Hemicarceplex formation with a cyclotriveratrylene-based molecular cage allows isolation of high-purity (≥99.0%) C70 directly from fullerene extracts

Article abstract of DOI:10.1021/ol3027957

A cyclotriveratrylene-based molecular cage that favors the formation of a room temperature isolable hemicarceplex with C₇₀, in the presence of C₆₀, has been developed. Significant differences in the association and dissociation kinetics of the molecular cage and buckyballs allowed the isolation of C₇₀ in high purity (≥99.0%) from a commercial fullerene extract without the need for recrystallization or HPLC.

Full text of DOI:10.1021/ol3027957

ORGANIC
LETTERS
2012
Vol. 14, No. 24
6146–6149
Hemicarceplex Formation With a
Cyclotriveratrylene-Based Molecular Cage
Allows Isolation of High-Purity (g99.0%)
C70 Directly from Fullerene Extracts
Ming-Jhe Li,† Chi-Hao Huang,† Chien-Chen Lai,‡ and Sheng-Hsien Chiu*,†
Department of Chemistry, National Taiwan University, No. 1, Sec. 4, Roosevelt Road,
Taipei, Taiwan, 10617, R.O.C., and Institute of Molecular Biology,
National Chung Hsing University and Department of Medical Genetics,
China Medical University Hospital, Taichung, Taiwan, R.O.C.
shchiu@ntu.edu.tw
Received October 11, 2012
ABSTRACT
A cyclotriveratrylene-based molecular cage that favors the formation of a room temperature isolable hemicarceplex with C70, in the presence of
C60, has been developed. Significant differences in the association and dissociation kinetics of the molecular cage and buckyballs allowed the
isolation of C70 in high purity (g99.0%) from a commercial fullerene extract without the need for recrystallization or HPLC.
Because of their versatile configurations and attractive
properties, fullerenes, including cylindrical carbon nano-
tubes (CNTs) and spherical and spheroidal buckyballs,
have found applications in a wide range of fields.1 Ignoring
CNTs, which lack uniform diameters or lengths, the most
abundant structurally distinct species in a typical fullerene
extract are two buckyballs: C60 and C70.2 Unfortunately,
the poor solubilities of these buckyballs in organic solvents
seriously complicate their isolation, purification, and prac-
tical application. Several elegant methods have been devel-
oped for the isolation of the more-abundant C60 from ful-
lerene extracts;2,3 in contrast, isolating the less symmetrical
Figure 1. Chemical structures of (a) C60, (b) C70, and(c) CTV-based
molecular cages 1 and 2.
† National Taiwan University.
‡ National Chung Hsing University and China Medical University
Hospital.
(1) (a) Hirsch, A.; Brettreich, M. Fullerenes: Chemistry and Reac-
and photovoltaically more-interesting C704 in high purity
from the same mixtures has been less straightforward.
Accordingly, relatively limited research has been undertaken
to discover and expand the practical applications of C70.
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Fullerenes: Principles and Applications; Royal Society of Chemistry:
Cambridge, 2007.
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voltaics: Materials, Device Physics, and Manufacturing Technologies;
Wiley-VCH: Weinheim, 2008.
r
10.1021/ol3027957
Published on Web 12/10/2012
2012 American Chemical Society

