Templated conversion of a crown ether-containing macrobicycle into [2]rotaxanes

Article abstract of DOI:10.1021/jo0162787

A crown ether-containing macrobicycle was used as the wheel component in a templated synthesis of a [2]rotaxane with an acetal-containing axle. The molecular structures of the macrobicycle and the [2]rotaxane were characterized by NMR spectroscopy and X-ray crystallography. The chloride-binding ability of the macrobicycle, either free in solution or when it is part of a [2]rotaxane, is quite weak as determined by NMR titration experiments. A second analogous [2]rotaxane, with a longer axle, was synthesized, and its solvent-dependent co-conformation was characterized by 2D NMR spectroscopy. The position of the wheel along the axle can be controlled by the solvent polarity, however, attempts to use metal cations such as Na⁺, K⁺, Ba²⁺, and Ag⁺ to switch the wheel position in polar solvents were unsuccessful.

Full text of DOI:10.1021/jo0162787

1436
J . Org. Chem. 2002, 67, 1436-1440
Tem p la ted Con ver sion of a Cr ow n Eth er -Con ta in in g Ma cr obicycle
in to [2]Rota xa n es
J oseph M. Mahoney, Rameshwer Shukla, R. Andrew Marshall, Alicia M. Beatty,
J aroslav Zajicek, and Bradley D. Smith*
Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, Indiana 46556-5670
smith.115@nd.edu
Received November 11, 2001
A crown ether-containing macrobicycle was used as the wheel component in a templated synthesis
of a [2]rotaxane with an acetal-containing axle. The molecular structures of the macrobicycle and
the [2]rotaxane were characterized by NMR spectroscopy and X-ray crystallography. The chloride-
binding ability of the macrobicycle, either free in solution or when it is part of a [2]rotaxane, is
quite weak as determined by NMR titration experiments. A second analogous [2]rotaxane, with a
longer axle, was synthesized, and its solvent-dependent co-conformation was characterized by 2D
NMR spectroscopy. The position of the wheel along the axle can be controlled by the solvent polarity,
however, attempts to use metal cations such as Na+, K+, Ba2+, and Ag+ to switch the wheel position
in polar solvents were unsuccessful.
Sch em e 1
In tr od u ction
The field of mechanically interlocked molecules con-
tinues to grow as researchers design, synthesize, and
characterize increasingly complicated structures.1 Our
research group is interested in preparing [2]rotaxanes,
interlocked molecules that comprise two components, a
wheel and a penetrating axle. More specifically, we are
investigating [2]rotaxanes with salt-binding wheels,2 with
the eventual goal of making molecular devices with salt-
dependent properties. Recently, we reported that mac-
robicycle 1 (Scheme 1) is able to extract and bind alkali
halide salts as their contact ion pairs.3 Molecular models
of 1 indicate that its cavity is not large enough to
accommodate a penetrating axle. Therefore, we designed
the larger macrobicycles 2 and 3 with the idea that they
could be converted into novel benzyl amide [2]rotaxanes.4
Here, we describe the synthesis and structural charac-
terization of 2 and 3 and demonstrate how 2 can be used
to make [2]rotaxanes with acetal-linked axles. We also
provide a comparison of the chloride-binding ability of 2
when it is the free macrobicycle to that when it is part
* Corresponding author.
(1) (a) Molecular Catenanes, Rotaxanes and Knots; Sauvage, J . P.,
Dietrich-Bucheker, C. O. Eds.; VCH-Wiley: Winheim, 1999. (b) Brou-
wer, A. M.; Frochot, C.; Gatti, F. G.; Leigh, D. A.; Mottier, L.; Paolucci,
F.; Roffia, S.; Wurpel, G. W. H. Science 2001, 291, 2124-2128. (c)
Reuter, C.; Schmieder, R.; Vo¨gtle, F. Pure Appl. Chem. 2000, 72, 2233-
2241. (d) J eppesen, J . O.; Perkins, J .; Becher, J .; Stoddart, J . F. Angew.
