Synthesis, structures, and conformational characteristics of triptycene-derived calix[5]arenes

Article abstract of DOI:10.1021/ol902758g

[Chemical equation presented] A series of novel calix[5]arenes 5 containing one 1,8-dimethoxytriptycene moiety were synthesized through an efficient fragment coupling strategy. The subsequent demethylatlon of 5 with BBr ³ In dry dichloromethane gave the callx[5]arenes 6. Debutylatlon of both 5a～b and 6a～b with AlCl₃ resulted in the same products 7a～7b. The structural studies revealed that all of the macrocyclic compounds have well-defined structures with fixed cone conformations in both solution and solid state. Moreover, it was also found that the triptycene-derived calix[5]arenes could encapsulate small neutral molecules In the solid state.

Full text of DOI:10.1021/ol902758g

ORGANIC
LETTERS
2010
Vol. 12, No. 3
524-527
Synthesis, Structures, and
Conformational Characteristics of
Triptycene-Derived Calix[5]arenes
Xiao-Hong Tian†,‡ and Chuan-Feng Chen*,†
Beijing National Laboratory for Molecular Sciences, CAS Key Laboratory of
Molecular Recognition and Function, Institute of Chemistry, Chinese Academy of
Sciences, Beijing 100190, China, and Graduate School, Chinese Academy of Sciences,
Beijing 100049, China
cchen@iccas.ac.cn
Received November 30, 2009
ABSTRACT
A series of novel calix[5]arenes 5 containing one 1,8-dimethoxytriptycene moiety were synthesized through an efficient fragment coupling
strategy. The subsequent demethylation of 5 with BBr3 in dry dichloromethane gave the calix[5]arenes 6. Debutylation of both 5a∼b and 6a∼b
with AlCl3 resulted in the same products 7a∼7b. The structural studies revealed that all of the macrocyclic compounds have well-defined
structures with fixed cone conformations in both solution and solid state. Moreover, it was also found that the triptycene-derived calix[5]arenes
could encapsulate small neutral molecules in the solid state.
Design and synthesis of a new class of hollow host
compounds with the interior cavities large enough to
encapsulate organic guests is always an interesting and
exciting research topic in supramolecular chemistry. Among
various types of known macrocyclic molecules, calixarenes1,2
as a class of well-defined phenol-derived cyclic oligomers
bridged by methylene groups have been the focus of
considerable attention in the last two decades. However,
compared with other hollow hosts such as cyclodextrins,
cyclotriveratrylenes, or resorcinarenes, the calixarenes exhibit
a higher degree of conformational mobility. Although in the
family of calixarenes the calix[4]arenes have been most
extensively studied owing to their readily available and easy
chemical modification on either smaller (lower) or larger
(upper) rims,1,3 they have cavities too small to complex with
ordinary organic guests. Comparatively, the calix[5]arenes
are more sizable and appropriate for the inclusion of organic
(2) Some recent examples, see: (a) Sameni, S.; Jeunesse, C.; Matta, D.;
Harrowfield, J. Chem. Soc. ReV. 2009, 38, 2117. (b) Li, G.-K.; Xu, Z.-X.;
Chen, C.-F.; Huang, Z.-T. Chem. Commun. 2008, 1774. (c) Xu, Z.-X.;
Zhang, C.; Yang, Y.; Chen, C.-F.; Huang, Z.-T. Org. Lett. 2008, 10, 477.
(d) Kogan, K.; Biali, S. E. J. Org. Chem. 2009, 74, 7172. (e) Zorzi, R.;
Guidolin, N.; Randaccio, L.; Purrello, R.; Geremia, S. J. Am. Chem. Soc.
2009, 131, 2487. (f) Mendoza-Espinosa, D.; Hanna, T. A. Inorg. Chem.
2009, 48, 10312. (g) Mendoza-Espinosa, D.; Hanna, T. A. Inorg. Chem.
2009, 48, 7452.
† Institute of Chemistry.
‡ Graduate School.
