Efficient synthesis of copillar[5]arenes and their host-guest properties with dibromoalkanes

Article abstract of DOI:10.1039/c1ob05871a

An efficient method for the synthesis of copillar[5]arenes was developed with FeCl₃ as catalyst and different 1,4-dialkoxybenzenes and paraformaldehyde as reactants (yields: 50-85%). The host-guest property of (co)pillar[5]arenes and terminal dibromoalkanes was investigated by ¹H NMR measurements and an X-ray study. The complexation behavior of the copillar[5]arenes can be tuned by changing the substituents on the host. A complete complexation selectivity was found between pillar[5]- and pillar[6]arenes, which is an interesting aspect for sensor techniques.

Full text of DOI:10.1039/c1ob05871a

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PAPER
Efficient synthesis of copillar[5]arenes and their host–guest properties with
dibromoalkanes†
Luzhi Liu,a Derong Cao,*a,b Yi Jin,a Hongqi Tao,a Yuhui Koua and Herbert Meier*c
Received 1st June 2011, Accepted 12th July 2011
DOI: 10.1039/c1ob05871a
An efficient method for the synthesis of copillar[5]arenes was developed with FeCl3 as catalyst and
different 1,4-dialkoxybenzenes and paraformaldehyde as reactants (yields: 50–85%). The host–guest
property of (co)pillar[5]arenes and terminal dibromoalkanes was investigated by 1H NMR
measurements and an X-ray study. The complexation behavior of the copillar[5]arenes can be tuned by
changing the substituents on the host. A complete complexation selectivity was found between pillar[5]-
and pillar[6]arenes, which is an interesting aspect for sensor techniques.
a monofunctionalized copillar[5]arene containing a bromoalkyl
chain by condensation of 1-(2-bromoethoxy)-4-methoxybenzene
Introduction
Pillar[n]arenes,1–18 a new class of macrocyclic hosts, are attracting
considerable attention because of their applications in host-
guest chemistry,1,5–7 self-assembly chemistry8,11,12 and fluorescence
and 1,4-dimethoxybenzene in the presence of BF3·O(C2H5)2.
Recently, Huang et al.12 synthesized a copillar[5]arene bearing
an octyl group by the same way in a yield of 9% and studied the
chemistry. As electron donors with the character of hydroquinone
formation of linear supramolecular polymers. However, syntheses
derivatives, pillararenes have shown very interesting host-guest
of copillar[5]arenes meet two problems: low yields and separation
binding properties and three types of structures (Scheme 1) were
difficulties. In fact, many different types of copillar[5]arenes can
reported. In contrast to the fully symmetrical pillar[5]arenes
be expected as reaction products of two different hydroquinone
(structure type I) and the unsymmetrical pillar[5]arenes (struc-
derivatives (Scheme 2). Therefore, it is very important to develop
ture type P), copillar[5]arenes (structure type III) have some
advantages. Firstly, they can easier be selectively functionalized
a new method for the synthesis of copillar[5]arenes with high
selectivity and high yield.
to synthesize various other copillar[5]arenes. Secondly, they can
bear substituents, which are suitable for self-complexation. Thus,
the copillar[5]arenes obtained considerable attention.
Scheme 1 Three types of pillar[5]arenes.
Huang and coworkers prepared copillar[5]arenes by the co-
oligomerization of two different monomers with [BF3·O(C2H5)2]
as catalyst in a yield of 9%–27%.9 Stoddart et al.13 synthesized
aSchool of Chemistry and Chemical Engineering, South China University
Scheme 2 Formation of pillar[5]arenes and copillar[5]arenes by the
reaction of two different hydroquinone derivatives.
of Technology, Guangzhou, 510640, China. E-mail: drcao@scut.edu.cn;
Fax: +86-20-87110245; Tel: +86-20-87110245
bState Key Laboratory of Luminescent Materials and Devices, South China
Pillararenes serve as an important class of hosts for a variety
of guest molecules including electron accepting molecules such as
viologen, pyridinium salts, acetonitrile, amines and alkanes.4,7,9,13
Among the various guest molecules, alkanes have been employed
as model molecules to study the influence of host-guest self-
assembled structures.19 However, until now, the host-guest binding
University of Technology, Guangzhou, 510640, China
cInstitute fu¨r Organishche Chemie, Johannes Gutenberg-Universita¨t Mainz,
Duesbergweg 10-14, 55099, Mainz, Germany. E-mail: hmeier@uni-mainz.de
† Electronic supplementary information (ESI) available: Fundamental
characteristics (1H NMR and 13C NMR spectra) of the compounds (3b–i).
