Assembly and Binding Properties of Osmate Ester-Bridged Binuclear Macrocycles

Article abstract of DOI:10.1021/jo9910841

Osmium (VI)-bridged macrocycles 1a-c, 2, and 3 assemble spontaneously when osmium tetraoxide, olefins, and L-shaped bispyridyl ligands are mixed in CHCl₃. The macrocycles possess well-defined square or rectangular cavities enclosed by aryl walls and act as host molecules. Hydrogen-bond donors on the inner surface of the hosts offer binding sites to acceptors of guests with complementary dimensions. The host 1a binds adipamide G2 (K_a = 3.6 × 10⁴ M^-1) and terephthalamide G6 (K_a = 2.0 × 10⁴ M^-1), while it binds negligibly (K_a < 10 M^-1) benzamide G5, isophthalamide G9, or 1,4-naphthalenedicarboxamide G10. The larger hosts 2 and 3 bind the longer guests biphenyldicarboxamide G12 and terphenyldicarboxamide G17, respectively, but shorter guests such as adipamide G2 and terephthalamide G6 are not well-bound (K_a < 10 M^-1). Hosts 1a-c with different remote substituents (H, OMe, NO₂) but identical cavity size were prepared and their binding affinities were measured. The relative binding affinities of the hosts 1a-c to the keto amide G19, ester amide G20, and diester G21 are in the order of 1c (NO₂) ? 1a (H) > 1b (OCH₃). The substituent effects on the binding strength are interpreted in terms of the electron density at the pyridine nitrogen of the hosts and its effect on bifurcated hydrogen bonding.

Full text of DOI:10.1021/jo9910841

J . Org. Chem. 1999, 64, 9459-9466
9459
Assem bly a n d Bin d in g P r op er ties of Osm a te Ester -Br id ged
Bin u clea r Ma cr ocycles
Kyu-Sung J eong,* Young Lag Cho, Sung-Youn Chang, Tae-Yoon Park, and J ung Uk Song
Department of Chemistry, Yonsei University, Seoul 120-749, Korea
Received J uly 6, 1999
Osmium (VI)-bridged macrocycles 1a -c, 2, and 3 assemble spontaneously when osmium tetraoxide,
olefins, and L-shaped bispyridyl ligands are mixed in CHCl3. The macrocycles possess well-defined
square or rectangular cavities enclosed by aryl walls and act as host molecules. Hydrogen-bond
donors on the inner surface of the hosts offer binding sites to acceptors of guests with complementary
dimensions. The host 1a binds adipamide G2 (Ka ) 3.6 × 104 M-1) and terephthalamide G6 (Ka )
2.0 × 104 M-1), while it binds negligibly (Ka < 10 M-1) benzamide G5, isophthalamide G9, or 1,4-
naphthalenedicarboxamide G10. The larger hosts 2 and 3 bind the longer guests biphenyldicar-
boxamide G12 and terphenyldicarboxamide G17, respectively, but shorter guests such as adipamide
G2 and terephthalamide G6 are not well-bound (Ka < 10 M-1). Hosts 1a -c with different remote
substituents (H, OMe, NO2) but identical cavity size were prepared and their binding affinities
were measured. The relative binding affinities of the hosts 1a -c to the keto amide G19, ester
amide G20, and diester G21 are in the order of 1c (NO2) . 1a (H) > 1b (OCH3). The substituent
effects on the binding strength are interpreted in terms of the electron density at the pyridine
nitrogen of the hosts and its effect on bifurcated hydrogen bonding.
In tr od u ction
checking and cooperativity during assembly.5 Maverick
reported the first example of a discrete, self-assembled
macrocycle, a Cu(II) and â-diketone complex that bound
1,4-diazabicyclo[2.2.2]octane.6 Subsequently, impressive
systems were reported by Fujita, who prepared molecular
squares and cages. These featured hydrophobic cavities
created by self-assembly of rigid tertiary amine ligands
with transition metals that prefer square planar coordi-
nation such as Pd(II) and Pt(II).11 These assemblies
encapsulated aromatic and adamantane guests through
hydrophobic interactions in aqueous solution. Stang
Macrocycles such as cyclodextrins, crown ethers, calix-
arenes, carcerands, and other related molecules have
been used as a powerful tool for the study and evolution
of host-guest or supramolecular chemistry over the last
3 decades.1 These compounds have advanced the under-
standing of weak, noncovalent interactions and have
provided models for recognition in biological systems.
More recently, self-assembled macrocycles have attracted
a great deal of attention. In these frameworks some
covalent bonds are replaced by relatively weak inter-
molecular forces including hydrogen bonding2,3 and metal-
ligand interactions.4-13 These features give the systems
the advantages of reversible formation such as error
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* To whom correspondence should be addressed. Tel: +82-2-361-
2643. Fax: +82-364-7050. E-mail: ksjeong@alchemy.yonsei.ac.kr.
(1) (a) Comprehensive Supramolecular Chemistry; Lehn, J .-M., Chair
Ed.; Atwood, J . L., Davies, J . E. D., MacNicol, D. D., Vo¨gtle, F., Eds.;
Pergamon: Oxford, 1996; Vol. 1-3. (b) Lehn, J .-M. Supramolecular
Chemistry: Concepts and Perspectives; VCH: Weinheim, 1995.
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10.1021/jo9910841 CCC: $18.00 © 1999 American Chemical Society
Published on Web 12/01/1999

9460 J . Org. Chem., Vol. 64, No. 26, 1999
J eong et al.
developed a parallel self-assembling motif for the con-
struction of a series of molecular boxes soluble in organic
solvents and capable of binding neutral organic guests.12
Hunter synthesized a self-assembled Zn-porphyrin com-
plex containing hydrogen-bonding sites inside the cavity
and reported a strong complexation with terephthalamide
through hydrogen-bonding interactions in CDCl3.13
Osmium tetraoxide is a reliable oxidant for converting
olefins to the corresponding cis-1,2-diols. The reaction
proceeds efficiently in the presence of tertiary amines
such as pyridine via Os(VI)-ester intermediate.14 The
structural features of the octahedral intermediates have
been characterized in the solid state and in solution,
wherein two pyridines are coordinated in the equatorial
position with a cis relationship.14c,15 On the basis of this
feature we were able to assemble octahedral osmium(VI)
ester-bridged molecular squares having well-defined
cavities.16 The macrocycles were spontaneously as-
sembled from osmium tetroxide, olefins, and bispyridyl
ligands. This self-assembling motif was further extended
to the macrocyclic host 1a by introducing two hydrogen-
bonding sites at the diagonal corners into the cavity and,
in the present work, to four related hosts 1b, 1c, 2, and
3.
