Two [2]pseudorotaxane-like complexes and their corresponding [2]rotaxanes stabilized via interactions on opposite ends of the same macrocycle

Article abstract of DOI:10.1016/j.tetlet.2008.10.153

A multiple-use macrocycle recognizes dibenzylammonium ions and 2,6-lutidine derivatives, each in a [2]pseudorotaxane-like manner, through interactions with its diethylene glycol (hydrogen bonding) and 2,6-pyridinedicarboxamide (Pd²⁺ chelation)

Full text of DOI:10.1016/j.tetlet.2008.10.153

Tetrahedron Letters 50 (2009) 267–270
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Tetrahedron Letters
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Two [2]pseudorotaxane-like complexes and their corresponding
[2]rotaxanes stabilized via interactions on opposite ends
of the same macrocycle
Wei-Chung Hung a, Liang-Yun Wang a, Chien-Chen Lai b, Yi-Hung Liu a,
Shie-Ming Peng a, Sheng-Hsien Chiu a,
*
a Department of Chemistry, National Taiwan University, No. 1, Sec. 4, Roosevelt Road, Taipei 10617, Taiwan, ROC
b Institute of Molecular Biology, National Chung Hsing University and Department of Medical Genetics, China Medical University Hospital, Taichung, Taiwan, ROC
a r t i c l e i n f o
a b s t r a c t
Article history:
A multiple-use macrocycle recognizes dibenzylammonium ions and 2,6-lutidine derivatives, each in a
[2]pseudorotaxane-like manner, through interactions with its diethylene glycol (hydrogen bonding)
and 2,6-pyridinedicarboxamide (Pd2+ chelation) spacers, respectively. We characterized these complexes
in the solid state (X-ray crystallography) and in solution (1H NMR spectroscopy). The synthesis of two
corresponding [2]rotaxanes confirmed that these recognition systems possess [2]pseudorotaxane geo-
metries in solution.
Received 21 August 2008
Revised 10 October 2008
Accepted 10 October 2008
Available online 7 November 2008
Ó 2008 Elsevier Ltd. All rights reserved.
Rotaxanes and catenanes attract a great deal of attention be-
cause of their potential for applications in mesoscale devices and
molecular machinery on the nanoscale.1 The synthesis of these
interlocked systems usually requires the recognition of a macrocy-
clic unit by a recognition unit on a threadlike component.2 For the
realization of interlocked molecular switches and actuators, how-
ever, more than one type of recognition site is generally needed
to allow itinerant migration of the macrocycle(s) between different
recognition sites under the influence of an external stimulus; this
binding must not only be discriminative but also sufficiently strong
at each of these recognition stations.3 Nevertheless, macrocycles
that can recognize more than one type of guest in a pseudorotax-
ane-like manner in solution with reasonable binding affinity are
relatively rare. The crown ethers dibenzo[24]crown-8 (DB24C8)
and bis-p-phenylene[34]crown-10 (BPP34C10) are particularly
notable examples that have been used to construct several mole-
cular switches because they can recognize several guests—diben-
zylammonium ions (DBA+),4 1,2-bis(pyridinium)ethane units,5 or
bipyridinium dications6—in [2]pseudorotaxane-like geometries in
solution with sufficiently high binding affinities. Intuitively, dual-
or multiple-use macrocycles for future supramolecular catalytic
systems or for the preparation of sensitive molecular switches
can be developed by linking two or more different recognition sys-
tems as loops within a single macrocycle. The design of such a sys-
tem requires a delicate balance in the molecular structure to
ensure that both recognition systems operate independently. Pre-
viously, we reported that macrocycle 1, which possesses two xylyl
rings linked by diethylene glycol and 2,6-pyridinedicarboxamide
spacers, acts as a host molecule that complexes diphenylurea
derivatives through the cooperative interactions with its two
opposing recognition units.7 Herein, we report that the opposing
diethylene glycol and 2,6-pyridinedicarboxamide units of this
macrocycle also act independently to recognize both the DBA+
ion and 2,6-lutidine in solution.
