One-pot synthesis of tweezer-like calix[4]resorcinarene decorated with pendant heterocyclic moieties: An efficient and recyclable heterogeneous PTC for the preparation of azidohydrins in water

Article abstract of DOI:10.1007/s10562-014-1300-y

Direct incorporation of ionic liquid onto the upper rim of calix[4]resorcinarene led to the formation of tweezer-like calix[4]resorcinarene via one-pot strategy. The formation of this cationic supramolecular structure was confirmed by ¹H NMR, <

Full text of DOI:10.1007/s10562-014-1300-y

Catal Lett (2014) 144:1636–1641
DOI 10.1007/s10562-014-1300-y
One-Pot Synthesis of Tweezer-Like Calix[4]resorcinarene
Decorated with Pendant Heterocyclic Moieties: An Efficient
and Recyclable Heterogeneous PTC for the Preparation
of Azidohydrins in Water
Arash Mouradzadegun
Fatemeh Abadast
•
Somayeh Elahi
•
Received: 7 May 2014 / Accepted: 12 June 2014 / Published online: 4 July 2014
Ó Springer Science+Business Media New York 2014
Abstract Direct incorporation of ionic liquid onto the
Resorcinarene, commonly referred to as one of the pil-
upper rim of calix[4]resorcinarene led to the formation of
tweezer-like calix[4]resorcinarene via one-pot strategy.
The formation of this cationic supramolecular structure
lars in supramolecular chemistry, is well-known tetrameric
macrocyclic octols that possess a bowl-shaped molecular
cavity formed by four resorcinol units. The possibility of
modifying this structure either via substitutions on the
aromatic ring, the phenol hydroxyl groups, or the lower rim
increases its potential for forming multifunctional com-
pounds. Acylation and alkylation of hydroxyl group in
upper rim were usually used for the synthesis of neutral,
positively and negatively charged supramolecular struc-
tures [5].
1
13
was confirmed by H NMR, C NMR, CHNS, TGA and
DTA techniques. The hydrophobic central cavity and
hydrophilic cationic arms render it a suitable heteroge-
neous phase transfer catalyst for the preparation of valuable
azidohydrins in water. The recovered catalyst could be
used for several times without any significant loss of
activity.
The cationic heterocyclic moiety is one of the valuable
headgroups that can be used in the synthesis of cationic
supramolecular structures. In recent years, the positively
charged imidazolium groups have been incorporated onto
various molecular frameworks such as calixarene, cavitand
based on resorcinarene and in lower rim of calix[4]resor-
cinarene. However, functionalization of these molecular
frameworks has several drawbacks such as stepwise pro-
cedures, long reaction times, require tedious HPLC and
large amounts of toxic organic solvents or reverse phase
separations [6–8]. Moreover, numbers of these supramo-
lecular imidazolium salts are expensive, non-recyclable
and susceptible to moisture, which render them unsuitable
for using in some of the reaction conditions. Hence, the
exploration of newer and greener method for the synthesis
of such structures with improved properties is still desir-
able in synthetic organic chemistry.
Keywords Dicationic calix[4]resorcinarene Á Tweezer-
like Á Heterogeneous phase transfer catalyst Á
Azidohydrins Á Eco-benign strategy
1
Introduction
Nowadays, heterogeneous phase-transfer catalysis (PTC)
appears to be a prime synthetic tool, being appreciated not
only in various fields of organic chemistry but also among
widespread industrial applications. In this context, the
utilization of supramolecular PTC has become an area of
tremendous importance and a significant amount of
research has been carried out in this direction [1–4].
One-pot synthesis is a strategy to improve the chemical
reaction efficiency whereby a reactant is sequentially sub-
jected to reactions in just one reactor. To our best knowl-
edge, there is no report on the functionalization of
calix[4]resorcinarene via one-pot method.
Electronic supplementary material The online version of this
article (doi:10.1007/s10562-014-1300-y) contains supplementary
material, which is available to authorized users.
A. Mouradzadegun (&) Á S. Elahi Á F. Abadast
Department of Chemistry, Faculty of Science, Shahid Chamran
University, Ahvaz, Iran
Considering the above-mentioned points and in light of
our success in the development of simple and
e-mail: arash_m@scu.ac.ir
1
23