In the preliminary communication,16 we reported two
X-ray crystal structures of osmate ester-bridged macro-
cyclic boxes. The Os(VI) ester has a distorted octahedral
geometry, where two pyridine ligands are coordinated in
the equatorial position with an approximately right
N-Os-N angle (89.5°). This geometry is nearly ideal for
assembly of molecular squares or rectangles. The ligands
4a -c, 5, and 6 comprise the 2,6-pyridinedicarboxamide
unit in which internal N(pyridyl)‚‚‚H-N(amide) hydrogen
bonds17 (about which more, later) can accommodate an
angle near 90° and provide a bend in the structure to
form the macrocycle. The juxtaposition of the osmate
esters with the ligands results in the formation of discrete
macrocyclic boxes with a square or rectangular geometry.
The o-methyl substituents on the aromatic ring enforce
a boxlike (as opposed to a flattened) shape for the
molecule. Moreover, these substituents increase the
solubility of the ligands and their derived macrocycles.
The incorporation of polar binding sites inside the mac-
rocycle offers an opportunity to bind guests with comple-
mentary functions on their outer surfaces.
Resu lts a n d Discu ssion
Syn th esis. The dichlorides 7b and 7c18 and 4-amino-
3,5-lutidine (8)19 were prepared according to literature
procedures. The amine 9 was synthesized from 4-bromo-
2, 6-dimethylaniline as described in Scheme 1 (35%
yield).20 The coupling reactions of dichlorides 7a -c with
2 equiv of amine 8 or 9 provided the corresponding
ligands 4a -c and 6 (52-76% yield). The unsymmetrical
ligand 5 was obtained by reaction of the acid chloride 7a
with 1 equiv of each of the amines 8 and 9 in 30% yield.
The macrocycles 1a -c, 2, and 3 were formed in CHCl3
from osmium tetraoxide and a 1:1 mixture of olefin and
ligands 4a -c, 5, and 6, respectively. More soluble square
macrocycles 1a -c and 3 were assembled in the presence
of 5,6-dibutyl-5-decene; however, 9,10-dioctyl-9-octa-
decene21 was used for the preparation of less soluble
rectangular macrocycle 2. The reactions went to comple-
tion usually within a few minutes at room temperature,
and the desired macrocycles were obtained in 61-89%
yield.
Ch a r a cter iza tion of Ma cr ocycles. The products
1a -c, 2, and 3 are soluble in various organic solvents
(14) For reviews, see: (a) Berrisford, D. J .; Bolm, C.; Sharpless, K.
B. Angew. Chem., Int. Ed. Engl. 1995, 34, 1059-1070. (b) Kolb, H. C.;
VanNieuwenhze, M. S.; Sharpless, K. B. Chem. Rev. 1994, 94, 2483-
2547. (c) Schro¨der, M. Chem. Rev. 1980, 80, 187-213.
(15) (a) Hawkins, J . M.; Meyer, A.; Lewis, T. A.; Loren, S. Hollander,
F. J . Science 1991, 252, 312-313. (b) Wallis, J . M.; Kochi, J . K. J . Am.
Chem. Soc. 1988, 110, 8207-8223.
(16) J eong, K.-S.; Cho, Y. L.; Song, J . U.; Chang, H.-Y.; Choi, M.-G.
J . Am. Chem. Soc. 1998, 120, 10982-10983.
(17) Hunter, C. A.; Purvis, D. H. Angew. Chem., Int. Ed. Engl. 1992,
31, 792-795. See also Crisp, G. T.; J iang, Y.-L. Tetrahedron 1999, 55,
549-560.
(18) Bradshaw, J . S.; Maas, G. E.; Lamb, J . D.; Izatt, R. M.;
Christensen, J . J . J . Am. Chem. Soc. 1980, 102, 467-474.
(19) (a) Malinowski, M.; Kaczmarek, L. J . prakt. Chem. 1988, 330,
154-158. (b) Essery, J . M.; Schofield, K. J . Chem. Soc. 1960, 4953-
4959.
(20) For a related coupling reaction, see: Anderson, H. L.; Walter,
C. J .; Vidal-Ferran, A.; Hay, R. A.; Lowden, P. A.; Sanders, J . K. M. J .
Chem. Soc., Perkin Trans. 1 1995, 2275-2279.
(21) For a review of the highly substituted olefin synthesis, see:
Lenoir, D. Synthesis 1989, 883-897.

Ester-Bridged Binuclear Macrocycles Os(VI)
J . Org. Chem., Vol. 64, No. 26, 1999 9461
Sch em e 1
Ch a r t 1
the titration conditions. The chemical shifts and splitting
patterns in the 1H NMR spectra of macrocyclic hosts 1a -
c, 2, and 3 remain constant in a wide range of the
concentration (0.25-20 mM) in CDCl3. This precludes
aggregation or dissociation of 1a -c, 2, and 3 under
1
titration conditions. Therefore, any changes in H NMR
spectra of 1a -c, 2, and 3 upon guest addition are only
due to host-guest complexation. The experiments were
performed by adding the guest solution (5-10 mM in
CDCl3) to the host stock solution (1-2 mM in CDCl3) in
small portions and monitoring the downfield shift of the
host NH signal. The association constants (Kas, M-1) were
determined by nonlinear least-squares fitting analysis of
the titration curves: plots of ∆δ(N-H) vs equivalents of
guest were well-fitted to the expression of a 1:1 binding
isotherm (see the Experimental Section).22 Each titration
experiment was duplicated and the association constants
(Ka) were reproducible within 20%.
Bin d in g P r op er ties of 1a . Diamide guests evaluated
for host 1a are given in Chart 1. Flexible dicarboxamides
G1-G4 with various chain lengths were first examined.
The signal for the amide N-H of the host 1a was
gradually downfield shifted on the guest addition (Figure
1a), indicative of intermolecular hydrogen-bond forma-
tion. For example, the addition of adipamide G2 (n ) 4)
caused the N-H signal of 1a to shift downfield from 9.2
to 10.7 ppm, and the saturation was reached at about 1
equiv of added guest. This suggested a 1:1 stoichiometry
with a high association constant (Ka ) 3.6 × 10-4 M-1).