In an earlier study, we found that the recognition of a DBA+ ion
requires a macrocycle featuring only one diethylene glycol chain
and two phenolic rings.8 Because the 2,6-pyridinedicarboxamide
motif places the two phenolic rings a suitable distance apart for
O
O
+
NH
O
N
_
_
H
H
O
H2
PF6
N
O
N
.
+
PF6
NH
Hc
NH
O
O
Hb
O
Hd
He
[(1
DBA) PF6]
Ha
N
O
1
NH
O
O
O
Hf
H3C
N
O
1. Pd(OAc)2
2.
N
Pd
O
N
N
O
N
H3C
* Corresponding author.
E-mail address: shchiu@ntu.edu.tw (S.-H. Chiu).
Scheme 1.
0040-4039/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2008.10.153

268
W.-C. Hung et al. / Tetrahedron Letters 50 (2009) 267–270
the binding of a guest,9 we suspected that macrocycle 1 (Scheme 1)
would form a pseudorotaxane-like complex with the DBA+ ion, sta-
bilized primarily through [N+–HꢀꢀꢀO] and [N+C–Hꢀꢀꢀ
p] interactions.
The 1H NMR spectrum of an equimolar (10 mM) mixture of
macrocycle 1 and DBAꢀPF6 in CD3NO2 at room temperature dis-
plays changes in the chemical shifts of the protons of the complex
relative to those of its free components (Fig. 1); these time-aver-
aged signals suggest that the rates of complexation and decom-
plexation of 1 and DBA+ are rapid under these conditions. The
spectrum of the complex reveals an upfield shift of the signal for
the protons of the benzylic methylene groups adjacent to the
NH2 center of the DBA+ ion as well as a separation of the ‘tight’
þ
multiplet (d 3.52–3.62) for the methylene protons of the OCH2-
CH2O units of the free macrocycle into two signals (d 3.41 and d
3.62) for the complex; these features suggest the existence of
[N+–HꢀꢀꢀO] and [N+C–Hꢀꢀꢀ
p] hydrogen bonds between macrocycle
1 and the DBA+ ion.8 Accordingly, we suspected the [2]pseudoro-
taxane-like assembly [1ꢁDBA+] (Scheme 1) to be the likely struc-
ture of the complex formed between 1 and the DBA+ ion in
CD3NO2. From a 1H NMR spectroscopic dilution experiment, we
determined the association constant (Ka) for this complex in
CD3NO2 to be 330 30 Mꢂ1 10
.
We grew single crystals suitable for X-ray crystallography
through liquid diffusion of iPr2O into a CH3NO2 solution of macro-
cycle 1 and DBAꢀPF6. The solid state structure11,12 (Fig. 2) reveals a
[2]pseudorotaxane-like molecular geometry for the complex
[1ꢁDBA+]; it also indicates that the complex is stabilized through
both [N+–HꢀꢀꢀO] hydrogen bonds and [N+C–Hꢀꢀꢀ
p] interactions (the
distances between the phenolic rings’ centroids and the sand-
wiched methylene carbons are both around 3.6 Å).
This result confirms our previous finding8 that, with suitable
design, weak noncovalent interactions can be harnessed to play ex-
tremely important roles in stabilizing macrocycle/dialkylammoni-
um ion complexes.
