Is [N+-H...O] hydrogen bonding the most important noncovalent interaction in macrocycle-dibenzylammonium ion complexes?

Article abstract of DOI:10.1021/jo052411+

We report a new host molecule in which one diethylene glycol chain (i.e., a loop possessing only three oxygen atoms) incorporated along with two phenolic aromatic rings is linked by a xylene spacer into a macroring. The design of the molecular structure of this macrocycle "amplifies" any potential [cation...π], [N⁺-H...π], and [N⁺C- H...π] interactions between the dibenzylammonium (DBA⁺) ion and the phenolic rings of the macrocycle; as such, these species display a very strong binding affinity in CD₃NO₂ (K_a = 15 000 M^-1). The macroring also coordinates to bipyridinium ions in a [2]pseudorotaxane fashion, which makes it the smallest macrocycle (i.e., a 25-membered ring) known to complex both DBA⁺ and bipyridinium ions in solution. To confirm unambiguously that these pseudorotaxanes exist in solution, we synthesized their corresponding interlocked molecules, namely rotaxanes and catenanes.

Full text of DOI:10.1021/jo052411+

Is [N+-H‚‚‚O] Hydrogen Bonding the Most Important Noncovalent
Interaction in Macrocycle-Dibenzylammonium Ion Complexes?
Pin-Nan Cheng,† Po-Yi Huang,† Wan-Sheung Li,‡ Shau-Hua Ueng,† Wei-Chung Hung,†
Yi-Hung Liu,† Chien-Chen Lai,§ Yu Wang,† Shie-Ming Peng,† Ito Chao,*,‡ and
Sheng-Hsien Chiu*,†
Department of Chemistry, National Taiwan UniVersity, Taipei, Taiwan, R.O.C.,
Institute of Chemistry, Academia Sinica, Nankang, Taipei, Taiwan, R.O.C., and
Department of Medical Genetics and Medical Research, China Medical UniVersity Hospital,
Taichung, Taiwan, R.O.C.
shchiu@ntu.edu.tw; ichao@chem.sinica.edu.tw
ReceiVed NoVember 22, 2005
We report a new host molecule in which one diethylene glycol chain (i.e., a loop possessing only three
oxygen atoms) incorporated along with two phenolic aromatic rings is linked by a xylene spacer into a
macroring. The design of the molecular structure of this macrocycle “amplifies” any potential [cation‚‚‚π],
[N+-H‚‚‚π], and [N+C-H‚‚‚π] interactions between the dibenzylammonium (DBA+) ion and the phenolic
rings of the macrocycle; as such, these species display a very strong binding affinity in CD3NO2 (Ka )
15 000 M-1). The macroring also coordinates to bipyridinium ions in a [2]pseudorotaxane fashion, which
makes it the smallest macrocycle (i.e., a 25-membered ring) known to complex both DBA+ and
bipyridinium ions in solution. To confirm unambiguously that these pseudorotaxanes exist in solution,
we synthesized their corresponding interlocked molecules, namely rotaxanes and catenanes.
Introduction
The more-recent finding6 that crown ethers form pseudorotax-
ane-like7 complexes with dialkylammonium ions in solution has
been a boon to research efforts aimed at the development of
functional interlocked molecular machinery.8 Many diverse
interlocked molecular structures, such as molecular shuttles,9
molecular switches,10 and molecular elevators,11 have been
After their serendipitous discovery by Pedersen,1 crown ethers
have been applied extensively as phase-transfer agents,2 mo-
lecular sensors,3 and chiral separators4 because of their ability
to form complexes with metal and quarternary ammonium ions.5
(3) (a) Takagi, M.; Nakano, K.; Nakashima, N. Pure Appl. Chem. 1989,
61, 1605-1612. (b) Gokel, G. W.; Leevy, W. M.; Weber, M. E. Chem.
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* Address correspondence to this author.
† National Taiwan University.
‡ Academia Sinica.
§ China Medical University Hospital.
(1) Pedersen, C. J. Angew. Chem., Int. Ed. Engl. 1988, 27, 1021-1027.
(2) Polymer Science and Technology; Crown Ethers and Phase Transfer
Catalysis in Polymer Science, Vol. 24; Mathias, L. J., Carraher, C. E., Jr.,
Eds.; Plenum Press: New York, 1984.
10.1021/jo052411+ CCC: $33.50 © 2006 American Chemical Society
Published on Web 02/11/2006
J. Org. Chem. 2006, 71, 2373-2383
2373

Cheng et al.
FIGURE 1. Cartoon and structural representations of the concept of deriving the oxygen-deficient macrocycle.
developed on the basis of such crown ether/dibenzylammonium
(DBA+) ion12 complexation. In this supramolecular system,
[N+-H‚‚‚O] and [N+C-H‚‚‚O] hydrogen bonding between the
host and guest units has always been considered to be the most
important stabilizing noncovalent interaction.6,13 For example,
the solid-state structure of the [2]pseudorotaxane formed
between the DBA+ ion and dibenzo[24]crown-8 (DB24C8)
displays both of these types of interactions.6a Indeed, it appears
that aliphatic ether oxygen atoms are better hydrogen bond
acceptors than are aromatic ether oxygen atoms. For example,
consider the decrease in association constants that occurs upon
the incorporation of additional benzo units into 24C8 macro-
cycles: the strength of binding to the DBA+ ion follows the
order [24]crown-8 > benzo[24]crown-8 > dibenzo[24]crown-
8 > tribenzo[24]crown-8 > tetrabenzo[24]crown-8.14 Macro-
cyclic effects15 play a role in these systems, too; bis-m-
phenylene[26]crown-8 is a weaker binder than its isomer
DB24C8 because its ring of eight oxygen atoms is not as well
preorganized for effective hydrogen bonding to the CH2-
NH2+CH2 unit of the DBA+ ion.13,16 That is not to say that
larger-ring crown ethers are necessarily always poorer binders.
Bis-p-phenylene[34]crown-10 (BPP34C10), for instance, is
capable of binding two DBA+ ions simultaneously in solution
in a 1:2 (host:guest) complex;17 in this case, the benefits of a
five-oxygen-atom oligoether loop (featuring three “good”
aliphatic ether oxygen atoms) outweigh the macrocycle’s
inability to completely encircle the CH2NH2+CH2 center of each
ion. Indeed, the even-larger crown ethers tris-p-phenylene[51]-
crown-15 and tetrakis-p-phenylene[68]crown-20 also form
complexes with DBA+ ions (three and four of them, respec-
tively), which suggests that single tetraethylene glycol loops
are all that is really required for generating pseudorotaxane-
like complexes in solution and in the solid state.18 This concept
suggests that a more diverse set of macrocyclessnot just those
that technically could be called “crown ethers”sshould also bind
to DBA+ ions (Figure 1). Naively, we might consider that as
long as we place a suitable number of ether oxygen atoms (say,
five of them) into a macrocycle then its remaining structure
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2374 J. Org. Chem., Vol. 71, No. 6, 2006

Macrocycle-Dibenzylammonium Ion Complexes
SCHEME 1
would be replaceablesas long as there is enough room, of
course, for the threading of the guest ion (i.e., at least 24 ring
atoms,19 or thereabout). In this paper, we demonstrate, however,
that this logic is not entirely correct. We have found that a
macrocycle containing merely a diethylene glycol loop (i.e., one
with just three ether oxygen atoms) is an unusually strong binder
toward DBA+ ions.20 In fact, it binds more strongly to the DBA+
ion than does the corresponding macrocycle containing an extra
ethylene glycol unit (i.e., a triethylene glycol loop). This
enigmatic behavior suggests that there may be other noncovalent
interactions that stabilize these complexes. We suggest that, in
some cases, the [cation‚‚‚π]21 interactionsalong with other
relatively weak noncovalent interactions, such as [N+-H‚‚‚π]22
and [N+C-H‚‚‚π]22c,d,23 bondingsthat exists between the DBA+
ion and π-electron-rich aromatic rings of the macrocycle can
be as stabilizing as the more-traditional [N+-H‚‚‚O]24 and
[N+C-H‚‚‚O]25 hydrogen bonds.