Any small variation in the chain length of the guests
greatly decreases the association constants: Ka ) 1.5 ×
103 for G1 (n ) 3), 9.3 × 102 for G3 (n ) 5), and 3.3 ×
including dichloromethane, chloroform, tetrahydrofuran,
acetone, and dimethyl sulfoxide. The 1:1:1 stoichiometry
of the osmium tetroxide, the olefin, and the ligand was
confirmed by elemental analysis of the products. The
infrared spectra show a strong, characteristic band near
830 cm-1, diagnostic of the trans OdOsdO moiety of the
1
octahedral dioxoosmium(VI) complexes.14c,15 The H and
13 C NMR spectra of 1a -c, 2, and 3 were well-correlated
to the symmetrical structures. The 1H NMR integrations
confirmed a 1:1 molar ratio of olefin and ligand. The
coordinating pyridyl C-H (R to the nitrogen) resonances
of the macrocycles are shifted downfield from those for
free ligands (∆δ ) 0.2-0.3 ppm). In the FAB-MS analy-
ses, the molecular ion peak [M]+ could not be detected,
probably due to the presence of labile Os(VI)-N and Os
(VI)-O bonds under ionization conditions. Nevertheless,
peaks of a weak intensity (0.1-0.2%) were observed
which could be attributed to one and two glycol loss from
the binuclear macrocycles, [M - ((OC (C4H9) ) ]+ and
2
2
[M - 2(OC (C4H9) 2)2]+, respectively. In addition to these
physical and spectroscopic properties, the binding data
described below strongly support the formation of discrete
binuclear macrocycles in solution.
1H NMR Titr a tion s. The binding properties were
revealed in CDCl3 at 24 ( 1 °C by 1H NMR titration
experiments, and time-averaged resonances for the free
and the complexed species were always observed under
(22) For more details, see: Macomber, R. S. J . Chem. Educ. 1992,
69, 375-378.

9462 J . Org. Chem., Vol. 64, No. 26, 1999
J eong et al.
Ta ble 1. Associa tion Con sta n ts (Ka ( 20%, M-1) a t 297 (
1 K in CDCl3 a n d th e Obser ved a n d Ca lcu la ted Ma xim u m
Ch em ica l Sh ift Ch a n ges of th e Host NH Sign a ls
∆δmax(obsd) ∆δmax(calcd)
entry
guest
(NH, ppm)a
(NH, ppm)a
Ka (M-1
)
Host 1a
1.23
1.47
1.16
0.90
0.12
1.23
0.95
0.95
1
2
3
4
5
6
7
8
9
G1 (n ) 3)
G2 (n ) 4)
G3 (n ) 5)
G4 (n ) 6)
G5
G6
G7
G8
G9
1.38
1.47
1.37
1.36
1.24
1.23
1.09
1.18
1.24
1450
35,500
930
330
6
20,000
910
640
0.08
<0.02
<0.02
4
10
11
G10
G11
ndb
ndb
Host 2
12
13
14
15
16
17
G6
G12
G13 (n ) 7)
G14 (n ) 8)
G15 (n ) 9)
G16 (n ) 10)
0.07, 0.10
1.37, 1.91
0.69, 0.81
1.26, 1.41
1.29, 1.37
1.09, 1.19
0.84, 0.94
1.46, 1.91
1.26, 1.37
1.39, 1.52
1.40, 1.50
1.27, 1.41
8
45,000
170
2150
1650
1030
Host 3
1.27
1.26
18
19
G17
G18
1.58
1.53
780
910
a
The NH chemical shifts of the free hosts are 9.19 ppm for 1a ,
b
8.98 and 9.30 ppm for 2, and 9.08 ppm for 3. Not determined.
F igu r e 1. (a) Titration curves between host 1a and guests
G1-G4, plotting the host NH chemical shift changes (∆δ) vs
molar equivalents of the guest and (b) Continuous variation
method (J ob plots) between 1a and G1-G4.
F igu r e 2. Energy-minimized (Tripos) CPK models of hosts
1a (left) and 2 (right). The butyl groups in the Os(VI) corners
have been replaced by methyl groups and some hydrogens
omitted for clarity.
102 M-1 for G4 (n ) 6) (Table 1). All guests in this series
showed a 1:1 complexation with 1a , as confirmed by J ob’s
plots23 (Figure 1b).
CDCl3. On complexation of 2 with 4,4′-biphenylcarboxa-
mide G12, characteristic downfield shifts of both N-H
signals were observed: ∆δ 1.25 ppm for the lutidyl N-H
and ∆δ 1.70 ppm for the pyridylethynylphenyl N-H. The
titration curves plotted using either ∆δ gave essentially
identical association constants within experimental error
(<5%), indicating that both NHs are involved in a single
binding event. Rigid carboxamide G12 is nearly a perfect
fit for the space inside the rectangular box 2 and binds
strongly (Ka ) 4.5 × 104 M-1). However, smaller guests
such as adipamide G2 and terephthalamide G6 enjoy the
freedom of entering and leaving the host’s cavity without
sticking (Ka < 10 M-1). In a series of experiments with
flexible guests G13-G16, the chain length selectivity of
2 was shown to be less than that of 1a (Table 1). This is
a reasonable consequence of the larger cavity presented
by 2.
Rigid diamides, terephthalamide G6, 1,4-cyclohex-
anedicarboxamide G7, and 2,5-thiophenedicarboxamide
G8, exhibited high affinities for 1a , while the monoamide
G5 shows nearly no binding.24 This suggests that two
hydrogen-bonding sites of the host 1a must be simulta-
neously involved in the association with diamide guests.
Remarkably, 1,4-napnthalenedicarboxamide G10 bound
negligibly, despite its similarity in structure to G6.24
Likewise, G9sonly slightly larger than G8sshowed
nearly no binding. For the poor guests G9 and G10, the
CPK models indicated severe steric repulsion between
the host lutidyl surfaces and the guest aryl residues (see,
for example Figure 3).
Bin d in g P r op er ties of 2 a n d 3. The 1H NMR
spectrum of the macrocycle 2 with a rectangular shape
showed two distinct N-H signals: N-H (lutidyl) δ 8.98
ppm and N-H (pyridylethynylphenyl) δ 9.30 ppm in
The even larger size of the square macrocycle 3
permitted inclusion of dicarboxamide G17 (containing a
terphenyl spacer) or G18 (having a diphenylbutadienyl
spacer). The association constants, 780 and 910 M-1
,
(23) Corners, K. A. Binding Constants; J ohn Wiley & Sons: New
York, 1984; p 24.
(24) In the cases of the guests G5, G9, G10, and G11, the chemical
shift changes of the host NH signal were too small (∆δmax e ∼0.1 ppm)
to determine the association constants accurately under the titration
conditions.
respectively, are lower than those expected for an ideal
guest as established by 1a and 2.
Su bstitu en t Effects on th e Host-Gu est Com p lex
Sta bility. Three hosts, 1a , 1b, and 1c, contain different

Ester-Bridged Binuclear Macrocycles Os(VI)
J . Org. Chem., Vol. 64, No. 26, 1999 9463
case of secondary effects on hydrogen bonding as intro-
duced by J orgensen.25
Com p lex Geom etr y. Computer modeling studies26
were used to characterize the hydrogen-bonding sites of
the macrocyclic hosts 1a and 2 (Figure 2). The diagonal
distances between the amide hydrogens of the two
binding sites are approximately 9 Å in 1a and 13 Å in 2.