To confirm the existence of the [2]pseudorotaxane [(1ꢁDBA+] in
solution, we constructed a [2]rotaxane based on this recognition
system. Adding triethyl phosphite (200 mM) to a solution of the
benzylic azide 2-HꢀPF6 (100 mM) and macrocycle 1 (150 mM) in
CH2Cl2 gave the corresponding rotaxane, which dissociated slowly
during the purification process, presumably because the stopper-
ing groups were not bulky enough.13 Indeed, when we added trib-
utyl phosphite under otherwise identical conditions, we isolated
Figure 2. (a) Top and (b) side views of the solid state structure of the [2]pseud-
orotaxane [1ꢁDBA+]. The hydrogen bonding geometries, DꢀꢀꢀA, HꢀꢀꢀA [Å], and D–HꢀꢀꢀA
[°]: (a) 2.98, 2.11, 168.9; (b) 2.88, 2.00, 174.1; (c) 3.64, 2.97, 135.5; (d) 3.72, 2.75,
152.0. D = hydrogen bond donor, A = hydrogen bond acceptor.
the [2]rotaxane 3-HꢀPF6 in 23% yield (Scheme 2).14 After dissolving
the phosphoramidate-stoppered [2]rotaxane 3-HꢀPF6 in CD3SOCD3,
we observed no signals for the free macrocycle 1 in the 1H NMR
spectrum, confirming the interlocked nature of its components
(Fig. 3). To test the thermal stability of 3-HꢀPF6, we heated this
a
Hb
Hd / He
Ha
Hf
OCH2CH2O
N-H
Hc
O
NH
NH
O
O
+
N
1
O
N3
N
N3
+
b
c
H2
_
PF6
.
-H PF
2
O
6
P(OBu)3 CH2Cl2
23%
OBu
P
O
BuO
N
H
O
NH
O
Ar-H
N+CH2
H
H
_
N
O
+N
PF6
NH
O
O
H
O
P
OBu
9
8
7
6
5
4
3
N
BuO
δ
.
-H PF
3
6
Figure 1. Partial 1H NMR spectra (400 MHz, CD3NO2, 298 K) of (a) macrocycle 1, (b)
an equimolar mixture of 1 and DBAꢀPF6 (10 mM), and (c) DBAꢀPF6.
Scheme 2.

W.-C. Hung et al. / Tetrahedron Letters 50 (2009) 267–270
269
H
H
H
H
a
b
CH2
N
OCH2CH2O
#
+
O
H
CH2N
O P N CH2
*
*
O
+
NH2
#
Hf
4
Hc
8
7
6
5
3
δ
Figure 3. Partial 1H NMR spectra (400 MHz, CD3SOCD3, 298 K) of (a) the [2]rotaxane 3-HꢀPF6 and (b) macrocycle 1. #: The signal of H2O.
solution at 323 K while monitoring its 1H NMR spectra. Again, we
did not observe any signals for the free macrocycle within 2 h, sug-
gesting that the dibutyl phosphoramidate groups are stoppers that
can mechanically interlock the macrocycle 1 along the rodlike
component of the dumbbell-shaped moiety.
sion of iPr2O into a CH3CN solution of complex 5. The solid state
structure16 reveals (Fig. 4) a [2]pseudorotaxane-like molecular
geometry in which the Pd(II) atom holds the 2,6-lutidine and
2,6-pyridinedicarboxamide units together with their aromatic
planes aligned perpendicularly.
Having proved that the diethylene glycol unit appended to the
two aromatic rings in 1 was capable of complexing DBA+ ions in
CD3NO2, we turned our attention to the complexing behavior of
the opposing 2,6-pyridinedicarboxamide moiety, which is known
to complex lutidine units via chelation of palladium(II).15 Thus,
we treated macrocycle 1 with Pd(OAc)2 in CH3CN for 3 h at room
temperature to afford (Scheme 3) the corresponding Pd(II) com-
plex 4 (75% yield), which we then mixed with 2,6-lutidine in CHCl3
to produce the Pd(II) complex 5 in quantitative yield. We obtained
single crystals suitable for X-ray crystallography upon liquid diffu-
To construct a [2]rotaxane based on this recognition system, we
reacted the diol 6 with the Pd(II) complex 4 in CHCl3 to generate
the [2]pseudorotaxane complex 7 presenting hydroxyl groups at
its termini. Reacting complex 7 with the bulky isocyanate 8 in
the presence of di-n-butyltin dilaurate in CH2Cl2 at room tempera-
ture led us to isolate the [2]rotaxane 9 in 83% yield after column
chromatography (Scheme 3).17 The successful preparation of this
[2]rotaxane suggests that the 2,6-pyridinedicarboxamide unit
within macrocycle 1 is capable of recognizing pyridine derivatives
such as 6 in a pseudorotaxane-like manner in solution under the
templating influence of Pd(II).18
O
O
N
N
H
O
O
Pd(OAc)2
N
Pd
N
O
1
N
O
CH3CN
75 %
H
N
O
O
N
O
O
4
R
O
Ph
Ph
Ph
NCO
CHCl3
O
O
N
8
N
Pd
N
N
R
O
di-
n-butyltin dilaurate
N
CH2Cl2
O
83 %
R
R
R = Me
5
R = Me
2,6-lutidine
Ph
Ph
R = C CCH2OH
O
7
R = C CCH2OH
6
Ph
N
H
O
O
O
O
O
N
Pd
N
N
N
O
H
N
O
9
Ph
O
Ph
Ph
Scheme 3.
