Synthesis and optical properties of 6-substituted-β-cyclodextrin derivatives

Article abstract of DOI:10.2174/157017809790442899

β-Cyclodextrin derivatives with varying lengths of π-conjugated arms have been synthesized. Their structures have been confirmed by 1H NMR, elemental analysis, mass spectrometry and X-ray crystal structure determination. Their self-inclusion properties ar

Full text of DOI:10.2174/157017809790442899

604
Letters in Organic Chemistry, 2009, 6, 604-612
Synthesis and Optical Properties of 6-Substituted-ꢀ-cyclodextrin
Derivatives
Ruiyun Guo1, Mahuya Bagui1, Yongge Wei2 and Zhonghua Peng*,1
1Department of Chemistry, University of Missouri-Kansas City, Kansas City, MO 64110, USA;
2Department of Chemistry, Tsinghua University, Beijing, China
Received March 24, 2009: Revised August 13, 2009: Accepted November 05, 2009
Abstract: ꢀ-Cyclodextrin derivatives with varying lengths of ꢁ-conjugated arms have been synthesized. Their structures
have been confirmed by 1H NMR, elemental analysis, mass spectrometry and X-ray crystal structure determination. Their
1
self-inclusion properties are evaluated using Circular Dichroism, 1D and 2D H NMR measurements. It is found that,
when the length of the ꢁ-conjugated arm is extended from 4 to 5 and to 6, the self-inclusion of the ꢁ-conjugated arm to the
CD ring is enhanced. The effect of the self-inclusion on the optical properties of the CD-linked ꢁ-conjugated systems has
been explored. Stronger inclusion leads to enhanced excitation-energy transfer.
Keywords: ꢀ-cyclodextrin, inclusion complex, ꢁ-conjugation, excitation energy transfer.
INTRODUCTION
synthesized according to literature procedures [21, 22]. 3,5-
Diethynylaniline (2) was prepared by the Sonogashira
coupling of 3,5-diiodoaniline (1) with trimethylsilyl-
acetylene, followed by desilylation, while compound (3) was
synthesized by the coupling of 1 with ethynylbenzene.
Targeted ꢀ-CD derivatives (4), (5) and (6) were realized by
reductive amination of mono-6-formyl-ꢀ-cyclodextrin with
their respective aniline derivatives in mixed solvents of
methanol/water with 0.2 M acetate buffer (pH = 5) at room
temperature. Na(CN)BH3 was used as the reducing agent.
The products were purified by reversed-phase column
chromatography, eluting with water, followed by 10%
aqueous methanol, and then 20% aqueous methanol. The
yields are 20, 15, and 15%, for Compounds (4), (5) and (6),
respectively. Single crystals suitable for X-ray diffraction
analysis were grown in water by dissolving Compound (4) in
hot water and letting the solution stand at room temperature
for several days. Attempts in growing single crystals out of
Comounds (5) and (6) have not been successful.
Cyclodextrins (CDs) are among the most captivating
molecules, not only due to their unique and appealing hollow
truncated conical cylindrical structures, but also due to their
ubiquitous molecular-encapsulation properties which have
found broad applications as drug delivery systems, enzyme
mimics, molecular receptors, and chemical and biological
sensors [1-5]. More recently, CD rings have been used to
encapsulate individual ꢁ-conjugated oligomers or polymers,
leading to not only improved solubility in polar media but
also a step closer to realize insulated molecular wires [6-11].
Inclusion occurs when
a suitable hydrophobic guest
molecule replaces the high-enthalpy water molecules from
the CD’s hydrophobic cavity [12]. Although inclusion-
complex formation is usually favored thermodynamically,
and in many cases the formed inclusion complexes can be
isolated as stable crystalline substances [13-19], the
formation and the dissociation of the inclusion complexes in
solution is nonetheless a dynamic process. End-capping is
thus required to prevent unthreading of the CDs from their
inclusion complexes [6-11]. While a number of CD-threaded
ꢁ-conjugated systems have been studied, very few have the
ꢁ-system and the CD ring covalently linked [20]. In this
paper, we report the synthesis and optical properties of three
ꢀ-CD derivatives containing covalently linked short ꢁ-
conjugated systems. Their self-inclusion phenomenon and
optical properties have been studied.
Structural Characterization
All three compounds are soluble in common polar
solvents such as methanol, DMSO, DMF, etc. Compounds
(4) and (5) are partially soluble in water while 6 is insoluble.
1
The H NMR spectra of 4 and 5 in DMSO-d6 are shown in
1
Fig. (1). The aromatic region of the H NMR spectrum of 4
shows well-resolved one triplet (J = 1.2 Hz) at 7.10 ppm and
one doublet (J = 1.2 Hz) at 6.99 ppm, which can be assigned
to para and ortho aryl protons (in relation to the amino
group), respectively. The rest of the spectrum resembles that
of ꢀ-CD. The broad peak at 5.82 ppm is attributed to the
secondary hydroxyl group and NH, while primary hydroxyl
protons appear at 4.43 ppm. The protons linked to C1 (see
Scheme 1 for labeling) give a relatively sharp signal at 4.81
ppm. Compound (5) gives two singlets in the aromatic
region. A sharp singlet at 4.01 ppm is observed which can be
attributed to the ethynyl protons. The rest of the signals can
RESULTS AND DISCUSSION
Synthesis
Scheme 1 shows the structures and synthesis of the three
ꢀ-CD derivatives. 6-Deoxy-6-formyl-ꢀ-cyclodextrin was
*Address correspondence to this author at the Department of Chemistry,
University of Missouri-Kansas City, Kansas City, MO 64110, USA;
Tel: 816-235-2288; Fax: 816-235-2290; E-mail: pengz@umkc.edu
1570-1786/09 $55.00+.00
© 2009 Bentham Science Publishers Ltd.