One attractive approach for the selective isolation of C70
involves exploiting its hostꢀguest complexation behavior.5
Although a few judiciously designed synthetic host mole-
cules do form complexes with C60 and C70 in solution,6 using
such hostꢀguest complexes as a means of separating mix-
tures of buckyballs (i.e., with high degrees of selectivity and
stability) remains a challenge. Unlike carcerands, which
cannot release their entrapped guests, hemicarcerands allow
sequestration of complementary guests (forming room tem-
peratureꢀisolable hemicarceplexes) as well as their release at
elevated temperatures.7 We suspected that such an approach
might allow the isolation of C70 in high purity from fullerene
extracts. Herein, we report a cyclotriveratrylene (CTV)-based
molecular cage that favors the formation of a hemicarceplex
with C70, rather than with C60, and its application to the direct
isolation of high-purity (g99.0%) C70 from fullerene extracts
on a scale of tens of milligrams, through a simple and concise
route without the need for crystallization or HPLC.
Scheme 1. Synthesis of Molecular Cages 1 and 2
We suspected that structural complementarity between
two covalently linked CTV units and the spheroidal full-
erenes would provide sufficient binding affinity in solution
to abrogate the need for additional stabilizing aromatic
units in the linkers.6a,b,8 In theory, we could select linkers of
a suitable length to allow the smaller C60 to freely enter and
exit the host cavity while restricting the passage of the
larger C70 under the same conditions. To minimize the
energy cost of structural reorganization during the guest
binding event, we chose zigzagging alkyl chains as spacers
linking the two CTV units, giving suitably preorganized
hosts for complexation with C70 (Figure 1).
The molecular cage 1 was synthesized from 3,4-dihy-
droxybenzaldehyde (3) and 1,12-dibromododecane (4) in
seven steps (Scheme 1). The selective alkylation of the
dibromide 4 at the most-acidic phenol group (para
position) of the benzaldehyde 3 gave a crude dialdehyde
6, which we used directly in the subsequent macrocycliza-
tion reaction to produce the dialdehyde 8 (34% yield, two
steps). NaBH4-mediated reduction of both formyl groups
in the dialdehyde 8, followed by PCC-mediated oxidation
of one of the hydroxyl groups of the resulting diol 10,
afforded the alcohol 12. We synthesized the triol 14
through Sc(OTf)3-catalyzed condensation of three units
of the alcohol 12 into a CTV9 and subsequent NaBH4-
mediated reduction of the resulting trialdehyde. The mole-
cular cage 1 was isolated in 34% yield after another
Sc(OTf)3-catalyzed condensation of the triol 14. The mole-
cular cage 2 was synthesized from aldehyde 3 and 1,10-
dibromodecane (5) through procedures similar to those
used for the synthesis of the molecular cage 1.
(5) (a) Andersson, T.; Nilsson, K.; Sundahl, M.; Westman, G.;
Wennerstrom, O. J. Chem. Soc., Chem. Commun. 1992, 604–606. (b)
Atwood, J. L.; Barbour, L. J.; Raston, C. L.; Sudria, I. B. N. Angew.
Chem., Int. Ed. 1998, 37, 981–983. (c) Felder, D.; Heinrich, B.; Guillon, D.;
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Takeuchi, M.; Shinkai, S. Org. Lett. 2002, 4, 925–928. (e) Kawase, T.;
Tanaka, K.; Fujiwara, N.; Darabi, H. R.; Oda, M. Angew. Chem., Int. Ed.
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Murata, Y.; Komatsu, K.; Aida, T. J. Am. Chem. Soc. 2005, 127, 13086–
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J.-F. Supramolecular Chemistry of Fullerenes and Carbon Nanotubes;
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Wang, Q.; Long, H.; Zhang, W. J. Am. Chem. Soc. 2011, 133, 20995–21001.
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2011, 133, 11438–11441. (e) Jurow, M.; Farley, C.; Pabon, C.; Hageman, B.;
Dolor, A.; Drain, C. M. Chem. Commun. 2012, 48, 4731–4733.
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The 1H NMR spectrum of anequimolar mixture (3 mM)
of the host 1 and C60 in CDCl2CDCl2 displays (Figure 2b)
a new set of signals corresponding to their complex,
suggesting that the rates for guest entry into and exit from
1
the internal cavity of 1 are slow on the time scale of H
NMR spectroscopy at 400 MHz. When mixing the host 1
with a commercial fullerene extract, the same complex
appeared initially; after heating the solution at 323 K for
48 h, however, a new set of signals appeared for another
complex. The 1H NMR spectrum of an equimolar mixture
of pure C70 and the host 1 heated at 333 K for 48 h in
CDCl2CDCl2 displayed the same set of signals (Figure 2d).
Unlike the complex C60@1, which was not sufficiently
stable for isolation through column chromatography at
ambient temperature, the complex C70@1 could be purified
(8) For a recent review of CTVs, see: (a) Hardie, M. J. Chem. Soc.
Rev. 2010, 39, 516–527. For examples of complexes generated from
fullerenes and CTV dimers linked covalently or noncovalently, see:
(b) Matsubara, H.; Hasegawa, A.; Shiwaku, K.; Asano, K.; Uno, M.;
Takahashi, S.; Yamamoto, K. Chem. Lett. 1998, 923–924. (c) Matsubara,
H.; Shimura, T.; Hasegawa, A.; Semba, M.; Asano, K.; Yamamoto, K.
Chem. Lett. 1998, 1099–1100. (d) Huerta, E.; Cequier, E.; de Mendoza, J.
Chem. Commun. 2007, 5016–5018.
(9) Brotin, T.; Roy, V.; Dutasta, J.-P. J. Org. Chem. 2005, 70, 6187–6195.
Org. Lett., Vol. 14, No. 24, 2012
6147

