Catalytic approach for the synthesis of bis-calixarenes

Article abstract of DOI:10.1080/00397910601055040

Three new tail-to-tail linked biscalix[6]arenes joined via ether linkages have been synthesized. These bis calix[6]arenes have been characterized by 1H NMR, 13C NMR, and mass spectroscopy and elemental analysis. Copyright Taylor & Francis Group, LLC.

Full text of DOI:10.1080/00397910601055040

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Catalytic Approach for the Synthesis of
bis‐Calixarenes
Y. K. Agrawal a & S. K. Bhatt a
a Analytical Laboratory, Institute of Pharmacy and Faculty of Science, Nirma
University of Science and Technology, Ahmedabad, India
Published online: 05 Mar 2007.
To cite this article: Y. K. Agrawal & S. K. Bhatt (2007) Catalytic Approach for the Synthesis of bis‐Calixarenes,
Synthetic Communications: An International Journal for Rapid Communication of Synthetic Organic Chemistry,
37:4, 551-557, DOI: 10.1080/00397910601055040
To link to this article: http://dx.doi.org/10.1080/00397910601055040
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Synthetic Communicationsw, 37: 551–557, 2007
Copyright # Taylor & Francis Group, LLC
ISSN 0039-7911 print/1532-2432 online
DOI: 10.1080/00397910601055040
Catalytic Approach for the Synthesis
of bis-Calixarenes
Y. K. Agrawal and S. K. Bhatt
Analytical Laboratory, Institute of Pharmacy and Faculty of Science,
Nirma University of Science and Technology, Ahmedabad, India
Abstract: Three new tail-to-tail linked biscalix[6]arenes joined via ether linkages have
been synthesized. These bis calix[6]arenes have been characterized by 1H NMR,
13C NMR, and mass spectroscopy and elemental analysis.
Keywords: bis-calix[6]arenes, methyl calix[6]arenes, phase-transfer catalyst
bis-Calixarenes have attracted great interest because of their peculiar multi-
cavity structure and molecular recognition abilities. In the case of tail-to-tail
linkage, the bis-calixarenes, providing two diverging cavities, have been
used as tectons for poly-cap self-assemblies. bis-Calixarene derivatives lend
themselves well to many applications like cation complexation, anion recog-
nization, organic neutral and charged molecular recognization, redox active
ionophore, ion selective electrodes, and ditopic receptors.[1–10]
In this article we have for the first time reported the single-step synthesis
of methyl calix[6]arene (3), which was obtained by the acid-catalyzed conden-
sation of p-cresol (1) and formaldehyde (2). Methyl calix[6]arene (3) was
refluxed with bis[2-chloroethyl]ether (4) in the presence of NaOH and
phase-transfer catalyst triethyl benzyl ammonium chloride using acetone as
a solvent at 50–558C for 18 h to yield bis-calix[6]arene (5) (Fig. 1).
Received July 10, 2006
Address correspondence to Y. K. Agrawal, Analytical Laboratory, Institute of
Pharmacy and Faculty of Science, Nirma University of Science and Technology,
Ahmedabad, India. E-mail: drykagrawal@yahoo.com
551

552
Y. K. Agrawal and S. K. Bhatt
Figure 1. Synthetic scheme for compound 5.
Tetra carboxy methyl calix[6]arene (7) was obtained by refluxing methyl
calix[6]arene (3) and bromo acetic acid (6) for 24 h. Compound (7) was
refluxed with bis[2-chloroethyl]ether (4) in the presence of NaOH and
phase-transfer catalyst triethyl benzyl ammonium chloride using acetone as
a solvent at 50–558C for 15 h to yield the bis-calix[6]arene derivative,
which possesses carboxy functional groups as ligating sites (8) (Fig. 2).
The bis-calix[6]arene hydroxamic acid (10) was synthesized to explore
good metal ion receptors based on bis-calixarenes. Compound (8) was
refluxed with thionylchloride at 75–808C for 6–8 h to obtain corresponding
acid chloride (9), which was condensed with N-phenylhydroxylamine in the
presence of an aqueous suspension of sodium carbonate at 0–18C for 2 h to
form bis-calix[6]arene hydroxamic acid (10) (Fig. 3).
If the synthesis of bis-calix[6]arene derivatives was carried out without
using a phase-transfer catalyst, the reactions required a large amount of
solvents and a long time for completion (Table 1).
All new synthesized tail-to-tail linked bis-calix[6]arenes have been
1
characterized by H NMR, 13C NMR, and fast atom bombardment (FAB)
mass spectrometry and elemental analysis.