If good hydrogen bonds are to be formed, the carboxamide
O‚‚‚O distance of the guest should complement the
diagonal distance of the host.
Guests G6 and G12 were the best fits for 1a and 2,
respectively. Binding of G6 to the rectangular host 2 was
not favorable because the cavity was too roomy for this
small guest. These results clearly indicate that two
binding sites are simultaneously involved in the recogni-
tion event. The structure proposed for the complex
between the host 1a and terephthalamide derivative is
shown in Figure 3. The N,N-dialkyl groups twist the
planes of amide and aromatic of the guest in such a way
that additional substituents on the aromatic ring are
directed at the walls of the host. The limited space
remaining in the cavity explains the difficulty in binding
the isophthalamide G9 and 1,4-naphthalenedicarboxa-
mide G10.
F igu r e 3. Energy-minimized (Tripos)26 structure of the
complex between hosts 1a and N,N,N′N′-tetramethyltereph-
thalamide. Some hydrogens have been omitted for clarity.
Ta ble 2. Associa tion Con sta n ts (Ka ( 20%, M-1) of th e
Hosts 1a -c w ith Gu ests G19-G21 a t 297 ( 1 K in CDCl3
association constants (Ka, M-1
)
guest
host 1a (H) host 1b (OCH3) host 1c (NO2)
G19 (keto-amide)
G20 (ester-amide)
G21 (diester)
2230
1200
60
1170
740
45
25000
17000
350
substituents (H, OMe, and NO2) at the para position of
the corner pyridine ring. Attempts to find differences in
binding affinities of 1a -c with adipamide G2 were
unsuccessful, since this guest bound too strongly to all
4
of the hosts (Ka > 10 M-1). Differences were found in
Additional evidence for locating the guests inside the
the binding abilities of these hosts to guests G19-G21,
containing a poor hydrogen-bond acceptor. These guests
bind more weakly to the host 1b (OMe) but much more
strongly to the host 1c (NO2) than to the reference host
1a (H) (Table 2). These differences were outside the
experimental errors of the titration protocols but were
not easily explained. The remote substituents should
have little effect on the acidity of hydrogen-bond donors
of the amides. Indeed, the NH resonance of 1b appeared
at δ 9.24 ppm, 1c at δ 9.05 ppm, and 1a at δ 9.19 ppm.
This order is inconsistent with direct inductive effects
on the N-H because the most electron-withdrawing
group has the most shielded proton. The substituent
effects, we believe, are due to changes in the electron
density at the pyridine nitrogen. As mentioned earlier,
the conformations of the amides at the pyridine-2,6-
dicarboxamide corners are those that are expected from
intramolecular hydrogen bonds between the secondary
amides and the pyridyl nitrogen. This is not a good
intramolecular hydrogen bond (the N‚‚‚H-N angle is far
from ideal), but the hydrogen and heavy atoms are
polarized as expected. On complexation, the hydrogen-
bond donors of the host converge on the guest’s carbonyl
oxygen acceptor. The oxygen will experience the pyridyl
nitrogen in a repulsive way. Such repulsion is a universal
feature of bifurcated hydrogen bonding, and the sub-
stituent can effect the degree of this repulsion. The host
1b (OMe), with an electron-donating group, is therefore
the poorest host, but the host 1c (NO2) with a strong
electron-withdrawing group is the best host for the guests
G19, G20, and G21. This can also be viewed as another
1
cavity was obtained from H NMR spectroscopy (Figure
1
4). As mentioned earlier, time-averaged H NMR signals
between free and complex species were observed at room
temperature (the exchange rate is fast on the NMR time
scale). The separated signals could be, however, seen in
the cases of Ka > 104 M-1 in CDCl3 by lowering temper-
ature down to -40 °C. Shielding by the anisotropic
environment of the aromatic walls of the host 1a caused
characteristic upfield shifts of the aryl C-H signals of
the terephthalamide G6 (∆δ ) 2.0 ppm). Additionally,
in the homonuclear NOE difference experiment using a
1:1 molar mixture of the host 1a and the guest G6,
irradiation of the guest aryl resonance yielded the NOE
enhancement (∼1%) of the host aryl signal. These two
observations support the proposed complex structure in
Figure 3. Likewise, upon complexation of the guest G12
with the host 2, the guest aryl signal for the ortho
hydrogens (H3) to the carboxamide group experiences an
upfield shift of ∆δ ) 1.3 ppm, while the meta hydrogen
(H2) signal remains nearly unchanged. The CPK molec-
ular models show that the H3 hydrogens are directed to
(25) (a) Pranata, J .; Wierschke, S. G.; J orgensen, W. L. J . Am. Chem.
Soc. 1991, 113, 2810-2819. (b) J orgensen, W. L.; Pranata, J . J . Am.
Chem. Soc. 1990, 112, 2008-2010. For related experimental studies,
see: (a) Gardner, R. R.; Gellman, S. H. J . Am. Chem. Soc. 1995, 117,
10411-10412. (b) Murray, T. J .; Zimmerman, S. C. J . Am. Chem. Soc.
1992, 114, 4010-4011. (c) J eong, K.-S.; Tjivikua, T.; Rebek, J ., J r. J .
Am. Chem. Soc. 1990, 112, 3215-3217.
(26) Molecular modeling was performed on a Silicon Graphics Indigo
2 workstation with Tripos force field in the Sybyl 6.3 program. Clark,
M.; Cramer, R. D., III.; Opdenbosch, N. V. J . Comput. Chem. 1989,
10, 982-1012.

9464 J . Org. Chem., Vol. 64, No. 26, 1999
J eong et al.
F igu r e 4. 1H NMR spectra (left) of (a) 1a (5.0 mM) at 23 °C, (b) 1a (5.0 mM) + G6 (7.5 mM) at 23 °C, (c) 1a (5.0 mM) + G6 (7.5
1
mM) at -40 °C, and (d) G6 (5.0 mM) at -40 °C, and H NMR spectra (right) of (e) 2 (2.0 mM) at 23 °C, (f) 2 (2.0 mM) + G12 (4.0
mM) at 23 °C, (g) 2 (2.0 mM) + G12 (4.0 mM) at -40 °C, and (h) G12 (4.0 mM) at -40 °C
52%): mp 228-230 °C; IR (KBr) 3308, 3224, 1683, 1659 cm-1
;
the π face of the aryl wall of the host 2, but the H2
hydrogens are not.