Self-Inclusion of ꢀ-CD Derivatives
Letters in Organic Chemistry, 2009, Vol. 6, No. 8
605
Scheme 1. Structures and synthesis of ꢀ-CD derivatives.
be assigned to protons associated with the CD ring. The 13C
NMR spectrum of 4 and 5 showed all the normal peaks of ꢀ-
CD at around 60 (C6), 72-73 (C5, C2, C3), 81 (C4), and 102
(C1) ppm [23]. The substituted glucose of cyclodextrin gives
13C signals at around 43, 69 and 83 ppm, which correspond
to C6’, C5’ and C4’, respectively. Four peaks for the 3,5-
diiodoaniline moiety at 96.0, 119.9, 130.7 and 151.3 ppm are
observed. For 5, four aromatic carbon signals at 115.8,
121.9, 122.5, and 149.0 ppm and two alkyne carbons at 83.1
and 83.4 ppm are observed. These results are consistent with
their structures. The structure of 4 was further confirmed by
elemental analysis and X-ray crystal structure determination
while the structure of 5 was confirmed by mass spectrometry
measurements (see experimental section).
Fig. (2). 1H NMR spectra of 3, 6 and ꢀ-CD in DMSO-d6.
Fig. (1). 1H NMR spectra of 4 and 5 in DMSO-d6.
Conformational Analysis
1
Fig. (3) shows the UV/Vis absorption and circular
dichroism spectra of the aqueous solutions of compounds
(4), (5) and (6). Compound (4) shows one n-ꢁ* transition
band at 311 nm and two ꢁ-ꢁ* transitions at 260 nm (1Lb) and
230 nm (1La). The same three types of transitions are also
observed for 5 with moderate red-shifts, appearing at 340,
270 and 240 nm, respectively. From 5 to 6, the ꢁ-ꢁ*
transitions are significantly red-shifted while the n-ꢁ*
Fig. (2) shows the H NMR spectrum of 6, which is
proximately the summation of the spectra of 3 and ꢀ-CD
(both spectra are shown in Fig. (2) as well). Again, all
signals are well resolved and can be unambiguously
assigned. MALTI-TOF mass spectrometry of 6 gave a major
peak at 1432.6 which corresponds to the (M+Na+)
(calculated M = 1409.5). These results validate the structure
of 6.

606 Letters in Organic Chemistry, 2009, Vol. 6, No. 8
Guo et al.
transition is only slightly so. The circular dichroism spectra
cavity while the other pointing away which is confirmed by
its crystal structure, described later.
of 4 show positive Cotton effect for all three bands. For 5,
1
the Lb band gives a weak negative Cotton effect. For 6,
When the two iodo groups in 4 are converted to two
ethynyl groups, compound (5) now possesses longer “hands”
which may reach into the CD cavity. To facilitate this
inclusion, the phenyl ring is now severely twisted with its
axis now nearly perpendicular to the CD axis (ꢂ<30°, Fig.
negative Cotton effects are observed for both the n-ꢀ* band
and the major ꢀ-ꢀ* bands (at 301 and 285 nm). It is known
that the sign of the induced circular dichroism signal of an
achiral guest molecule depends mainly on its location and
orientation in relation to the CD cavity [24, 25]. For a guest
molecule located inside the CD cavity, its electronic
transitions with transition dipole moments parallel to the CD
axis (or the angle between the transition dipole and the CD
axis is less than 30°) give positive induced circular
dichroism signals while those transitions having a higher-
than 30° angle with the CD axis give negative signals. The
situation is reversed if the guest molecule is located outside
but near the CD cavity. Thus, all positive Cotton effects
observed on 4 indicate that the phenyl ring was located at the
exterior of the CD cavity and is more or less parallel to the
1
(4b)), resulting in a weak negative Lb signal and a positive
1La signal (1La is still nearly perpendicular to the CD axis).
For compound (6), one arm is now deeply included inside
the CD cavity (Fig. (4c)). The phenylacetylene arm,
however, is not included in the CD cavity in a straight-down
fashion, but rather in a perched way (ꢁ>30°), presumably
due to the short binding bridge between the conjugated ꢀ-
system and the CD rim, resulting in negative Cotton effects
for the major ꢀ-ꢀ* transitions (at 301 and 285 nm) associated
with the partially included diphenylacetylene segment.
1
1
Similar to 5, the La and Lb transitions associated with the
center phenyl ring give positive (225 nm) and negative
signals (250 nm), respectively.
1
1
narrow CD rim. As shown in Fig. (4a), both La and Lb
transitions have angles more than 30° in relation to the CD
axis (ꢁ,ꢂ>30°) and thus give positive circular dichroism
signals. If the angle ꢂ is less than 90°, the twisting of the
phenyl ring will result in one iodo group closer to the CD
The structure of 4 deduced from the CD spectrum is
confirmed by its crystal structure. Compound (4) crystallizes
in the monoclinic space group P21. There are two
crystallographically dependent but chemically equivalent CD
molecules A and B in the asymmetric unit. For the sake of
simplicity, only the structure of molecule A is shown in Fig.