Chem., Int. Ed. 2001, 99, 11216-1221. (e) Bryant, W. S.; Guzei, I. A.;
Reingold, A. L.; Gibson, H. W. Org. Lett. 1999, 1, 47-50. (f) Chang, S.
Y.; Choi, J . S.; J eong, K.-S. Chem.sEur. J . 2001, 7, 2687-2697. (g)
Hunter, C. A.; Low, C. M. R.; Packer, M. J .; Spey, S. E.; Vinter, J . G.;
Vysotsky, M. O.; Zonta, C. Angew. Chem., Int. Ed. 2001, 40, 2678-
2682. (h) J ime´nez, M. C.; Dietrich-Buchecker, C.; Sauvage, J . P. Angew.
Chem., Int. Ed. 2000, 39, 3284-3287. (i) MacLachlan, M. J .; Rose, A.;
Swager, T. M. J . Am. Chem. Soc. 2001, 123, 9180-9181.
(2) Shukla, R.; Deetz, M. J .; Smith, B. D. Chem. Commun. 2000,
2397-2398. Shukla, R.; Deetz, M. J .; Smith, B. D. Tetrahedron 2002,
58, 799-806.
of a [2]rotaxane. Finally, we evaluate the ability of a [2]-
rotaxane analogue with a long axle to act as a molecular
shuttle.
Resu lts a n d Discu ssion
Ma cr ocycle Syn th esis a n d Str u ctu r e. Macrobi-
cycles 2 and 3 were prepared in yields of 45 and 15%,
respectively, by reacting the known diamine 45 with
isophthaloyl dichloride or 2,6-pyridine di(carbonyl chlo-
1
ride), respectively. The H NMR spectrum of 2 in CDCl3
(3) Mahoney, J . M.; Beatty, A. M.; Smith, B. D. J . Am. Chem. Soc.
2001, 123, 5847-5848.
contains broad lines, indicating slow conformational
(4) Leigh, D. A.; Murphy, A.; Smart, J . P.; Slawin, A. M. Z. Angew.
Chem., Int. Ed. Engl. 1997, 36, 728-732.
(5) Rammo, J .; Schneider, H.-J . Liebigs Ann. 1996, 1757-1767.
10.1021/jo0162787 CCC: $22.00 © 2002 American Chemical Society
Published on Web 02/07/2002

Conversion of Macrobicycle into [2]Rotaxanes
J . Org. Chem., Vol. 67, No. 5, 2002 1437
F igu r e 1. Two views of the X-ray crystal structure of 2‚HCl‚
H2O. Only relevant hydrogen atoms are shown, and the second
water is omitted for clarity. Structure shows 50% ellipsoid
probability.
Sch em e 2
exchange, whereas the CDCl3 spectrum of 3 is more
resolved, suggesting that 3 is more rigid. This rigidity is
probably related to the ability of the pyridyl nitrogen in
3 to form internal hydrogen bonds with the adjacent NH
residues.4-6 The HCl salt of 2 is also soluble in organic
solvents, and its structure was characterized by mass
spectrometry, NMR spectroscopy, and X-ray crystal-
lography. Two views of the X-ray crystal structure of the
2‚HCl salt are shown in Figure 1. The plane of the
bridging isophthalamide unit is almost parallel to the
plane of the diazacrown ring, and the Cl- is hydrogen-
bonded to the two NH residues on the exo face of the
macrocyclic cavity (N-Cl ) 3.27 Å). One of the crown
nitrogen atoms is protonated and hydrogen-bonded to a
water molecule that is bound deeply within the cavity
(N-OH2 ) 2.80 Å). The electron density is sufficiently
defined to show that the structure is not a bound H3O+
inside the free base of 2.
Rota xa n e Syn th esis a n d Str u ctu r e. [2]Rotaxane 5
was prepared by the anion template method.2,7 The free
base of macrobicycle 2 was treated with 2 molar equiv of
potassium 4-tritylphenolate in methylene chloride. The
tritylphenolate presumably reacts with the methylene
chloride to form a chloromethyl ether,8 which then reacts
in situ with a second potassium tritylphenolate inside
the cavity of 2 to give 5 in 15% yield (Scheme 2).
