Calix[4]resorcinarene-Chitosan Hybrid via Amide Bond Formation

Article abstract of DOI:10.14233/ajchem.2015.18735

Hybrid of calix[4]resorcinarene and chitosan has been prepared via amide bond formation as the key step between ester groups attached on calix[4]resorcinarene and amine group of chitosan. The synthesis was commenced by functionalizing hydroxyl group of vanillin with methyl-2-chloroacetate via Williamson synthesis. The acid catalyzed-tandem condensation-cyclization of vanillin derivative and resorcinol gave C-4-methoxycarbonylmethoxy-3-methoxyphenylcalix[4]resorcinarene. The calix[4]resorcinarene installed with the ester group was then coupled with amine group of chitosan to form hybrid of calix[4]resorcinarene and chitosan. The IR, XRD and SEM analyses of the hybrid revealed that physical properties of the hybrid were similar to chitosan.

Full text of DOI:10.14233/ajchem.2015.18735

Asian Journal of Chemistry; Vol. 27, No. 6 (2015), 2273-2276
A
SIAN
J
OURNAL OF HEMISTRY
C
http://dx.doi.org/10.14233/ajchem.2015.18735
Calix[4]resorcinarene-Chitosan Hybrid via Amide Bond Formation
1,*
1
1
1
2
3
JUMINA , DWI SISWANTA , MAYLIANA ANGGRAENI , MUHAMAD IDHAM DARUSALAM MARDJAN , PANUT MULYONO and KEISUKE OHTO
1
2
3
Department of Chemistry, Faculty of Mathematics and Natural Sciences, Universitas Gadjah Mada, Yogyakarta 55281, Indonesia
Department of Chemical Engineering, Faculty of Engineering, Universitas Gadjah Mada, Yogyakarta 55281, Indonesia
Department of Chemistry and Applied Chemistry, Faculty of Science and Engineering, Saga University, 1-Honjo, Saga 840-8502, Japan
*
Corresponding author: E-mail: jumina@ugm.ac.id, pak_jumina@yahoo.com
Received: 11 September 2014; Accepted: 8 December 2014;
Published online: 17 March 2015;
AJC-17009
Hybrid of calix[4]resorcinarene and chitosan has been prepared via amide bond formation as the key step between ester groups attached
on calix[4]resorcinarene and amine group of chitosan. The synthesis was commenced by functionalizing hydroxyl group of vanillin with
methyl-2-chloroacetate via Williamson synthesis. The acid catalyzed-tandem condensation-cyclization of vanillin derivative and resorcinol
gave C-4-methoxycarbonylmethoxy-3-methoxyphenylcalix[4]resorcinarene. The calix[4]resorcinarene installed with the ester group was
then coupled with amine group of chitosan to form hybrid of calix[4]resorcinarene and chitosan. The IR, XRD and SEM analyses of the
hybrid revealed that physical properties of the hybrid were similar to chitosan.
Keywords: Hybrid, Calix[4]resorcinarene, Chitosan.
compounds. Moreover, calix[4]arenes have been combined
INTRODUCTION
6
,7
8
9,10
with simple organic molecules , MCM-41 , polymer
,
Calixarenes are versatile macrocyclic compounds which
11
sugars, peptides and oligonucleotides . Various routes have
been employed to develop the hybrids such as carbonyl group
posses unique and intriguing structure. Their versatilities and
selective properties were obtained from their molecular cavi-
ties, their variety of conformations and various functionalization
7,11
addition , nucleophilic substitution, ionic hydrogenation and
12
transition-metal-mediated reactions .
1,2
on their cyclic structure . Many examples of calix[4]arenes
have been synthesized and applied in various fields as host
Searching for the precursor to be coupled with calix[4]-
resorcinarenes, we considered to use chitosan. It could be
derived from chitin (which is abundantly available from the
exoskeleton of crustaceans) via deacetylation reaction. Chitosan
is a linear polysaccharide which is primarily composed of (1 →
3
4
5
molecule, adsorbent , extractant , catalyst , etc. However, another
member of calixarenes, i.e. calix[4]resorcinarenes derived from
resorcinol and aldehyde, have been less studied compared to
calix[4]arenes.
4
2
) linked 2-amino-2-deoxy-d-glucopyranose units and residual
-acetamido-2-deoxy-d-glucopyranose units. The presence of
Several studies, such as on sorption of metal ions, reported
that calix[4]resorcinarenes displayed high affinity toward either
metal anions or cations. Several functionalized calix[4]-resor-
cinarenes were proved to effectively remove metal cations,
hydroxyl (OH) and amino group (NH
chitosan to coordinate with heavy metal ions . The important
property of this biopolymer is the amine (NH ) group which
2
) along the chain enables
13,14
2
1
such as Pb(II) and Cd(II) . Despite the facts that calix[4]-
could be coupled with calix[4]resorcinarenes via carbonyl
group addition, i.e. amide bond formation. In this paper, we
would functionalize calix[4]resorcinarene with carboxylic acid
derivative (ester) and couple it with chitosan via amidation
reaction to construct the hybrid of calix[4]resorcinarene-
chitosan.
resorcinarenes displayed good performance on the cation
removal, the application of those sorbents in the industrial scale
seems to be quite difficult due to the loss of sorbent on the
sorption process and also the low efficiency for the regene-
ration. To address the problems, one strategy proposed was to
chemically couple the calix[4]resorcinarenes with polymeric
material in order to give hybrid with better performances such
as higher sorption capacity and mechanical strength.
EXPERIMENTAL
Hybrids prepared from calix[4]arenes and other materials
have been widely studied and applied as host molecules
installed with efficient ligands as well as biologically active
All the chemicals were purchased in pro analysis (p.a.)
grade and utilized without further purification. Vanillin,
2-chloroacetic acid, resorcinol, sodium metal, H
2
SO , HCl,
4