[Cation‚‚‚π] interactions are very important interactions that
exist between quarternary ammonium ions and aromatic host
macrocycles such as calix[4]arenes26 and cyclophanes.27 Al-
though [N+-H‚‚‚π] and [N+C-H‚‚‚π] interactions have not
yet been considered as important primary interactions in host-
guest systems in solution, they are recognized to play an
important role in molecular packing in the solid state.28 Because
we believed that DBA+ ions should interact favorably with
π-electron-rich aromatic rings through [N+-H‚‚‚π], [N+C-
H‚‚‚π], and [cation‚‚‚π] interactions, it seemed reasonable to
consider replacing the two terminal ethylene glycol units in a
tetraethylene glycol strand with two π-electron-rich benzyl units
such that the [cation‚‚‚π] interaction and potential [N+-H‚‚‚π]
and [N+C-H‚‚‚π] interactions that may form between the
aromatic rings and the CH2NH2+CH2 unit of the DBA+ ion will
compensate for the loss of any [N+-H‚‚‚O] and [N+C-H‚‚‚O]
hydrogen bonds. To enhance any macrocyclic effect, we closed
the loop of this macrocycle by linking the two phenol units
through a p-xylyl spacer. This macrocycle displays a very strong
binding affinity toward the DBA+ ion in CD3NO2 (Ka ) 15 000
M-1) and, remarkably, it binds much more tightly to these ions
than do its corresponding symmetrical crown ether (bis-p-xylyl-
[26]crown-6) and an analogous macrocycle containing a trieth-
ylene glycol loop. Relative to normal crown ethers, these
macrocycles belong to a new class of “oxygen-deficient” hosts
for DBA+ ions; they feature aromatic rings as crucial structural
elements and not just as linkers or synthetically amenable
components. Moreover, we have found that these hosts also
recognize bipyridinium ions; indeed, they are the smallest
macrocycles known to date that form pseudorotaxane-like
complexes with both DBA+ and bipyridinium ions in solution.
To confirm unambiguously the existence of these pseudorotax-
ane-like complexes in solution, we have synthesized and
characterized a number of interlocked moleculessrotaxanes and
catenanessincorporating the new macrocycles.
(11) Badjic, J. D.; Balzani, V.; Credi, A.; Silvi, S.; Stoddart, J. F. Science
2004, 303, 1845-1849.
(12) (a) Cantrill, S. J.; Pease, A. R.; Stoddart, J. F. J. Chem. Soc., Dalton
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Proc. Natl. Acad. Sci. U.S.A. 2002, 99, 4830-4836. (c) Gibson, H. W.;
Yamaguchi, N.; Jones, J. W. J. Am. Chem. Soc. 2003, 125, 3522-3533.
(13) For example, it has been stated that “the hydrogen bonding is the
much stronger, primary stabilizing variable in these systems”; see: Bryant,
W. S.; Guzei, I. A.; Rheingold, A. L.; Merola, J. S.; Gibson, H. W. J. Org.
Chem, 1998, 63, 7634-7639.
(14) Ashton, P. R.; Bartsch, R. A.; Cantrill, S. J.; Hanes, R. E., Jr.;
Hickingbottom, S. K.; Lowe, J. N.; Preece, J. A.; Stoddart, J. F.; Talanov,
V. S.; Wang, Z.-H. Tetrahedron Lett. 1999, 40, 3661-3664.
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604. (b) Haack, K.-J.; Goddard, R.; Poerschke, K.-R. J. Am. Chem. Soc.
1997, 119, 7992-7999.
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J. F.; White, A. J. P.; Williams, D. J. Chem. Eur. J. 2000, 6, 2274-2287.
(17) Ashton, P. R.; Chrystal, E. J. T.; Glink, P. T.; Menzer, S.; Schiavo,
C.; Stoddart, J. F.; Tasker, P. A.; Williams, D. J. Angew. Chem., Int. Ed.
Engl. 1995, 34, 1869-1871.
(18) Ashton, P. R.; Fyfe, M. C. T.; Glink, P. T.; Menzer, S.; Stoddart,
J. F.; White, A. J. P.; Williams, D. J. J. Am. Chem. Soc. 1997, 119, 12514-
12524.
(19) (a) Gibson, H. W.; Ganguly, S. Macromolecules 1993, 26, 2408-
2412. (b) Glink, P. T.; Schiavo, C.; Stoddart, J. F.; Williams, D. J. Chem.
Commun. 1996, 1483-1490.
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46, 4239-4242.
(21) (a) Ma, J. C.; Dougherty, D. A. Chem. ReV. 1997, 97, 1303-1324.
(b) Cametti, M.; Nissinen, M.; Dalla Cort, A.; Mandolini, L.; Rissanen, K.
J. Am. Chem. Soc. 2005, 127, 3831-3837. The stablization energies of
cation-π interactions range from -0.71 to -2.63 kcal/mol; see: (c)
Schneider, H. J.; Blatter, T.; Zimmerman, P. Angew. Chem., Int. Ed. Engl.
1990, 29, 1161-1162. (d) Kearney, P. C.; Mizoue, L. S.; Kumpf, R. A.;
Forman, J. E.; McCurdy, A.; Dougherty, D. A. J. Am. Chem. Soc. 1993,
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(22) (a) Palit, S. R.; Mukherjee, S.; De, S. K. J. Phys. Chem. 1971, 75,
2404-2405. (b) Nikolic, A. D.; Kobilarov, N. L.; Brzic, A. N. J. Mol. Struct.
1983, 99, 179-188. The interaction energies of benzene-methane (C-
H‚‚‚π) and benzene-ammonia (N-H‚‚‚π) complexes have been calculated
to be -1.45 and -2.22 kcal/mol, respectively; i.e., ca. 30-40% of the
hydrogen bonding energy of the water dimer. See: (c) Tsuzuki, S.; Honda,
K.; Uchimaru, T.; Mikami, M.; Tanabe, K. J. Am. Chem. Soc. 2000, 122,
11450-11458. (d) Tsuzuki, S.; Honda, K.; Uchimaru, T.; Mikami, M.;
Tanabe, K. J. Am. Chem. Soc. 2000, 122, 3746-3753.
Result and Discussion
Design, Syntheses, and Complexation of the New Macro-
cycles. Macrocycles 1a and 1b (Scheme 1) were both synthe-
sized with use of a simple two-step approach. The reaction
(24) The strength of a hydrogen bonding interaction depends on the
characteristics of the donor and acceptor as well as their environment, but
generally it ranges between 1 and 5 kcal/mol. For detailed descriptions of
hydrogen bonding interaction, see: (a) Jeffrey, G. A. An Introduction to
Hydrogen Bonding; Oxford University Press: New York, 1997. (b) Desiraju,
G. R.; Steiner, T. The Weak Hydrogen Bond in Structural Chemistry and
Biology; Oxford University Press: New York, 1999.
(25) According to calculations, the C-H‚‚‚O interactions between CH4
and H2O vary in strength between 0.3 and 0.7 kcal/mol. Replacing each H
atom of CH4 with an F atom adds ca. 1 kcal/mol to the binding energy.
See: (a) Novoa, J. J.; Mota, F. Chem. Phys. Lett. 1997, 266, 23-30. (b)
Gu, Y.; Kar, T.; Scheiner, S. J. Am. Chem. Soc. 1999, 121, 9411-9422.
(23) (a) Nishio, M.; Umezawa, Y.; Hirota, M.; Takeuchi, Y. Tetrahedron
1995, 51, 8665-8701. (b) Iwamoto, H.; Takahashi, N.; Maeda, T.; Hidaka,
Y.; Fukazawa, Y. Tetrahedron Lett. 2005, 46, 6839-6842.
J. Org. Chem, Vol. 71, No. 6, 2006 2375

Cheng et al.