(5), which reveals that the CD skeleton maintains a round
belt shape. The seven bridge oxygen atoms are nearly
coplanar, forming a heptagon with edge lengths in the range
of 4.241-4.423 Å for A and 4.189-4.510 Å for B and angles
in the range of 123.8-134.6 ° for A and 124.3-132.3 for B,
respectively. As seen in many mono-6-aryl-ꢂ-CDs, the
introduction of 3,5-diiodophenyl substituent does not lead to
significant geometrical changes for the CD skeleton [26-29].
The 3,5-diiodophenyl group bends inward towards the cavity
with a dihedral angle C43A-N1A-C42A-C41A for A and
C43B-N1B-C42B-C41B for B of ca 72° (72.1° and 72.2° for
A and B, respectively). The angle between the C2 rotational
axis of the phenyl ring and the normal of the CD ring for
both A and B is around 76°. The phenyl ring is further
twisted around its rotational axis, resulting in a dihedral
angle between the phenyl ring and the CD ring of 43.8 and
45.8°, for A and B, respectively. One iodo group sits at the
outskirts of the cavity of its own CD ring, while the other
iodo group points away. The angle between the 1La transition
1
Fig. (3). UV/Vis absorption and circular dichroism spectra of 4-6 in
aqueous solutions.
and the CD axis is thus 76°, while that between Lb and the
CD axis is around 44°. Both should give positive ICD
signals, consistent with its CD spectrum.
The protruding iodo group is actually included into the
cavity of an adjacent CD ring from the secondary hydroxyl
side to form a one-dimensional quasi-columnar supers-
tructure. As shown in Fig. (6), there are two sets of CD rings
of A and B, each containing alternate parallel CD rings, in
one moderately displaced columnar superstructure. The two
sets of CD rings are horizontally offset by ca 2.50 Å. All CD
rings are arranged nearly perpendicular to the columnar axis
with a cross angle of 94°. The adjacent 3,5-diiodophenyl
moieties are nearly orthogonal to each other (96° dihedral
angle), forming a zigzag core. While similar columnar
superstructures have been observed in many other mono-6-
Fig. (4). Schematic structures of 4-6 deduced from circular
dichroism spectra.

Self-Inclusion of ꢀ-CD Derivatives
Letters in Organic Chemistry, 2009, Vol. 6, No. 8
607
Fig. (5). Ortep (left, cavity view) and Rasmol (right, side view) representations of the molecular structure of 4.
Fig. (6). Moderately displaced columnar superstructure formed by intermolecular encapsulation. Left, rasmol drawing of a side view of the
columnar structure; right, top: side view of the core; right, bottom: cavity view of the column.
substituted-ꢀ-CDs [26-29], the CD rings in those
superstructures are significantly tilted, resulting in less
regular columnar structures.
of the seven-fold symmetry due to self-inclusion into the CD
cavity or fixation near the rim of the cavity by the covalently
linked pendant [29-31]. The 2D ROESY spectrum (Fig. (8))
showed very weak interactions between aromatic protons
and the CD protons. The fact that no cross peak is observed
for proton b and the CD’s H3 protons, indicates that the
phenyl ring is not deeply included. Compared to proton b,
proton a showed relatively stronger crosspeaks with CD’s
H5 protons. This result, coupled with the overall weak NOE
correlations between protons a, b and CD’s protons, yields a
consistent picture that the phenyl ring sits over the CD’s
narrow rim with the phenyl ring significantly twisted so that
one proton a is much closer to the CD rim than the proton b
is.
While our efforts in growing single crystals suitable for
X-ray crystallography were not fruitful for compound (5), its
1D and 2D 1H NMR spectra do provide valuable information
1
in regard to its conformation. In DMSO-d6, the H NMR
spectrum of 5 shows only one signal corresponding to H1
(Fig. (7)) and see Scheme 1 for proton labeling). In D2O,
however, the seven H1 protons give five adequately
dispersed signals in the range of 4.85~5.20 ppm with
integration ratio of 1:1:1:2:2. The significant dispersion
(over 0.3 ppm) of the anomeric signals reflects the reduction

608 Letters in Organic Chemistry, 2009, Vol. 6, No. 8
Guo et al.
can notice their n-ꢀ* transitions which are not only
significantly
suppressed
in
intensity,
but
also
hypsochromically shifted by more than 20 nm (dotted
curves), compared with those in DMSO (solid curves). The
ꢀ-ꢀ* transition peaks shown in their DMSO solutions are
also significantly blue-shifted and merged to the new broad
peak. For 4 and 5, however, one still observes the n-ꢀ* and
ꢀ-ꢀ* transitions appearing at only slightly blue-shifted
wavelengths in water versus their counter-peaks in DMSO.
Apparently, by linking to ꢁ-CD, the aryl systems of 4 and 5
in water are able to at least partially maintain a hydrophobic
environment similar to what they experience in DMSO,
presumably due to the formation of inclusion complexes or
self-inclusion.
Fig. (7). 1H NMR spectra of 5 in DMSO-d6 and D2O.
Fig. (9). Absorption spectra of 1,2,4 and 5 in DMSO and water.