CCDC reference number 821446. For ESI and crystallographic data in
CIF or other electronic format see DOI: 10.1039/c1ob05871a
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properties between pillararenes and bromoalkyl chains or dibro-
moalkanes have not been studied.
Under these reaction conditions, a series of new copillar[5]arenes
3c–i were synthesized in isolated yields of 50–78% (Scheme 4).
In this paper, we develop a new method for the synthesis of
copillar[5]arenes in high yields by using FeCl3 as catalyst and
study their host-guest properties with terminal dibromoalkanes
and bromoalkyl pendants.
Results and discussion
Synthesis
Generally, there are two major ways to make fully symmetrical
pillar[5]arenes with BF3·O(C2H5)2 or p-toluenesulfonic acid as
catalyst. However, the yields of copillar[5]arenes are too low
by applying these methods (9–27%).9,12,13 We tried to synthesize
copillar[5]arenes by direct co-oligomerization of different 1,4-
dialkoxybenzenes. After screening a variety of catalysts, sol-
vents and mixture ratios of the related 1,4-dialkoxybenzenes,
we found that FeCl3 in CH2Cl2 as solvent is an excellent
catalyst. Scheme 3 shows the product formation of the re-
action of paraformaldehyde,1,4-dimethoxybenzene (1) and 1-
(6-bromohexyloxy)-4-methoxybenzene (2b). A 4/1 mixture of
equally reactive compounds 1 and 2b should give the product
distribution 3a:3b:4b = 45:5 ¥ 44:10 ¥ 43 (Bernoulli chain) and a
small amount of products which contain 3, 4 or 5 components 2b.
This corresponds for example to a distribution: 24% 3a, 30% 3b,
15% 4b. The obtained absolute yields are very close to this ratio
(Table 1). A 16/1 ratio of 1 and 2b enhanced the yield of 3b to 85%.
Scheme 4 Preparation of copillar[5]arenes by oligomerization of different
1,4-dialkoxybenzenes.
Host-guest properties
1
In the H NMR spectrum of 3b in CDCl3, the protons signals
(-2.0–2.5 ppm) of the bromoalkyl group are shifted significantly
to high field (accompanied with line broadening) in comparison to
6-bromohexanol. This phenomenon indicates that alkyl bromides
could complex with pillar[5]arenes. To confirm this hypothesis,
we studied the 1H NMR spectra of the mixtures of 3a with
different terminal dibromoalkanes and found that protons of the
alkyl chains showed analogous up-field shifts. For example, in
the complex of 3a with 1,6-dibromohexane (DBH), the protons
of DBH showed strong up-field shifts (Dd = 0.93, 1.41 and
2.65 ppm for peak H1, H2 and H3, respectively) (Fig. 1). The Dd
values are much larger than those of the complexes with viologen
Scheme 3 Optimization of reaction conditions by varying the mixture
ratio of 1 and 2b.
Fig. 1 The 1H NMR spectra (400 MHz, CDCl3, 298 K) of (a) DBH, (b)
3a, and (c) an equimolar mixture of 3a and DBH (18.8 mM).
Table 1 Optimization of reaction conditions
Entry
Molar Ratio (1/2b)
Yielda (3a)
Yieldb (3b)
Yieldb (4b)
Molar Ratio (3b/4b)
1
2
3
4/1
8/1
16/1
24%
47%
59%
27%
64%
85%
11%
7%
None
5/1
18.6/1
—
a Isolated yields, calculated based on the feed amount of compound 1. b Isolated yields, calculated based on the feed amount of compound 2b.
7008 | Org. Biomol. Chem., 2011, 9, 7007–7010
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or pyridinium salts.10 Fig. 2 shows the crystal structure of 3a
in whose cavity a 1,6-dibromohexane is symmetrically threaded.
There are two interesting interactions for the inclusion of 1,6-
dibromohexane, documented by the short distances O . . . H2CBr
and CH2 . . . p cloud (benzene).
1
Fig. 3 The H NMR spectra (CDCl3) of (a) DBH, (b) BEOP6, and (c)
an equimolar mixture of BEOP6 and DBH (18.8 mM).