1H NMR (250 MHz, CDCl3) δ 9.33 (s, NH, 2H), 8.57 (d, J )
7.7 Hz, 2H), 8.36 (s, 4H), 8.21 (t, J ) 7.7 Hz, 1H), 2.29 (s, 12H);
13C NMR (63 MHz, CDCl3) δ 162.1, 149.8, 142.8, 140.3, 131.2,
126.8, 16.2. Anal. Calcd for C21H21N5O2: C, 67.37; H, 5.38; N,
18.70. Found: C, 67.30; H, 5.26; N, 18.79.
Con clu sion s. Five cyclophane-like macrocycles, 1a -
c, 2, and 3, with square and rectangular cavities were
spontaneously assembled in one pot by simply mixing
osmium tetraoxide, symmetrical olefins, and L-shaped
bispyridyl ligands. The cavity size and shape of the
macrocycles were varied by modification of the ligands.
Specifically, incorporation of inwardly directed hydrogen-
bond donors on the ligands resulted in the macrcocyclic
hosts that strongly and selectively bound the diamide
guests with complementary dimensions. In addition, the
stability of host-guest complexes could be influenced by
the subtle effect of the remote substituents with different
electronic natures.
Liga n d 4b. The preparation of 4b was performed under the
same conditions as those described for 4a , except that 4-meth-
oxy-2,6-pyridinedicarbonyl dichloride (7b)18 was used instead
of 2,6-pyridinedicarbonyl dichloride. 4b was obtained in 65%
yield as a white solid: mp 222-224 °C; IR (KBr) 3321, 3186,
1
1690, 1665 cm-1; H NMR (250 MHz, CDCl3) δ 9.34 (s, NH,
2H), 8.36 (s, 4H), 8.02 (s, 2H), 4.05 (s, 3H), 2.29 (s, 12H); 13C
NMR (126 MHz, CDCl3) δ 169.2, 161.5, 150.5, 149.5, 142.1,
130.4, 112.2, 56.5, 15.7. Anal. Calcd for C22H23N5O3: C, 65.16;
H, 5.72; N, 17.27. Found: C, 65.09; H, 5.90; N, 17.35.
Liga n d 4c. The preparation of 4c was performed under the
same conditions as those described for 4a except that 4-nitro-
2,6-pyridinedicarbonyl dichloride (7c)18 was used instead of
2,6-pyridinedicarbonyl dichloride. 4c was obtained in 76% yield
as a pale yellow solid: mp 266-268 °C; IR (KBr) 3278, 3232,
1695 cm-1; 1H NMR (250 MHz, CDCl3) δ 9.44 (s, NH, 2H), 9.21
(s, 2H), 8.36 (s, 4H), 2.28 (s, 12 H); 13C NMR (126 MHz, CDCl3)
δ 159.7, 157.2, 152.1, 149.5, 141.9, 130.8, 119.5, 15.7. Anal.
Calcd for C21H20N6O4: C, 59.99; H, 4.79; N, 19.99. Found: C,
59.95; H, 4.98; N, 19.99.
Exp er im en ta l Section
Gen er a l. All commercial reagents, unless otherwise noted,
were ACS reagent grade and used without further purification.
Methylene chloride, chloroform, and dimethoxyethane (DME)
were distilled from CaH2 under nitrogen. Toluene and ethyl
ether were distilled from Na/benzophenone under nitrogen.
Diethylamine was distilled from KOH. All of the amide guests
were prepared by coupling reactions of the corresponding
commercially available acids or acid chlorides with diethyl-
amine.
2,6-Dim eth yl-4-(p yr id in -4-yl-eth yn yl)a n ilin e (9). To a
degassed solution of 4-bromo-2,6-dimethylaniline (3.0 g, 15
mmol) in Et2NH (50 mL) under argon were added 2-methyl-
3-butyn-2-ol (2.9 mL, 30 mmol), CuI (0.19 g, 1.0 mmol), and
(PPh3)4Pd (0.32 g, 0.28 mmol). The reaction mixture was
heated at reflux for 2 days, cooled to room temperature, and
evaporated. The residue was redissolved in EtOAc (50 mL),
filtered, and concentrated. Purification by flash column chro-
matography (EtOAc/hexanes 1:2) to give 4-(3-hydroxy-3-me-
thylbutynyl)-2,6-dimethylaniline as pale yellow solid (2.0 g,
Melting points were uncorrected. 1H NMR spectra were
recorded at 250 or 500 MHz spectrometer, and 13C NMR
spectra were recorded at 62 or 125 MHz spectrometer. Mass
spectra were obtained with a J MS-HS 110/110A mass spec-
trometer (J EOL Inc., J apan) and nitrobenzyl alcohol was used
as a matrix in CHCl3 as solvent. Molecular modeling26 was
performed on a Silicon Graphics Indigo 2 workstation with
Tripos force field in the Sybyl 6.3 program.
N,N′-Bis(3,5-d im eth ylp yr id in -4-yl)-p yr id in e-2,6-d ica r -
boxa m id e (4a ). To a CH2Cl2 (20 mL) solution of pyridine-
2,6-dicarbonyl dichloride (7a ) (0.61 g, 3.0 mmol) at 0 °C were
added 4-amino-3,5-lutidine (0.77 g, 6.3 mmol)19 and 2.5 equiv
of N,N-diisopropylethylamine (1.3 mL, 7.5 mmol). The solution
was stirred at room temperature for 2 h and subsequently
heated at reflux for 2 h. The reaction mixture was diluted with
CH2Cl2 (20 mL), washed with saturated NaHCO3 and brine,
dried over anhydrous MgSO4, and evaporated. The solid
residue was washed with diethyl ether and recrystallized in
CH2Cl2/EtOAc solvent to provide 4a as a white solid (0.59 g,
66%): mp 78-79 °C; IR (KBr) 3432, 3353, 2215, 1633 cm-1
;
1H NMR (250 MHz, CDCl3) δ 7.03 (s, 2H), 3.69 (br s, NH2,
2H), 2.13 (s, 6H), 1.97 (s, OH, 1H), 1.59 (s, 6H); 13C NMR (63
MHz, CDCl3) δ 143.2, 131.8, 121.5, 111.5, 91.4, 82.9, 65.7, 31.7,
31.1, 17.4. Anal. Calcd for C13H17N1O1: C, 76.81; H, 8.43 N,
6.89. Found: C, 76.83; H, 8.40; N, 6.87.
A suspension of 4-(3-hydroxy-3-methylbutynyl)-2,6-dimethyl-
aniline and KOH (1.1 g, 20 mmol) in toluene (30 mL) was
heated at reflux for 9 h. The reaction mixture was filtered,
concentrated, and purified with flash column chromatography
(EtOAc/hexane 1:3) to furnish 4-acetylenyl-2,6-dimethylaniline
as pale yellow oil (2.6 g, 91%): IR (KBr) 3397, 3289, 2104, 1625

Ester-Bridged Binuclear Macrocycles Os(VI)
J . Org. Chem., Vol. 64, No. 26, 1999 9465
cm-1. 1H NMR (250 MHz, CDCl3) δ 7.11(s, 2H), 3.73(br s, NH2,
2H), 2.92(s, 1H), 2.14 (s, 6H); 13C NMR (63 MHz, CDCl3) δ
143.8, 132.2, 121.3, 110.5, 84.9, 74.6, 17.4. Anal. Calcd for
C10H11N1: C, 82.72; H, 7.64; N, 9.65. Found: C, 82.70; H, 7.52;
N, 9.63.
