[2]Pseudorotaxane formation with N-benzylanilinium axles and 24-crown-8 ether wheels

Article abstract of DOI:10.1021/ol051786e

(Chemical Equation Presented) As a hybrid of the N,N-dibenzylammonium and 1,2-bis(pyridinium)ethane axles, various N-benzylanilinium cations were investigated as suitable axles for the formation of [2]pseudorotaxanes with the 24-membered crown ethers 24C8 and DB24C8. The effect of electron-donating OCH₃ and electron-withdrawing CF₃ groups on both the anilinium and benzyl aromatic rings was studied. Formation constants and structural details were compared to the [2]pseudorotaxanes formed by the two aforementioned dibenzylammonium and 1,2-bis(pyridinium)ethane axles.

Full text of DOI:10.1021/ol051786e

ORGANIC
LETTERS
2005
Vol. 7, No. 22
4923-4926
[2]Pseudorotaxane Formation with
N-Benzylanilinium Axles and 24-Crown-8
Ether Wheels
Stephen J. Loeb,* Jorge Tiburcio, and Sarah J. Vella
Department of Chemistry & Biochemistry, UniVersity of Windsor,
Windsor, ON, Canada N9B 3P4
loeb@uwindsor.ca
Received July 27, 2005
ABSTRACT
As a hybrid of the N,N-dibenzylammonium and 1,2-bis(pyridinium)ethane axles, various N-benzylanilinium cations were investigated as suitable
axles for the formation of [2]pseudorotaxanes with the 24-membered crown ethers 24C8 and DB24C8. The effect of electron-donating OCH3
and electron-withdrawing CF3 groups on both the anilinium and benzyl aromatic rings was studied. Formation constants and structural details
were compared to the [2]pseudorotaxanes formed by the two aforementioned dibenzylammonium and 1,2-bis(pyridinium)ethane axles.
A variety of [2]pseudorotaxanes have been reported that
involve the interpenetration of dibenzo-24-crown-8 ether
(DB24C8) by linear cationic molecules, thus acting as wheel
and axle, respectively.1 The first, extensively studied by
Stoddart, uses secondary ammonium cations such as N,N-
dibenzylammonium as the axle component.2 A second,
reported by us, utilizes 1,2-bis(pyridinium)ethane dications
as the axles.3 The dibenzylammonium cation binds to the
crown ether by way of strong NH‚‚‚O hydrogen bonds and
N+‚‚‚O ion-dipole interactions whereas the bis(pyridinium)-
ethane axle relies on a series of much weaker CH‚‚‚O hydro-
gen bonds, two sets of N+‚‚‚O interactions, and significant
π-stacking between electron-poor pyridinium rings and elec-
tron-rich catechol rings on DB24C8. As these two pseu-
dorotaxanes systems display approximately the same range
of association constants4 (MeCN at 25 °C), we were inter-
ested to know if a new hybrid axle could be created using
what may be described as the “best” properties of each of
the two axles.
To this end, we designed an axle that contains character-
istics of both N,N-dibenzylammonium and bis(pyridinium)-
ethane axles. This new axle contains a two-atom bridge
(1) Raymo, F. M.; Stoddart, J. F. In Molecular Catenanes, Rotaxanes
and Knots; Sauvage, J.-P., Dietrich-Buchecker, C., Eds.; VCH-Wiley:
Weinheim, 1999; pp 143-176.
+
consisting of a -CH2NH2 - unit between two aromatic
(2) (a) Ashton, P. R.; Campbell, P. J.; Chrystal, E. J. T.; Glink, P. T.;
Menzer, S.; Philp, D.; Spencer, N.; Stoddart, J. F.; Tasker, P. A.; Williams,
D. J. Angew. Chem., Int. Ed. Engl. 1995, 34, 1865-1869. (b) 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. (c) Glink, P. T.; Schiavo, C.; Stoddart, J. F.; Williams,
D. J. Chem. Commun. 1996, 1483-1490. (d) Cantrill, S. J.; Pease, A. R.;
Stoddart, J. F. J. Chem. Soc., Dalton Trans. 2000, 3715-3734. (e)
Kolchinski, A. G.; Busch, D. H.; Alcock, N. W. J. Chem. Soc., Chem.