FIGURE 2. (a) Lowest energy structure obtained after optimization of sampled structures obtained from 5000-ps MD of 1a⊃DBA+ in a water
continuum model. (b) A structure 1.22 kcal/mol above the lowest energy structure displays a different set of binding interactions. All of the H‚‚‚π
contacts are measured relative to the centroid of the relevant phenyl ring; the DBA+ ion is light blue; its +NH2 unit is dark blue.
between 4-hydroxybenzyl alcohol and R,R′-dibromo-p-xylene
under basic conditions afforded the diol 2 in 90% yield and the
following [1+1] macrocyclization reactions between diol 2 and
the diethylene and triethylene glycol ditosylates (3 and 4) gave
the desired macrocycles 1a and 1b, respectively.29 The lowest
energy structure of 1a⊃DBA+ located in the gas phase (see
the computational details below) is similar to one found in water
(Figure 2a); this finding suggests that macrocycle 1a presents
the oxygen atoms of its diethylene glycol chain and the two
π-electron-rich phenolic rings in an appropriate position to
provide a good receptor site for [N+-H‚‚‚O] and [N+C-H‚‚‚
π] interactions with the CH2NH2+CH2 center of a threaded
DBA+ ion. Because one local minimum of the same complex,
one that displays an [N+-H‚‚‚π] interaction between the two
components, is located only 1.22 kcal/mol above the lowest
1
FIGURE 3. Partial H NMR spectra [400 MHz, CDCl3/CD3CN (1:
energy structure (Figure 2b), it appears that such interactions
1), 298 K] of (a) macrocycle 1a, (b) an equimolar mixture of 1a and
DBA‚PF6 (10 mM), and (c) DBA‚PF6. The descriptors (c) and (uc)
refer to complexed and uncomplexed states of the components.
may also play a role in stabilizing this supramolecular complex.
To test this hypothesis, we examined the 1H NMR spectrum
(Figure 3b) of an equimolar mixture (10 mM) of macrocycle
1a and DBA‚PF6 in CDCl3/CD3CN (1:1). We observe three sets
of resonances, which represent the free macroring 1a (cf. Figure
3a), free DBA‚PF6 (cf. Figure 3c), and the 1:1 complex formed
between 1a and the DBA+ ion. This phenomenon implies that
the rates of complexation and decomplexation are both slow
on the 1H NMR time scale at 400 MHz and 298 K. The splitting
of the originally overlapping signals for the protons of the
diethylene glycol unit’s two methylene groups in macrocycle
1a into two separate multipletssone shifted upfield to δ 3.06
and the other downfield to δ 3.59sin the presence of the salt
suggests that hydrogen bonding probably takes place between
the host and guest, but the most remarkable shift occurs for the
methylene protons adjacent to the ammonium center. When
uncomplexed, these protons resonate at ca. 4.17 ppm, but this
signal experiences an upfield shift of >2 ppm (to δ 1.95) upon
+
complexation with 1a, which suggests that the NH2 center is
positioned in the shielding zone between the two phenol units
of 1a, as would be expected for the coexistence of [N+-H‚‚‚O]
hydrogen bonding with [N+C-H‚‚‚π] interactions. Unfortu-
nately, we were not able to detect, possibly because of severe
+
broadening, the signal for the resonance of the NH2 protons,
which we expect to also undergo a significant upfield shift. The
resonances of the phenolic CH protons shifted upfield to 6.60
and 6.74 ppm from their original positions (δ 6.74 and 7.06,
respectively), which suggests the existence of possible aryl-
aryl interactions30 caused by the threading of the DBA+ ion
into the cavity of macroring 1a. Thus, these shifts suggest that
the complex formed between macrocycle 1a and the DBA+ ion
in solution is likely to have the geometry of a [2]pseudorotaxane
[(1a⊃DBA)‚PF6] (Scheme 2). Using a single-point method,31
we determined the association constants (Ka) of this system to
be 550 M-1 in CDCl3/CD3CN (1:1) and 15 000 M-1 in CD3NO2;
i.e., the binding strength is comparable to those of crown ether-
containing complexes.32 This result suggests that noncovalent
interactions, such as [cation‚‚‚π], [N+-H‚‚‚π], and [N+C-
H‚‚‚π] interactions between the two phenolic rings and the
DBA+ ion, must contribute significantly toward stabilizing the
pseudorotaxane complex because macrocycle 1a contains only
three oxygen atoms that may behave as [N+-H‚‚‚O] and
[N+C-H‚‚‚O] hydrogen bond receptors.
(26) (a) Lhotak, P.; Shinkai, S. J. Phys. Org. Chem. 1997, 10, 273-
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(29) The yield of the reaction is ca. 5%; adding 10 equiv of LiClO4,
KPF6, or Cs2CO3 to the reaction mixture did not increase the yield
significantly, suggesting that the templating effects of these alkali metal
ions are very weak in these macrocyclization reactions.
To elucidate the effect that an extra oxygen atom in the
oligoethylene glycol motif has on the binding of this category
2376 J. Org. Chem., Vol. 71, No. 6, 2006

Macrocycle-Dibenzylammonium Ion Complexes
complexation (see the Supporting Information). According to
these results, a [2]pseudorotaxane-like assembly, [(1b⊃DBA)‚PF6]
(Scheme 2), seems to be the likely structure of the complex
1
formed between 1b and DBA+ ions in CD3NO2. From a H
NMR spectroscopic dilution experiment, we determined the
association constant (Ka) for this complex in CD3NO2 to be 2200
( 40 M-1, which is ca. 7-fold weaker than that for the complex
formed between 1a and DBA+ in the same solvent (Ka ) 15 000
M-1). This result suggests that although macrocycle 1b contains
an additional hydrogen bond receptor (i.e., four oxygen atoms,
cf. three for 1a), which, intuitively, should enhance the
favorability of [N+-H‚‚‚O] and [N+C-H‚‚‚O] hydrogen bond-
ing, its larger ring size leads to a structure that is less
preorganized to accommodate a more-complete range of non-
covalent interactions simultaneously (i.e., a diminished macro-
cyclic effect). The noncovalent interactions that exist in the
lowest energy structure of the complex 1b⊃DBA+ in the gas
phase are similar to the ones found in 1a⊃DBA+ (Figure 2a).
The larger size of macrocycle 1b, however, causes the distance
between the proton and the aromatic ring in one of the [N+C-
H‚‚‚π] interactions to be elongated significantly. Interestingly,
the lowest energy structure located for 1b⊃DBA+ in water
features [N+-H‚‚‚O], [N+C-H‚‚‚O], [N+-H‚‚‚π], and [N+C-
H‚‚‚π] interactions (Figure 5). Thus, in the complexation of the
DBA+ ion by crown ether-type hosts, our previous assumption
that electron-rich aromatic rings can replace some oxygen atoms
seems to be supported by both experimental and calculated
results, i.e., the loss of [N+-H‚‚‚O] and [N+C-H‚‚‚O] hydrogen
bonds can be compensated for by [N+-H‚‚‚π] and [N+C-
H‚‚‚π] interactions between aromatic rings and the
CH2NH2+CH2 unit of the DBA+ ion.
1
FIGURE 4. Partial H NMR spectra (400 MHz, CD3NO2, 298 K) of
(a) macrocycle 1b, (b) an equimolar mixture of 1b and DBA‚PF6 (10
mM), and (c) DBA‚PF6.
of macrocycles to DBA+ ions, we examined the interaction
between DBA‚PF6 and macrocycle 1b, which contains an extra
CH2CH2O unit. The 1H NMR spectrum of an equimolar mixture
of 1b and DBA‚PF6 in CD3NO2 (10 mM) at room temperature
displays significant changes in the chemical shifts of the protons
of the complex relative to those of its free components (Figure
4). Unlike the 1a/DBA+ ion system, whose rates of complex-
ation and decomplexation are slow at 400 MHz and 298 K, the
exchange rates for the complexation of 1b and the DBA+ ion
are fast under the same conditions so that we observe time-
averaged signals in this spectrum.
