Pseudorotaxanes from T-shaped benzimidazolium axles and [24]crown-8 wheels

Article abstract of DOI:10.1021/ol300761q

A new templating motif for the formation of [2]pseudorotaxanes is described in which T-shaped axles with a benzimidazolium core and aromatic substituents at the 2-, 4-, and 7-positions interact with [24]crown-8 ether wheels ([24]crown-8, dibenzo[24]crown-

Full text of DOI:10.1021/ol300761q

ORGANIC
LETTERS
XXXX
Vol. XX, No. XX
000–000
[2]Pseudorotaxanes from T-Shaped
Benzimidazolium Axles and [24]Crown-8
Wheels
Nadim Noujeim, Kelong Zhu, V. Nicholas Vukotic, and Stephen J. Loeb*
Department of Chemistry and Biochemistry, University of Windsor, Windsor,
Ontario N9B 3P4, Canada
loeb@uwindsor.ca
Received March 24, 2012
ABSTRACT
A new templating motif for the formation of [2]pseudorotaxanes is described in which T-shaped axles with a benzimidazolium core and aromatic
substituents at the 2-, 4-, and 7-positions interact with [24]crown-8 ether wheels ([24]crown-8, dibenzo[24]crown-8, and dinaphtho[24]crown-8).
The T-shape greatly enhances the association between axle and wheel when compared to simple imidazolium or benzimidazolium cations. A
series of interpenetrated molecules are characterized by 1H NMR spectroscopy and single crystal X-ray crystallography.
[2]Pseudorotaxanes formed between electron-rich macro-
cyclic wheels and charged, electron-poor axles are often
essential precursors for the synthesis of [2]rotaxanes via the
threading-followed-by-stoppering protocol.1,2 Indeed, dis-
covering new templating pairs of axles and wheels for
[2]pseudorotaxane formation and investigating the funda-
mental nature of their interactions is vital for the development
of new mechanically interlocked molecules (MIMs) and
their applications as molecular switches and machinery.3,4
In our search for new axles to create [2]rotaxane ligands
for applications in condensed materials,5,6 we were intri-
gued by the 2,4,7-substitution pattern of the benzimidazo-
lium ion because this arrangement provides a rare example
of an organic molecule with a rigid core and right angle
(90°) turn. Unfortunately, the interaction of dibenzo-
[24]crown-8 (DB24C8) with either the imidazolium (Ka =
8 Mꢀ1)7 or phenylbenzimidazolium8 (Ka = 54 Mꢀ1) cation
is quite weak. Tiburcio9 and Clarkson10 have reported
(1) (a) Huang, F.; Gibson, H. W. Prog. Polym. Sci. 2005, 30, 982. (b)
Suzuki, S.; Nakazono, K.; Takata, T. Org. Lett. 2010, 12, 712. (c)
Makita, Y.; Kihara, N.; Takata, T. J. Org. Chem. 2008, 73, 9245. (d)
Makita, Y.; Kihara, N.; Takata, T. Chem. Lett. 2007, 36, 102. (e)
Kawasaki, H.; Kihara, N.; Takata, T. Chem. Lett. 1999, 1015. (f) Ko,
J.-L.; Ueng, S.-H.; Chiu, C.-W.; Lai, C.-C.; Liu, Y.-H.; Peng, S.-M.;
Chiu, S.-H. Chem.;Eur. J. 2010, 16, 6950. (g) Li, S.; Liu, M.; Zhang, J.;
Zheng, B.; Zhang, C.; Wen, X.; Li, N.; Huang, F. Org. Biomol. Chem.
2008, 6, 2103. (h) Braunschweig, A. B.; Dichtel, W. R.; Miljanic, O. S.;
Olson, M. A.; Spruell, J. M.; Khan, S. I.; Heath, J. R.; Stoddart, J. F.
Chem. Asian J. 2007, 2, 634. (i) Braunschweig, A. B.; Ronconi, C. M.;
Han, J.-Y.; Arico, F.; Cantrill, S. J.; Stoddart, J. F.; Khan, S. I.; White,
A. J. P; Williams, D. J. Eur. J. Org. Chem. 2006, 1857. (j) Rowan, S. J.;
Cantrill, S. J.; Stoddart, J. F. Org. Lett. 1999, 1, 129.