Figure 3. Partial 13C NMR spectra (100 MHz, CDCl2CDCl2,
298 K) of (a) an equimolar mixture of 1 and C60 (2.5 mM); (b) the
free host 1; (c) free C70; and (d) the purified hemicarceplex
C70@1. The descriptors (c) and (uc) refer to the complexed and
uncomplexed states, respectively, of the components.
1
Figure 2. Partial H NMR spectra (400 MHz, CDCl2CDCl2,
298 K) of (a) the free host 1; (b) an equimolar mixture of 1 and
C60 (3 mM); (c) a mixture (0.5 mL) of 1 (2 mg) and fullerene
extract (10 mg); (d) the solution in (c) after heating at 323 K for
48 h; (e) an equimolar mixture of 1 and C70 (3 mM) after heating
at 333 K for 48 h; and (f) the purified hemicarceplex C70@1.
equilibrium had been reached, obtaining an association
constant (Ka) for the hemicarceplex of 4200 Mꢀ1 and its
association rate constant (k) of 0.026 Mꢀ1 sꢀ1 (Figure 4).
The intrinsic and constrictive binding energies for the hemi-
carceplex C70@1 were, therefore, 4.9 and 19.7 kcal molꢀ1
,
respectively. Although we could not isolate the complex
C60@1, its association in CDCl2CDCl2 was sufficiently
1
slow to allow H NMR spectroscopy to be used to deter-
chromatographically (SiO2; CH2Cl2/hexanes, 3:2). An elec-
trospray ionization (ESI) mass spectrum of the purified
C70@1 revealed an intense peak at m/z 2569.3 correspond-
ing to the ion [C70@1]þ. The good match between the
observed and calculated isotope patterns of this ion sup-
ports the successful synthesis of the hemicarceplex C70@1.
The 13C NMR spectrum of the isolated complex
C70@1 displays (Figure 3d) all five signals belonging to
C70, shifted upfield by 0.6ꢀ1.2 ppm relative to those of the
free fullerene (Figure 3c), suggesting encapsulation of spher-
oidal C70 within the cavity of 1. The same trend in upfield
shifting of the signals of C60 within its complex with the host
1 in the 13C NMR spectrum (Figure 3a) of their equimolar
mixture (2.5 mM) implied that the spherical fullerene could
also be positioned favorably within the cavity of this host in
mine its rate constant by monitoring the initial hostꢀguest
mixture; accordingly, we determined the equilibrium con-
stant and the association rate constant of complexation to
be 500 Mꢀ1 and 0.164 Mꢀ1 sꢀ1, respectively, corresponding
to a free energy and an activating energy of complexation of
3.7 and 18.5 kcal molꢀ1, respectively. Thus, the physical
barrier encountered by the more sizable C70 was greater
than that of C60 when entering the cavity of the host 1
through the openings formed by the alkyl linkers, and the
binding of the host 1 to C70 was stronger than that to C60.
After investigating the kinetic and thermodynamic beha-
vior of the hemicarceplex C70@1, we turned our attention to
applying this system to the direct isolation of C70 from
fullerene extracts. The isolation process involved three steps
(see Supporting Information (SI) for the flowchart): (i)
Formation of the hemicarceplex;A CHCl2CHCl2 (5 mL)
solution of the fullerene extract (300 mg, SES Research)
and the hemicarcerand 1 (50 mg) was heated at 313 K for
16 h; the organic solvent was evaporated under reduced
pressure, and the solid residue was suspended in CH2Cl2
(40 mL); the solid fullerenes were filtered off. (ii) Isolation
of the hemicarceplex;The filtrate was concentrated,
loaded onto a short column of SiO2 (5 g), and eluted with
CS2 (50 mL) to remove any uncomplexed and/or dissociated
fullerenes; the hemicarceplex C70@1 and the free hemicarcer-
and 1 were then isolated by eluting the column with mixtures
of CH2Cl2 and hexanes (3:2, 250 mL) and CH2Cl2 and
1
the complex. The signals in the H NMR spectra of equi-
molar mixtures (4 mM) of the host 2 and the guests C60 and
C70, respectively, in CDCl2CDCl2 were shifted only negli-
gibly, even after heating the mixture at 333 K for 48 h, sug-
gesting that neither guest could enter the cavity of host 2 by
penetrating its smaller openings.
Cram defined the free energy for the formation of a
hemicarceplex and the activation energy required for a
guest to enter the cavity of a hemicarcerand as the intrinsic
and constrictive binding energies, respectively.10 We used
1H NMR spectroscopy to monitor the dissociation of
the hemicarceplex C70@1 at 298 K in CDCl2CDCl2 until
(10) (a) Quan, M. L. C.; Cram, D. J. J. Am. Chem. Soc. 1991, 113,
2754–2755. (b) Houk, K. N.; Nakamura, K.; Sheu, C.; Keating, A. E.
Science 1996, 273, 627–629.
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Org. Lett., Vol. 14, No. 24, 2012