One-Pot Synthesis of Tweezer-Like Calix[4]resorcinarene
1637
environmentally friendly experimental procedure for the
synthesis of significant compounds [9–12], in this work we
propose, for the first time, functionalization of
calix[4]resorcinarene via one-pot strategy for the synthesis
of novel tweezer-like dicationic calix[4]resorcinarene
containing two pendant imidazolium salt that might act as
heterogeneous PTC.
removed by filtration. The products were obtained upon
extraction with ethyl acetate (3 9 5 mL). The extract was
dried over CaCl , and then solvent was evaporated under
2
high vacuum to give the azidohydrins.
The recovered catalyst was washed with water, ethanol
and ethyl acetate, respectively. Then was dried under
vacuum and reused for the next reaction.
2
Experimental
3 Results and Discussions
2
.1 General
Initially, [pmim]Cl was prepared according to literature
procedure, starting from 3-chloro trimethoxysilane and
methyl imidazole [13] (Scheme 1). Then, calix[4]resorcin-
arene (1) was added to the same pot to form functionalized
calix[4]resorcinarene containing ionic liquid (IL) arms. To
remove unreacted calix[4]resorcinarene and ([pmim]Cl),
the resulting solid was washed several times with ethanol
and distilled water. The formation of functionalized
Chemicals were purchased from Fluka, Merck and Aldrich
chemical companies and used without further purification.
1
Products were characterized by physical data, IR, H and
1
3
C NMR. IR spectra were obtained on a Bomen MB:102
1
13
FT-IR spectrophotometer. H and C NMR spectra were
recorded on a Brucker spectrometer at 400 and 100 MHz,
1
13
respectively, in CDCl or DMSO. Elemental analysis was
3
calix[4]resorcinarene was confirmed by H NMR and
C
performed at Thermo Finnigan Flash EA 1112 CHNS-
Analyzer and thermal stability of the catalyst was investi-
gated by NETZSCH STA 409 PC/PG.
NMR spectra (see Supplementary Data).
1
Along with the usual calix[4]resorcinarene peaks, H
NMR spectrum of the product displayed the characteristic
peaks of the imidazolium protons, indicating successful
incorporation of the IL onto calix[4]resorcinarene.
Inspection of the integral ratio of calix[4]resorcinarene and
imidazolium peaks clearly show that two imidazolium salts
built onto calix[4]resorcinarene skeleton which could be
exist at 1,2- or 1,3-position. Since an increase in the
amount of IL did not improve the number of cationic
groups, it can be concluded that the steric effect play a
critical role in the position of the cationic groups. This
finding further supports this assumption that the cationic
groups are at 1,3-position (Scheme 1) (the detailed char-
acterization study is available in Supplementary Materials).
2
.2 Synthesis of Tweezer-Like Dicationic
Calix[4]resorcinarene (2)
The mixture of 12 mmol (3-chloropropyl)trimethoxysilane
and 12 mmol of 1-methylimidazole (freshly distilled) was
refluxed at 95 °C for 24 h under nitrogen atmosphere. The
reaction mixture was cooled down and 1-methyl-3-(trim-
ethylsilylpropyl) imidazolium chloride ([pmim]Cl) (slightly
yellow viscous oil) was obtained with 98 % yield [13].
Then, 0.5 g (1 mmol) of calix[4]resorcinarene in 10 mL of
toluene was added to 1.5 g (6 mmol) of [pmim]Cl. After
heating the slurry at 90 °C for 24 h the solid was isolated by
filtration. Owing to the solubility of unreacted calix[4]res-
orcinarene in ethanol and ([pmim]Cl) in water, the resulting
solid was washed several times with ethanol and distilled
water to remove unreacted materials. Then, the solid was
dried under high vacuum to give violet powder with 89 %
yield.
1
It is worth noting that, the broadened signals in H NMR
of 2 testify to the existing equilibrium between the crown,
chair and diamond conformers of 2, which is completely
adapted with the previously reported data for functional-
ized calix[4]resorcinarene [14–17] (more details are
available in Supplementary Materials).
To shed more light on the purity of product, elemental
analysis was performed (Calcd for C H N O Si Cl : C,
4
6
58
4
12
2
2
2
.3 Synthesis of Azidohydrin Derivatives
56.02; H, 5.92; N, 5.68 %. Found: C, 55.99; H, 5.94; N,
5.71). This result gave us confidence that, the product to be
pure enough and calix[4]resorcinarene bearing two IL arms
have been successfully prepared. This coincides well with
in the Presence of Novel Phase Transfer Catalyst
(
2)
1
NaN3 (2 mmol) was added to a mixture of epoxide
1 mmol) and dicationic calix[4]resorcinarene (0.03 g) in
water (1.5 mL). The suspension was magnetically stirred at
the integrals of each proton in the H NMR spectrum of
(
this compound.
Thermal stability of compound (2) was investigated by
thermal gravimetric analysis (Fig. 1) at a heating rate of
10 °C per min under nitrogen atmosphere. Compound (2)
shows three distinct steps of weight loss in the combined
70 °C for the lengths of time shown in Table 1. After
completion of the reaction as judged by TLC (using n-
hexane/ethyl acetate (4:2) as eluent), the catalyst was
123