To estimate the structural importance of the xylene spacer,
we synthesized the corresponding symmetrical crown ether 5
from R,R′-dibromo-p-xylene and diethylene glycol through a
one-step [2+2] macrocyclizaton (Scheme 3). When we mixed
equamolar amounts of macrocycle 5 and DBA‚PF6 in CD3NO2
at room temperature, we observed a noticeable shifting of signals
In the spectrum of the complex, the large upfield shift (from
δ 4.50 to 3.64) of the signal for the protons of the benzylic
methylene groups adjacent to the NH2 center of the DBA+
+
ion suggests that the NH2+ center is positioned within the cavity
of the macrocycle and is stabilized possibly through [N+-
H‚‚‚O] and [N+C-H‚‚‚π] interactions. This hypothesis is
supported by the observation that, upon complexation, the
formerly “tight” multiplet (δ 3.48-3.57) for the methylene
protons of the OCH2CH2O units becomes dispersed over a wider
range of chemical shifts (δ 3.39-3.61) and is resolved into three
signals (Figure 4b). The shifts in the signals of the aromatic
protons suggest the existence of interactions between the
electronically complementary aromatic rings of macrocycle 1b
and DBA+ ion. A Job plot based on the 1H NMR spectroscopic
data obtained in CD3NO2 provided conclusive evidence for 1:1
1
in the H NMR spectrum relative to those of the free species
(Figure 6); the rates of the complexation and decomplexation
processes were fast on the NMR spectroscopic time scale under
these conditions. The upfield shift of the benzylic methylene
groups adjacent to the NH2 center of the DBA+ ion and the
+
dispersal of the methylene protons of the OCH2CH2O units into
two multiplets over a range of chemical shifts (δ 3.62-3.72)
suggest that the NH2+ center is stabilized possibly through [N+-
H‚‚‚O] and [N+C-H‚‚‚π] interactions. Again, a Job plot based
on the 1H NMR spectroscopic absorption in CD3NO2 afforded
conclusive evidence for 1:1 complexation (see the Supporting
FIGURE 5. (a) Lowest energy structure obtained after optimization of sampled structures obtained from 5000-ps MD of 1b⊃DBA+ in a water
continuum model; (b) alternative view of the same structure.
J. Org. Chem, Vol. 71, No. 6, 2006 2377

Cheng et al.
SCHEME 2
SCHEME 3
SCHEME 4
Information). We determined, through a 1H NMR spectroscopic
dilution experiment, the association constant for the interaction
between macrocycle 5 and the DBA+ ion in CD3NO2 to be 340
( 40 M-1, which is ca. 50-fold weaker than the one between
macrocycle 1a and the DBA+ ion. This result suggestssagain,
counterintuitivelysthat the presence of a p-xylyl unit is more
beneficial for the binding of a DBA+ ion than is a diethylene
glycol chain, possibly because of the macrocyclic effect due to
(a) its structural rigidity, which places the two phenolic aromatic
rings in a better position to take part in the noncovalent
interactions between the CH2NH2+CH2 center of the threaded
DBA+ ion, (b) the more-electron-rich aromatic rings, which
favor these noncovalent interactions (i.e., a phenolic ring for
1a vs a xylyl group for 5), and (c) the slightly smaller size of
the macrocycle (25 ring atoms for 1a, 26 for 5).
Rotaxanes Formed From “Oxygen-Deficient” Macrocycles
and DBA+ Ions: Synthesis and Thermal Stability. To prove
unambiguously that [2]pseudorotaxane complexes form in
solution between macrocycles 1a and 1b and DBA+ ions, we
chose to stopper such complexes to form their corresponding
[2]rotaxanes. From a CPK molecular model, it appeared that
because compound 1a is a 25-membered-ring macrocycle that
incorporates three rigid benzene rings, diethyl phosphoramidate
groups33 would serve as suitable stoppers. Thus, we added
triethyl phosphite (200 mM) to a solution of benzylic azide
6-H‚PF6 (100 mM) and macrocycle 1a (150 mM) in CH2Cl2
(30) Chemical double-mutant cycles have been used to measure the
strengths of aromatic stacking interactions; the estimated stabilization
energies are less than 0.34 kcal/mol, depending on the interacting aromatic
system. See: (a) Carver, F. J.; Hunter, C. A.; Jones, P. S.; Livingstone, D.
J.; McCabe, J. F.; Seward, E. M.; Tiger, P.; Spey, S. E. Chem. Eur. J.
2001, 7, 4854-4862. (b) Adams, H.; Hunter, C. A.; Lawson, K. R.; Perkins,
J.; Spey, S. E.; Urch, C. J.; Sanderson, J. M. Chem. Eur. J. 2001, 7, 4863-
4878.
1
FIGURE 6. Partial H NMR spectra (400 MHz, CD3NO2, 298 K) of
(a) macrocycle 5, (b) an equimolar mixture of 5 and DBA‚PF6 (20
mM), and (c) DBA‚PF6.
2378 J. Org. Chem., Vol. 71, No. 6, 2006

Macrocycle-Dibenzylammonium Ion Complexes
FIGURE 7. Partial 1H NMR spectra (400 MHz, CD3CN, 10 mM, 298
K) of (a) [2]rotaxane 7-H‚PF6, (b) an equimolar mixture of rotaxane
7-H‚PF6 and macrocycle 1a, and (c) macrocycle 1a.
1
FIGURE 8. Partial H NMR (400 MHz, 323 K) spectra displaying
the dissociation of [2]rotaxane 8-H‚PF6 in CD3SOCD3 over time: (a)
0 min, (b) 20 min, (c) 60 min, and (d) 3 h.
and isolated the corresponding [2]rotaxane 7-H‚PF6 in 57% yield
after column chromatography over silica gel. The reaction
between macrocycle 1b, benzylic azide 6-H‚PF6,33 and triethyl
phosphite, however, gave no corresponding [2]rotaxane, prob-
ably because macrocycle 1b contains a 28-membered ring,
which it too large to be entrapped by the diethyl phosphora-
midate stoppering units. After inspecting CPK molecular models,
we believed that the sterically more sizable dibutyl phospho-
ramidate groups would be more reasonable choices as stoppers.
Gratifyingly, when we added tributyl phosphate (200 mM) to
an equimolar mixture of the benzyl azide 6-H‚PF6 and macro-
cycle 1b in CH2Cl2 (100 mM) we isolated the corresponding
tutional integrity of [2]rotaxane 8-H‚PF6 (see the Supporting
Information).
To test the thermal stability of the phosphoramidate-stoppered
[2]rotaxanes 7-H‚PF6 and 8-H‚PF6, we dissolved them individu-
ally in CD3SOCD3 (5 mM) and heated them to 323 K while
1
1
monitoring their H NMR spectra. The H NMR spectrum of
[2]rotaxane 7-H‚PF6, in which macrocycle 1a is entrapped by
diethyl phosphoramidate stoppers, was unchanged after heating
for 2 h under these conditions. In contrast, the 1H NMR spectra
of the [2]rotaxane 8-H‚PF6 (Figure 8) indicate that the intensity
of the signals of the free macrocycle 1b increased, and those
for 8-H‚PF6 decreased; i.e., dissociation of the macrocyclic unit
of 8-H‚PF6 occurred in CD3SOCD3 at 323 K. Thus, the di-n-
butyl phosphoramidate terminus/macrocycle 1b pair does not
constitute a true interlocking system, but rather one that is a
slippage-amenable rotaxane system. This result led us to prepare
the [2]rotaxane 9-H‚PF6, in which macrocycle 1b is confined
between two slightly larger di-n-hexyl phosphoramidate stop-
pers; this rotaxane is stable as a supramolecular entity in
CD3SOCD3 at 323 K for at least 2 h.