Compounds (2) and (5) are highly fluorescent and thus
their fluorescent emission properties were explored. The
emission spectra of 2 and 5 were studied in both DMSO and
H2O, under different excitation wavelengths corresponding
to their absorption peaks. As shown in Fig. (10), compound
(2) shows nearly identical emission wavelengths whether in
DMSO or in water and whether it was excited at the n-ꢀ*
transition wavelength or the ꢀ-ꢀ* transition wavelength. The
excitation wavelength-independent emission indicates
energy transfer from the ꢀ-ꢀ* transition to the n-ꢀ*
transition. The excitation spectra of 2 in both DMSO and
water match their corresponding absorption spectra in terms
of peak positions. By comparing the absorption spectra with
the corresponding excitation spectra, one can estimate the
ꢀꢂꢀ* to n-ꢀ* energy transfer efficiency to be 55% (at 271
nm) and 42% (at 233 nm) in DMSO and water, respectively.
For compound (5), its fluorescence emission is again
independent of the excitation wavelengths. The energy
transfer efficiency from the ꢀꢂꢀ* to n-ꢀ* transition is
markedly higher (67% at 276 nm) in DMSO than that of
compound (2). The excitation spectra of 5 in water show
three peaks, again matching its absorption spectra. At 276
nm, the excitation energy transfer efficiency in water is even
higher at 75%.
Fig. (8). Partial 1H 2D ROESY spectrum of 5 in D2O at 298 K.
Electronic Properties
Compounds (1), (2), (4), and (5) exhibit enough
solubility in water so that their optical properties in DMSO
and water can be compared. As shown in Fig. (9), all four
compounds show two absorption peaks in DMSO, one at
longer wavelengths and with lower intensity associated with
the n-ꢀ* transition while the other due to the ꢀ-ꢀ* transition.
In water, a new intense peak at shorter wavelengths appeared
for all four compounds. Besides the new broad peaks at 224
nm and 230 nm for compounds (1) and (2), respectively, one
As stated earlier, circular dichroism measurements
indicate that the self-inclusion is much stronger in 6 than in 4

Self-Inclusion of ꢀ-CD Derivatives
Letters in Organic Chemistry, 2009, Vol. 6, No. 8
609
Fig. (10). FL emission and excitation spectra of 2 (left) and 5 (right) in DMSO (solid curves) and water (dotted curves).
and 5. It would thus be interesting to see how the optical
properties of 6 change in water versus DMSO, and how they
compare with those of 3. Unfortunately, 3 is totally insoluble
in water. However, 6 shows enough solubility for absorption
and fluorescence measurements. Fig. (11) shows the
absorption, excitation and emission spectra of 6 in DMSO
and water. The absorption spectrum shows that, similar to 4
and 5, the n-ꢀ* transition of 6 in water is slightly blue-
shifted. Its ꢀ-ꢀ* transitions, however, give nearly identical
peaks in both DMSO and water. More significantly, the
absorption spectrum of 6 in water shows no new peak around
230 nm, the one which was observed in all four other
compounds (1,2,4,5). Overall, the difference between the
two absorption spectra, one in water and one in DMSO, is
much smaller in 6 than those observed in 4 and 5, consistent
with the previous suggestion that the aryl system is strongly
included in 6. The excitation spectrum of 6 in water matches
very well with its absorption spectrum. The excitation
energy transfer efficiency from the ꢀꢁꢀ* to n-ꢀ* transition is
nearly quantitative (>98%). These results clearly indicate
that self-inclusion of an aryl system into a CD cavity exhibits
significantly beneficial effects on their optical properties [6,
32].
CONCLUSION
In conclusion, three ꢂ-CD derivatives with varying
lengths of ꢀ-conjugated arms have been synthesized.
Circular dichroism measurements indicate that when the ꢀ-
conjugated arms are extended from 4 to 5 and to 6, the self-
inclusion of the ꢀ-conjugated arm to the CD ring is
enhanced. The extent of inclusion results in very different
solvent-dependent optical properties for these compounds. In
aqueous solutions, stronger inclusion leads to enhanced
excitation energy transfer.
Fig. (11). Absorption, excitation and emission spectra of 6 in
DMSO (solid curves) and water (dotted curves).
EXPERIMENTAL SECTION
1H and 13C NMR spectra were recorded on a Varian 400-
MHz spectrometer. The 2D ROESY spectra were recorded

610 Letters in Organic Chemistry, 2009, Vol. 6, No. 8
Guo et al.
on a Varian 400-MHz spectrometer by dissolving 6.0 mg of
compound 5 in 1mL D2O with scan per Inc 64, number of
Inc 512, mixing time 200 ms, relaxation time 2 s at 298 K.
Thin layer chromatography was performed on aluminum-
backed silica gel plates with solvent system (n-
butanol/ethanol /water, 5:4:3). Cyclodextrin compound was
visualized by charring with 50% sulfuric acid in ethanol
spray, whereas UV exposure revealed the aromatic
substituted product. C18-Reversed phase, 24 %C silica gel
was used for reverse-phase column chromatography.
(6H, m, ArH), 6.85 (t, J = 1.2 Hz, 1H, ArH), 6.76 (d, J =
1.2Hz, 2H, ArH), 5.49 (s, 2H, NH2). 13C NMR (DMSO-d6,
TMS): ꢂ 149.4 , 131.5 , 128.9 , 128.8 , 123.1 , 122.3, 121.5 ,
116.6, 89.2, 88.6.