recovery, containing 64 mg of 1); therefore, the mass loss of the
host 1 throughout the whole isolation process was approxi-
mately 15%. Because the dissociation of the hemicarceplex
required no competing guests, the recycled host 1 could be
used directly in a subsequent isolation cycle without the need
for any specific treatment or purification process.
Dissociation of the recycled hemicarceplex under similar
conditions afforded C70 in 92.6% purity (HPLC analysis).
Notably, based on HPLC analysis, the C70 isolated using this
method was only negligibly contaminated with C60 (see SI);11
its major impurity was C76. Therefore, the hemicarcerand 1
appears to also sequester C76 from the fullerene extract. Based
on HPLC analysis of the commercial fullerene extract that
we tested in this study, the ratio of C76, C78, and C84 was
approximately 1:1.1:1.6 (i.e., C76 was a relatively minor
component; see SI). Therefore, our host 1 appears to be
capable of kinetically differentiating these three buckyballs
through the effective formation of the hemicarceplex C76@1
under the developed experimental conditions. This result
suggests that judicious extension or modification of the
linkers in host 1 might allow a methodology to be developed
to selectively stabilize;and, therefore, isolate;potentially
photovoltaically useful higher fullerenes,12 heterofullerenes,13
and/or endohedral fullerenes14 in high purity.
Although Cram first proposed, in 1995, that the internal
spaceofa cavitand dimer might be a suitablehostfor C60,15
hemicarcerands that can selectively imprison guests as big
as C60 and C70 have never been realized previously.
Significant differences in the association and dissociation
kinetics for the complexes formed between the hemicarcer-
and 1 and various buckyballs allowed us to isolate C70 in
high purity (g99.0%) from a commercial fullerene extract
through selective sequestration in solution, without the
need for recrystallization or HPLC. The preparation of
hemicarcerands that sequester C70 and higher fullerenes
suggests the possibility of not only isolating and stabilizing
these novel molecules, their analogues, and derivatives but
also applying them practically as useful photovoltaic
materials by significantly increasing their solubility in less
polar solvents without covalently disrupting their unique
π-surfaces. We are currently working on enlarging the
cavity of the hemicarcerand 1, by elongating the linking
spacers, to allow selective trapping of larger fullerenes.
Figure 4. Constrictive and intrinsic binding energies for the
complexation of C60 and C70 with the host 1 in CDCl2CDCl2.
MeOH (98:2, 50 mL), respectively. (iii) Dissociation of the
hemicarceplex;The hemicarceplex C70@1 (33.1 mg) ob-
tained after concentrating the appropriate eluate from the
previous step was dissolved in toluene (10 mL), and then the
solution was heated at 303 K for 12 h. The hemicarcerand 1
precipitated as a white solid, and the toluene solution, which
contained mainly free C70 and the hemicarceplex C70@1, was
removed via pipet after centrifugation; another charge of
toluene (5 mL) was added to wash the white solid, and then
the mixture was centrifuged again. The residue obtained after
concentrating the combined toluene phases was suspended in
CH2Cl2 (5 mL), in which the hemicarceplex C70@1 is highly
soluble, forming a red precipitate of C70, which was collected
through centrifugation. The solid C70 was then resuspended
in CH2Cl2 (5 mL), centrifuged, separated from the solvent,
and dried; the purity of the isolated C70 (6.5 mg), determined
through HPLC analysis, was 99.0%.
After obtaining consistent results when repeating this
isolation scheme another two times (isolating 7.1 and
6.7 mg of C70, both in 99.1% purity; see SI), we scaled
upthe process10-fold (using 3 g of the fullerene extract and
500 mg of the hemicarcerand 1). Gratifyingly, we isolated
C70 not only in approximately 10 times the amount
(72.6 mg) but also in similar purity (99.0%). Thus, the
amount of C70 isolated in a single purification cycle should
be scalable to even greater levels if we were to apply a
greater amount of the host 1. In this large-scale experi-
ment, the total amount of the host 1 that we recovered after
chromatography and precipitation from toluene was 360 mg
(72% recovery). Concentrating the CH2Cl2 phase obtained
after dissociation of the hemicarceplex under reduced pressure
allowed recycling of 96 mg of the hemicarceplex C70@1 (26%
Acknowledgment. This study was supported by the Na-
tional Science Council (Taiwan) (NSC-101-2628-M-002-
010) and National Taiwan University (NTU-101-R890913).
Supporting Information Available. Synthetic proce-
dures and characterization data for hemicarcerand 1
and hemicarceplex C70@1. This material is available free
of charge via the Internet at http://pubs.acs.org
(11) Based on HPLC analysis, the main impurity of the commercial
high purity C70 (g98.5%) was C60
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The authors declare no competing financial interest.
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