Surprisingly, attempts to convert 3 into an analogue of
5 were unsuccessful; only the unthreaded free axle was
isolated. There appear to be two possible reasons for this
outcome: (a) repulsion between the pyridyl nitrogen and
the phenolate oxygen may preclude wheel threading or
(b) the wheel-threading step may require a flexible
macrocycle cavity space that can accommodate the react-
ing partners and the changing geometry of the nucleo-
philic substitution reaction. Macrocbicycle 3 may be
unable to do this step because it has a more rigid
structure and a less accessible cavity.
F igu r e 2. Two views of the X-ray crystal structure of 5. Axle
carbons are shown in gray for clarity. Prominent aromatic
edge-to-face interactions are indicated with dashed lines.
Amide hydrogens are shown in the second view; all other
hydrogens and three waters are omitted for clarity. Structure
shows 50% ellipsoid probability.
A sample of 5 was crystallized, and its structure was
determined by X-ray diffraction (Figure 2). The X-ray
structure shows a number of notable features: (1) There
is apparently a long, weak hydrogen bond between one
of the acetal oxygens and one of the wheel NH groups
(N-O ) 3.95 Å), while the other acetal oxygen contacts
a crown CH residue (C-O ) 3.11 Å). (2) There are a
number of aromatic stacking interactions, particularly
edge-to-face, between the wheel and the axle aromatic
groups. (3) One of the crown nitrogen atoms points a lone
pair into the macrobicyclic cavity, whereas the other
points its lone pair out. (4) One of the acetal CH bonds
is directed toward the crown nitrogen (C-N ) 3.65 Å)
and its adjacent aromatic group (CH-p interaction).
The X-ray structure of 5 helps rationalize many of its
solution-state NMR spectral features. For example, the
axle’s central acetal protons in 5 are located between the
wheel’s two aromatic side-units, which explains why the
acetal chemical shift is significantly upfield (4.17 ppm
in CDCl3) compared to that of the free axle (5.69 ppm).
Signals for the wheel aromatic protons F and G and axle
aromatic protons a and b are shielded because of aromatic
stacking. The structure of 5 appears to be fairly rigid
(6) Hunter, C. A.; Purvis, D. H.; Angew. Chem., Int. Ed. Engl. 1992,
31, 792-795.
(7) Seel, C.; Vo¨gtle, F. Chem.sEur. J . 2000, 6, 21-24.
(8) Reuter, C.; Wienand, W.; Hu¨bner, G. M.; Seel, C.; Vo¨gtle, F.
Chem.sEur. J . 1999, 5, 2692-2697.
1
because even at -60 °C the H NMR in CDCl3 shows no
signal splitting due to slow conformational exchange. In
1
addition, a H spectrum in DMSO-d6 shows sharp signals,

1438 J . Org. Chem., Vol. 67, No. 5, 2002
Mahoney et al.
-
Ta ble 1. Ch lor id e Associa tion Con sta n ts, KCl (M-1), for
Recep tor s 1, 2, a n d 5 in th e P r esen ce or Absen ce of 1
Mola r Equ iva len t of Meta l Tetr a p h en ylbor a tea
-
-
receptor
KCl
receptor
KCl
1
35b
50b
460b
2
2
5
5
15
2
1 + Na+
1 + K+
5
2 + Na+
2 + K+
5 + Na+
5 + K+
5
a
In DMSO-d6 at T ) 295 K; initial [receptor] ) 10 mM;
b
uncertainty (15%. From ref 3.
Sch em e 3a
F igu r e 3. [2]Rotaxane, 6, shown with protons labeled (Tr )
C(Ph)3).