(2) Loeb, S. J.; Wisner, J. A. Angew. Chem., Int. Ed. 1998, 37, 2838.
(3) (a) Balzani, V.; Credi, A.; Venturi, M. Molecular Devices and
Machines ꢀ Concepts and Perspectives for the Nanoworld; Wiley Inter-
Science, Wiley-VCH: Weinheim, 2008. (b) Kay, E. K.; Leigh, D. A.;
Zerbetto, F. Angew. Chem., Int. Ed. 2007, 46, 72. (c) Coskun, A.;
Banaszak, M.; Astumian, R. D.; Stoddart, J. F.; Grzybowski, B. A.
Chem. Soc. Rev. 2012, 41, 19.
(4) (a) Davidson, G. J. E.; Sharma, S.; Loeb, S. J. Angew. Chem., Int.
Ed. 2010, 49, 4938. (b) Loeb, S. J.; Tiburcio, J.; Vella, S. J. Chem.
Commun 2006, 1598. (c) Suhan, N. D.; Allen, L.; Gharib, M. T.; Viljoen,
E.; Vella, S. J.; Loeb, S. J. Chem. Commun. 2011, 47, 5991.
(5) Loeb, S. J. Rotaxanes as Ligands: From Molecules to Materials in
Organic Nanostructures InterScience; Steed, J. W., Atwood, J. L., Eds.;
Wiley-VCH: Weinheim, 2008; p 33.
(6) (a) Loeb, S. J. Chem. Soc. Rev. 2007, 36, 226. (b) Davidson,
G. J. E.; Loeb, S. J. Angew. Chem., Int. Ed. 2003, 42, 74. (c) Hoffart, D. J.;
Loeb, S. J. Angew. Chem., Int. Ed. 2005, 44, 901. (d) Hoffart, D. J.; Loeb,
S. J. Supramol. Chem. 2007, 19, 89. (e) Knight, L. K.; Vukotic, V. N.;
Viljoen, E.; Caputo, C. B.; Loeb, S. J. Chem. Commun. 2009, 5585. (f)
Vukotic., V. N.; Loeb, S. J. Chem.;Eur. J. 2010, 16, 13630. (g) Mercer,
D. J.; Vukotic, V. N.; Loeb, S. J. Chem. Commun. 2011, 47, 896.
(7) Kiviniemi, S.; Nissinen, M.; Jorma-Jalonen, M. T.; Rissanen, K.;
€
€
Lamsa, M.; Pursiainen, J. New J. Chem. 2000, 24, 47.
r
10.1021/ol300761q
XXXX American Chemical Society

Scheme 1. Synthesis of 2,4,7-Triphenylbenzimidazolium Axlesa,b
a See the Supporting Information for details.
b For 5a: MX = NH4BF4, NH4PF6, NH4OTf, LiClO4 or LiNTf2. For 5bꢀi: MX = NH4BF4 only.
that, similar to 1,2-bis(pyridinium)ethane axles,2,11,12
when benzimidazolium groups are linked by a two-carbon
chain, the association constant can be effectively increased,
but this type of flexible axle was not suitable for our
purposes and is not easily functionalized.13
Table 1. Effect of Solvent and Counterion on Association
Constant for [2]Pseudorotaxane [5a⊂DB24C8]þa
counterionb
solvent
Kassocc (Mꢀ1
)
As a preliminary test, we prepared the T-shaped 2,4,7-
triphenylbenzimidazolium cation as the BF4 salt (Scheme 1)
and measured the association constant for [2]pseudoro-
taxane formation with DB24C8. The 1H NMR spectrum
of a CD3CN solution comprising equimolar amounts of
[5a]þ and DB24C8 (1.0 ꢁ 10ꢀ3 M, 298 K) showed efficient
formation of [2]pseudorotaxane [5a⊂DB24C8]þ. Surpris-
PF6
OTf
NTf2
ClO4
BF4
BF4
BF4
BF4
BF4
CD3CN
CD3CN
CD3CN
CD3CN
CD3CN
CD3OD
(CD3)2CO
CD3NO2
CD2Cl2
1290
300
370
390
1780
90
400
3900
75200
ingly, the resulting association constant (1.78 ꢁ 103 Mꢀ1
)
was orders of magnitudelarger thanthose foundfor simple
imidazolium or benzimidazolium derivatives.7,8
a 1H NMR spectroscopy (1.0 ꢁ 10ꢀ3 M, 298 K). b OTf = CF3SO3,
NTf2 = N(CF3SO2)2. c Errors are estimated to be less than 10%.