1
[2]rotaxane 8-H‚PF6 in 14% yield.34 The H NMR spectrum
(Figure 7a) of the [2]rotaxane 7-H‚PF6 recorded in CD3CN
displays upfield shifts in the positions of the signals of the
resonances of (a) the methylene protons adjacent to the
ammonium center (cf. the corresponding signal for 6-H‚PF6)
and (b) the ethylene protons of the encircled macrocyclic
component of 7-H‚PF6, relative to the positions of these signals
in their free components; these shifts confirm that the interac-
tions between these components in the rotaxane are similar to
those present in the initial [1a⊃DBA]+ complex. The 1H NMR
spectrum (Figure 7b) of an equimolar mixture of 7-H‚PF6 and
macrocycle 1a (10 mM each) in CD3CN at 298 K corresponds
to a superimposition of the two spectra (cf. Figure 7a,c) of the
separate components. These spectra establish that no exchange
occurs between the macrocycle and dumbbell components in
solution and, therefore, proves the constitutional integrity of the
[2]rotaxane.35 We used a similar method to prove the consti-
The fact that it is possible to generate [2]pseudorotaxane
complexes in solution from the interaction of DBA+ ions with
macrocycles 1a and 1b that contain loops of just three or four
oxygen atoms suggests that the cooperative effect of at least
five oxygen atoms found in the recognition sites of most of the
crown ethers that have been used previously to complex DBA+
ions is not a necessary prerequisite for efficient binding. Indeed,
it appears that [cation‚‚‚π], [N+-H‚‚‚π], and [N+C-H‚‚‚π]
interactions can be harnessed to play extremely important roles
in stabilizing macrocycle/dialkylammonium ion complexes.
Macrocycles 1a and 1b Recognize Bipyridinium Ions.
Because the two electron-rich phenol rings linked by an ethylene
glycol chain are placed in a distance (ca. 7.0 Å) suitable for
π-stackingsbased on CPK molecular models and molecular
mechanics calculationsswe suspected that macrocycles 1a and
1b may be able to recognize electron-deficient bipyridinium ions
in addition to dialkylammonium ions.36 When we mixed
equimolar amounts (10 mM) of 1b and methyl viologen bis-
(hexafluorophosphate) 10‚2PF6 in CD3NO2, the solution turned
yellow immediately. The observation of upfield shifts for the
signals of aromatic protons of both 1b and 10‚2PF6 in 1H NMR
spectra, relative to those of the free species, implies that the
π-electron-deficient bipyridinium ion may be positioned within
the cavity of 1b such that it stacks with the π-electron-rich
(31) (a) Ashton, P. R.; Chrystal, E. J. T.; Glink, P. T.; Menzer, S.;
Schiavo, C.; Spencer, N.; Stoddart, J. F.; Tasker, P. A.; White, A. J. P.;
Williams, D. J. Chem. Eur. J. 1996, 2, 709-728. (b) Ashton, P. R.; Fyfe,
M. C. T.; Hickingbottom, S. K.; Stoddart, J. F.; White, A. J. P.; Williams
D. J. J. Chem. Soc., Perkin Trans. 2 1998, 2117-2124.
(32) The association constant (Ka) between DB24C8 and DBA+ ion in
CD3NO2 has been reported to be 8000 M-1; see: Chiu, S.-H.; Liao, K.-S.;
Su, J.-K. Tetrahedron Lett. 2004, 45, 213-216.
(33) Hung, W.-C.; Liao, K.-S.; Liu, Y.-H.; Peng, S.-M.; Chiu, S.-H. Org.
Lett. 2004, 6, 4183-4186.
(34) The lower yield of this reaction may be the result of the lower
association constant of the interaction between the DBA+ ion and
macrocycle 1b, relative to that of macrocycle 1a. Shielding of the
ammonium center by the macrocycle has been suggested as an important
factor in the success of these stoppering reactions; see ref 33.
(35) A similar method had been applied previously to prove the structural
integrity of rotaxanes; see: Chiu, S.-H.; Stoddart, J. F. J. Am. Chem. Soc.
2002, 124, 4174-4175.
J. Org. Chem, Vol. 71, No. 6, 2006 2379

Cheng et al.
SCHEME 5
SCHEME 6
phenol rings to form a [2]pseudorotaxane-like complex. The
dispersion of the “tight” multiplet (δ 3.48-3.57) for the protons
of the OCH2CH2O units of uncomplexed 1b into three distinct
signals and the upfield shift of the R-protons on the bipyridinium
ion (Figure 9) suggest that weak [C-H‚‚‚O] hydrogen bonds
may exist along with π-stacking interactions in this [2]-
pseudorotaxane-like complex [(1b⊃10)‚2PF6] (cf. the similar
shifts observed in the NMR spectra of the complex formed
between BPP34C10 and 10‚2PF6).36a,37 From a 1H NMR
spectroscopic dilution experiment, we determined the association
constant (Ka) for the complexation between 1b and 10‚2PF6 in
case is 60 ( 7 M-1, i.e., about half that of the interaction
between 1b and 10‚2PF6. This finding implies that even through
1b is less preorganized for the binding of DBA+ ions than is
1a, the extra hydrogen-bond-accepting oxygen atom of its
oligoethylene glycol loop and its increased cavity size may be
more accommodating for bipyridinium ions such that it may
provide simultaneous π-stacking and [C-H‚‚‚O] hydrogen
bonding interactions.
To prove that the complexes that form between 10‚2PF6 and
macrocycles 1a and 1b have [2]pseudorotaxane-like architec-
tures in solution, we synthesized the corresponding interlocked
molecules. We isolated the [2]catenane 12b‚4PF6 (Scheme 6)
comprising the macrocycles 1b and cyclobis(paraquat-p-phe-
nylene) (CBPQT4+) as a yellow solid in 29% yield after reacting
1b, 11‚2PF6,37 and R,R′-dibromo-p-xylene in DMF at ambient
temperature. Reacting macrocycle 1a under the same conditions
gave the corresponding [2]catenane 12a‚4PF6 in 21% yield.
Because these syntheses must proceed via pseudorotaxane-like
CD3NO2 to be 130 ( 3 M-1
.
We observed similar shifts in the signals of an equimolar
mixture of the smaller macrocycle 1a and 10‚2PF6 under the
same conditions (Figure 10); the association constant in this
1
FIGURE 9. Partial H NMR spectra (400 MHz, CD3NO2, 298 K) of
FIGURE 10. Partial 1H NMR spectra (400 MHz, CD3NO2, 298 K) of
(a) macrocycle 1a, (b) an equimolar mixture of 1a and 10‚2PF6 (10
mM), and (c) 10‚2PF6.
(a) macrocycle 1b, (b) an equimolar mixture of 1b and 10‚2PF6 (10
mM), and (c) 10‚2PF6.
2380 J. Org. Chem., Vol. 71, No. 6, 2006

Macrocycle-Dibenzylammonium Ion Complexes
of molecular switches. Although large crown ethers, such as
BPP34C10 and BMP32C10, can also recognize both of these
guests in solution, small crown ethers, such as DB24C8 and
BMP26C8, seem to lack this ability.38 To the best of our
knowledge, macrocycle 1a is the smallest macrocycle (a 25-
membered ring) that is capable of complexing both guests in a
[2]pseudorotaxane-like fashion in solution. The much smaller
ring size of macrocycles 1a and 1b, when compared to that of
BPP34C10, may make the syntheses of their corresponding
functional interlocked molecules much easier because they do
not require relatively enormous groups,36c,39 such as tris(4-tert-
butylphenyl)methyl units, to serve as effective stopper moieties.
Conclusions
FIGURE 11. Solid-state structure of the [2]catenane 12b4+. Disorder
of atoms is observed in the ethylene glycol chain (from O3 to O6).
Hydrogen bond geometries (C‚‚‚O and H‚‚‚O distances [Å] and
C-H‚‚‚O angles [deg]): (a) 3.321(7), 2.45, 153.0; (b) 3.501(7), 2.59,
153.8.
We have synthesized a new category of macrocycles,
containing suitably positioned oligoethylene glycol chains and
aromatic rings, that form [2]pseudorotaxane-like complexes with
both dialkylammonium and bipyridinium ions in solution. The
chemical structures of crown ethers that have been reported to
bind DBA+ ions have generally comprised oligoethylene glycol
chains that provide a cooperative effect of at least five oxygen
atoms; in this paper, however, we demonstrate that such a
prerequisite is not a necessary one for efficient binding. With
suitable design, the cooperative effects of [N+C-H‚‚‚π], [N+-
H‚‚‚π], and [cation‚‚‚π] interactions in conjunction with more-
traditional hydrogen bonds between the macrocycles and DBA+
ions can result in extremely stable pseudorotaxane complexes.
That is to say, the oxygen atoms of crown ethers can be replaced
by phenol units and still retain their effective binding properties
toward DBA+ ions. We are currently trying to identify the major
noncovalent interactions that occur between macrocycle 1a and
the DBA+ ion and stabilize this pseudorotaxane complex.