Finally, 4-bromopyridine hydrochloride (1.88 g, 9.67 mmol),
CuI (0.092 g, 0.48 mmol), and (PPh3)4Pd (0.17 g, 0.15 mmol)
were added to a degassed solution of 4-ethynyl-2,6-dimethyl-
aniline (0.70 g, 4.82 mmol) in Et2NH (50 mL) under argon.
The mixture was heated at reflux for 9 h and Et2NH was
removed in vacuo. The residue was taken up in CH2Cl2,
washed with saturated aqueous NaHCO3 and brine, and dried
over MgSO4. The crude product was purified with flash column
chromatography (EtOAc/CH2Cl2 1:2) to give 2,6-dimethyl-4-
(4-pyridylethynyl)aniline (9) as pale yellow solid (0.60 g,
- 2(OC(C4H9)2)2]+. Anal. Calcd for C78H114N10O12Os2: C, 53.10;
H, 6.51 N, 7.94. Found: C, 53.15; H, 6.57; N, 7.98.
1b: 74% yield; mp >200 °C (dec). IR (KBr) 3305, 1695, 829
1
cm-1; H NMR (500 MHz, CDCl3) δ 9.24 (s, NH, 4H), 8.54 (s,
8H), 8.04 (s, 4H), 4.06 (s, 6H), 2.26 (s, 24H), 2.03-2.01 (m,
8H), 1.83-1.79 (m, 8H), 1.50-1.38 (m, 32H), 0.96 (t, J ) 6.6
Hz, 24H); 13C NMR (126 MHz, CDCl3) δ 169.5, 160.7, 150.1,
149.0, 145.2, 130.9, 112.5, 93.8, 56.7, 34.2, 27.0, 24.1, 16.3, 14.6;
FAB-MS m/z ) 1540 [M - (OC(C4H9)2)2] +, 1256 [M -
2(C4H9)2)2]+. Anal. Calcd for C80H118N10O14Os2: C, 52.67; H,
6.52 N, 7.68. Found: C, 52.73; H, 6.50; N, 7.65.
1c: 61% yield; mp >200 °C (dec). IR (KBr) 3232, 1695, 829
1
cm-1; H NMR (250 MHz, CDCl3) δ 9.25 (s, 4H), 9.05 (s, NH,
4H), 8.57 (s, 8H), 2.28 (s, 24H), 2.03-2.01 (m, 8H), 1.83-1.79
(m, 8H), 1.50-1.38 (m, 32H), 0.96 (t, J ) 6.4 Hz, 24H); 13C
NMR (126 MHz, CDCl3) δ 159.2, 157.2, 151.7, 149.1, 144.7,
131.4, 119.7, 93.9, 34.2, 27.0, 24.1, 16.3, 14.6; FAB-MS m/z )
1570 [M - (OC(C4H9)2)2]+, 1286 [M - 2(OC(C4H9)2)2]+. Anal.
56%): mp 121-122 °C; IR (KBr) 3354, 3225, 2202, 1626 cm-1
;
1H NMR (250 MHz, CDCl3) δ 8.55 (dd, J 1 ) 6.1 Hz, J 1 ) 1.5
Hz, 2H), 7.32 (dd, J 1 ) 6.1 Hz, J 1 ) 1.5 Hz, 2H), 7.17 (s, 2H),
3.83 (br s, NH2, 2H), 2.18 (s, 6H); 13C NMR (63 MHz, CDCl3)
δ 149.9, 144.8, 132.5, 121.8, 110.6, 96.4, 85.2, 17.8. Anal. Calcd
for C15H14N2: C, 81.05; H, 6.35; N, 12.60. Found: C, 81.09; H,
6.48; N, 12.53.
Calcd for
C78H112N12O16Os2: C, 50.53; H, 6.09; N, 9.06.
Found: C, 50.54; H, 6.05; N, 9.13.
2: 67% yield; mp >200 °C (dec). IR (KBr) 3312, 2212, 1695,
830 cm-1; 1H NMR (250 MHz, CDCl3) δ 9.30 (s, NH, 2H), 8.97
(s, NH, 2H), 8.75 (d, J ) 5.3 Hz, 4H), 8.55-8.58 (m, 8H), 8.24
(t, J ) 7.7 Hz, 2H), 7.45 (d, J ) 6.4 Hz, 4H), 7.32 (s, 8H), 2.30
(s, 24H), 1.96-2.01 (m, 8H), 1.78-1.82 (m, 8H), 1.28-1.42(m,
96H), 0.86-0.95(m, 24H); 13C NMR (126 MHz, CDCl3) δ 161.0,
160.6, 149.4, 148.8, 148.0, 145.5, 140.3, 140.0, 135.8, 135.0,
132.3, 130.9, 126.7, 126.4, 120.6, 97.0, 93.0, 85.8, 34.4, 32.1,
31.1, 30.0, 29.6, 24.7, 22.9, 18.8, 16.4, 14.3; FAB-MS m/z )
1903 [M - (OC(C8H17)2)2]+, 1395 [M - 2(OC(C8H17)2)2]+. Anal.
Calcd for C126H186N10O12Os2: C, 62.71; H, 7.76; N, 5.80.
Found: C, 62.72; H, 7.71; N, 5.86.
3: 89% yield; mp >200 °C (dec). IR (KBr) 3315, 2211, 1689,
834 cm-1; 1H NMR (250 MHz, CDCl3) δ 9.08 (s, NH, 4H), 8.71
(s, 8H), 8.57 (d, J ) 7.7 Hz, 4H), 8.22 (t, J ) 7.5 Hz, 2H), 7.46
(s, 8H), 7.37 (s, 8H), 2.33 (s, 24H), 2.02-2.20 (m 8H), 1.74-
1.82 (m, 8H), 1.38-1.43 (m, 32H), 0.95 (t, J ) 7.5 Hz, 24H);
13C NMR (126 MHz, CDCl3) δ 161.3, 149.3, 148.7, 140.1, 135.9,
135.2, 132.3, 126.9, 126.2, 120.6, 97.2, 93.9, 85.8, 34.2, 27.0,
24.1, 18.8, 14.6; FAB-MS m/z ) 1594 [M - 2(OC(C4H9)2)2]+.