Based on the efficient [2]pseudorotaxane formation
observed for [5a⊂DB24C8]þ, we undertook a detailed
study of this new templating motif to (1) pinpoint the
source of the dramatic increase in association relative to
simple imidazolium cations and (2) determine the breadth
and tunability of the interaction. Three 24-membered
Table 2. Effect of Axle Substituents on Association Constantsa
Kassocb (Mꢀ1
)
(8) Zhu, K.; Vukotic, V. N.; Loeb, S. J. Angew. Chem., Int. Ed. 2012,
51, 2168.
ꢀ
(9) Castillo, D.; Astudillo, P.; Mares, J.; Gonzalez, F. J.; Vela, A.;
Tiburcio, J. Org. Biomol. Chem. 2007, 5, 2252.
(10) Li, L.; Clarkson, G. J. Org. Lett. 2007, 9, 497.
(11) (a) Mercer, D. J.; Vella, S. J.; Guertin, L.; Suhan, N. D.;
Tiburcio, J.; Vukotic, V. N.; Wisner, J. A.; Loeb, S. J. Eur. J. Org.
Chem. 2011, 1763. (b) Loeb, S. J.; Tiburcio, J.; Vella, S. J.; Wisner, J. A.
Org. Biomol. Chem. 2006, 4, 667.
(12) (a) Loeb, S. J.; Tiburcio, J.; Vella, S. J. Org. Lett. 2005, 7, 4923.
(b) Georges, N.; Loeb, S. J.; Tiburcio, J.; Wisner, J. A. Org. Biomol.
Chem. 2004, 2, 2751. (c) Vella, S. J.; Tiburcio, J.; Gauld, J. W.; Loeb, S. J.
Org. Lett. 2006, 8, 3421. (d) Sharma, S.; Davidson, G. J. E.; Loeb, S. J.
Chem. Commun. 2008, 582.
axle
R1
R2
DN24C8
24C8
DB24C8
[5a]þ
[5b]þ
[5c] þ
[5d]þ
[5e] þ
[5f] þ
[5g]þ
[5h]þ
[5i] þ
H
H
H
H
H
H
1300
820
1670
1170
1180
3720
5970
1350
1030
1710
2430
1780
760
OMe
Me
880
850
COOMe
NO2
H
3840
6180
1880
1520
2810
2900
4410
6930
1120
890
OMe
Me
H
H
COOMe
NO2
2580
3520
H
a 1H NMR spectroscopy (CD3CN, 1.0 ꢁ 10ꢀ3 M, 298 K). b Errors
(13) (a) Noujeim, N.; Leclercq, L.; Schmitzer, A. R. J. Org. Chem.
2008, 73, 3784. (b) Mukhapadhyay, C; Ghosh, S.; Schmiedekamp, A. M.
Org. Biomol. Chem. 2012, 10, 1434.
are estimated to be less than 10%.
B
Org. Lett., Vol. XX, No. XX, XXXX

Figure 1. 1H NMR spectra (298 K, CD3CN, 1.0 ꢁ 10ꢀ2 M) of (a) wheel DB24C8; (b) an equimolar solution of [5d][BF4] and DB24C8
showing formation of [2]pseudorotaxane [5d⊂DB24C8][BF4]; (c) axle [5d][BF4].
crown ether wheels, 24C8 ([24]crown-8), DB24C8, and
DN24C8 (dinaphtho[24]crown-8), were combined with
benzimidazolium axles containing various electron-donat-
ing (EDG) and withdrawing groups (EWG) as substitu-
ents (R1 and R2) on the three aromatic rings.