Hopefully, these studies will lead us to a greater understanding
and control over less-traditional noncovalent interactions.
FIGURE 12. Solid-state structure of the [2]catenane 12a4+. Hydrogen
bond geometries (C‚‚‚O and H‚‚‚O distances [Å] and C-H‚‚‚O angles
[deg]): (a) 2.883(18), 2.39, 112.1; (b) 3.021(18), 2.16, 150.7.
intermediates, we believe that the successful isolation of these
two [2]catenanes proves that macrocycles 1a and 1b each bind
bipyridinium ions in the form of [2]pseudorotaxane complexes.
We used vapor diffusion of isopropyl ether into respective
CH3CN solutions of 12a‚4PF6 and 12b‚4PF6 to obtain single
crystals, which were suitable for X-ray crystallographic analysis,
of both of these [2]catenanes. The solid-state structures (Figures
11 and 12) of these two catenanes reveal the expected π-stacking
interactions and [C-H‚‚‚O] hydrogen bonds between their
interlocked macrocycles.
Experimental Section
Computational Details. Stochastic molecular dynamics simula-
tions were performed with MacroModel V9.0 in conjunction with
the all-atom AMBER* force-field.40,41 The continuum GB/SA
model in MacroModel was used for simulations in water.42 Constant
dielectric treatment was used to estimate the electrostatic interac-
tions. A 200-ps equilibration step with a 1-fs time step was followed
(38) The interaction between N,N-dibenzylbipyridinium bis(hexafluoro-
phosphate) and DB24C8 is negligible; see: (a) Mart´ınez-D´ıaz, M.-V.;
Spencer, N.; Stoddart, J. F. Angew. Chem., Int. Ed. Engl. 1997, 36, 1904-
1907. (b) Ashton, P. R.; Langford, S. J.; Spencer, N.; Stoddart, J. F.; White,
A. J. P.; Williams, D. J. Chem. Commun. 1996, 1387-1388. The interaction
between the DBA+ ion and BMP26C8 is also negligible; see refs 13 and
16. When applying the concept of multivalency, however, DB24C8 can
interact quite strongly with bipyridinium ions in solution; see: Badjiæ, J.
D.; Cantrill, S. J.; Stoddart, J. F. J. Am. Chem. Soc. 2004, 126, 2288-
2289.
(39) (a) Ashton, P. R.; Philp, D.; Spencer, N.; Stoddart, J. F. J. Chem.
Soc., Chem Commun. 1992, 1124-1128. (b) Vignon, S. A.; Jarrosson, T.;
Iijima, T.; Tseng, H.-R.; Sanders, J. K. M.; Stoddart, J. F. J. Am. Chem.
Soc. 2004, 126, 9884-9885. BPP34C10-based rotaxanes are generally
synthesized using slippage approaches. See: (c) Belohradsky, M.; Elizarov,
A. M.; Stoddart, J. F. Collect. Czech. Chem. Commun. 2002, 67, 1719-
1728.
(40) Mohamandi, F.; Richards, N. G. J.; Guida, W. C.; Liskamp, R.;
Liption, M.; Caufield, C.; Chang, G.; Hendrickson, T.; Still, W. C. J.
Comput. Chem. 1990, 11, 400-467.
(41) (a) Weiner, S. J.; Kollman, P. A.; Case, D. A.; Singh, U. C.; Chio,
C.; Alagona, G.; Profeta, S.; Weiner, P. J. Am. Chem. Soc. 1984, 106, 765-
784. (b) Weiner, S. J.; Kollman, P. A.; Case, D. A. J. Comput. Chem. 1986,
7, 230-252.
The fact that macrocycles 1a and 1b form pseudorotaxane-
like complexes with both DBA+ and bipyridinium ions in
solution makes them suitable candidates for the construction
(36) Bipyridinium ions form pseudorotaxane-like complexes with several
sizable crown ethers; see: (a) Allwood, B. L.; Spencer, N.; Shahriari-
Zavareh, H.; Stoddart, J. F.; Williams, D. J. J. Chem. Soc., Chem. Commun.
1987, 1064-1066. (b) Allwood, B. L.; Shahriari-Zavareh, H.; Stoddart, J.
F.; Williams, D. J. J. Chem. Soc., Chem. Commun. 1987, 1058-1061. (c)
Asakawa, M.; Ashton, P. R.; Ballardini, R.; Balzani, V.; Belohradsky, M.;
Gandolfi, M. T.; Kocian, O.; Prodi, L.; Raymo, F. M.; Stoddart, J. F.; Venturi
M. J. Am. Chem. Soc. 1997, 119, 302-310. (d) Yamaguchi, N.; Nagvekar,
D. S.; Gibson, H. W. Angew. Chem., Int. Ed. Engl. 1998, 37, 2361-2364.
(e) Bryant, W. S.; Jones, J. W.; Mason, P. E.; Guzei, I.; Rheingold, A. L.;
Fronczek, F. R.; Nagvekar, D. S.; Gibson, H. W. Org. Lett. 1999, 1, 1001-
1004. (f) Huang, F.; Zakharov, L. N.; Rheingold, A. L.; Ashraf-Khorassani,
M.; Gibson, H. W. J. Org. Chem. 2005, 70, 809-813.
(37) Anelli, P. L.; Ashton, P. R.; Ballardini, R.; Balzani, V.; Delgado,
M.; Gandolfi, M. T.; Goodnow, T. T.; Kaifer, A. E.; Philp, D.; Pietraszk-
iewicz, M.; Prodi, L.; Reddington, M. V.; Slawin, A. M. Z.; Spencer, N.;
Stoddart, J. F.; Vicent, C.; Williams, D. J. J. Am. Chem. Soc. 1992, 114,
193-218.
J. Org. Chem, Vol. 71, No. 6, 2006 2381

Cheng et al.
by a 5000-ps MD run with a 1-fs time step at 300 K. Structures
were sampled at regular intervals of 1 ps during the simulations.
The sampled structures were then minimized with use of the PR
conjugated gradient method to obtain the lowest energy structure
in each simulation. A previous study on â-cyclodextrin complexes
has shown this method of locating low-energy structures to be
superior to using the Monte Carlo multiple minimum (MCMM)
search in MacroModel.43 During the MD simulations, the guest
changes orientation and position in the host, but no decomplexation
was observed. The lowest energy structures of 1a⊃DBA+ and
1b⊃DBA+ are stabilized through a combination of [N+-H‚‚‚π],
[N+C-H‚‚‚π], [N+-H‚‚‚O], and [N+C-H‚‚‚O] contacts between
the CH2NH2+CH2 unit of a threaded DBA+ ion and the oxygen
atoms and aromatic rings of the macrocycles. Face-to-face and
T-shaped π-π interactions were also observed between the aromatic
rings of both the DBA+ ion and the macrocycles.
X-ray Diffraction Analyses. The crystals were mounted on a
glass fiber. Crystal data were collected on diffractometers installed
with monochromatized Mo KR radiation, λ ) 0.71073 Å at T )
150 K. All structures were solved by using the SHELXS-9744 and
refined with SHELXL-9745 by full matrix least squares on F2 values
with restraints of the disordered motifs. Hydrogen atoms were fixed
at calculated positions and refined by using a riding mode. For
[2]catenane 12a‚4PF6, the final indices were R1 ) 0.0599, wR2 )
0.1360 with goodness-of-fit on F2 ) 0.848. For [2]catenane
12b‚4PF6, the final indices were R1 ) 0.0669, wR2 ) 0.1533 with
goodness-of-fit on F2 ) 0.987.
tosylate 4 (2.30 g, 5.0 mmol) was added slowly to a solution of
diol 2 (1.74 g, 5.0 mmol) and NaH (368 mg, 15.0 mmol) in DMF
(500 mL); the resulting mixture was stirred at room temperature
for 7 days. The reaction was quenched by the addition of MeOH
(5 mL) and the organic solvent was evaporated under reduced
pressure. The residue was partitioned between H2O (300 mL) and
CH2Cl2 (300 mL); the organic layer was collected, dried (MgSO4),
and concentrated to afford a crude product, which was then purified
by column chromatography (SiO2; EtOAc/hexane, 3:7) to give the
1
macrocycle 1b as a white solid (116 mg, 5%). Mp 78-79 °C; H
NMR (400 MHz, CDCl3) δ 3.50-3.55 (m, 4H), 3.60-3.64 (m,
8H), 4.40 (s, 4H), 5.19 (s, 4H), 6.75 (d, J ) 8 Hz, 4H), 7.11 (d, J
) 8 Hz, 4H), 7.26 (s, 4H); 13C NMR (100 MHz, CDCl3) δ 69.2,
69.5, 70.6, 71.0, 72.9, 115.2, 126.6, 129.0, 130.2, 136.8, 157.3;
HR-MS (ES) C28H33O6 [M + H]+ calcd m/z 465.2272, found m/z
465.2282. Anal. Calcd for C28H32O6: C, 72.39; H, 6.94; O, 20.66.
Found: C, 72.23; H, 7.02; O, 20.75.