Commun. 1995, 1289-1291.
rings; an N-benzylanilinium. This recognition site should
provide (i) a positively charged group suitable for electro-
static ion-dipole interactions with the crown ether oxygen
atoms, (ii) two strongly acidic N-H protons for NH‚‚‚O
hydrogen bonding, (iii) two acidic benzyl CH protons for
(4) (a) Elizarov, A. M.; Chiu, S.-H.; Stoddart, J. F. J. Org. Chem. 2002,
67, 9175-9181. (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, 2117-2128.
(3) Loeb, S. J.; Wisner, J. A. Angew. Chem., Int. Ed. 1998, 37, 2838-
2840.
10.1021/ol051786e CCC: $30.25
© 2005 American Chemical Society
Published on Web 09/29/2005

CH‚‚‚O hydrogen bonding, and (iv) electron-poor aromatic
rings for π-interactions with the catechol rings on the crown
ether. Thus, potentially these new axles would be an excellent
match, in size and shape, with the bis(pyridinium)ethane
motif while providing the versatility of acid-base control
reminiscent of the N,N-dibenzylammonium axles.
Herein, we present the synthesis of a series of new axles
1a+-1d+ and their complexation by both DB24C8 and 24C8
(24-crown-8) to yield pH-controllable [2]pseudorotaxanes
(Scheme 1). Substituted N-benzylanilines were easily syn-
resembles the geometry observed for analogous 1,2-bis-
(pyridinium)ethane cations.6
As a result of the enhanced acidity of these anilinium-
based axles, the protonated (HA+) and nonprotonated (A)
axles are in equilibrium in solution. Both species are involved
in fast exchange on the NMR time scale and only a single,
averaged set of resonances is observed. The limiting chemical
shifts and acidity constants (Ka) were obtained from titration
experiments. In this method, each N-benzylaniline was
titrated with increasing amounts of trifluoromethanesulfonic
acid until saturation was indicated (see the Supporting Infor-
mation). The chemical shift data were fitted using a nonlinear
least-squares model.7 Variation of the substituents in the
4-position on the aromatic rings of the axles allowed study
of the effects of EWG or EDG on the acidity and ability to
form [2]pseudorotaxanes. Results indicate a 100-fold increase
in the acidity constants (Ka) between the axles with the
change of a OCH3 group for a CF3 group on the aniline ring,
regardless of the nature of the group on the benzyl ring.
When equimolar solutions of an axle and a 24-crown-8
ether macrocycle were mixed together at 25 °C in CD3CN
equilibrium was rapidly attained and a new set of peaks, in
addition to those assigned to the free components, was
Scheme 1. Synthesis of Axles and [2]Pseudorotaxanes
1
observed in the H NMR spectrum (see Figure 2).
thesized in high yields via a one step alkylation reaction from
commercially available reagents. Two equivalents of the
aniline and 1 equiv of the benzyl bromide are required as 1
equiv of the aniline acts as a base and helps to prevent the
formation of tertiary amines.5 The N-benzylanilinium axles
1a+-1d+ are precipitated as the triflate salt from a solution
of the corresponding N-benzylaniline in isopropyl ether upon
addition of trifluoromethanesulfonic acid.
The X-ray structure of 1c+ (Figure 1) shows that in the
solid state the N-benzylanilinium cations display the antici-
pated anti conformation about the central C-N bond, which
Figure 2. 1H NMR spectrum in CD3CN at 1.0 × 10-2 M of an
equimolar solution of [1a][OTf] and DB24C8 showing formation
of [1a⊂DB24C8]+ (red and blue labels ) complexed components
of the [2]pseudorotaxane, [1a⊂DB24C8]+; black labels ) uncom-
plexed axle, [1a]+ and wheel DB24C8).