1
638
A. Mouradzadegun et al.
CH3
N
Cl
N
-
Cl
CH3
N
N
Neat condition
5 °C
+
+
Si
O
O
O
Si
O
9
O
O
H C
3
CH3
CH3
CH3
CH3
CH3
H C
3
CH3
CH3
CH3
(1)
1) Toluene/ 90 °C
2
) H O
2
CH3
N
CH3
N
N
N
-
-
Cl
Cl
OH
HO
OH
HO
Si
Si
CH3
CH3
CH3
CH3
(2)
Scheme 1 Synthesis of novel tweezer-like dicationic calix[4]resorcinarene
Fig. 1 TGA and DTG profile of
compound 2
1
23

One-Pot Synthesis of Tweezer-Like Calix[4]resorcinarene
1639
Table 1 Reaction of various epoxides with sodium azide in the presence of the representative catalyst in water
OH
O
N3
Cat. 0.03 g
N3
NaN3
OH
+
°
R
water / 70 C
R
R
(
I)
(II)
Entry
1
Substrate
Product
Time (min)
Yield (%)
89
OH
N3
10
O
O
2
O
OH
25
91
O
N3
O
O
3
4
O
OH
50
15
73
87
N3
PhOH C
2
PhOH C
2
O
OH
O
N3
O
5
6
O
OH
75
78
0
N3
O
O
–
360
O
TGA/DTG curves. The initial slight weight loss occurs
before 150 °C, which can be attributed to the evaporation
of hydrated water or residual solvent. The compound (2)
then displayed a stage decomposition caused by the loss of
the IL arms at about 350 °C followed by degradation of the
calix[4]resorcinarene backbone. Therefore, compound (2)
demonstrated high thermal stability, with decomposition
starting at around 350 °C.
The thermally stability of this compound allows heat
demanding chemical transformations along its backbone
and side chains without leaching of the active species in the
reaction media. Moreover, tweezer-like calix[4]resorcina-
rene is effectively insoluble in water, thereby providing an
excellent heterogeneous catalyst for conducting chemical
transformations in water.
To develop suitable reaction conditions, 2,3-epoxy-
propyl methacrylate was chosen as a model compound
and parameters including temperature, molar ratio of the
reagent/substrate and amount of catalyst were examined
in detail. After some experiments, it was found that the
use of 2 equivalent of NaN per epoxide in the presence
3
of the catalyst 2 (0.03 g) at 70 °C were the best
conditions.
The success of the first set of experiments using dicat-
ionic calix[4]resorcinarene as PTC promoted us to increase
the scope and generality of the present reaction to other
epoxides (entries 1–5, Table 1).
The reactions of all epoxides with sodium azide were
found to be highly regioselective and only one isomer
(I) was obtained (entries 1–5, Table 1). It is noteworthy
that no evidence for the formation of diol as by-product
was observed. Hence, all products were obtained in pure
form without further purification. The structure of products
were established unambiguously from spectroscopic (IR,
In light of the aforementioned points and considering
this assumption that the cavity of this novel dicationic
calix[4]resorcinarene can act as a host for wide variety of
compounds, we became interested to evaluate the ability of
this novel water-sustainable supramolecular imidazolium
salts as PTC in nucleophilic substitution reaction in water.
Importance of azidohydrins as precursors in the syn-
thesis of vicinal amino alcohols, carbohydrates, nucleo-
sides, lactames and oxazolines [18–20], encouraged us to
survey the reaction of epoxides with sodium azide for the
synthesis of these valuable compounds in water.
1
13
H NMR, C NMR) data and by direct comparison with
authentic samples [10, 21].
The formation of these products (entries 1–5, Table 1)
by this methodology are of considerable interest since this
is the first attempt to the synthesis of these privileged
compounds in the presence of cationic supramolecular
structure as an efficient heterogeneous PTC.
123