Compound (4)
6-Deoxy-6-formyl-ꢀ-cyclodextrin (1 g, 0.88 mmol), and
3, 5-diiodoaniline (3.73 g, 10.81 mmol) were dissolved in
mixed solvents containing an acetate buffer solution
(NaOAc/AcOH, pH = 5) and methanol in a ratio of 1:2 at 25
oC. After stirring for 1 h, Na(CN)BH3 (276 mg, 4.4 mmol)
was added to the resulting solution. The mixture was stirred
for 10 d, and then neutralized with 2 M sodium hydroxide.
The solution was added dropwise to acetone (1 L). After
being kept in the refrigerator for 2 h, the precipitate was
collected and rinsed with acetone. Purification was accom-
plished utilizing reversed phase column chromatography,
eluting with water (1.5 L), followed by 10% aqueous
methanol (1 L), and then 20% aqueous methanol (2.5 L).
The appropriate fractions were concentrated to 15 mL under
vacuum and lyophilized to give the desired product as a
colorless solid (250 mg, 20%. Decompose at 254 °C before
melting). Rf 0.55 (n-butanol/ethanol /water, 5:4:3). The
product was dissolved in hot water and the solution was
allowed to stand at room temperature for several days, giving
crystals suitable for X-ray analysis. 1H NMR (DMSO-d6, 400
MHz, 25 °C, ppm): ꢂ 7.10 (t, J =1.2 Hz, 1H), 6.99 (d, J = 1.2
Hz, 2 H), 5.82 (br, 15 H, 2oOH and NH), 4.81 (m, 7H), 4.43
(br, 6H), 3.90-3.05 (m). 13C NMR (DMSO-d6, 400 MHz, 25
°C, ppm): ꢂ 42.9, 60.2, 69.0, 72.0, 72.4, 73.1, 81.4, 83.1,
96.0, 102.0, 119.9, 130.7, 151.3. Anal. Calc. for
C48H73I2NO34· 9.5 H2O: C, 35.30; H, 5.68; N, 0.86. Found:
C, 35.03; H, 5.21; N, 0.92.
6-Deoxy-6-formyl-6-ꢀ-cyclodextrin [22] and 1, 3-diiodo-
aniline [33] were synthesized according to literature
procedures. Water used for the purification was 18 Mꢁ Ultra
pure water obtained from LABCONCO water purification
system. All the other chemicals are purchased from either
ACROS or Aldrich and used as received unless otherwise
stated.
3,5-Diethynylaniline
To the solution of 3,5-diiodoaniline (3.45 g, 10 mmol) in
THF (10 mL) and Et3N (8 mL), Pd(PPh3)2Cl2 (280 mg, 0.4
mmol) and CuI (152 mg, 0.8 mmol) were added at room
temperature. The solution was degassed by bubbling N2
through it. Trimethylsilylacetylene (2.94 g, 30 mmol) was
then added and the mixture was stirred overnight. The
resulting solution was filtered. The filtrate was concentrated
and redissolved in CH2Cl2. The resulting solution was
washed with water, dried over anhydrous MgSO4 and
concentrated to get crude product. The crude product was
purified by flash column chromatography eluting with 4:1
(hexane/ethyl acetate) to yield 3,5-bis(trimethyl-silylethynyl
)aniline. To the solution of this compound in CH2Cl2 (20
mL), t-butylammonium fluoride (22 mL, 22 mmol) was
added. The reaction mixture was stirred for 20 min and was
then poured into water. The aqueous solution was extracted
with CH2Cl2. The organic layer was collected, dried over
anhydrous MgSO4, and the solvent was then evaporated. The
resulting crude product was purified by flash column
chromatography eluting with 4:1 hexane / ethyl acetate to
give the title compound as light brown needle crystals
Compounds (5) and (6) were synthesized using the same
approach and workup procedures as those of 4.
Compound (5)
190 mg was obtained as light yellow powder (yield 15%,
decomposed at 230 °C before melting). 1H NMR (DMSO-d6,
TMS): ꢂ 6.74 (s, 2H, ArH), 6.66 (s, 1H, ArH), 5.76 (br, 14H,
2oOH), 5.66 (t, 1H, J = 5.6 Hz, NH), 4.84 (br, 7H, H1), 4.48
(br, 6H, 1 oOH), 4.01 (s, 2H, ꢃCH), 3.82 (m, 1H, H6b’), 3.63
(m, 27H,H3, H5, H6, H6a’), 3.30 (m). 13C NMR (DMSO-d6,
TMS): ꢂ 43.2 (C6’), 59.7(C6), 59.9(C6), 69.4(C’5), 72.1(C5),
72.2(C5), 72.4(C5), 73.0(C5), 73.1(C5), 79.9 (ꢃCH), 81.3(C4),
81.4(C4), 81.5 (C4), 83.1(C’4), 83.4(ꢃC), 101.9(C1),
102.2(C1’), 115.8(Cc), 121. 9(Cf), 122.5(Cb), 149.0(Ca). MS
(MALDI) calcd for C52H75O34N: 1257.4, found 1280.1 (M +
Na+).
o
(overall yield 1.23 g, 80%, m.p. 126-127 C, lit 125-127 oC
[34]). 1H NMR (DMSO-d6, TMS): ꢂ 6.67 (d, J = 1.2 Hz, 2H,
ArH), 6.64 (t, J = 1.2 Hz, 1H, ArH), 5.44 (s, 2H, NH2), 4.07
(s, 2H, ꢃCH). 13C NMR (DMSO-d6, TMS): ꢂ 149.1, 122.5,
121.8, 117.2, 83.2, 80.0.