The chemical shifts of the new resonances are consistent
with the formation of a [2]pseudorotaxane complex in
solution with a rate of association-dissociation slow on the
NMR time scale. Chemical exchange between the free
components and the [2]pseudorotaxane was also confirmed
by EXSY NMR experiments.8
(5) For other examples, see (a) Onaka, M.; Umezomo, A.; Kawai, M.;
Izumi, Y. J. Chem. Soc., Chem. Commun. 1985, 1202-1203. (b) Hayat,
S.; Rahman, A.; Choudhary, M. I.; Khan, K. M.; Schumann, W.; Bayer, E.
Tetrahedron 2001, 57, 9951-9957.
(6) (a) Hubbard, A. L.; Davidson, G. J. E.; Patel, R. H.; Wisner, J. A.;
Loeb, S. J. Chem. Commun. 2004, 138-139. (b) Davidson, G. J. E.; Loeb,
S. J.; Parekh, N. A.; Wisner, J. A. J. Chem. Soc., Dalton Trans. 2001, 3135-
3136. (c) Loeb, S. J.; Wisner, J. A. Chem. Commun. 2000, 845-846. (d)
Loeb, S. J.; Wisner, J. A. Chem. Commun. 1998, 2757-2758.
(7) Hynes, M. J. J. Chem. Soc., Dalton Trans. 1993, 311-312.
Figure 1. Ball-and-stick representation of the X-ray structure of
1c+ showing an anti conformation: dihedral angle ) 171.8° (carbon
) black, oxygen ) red, nitrogen ) blue, fluorine ) yellow,
hydrogen ) white).
4924
Org. Lett., Vol. 7, No. 22, 2005

In the case of the 24C8 complexes, the resonances due to
NH2, CH2, and ortho aromatic C-H protons were shifted
downfield relative to the free axle, which is indicative of
hydrogen bonding. Thus in solution, a total of eight hydrogen
bonds are responsible for maintaining the [2]pseudorotaxane
structure (see Table 1).
ether used, the association constants are higher for the axles
bearing electron withdrawing CF3 groups (versus OCH3) as
would be expected on a purely electrostatic basis resulting
in increased ion dipole interactions and stronger NH‚‚‚O and
CH‚‚‚O hydrogen bonding. (2) Similar to the trend exhibited
by dibenzylammonium axles9 and contrary to that observed
for bis(pyridinium)ethane cations,3 higher Kassoc were ob-
served with 24C8 than with DB24C8. This can be attributed
to the better ability of aliphatic ether oxygen atoms to engage
in ion-dipole interactions and hydrogen bonding relative to
the aromatic catechol oxygen atoms. (3) For pseudorotaxanes
formed with 24C8, an EWG is more effective when placed
on the anilinium ring than the benzyl ring consistent with
NH‚‚‚O hydrogen bonding being a major contribution to the
overall Kassoc. (4) There appears to be significant π-stacking
involved in binding when DB24C8 is the wheel as indicated
by upfield shifts for meta protons A2 and B2. The π-stacking
is influenced equally by the inclusion of electron withdrawing
groups on either the benzyl or anilinium ring and is
magnified considerably when both rings contain the electron-
withdrawing CF3 (see Figure 3).10 This is reminiscent of the
Table 1. Summary of Changes in Chemical Shift (∆δ in ppm)
of the [2]Pseudorotaxanes Relative to the Free Axlesa
complex
B2
B1
Bn
A1
A2
[1a⊂24C8]+
+0.07
+0.12
+0.09
+0.14
-0.24
-0.13
-0.34
-0.18
+0.26
+0.29
+0.26
+0.28
+0.01
+0.13
-0.04
+0.07
+0.58
+0.55
+0.58
+0.55
+0.76
+0.73
+0.77
+0.72
+0.36
+0.39
+0.25
+0.27
+0.09
+0.11
+0.19
+0.22
-0.03
+0.02
+0.11
+0.09
-0.29
-0.37
-0.16
-0.21
[1b⊂24C8]+
[1c⊂24C8]+
[1d⊂24C8]+
[1a⊂DB24C8]+
[1b⊂DB24C8]+
[1c⊂DB24C8]+
[1d⊂DB24C8]+
a Positive: downfield shift; negative: upfield shift.