1
640
A. Mouradzadegun et al.
Table 2 Comparison of
azidolysis of model compound
with different catalysts in water
Entry Catalyst
Catalyst Reagent/
g) substrate
mmol)
Temp
Time
(h)
Yield
(%)
(
(
1
2
(2)
0.03
0.1
2
3
70
80
0.25 91
1.40 84
3D-Network porous polymer based on
calix[4]resorcinarenes [10]
3
4
5
Dowex-PEG300 [21]
0.1
0.1
1.2
3
Reflux
Reflux
RT
1.5
2
90
90
95
2
SiO -PEG [22]
Poly[N-(2-aminoethyl)acrylamido]-trimethyl 0.2
ammonium iodide [23]
5
12
CH3
N
CH3
aqueous phase via well-known ion exchange reaction,
which increases the nucleophilicity of the azide anion
owing to the weak interaction between azide anion and the
imidazolium moieties onto compound 2 (Fig. 2).
N
N
N
-
-
N3
To exhibit a more clear understanding of the reaction
mechanism and the promoting effect of the inclusion
complex on the catalytic efficiency, the reaction of bulky
epoxide 12-oxa-bicyclo[9.1.0]dodecane with sodium azide
under optimized reaction conditions was investigated.
Interestingly, no evidence for the formation of corre-
sponding azidohydrin was observed, even after prolonged
reaction time (entry 6, Table 1). It could be concluded that
in this case probably inclusion complex has not been
formed. In this way the promoting effect of inclusion
complex was confirmed.
N3
Hydrogen bonding
Ion exchange
OH
HO
OH
O
HO
Si
Si
R
CH3
CH3
Inclusion complex
CH3
CH3
Fig. 2 Proposed catalytic mechanism
As illustrated in Table 2, catalyst 2 show a much higher
catalytic activity than polymeric calix[4]resorcinarene
(entries 1, 2, Table 2). This result further supports this
assumption that besides the hydrophobic cavity of 2, cat-
ionic arms play a crucial role in its catalytic activity and
contribute to the rapid progress of the nucleophilic
reaction.
The promoting effect of catalyst was definitely con-
firmed by the reaction of model compound with sodium
azide, without adding catalyst or in the presence of the
initial calix[4]resorcinarene under optimized reaction
conditions. TLC analysis of the reaction mixture did not
show completion of the reaction after 8 h [10].
Under these results, we expect that this cationic catalyst
(2) will be a suitable alternative to the existing catalysts.
In order to show the merit of this novel catalyst, Table 2
compares our results obtained from the model reaction in
the presence of 2 with the same results reported in litera-
ture. To our delight, heterogeneous catalyst 2 exhibited
significantly higher catalytic activity in terms of the reac-
tion time and amount of catalyst (entry 1, Table 2).
4 Conclusions
In the present study we disclose a new and fascinating
approach for the synthesis of supramolecular imidazolium
salts based on calix[4]resorcinarene skeleton. A survey of
the literatures indicate that, this is the first report on the
one-pot synthesis of this cationic calix[4]resorcinarene via
silylation of hydroxyl groups on the upper rim of
calix[4]resorcinarene without the use of acidic or basic
catalyst. The reaction procedure is convenient, involving
simple experimental procedure and product isolation, thus
dispense with expensive chromatographic purification
steps. Hence, the procedure opens a novel entry to the
convenient synthesis of a number of functionalized
resorcinarene.
The catalytic activity of water-sustainable supramolec-
ular imidazolium salts (2) could be attributed to the syn-
ergetic effect of its hydrophobic cavity and hydrophilic
arms. In water, the hydrophobic cavity of 2 could act as
microvessel and accommodate nonpolar epoxide deriva-
tives based on hydrophobic interaction. Meanwhile, the
hydrogen bonding of the epoxide oxygen to the outer OH
of the catalyst could promote the formation of this inclu-
sion complex. The hydrogen bonding could also activate
the epoxide and accelerate the nucleophilic substitution
reaction. Moreover, the hydrophilic exterior imidazolium
moieties could form a complex with nucleophile in the
1
23

One-Pot Synthesis of Tweezer-Like Calix[4]resorcinarene
1641
Following the synthetic strategy, the application of this
novel three dimensional imidazolium salt as PTC for the
preparation of azidohydrins was investigated. The catalytic
activity of this valuable compound could be attributed to
the synergetic effect of methylimidazolium cation and
cavity of skeleton. Further studies on the other applications
of novel tweezer-like dicationic calix[4]resorcinarene
which concluded from its structure, are currently under
way in our laboratory.
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