SiO2Nanoparticle-catalyzed Facile and Efficient One-pot Synthesis of N-alkyl-2,5-bis[(E)-2-phenylvinyl]-1,3-dioxol-4-amine Under Solvent-free Conditions

Article abstract of DOI:10.1002/jhet.2450

1,3-Dioxole-4-amine derivatives have been prepared efficiently in one-pot reaction using nanosized SiO₂as a heterogeneous catalyst. The present method does not involve any hazardous organic solvents or catalysts. The high surface-to-volume rati

Full text of DOI:10.1002/jhet.2450

Month 2015
SiO2 Nanoparticle-catalyzed Facile and Efficient One-pot Synthesis of
N-alkyl-2,5-bis[(E)-2-phenylvinyl]-1,3-dioxol-4-amine Under
Solvent-free Conditions
*
Mohammad Bayat and Hamideh Nasehfard
Chemistry Department, Imam Khomeini International University, Qazvin, Iran
*
E-mail: bayat_mo@yahoo.com
Received November 29, 2014
DOI 10.1002/jhet.2450
Published online 00 Month 2015 in Wiley Online Library (wileyonlinelibrary.com).
1,3-Dioxole-4-amine derivatives have been prepared efficiently in one-pot reaction using nanosized SiO2
as a heterogeneous catalyst. The present method does not involve any hazardous organic solvents or cata-
lysts. The high surface-to-volume ratio of SiO2 nanoparticle has promising features for the reaction response
such as the short reaction time, good to excellent yields, easy of operation and work-up procedure, and pu-
rification of products by non-chromatographic methods.
J. Heterocyclic Chem., 00, 00 (2015).
INTRODUCTION
applications in the treatment of cardiovascular diseases and
lung cancer [13,14]. Several methods have been published
on benzodioxoles [12–15], and only a few procedures for
1,3-dioxoles have been described [16].
The efficiency of heterogeneous catalysis in organic
synthesis can be improved by employing nanosized
catalysts. The field of nanocatalysis has attracted the
attention of researchers working in the fields of catalysis
and nanoparticles, because of their high surface-to-
volume ratio that increases the efficiency as well as
selectivity of the catalysts [1]. Furthermore, nanocatalysis
has the advantages of high atom efficiency, easy product
purification, and reusability of the catalyst [2]. Clearly,
the development of free nanoparticles with tunable
catalytic activity is of great significance for both acade-
mia and industry [3].
In continuation of our work on the synthesis of
1,3-dioxole and interesting organic compounds [17], there
has been a great interest in finding ways to improve
reaction conditions and efficient methods. We report herein
a novel method synthesis of 1,3-dioxole heterocycles using
simple starting materials. To the best of our knowledge,
there have been no examples of the use of SiO2 nanoparti-
cles for the synthesis of 1,3-dioxole derivatives through
isocyanide-based reaction including aromatic aldehydes
to give these compounds in one-pot reaction.
Nanoparticles have also been widely used for the or-
ganic synthesis in both homogeneous and heterogeneous
conditions [4]. Among the readily available catalysts, the
use of silica nanoparticles has increased because of their
unique properties and potential applications in various
fields. The stability, high surface area, and non-toxicity
made the silica nanoparticles ideal candidates for catalyst
or catalyst support [5]. Furthermore, the possibility of
performing multicomponent reactions under solvent-free
conditions with heterogeneous catalysts like SiO2 nanopar-
ticles could enhance their efficiency from an economic as
well as a green point of view.
RESULTS AND DISCUSSION
The reaction of alkyl isocyanides 1 and aromatic
aldehydes 2 in the presence of SiO2 nanoparticle proceeds
in one-pot under solvent-free condition, at 80°C to produce
the 1,3-dioxole compounds 3 in excellent yields (Scheme 1).
The structures of the products were deduced from their
1
elemental analyses and IR, H, and 13CNMR spectra. The
1H and 13CNMR spectra of the crude products clearly indi-
cated the formation of the products. Any product other than
1
3 could not be detected by HNMR spectroscopy. The
The chemistry of 1,3-dioxole heterocycles has attracted
much attention owing to their biological activities and their
potent utility as anti-HIV (e.g., AHE) [6–8], anticancer
[9,10], antidepressive, antitumor, anticonvulsant, and anti-
pyretic agents [11,12]. Their significance is also because of
mass spectra of these compounds displayed molecular ion
peaks at appropriate m/z values. The run of this reaction
at r.t. with SiO2 and without for 2 h did not work. TLC
and H NMR spectrum of the reaction mixture indicated
the formation of trace of product.
1
© 2015 HeteroCorporation