bis-Calixarenes
553
Figure 2. Synthetic scheme for compound 8.
The 1H NMR dimethylsulphoxide (DMSO) spectrum of compound 5
displayed two singletes at 6.64 and 6.77 ppm for ArH and 2.06–2.20 ppm for
CH3, and compound 8 and 10 displayed four singletes at 6.64–6.88 ppm for
ArH and 2.06–2.39 ppm for CH3. Compound 5, 8, and 10 displayed a singlet
at 8.55 ppm for OH, 3.72–3.86 ppm for Ar-CH2-Ar, and 4.65–4.81 ppm
for ArOCH2. In addition, compound 8 displayed a singlet at 9.55 ppm for
COOH, and compound 10 displayed singlet at 10.50 ppm for N-OH.
The 13C NMR (DMSO) spectrum of compound 5 displayed aromatic
carbon adsorption in the region between 128.7 and 150.7 ppm, compound 8
displayed aromatic carbon adsorption in the region between 112.0 and
153.1 ppm, and compound 10 displayed aromatic carbon adsorption in the
region between 112.0 and 153.1 ppm. In addition, compound 5 displayed a
singlet at 21.29 ppm for CH3 and 31.26 ppm for Ar-CH2-Ar; compound
8 and 10 displayed a singlet at 21.30 ppm for CH3 and 31.16 ppm for
A-CH2-Ar. In addition, compound 10 displayed a singlet at 161.5 ppm for
CO-N(OH).
In conclusion, the three different bis-calix[6]arene derivatives have been
synthesized using a phase-transfer catalyst. This methodology is a rapid
and convenient approach for the synthesis of a multicavity calixarene
framework.

554
Y. K. Agrawal and S. K. Bhatt
Figure 3. Synthetic scheme for compound 10.
Table 1. Comparison of conventional and phase transfer catalyzed
synthetic methodologies for bis-calix[6]arenes
Phase transfer catalyzed
method
Conventional method
Mp
(8C)
Reaction
time
Mp
(8C)
Reaction
time
Compounds
5
8
215–220
178–182
18 h
15 h
215–220
178–182
50 h
48 h

bis-Calixarenes
555
EXPERIMENTAL
Melting points were determined in a sealed capillary tube using a Toshniwal
1
(India) melting-point apparatus and are uncorrected. H NMR and 13C NMR
spectra were recorded on a DRX 300 spectrophotometer operating at
300 MHz in DMSO-d6 with TMS as an internal standard.
Synthesis of Compound (3)
The synthesis of methyl calix[6]arene 3 was achieved by reacting p-cresol
(23.6 ml, 0.22 M) and formaldehyde (35%, 33.0 ml, 1.10 M) in the presence
of benzene (75 ml) and concentrated HCl (23.6 ml) at reflux temperature for
8 h. The obtained product was resinous in nature. The crude product was
washed with hot distilled water. After washing, the product was passed
through column containing silica gel (60 mm size) with the use of CHCl3–
toluene (9:1 v/v) to obtained cyclic hexamer methyl calix[6]arene.
Data
Yield 90%, mp . 378C. 1H NMR (DMSO, d): 8.99 (s, 6H, OH), 6.79 (s, 12H,
ArH), 3.77 (s, 12H, ArCH2Ar), 2.16 (s, 18H, CH3).13C NMR (DMSO, d): 21.5
(s, CH3), 31.4 (s, ArCH2Ar), 115.9–150.7 (s, ArC). The FAB-MS spectra of
compound 3 showed a molecular ion peak at 743 (M þ Na)þ. Anal. calcd. for
C48H48O6: C, 79.97; H, 6.71; O, 13.32. Found: C, 79.92; H, 6.66; O, 13.30.
Synthesis of Compound (5)
With Phase-Transfer Catalyst
The bis-calix[6]arene 5 was synthesized by reacting methyl calix[6]arene
(1.0 g, 0.001 M), NaOH (0.16 g), and bis-[2-chloro ethyl] ether (1.1 ml,
0.007 M) in refluxing acetone medium for 18 h in the presence of a catalytic
amount of triethyl benzyl ammonium chloride. The resulted alkaline
solution was neutralized with 50% HCl. The colorless product was filtered
and isolated.
Without Phase-Transfer Catalyst
The bis-calix[6]arene 5 was synthesized by reacting methyl calix[6]arene
(1.0 g, 0.001 M), NaOH (0.3 g), and bis-[2-chloro ethyl] ether (2.1 ml,
0.015 M) in refluxing acetone medium for 50 h. The resulted alkaline
solution was neutralized with 50% HCl. The colorless product was filtered
and isolated.