Bis-p-xylyl[26]crown-6 (5). R,R′-Dibromo-p-xylene (5.0 g, 19
mmol) was added slowly to a solution of diethylene glycol (2.0 g,
19 mmol) and NaH (0.98 g, 40 mmol) in DMF (800 mL); the
resulting mixture was stirred at room temperature for 7 days. The
reaction was quenched by the addition of MeOH (10 mL) and the
organic solvent was removed under reduced pressure. The residue
was partitioned between H2O (500 mL) and CH2Cl2 (500 mL); the
organic layer was collected, dried (MgSO4), and concentrated to
afford a crude product, which was then purified by column
chromatography (SiO2; EtOAc/hexane, 4:6) to give the macrocycle
1
[1,4-Phenylenebis(methyleneoxy-4,1-phenylene)]dimethanol
(2). A mixture of 4-hydroxybenzyl alcohol (3.72 g, 30 mmol), R,R′-
dibromo-p-xylene (2.63 g, 10 mmol), and K2CO3 (10 g, 72.4 mmol)
in DMF (50 mL) was heated at 50 °C for 2 days. The reaction
mixture was cooled to room temperature and the organic solvent
was evaporated under reduced pressure. The residue was washed
with CH2Cl2 (500 mL), H2O (500 mL), and MeOH (150 mL) to
5 as a white solid (400 mg, 5%). Mp 69-70 °C; H NMR (400
MHz, CDCl3) δ 3.66-3.72 (m, 16H), 4.59 (s, 8H), 7.31 (s, 8H);
13C NMR (100 MHz, CDCl3) δ 69.8, 71.2, 73.1, 127.5, 137.5; HR-
MS (ES) C24H33O6 [M + H]+ calcd m/z 417.2277, found m/z
417.2201. Anal. Calcd for C24H32O6: C, 69.21; H, 7.74; O, 23.05.
Found: C, 69.01; H, 7.82; O, 23.17.
[2]Rotaxane 7-H‚PF6. Triethyl phosphite (0.05 mL, 0.28 mmol)
was added slowly to a solution of 6-HPF6 (60 mg, 0.14 mmol) and
macrocycle 1a (90 mg, 0.22 mmol) in CH2Cl2 (1.4 mL). After the
mixture had been stirred at ambient temperature for 16 h, the solvent
was evaporated under reduced pressure. The residue was purified
chromatographically (SiO2: CH2Cl2/MeOH, 98:2) and the desired
[2]rotaxane 7-HPF6 was isolated as a white solid (90 mg, 57%).
1
afford the desired product 2 (3.14 g, 90%). Mp 196-198 °C; H
NMR (400 MHz, CD3SOCD3) δ 4.40 (s, 4H), 5.08 (s, 4H), 6.94
(d, J ) 8 Hz, 4H), 7.21 (d, J ) 8 Hz, 4H), 7.43 (s, 4H); 13C NMR
(100 MHz, CD3SOCD3) δ 62.4, 68.7, 113.9, 127.0, 127.3, 134.1,
136.0, 156.2; HR-MS (ES) C22H22O4Na [M + Na]+ calcd m/z
373.1416, found m/z 373.1450. Anal. Calcd for C22H22O4: C, 75.41;
H, 6.33; O, 18.26. Found: C, 75.62; H, 6.27; O, 18.11.
1
Mp 85-87 °C; H NMR (400 MHz, CD3CN) δ 1.42 (t, J ) 6.8
2,9,15,18,21-Pentaoxatetracyclo[21.2.2.24,7.210,13]hentriaconta-
1(25),4,6,10,12,23,26,28,30-nonaene (1a). Diethylene glycol di-
tosylate 3 (5.95 g, 14.4 mmol) was added slowly to a solution of
diol 2 (5.0 g, 14.4 mmol) and NaH (1.75 g, 42.8 mmol) in DMF
(700 mL) and the resulting mixture was stirred at room temperature
for 7 days. The reaction was quenched by the addition of MeOH
(10 mL) and then the organic solvent was evaporated under reduced
pressure. The residue was partitioned between H2O (500 mL) and
CH2Cl2 (500 mL); the organic layer was collected, dried (MgSO4),
and concentrated to afford a crude product, which was then purified
by column chromatography (SiO2; EtOAc/hexanes, 3:7) to give
Hz, 12H), 2.14 (t, J ) 6.8 Hz, 4H), 3.26-3.29 (m, 4H), 3.72-
3.74 (m, 4H), 3.97-4.00 (m, 2H), 4.09-4.17 (m, 8H), 4.19 (s,
4H), 4.23-4.27 (m, 4H), 5.44 (s, 4H), 6.76 (d, J ) 10.8 Hz, 4H),
6.84 (d, J ) 7.6 Hz, 4H), 6.89 (d, J ) 10.8 Hz, 4H), 7.54 (d, J )
7.6 Hz, 4H), 7.59 (s, 4H); 13C NMR (100 MHz, CH3CN) δ 17.8
(d, JPC ) 6.9 Hz), 46.3, 52.2, 63.8 (JPC ) 5.3 Hz), 69.1, 70.8, 72.1,
75.2, 117.3, 128.7, 128.8, 129.6, 129.7, 130.5, 132.4, 138.6, 142.9
(d, JPC ) 5.3 Hz), 158.6; HR-MS (ES) C50H68N3O11P2 [7-H]+ calcd
m/z 948.4329, found m/z 948.4332.
[2]Rotaxane 8-H‚PF6. Tributyl phosphite (0.1 mL, 0.36 mmol)
was added slowly to a solution of 6-H‚PF6 (81 mg, 0.18 mmol)
and macrocycle 1b (83 mg, 0.18 mmol) in CH2Cl2 (1.8 mL). After
the mixture had been stirred at ambient temperature for 16 h, the
solvent was evaporated under reduced pressure. The residue was
purified by chromatography (SiO2: CH2Cl2/MeOH, 98:2) and the
desired [2]rotaxane 8-H‚PF6 was isolated as a colorless oil (30 mg,
1
macrocycle 1a as a white solid (183 mg, 3%). Mp 96-98 °C; H
NMR (400 MHz, CDCl3) δ 3.48-3.52 (m, 4H), 3.58-3.62 (m,
4H), 4.39 (s, 4H), 5.17 (s, 4H), 6.65 (d, J ) 8 Hz, 4H), 7.06 (d, J
) 8 Hz, 4H), 7.27 (s, 4H); 13C NMR (100 MHz, CDCl3) δ 69.1,
69.6, 70.5, 72.6, 115.6, 127.0, 129.0, 130.3, 136.8, 157.0; HR-MS
(ES) C26H29O5 [M + H]+ calcd m/z 421.2015, found m/z 421.2008.
Anal. Calcd for C26H28O5: C, 74.26; H, 6.71; O, 19.02. Found: C,
74.37; H, 6.78; O, 18.85.