M. Bayat and H. Nasehfard
Vol 000
The 1HNMR spectrum of 3a consisted of a multiplet for the
cyclohexyl group (δ 1.01–2.01), a broad signal for the N―CH
proton (δ 3.77–3.87), a singlet at δ 6.30 for the hemiacetal pro-
ton, and a doublet (δ 6.10, 3JHH =7.5Hz) for the N―H group
in agreement with the suggested structure. The 1H decoupled
13CNMR spectrum of 3a showed 17 distinct signals in agree-
ment with proposed structure. The characteristic signal of
hemiacetal carbon was observed at δ 75.93. The olefinic
C-atoms of the 1,3-dioxole ring were observed at δ 164.95
Scheme 1. SiO2 nanoparticle catalyzed synthesis of 1,3-dioxole 3 under
solvent-free conditions. [Color figure can be viewed in the online issue,
which is available at wileyonlinelibrary.com.]
1
and 167.37. The H and 13C NMR spectra of compounds
3b–i were similar to that of 3a except for the signals of the
Table 1
SiO2 nanoparticles catalyzed synthesis of 1,3-dioxole derivatives 3a–i.
Entry
Aldehyde
Isocyanide
Cy-NC
Product
Yields (%)
97
a
b
c
Cy-NC
Cy-NC
95
94
d
Cy-NC
Cy-NC
85
94
e
f
t-BuNC
99
(Continued)
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Synthesis of N-alkyl-2,5-bis[(E)-2-phenylvinyl]-1,3-dioxol-4-amine
Table 1
(Continued)
Entry
Aldehyde
Isocyanide
Product
Yields (%)
95
g
t-BuNC
h
t-BuNC
98
94
i
Cy-NC
substituted alkyl and aryl rings, which exhibited characteristic
resonances with appropriate chemical shifts (all characteriza-
tion data are reported in Helv. Chem. Acta) [17].
As shown in Table 1, we found that aromatic alde-
hydes containing different functional groups at different
position worked well and did not show differences in
the yield of products.
The proposed mechanism for the role of nano-SiO2 as a
solid acid catalyst is shown in Scheme 2. On the basis of
the well-established chemistry of isocyanides [18,19] it is
reasonable to assume that the reaction involves initial
formation of a 1,3-dipolar intermediate between the alkyl
isocyanide and aldehyde, which undergoes addition to the
carbonyl group of another aldehyde molecule to give 5. This
intermediate is converted into product 3 via proton transfer.
To determine the appropriate concentration of the
catalyst SiO2 nanoparticles, we have investigated the model
reaction of benzaldehyde and cyclohexyl isocyanide at
different concentrations of SiO2 nanoparticles such as 10,
20, and 30mol%. We found that 30mol% of SiO2 nanopar-
ticles produces the best results with respect to product yield.
We have examined the recovery and reuse of the cata-
lyst. The catalyst was recovered by a simple work-up using
the filteration and reused during three consecutive runs
without any apparent loss activity for the same reaction.
It is noteworthy that the yield of the product in the sec-
ond and third uses was almost the same as that in the first
run as has been shown in Table 2.
Figure 1 shows the broadened X-ray diffraction (XRD)
analysis. The broad peak at 21.91° corresponds to the
amorphous nature of silica.
The size and structure of the SiO2 nanoparticles were
also evaluated using scanning electron microscopy
(SEM). According to the SEM (Fig. 2), it was observed
that the silica has a nanodimension ranging from 60 to
90nm. The SEM pictures show good agglomeration of
particles of silica that is spherical in shape.
Characteristic properties of the commercially SiO2 nano-
particles (CAB-O-SIL M5) were summarized in Table 3.
Scheme 2. Proposed mechanism.
SUMMARY
We have developed a straightforward and efficient
method for the preparation of 1,3-dioxole derivatives via
Table 2
Reutilization of SiO2 nanoparticles in the synthesis of 3a.
Run
Fresh
97
1
2
3
Yield (%)
96
95
95
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M. Bayat and H. Nasehfard