Ta ble 2. P r oton Assign m en ts for Rota xa n e, 6, in CDCl3
proton
δ (ppm)
proton
δ (ppm)
a
Key: (a) 1,8-dibromooctane, KI (cat.), CH3CN, reflux, 18 h,
A
B
C
D
E
F
G
H
I
7.59
8.22
8.19
6.91
4.43
6.88
6.93
3.48, 3.47
2.67, 2.74
3.60, 3.62
3.59
a
b
c
d
e
f
g
h
i
7.10
6.66
3.54
1.52
1.22
1.19
1.19
1.27
1.57
3.64
6.73
6.96
5.54
53%; (b) 4-benzyloxyphenol, KI (cat.), K2CO3, CH3CN, reflux, 24
h, 66%; (c) H2, Pd/C, MeOH/THF 1:1, 3 h, 88%; (d) 2, K2CO3,
CH2Cl2, 24 h, 14%.
which is in contrast with our previously reported [2]-
rotaxane system.2
Ch lor id e-Bin d in g Abilities. The chloride-binding
properties of macrobicycle 2 and [2]rotaxane 5 were
evaluated in the following way. Receptor/Cl- association
constants in highly polar DMSO-d6 were determined by
adding aliquots of tetrabutylammonium chloride to a
solution of receptor 2 or 5 in the absence or presence of
1 molar equiv of potassium or sodium tetraphenylborate.
The diffuse tetrabutylammonium cation and tetraphen-
ylborate anion have negligible affinity for the receptors,
thus they are simply “spectator ions”. The complex-
induced changes in chemical shift are consistent with the
Cl- forming hydrogen bonds with the isophthalamide NH
residues, and association constants were obtained by
fitting the titration isotherms to a 1:1 binding model
using an iterative computer method.9 As shown in Table
1, the benzyl amides 2 and 5 have similar and signifi-
cantly weaker affinities for Cl- than does the more acidic
aromatic amide 1. In addition, their Cl- association
constants are not affected by the presence of Na+ and
increase by a factor of 2-3 only in the presence of K+.
This modest binding enhancement is most likely at-
tributable to the relatively large distance between the
anion and cation binding sites in 2 and 5.
Eva lu a tion of a P oten tia l Molecu la r Sh u ttle. To
demonstrate further the utility of 2 as a wheel compo-
nent, we used the same anion template method (Schemes
2 and 3) to prepare [2]rotaxane 6 (Figure 3) in 16% yield.
[2]Rotaxane 6 has a longer acetal-containing axle, and a
battery of NMR methods (COSY, HETCOR, TOCSY,
ROESY) were used to characterize its co-conformation
in CDCl3 (Table 2) and DMSO-d6. In both solvents, the
peaks are sharp at room temperature. The chemical shift
of the acetal signal is hardly changed compared to that
of the free axle, and the acetal protons do not cross-relax
any wheel protons, suggesting that the acetal linkage is
J
K
j
k
l
m
not inside the wheel. In CDCl3, it appears that the wheel
spends most of its time over the phenoxy rings attached
to the axle-stoppers. In particular, a ROESY spectrum
shows a cross-peak between wheel proton C and the
shielded aromatic axle protons b. Presumably, this
preferred co-conformation is stabilized by aromatic stack-
ing interactions that are similar to those seen in Figure
1
2. The symmetrical simplicity of the H NMR spectrum
of 6 in CDCl3 indicates that the spinning of the wheel
and the shuttling of the wheel along the axle are both
very rapid, even at -60 °C.
A ROESY spectrum in DMSO-d6 shows no cross-peaks
between wheel proton C and any axle aromatic protons,
but cross-peaks are observed with the axle alkyl protons,
suggesting that the wheel resides on one of the two alkyl
chains. This result is reminiscent of the solvophobic effect
previously reported by Leigh and co-workers.10 The
rotaxane adopts a co-conformation that reduces exposure
of the lipophilic alkyl chains to the polar solvent and
increases exposure of the relatively more polar phenoxy
rings attached to the axle-stoppers. This solvophobic
effect is apparently stronger than any available aromatic
stacking effect. Attempts to use metal cations to induce
the wheel in [2]rotaxane 6 to reside over the central
acetal linkage were unsuccessful. Addition of excess Na+,
K+, Ba2+, or Ag+ perchlorate salts to solutions of 6 in
DMSO-d6 does not induce any significant change in the
chemical shift of the axle acetal protons. The NMR
(10) Lane, A. S.; Leigh, D. A.; Murphy, A. J . Am. Chem. Soc. 1997,
119, 11092-11093.