Figure 4. (a) Top and (b) side views of the solid state structure of complex 5.

270
W.-C. Hung et al. / Tetrahedron Letters 50 (2009) 267–270
8. (a) Cheng, P.-N.; Hung, W.-C.; Chiu, S.-H. Tetrahedron Lett. 2005, 46, 4239–4242;
Macrocycle 1 is a multiple-use macrocycle that recognizes
(b) Cheng, P.-N.; Huang, P.-Y.; Li, W.-S.; Ueng, S.-H.; Hung, W.-C.; Liu, Y.-H.; Lai,
C.-C.; Peng, S.-M.; Chao, I.; Chiu, S.-H. J. Org. Chem. 2006, 71, 2373–2383; (c)
Cheng, K.-W.; Lai, C.-C.; Chiang, P.-T.; Chiu, S.-H. Chem. Commun. 2006, 2854–
2856; (d) Chiu, C.-W.; Lai, C.-C.; Chiu, S.-H. J. Am. Chem. Soc. 2007, 129, 3500–
3501; (e) Hsueh, S.-Y.; Cheng, K.-W.; Lai, C.-C.; Chiu, S.-H. Angew. Chem., Int. Ed.
2008, 47, 4436–4439.
diphenylurea, DBA+, and 2,6-lutidine derivatives through interac-
tions with either its diethylene glycol or Pd2+-chelated 2,6-pyridine
diamide moieties. The solid state structure of [1ꢁDBA+] confirmed
that [N+C–Hꢀꢀꢀ
p] interactions play an important role in stabilizing
this complex. We aim to use multiple-guest-binding hosts such
as 1 as components of future molecular catalytic systems and
controllable molecular switches.
9. Bisson, A. P.; Lynch, V. M.; Monahan, M.-K. C.; Anslyn, E. V. Angew. Chem., Int.
Ed. 1997, 36, 2340–2342.
10. Connors, K. A. Binding Constants; Wiley: New York, 1987.
11. CCDC 703716 and 703717 contain the supplementary crystallographic data for
[1ꢁDBA][PF6] and 5, respectively. These data can be obtained free of charge
from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/
data_request/cif.
Acknowledgment
12. Crystal data for [1ꢁDBA][DBA][2PF6]: [C55H61N5O5][PF6]2; Mr = 1162.03;
We thank the National Science Council for financial support
(NSC 95-2113-M-002-016-MY3).
ꢀ
triclinic; space group P1; a = 11.1624(4); b = 13.2258(5); c = 19.4664(7) Å;
V = 2797.18(18) Å3;
q
calcd = 1.380 g cmꢂ3
;
l
(Mo
Ka
) = 0.169 mmꢂ1
;
T =
295(2) K; colorless needle; 10,657 independent measured reflections; F2
refinement; R1 = 0.0764; wR2 = 0.1775.