3,5-Bis(phenylacetylene)aniline
Triethylamine (8 mL) was added to a mixture containing
3,5-diiodoaniline (3.45 g, 10 mmol), phenylacetylene (2.55
g, 25 mmol), Pd(PPh3)2Cl2 (280 mg, 0.4 mmol), CuI (152
mg, 0.8 mmol), and THF (10 mL) at r.t.. The resulting
solution was stirred at r.t. overnight and was then filtered.
The filtrate was concentrated and redissolved in CH2Cl2. The
resulting solution was washed with water, dried over
anhydrous MgSO4 and the solvent was then stripped off. The
crude product was purified by flash column chromatography
eluting with 4:1 hexane / ethyl acetate. The title compound
was obtained as a brown solid (2.30 g, 78%, m.p. 118-120
Compound (6)
208 mg was obtained as earth yellow powder (yield 15%,
decomposed at 240 °C before melting). 1H NMR (DMSO-d6)
ꢂ 7.57 (m, 4H, ArH), 7.43 (m, 6H, ArH), 6.88 (s, 3H, ArH),
5.77 (m, 14H, 2oOH), 5.56 (t, J = 5.2 Hz, 1H, NH), 4.87 (m,
7H, C1H), 4.63 (t, 1H, 1oOH), 4.47 (m, 5H, 1oOH ), 3.82 (br,
1H, H6b’), 3.66 (m, 27H, H3, H6, H6a’, H5), 3.28 (m). 13C
NMR (DMSO-d6, TMS): ꢂ 43.2(C6’), 59.9(C6), 60.2(C6),
70.0(C5’), 72.1(C5), 72.2(C5), 72.5(C5), 73.0(C5), 73.1(C5),
81.4(C4), 81.6(C4), 82.9(C4’), 88.7 (ꢃC), 89.4(ꢃC),
102.0(C1), 102.2(C1’), 115.5(Cb), 121.6, 122.4, 123.1, 128.8,
1
°C). H NMR (DMSO-d6, TMS): ꢂ 7.55 (4H, m, ArH), 7.42

Self-Inclusion of ꢀ-CD Derivatives
Letters in Organic Chemistry, 2009, Vol. 6, No. 8
611
[4]
(a) Khan, A. R.; Forgo, P.; Stine, K. J.; D’Souza, V. T. Chem. Rev.,
1998, 98, 1977; (b) Saenger, W.; Jacob, J.; Gessler, K.; Steiner, T.;
Hoffmann, D.; Sanbe, H.; Koizumi, K.; Smith, S. M.; Takaha, T.
Chem. Rev., 1998, 98, 1787; (c) Rekharsky, M. V.; Inoue, Y.
Chem. Rev., 1998, 98, 1875; (d) Lebilla, C. B. Acc. Chem. Res.,
2001, 34, 653; (e) Connors, K. A. Chem. Rev., 1997, 97, 1325.
(a) Yu, L.; Chen, Y. Acc. Chem. Res., 2006, 39, 681; (b) Liu, Y.;
Han, B.; Zhang, H. Curr. Org. Chem., 2004, 8, 35; (c) Liu, Y.;
Zhang, N.; Chen, Y.; Wang, L. H. Org. Lett., 2007, 9, 315.
(a) Taylor, P. N.; O'Connell, M. J.; McNeill, L. A.; Hall, M. J.;
Aplin, R. T.; Anderson, H. L. Angew. Chem. Int. Ed. Engl., 2000,
39, 3456; (b) Cacialli, F.; Wilson, J. S.; Michels, J. J.; Daniel, C.;
Silva, C.; Friend, R. H.; Severin, N.; Samorì, P.; Rabe, J. P.;
O'Connell, M. J.; Taylor, P. N.; Anderson, H. L. Nat. Mater., 2002,
1, 160; (c) Michels, J. J.; O'Connell, M. J.; Taylor, P. N.; Wilson, J.
S.; Cacialli, F.; Anderson, H. L. Chem.-Eur. J., 2003, 9, 6167.
Nepal, D.; Samal, S.; Geckeler, K. E. Macromolecules, 2003, 36,
3800.
Farcus, A.; Grigoras, M. Polymer Int., 2003, 52, 1312.
Okumura, H.; Kawaguchi, Y.; Harada, A. Macromol. Rapid
Commun., 2002, 23, 781.
Liu, Y.; Zhao, Y.; Zhang, H.; Li, X.; Liang, P.; Zhang, X.; Xu, J.
Macromolecules, 2004, 37, 6362..
Van den Boogaard, M.; Bonnet, G.; van’t Hof, P.; Wang, Y.;
Brochon, C.; van Hutten, P.; Lapp, A.; Hadziioannou, G. Chem.
Mater., 2004, 16, 4383.
(a) Szejtli, J. Chem. Rev., 1998, 98, 1743; (b) Harata, K. Chem.
Rev., 1998, 98, 1803.
(a) Clark, J. L.; Stezowski, J. J. J. Am. Chem. Soc., 2001, 123,
9880; (b) Alexander, J. M.; Clark, J. L.; Brett, T. J.; Stezowski, J. J.