(1) (a) Calixarenes 2001; Asfari, Z., Bo¨hmer, V., Harrowfield, J., Vicens,
J., Eds.; Kluwer, Academic Publishers: Dordrecht, Holland, 2001; (b)
Gutsche, C. D. Calixarenes ReVisited Monographs in Supramolecular
Chemistry; Stoddart, J. F., Ed.; Royal Society of Chemistry: Cambridge,
1998
.
10.1021/ol902758g  2010 American Chemical Society
Published on Web 01/12/2010

guests.4 However, the development of calix[5]arenes has
lagged behind due to the synthetic elusiveness and increasing
mobility in comparison with their tetramer analogues.5
Scheme 1. Synthesis of the Trimers 3a,b
p-toluenesulfonic acid, the 1 + 2 product 3a was obtained
in 89% yield. Similarly, the trimer 3b was also synthesized
by the reaction of 1 with the p-phenylphenol in 83% yield
(Scheme 1). With the trimers 3 in hand, we first tested the
synthesis of the triptycene-derived calix[5]arenes 5 by the
heat-induced fragement coupling reactions. Consequently,
when the trimer 3a reacted with the 2,6-dihydroxymethyl-
4-tert-butylphenolinrefluxedxylenefortwodays,calix[5]arene
5a could be produced in 25% yield. Under the same
conditions, the triptycene-derived calix[5]arenes 5b and 5c
were obtained in 23% and 21% yield, respectively (Scheme
2). Furthermore, it was found that when 5a-c were treated
with BBr3 in dry CH2Cl2 the demethylated compounds 6a-c
could be obtained in high yields. Treatment of 6a and 6b
with AlCl3 in toluene at room temperature resulted in the
debutylated products 7a and 7b in 82% and 75% yield,
respectively. Under the same conditions, we also found that
the macrocycles 5a and 5b could be not only debutylated
but also demethylated to yield 7a and 7b in high yields,
respectively (Scheme 2).
Figure 1. Structures of calix[4]arenes (left), triptycene-derived
calix[5]arenes (middle), and calix[5]arenes (right).
Recently, we6 have proven that the triptycenes with unique
3D rigid structure could be used as useful building blocks
for the synthesis of different kinds of novel macrocyclic hosts
with specific structures and properties. Thus, we envisioned
that if a suitable triptycene moiety with the 3D rigid structure
took the place of one or more phenol group(s) in the
calix[4]arenes a new class of calixarenes with large cavities
and fixed conformations could thus be obtained. As a result,
we7 recently reported a couple of novel triptycene-derived
calix[6]arenes with fixed conformations. Herein, we report
the synthesis of a series of novel calix[5]arenes 5a-c
containing one 1,8-dimethoxytriptycene moiety and their
demethylated and debutylated derivatives (Figure 1). The
structural studies show that owing to the 3D rigid structure
of the triptycene moiety the triptycene-derived calix[5]arenes
all exhibit the fixed cone conformations in both solution and
solid state. Moreover, it is found that the calix[5]arenes can
also encapsulate the small neutral molecules inside their
cavities in the solid state.
Scheme 2. Synthesis of the Triptycene-Derived Calix[5]arenes
1,8-Dimethoxy-2,7-dihydroxymethyltriptycene 1 was pre-
pared according to our previously reported method.7 When
we treated compound 1 with excess p-tert-butylphenol 2 in
refluxed toluene in the presence of a catalytic amount of
(3) (a) Ikeda, A.; Shinkai, S. Chem. ReV. 1997, 97, 1713. (b) Shimizu,
S.; Moriyama, A.; Kito, K.; Sasaki, Y. J. Org. Chem. 2003, 68, 2187. (c)
Lhota´k, P.; B´ıla´, A.; Budka, J.; Pojarova´b, M.; Stibor, I. Chem. Commun.
2008, 1662.
(4) (a) Gargiulli, C.; Gattuso, G.; Liotta, C.; Notti, A.; Parisi, M. F.;
Pisagatti, I.; Pappalardo, S. J. Org. Chem. 2009, 74, 4350. (b) Garozzo,
D.; Gattuso, G.; Notti, A.; Pappalardo, A.; Pappalardo, S.; Parisi, M. F.;
Perez, M.; Pisagatti, I. Angew. Chem., Int. Ed. 2005, 44, 4892. (c) Haino,
T.; Yanase, M.; Fukunaga, C.; Fukazawa, Y. Tetrahedron 2006, 62, 2025.