References and notes
13. For more details of this synthetic method, see: Hung, W.-C.; Liao, K.-S.;
Y.-H. Liu; Peng, S.-M.; Chiu, S.-H. Org. Lett. 2004, 6, 4183–4186.
1. (a) Collier, C. P.; Mattersteig, G.; Wong, E. W.; Luo, Y.; Beverly, K.; Sampaio, J.;
Raymo, F. M.; Stoddart, J. F.; Heath, J. R. Science 2000, 289, 1172–1175; (b) Saha,
S.; Leung, K. C.-F.; Nguyen, T. D.; Stoddart, J. F.; Zink, J. I. Adv. Funct. Mater. 2007,
17, 685–693; (c) Green, J. E.; Choi, J. W.; Boukai, A.; Bunimovich, Y.; Johnston-
Halperin, E.; DeIonno, E.; Luo, Y.; Sheriff, B. A.; Xu, K.; Shin, Y. S.; Tseng, H.-R.;
Stoddart, J. F.; Heath, J. R. Nature 2007, 445, 414–417.
2. Molecular Catenanes Rotaxanes and Knots; Sauvage, J.-P., Dietrich-Buchecker, C.,
Eds.; VCH-Wiley: Weinheim, 1999.
3. (a) Molecular Switches; Feringa, B. L., Ed.; Wiley-VCH: Weinheim, 2001;
(b) Elizarov, A. M.; Chiu, S.-H.; Stoddart, J. F. J. Org. Chem. 2002, 67, 9175–
9181; (c) Huang, F.; Switek, K. A.; Gibson, H. W. Chem. Commun. 2005, 3655–
3657.
4. (a) Fyfe, M. C. T.; Stoddart, J. F. Adv. Supramol. Chem. 1999, 5, 1–53; (b) Cantrill,
S. J.; Pease, A. R.; Stoddart, J. F. J. Chem. Soc., Dalton Trans. 2000, 3715–3734; (c)
Clifford, T.; Abushamleh, A.; Busch, D. H. Proc. Natl. Acad. Sci. U.S.A. 2002, 99,
4830–4836; (d) Gibson, H. W.; Yamaguchi, N.; Jones, J. W. J. Am. Chem. Soc.
2003, 125, 3522–3533; (e) Arico, F.; Badjic, J. D.; Cantrill, S. J.; Flood, A. H.;
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Griffiths, K. E.; Stoddart, J. F. Pure Appl. Chem. 2008, 80, 485–506.
5. (a) Loeb, S. J.; Wisner, J. A. Chem. Commun. 1998, 2757–2758; (b) Hoffart, D. J.;
Loeb, S. J. Angew. Chem., Int. Ed. 2005, 44, 901–904; (c) Vella, S. J.; Tiburcio, J.;
Loeb, S. J. Chem. Commun. 2007, 4752–4754.
6. (a) Allwood, B. L.; Spencer, N.; Shahriari-Zavareh, H.; Stoddart, J. F.; Williams, D.
J. J. Chem. Soc., Chem. Commun. 1987, 1064–1066; (b) 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; (c) Miljanic, O. S.; Stoddart, J. F. Proc. Natl. Acad. Sci. U.S.A. 2007, 104,
12966–12970; (d) Huang, F.; Jones, J. W.; Gibson, H. W. J. Org. Chem. 2007, 72,
6573–6576; (e) Wang, F.; Han, C.; He, C.; Zhou, Q.; Zhang, J.; Wang, C.; Li, N.;
Huang, F. J. Am. Chem. Soc. 2008, 130, 11254–11255.