Proc. Natl. Acad. Sci. USA, 2002, 99, 5115.
(a) Udachin, K. A.; Ripmeester, J. A. J. Am. Chem. Soc., 1998,
120, 1080; (b) Udachin, K. A.; Wilson, L. D.; Ripmeester, J. A. J.
Am. Chem. Soc., 2000, 122, 12375.
Liu, Y.; Zhao, Y. L.; Zhang, H. Y.; Song, H. B. Angew. Chem. Int.
Ed. Engl., 2003, 42, 3260.
Kamitori, S.; Matsuzaka, O.; Kondo, S.; Muraoka, S.; Okuyama,
K.; Noguchi, K.; Okada, M.; Harada, A. Macromolecules, 2000,
33, 1500.
(a) Hamilton, J. A.; Chen, L. J. Am. Chem. Soc., 1988, 110, 4379;
(b) Hamilton, J. A.; Chen, L. J. Am. Chem. Soc., 1988, 110, 5833.
(a) Onagi, H.; Carrozzini, B.; Cascarano, G. L.; Easton, C. J.;
Edwards, A. J.; Lincoln, S. F.; Rae, A. D. Chem. Eur. J., 2003, 9,
5971; (b) Onagi, H.; Blake, C. J.; Easton, C. J.; Lincoln, S. F.
Chem. Eur. J., 2003, 9, 5978.
Terao, J.; Tang, A.; Michels, J. J.; Krivokapic, A.; Anderson, H. L.
Chem. Commun., 2004, 56.
Liu, Y.; Zhao, Y. L.; Zhang, H. Y.; Fan, Z.; Wen, G. D.; Ding, F.
J. Phys. Chem. B, 2004, 108, 8836.
131.5, 149.4. MS (MALDI) calcd for C64H83O34N: 1409.5,
found 1432.6 (M + Na+).
X-Ray Single Crystal Structure Analysis
[5]
[6]
A colorless needle-shaped crystal of dimensions 0.40 x
0.08 x 0.06 mm was selected for structural analysis. Intensity
data for this compound were collected using a Bruker APEX
ccd area detector using graphite-monochromated Mo Kꢀ
radiation (ꢁ = 0.71073 Å) [35]. The sample was cooled to
100(2) K. The intensity data were measured as a series of ꢂ
oscillation frames each of 0.3 ° for 60 sec / frame. Coverage
of unique data was 99.8 % complete to 21.97 degrees in ꢃ.
Cell parameters were determined from a non-linear least
squares fit of 7740 peaks in the range 2.36 < ꢃ < 22.87°. A
total of 33612 data were measured in the range 2.14 < ꢃ <
21.97°. The data were corrected for absorption by the semi-
empirical method giving minimum and maximum
transmission factors of 0.6772 and 0.9393 [36]. The data
were merged to form a set of 15478 independent data with
R(int) = 0.0630.
[7]
[8]
[9]
[10]
[11]
[12]
[13]
The monoclinic space group P21 was determined by
systematic absences and statistical tests and verified by
subsequent refinement. The structure was solved by direct
methods and refined by full-matrix least-squares methods on
F2 [37]. Hydrogen atom positions were initially determined
by geometry and refined by a riding model. Non-hydrogen
atoms were refined with anisotropic displacement
parameters. Hydrogen atom displacement parameters were
set to 1.2 (1.5 for methyl) times the displacement parameters
of the bonded atoms. A total of 1698 parameters were
refined against 1623 restraints and 15478 data to give
wR(F2) = 0.2106 and S = 1.035 for weights of w = 1/[ꢄ2 (F2)
[14]
[15]
[16]
[17]
[18]
+ (0.1270 P)2 + 24.9400 P], where P = [Fo + 2Fc ] / 3. The
final R(F) was 0.0795 for the 12733 observed, [F > 4ꢄ(F)],
data. The largest shift/s.u. was 0.001 in the final refinement
cycle. The final difference map had maxima and minima of
2
2
[19]
[20]
[21]
[22]
3
1.677 and -1.078 e/Å , respectively. The absolute structure
was determined by refinement of the Flack parameter [38].
The polar axis restraints were taken from Flack and
Schwarzenbach [39]. CCDC-246676 contains the
supplementary crystallographic data for this paper. These
data can be obtained free of charge via www.ccdc.
cam.ac.uk/conts/retrieving.html (or from the Cambridge
Crystallographic Data Center, 12 Union Road, Cambridge
CB21EZ, UK; fax: (+44)1223-336-033; or deposit@ccdc.
cam.ac.uk).
Yoon, J.; Hong, S.; Martin, K. A.; Czarnic, A. W. J. Org. Chem.,
1995, 60, 2792.
(a) Martin, K. A.; Czarnic, A. W. Tetrahedron Lett., 1994, 35,
6781; (b) Huff, J. B.; Bieniarz, C. J. J. Org. Chem., 1994, 59, 7511;
(c) Cornwell, M. J.; Huff, J. B.; Bieniarz, C. Tetrahedron Lett.,
1995, 36, 8371.
Rong, D.; Ye, H.; Boehlow, R.; D’Souza, V. T. J. Org. Chem.,
1992, 57, 163.
(a) Kajtar, M.; Horvath, T. C.; Kuthi, E.; Szejtli, J. Acta Chim.