1H NMR spectroscopy. A crystal structure analysis proved that
the dibromoalkane is symmetrically threaded in the pillar[5]arene
cavity. 6-Bromohexyl pendants on the copillar[5]arene lead to
a self-complexation. The cavity of pillar[6]arene is too large
and therefore not suitable to complex dibromoalkanes. Such a
complete selectivity has a highly interesting aspect for sensor
techniques. Furthermore, the bromoalkyl pendants opens the door
to many functionalized hosts and their supramolecular chemistry.
Fig. 2 The host-guest system of 3a and DBH: (a) view from above, (b)
view from the side.
Some 1 : 1 complexes are so strong that they can be observed in
the ESI-MS. For 3f-DBB the cation [3f-DBB-NH3-K]+ with m/z
= 1061.8 could be found.
Based on these results, we can say pillar[5]arenes such as 3a
have excellent host-guest properties. To examine the influence of
pendants on the binding interaction, we studied the complexation
of 1,4-dibromobutane (DBB) and the (co)pillar[5]arenes 3a, 3b,
3d–3h. Table 2 shows the chemical shifts of DBB in CDCl3 and
its changes Dd in the presence of approximately 1 equiv of the
different hosts. According to the size of the Dd values, the binding
interactions of 3a, 3b, 3f and 3h are high, whereas they are low for
3d, 3e and 3g. Further experiments have to clarify this effect of
different side chains.
In order to investigate the binding selectivity of dibromoalkanes
to different hosts, we also examined the interaction of DBH with
1,4-bis(ethoxy)pillar[6]arene (BEOP6).2 The results show that no
complexation between BEOP6 and DBH in CDCl3 occurs. Fig. 3
shows the 1H NMR spectrum of an equimolar solution of BEOP6
and DBH and the spectra of the corresponding compounds. The
Experimental section
Reagents and instruments
Pillar[5]arene 3a and 1,4-bis(ethoxy)pillar[6]arene were synthe-
sized according to the literature procedure.2 Solvents were either
employed as purchased or dried according to procedures described
in the literatures. 1H NMR (400 MHz) and 13C NMR (100 MHz)
spectra were recorded with a Bruker DRX 400 spectrometer by
using CDCl3 as solvent and TMS as an internal standard. Matrix-
assisted laser desorption ionization time-of-flight (MALDI-TOF)
mass measurements were performed with an Autoflex III smart-
beam spectrometer. Thin layer chromatography was performed
by using commercial Merck silica gel plates (GF254), and
visualization was carried out at 254 nm.
˚
distance of the cavity of BEOP6 is too large: 9.5 0.5 A in
comparison to 8.1 A for pillar[5]arenes.
4
˚
General procedure for the preparation of copillar[5]arenes
To a solution of 1 (0.55 g, 4.0 mmol) and 2 (0.25 mmol) in CH2Cl2
(80 mL), paraformaldehyde (0.36 g, 12 mmol) was added in a
nitrogen atmosphere. Then, anhydrous ferric chloride (103.25 mg,
0.64 mmol) was added to the solution and the mixture was stirred
at 25–30 ◦C. After the completion of the reaction, water (63 mL)
was added and the product was extracted with CH2Cl2 (3 ¥ 20
mL). The combined organic phase was dried over with anhydrous
Na2SO4. The crude mixture was chromatographed over silica gel
column using a mixture of ethyl acetate and petroleum ether.