2
274 Jumina et al.
Asian J. Chem.
NaCl, NaHCO
3
, Na
2
SO
4
, methanol, ethanol, dichloromethane
refluxed for 24 h. Then, water was added into the cooled
reaction mixture to give the solid. The solid was filtered and
dried to produce the calix[4]resorcinarene-chitosan hybrid as
dark orange solid (28 % yield). IR (KBr, νmax, cm ): 3448 (NH)
and 1658 (C=O amide).
and DMF were obtained from E. Merck, while chitosan was
purchased from CV. Chemix Pratama.
The products were characterized by using melting point
apparatus (Electrothermal 9100, without any correction),
-1
1
13
infrared (FTIR, Shimadzu Prestige 21), H- and C nuclear
1
13
RESULTS AND DISCUSSION
magnetic resonance ( H- and C NMR, Agilent VNMR 400
MHz) as well as gas chromatography-mass spectrometers (GC-
MS, Shimadzu QP-2010S). Further characterizations of the
hybrid calix[4]resorcinarene-chitosan were carried out by
means of X-ray diffractometer (XRD, Shimadzu 6000) and
scanning electron microscope (SEM, Jeol JSM T300).
Synthesis of methyl-2-chloroacetate (2): 2-Chloroacetic
acid (1) (9.45 g, 0.1 mol) and methanol (9.60 g, 0.3 mol) were
mixed together in the presence of concentrated sulfuric acid
In this study, calix[4]resorcinarene was employed as the
main framework as it is rapid and easy to prepare comparing
1
5,16
to calix[4]arene and calix[6]arene . Design of calix[4]-
resorcinarene as an adsorbent for heavy metal cation was
conducted by introducing functional groups which have
affinity towards the metal ion. Previous studies showed that
incorporation of carboxylic acid or its derivatives on calix-
arenes could give high either adsorption or extraction perfor-
2
,4,17
(
0.1 mL). The mixture was then refluxed for 5 h. The reaction
was quenched by the addition of saturated solution of NaCl
50 mL). The mixture was extracted with dichloromethane.
The combined organic layer was, respectively washed with
0 % NaHCO solution, water, dried and evaporated to give
methyl-2-chloroacetate (2) as yellowish oil (70 % yield). H
NMR (400 MHz, CDCl = 4.00 (s, 2H) and 3.70 (s, 3H)
mances for metal ion, such as Pb(II) ion . In addition, such
groups offer various conversions into other groups and also
enable calix[4]resorcinarene to be combined with polymeric
material of chitosan to form calix[4]resorcinarene-chitosan
hybrid.
(
1
3
1
Functionalization of calix[4]resorcinarene was performed
on the benzaldehyde residues. On the other hand, the resorcinol
residues were remained unfunctionalized as it could serve as
coordinating site for metal ion. The benzaldehyde (4) was
prepared from methyl ester (2 )(derived from the corresponding
acid via esterification) and vanillin (3) based on Williamson
ether synthesis and was afforded in quantitative yield. Next,
acid-catalyzed-condensation followed with cyclization
reactions betweed aldehyde (4) and resorcinol (5) gave C-4-
methoxycarbonylmethoxy-3-methoxyphenylcalix[4]reso-
rcinarene (6) in 88 % yield.As predicted before, the ester group
on the benzaldehyde residues was transesterified from methyl
ester to ethyl ester as the reaction was carried out in ethanol in
the presence of acid catalyst. This transformation was
confirmed by NMR analysis. With the cyclic tetramer 6 in
hand, we then prepared the calix[4]resorcinarene-chitosan
hybrid (8). The key step of the hybrid formation was the amide