The 2,4,7-triphenylbenzimidazoliuum cations ([5a]þꢀ[5i]þ)
were prepared in good yields as outlined in Scheme 1. Only
those axles with either R1 or R2 = H were studied to
simplify the analysis of EDG and EWG contributions. As
outlined in Scheme 1, two synthetic routes were employed;
(1) R1 groups were introduced using a condensation/
oxidation step14 from the diamine 3 where R2 = H and
(2) R2 groups were introduced via Suzuki coupling using
the 4,7-dibromobenzimidazole 4 where R1 = H.
1
Association constants were determined by H NMR
spectroscopy and are summarized in Tables 1 and 2.
Exchange between complexed and uncomplexed species
was slow on the NMR time scale for all samples. In each
case, significant shifts to higher frequency were observed
for the NH and c resonances on the axle indicative of
hydrogen-bonding between axle and wheel. Shifts to lower
frequency for aromatic proton d on the axle and Ar
protons on the wheel also occur with DB24C8 or
DN24C8 due to efficient π-stacking between the electron
poor benzimidazolium ring and the electron-rich catechol
rings of the crown ether (Figure 1).
Figure 2. Plot illustrating the variation in association constant
for [2]pseudorotaxane formation as a function of axle substitu-
ents and crown ether wheel.
largest association constants under these conditions
(Table 1).15 The effect of solvent on the formation of
[5a⊂DB24C8]þ was shown to be CD3OD < (CD3)2CO
< CD3CN < CD3NO2 < CD2Cl2 (Table 1).16 The
combination of X = BF4 and CD3CN was chosen for
the detailed study involving variation of the axle substitu-
ents in order to allow for a large range in association
constants and ensure the solubility of all the components.
Association constants for [2]pseudorotaxane formation
Initially, the salts [5a][X] (X = PF6, CF3SO3,
N(CF3SO2)2, ClO4, and BF4) were studied with DB24C8
in CD3CN. It was observed that the BF4 salts yielded the
(14) Akpinar, H.; Balan, A.; Baran, D.; Unver, E.; Toppare, L.
Polymer 2010, 51, 6123.
(15) Gibson, H. W.; Jones, J. W.; Zakharov, L. N.; Rheingold, A. L.;
Slebodnick, C. Chem.;Eur. J. 2011, 17, 3192. (b) Zhu, K.; Li, S.; Wang,
F.; Huang, F. J. Org. Chem. 2009, 74, 1322. (c) Jones, J. W.; Gibson,
H. W. J. Am. Chem. Soc. 2003, 125, 7001.
(16) (a) Horn, J. R.; Russell, D.; Lewis, E. A.; Murphy, K. P.
Biochemistry 2001, 40, 1774. (b) Horn, J. R.; Brandts, J. F.; Murphy,
K. P. Biochemistry 2002, 41, 7501. (c) Smithrud, D. B.; Wyman, T. B.;
Diederich, F. J. Am. Chem. Soc. 1991, 113, 5420. (d) Stauffer, D. A.;
Barrans, R. E., Jr.; Dougherty, D. A. J. Org. Chem. 1990, 55, 2762.
Org. Lett., Vol. XX, No. XX, XXXX
C

(24C8) pairing. There are three pairs of hydrogen-bonding
interactions between axle and wheel; NH O (bifurcated
3 3 3
˚
˚
˚
˚
2.85 A, 143°; 3.04 A, 138°; bifurcated 2.93 A, 138°; 3.03 A,
˚
˚
143°), CHc O (bifurcated 3.44 A, 137°; 3.69 A, 147°;
3 3 3
˚
˚
˚
bifurcated 3.33 A, 130°; 3.64 A, 149°), and CHe O (3.89 A,
3 3 3
˚
173°; 3.83 A, 171°). This hydrogen-bonding array is
accompanied by significant ion-dipole interactions be-
tween the cationic charge on the benzimidazolium ring
and the crown ether oxygen atoms. The extra stability
afforded by the 2,4,7-substitution pattern appears to come
from the extra CH O hydrogen-bonding provided by
the added aromatic rings; this is consistent with shifts
3 3 3
1
observed for these protons (c and e) in solution by H
NMR spectroscopy. The rigidity of the axles also probably
contributes to an increase in association constant by limit-
ing entropic effects.