(9) Hughes, M. P.; Smith, B. D. J . Org. Chem. 1997, 62, 4492-4501.

Conversion of Macrobicycle into [2]Rotaxanes
J . Org. Chem., Vol. 67, No. 5, 2002 1439
Hz), 8.00 (s, 1H), 7.43 (t, 1H, J ) 8.0 Hz), 7.29-7.19 (m, 30H),
7.04 (d, 4H, J ) 9.0 Hz), 6.71 (AB q, 8H, J ) 8.0 Hz), 6.66 (t,
2H, J ) 5.0 Hz), 6.24 (d, 4H, J ) 9.0 Hz), 4.38 (d, 4H, J ) 4.5
Hz), 4.17 (s, 2H), 3.51 (s, 4H), 3.43 (t, 8H, J ) 5.5 Hz), 3.33 (s,
br, 4H), 3.17 (s, br, 4H), 2.70 (s, br, 4H), 2.62 (s, br, 4H); 13C
NMR (75 MHz, CDCl3) δ 166.8, 153.4, 147.0, 141.3, 137.2,
136.2, 134.5, 132.6, 131.8, 131.2, 129.9, 129.4, 128.6, 127.9,
126.2, 123.5, 114.3, 70.7, 70.1, 64.6, 59.7, 52.3, 44.6. MS (FAB+,
[M + H]+) calcd for C87H86N4O8 1314.64, found 1314.52 m/z.
X-ray data for 5: C87H86N4O8, triclinic, P1h, a ) 12.784(3) Å, b
) 15.522(3) Å, c ) 19.931(4) Å, R ) 90.145(4)°, â ) 104.412-
(4)°, γ ) 93.480(4)°, V ) 3823.0(13) Å3, Z ) 2, T ) 170(2) K,
µ(Mo KR) ) 0.078 mm-1, Dcalcd ) 1.190 mg/m3, R1 (I > 2θ(I))
) 7.23%, wR2 (I > 2θ(I)) ) 18.41% for 10968 observed
independent reflections (4° ) 2θ ) 46°). The X-ray data for 5
can be retrieved from the Cambridge Crystallographic Data
Center using deposition number CCDC 171663. Crystals were
grown by slow evaporation from ethanol.
signals for the crown protons do change appreciably,
however, indicating that the metal cations do bind to the
rotaxane.
Su m m a r y
We have shown how crown ether-containing macrobi-
cycle 2 can be used to make novel benzyl amide [2]-
rotaxanes 5 and 6 with acetal-containing axles. The co-
conformation of 6 is quite sensitive to solvent polarity;
however, unlike our previously reported example,2 the
co-conformation is apparently not affected by the pres-
ence of metal cations. Further studies of this class of [2]-
rotaxanes as potential molecular devices such as shuttles
and triggered release agents will be reported in due
course.