(d) Makha, M.; McKinnon, J. J.; Sobolev, A. N.; Spackman, M. A.; Raston,
C. L. Chem.sEur. J. 2007, 13, 3907.
(5) (a) Gutsche, C. D.; Bauer, L. J. J. Am. Chem. Soc. 1985, 107, 6052.
(b) Markowitz, M. A.; Janout, V.; Castner, D. G.; Regen, S. L. J. Am. Chem.
Soc. 1989, 111, 8192. (c) Stewart, D. R.; Krawiec, M.; Kashyap, R. P.;
Watson, W. H.; Gutsche, C. D. J. Am. Chem. Soc. 1995, 117, 586. (d)
Arnaud-Neu, F.; Asfari, Z.; Souley, B.; Vicens, J.; Thue´ry, P.; Nierlich,
M. J. Chem. Soc., Perkin Trans. 2 2000, 495.
(6) (a) Zhu, X.-Z.; Chen, C.-F. J. Am. Chem. Soc. 2005, 127, 13158.
(b) Zong, Q.-S.; Chen, C.-F. Org. Lett. 2006, 8, 211. (c) Han, T.; Chen,
C.-F. Org. Lett. 2006, 8, 1069. (d) Peng, X.-X.; Lu, H.-Y.; Han, T.; Chen,
C.-F. Org. Lett. 2007, 9, 895. (e) Xue, M.; Chen, C.-F. Chem. Commun.
2008, 6128. (f) Xue, M.; Chen, C.-F. Org. Lett. 2009, 11, 5294.
(7) Tian, X.-H.; Hao, X.; Liang, T.-L.; Chen, C.-F. Chem. Commun.
2009, 6771.
We first investigated the structures of the triptycene-
1
derived calix[5]arenes 5a-c in solution by H NMR spec-
troscopy. As shown in Figure 2a, the 1H NMR spectrum of
Org. Lett., Vol. 12, No. 3, 2010
525

their p-tert-butylcalix[5]arene analogue, in which the signal
of the bridged methylene protons showed a broad singlet at
room temperature and a pair of doublets at lower
temperature.5a,c For the debutylated macrocycles 7a (Figure
1
2c) and 7b, their H NMR and 13C NMR spectral features
for the bridged methylene protons are quite similar to those
of their precursors 5 and 6, indicating that 7a and 7b have
likewise fixed cone conformations. These cases are also in
contrast to their debutylated calix[5]arene analogue, which
showed an even more flexible conformation arising from lack
of steric hindrance.9
1
Figure 2. Partial H NMR spectra (300 MHz, CDCl3) of (a) 5a,
(b) 6a, and (c) 7a.
5a in CDCl3 showed two singlets (2:1 ratio) at 1.18 and 1.29
ppm, respectively, for the p-tert-butyl groups, one singlet at
3.97 ppm for the methoxyl groups, and two singlets at 5.29
and 6.01 ppm for the bridgehead protons of the triptycene
moiety. Especially, two pairs of doublets at 3.30, 3.48, 3.99,
and 4.47 ppm for the bridged methylene protons in 5a were
observed, which are quite similar to those of the p-tert-
butylcalix[4]arene with a cone conformation.1b Moreover,
it was found that the 13C NMR spectrum of 5a showed only
two signals for the p-tert-butyl carbons, one signal for the
methoxyl carbons, two signals for the methylene carbons,
and two signals for the bridgehead carbons in the triptycene
moiety. The NOE contacts between the bridged methylene
protons and the aromatic and hydroxyl protons in 5a were
also observed.8 In addition, we further found that the IR
spectrum of 5a showed low stretching frequency of the OH
bonds (ca. 3303 cm-1)8 similar to that of the p-tert-
butylcalix[4]arene with cone conformation,5b indicating that
there existed the strong intramolecular hydrogen bonding in
5a. In the case of the macrocycles 5b,c, they also showed
the spectral features similar to those of 5a.8 These indicated
that the triptycene-derived calix[5]arenes 5a-c containing
two dimethoxy groups not only have Cs symmetric structures
but also adopt a fixed cone conformation in solution. These
results are obviously different from their p-tert-
butylcalix[5]arene analogue with two adjacent methoxyl
groups, which showed a highly flexible conformation with
the coalescence temperature of -31 °C corresponding to an
inversion barrier of 11.1 kcal mol-1.5c
Figure 3.