Acad. Sci. Hung., 1982, 10, 327; (b) Kodaka, M. J. Am. Chem.
Soc., 1993, 115, 3702; (c) Bright, F. V.; Catena, G. C. Anal. Chem.,
1989, 61, 905.
[23]
[24]
[25]
[26]
(a) Zhang, X.; Nau, W. M. Angew. Chem. Int. Ed. Engl., 2000, 39,
544; (b) Liu, Y. ; Song, Y.; Chen, Y.; Yang, Z. X.; Ding, F. J.
Phys. Chem. B, 2005, 109, 10717.
(a) Ueno, A.; Ikeda, A.; Ikeda, H.; Ikeda, T.; Toda, F. J. Org.
Chem., 1999, 64, 382; (b) Hamasaki, K.; Ikeda, H.; Nakamura, A.;
Ueno, A.; Toda, F.; Suzuki, I.; Osa, T. J. Am. Chem. Soc., 1993,
115, 5035; (c) Kuwabara, T.; Nakamura, A.; Ueno, A.; Toda, F. J.
Phys. Chem., 1994, 98, 6297.
ACKNOWLEDGEMENTS
We thank Dr. Douglas R. Powel of the University of
Kansas for the X-ray crystal structure determination.
REFERENCES
[27]
[28]
Yoon, J.; Hong, S.; Martin, K. A.; Czarnic, A. W. J. Org. Chem.,
1995, 60, 2792.
[1]
Szejtli, J. Cyclodextrin Technology, Kluwer Academic Publishers:
Dordrecht, 1988.
Wenz, G. Angew. Chem., Int. Ed. Engl., 1994, 33, 803.
Szejtli, J.; Osa, T. In: Comprehensive Supramolecular Chemistry;
Atwood, J. L.; Davies, J. E. D.; MacNicol, D. D.; Vögtle, F.; Eds.
Elsevier: Oxford, UK, 1996, Vol. 3.
(a) Liu, Y.; Han, B. H.; Li, B.; Zhang, Y. M.; Zhao, P.; Chen, Y.
T.; Wada, T.; Inoue, Y. J. Org. Chem., 1998, 63, 1444; (b) Liu, Y.;
You, C. C.; Zhang, M.; Weng, L. H.; Wada, T.; Inoue, Y. Org.
Lett., 2000, 2, 2761; (c) Liu, Y.; You, C. C.; Kunieda, M.;
Nakamura, A.; Wada, T.; Inoue, Y. Supramol. Chem., 2000, 12,
299; (d) Liu, Y.; Fan, Z.; Zhang, H.; Diao, C. Org. Lett., 2003, 5,
[2]
[3]

612 Letters in Organic Chemistry, 2009, Vol. 6, No. 8
Guo et al.
251; (e) Liu, Y.; Fan, Z.; Zhang, H.; Yang, Y.; Ding, F.; Liu, S.;
Wu, X.; Wada, T.; Inoue Y. J. Org. Chem., 2003, 68, 8345.
[34]
[35]
Chimenti, F.; Bolasco, A.; Secci, D.; Chimenti, P.; Granese, A.
Synth. Commun., 2004, 34, 2549.
[29]
[30]
Eliadou, K.; Giastas, P.; Yannakopoulou, K.; Mavridis, I. M. J.
Org. Chem., 2003, 68, 8550.
(a) Ikeda, H.; Nakamura, M.; Ise, N.; Toda, F.; Ueno, A. J. Org.
Chem., 1997, 62, 1411; (b) Hamasaki, K.; Ikeda, H.; Nakamura, A.;
Ueno, A.; Toda, F.; Suzuki, I.; Osa, T. J. Am. Chem. Soc., 1993,
115, 5035.
Nelissen, H. F. M.; Feiters, M. C.; Nolte, R. J. M. J. Org. Chem.,
2002, 67, 5901.
(a) Liu, Y.; Liang, P.; Chen, Y.; Zhao, Y.; Ding, F.; Yu, A. J. Phys.
Chem. B, 2005, 109, 23739; (b) Demore, D.; Kasselouri, A.;
Bourdon, O.; Blais, J.; Mahuzier, G.; Prognon, P. Appl. Spectrosc.,
1999, 53, 523.
(a) Data Collection: SMART Software Reference Manual (1994).
Bruker-AXS, 6300 Enterprise Dr., Madison, WI 53719-1173, USA;
(b) Data Reduction: SAINT Software Reference Manual (1995).
Bruker-AXS, 6300 Enterprise Dr., Madison, WI 53719-1173, USA.
Sheldrick G. M. SADABS. Program for Empirical Absorption
Correction of Area Detector Data. 1995, University of Göttingen,
Germany.
(a) Sheldrick, G. M. SHELXTL Version 5 Reference Manual.
1994, Bruker-AXS, 6300 Enterprise Dr., Madison, WI 53719-1173,
USA. (b) International Tables for Crystallography, Vol C, Tables
6.1.1.4, 4.2.6.8, and 4.2.4.2, Kluwer: Boston, 1995.
Flack, H. D. Acta Crystallogr., 1983, A39, 876.
[36]
[37]
[31]
[32]
[38]
[39]
[33]
Hoger, S.; Bonrad, K.; Mourran, A.; Beginn, U. J. Am. Chem. Soc.,
2001, 123, 5651.
Flack, H. D.; Schwarzenbach, D. Acta Crystallogr., 1988, A44,
499.