For the DB24C8 adducts, the signals due to NH2 and CH2
protons were shifted downfield, but due to the lower basicity
of the aromatic oxygen atoms on the crown ether, there are
not significant aromatic CH‚‚‚O interactions, regardless of
the substituent group on the axle. However, the resonances
due to the hydrogen atoms in meta positions on the CF3-
substituted rings are shifted upfield because of the shielding
generated by the ring current of the catechol rings on the
crown ether, indicating the presence of π-stacking interac-
tions in a fashion similar to that observed in the bis-
(pyridinium)ethane [2]pseudorotaxanes (see Table 1).
Due to the presence of simultaneous equilibria between
protonated/nonprotonated and complexed/uncomplexed spe-
cies, an equation was derived (see the Supporting Informa-
tion) to determine the association constants (Kassoc) from the
measured experimental constant (Kexp), the acidity constant
of the thread (Ka) and the solution concentration of thread
at equilibrium that is nonprotonated, [A]. The concentration
of (A) was calculated from integration and the observed
chemical shift of the uncomplexed peak in the NMR
spectrum. The results are summarized in Table 2.
Figure 3. Bar graph comparing the relative association constants
for the four different axles with 24C8 and DB24C8. For comparison
purposes, the two sets of data have been normalized to 1d+.
trends observed for bis(pyridinium)ethane cations and DB24C8
and is probably a direct result of the observed anti conforma-
tion of the two atom bridge between the aromatic rings.
In a fashion similar to that for the dibenzylammonium
axles,11 the addition of one equivalent of base (triethylam-
mine) to solutions containing the [2]pseudorotaxanes caused
Table 2. Summary of Equilibrium Constantsa
24C8
DB24C8
pKa
Kexp
Kassoc
Kexp
Kassoc
1a
1b
1c
1d
2.7
2.8
4.3
4.3
1163
1274
1569
364
2604
2329
1605
371
655
237
310
84
1100
322
314
85
(8) Perrin, C. L.; Dwyer, T. J. Chem. ReV. 1990, 90, 935-967.
(9) 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.
(10) (a) Hunter, C. A.; Sanders, J. K. M. J. Am. Chem. Soc. 1990, 112,
5525-5534. (b) Hunter, C. A.; Lawson, K. R.; Perkins, J.; Urch, C. J. J.
Chem. Soc., Perkin Trans. 2 2001, 651-669.
a The values for pKa and Kexp were obtained using 0.01 M solutions in
CD3CN at 25 °C. Kassoc were calculated using the following equation (see
the Supporting Information): Kassoc ) Kexp(1 + (Ka/[A])).
(11) (a) Montalti, M.; Ballardini, R.; Prodi, L.; Balzani, V. Chem.
Commun. 1996, 2011-2012. (b) Ashton, P. R.; Ballardini, R.; Balzani, V.;
Gomez-Lopez, M.; Lawrence, S. E.; Martinez-Diaz, M. V.; Montalti, M.;
Piersanti, A.; Prodi, L.; Stoddart, J. F.; Williams, D. J. J. Am. Chem. Soc.
1997, 119, 10641-10651.
Four general observations can be made regarding the
measured association constants. (1) Regardless of the crown
Org. Lett., Vol. 7, No. 22, 2005
4925

dethreading of the macrocycle from the axle and shifted the
equilibrium toward the nonprotonated species (A) which is
incapable of complexation. This process can be reversed by
the addition of one equivalent of acid (trifluoromethanesul-
fonic) which gives rise to the restoration of the [2]pseu-
dorotaxane.