Anal. Calcd for C110H130N10O12Os2: C, 61.03; H, 6.05; N, 6.47.
Found: C, 61.06; H, 6.01; N, 6.51.
N-(3,5-d im eth ylp yr id in -4-yl)-N′-(4-(p yr id in -4-yl-eth yl-
n yl)-2,6-d im eth ylp h en yl)p yr id in e-2,6-d ica r boxa m id e (5).
To a solution of pyridine-2,6-dicarbonyl dichloride (7a ) (0.33
g, 1.62 mmol) in CH2Cl2 (25 mL) at 0 °C were added 4-amino-
3,5-lutidine (0.20 g, 1.62 mmol), 2,6-dimethyl-4-(pyridin-4-
ylethynyl)aniline (9) (0.36 g, 1.62 mmol), DMAP (0.1 g), and
N,N-diisopropylethylamine (1 mL). The reaction mixture was
heated at reflux for 2 h, diluted with CH2Cl2, washed with
saturated aqueous NaHCO3 and brine, and dried over MgSO4.
The crude product was purified by flash column chromatog-
raphy (EtOAc) to give 5 as a pale yellow solid (0.23 g, 30%)
(side products were 0.09 g of 4a and 0.19 g of 6): mp 238-
1
239 °C; IR (KBr) 3288, 2214, 1686 cm-1; H NMR (250 MHz,
CDCl3) δ 9.35 (s, NH, 1H), 9.30 (s, NH, 1H), 8.52-8.58 (m,
4H), 8.34 (s, 2H), 8.20 (t, J ) 7.8 Hz, 1H), 7.33-7.35 (m, 4H),
2.31 (s, 6H), 2.28 (s, 6H); 13C NMR (126 MHz, CDCl3) δ 161.9,
161.4, 149.6, 149.4, 149.1, 148.3, 142.0, 139.8, 136.0, 135.0,
131.9, 131.7, 130.4, 126.4, 126.0, 125.8, 121.3, 94.1, 86.7, 18.6,
15.7. Anal. Calcd for C29H25N5O2: C, 73.25; H, 5.30; N, 14.73.
Found: C, 73.22; H, 5.38; N, 14.67.
N ,N ,N ′,N ′-Te t r a e t h yl-p -t e r p h e n yl-4,4′′-d ica r b oxa m -
id e (G17). A mixture of N,N-diethyl-4-bromobenzamide (0.37
g, 1.44 mmol) and (PPh3)4Pd (0.05 g, 0.04 mmol) in dimethoxy-
ethane (8 mL) was stirred under argon. To this was added a
solution of 1,4-benzenediboronic acid27 (0.12 g, 0.72 mmol) in
ethanol (5 mL) and 2 M aqueous Na2CO3 (8 mL). The resulting
mixture was heated at reflux for 19 h. The reaction mixture
was cooled to room temperature, extracted with diethyl ether
(20 mL x 2), dried over anhydrous MgSO4, and concentrated.
The crude product was purified by flash column chromatog-
raphy (EtOAc) to give 0.15 g of G17 as a white solid (48%):
N ,N ′-B i s (4-(p y r i d i n -4-y l-e t h y ln y l)-2,6-d i m e t h y l-
p h en yl)p yr id in e-2,6-d ica r boxa m id e (6). To a solution of
pyridine-2,6-dicarbonyl dichloride (7a ) (0.22 g, 1.08 mmol) in
CH2Cl2 (25 mL) at 0 °C was added 2,6-dimethyl-4-(pyridin-4-
ylethynyl)aniline (9) (0.48 g, 2.16 mmol), DMAP (0.1 g), and
N,N-diisopropylethylamine (1 mL). The reaction mixture was
refluxed for 2 h and worked up under the same conditions used
for 5. The desired product 6 was obtained as a pale yellow solid
(0.38 g, 62%): mp 298-299 °C; IR (KBr) 3297, 2213, 1685
1
cm-1; H NMR (250 MHz, CDCl3) δ 9.36 (s, NH, 2H), 8.53-
8.56 (m, 6H), 8.22 (t, J ) 8.0 Hz, 1H), 7.29-7.33 (m, 8H), 2.30
(s, 12H); 13C NMR (126 MHz, CDCl3) δ 161.7, 149.7, 148.9,
139.8, 135.9, 134.8, 131.9, 131.7, 126.1, 125.7, 121.3, 94.0, 86.8,
18.7. Anal. Calcd for C37H29N5O2: C, 77.20; H, 5.08; N, 12.17.
Found: C, 77.28; H, 5.03; N, 12.08.
Gen er a l P r oced u r e for th e P r ep a r a tion of Hosts 1a -
c, 2, a n d 3. To a solution of ligand (0.5 mmol, 4a -c, 5, or 6)
and olefin (0.6 mmol, 5,6-dibutyl-5-decene was used for the
preparation of hosts 1a -c and 3, and 9,10-dioctyl-9-octadecene
for host 2) in CHCl3 (10 mL) was added a 0.1 M solution of
OsO4 in toluene (6 mL, 0.6 mmol) at room temperature. After
the solution was stirred for 10-30 min, the solvent was
removed. The dark-brown residual solid was repeatedly washed
with hexane and diethyl ether, and dried under vacuum to
give the corresponding host (1a -c, 2, or 3).
mp 201-202 °C; IR (KBr) 2974, 1620, 1289, 1098 cm-1 1H
;
NMR (250 MHz, CDCl3) δ 7.69 (s, 4H), 7.67 (d, J ) 8.5 Hz,
4H), 7.47(d, J ) 8.4 Hz, 4H), 3.56 (br s, 4H), 3.35 (br s, 4H),
1.22 (br s, 12H); 13C NMR (126 MHz, CDCl3) δ 171.1, 141.4,
139.7, 136.4, 127.6, 127.0, 43.4, 39.4, 14.4, 13.0. Anal. Calcd
for C28H32N2 O2: C, 78.47; H, 7.53; N, 6.54. Found: C, 78.55;
H, 7.50; N, 6.47.
p-(4-(p-Dieth ylca r ba m oylp h en yl)-1,3-bu ta d iyn yl)-N,N-
d ieth ylben za m id e (G18).20 To a degassed solution of N,N-
diethyl-4-bromobenzamide (2.55 g, 9.92 mmol) were added
2-methyl-3-butyn-2-ol (2.9 mL, 30 mmol), CuI (0.19 g, 1.0
mmol), and (PPh3)4Pd (0.32 g, 0.28 mmol) in Et2NH (50 mL)
under argon. The solution was heated at reflux for 11 h, cooled
to room temperature, and concentrated by rotary evaporation.