bond formation between ethyl ester groups of calix[4]resor-
cinarene (6) and amine groups of chitosan 7 (Fig. 1).
): δ
3 H
-1
ppm. IR (neat, cm ): 1751 (C=O ester) and 1172 (C-O ester).
MS (EI): m/z: 108 (M ).
+
Synthesis of 4-methoxycarbonylmethoxy-3-methoxy-
benzaldehyde (4): Sodium metal (0.38 g, 16.5 mmol) was
added into 10 mL of methanol and the mixture was stirred
until the metal was dissolved. The methanolate solution was
then stirred with vanillin (3) (1.25 g, 8.2 mmol) for 15 min at
4
2
0 °C. The produced mixture was added dropwise into methyl
-chloro acetate (2) (2.67 g, 24.6 mmol). The mixture was
refluxed for 20 h. The reaction mixture was then evaporated
to give the residue, which was then dissolved in water and
was treated with 2M NaOH. The mixture was extracted with
dichloromethane. The combined organic layer was washed
with water, dried and evaporated to yield 4-methoxy-carbonyl-
methoxy-3-methoxybenzaldehyde (4) as dark yellow solid (97
1
%
yield). H NMR (400 MHz, CDCl
3
): δ = 9.90 (s, 1H), 7.50
H
(
m, 2H), 6.80 (s, 1H), 4.80 (s, 2H), 4.00 (s, 3H) and 3.7 (s,
-1
3
H). IR (KBr, νmax, cm ): 2746 and 2854 (C-H aldehyde), 1751
Based on IR analysis (Fig. 2), the formation of the hybrid
could be indicated from the peaks at 3448, 1658 and 1080
which represented secondary amine (-NH-), carbonyl amide
(C=O) and C-N groups, respectively. Further analysis using
XRD (Fig. 3) showed that 6 had higher crystallinity comparing
to 7 and 8. The crystal lattice of the hybrid 8 was similar to
that of chitosan 7. Both of them displayed the diffraction
pattern at 2θ 10.1 and 20.1 representing the monoclinic system
(
(
C=O ester), 1689 (C=O aldehyde) and 1172 (C-O ester). MS
EI): m/z: 224 (M ).
+
Synthesis of C-4-methoxycarbonylmethoxy-3-methoxy-
phenylcalix[4]resorcinarene (6): The mixture of produced
benzaldehyde (4) (1.02 g, 4.54 mmol), resorcinol (5) (0.50 g,
4
.54 mmol), conc. HCl (0.5 mL) in ethanol (10 mL) was
refluxed for 20 h. The formed solid was filtered, washed with
ethanol and dried to afford C-4-methoxycarbonylmethoxy-3-
14,18
which was the main diffraction of chitosan . The SEM analysis
(Figs. 4 and 5) for the three materials gave similar results as
the XRD analysis. It was observed that both chitosan 7 and
hybrid 8 had similar shape and morphology. The measured
particle sizes of 6,7 and 8 were 23.85, 69.50, 179.25 µm.
Furthermore, the pore diameters of 6, 7 and 8 were 0.80, 1.56
and 5.7 µm. Among the three materials, the hybrid possessed
the highest either particle size or pore diameter, indicating
that calix[4]resorcinarene inserted to the lattice of chitosan
and interacted with the amine group of chitosan (7), hence
increased the pore diameter.
methoxyphenylcalix[4]resorcinarene (6) as white solid (88 %
1
yield). H NMR (400 MHz, DMSO-d
6
): δ = 8.40 (s, 4H),
H
6
8
1
1
.30 (m, 4H), 6.20 (s, 4H), 6.10 (s, 12H), 5.40 (s, 4H), 4.50 (s,
H), 4.20 (q, 7, 1 Hz, 8H), 3.4 (s, 12H) and 1.2 (t, 7,1 Hz,
2H). C NMR (400 MHz, DMSO-D
13
6
): δ = 169.70, 152.50,
C
53.30, 148.20, 144.50, 138.10, 122.00 and 120.50 ppm. IR
-1
+
(KBr, νmax, cm ): 1612 (C=C aromatic). MS (EI): m/z: 224 (M ).
Synthesis of calix[4]resorcinarene-chitosan hybrid (8):
Calix[4]resorcinarene (6) (0.53 g, 0.40 mmol) and chitosan
(
7) (0.71 g, 4 mmol) were mixed in DMF (25 mL) and were