Copillar[5]arene 3b: colorless crystals, in 85% yield (191 mg),
m.p. 202–203 C. H NMR (400 MHz, CDCl3, ppm) d 6.84–
7.11 (m, 10H), 3.70–3.91 (m, 40H), 1.56 (m, 1H), 1.24–1.35 (d,
2H), 0.31–1.14 (m, 2H), (-0.34)–0.30 (m, 2H), (-1.73)–(-0.50) (m,
2H); 13C NMR (100 MHz, CDCl3, ppm) d 151.11, 150.71, 150.38,
150.31, 150.20, 150.15, 149.53, 128.18, 128.11, 127.95, 127.74,
115.62, 115.58, 114.25, 114.04, 113.28, 113.00, 112.96, 112.88,
112.76, 68.89, 57.06, 56.47, 55.31, 55.28, 55.18, 55.14, 33.06, 30.67,
30.44, 29.64, 29.19, 29.13, 28.92, 27.69, 23.99. MS (MALDI-TOF)
Conclusion
In summary, an efficient method for the synthesis of
copillar[5]arenes has been developed with FeCl3 as catalyst (yields:
50–85%). Surprisingly strong host-guest interactions between the
copillar[5]arenes and dibromoalkanes were found and studied by
Table 2 Upfield shifts of 1,4-dibromobutane guest molecules ([G-DBB]
= 18.8 mM, CDCl3, 298 K) in different host-guest complexation
Compound d (H1)/ppm Dd (H1)/ppm d (H2)/ppm Dd (H2)/ppm
◦
1
DBB
3.45
1.55
1.55
3.15
3.22
1.37
3.31
2.04
0
2.04
0
2.5
3a + DBB
3b + DBB
3d + DBB
3e + DBB
3f + DBB
3g + DBB
3h + DBB
1.90
1.90
0.30
0.23
2.08
0.14
1.40
-0.46
-0.21
1.70
1.77
-0.67
1.80
2.25
0.34
0.27
2.70
0.24
3.18
-1.14
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calcd for C50H59BrO10 898.329, found 898.334 [M]+, 921.322 [M +
Na]+, 937.342 [M + K]+. Anal. Calc. for C50H59BrO10: C, 66.73; H,
6.61. Found: C, 66.80; H, 6.71.
10H), 3.78(s, 15H), 3.68–3.69(d, 23H), 1.75 (t, 4H), 1.00–1.02
(d, 6H); 13C NMR (100 MHz, CDCl3, ppm) d 150.75, 150.70,
149.95, 128.44, 128.29, 128.24, 128.14, 128.11, 114.89, 114.03,
113.97, 113.89, 69.96, 55.73, 55.68, 31.73, 31.44, 29.68, 29.59,
29.07, 23.05, 22.63, 14.15, 10.82. MS (MALDI-TOF) calcd for
C49H58O10 806.403, found 829.234 [M + Na]+, 845.209 [M + K]+.
Anal. Calc. for C49H58O10: C, 73.02; H, 7.13. Found: C, 72.93; H,
7.19.
Copillar[5]arene 3i: colorless crystals, in 63% yield (129 mg),
m.p. 147–148 ◦C. 1H NMR (400 MHz, CDCl3, ppm) d 6.82–7.01
(m, 10H), 3.68–3.80 (m, 39H), 1.38–1.75 (m, 6H), 1.12(m, 2H),
0.78–0.87(t, 3H); 13C NMR (100 MHz, CDCl3, ppm) d 150.49,
128.26, 128.17, 128.11, 115.27, 114.62, 113.58, 68.43, 55.54, 31.74,
29.72, 29.38, 26.09, 22.80, 14.37. MS (MALDI-TOF) calcd for
C50H60O10 820.419, found 820.443 [M]+, 843.432 [M + Na]+. Anal.
Calc. for C50H60O10: C, 73.15; H, 7.37. Found: C, 73.11; H, 7.48.
Copillar[5]arene 3c: colorless crystals, in 78% yield (170 mg),
◦
1
m.p. 161–162 C. H NMR (400 MHz, CDCl3, ppm) d 6.77 (s,
10H), 3.77 (s, 10H), 3.65 (s, 29H), 3.40 (s, 2H), 0.88–0.99 (m,
4H); 13C NMR (100 MHz, CDCl3, ppm) d 150.86, 150.82, 150.80,
150.77, 150.71, 150.67, 149.91, 128.33, 128.30, 128.24, 128.22,
128.15, 114.83, 114.37, 114.11, 114.04, 114.00, 113.84, 113.77,
67.45, 56.07, 55.95, 55.79, 55.77, 55.76, 55.71, 33.24, 29.78, 29.72,
29.69, 29.60, 29.38, 28.97, 28.36. MS (MALDI-TOF) calcd for
C48H55BrO10 870.298, found 870.080 [M]+, 893.117 [M + Na]+.
Anal. Calc. for C48H55BrO10: C, 66.13; H, 6.36. Found: C, 66.21;
H, 6.30.