The residue was dissolved in EtOAc (50 mL), filtered, and
purified by flash column chromatography (EtOAc/hexanes 1:1)
to give p-(3-hydroxy-3-methyl-1-butynyl)-N,N-diethylbenza-
mide as a pale yellow oil (1.64 g, 64%) that was slightly
contaminated with some impurity.
1a : 67% yield; mp >200 °C (dec); IR (KBr) 3307, 1691, 829
1
cm-1; H NMR (250 MHz, CDCl3) δ 9.19 (s, NH, 4H), 8.59 (d,
J ) 7.8 Hz, 4H), 8.55 (s, 8H), 8.28 (t, J ) 7.8 Hz, 2H), 2.28 (s,
24H), 2.08-1.98 (m, 8H), 1.87-1.75 (m, 8H), 1.52-1.29 (m,
32H), 0.96 (t, J ) 6.6 Hz, 24H); 13C NMR (63 MHz, CDCl3) δ
160.8, 149.5, 148.6, 145.7, 131.5, 127.3, 94.4, 34.7, 27.5, 24.6,
16.9, 15.1; FAB-MS m/z ) 1480 [M - (OC(C4H9)2)2]+, 1194 [M
(27) Nielsen. D. R.; McEwen. W. E. J . Am. Soc. Chem. 1957, 79,
3081-3084.

9466 J . Org. Chem., Vol. 64, No. 26, 1999
J eong et al.
Without further purification, a suspension of p-(3-hydroxy-
3-methyl-1-butynyl)-N,N-diethylbenzamide and KOH (0.39 g,
7.0 mmol) in toluene (15 mL) was heated at reflux for 1 h.
The mixture was filtered and concentrated to afford p-
acetylenyl-N,N-diethylbenzamide (0.65 g, 51%) as pale brown
oil: 1H NMR (250 MHz, CDCl3) δ 7.52 (d, J ) 8.4 Hz, 2H),
7.33 (d, J ) 8.4 Hz, 2H) 3.53 (br s, 2H), 3.24 (br s, 2H), 3.13
(s, 1H.), 1.26 (br s, 3H), 1.13 (br s, 3H).
against the molar equivalent of the guest. All of the titration
curves were well fitted to the expression of a 1:1 binding
isotherm shown below.
Ka
H + G y\z HG
∆δ
max[Ka + [H]t + [G]t] -
2[H]
-1
∆δ )
Tetramethylethylenediamine (0.28 mL, 1.9 mmol) was
added to a suspension of CuCl (0.056 g, 0.57 mmol) in acetone
(10 mL) under argon and stirred for 30 min at room temper-
ature, and then the resulting mixture was slowly added to an
acetone (20 mL) solution of p-ethynyl-N,N-benzamide (0.5 g,
2.5 mmol) at 0 °C (ice-water bath). The mixture was stirred
for 20 h under oxygen and concentrated. The residue was
redissolved in EtOAc (20 mL) and washed sequentially with
1 N HCl (20 mL), water (20 mL × 2), and brine. The crude
product was purified by flash column chromatography (EtOAc/
hexanes 1:1) to afford the desired product G18 as a pale yellow
solid (0.26 g, 53%): mp 123-124 °C; IR (KBr) 2973, 1623, 1287,
-1
(K
+ [H]t + [G]t)2 - 4[H]t[G]t
x
a
2
ø2 )
(∆δcalcd - ∆δobsd
)
∑
Here, [H]t and [G]t are the total concentrations of host and
guest, and Ka is the association constant. The ∆δ is the
chemical shift change at the each titration point, and the ∆δmax
-
(calcd) and ∆δmax(obsd) are the calculated and observed
maximum chemical shift change when complexation is com-
pleted. Minimizing the sum of the squared deviations ø2 affords
the association constant (Ka), along with ∆δmax(calcd).
1
1092 cm-1; H NMR (250 MHz, CDCl3) δ 7.56 (d, J ) 8.3 Hz,
Stoich iom etr y by J ob p lots. Stock solutions of host (5.0
mM) and guest (5.0 mM) in CDCl3 (4 mL) were prepared in
separate volumetric flasks. Ten 5 mm o.d. NMR tubes were
separately filled with 500 µL total solution of the host and
guest in the following ratios (µL, host/guest): 500:0, 450:50,
400:100, 350:150, 300:200, 250:250, 200:300, 150:350, 100:400,
4H), 7.35 (d, J ) 8.3 Hz, 2H) 3.53 (br s, 4H), 3.24 (br s, 4H),
1.25 (br s, 6H), 1.12 (br s, 6H); 13C NMR (126 MHz, CDCl3) δ
170.3, 138.0, 132.7, 126.6, 122.6, 81.4, 74.9, 43.3, 39.4, 14.3,
12.9. Anal. Calcd for C26H28N2 O2: C, 77.97; H, 7.05; N, 6.99.
Found: C, 77.96; H, 7.01; N, 6.95.
1H NMR Titr a tion s. Chloroform was stored over 4 Å
molecular sieves, and filtered through basic alumina prior to
use. A 1.0-5.0 mM solution of the host and 10-50 mM solution
of guest in CDCl3 (1.5-2 mL) were separately prepared where
the concentrations were decided on the basis of the magnitude
of the association constant approximately estimated by a rough
pretitration. A 500 µL portion of the host solution was
transferred to a NMR tube, and an initial NMR spectrum was
taken to determine the initial chemical shift (δfree) of free host.
Aliquots of the guest solution (10 µL initially, then 20-30 µL,
and finally 50-100 µL) were added to the host solution. The
spectrum was recorded after each addition, and overall 15-
20 data points were obtained. The association constants (Ka)
were determined by using the nonlinear least-squares fitting
of the titration curves plotting ∆δ of the host NH signals
1
50:450. The H NMR spectra were obtained for each tube and
the host NH signal was used to calculate the complex
concentration, [HG] ) [H]t(δobsd - δfree)/(δcom - δfree). This value
was plotted again the mole fraction of the guest, and the
resulting curve always showed a maximum at 0.5 mol fraction,
indicative of host/guest 1:1 binding.
Ack n ow led gm en t. This work was financially sup-
ported in part by the Korea Science and Engineering
Foundation (96-0501-04-01-03) and The Basic Science
Research Institute Program, Ministry of Education
(BSRI-98-3422).
J O9910841