1
14%). H NMR (400 MHz, CDCl3) δ 0.90-0.94 (t, J ) 7.6 Hz,
12H), 1.36-1.45 (m, 8H), 1.62-1.69 (m, 8H), 3.08-3.11 (m, 4H),
3.24 (s, 4H), 3.32-3.35 (m, 4H), 3.51-3.54 (m, 4H), 3.97-4.06
(m, 10H), 4.14 (d, J ) 8 Hz, 4H), 4.19 (s, 4H), 5.18 (s, 4H), 6.73
(d, J ) 8 Hz, 4 H), 6.79 (d, J ) 8 Hz, 4 H), 6.89 (d, J ) 8 Hz, 4
H), 7.28-7.35 (m, 8H); 13C NMR (100 MHz, CDCl3) δ 14.1, 19.2,
32.7 (d, JPC ) 7 Hz), 45.0, 51.2, 66.5, 66.6, 68.3, 70.4 (d, JPC ) 5
Hz), 74.1, 114.8, 126.8, 127.3, 128.3, 128.5, 128.6, 128.8, 129.6,
136.3, 141.5, 157.2; HR-MS (ES) C60H88N3O12P2 [8-H]+ calcd m/z
1104.5844, found m/z 1104.5816.
2,9,15,18,21,24-Hexaoxatetracyclo[24.2.2.24,7.210,13]tetratriaconta-
1(28),4,6,10,12,26,29,31,33-nonaene (1b). Triethylene glycol di-
(42) Still, W. C.; Tempczyk, A.; Hawley, R. C.; Hendrickson, T. J. Am.
Chem. Soc. 1990, 112, 6127-6129.
(43) Li, W.-S.; Chung, W.-S.; Chao, I. Chem. Eur. J. 2003, 9, 951-
962.
(44) Sheldrick, G. M. Acta Crystallogr. 1990, A46, 467-473.
(45) Sheldrick, G. M. SHELXL-97, Program for the Refinement of Crystal
Structures; University of Gottingen: Gottingen, Germany, 1997.
[2]Rotaxane 9-H‚PF6. Trihexyl phosphite (0.08 mL, 0.22 mmol)
was added slowly to a solution of 6-H‚PF6 (49 mg, 0.11 mmol)
2382 J. Org. Chem., Vol. 71, No. 6, 2006

Macrocycle-Dibenzylammonium Ion Complexes
and macrocycle 1b (50 mg, 0.11 mmol) in CH2Cl2 (0.7 mL). After
the mixture had been stirred at ambient temperature for 16 h, the
solvent was evaporated under reduced pressure. The residue was
purified by chromatography (SiO2: CH2Cl2/MeOH, 98:2) and the
desired [2]rotaxane 9-H‚PF6 was isolated as a colorless oil (37 mg,
142.2, 144.6, 144.9, 147.0, 154.4, 156.5 (one signal is missing,
presumably because of signal overlap); HR-MS (ES) C62H58N4O5
[12a-2H]2+ calcd m/z 469.2203, found m/z 469.2198.
[2]Catenane 12b‚4PF6. R,R′-Dibromo-p-xylene (26.2 mg, 0.1
mmol) was added slowly to a solution of 11 (70.6 mg, 0.1 mmol)
and 1b (46.6 mg, 0.1 mmol) in DMF (1 mL); the resulting mixture
was stirred at ambient temperature for 24 h. The organic solvent
was evaporated under reduced pressure, the residue was dissolved
in MeCN (10 mL), and then saturated aqueous NH4PF6 (20 mL)
was added. The solvent was evaporated and the precipitate was
collected and washed with H2O (5 mL) to afford a yellow solid,
which was recrystallized (MeCN/isopropyl ether) to afford the
desired [2]catenane 12b‚4PF6 (46 mg, 29%). Mp >228 °C dec; 1H
NMR (400 MHz, CD3CN) δ 3.43-3.52 (br, 4H), 3.53-3.55 (m,
4H), 3.67-3.69 (m, 4H), 3.78 (s, 4H), 5.16 (s, 4H), 5.68 (s, 8H),
7.27 (br, 8H), 7.74 (s, 4H), 7.83 (s, 8H), 8.71 (br, 8H) [one signal
(8H) is missing, presumably because of severe signal broadening];
13C NMR (100 MHz, CD3CN) δ 65.1, 67.7, 70.6, 70.7, 71.2, 71.7,
114.5, 126.6, 128.3, 129.3, 130.8, 137.1, 138.4, 144.2, 146.4, 155.3
(one signal is missing, presumably because of signal overlap); HR-
MS (FAB) C64H64N4O6P3F18 [12b‚3PF6]+ calcd m/z 1419.3751,
found m/z 1419.3778.
1
25%). H NMR (400 MHz, CDCl3) δ 0.88 (t, J ) 8 Hz, 12 H),
1.25-1.40 (m, 24H), 1.62-1.72 (m, 8H), 3.12 (s, 4H), 3.27 (s,
4H), 3.36 (s, 4H), 3.54 (s, 4H), 4.00-4.04 (m, 10H), 4.15, (d, J )
12 Hz, 4H), 4.20 (s, 4H), 5.20 (s, 4H), 6.74 (d, 4H), 6.79 (d, J )
8 Hz, 4H), 6.89 (d, J ) 8 Hz, 4H), 7.31-7.33 (m, 8H); 13C NMR
(100 MHz, CDCl3) δ 14.1, 22.6, 25.3, 29.8, 30.4, 30.5, 31.4 (d,
JPC ) 3 Hz), 44.9, 51.1, 66.7, 68.3, 70.3, 70.5, 74.1, 115.0, 127.6,
128.5, 128.7, 129.0, 129.8, 136.5, 141.5, 157.5; HR-MS (ES)
C68H104N3O12P2 [9-H]+ calcd m/z 1216.7095, found m/z 1216.7135.
[2]Catenane 12a‚4PF6. R,R′-Dibromo-p-xylene (32 mg, 0.12
mmol) was added slowly to a solution of 11‚2PF6 (85 mg, 0.12
mmol) and 1a (50 mg, 0.12 mmol) in DMF (1 mL); the resulting
mixture was stirred at ambient temperature for 24 h. The solvent
was evaporated under reduced pressure, the residue was dissolved
in MeCN (10 mL), and then saturated aqueous NH4PF6 (20 mL)
was added. The organic solvent was evaporated and the precipitate
was collected and washed with H2O (5 mL) to afford a yellow
solid, which was recrystallized (MeCN/isopropyl ether) to afford
the desired [2]catenane 12a‚4PF6 as a yellow solid (38 mg, 21%).
1
Acknowledgment. We thank the anonymous reviewers for
their helpful suggestions and the National Science Council,
Taiwan (NSC-93-2113-M-002-020), for the financial support.
Mp >252 °C dec; H NMR (400 MHz, CD3CN) δ 3.01 (s, 2H),
3.27 (d, J ) 8 Hz, 2H), 3.56-3.62 (m, 6H), 3.72-3.74 (m, 4H),
3.78-3.83 (m, 2 H), 5.05 (s, 2H), 5.09-5.11 (m, 2H), 5.32 (s,
2H), 5.58 (d, J ) 13 Hz, 2H), 5.70 (d, J ) 13 Hz, 2H), 5.74 (s,
4H), 6.08 (d, J ) 8 Hz, 2H), 6.40 (d, J ) 8 Hz, 2H), 7.74-7.77
(m, 2H), 7.83-7.87 (m, 12H), 7.97 (d, J ) 8 Hz, 2H), 8.35 (d, J
) 6 Hz, 2H), 8.48-8.54 (m, 2H), 8.72 (d, J ) 8 Hz, 2H), 8.85 (d,
J ) 8 Hz, 4H); 13C NMR (100 MHz, CD3CN) δ 65.0, 65.3, 67.5,
67.7, 70.1, 70.7, 71.7, 73.0, 113.6, 115.3, 125.3, 126.7, 128.0, 128.5,
129.9, 130.0, 130.1, 130.8, 131.1, 137.1, 137.6, 138.9, 139.4, 141.7,
Supporting Information Available: 1H and 13C NMR spectra
for all new compounds and Job plots for the complexation between
macrocycles 1a, 1b, and 5 and DBA‚PF6. This material is available
free of charge via the Internet at http://pubs.acs.org.
JO052411+
J. Org. Chem, Vol. 71, No. 6, 2006 2383