Copillar[5]arene 3d: colorless crystals, in 50% yield (97 mg),
◦
1
m.p. 129–130 C. H NMR (400 MHz, CDCl3, ppm) d 6.80–
6.83 (m, 10H), 3.76–3.82 (m, 13H), 3.68–3.69 (d, 24H), 3.43 (s,
2H), 1.75–1.83 (dd, 2H), 1.01–1.05 (t, 3H); 13C NMR (100 MHz,
CDCl3, ppm) d 150.65, 150.61, 150.50, 149.95, 128.48, 128.45,
128.36, 128.32, 128.26, 128.23, 114.59, 113.78, 69.94, 55.73, 55.69,
55.68, 52.37, 29.56, 29.53, 29.47, 29.43, 29.35, 23.15, 10.91. MS
(MALDI-TOF) calcd for C47H54O10 778.372, found 778.524 [M]+,
801.517 [M + Na]+. Anal. Calc. for C47H54O10: C, 72.47; H, 6.99.
Found: C, 72.41; H, 6.93.
Acknowledgements
We are grateful to the National Natural Science Foundation of
China (20872038, 21072064) and the Natural Science Foundation
of Guangdong Province, China (10351064101000000) for the
financial support.
Copillar[5]arene 3e: colorless crystals, in 54% yield (105 mg),
Notes and references
◦
1
m.p. 101–103 C. H NMR (400 MHz, CDCl3, ppm) d 6.51–
6.75 (m, 10H), 4.12–4.18 (m, 1H), 3.67–3.70 (m, 11H), 3.58–3.63
(m, 23H), 3.54 (s, 3H), 0.90–0.91 (d, 6H); 13C NMR (100 MHz,
CDCl3, ppm) d 150.77, 150.73, 150.71, 150.70, 150.64, 150.32,
148.54, 128.47, 128.40, 128.30, 128.26, 128.24, 128.21, 115.88,
114.21, 114.05, 114.04, 113.93, 113.89, 113.73, 114.69, 113.66,
69.33, 55.80, 55.72, 55.66, 52.52, 30.14, 29.64, 29.59, 29.48, 29.45,
21.81. MS (MALDI-TOF) calcd for C47H54O10 778.372, found
778.530 [M]+, 801.523 [M + Na]+. Anal. Calc. For C47H54O10: C,
72.47; H, 6.99. Found: C, 72.44; H, 6.89.
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Copillar[5]arene 3f: colorless crystals, in 62% yield (127 mg),
m.p. 139–140 ◦C. 1H NMR (400 MHz, CDCl3, ppm) d 6.77–6.80
(m, 10H), 3.82–3.86 (t, 2H), 3.77–3.79 (m, 10H), 3.66 (s, 27H),
1.71–1.77(m, 2H), 1.48–1.53(m, 2H), 0.93–0.97 (t, 3H); 13C NMR
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128.24, 128.19, 128.15, 128.13, 114.11, 68.11, 55.72, 55.71, 55.64,
31.80, 29.63, 19.50, 13.97. MS (MALDI-TOF) calcd for C48H56O10
792.387, found 792.402 [M]+, 815.395 [M + Na]+. Anal. Calc. for
C48H56O10: C, 72.70; H, 7.12. Found: C, 72.64; H, 7.05.
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Copillar[5]arene 3g: colorless crystals, in 71% yield (186 mg),
◦
1
m.p. 191–192 C. H NMR (400 MHz, CDCl3, ppm) d 6.90–
7.99 (m, 10H), 3.78–3.90 (m, 39H), 0.86–1.71 (m, 18H), -1.21(s,
1H); 13C NMR (100 MHz, CDCl3, ppm) d 150.67, 150.65, 150.47,
150.22, 150.18, 149.62, 128.83, 128.13, 128.09, 128.06, 127.82,
114.07, 113.66, 113.08, 112.88, 68.27, 55.91, 55.29, 55.22, 33.49,
30.10, 29.74, 29.30, 29.10, 27.85, 24.65. MS (MALDI-TOF) calcd
for C55H68Br2O10 1046.318, found 1046.538 [M]+, 1069.551 [M +
Na]+.. Anal. Calc. for C55H68Br2O10: C, 62.98; H, 6.53. Found: C,
62.90; H, 6.63.
Copillar[5]arene 3h: colorless crystals, in 52% yield (105 mg),
19 D. Wang, L.-J. Wan and C.-L. Bai, Mater. Sci. Eng., R, 2010, 70, 169–
187.
◦
1
m.p. 94–95 C. H NMR (400 MHz, CDCl3, ppm) d 6.802 (s,
7010 | Org. Biomol. Chem., 2011, 9, 7007–7010
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