Variable-temperature 1H NMR spectra of 5a in DMSO-
d6 at 300 MHz.
To further investigate the conformational mobility, the
variable-temperature 1H NMR experiments of 5a in DMSO-
d6 were also carried out. As shown in Figure 3, it was found
that no obvious changes of the methylene proton signals in
5a were observed with the increase of the temperature, which
not only is in accord with its fixed conformation but also
indicates that the conformational inversion barrier of 5a is
considerably high. Moreover, it was also found that the
1
variable-temperature H NMR experiments of 6a and 7a
showed the results similar to those of 5a. Therefore, it could
be concluded that the significant contributor in determining
the conformational mobility of the triptycene-derived
calix[5]arenes is not due to the intramolecular hydrogen
bonds and the bulky tert-butyl groups in the para position
of phenol groups but mainly attributed to the introduction
of the triptycene moiety with the 3D rigid structure.
Similarly, the 1H NMR spectra of the demethylated
compounds 6a (Figure 2b) and 6b in CDCl3 also showed
two pairs of doublets for the bridged methylene protons.
Meanwhile, two signals for the methylene carbons were
found in their 13C NMR spectra. These indicated that 6a and
6b have the same fixed cone conformation as their precursors
We further obtained the single crystals of 5a10 and 6a11
suitable for X-ray crystallography from a CH2Cl2/CH3OH
1
5. Because 6c is insoluble in CDCl3, its H NMR and 13C
(9) Harada, T.; Shinkai, S. J. Chem. Soc., Perkin Trans. 2 1995, 2231.
(10) Crystal data for 5a·1.5CH2Cl2: C57.50H63Cl2.5O5, M ) 922.70,
triclinic, space group P-1, a ) 11.632 (2) Å, b ) 11.974 (2) Å, c ) 20.206
(4) Å, R ) 86.16 (3)°, ꢀ ) 87.59 (3)°, γ ) 64.59 (3)°, V ) 2536.3 (9) Å3,
Z ) 2, T ) 113(2) K, 17 139 reflections measured, 8841 independent, 5617
used. R1 ) 0.0760, wR2 ) 0.2129 (I > 2σ(I)); R1 ) 0.1117, wR2 ) 0.2410
for all data.
NMR spectra were carried out in acetone-d6,8 and the results
were also consistent with its fixed cone conformation. These
triptycene-derived calix[5]arenes are obviously different from
(8) See Supporting Information for details.
526
Org. Lett., Vol. 12, No. 3, 2010

made 5a able to easily encapsulate guests inside its cavity.
Consequently, it was found that 5a could encapsulate a
CH2Cl2 molecule through a pair of C-H···π interactions
(dC-H···π ) 2.898 and 2.895 Å) between the protons of CH2Cl2
and the phenol rings (Figure 4b). For the macrocycles 6a
and 5c, it was found that they showed similar structural
features to those of 5a. The dihedral angles between the
coplanar of the four bridged methylene carbons and the
phenol ring opposite to the triptycene moiety are 43.4° and
32.6°, respectively. The cavity cross sections of 7.35 ×
10.96 Å (upper rim) and 6.64 × 7.18 Å (low rim) for 6a
and 8.12 × 11.08 Å (upper rim) and 6.57 × 7.23 Å (low
rim) for 5c were shown. Moreover, there existed intramo-
lecular hydrogen bondings between the adjacent phenol
hydroxyl groups or between the ether oxygen atoms and their
adjacent phenol hydroxyl protons, which might play an
important role in the formation of their fixed cone conforma-
tions. Furthermore, it was also found that a dichloromethane
molecule was encapsulated inside the cavity of 6a (Figure
4d), while in 5c a methanol molecule was encapsulated inside
its cavity (Figure 4f).
