Molecular engineering. 8.1 Kinetic and conformational studies of resorcin[4]arene-based C4 tetraoxatetrathiahemicarceplexes: Carceroisomerism and twistomerism

Article abstract of DOI:10.1021/jo015594i

New C_4v tetraoxatetrathiahemicarcerands and their six hemicarceplexes containing DMF, DMA, DMSO, or NMP were synthesized and characterized. Their conformations, kinetic properties, carceroisomerism, and twistomerism were studied by VT, 2D COSY, NOESY, and ROESY ¹H NMR experiments. The decomplexation rates of DMF or DMA were very slow with high activation energy barriers (73 and 104 kJ mol^-1, respectively) and the complexed guests feel more constriction than their free liquid state. The largest isomerization energy barrier of carceroisomers was 15.4 kcal mol^-1, and the isomerization energy barriers of twistomers are significantly larger than those of carceroisomers.

Full text of DOI:10.1021/jo015594i

5736
J . Org. Chem. 2001, 66, 5736-5743
Molecu la r En gin eer in g. 8.1 Kin etic a n d Con for m a tion a l Stu d ies of
Resor cin [4]a r en e-Ba sed C4 Tetr a oxa tetr a th ia h em ica r cep lexes:
Ca r cer oisom er ism a n d Tw istom er ism
Kyungsoo Paek,*,† Hyejae Ihm,† Sunggoo Yun,‡ Hee Cheon Lee,‡ and Kyoung Tai No†
Molecular Engineering Research Laboratory and Department of Chemistry, Soongsil University,
Seoul 156-743, Korea, and Department of Chemistry, Pohang University of Science & Technology,
Pohang 790-784, Korea
kpaek@saint.ssu.ac.kr
Received February 27, 2001
New C4v tetraoxatetrathiahemicarcerands and their six hemicarceplexes containing DMF, DMA,
DMSO, or NMP were synthesized and characterized. Their conformations, kinetic properties,
carceroisomerism, and twistomerism were studied by VT, 2D COSY, NOESY, and ROESY 1H NMR
experiments. The decomplexation rates of DMF or DMA were very slow with high activation energy
barriers (73 and 104 kJ mol-1, respectively) and the complexed guests feel more constriction than
their free liquid state. The largest isomerization energy barrier of carceroisomers was 15.4 kcal
mol-1, and the isomerization energy barriers of twistomers are significantly larger than those of
carceroisomers.
In tr od u ction
reoisomers, so-called twistomers,7d stabilized by the host’s
constrictive binding property. In C4v carcerand composed
of two different hemispheres, the different orientations
of unsymmetrical guests through the long (C4) axis of
these host could also lead different stereoisomers, which
Reinhoudt et al. called carceroisomer.7a
The potential applicabilities of container molecules2 are
being expanded from a molecular recognition system3 or
a supramolecular molecular storage4 to a controlled
molecular releasing system5 or molecular reactor.6 Also,
new types of isomerisms in a confined carceplex or a
hemicarceplex are emerging as a stimulating research
field due to their potential as a molecular spin or
molecular switch for data storage device and molecular
electronics.7 D4h and C4v container hosts composed of two
resorcin[4]arene moieties could lead pseudohelical ste-
Usually carceroisomer interconversion, which appears
to be faster than twistomer interconversion,7d could be
manipulated by the degree of confinement of interior and
the secondary interactions between host and guest such
as hydrogen bonding, dipole, or charge interactions,
whereas twistomer interconversion could be manipulated
by constrictive binding property of host. The constrictive
binding property mainly depends on the nature of
bridges, such as the number and length, connecting two
hemispheres as well as the nature of hemisphere.2 But
the effects of molecular symmetry or heavy atoms on
bridge have not been scrutinized.8 Here we report the