6. K2CO3 (0.019 g) was added to a solution of macrobicycle
2 (0.022 g, 0.034 mmol) and phenol 9 (0.038 g, 0.069 mmol) in
freshly distilled CH2Cl2 (5 mL), and the mixture was stirred
for 3 days. After removal of the solvent, the residue was
purified on a silica column by elution with CH2Cl2 to remove
the axle and unreacted phenol, followed by 95:5 CH2Cl2/MeOH
to obtain the desired rotaxane 6 (0.010 g, 16%): 1H NMR (600
MHz, CDCl3) δ 8.23 (d, 1H, J ) 1.2 Hz), 8.22 (d, 1H, J ) 1.2
Hz), 8.20 (s, 1H), 7.60 (t, 1H, J ) 7.8 Hz), 7.26-7.17 (m, 34H),
7.10 (d, 4H, J ) 5.4 Hz), 6.96-6.95 (m, 8H), 6.90 (t, 2H, J )
4.8 Hz), 6.88 (d, 4H, J ) 7.8 Hz), 6.74 (d, 4H J ) 9.0 Hz), 6.66
(d, 4H, J ) 6.7 Hz), 5.47 (s, 2H), 4.45 (d, 4H), 3.64-3.47 (m,
28H), 2.74 (s, br, 4H), 2.67 (s, br, 4H), 1.60-1.54 (m, 8H), 1.19-
1.28 (m, 16H); 13C NMR (150 MHz, CDCl3) δ 166.3, 156.7,
154.4, 151.0, 147.2, 139.3, 137.2, 135.8, 134.1, 132.4, 132.3,
132.2, 131.3, 131.2, 130.0, 129.8, 128.5, 127.6, 127.5, 126.1,
126.0, 123.1, 117.9, 115.4, 113.3, 92.9, 70.9, 70.1, 68.6, 68.0,
64.5, 62.1, 59.5, 52.4, 44.7, 29.5, 29.4, 29.3, 27.7, 26.1. MS (ESI,
[M + H]+) calcd for C115H126N54O12 1757.26, found 1757.52.
Exp er im en ta l Section
Ma cr obicycle 2. Diamine 45 (0.430 g, 0.86 mmol) was
dissolved in THF (250 mL). Separately, 5-(tert-butyl)isoph-
thaloyl dichloride (0.174 g, 0.86 mmol) was dissolved in the
same volume of THF. A 1 L three-neck, round-bottom flask
was charged with 100 mL of THF and triethylamine (260 µL,
1.89 mmol). Via two pressure-equalizing dropping funnels,
both reactants were added simultaneously dropwise to the
flask with vigorous stirring under nitrogen at ambient tem-
perature. The cloudy solution was stirred for 24 h, and the
solvent was removed under vacuum, leaving a yellow gos-
samer. The crude material was dissolved in CH2Cl2 and
washed successively with saturated NaHCO3 and deionized
water. Evaporation of the organic layer and purification on a
silica column (90:10 CH2Cl2/MeOH, then MeOH eluent) yielded
pure 2 (0.245 g, 45%); mp 99-101°; 1H NMR (300 MHz,
DMSO-d6) δ 8.92 (t, 2H, J ) 5.4 Hz), 8.28 (s, 1H), 7.95 (d, 1H,
J ) 7.8 Hz), 7.59 (t, 2H, J ) 7.8 Hz), 7.28 (AB q, 8H, J ) 8.1
Hz), 4.48 (d, 4H, J ) 5.7 Hz), 3.58 (s, 4H), 3.50 (t, 8H, J ) 5.4
Hz), 3.49 (s, 8H), 2.60 (t, 8H, J ) 5.4 Hz) ppm; 13C NMR (75
MHz, CDCl3): δ 167.1, 138.7, 136.7, 135.1, 131.0, 129.6, 129.5,
128.1, 124.3, 70.9, 70.1, 59.7, 53.9, 44.1. HRMS (FAB+, [M +
H]+) calcd for C36H46N4O6 631.3496, found 631.3507 m/z.