The X-ray structure18 of [5g⊂DB24C8]þ (Figure 3,
right) was also determined and the hydrogen-bonding
interactions are very similar to those observed for
Figure 3. Ball-and-stick representations of the cationic portions
of the single-crystal X-ray structures of [5a⊂24C8][BF4] (left)
and [5g⊂DB24C8][BF4] (right). H-atoms not involved in hydro-
gen bonding have been omitted for clarity.
[5g⊂DB24C8]þ; NH O (2.84 A, 160°; 2.86 A, 160°),
˚
˚
3 3 3
˚
˚
CHc O (3.81 A, 160°; 3.54 A, 151°) and CHe O (3.63
3 3 3
3 3 3
˚
˚
A, 152°; 3.55 A, 153°). The C-shape conformation adopted
by the DB24C8 macrocycle allows for the addition of
π-stacking interactions by clamping around the electron
between 24C8, DB24C8, and DN234C8 and nine axles
([5a]þꢀ[5i]þ) containing R1 or R2 = H, OMe, Me,
COOMe, NO2 were measured (Table 2).
˚
poor benzimidazolium ring (3.64ꢀ4.76 A).
The major advantages of this new templating motif
reported herein are (1) a much stronger association be-
tween axle and crown ether wheel due to the T-shape of the
benzimidazolium cation, (2) a modular synthesis which
allows for the incorporation of a wide variety of function-
alized aromatics onto the molecular scaffold utilizing
commercially available materials with well established
coupling methodologies, and (3) the potential to easily
incorporate this new template into MIMs by incorpo-
rating the appropriate functional group at R1, for
example, aldehyde for further condensation8 or olefin for
metathesis.
When either R1 or R2 is an EWG, the hydrogen-
bonding, ion-dipole, and π-stacking interactions are all
strengthened due to an increase in acidity of hydrogen-
bond donors and an increase in charge on the benzimida-
zolium rings; the presence of an EDG lowers the associa-
tionconstant by weakening these sameinteractions.12a The
effect is more pronounced for R1 because substitution at
the 2-position results in a more direct effect on the imida-
zolium moiety. A Van’t Hoff plot [5a⊂DB24C8]þ (see the
Supporting Information) shows that the interaction be-
tween axle and wheel is driven primarily by enthalpic
gain.16 Hammett plotsfor variationsinR1 witheachcrown
ether are linear, supporting the straightforward effect of
the added EDG/EWG substituents on hydrogen-bonding
(see the Supporting Information).17 Figure 2 shows the
variations in association constant with different axles and
wheels in graphical format. In general, the addition of a
larger aromatic ring system (changing from DB24C8 to
DN24C8) does not enhance binding due to increased steric
interactions with the R2-substituted rings at the 4- and
7-positions of the benzimidazolium ring.
Acknowledgment. This researchwork was supported by
a NSERC of Canada Discovery grant to S.J.L. N.N. is
grateful to the FQRNT (Quebec) for the awarding of a
postdoctoral fellowship. V.N.V. is grateful to NSERC of
Canada for the awarding of an Alexander Graham Bell
Graduate Doctoral Scholarship and to the ICDD for a
Ludo Frevel Crystallography Scholarship.
The X-ray structure18 of [5a⊂DB24C8]þ (Figure 3, left)
Supporting Information Available. Synthetic experi-
mental details, NMR spectra, details of association con-
stant measurements, Van’t Hoff plot, Hammett plots,
and X-ray structures (CIF). This material is available free
of charge via the Internet at http://pubs.acs.org.
represents the simplest of axle (R1 = R2 = H) and wheel
(17) Hansch, C.; Leo, A.; Taft, R. W. Chem. Rev. 1991, 91, 165.
(18) Crystallographic data for the two structures reported in this
communication have been deposited with the Cambridge Crystallo-
graphic Data Centre as supplementary publication nos. CCDC-872986
and -872987. Copies of the data can be obtained free of charge on
application to CCDC at email: deposit@ccdc.cam.ac.uk.
The authors declare no competing financial interest.
D
Org. Lett., Vol. XX, No. XX, XXXX