In conclusion, we have synthesized a series of novel
calix[5]arenes containing one 1,8-dimethoxytriptycene moi-
ety through an efficient fragment coupling strategy and also
conveniently obtained their demethylated and debutylated
calix[5]arene derivatives in high yields. The structural studies
showed that owing to the introduction of the 3D rigid
structure of triptycene, the triptycene-derived calix[5]arenes
all adopted fixed cone conformations in solution and solid
state, which are in contrast to their classical calix[5]arene
analogues. Moreover, it was also found that the triptycene-
derived calix[5]arenes with fixed cone conformations and
large enough cavities could encapsulate dichloromethane and
methanol molecules inside their cavities in the solid state.
We believe that the results presented here could have wide
potential applications in molecular recognitions and as-
semblies, which are now underway in our laboratory.
Figure 4. Crystal structures. (a) Top view of 5a and (b) side view
of 5a@CH2Cl2; (c) top view of 6a and (d) side view of 6a@CH2Cl2;
(e) top view of 5c and (f) side view of 5c@CH3OH. Other solvent
molecules and hydrogen atoms not involved in the hydrogen
bonding interactions are omitted for clarity.
solution and the single crystals of 5c12 from a CHCl3 and
CH3OH mixture solution. As shown in Figure 4, the crystal
structures of 5a, 6a, and 5c showed that they all adopted
cone conformations, which are consistent with the results in
solution. For 5a, the four bridged methylene carbons are
coplanar, and the dihedral angle between the coplanar and
the phenol ring opposite to the triptycene moiety is 36.7°.
The dihedral angle between the two face-to-face phenol
rings is 50.75°. The cavity cross-section ranges from
7.94 × 10.88 Å (upper rim) to 6.71 × 7.09 Å (low rim).
Moreover, there existed the O-H···O hydrogen bondings
between the ether oxygen atoms and their adjacent phenol
hydroxyl protons with the distances of 1.96 and 1.87 Å,
respectively, and between two adjacent phenol hydroxyl
groups with the distance of 2.16 Å. These structural features
Acknowledgment. We thank the National Natural Science
Foundation of China (20532030, 20625206, 20972162), the
Chinese Academy of Sciences, and the National Basic
Research Program (2007CB808004, 2008CB617501) of
China for financial support.
(11) Crystal data for 6a·CH2Cl2·2CH3OH: C57H66Cl2O7, M ) 934.00,
triclinic, space group P-1, a ) 11.303 (2) Å, b ) 12.251 (3) Å, c ) 21.395
(4) Å, R ) 75.70 (3)°, ꢀ ) 79.57 (3)°, γ ) 62.73 (3)°, V ) 2543.8 (9) Å3,
Z ) 2, T ) 113(2) K, 18 944 reflections measured, 8932 independent, 6408
used. R1 ) 0.0780, wR2 ) 0.2334 (I > 2σ(I)); R1 ) 0.1040, wR2 ) 0.2564
for all data.
(12) Crystal data for 5c·2CHCl3·CH3OH: C65H54Cl6O6, M ) 1143.78,
monoclinic, space group P2(1)/c, a ) 13.746 (3) Å, b ) 16.676 (3) Å, c )
24.705 (5) Å, ꢀ ) 90.44 (3)°, V ) 5662.7 (19) Å3, Z ) 4, T ) 173(2) K,
33 309 reflections measured, 9786 independent, 8768 used. R1 ) 0.1220,
wR2 ) 0.2673 (I > 2σ(I)); R1 ) 0.1337, wR2 ) 0.2768 for all data.
Supporting Information Available: Experimental pro-
cedures and characterization data for new compounds.
1
Variable-temperature H NMR spectra of 6a and 7a. The
X-ray crystallographic files (CIF) for compounds 5a, 6a, and
5c. This material is available free of charge via the Internet
at http://pubs.acs.org.
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