7. Potassium 4-tritylphenolate (0.2 g, 0.53 mmol), 1,8-
dibromooctane (0.14 g, 0.53 mmol), and a catalytic amount of
KI (0.010 g, 0.084 mmol) were dissolved in acetonitrile (30 mL)
and refluxed for 18 h. Evaporation of the solvent gave the
crude product, which was purified by chromatography (SiO2;
hexane/CH2Cl2; 70:30) to afford a white solid (0.15 g, 53%);
mp 133-137°; 1H NMR (300 MHz, CDCl3) δ 7.32-7.20 (m,
15H), 7.15 (d, 2H, J ) 9 Hz), 6.79 (d, 2H, J ) 9 Hz), 3.96 (t,
2H, J ) 6.9 Hz), 3.44 (t, 2H, J ) 6.9 Hz), 1.92-1.88 (m, 2H),
1
2‚HCl: H NMR (300 MHz, CDCl3) δ 7.92 (d, 2H, J ) 8.0
Hz), 7.86 (s, 1H), 7.40 (t, 1H, J ) 8.0 Hz), 7.20 (AB q, 8H, J )
8.0 Hz), 6.70 (t, br, 2H, J ) 5.4 Hz), 4.47 (d, 4H, J ) 5.5 Hz),
3.65 (s, 4H), 3.60 (m, 16H), 2.67 (t, 8H, J ) 5.5 Hz). MS (FAB,
1.83-1.75 (m, 2H), 1.53-1.48 (m, 4H), 1.46-1.40 (m, 4H); 13
C
[M + H + HCl]+) 667 m/z. Crystal data for 2‚HCl: C36H47
-
NMR (75 MHz, CDCl3) δ 157.2, 147.2, 138.9, 132.3, 131.3,
127.5, 126.0, 113.3, 67.9, 64.4, 34.1, 32.9, 29.4, 29.3, 28.8, 28.7,
28.2, 26.1. HRMS (FAB+, [M + H]+) calcd for C33H35BrO
526.1871, found 526.1864.
ClN4O6, monoclinic, P(2)1/ n, a ) 12.378(2) Å, b ) 18.341(3)
Å, c ) 17.614(3) Å, R ) 90°, â ) 102.507(5)°, γ ) 90°, V )
3904.2(11) Å3, Z ) 4, T ) 170(2) K, µ(Mo KR) ) 0.156 mm-1
,
Dcalcd ) 1.275 mg/m3, R1 (I > 2θ(I)) ) 5.27%, wR2 (I > 2θ(I))
) 8.84% for 5598 observed independent reflections. The X-ray
data for 2‚HCl can be retrieved from the Cambridge Crystal-
lographic Data Center using deposition number CCDC 171662.
Crystals were obtained by slow evaporation from ethanol.
3. The pyridyl macrobicycle 3 was prepared following the
same synthetic procedures for 2 and obtained in 15% yield.
1H NMR (300 MHz, CDCl3) δ 8.32 (d, 2H, J ) 7.8 Hz), 8.11 (t,
br, 2H), 8.02 (t, 1H, J ) 7.7 Hz), 7.41 (d, 4H, J ) 8.1 Hz), 7.27
(d, 4H, J ) 8.1 Hz), 4.60 (d, 4H, J ) 5.7 Hz), 3.75 (bs, 4H),
3.68 (t, 8H, J ) 5.4 Hz), 3.64 (s, 8H), 2.76 (t, 8H, J ) 5.4 Hz)
ppm; 13C NMR (125 MHz, CDCl3) δ 163.2, 148.9, 139.2, 136.6,
129.6, 128.1, 125.2, 125.0, 71.1, 69.9, 59.8, 54.4, 43.5 ppm.
HRMS (FAB+, [M + H]+) calcd for C35H45N4O6 632.3448, found
632.3445 m/z.
8. A solution of 7 (0.15 g, 0.28 mmol), 4-bezyloxyphenol
(0.056 g, 0.28 mmol), potassium carbonate (0.039 g, 0.028
mmol) and catalytic amount of KI (0.010 g, 0.084 mmol) were
refluxed in acetonitrile (30 mL) for 24 h. The solvent was
removed in vaccuo and the residue chromatographed (SiO2;
hexane:CH2Cl2; 70:30). A white solid was obtained after
removal of the solvents (0.12 g, 66%); mp 131-133°; 1H NMR
(300 MHz, CDCl3) δ 7.43-7.31 (m, 5H), 7.32-7.20 (m, 15H),
7.16 (d, 2H, J ) 9 Hz), 6.93 (d, 2H, J ) 9 Hz), 6.93-6.80 (m,
4H), 5.05 (s, 2H), 3.97-3.94 (m, 4H), 1.88-1.78 (m, 4H), 1.58-
1.40 (m, 8H) ; 13C NMR (75 MHz, CDCl3) δ 157.2, 153.7, 153.0,
147.2, 138.9, 137.5, 132.3, 131.3, 128.7, 127.6, 126.0, 116.0,
115.5, 113.4, 70.9, 68.7, 68.0, 64.5, 29.6, 29.5, 26.2, 26.1. HRMS
(FAB+, [M + H]+) calcd for C46H46O3 646.3447, found 646.3437.