High-resolution ESI mass spectrometry measurements
confirmed the presence of the 1:1 complex in the gas phase
and allowed for exact mass determinations (see the Sup-
porting Information). Solid-state structures of [1a⊂DB24C8]-
[OTf] and [1d⊂DB24C8][OTf] also verified the [2]pseu-
dorotaxane formation.
The structure of [1a⊂DB24C8]+ (see Figure 4) has the
crown ether arranged in a C-shaped conformation around
Figure 5. Ball-and-stick representation of the X-ray structure of
[1d⊂DB24C8]+ (carbon ) black, oxygen ) red, nitrogen ) blue,
hydrogen ) white).
the crown ether adopts an orientation which optimizes
hydrogen-bonding and ion-dipole interactions. Thus, in a
fashion similar to [1a⊂DB24C8]+, four hydrogen bonds
between the unit -CH2NH2 - of the axle 1d+ and DB24C8
+
are observed. The distances between N or C atoms and
O-atoms varies from 2.96 Å (aliphatic oxygen) to 3.24 Å
(aromatic oxygen) with NH‚‚‚O and CH‚‚‚O angles of 172°
and 157° respectively. The other two aliphatic oxygen atoms
are involved in ion-dipole interactions with N+ and Cδ+ at
3.05 Å. The torsion angle between O‚‚‚N-C‚‚‚O is linear;
180°.
Figure 4. Ball-and-stick representation of the X-ray structure of
[1a⊂DB24C8]+ (carbon ) black, oxygen ) red, nitrogen ) blue,
fluorine ) yellow, hydrogen ) white).
In summary, we have shown that the hybrid N-benzyl-
anilinium cations can function as suitable axles for the
formation of [2]pseudorotaxanes with 24-membered crown
ethers. These pseudorotaxanes are pH-sensitive and the
threading-unthreading process is controllable by the alternate
addition of acid and base. The binding behavior has
characteristics of both dibenzylammonium and bis(pyridini-
um)ethane axles but probably is more similar to the am-
monium ion axles. We are currently working toward the
incorporation of this new recognition site into molecular
shuttles and catenanes to complement our bis(pyridinium)-
ethane motif and generate acid-base controllable systems
from these two structurally related axle components.
the anilinium ring. Four hydrogen bonds are formed between
+
the -CH2NH2 - unit of the axle 1a+ and DB24C8. The
N‚‚‚O distances vary from 2.78 Å (aliphatic oxygen) to
3.02 Å (aromatic oxygen) with NH‚‚‚O angles of 170° and
147° respectively. The C‚‚‚O distances vary from 3.30 Å
(aliphatic oxygen) to 3.23 Å (aromatic oxygen) with
CH‚‚‚O angles of 172° and 159°, respectively. The other
two aliphatic oxygen atoms are involved in an ion-dipole
interaction with N+ and Cδ+ at 2.97 and 2.92 Å and a torsion
angle O‚‚‚N-C‚‚‚O essentially linear at 179.8°. The distances
between the centers of the aromatic rings on DB24C8 to
the center of the anilinium ring are 3.77 and 3.96 Å; these
distances are in the upper range for π-stacking interactions.10
In contrast to [1a⊂DB24C8]+, in the structure of
[1d⊂DB24C8]+ (see Figure 5), DB24C8 adopts the S-shaped
conformation familiar in the structures of pseudorotaxanes
formed with bis(pyridinium)ethane axles.6 The difference is
that there are no face-to-face π-stacking interactions between
aromatic rings. This is attributed to the fact that both sets of
aromatic rings are electron-rich which is known to be
unfavorable for stabilizing π-stacking.10 As a consequence,
Acknowledgment. S.J.L. thanks NSERC of Canada for
support of this research through a Discovery Grant.
Supporting Information Available: Synthesis, NMR,
and MS data for all compounds. Derivation of equation for
K
assoc. CIF files for [1c][OTf], [1a⊂DB24C8][OTf], and
[1d⊂DB24C8][OTf]. This material is available free of charge
via the Internet at http://pubs.acs.org.
OL051786E
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Org. Lett., Vol. 7, No. 22, 2005