556
Y. K. Agrawal and S. K. Bhatt
Data
Yield 43%, mp 215–2208C (decom). 1H NMR (DMSO, d): 8.55 (s, 6H, OH),
6.64–6.77 (s, 24H, ArH), 3.72–3.85 (s, 36H, ArCH2Ar and CH2OCH2),
2.06–2.20 (s, 36H, CH3), 4.65–4.81 (s, 12H, ArOCH2).13C NMR (DMSO, d):
21.29 (s, CH3), 31.26 (s, ArCH2Ar), 128.7–150.7 (s, ArC). m/z ¼ 1635
[M-CH3]þ. Anal. calcd. for C108H114O15: C, 78.52; H, 6.96; O, 14.53.
Found: C, 78.46; H, 6.94; O, 14.50.
Synthesis of Compound (8)
The tetra carboxy calix[6]arene 7 was synthesized by reacting methyl
calix[6]arene (1.0 g, 0.001 M), NaOH (0.2 g), and bromo acetic acid (2.0 g,
0.015 M) in refluxing acetone for 24 h. After completion of the reaction, the
reaction mass was kept at room temperature for 0.5 h. The reaction mixture
was filtered, and the collected product was washed with distilled water to
obtain tetracarboxy calix[6]arene as a colorless powder (mp 130–1358C).
With Phase-Transfer Catalyst
The carboxy bis-calix[6]arene 8 was synthesized by reacting tetra carboxy
methyl calix[6]arene 7 (1.0 g, 0.001 M), NaOH (0.16 g), and bis-[2-chloro
ethyl] ether (0.89 ml, 0.006 M) in the presence of a catalytic amount of
triethyl benzyl ammonium chloride in refluxing acetone for 15 h. The
resulted alkaline solution was neutralized with 50% HCl. The light brown
product was filtered and isolated.
Without Phase-Transfer Catalyst
The carboxy bis-calix[6]arene 8 was synthesized by reacting tetra carboxy
methyl calix[6]arene 7 (1.0 g, 0.001 M), NaOH (0.3 g), and bis-[2-chloro
ethyl] ether (2.1 ml, 0.015 M) in refluxing acetone medium for 48 h. The
resulted alkaline solution was neutralized with 50% HCl. The light brown
product was filtered and isolated.
Data
Yield 37%, mp 178–1828C (decom). 1H NMR (DMSO, d): 8.56 (s, 4H, OH),
9.55 (s, 2H, COOH), 6.64–6.88 (s, 24H, ArH), 3.72–3.86 (s, 36H, ArCH2Ar
and CH2OCH2), 2.06–2.39 (s, 36H, CH3), 4.66–4.81 (s, 16H, ArOCH2), 4.53
(s, 12H, CH2 CH2O CH2 CH2). 13C NMR (DMSO, d): 21.30 (s, CH3), 31.16
(s, ArCH2Ar), 112.0–153.1 (s, ArC). m/z ¼ 2114 [M]þ. Anal. calcd. for
C124H130O31: C, 70.37; H, 6.19; O, 23.44. Found: C, 70.32; H, 6.15; O, 23.41.

bis-Calixarenes
557
Synthesis of Compound (10)
A mixture of carboxy bis-calix[6]arene 8 (1.0 g, 0.0004 M) and thionyl
chloride (0.11 ml, 0.0009 M) was stirred at 75–808C for 6–8 h. The acid
chloride was condensed with freshly prepared N-phenylhydroxylamine
(0.3 g, 0.002 M) in the presence of an aqueous suspension of sodium
carbonate (1.5 g) at 0–108C for 2 h to obtain compound 10.
Data
Yield 30%, mp 225–2308C (decom). 1H NMR (DMSO, d): 8.56 (s, 4H, OH),
6.64–6.88 (s, 24H, ArH), 3.72–3.86 (s, 36H, ArCH2Ar and CH2OCH2),
2.06–2.39 (s, 36H, CH3), 4.66–4.81 (s, 16H, ArOCH2), 4.53 (s, 12H, CH2
CH2O CH2 CH2), 10.50 (s, 2H, N-OH), 7.00 (t, J ¼ 6 Hz, 2H, ArH), 7.24
(t, J ¼ 6 Hz, 4H, ArH), 7.64 (d, J ¼ 6 Hz, 4H, ArH). 13C NMR (DMSO, d):
21.30 (s, CH3), 31.16 (s, ArCH2Ar), 112.0–153.1 (s, ArC) 161.5 (s, CO).
m/z ¼ 2296 [M]þ. Anal. calcd. for C124H130O31: C, 70.37; H, 6.19; O,
23.44. Found: C, 70.32; H, 6.15; O, 23.41.
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