14. Data for 3-HꢀPF6: Mp 91–93 °C; 1H NMR (400 MHz, CD3SOCD3): 0.88 (t, J = 7 Hz,
12H), 1.29–1.38 (m, 8H), 1.51–1.58 (m, 8H), 2.47 (br, 4H), 3.32 (br, 4H), 3.58
(br, 4H), 3.75–3.89 (m, 8H), 3.90–3.95 (m, 4H), 4.24 (s, 4H), 4.62 (d, J = 6 Hz,
4H), 5.41–5.47 (m, 2H), 6.76 (d, J = 8 Hz, 4H), 6.96 (d, J = 8 Hz, 4H), 6.99 (d,
J = 8 Hz, 4H), 7.12 (d, J = 8 Hz, 4H), 7.33 (br, 2H), 8.33 (t, J = 7 Hz, 1H), 8.40 (d,
J = 7 Hz, 2H), 9.82 (br, 2H); 13C NMR (100 MHz, CD3OD): 14.2, 20.1, 33.7
(JPC = 7 Hz), 43.3, 45.5, 52.1, 67.6 (JPC = 6 Hz), 70.8, 71.8, 75.3, 126.6, 128.4,
129.6, 129.9, 130.7, 130.9, 136.4, 141.0, 141.8, 143.0 (JPC = 5 Hz), 150.2, 165.3;
31P NMR (162 MHz, CD3OD): ꢂ138.5 (septet, J = 707 Hz, PF ꢂ), 15.1; HRMS
(ESI): m/z calcd for [3-H]+ (C59H85N6O11P2) 1115.5752; found61115.5811.
15. (a) Furusho, Y.; Matsuyama, T.; Takata, T.; Moriuchib, T.; Hirao, T. Tetrahedron
Lett. 2004, 45, 9593–9597; (b) Fuller, A.-M.; Leigh, D. A.; Lusby, P. J.; Oswald, I.
D. H.; Parsons, S.; Walker, D. B. Angew. Chem., Int. Ed. 2004, 43, 3914–3918.
16. Crystal data for 5: [C34H36N4O5PdꢀH2O][PF6]; Mr = 705.08; monoclinic; space
group P21/n; a = 12.4078(2); b = 9.3147(1); c = 28.1577(3) Å; V = 2194.10(7)
Å3;
q ; l(Mo Ka ; T = 295(2) K; colorless
calcd = 1.466 g cmꢂ3 ) = 0.632 mmꢂ1
needle; 7303 independent measured reflections; F2 refinement; R1 = 0.0378;
wR2 = 0.0841.
17. Data for 9: Mp 247–249 °C; 1H NMR (400 MHz, CDCl3): 3.50–3.52 (m, 4H),
3.60–3.63 (m, 4H), 4.28 (s, 4H), 4.34 (s, 4H), 4.86 (s, 4H), 6.61 (d, J = 8 Hz, 4H),
6.85 (d, J = 8 Hz, 4H), 7.13–7.18 (m, 12H), 7.19–7.22 (m, 24H), 7.30 (d, J = 8 Hz,
4H), 7.42 (t, J = 8 Hz, 1H), 7.48–7.51 (m, 3H), 7.81 (br, 2H); 13C NMR (100 MHz,
CDCl3): 29.8, 50.2, 52.9, 64.5, 68.3, 70.2, 73.5, 82.9, 92.2, 117.4, 124.2, 125.7,
127.3, 127.4, 128.9, 130.8, 131.5, 135.1, 135.6, 137.8, 140.1, 140.3, 141.7, 143.9,
146.7, 152.2, 152.8, 171.0; HRMS (FAB): m/z calcd for [9]+ (C90H74N6O9Pd)
1488.4552; found 1488.4597. For more details of this synthetic method, see
Ref. 15a.
18. We were unable to remove the Pd(II) ion from the [2]rotaxane 9 when using
catalytic hydrogenolysis (Pd/C), hydrolysis under acidic (HCl) and basic (Et3N)
conditions, or high-pressure carbon monoxide (50 atm), suggesting that
relatively tight binding occurs between the components and supporting the
integrity of the purposed rotaxane-like molecular structure.
7. Huang, Y.-L.; Hung, W.-C.; Lai, C.-C.; Liu, Y.-H.; Peng, S.-M.; Chiu, S.-H. Angew.
Chem., Int. Ed. 2007, 46, 6629–6633.