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Switzerland) and used without further purification. The sil-
ica (CAB-O-SIL® M5) was purchased from Cabot Corpo-
ration. The particle size and structure of SiO2 nanoparticles
were observed by using a Seron AIF 2100 Scanning elec-
tron microscopy (SEM) operating at 25KV. XRD pattern
was taken through a Inel Equinox 3000 model with a Cu
kα source.1H and 13C NMR spectra were recorded on a
Bruker-DRX-300 Avance instrument, in CDCl3 using
MeSi4 as internal standard. Melting points were obtained by
Gallenkamp electrothermal-9100 apparatus; not corrected.
Elemental analyses were obtained by Heraeus-CHN-O-Rapid
analyzer. These results agreed favorably with the calculated
values. Mass spectra were recorded with a Shimadzu-QP-
GC-5050 spectrometer at 70eV; in m/z (%). IR spectra were
recorded on Bruker-Tensor-27 spectrophotometer.
Figure 1. XRD pattern of SiO2 nanoparticles. [Color figure can be viewed
in the online issue, which is available at wileyonlinelibrary.com.]
one-pot reaction of alkyl isocyanides and aromatic alde-
hydes promoted by SiO2 catalyst. The present method of-
fers several advantages such as short reaction time,
simple experimental procedure, and high yield of the prod-
ucts, and catalyst can be recycled and reused at least three
times without significant loss of activity.
Representative procedure for the preparation of
compounds 3.
To a magnetically stirred benzaldehyde
(0.212 g, 2 mmol) and nano SiO2 (30 mol.% based on
aldehyde) was added cyclohexyl isocyanide (0.109g,
1 mmol) under solvent-free condition. The reaction
mixture was stirred at 80°C for 2 h. The progress of the
reaction was monitored by TLC (eluent: ethyl acetate/n-
hexane, 2:8). After completion, the reaction mixture was
cooled at room temperature. Then, it was extracted with
EXPERIMENTAL
Alkyl isocyanides, aromatic aldehydes, and solvents
used in this work were obtained from Fluka (Buchs,
Figure 2. SEM pictures of SiO2 nanoparticles. [Color figure can be viewed in the online issue, which is available at wileyonlinelibrary.com.]
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Month 2015
Synthesis of N-alkyl-2,5-bis[(E)-2-phenylvinyl]-1,3-dioxol-4-amine
Table 3
Characteristic properties of the commercially SiO2 nanoparticles.
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B.E.T. surface area
pH (4% aqueous slurry)
Bulk density
Loss on heating
Loss on ignition (@ 1000°C)
Specific gravity
200 m2/g
3.7–4.3
3.0 lb/ft3 max.
<1.5% max.
<2 wt. %
2.2 g/cm3
1.46
Refractive index
X-ray form
Amorphous
~350 g/100 g oil
60–90 nm
>99.8
Oil adsorption
Average particle size
Assay (% SiO2)
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(3i). Yield: 0.361g (94%). White solid. IR: 3452, 3306,
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C25H27NO2 (373.5): C 80.40, H 7.29, N 3.75. Found: C
1
79.9, H 7.3, N 3.7. H-NMR: δ 1.09–2.02 (10H, m, Cy),
3
3.75–3.95 (1H, m, CHN), 5.88 (1H, dd, JHH =6.6,
4JHH =1.2Hz, CH), 6.10 (1H, br s, NH), 6.36 (1H, dd,
3
3JHH =15.9, JHH =6.6Hz, CHolefinic), 6.59 (1H, d,
3
3JHH =15.9Hz, CHolefinic), 6.75 (1H, d, JHH =16.5Hz,
CHolefinic), 7.25–7.65 (10H, m, CHarom.), 7.84 (1H, d,
3JHH =15.9Hz, CHolefinic).13C-NMR: δ 24.75, 25.41, 32.94
(Cy), 48.22 (CHN), 74.37 (CH), 116.74 (CHolefinic), 122.79
(CHolefinic), 126.80, 128.26, 128.55, 128.65, 129.22,
129.75 (CHarom.), 130.75 (CHolefinic), 133.95 (Carom.),
134.37 (CHolefinic), 135.71 (Carom.), 165.23, 167.15 (C¼C).
Acknowledgments. This work was supported by Imam Khomeini
International University Grants (project number 11454).
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Journal of Heterocyclic Chemistry
DOI 10.1002/jhet