9. Compound 8 (0.100 g, 0.006 mmol) was dissolved in
methanol/THF (1:1) (30 mL) and a catalytic amount (0.030 g)
of Pd/C (10% w/w) was added and stirred under H2 at room
temperature for 3 h. After complete reaction the solution was
filtered and the solvent removed using a rotary evaporator to
5. Macrobicycle 2 (0.037 g, 0.06 mmol) and potassium
4-tritylphenolate (0.045 g, 0.12 mmol, 2.0 equiv) were dissolved
in freshly distilled CH2Cl2 (5 mL) with stirring under nitrogen
at ambient temperature. Stirring was continued for 24 h, at
which time the solvent was removed by rotary evaporation.
The crude material was purified on a silica column by elution
with CH2Cl2 to remove the axle and unreacted phenol, followed
by 95:5 CH2Cl2/MeOH to obtain the desired rotaxane 5 (0.012
g, 15%): 1H NMR (300 MHz, CDCl3) δ 8.01 (d, 2H, J ) 8.0
1
give 9 (0.075 g, 88%) as a white solid; mp 80-83°; H NMR
(300 MHz, CDCl3) δ 7.32-7.20 (m, 15H), 7.11 (d, 2H, J ) 9
Hz), 6.81-6.76 (m, 6H), 3.94-3.90 (m, 4H), 1.79-1.77 (m, 4H),
1.47-1.40 (m, 4H), 1.40 (m, 4H); 13C NMR (75 MHz, CDCl3) δ

1440 J . Org. Chem., Vol. 67, No. 5, 2002
Mahoney et al.
157.2, 153.4, 149.6, 147.2, 138.9, 132.3, 131.3, 127.6, 126.0,
125.7, 116.2, 115.8, 113.4, 68.8, 68.0, 64.5, 30.5, 29.5, 29.4, 26.2,
26.1. HRMS (FAB+, [M + H]+) calcd for C39H40O3 556.2977,
found 556.2962.
addition. Care was taken to avoid water absorption from the
atmosphere. Titration isotherms for all receptor protons that
exhibited significant complexation-induced shifts were fitted
to a 1:1 binding model using an iterative curve-fitting method
that has been previously described.9 For each system, the
extracted association constants for the different isotherms
were within 15% of the average value.
1H NMR Titr a tion s. All salts and NMR solvents were
purchased from Aldrich and, after being checked for purity,
were used as supplied. K(BPh)4 was synthesized according to
a
literature procedure.11 The receptor was titrated with
tetrabutylammonium chloride in the presence and absence of
alkali tetraphenylborate. In each case, a 10 mM solution of
the receptor in DMSO-d6 was prepared in a 5 mm NMR tube
(solution volume 750 µL). Where applicable, the solution also
contained 1 molar equiv of alkali tetraphenylborate. Small
aliquots of tetrabutylammonium chloride stock solution (0.75
M) were added, and a spectrum was acquired after each
Ack n ow led gm en t. This work was supported by the
National Science Foundation, the University of Notre
Dame (Grace Fellowship for J .M.M.), and Eli Lilly &
Co. (Summer Undergraduate Fellowship for R.A.M.).
Su p p or tin g In for m a tion Ava ila ble: 1H NMR spectra for
5 and 6. This material is available free of charge via the
Internet at http://pubs.acs.org.
(11) Honda, H.; Ono, K.; Murakami, K. Macromolecules 1990, 23,
515-520.
J O0162787