average yield.
SiO2
Si
NH2
NR2
NR2
O
OEt
N
H
N
H
H
O
N
N
N
Nano-NAP
O
O
N
NR2
NR2
Solvent free
N
H
H
HN
HN
N
N
H
O
O
O
O
O
O
O
O
SiO2
Si
N
The Knoevenagel reaction is one of the most powerful pro-
cedures for the production of ꢀ,ꢁ-unsaturated carbonyl com-
pounds, which are important substrates as acceptors in Michael
reactions or as dienophiles in Diels–Alder reactions and as useful
building blocks with many applications in the synthesis of fine
chemicals.1 The Knoevenagel reaction can be catalyzed by a
broad range of catalysts ranging from homogeneous amine to
heterogeneous dendrimers,2 however, environmentally benign
and sustainable catalysts are increasingly desired due to the re-
quirements of green chemistry.3
OEt
NR2
NR2
N
H
N
H
H
N
N
N
12 nm
O
N
O
Nano-PAMAM R = H
Nano-PAMDMAM R = Me
NR2
N
H
N
H
O
NH
O
NR2
Based on this concept, we have successfully utilized amor-
phous aminopropylated-silica of micrometer particle size as
sustainable catalysts for 1,4-conjugate additions4 and self-aldol
condensations5 of naked aldehydes, transesterifications,6
Michael reactions,7 hydropyran synthesis by three component
condensations,8 Knoevenagel reactions,9 and subsequent
Mislow–Evans rearrangements10 in environmentally benign re-
action media such as water or ionic liquids.
Scheme 1. Nano-silica dendrimer, nano-PAMAM, nano-
PAMDMAM, and nano-silica NAP.
CO2Et
CO2Et
CN
Nano-PAMAM
+
R-CHO
n-Hexane, r.t.
CN
R
Scheme 2. Knoevenagel reaction catalyzed by nano-PAMAM.
We have recently developed an efficient solvent-free proto-
col for grafting aminopropyl residues on nano-silica particles
having an average size of 12 nm to provide aminopropylated
nano-silica (nano-NAP), in which a solution of (3-aminopropyl)-
triethoxy silane in ethanol is sprayed directly onto the silica
nanoparticles,11 which is environmentally benign and favorable
for large-scale preparation. Subsequently, syntheses of hyper-
branched polyamidoamine (PAMAM)-grafted nano-silica third
generation dendrimer (nano-PAMAM) and polyamidodimethyl-
amine (PAMDMAM)-grafted nano-silica third generation den-
drimer (nano-PAMDMAM) were achieved by spraying methyl
acrylate and then ethylenediamine alternately starting from
nano-silica NAP (Scheme 1).
As a part of our ongoing efforts directed towards the devel-
opment of supported-organocatalysts on silica,12 we investigated
the catalytic activity of the nano-silica dendrimers nano-
PAMAM and nano-PAMDMAM as novel supported-organoca-
talysts for the Knoevenagel reaction13 (Scheme 2). The catalytic
use of PAMAM in Knoevenagel reactions was quite limited until
a recent report by Kapoor et al., in which second generation
PAMAM was supported inside of mesoporous FSM silica in a
study to remove volatile organic compounds.14 Subsequently,
during the course of our study, Krishnan and Sreekumar publish-
ed their work on Knoevenagel reactions that were catalyzed by
polystyrene bead-supported third generation PAMAM.2b
Nano-silica dendrimers, nano-PAMAM, nano-
PAMDMAM, and nano-silica NAP, all disperse homogeneously
into various solvents—even into n-hexane—without forming a
gel, unlike the original nano-silica particles. The optimum reac-
tion conditions for the Knoevenagel reaction were investigated
using the reaction of benzaldehyde and ethyl cyanoacetate, and
the results are shown in Table 1. Our investigation into the opti-
mum reaction medium was first carried out employing nano-
PAMAM (amine residue: 2.4 mmol gꢁ1), and n-hexane was
found to give the best results (Table 1, Entries 4 and 6). Among
the catalysts, nano-PAMAM exhibited the best catalytic per-
formance in n-hexane at room temperature (Table 1, Entries 4
and 6). Nano-PAMDMAM was less reactive (Table 1, Entry
7), which suggests that the present reaction proceeds via initial
imine formation followed by nucleophilic attack of ethyl cya-
noacetate and subsequent elimination of the dendrimeric amine.
The high density of amino groups on the surface of nano-
PAMAM might be responsible for its catalytic activity.
Employing the optimized reaction conditions (Table 1,
Entry 4, TOF = 3), reactions with various aldehydes are shown
in Table 2. Aryl aldehydes bearing not only electron-withdraw-
ing (Table 2, Entries 2 and 3) but also electron-donating (Table 2,
Entries 4 and 5) substituents reacted in good yields to give unsat-
urated cyanoesters. The wide applicability of nano-PAMAM
Copyright Ó 2009 The Chemical Society of Japan