Vol. 27, No. 6 (2015)
Calix[4]resorcinarene-Chitosan Hybrid via Amide Bond Formation 2275
O
O
O
H
a
b
c
Cl
Cl
MeO
OH
OMe
O
O
OMe
1
2
4
HO
OH OH
HO
OH OH
HO
OH
OH
OH
HO
OH
HO HO
HO HO
d
OMe
OMe
OMe
OMe
OMe
OMe
OR1
OMe
OR2
OMe
OR
OR1
R O
2
2
O
R1O
O
NH
OEt
O
O
6
8
O
HO
OH
H
R = CH COOEt; R =CH CONH-Chitosan
1
2
2
2
HO
OMe
3
5
HOH C
2
HOH C
2
HOH C
2
O
O
O
HO
HO
O
O
OH
NH2
HO
=
HO
NH2
NH2
NH2
n
7
2 4
Fig. 1. Preparation of calix[4]resorcinarene-chitosan hybrid. Reaction condition: (a). MeOH, H SO , reflux, 5 h; (b). 3, Na, MeOH, reflux, 20 h; (c). 5, HCl,
EtOH, reflux, 20 h; (d). 7, DMF, reflux, 24 h
37.5
30.0
22.5
15.0
7.5
0
4
000 3500 3000 2500 2000 1750 1500 1250 1000 750 500
–1
Wavelength (cm )
Fig. 2. IR spectrum of calix[4]resorcinarene-chitosan hybrid
For the future works, the synthesized hybrid calix[4]-
resorcinarene-chitosan will be employed in the adsorption of
heavy metal ions such as Pb(II), Cd(II) and Cr(III).
Fig. 3. Diffractogram XRD of; (a) calix[4]resorcinarene-chitosan hybrid;
(b) calix[4]resorcinarene; and (c) chitosan

2
276 Jumina et al.
Asian J. Chem.
(
a)
(b)
(c)
Fig. 4. SEM image 100x scale of: (a) calix[4]resorcinarene-chitosan hybrid; (b) calix[4]resorcinarene; and (c) chitosan
(
a)
(b)
(c)
Fig. 5. SEM image 5,000x scale of: (a) calix[4]resorcinarene-chitosan hybrid; (b) calix[4]resorcinarene; and (c) chitosan
3
4
.
.
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Conclusion
Another example of calix[4]resorcinarene 6 has been
simply prepared from ester group-functionalized-vanillin 4 and
resorcinol 5 via acid-catalyzed-condensation and cyclization
reactions. The ester group installed on the benzaldehyde residue
of calix[4]resorcinarene (6) could be coupled with the amino
group of chitosan (7) to give the hybrid of calix[4]-resorcinarene-
chitosan (8). The IR, XRD and SEM analyses of the hybrid
revealed that the physical properties of the hybrid were similar
to chitosan.
5
6
.
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7
.
8
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ACKNOWLEDGEMENTS
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tion and Culture, Republic of Indonesia who has provided
financial support for the implementation of this research
through International Collaboration and International
Publication Grant Program budget year 2013-2014.
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