kinetic and conformational properties of new resorcin[4]-
arene-based C4 tetraoxatetrathiahemicarcerands, which
have sulfur-incorporated unsymmetric bridges between
two hemispheres. High-temperature stable carcero-
isomers and the unprecedented half-twistomers were
characterized.
* To whom correspondence should be addressed. Tel: (+) 82-2-820-
0435. Fax: (+) 82-2-822-2362.
† Soongsil University.
‡ Pohang University of Science and Technology.
(1) Paek, K.; Yoon, Y.; Suh, Y. J . Chem. Soc., Perkin Trans. 2 2001,
(6), 916.
(2) (a) Cram, D. J .; Cram, J . M. Container Molecules and Their
Guests, Monographs in Supramolecular Chemistry; Stoddart, J . F., Ed.;
The Royal Society of Chemistry Press: Cambridge, 1994; Vol. 4. (b)
Maverick, E. F.; Cram, D. J . In Comprehensive Supramolecular
Chemistry; Atwood, H. L., Davies, J . E. D., MacNicol, D. D., Voegtle,
F., Eds.; Pergamon: Oxford, U.K., 1996; Vol. 2, Chapter 12.
(3) (a) J udice, J . K.; Cram, D. J . J . Am. Chem. Soc. 1991, 113, 2790.
(b) Schally, C. A.; Martin, T.; Obst, U.; Rebek, J ., J r. J . Am. Chem.
Soc. 1999, 121, 2133. (c) Heinz, T.; Rudkevich, D. M.; Rebek, J ., J r.
Angew. Chem., Int. Ed. Engl. 1999, 38, 1136. (d) Rivera, J . M.; Craig,
S. L.; Martin, T.; Rebek, J ., J r. Angew. Chem., Int. Ed. Engl. 2000, 39,
2130.
(4) (a) Murayama, K.; Aoki, K. Chem. Commun. 1998, 607. (b)
Chopra, N.; Sherman, J . C. Angew. Chem., Int. Ed. 1999, 38, 1955. (c)
Chopra, N.; Naumann, C.; Sherman, J . C. Angew. Chem., Int. Ed. 2000,
39, 194. (d) Parac, T. N.; Scherer, M.; Raymand, K. N. Angew. Chem.,
Int. Ed. 2000, 39, 1239. (e) Yu, S.-Y.; Kusukawa, T.; Biradha, K.; Fujita,
M. J . Am. Chem. Soc. 2000, 122, 2665. (f) Yoshizawa, M.; Kusukawa,
T.; Fujita, M.; Yamaguchi, K. J . Am. Chem. Soc. 2000, 122, 6311.
(5) (a) Cram, D. J .; Blanda. M. T.; Paek, K.; Knobler, C. B. J . Am.
Chem. Soc. 1992, 114, 7765. (b) Piatnitski, E. L.; Deshayes, K. D.
Angew. Chem., Int. Ed. 1998, 37, 970. (c) Vysotsky, M. O.; Thondorf,
I.; Boehmer, V. Angew. Chem., Int. Ed. 2000, 39, 1264.
(6) (a) Cram, D. J .; Tanner, M. E.; Thomas, R. Angew. Chem., Int.
Ed. Engl. 1991, 30, 1024. (b) Robbins, T. A.; Knobler, C. B.; Bellew, D.
R.; Cram, D. J . J . Am. Chem. Soc. 1994, 116, 111. (c) Kang, J .;
Santamaria, J .; Hilmerssoon, G.; Rebek, J ., J r. J . Am. Chem. Soc. 1998,
120, 7389. (d) Warmuth, R.; Marvel, M. A. Angew. Chem., Int. Ed. 2000,
39, 1117. (e) Warmuth, R., J . Inclusion Phenom. 2000, 37, 1. (f)
Warmuth, R. Eur. J . Org. Chem. 2001, 423.
Resu lts a n d Discu ssion
Syn th esis of Hem ica r cer a n d a n d Hem ica r cep lex-
es. Tetrathiol 2 was obtained from tetrabromide 1 (92%),9
and tetrols 310 and 411 were obtained from the corre-
(7) (a) Timmerman, P.; Verboom, W.; van Veggel, F. C. J . M.; van
Duynhoven, J . P. M.; Reinhoudt, D. N. Angew. Chem., Int. Ed. Engl.
1994, 33, 2345. (b) Huisman, B.-H.; Rudkevich, D. M.; van Veggel, F.
C. J . M.; Reinhoudt, D. N. J . Am. Chem. Soc. 1996, 118, 3523. (c) van
Wageningen, A. M. A.; Timmermann, P.; van Duynhoven, J . P. M.;
Verboom, W.; van Veggel, F. C. J . M.; Reinhoudt, D. N. Chem. Eur. J .
1997, 3, 639. (d) Chapman, R. G.; Sherman, J . C. J . Am. Chem. Soc.
1999, 121, 1962.
(8) Paek, K.; Ihm, H.; Yun, S.; Lee, H. C. Tetrahedron Lett. 1999,
40, 8905.
10.1021/jo015594i CCC: $20.00 © 2001 American Chemical Society
Published on Web 07/28/2001

Molecular Engineering
J . Org. Chem., Vol. 66, No. 17, 2001 5737
Ch a r t 1
Ch a r t 2
Sch em e 1
(DMA), dimethyl sulfoxide (DMSO), N-methyl-2-pyrro-
lidinone (NMP), pyrazine, and 1,4-dioxane were used as
solvents. Although large templating effects of pyrazine
and 1,4-dioxane for resorcin[4]arene-based carcerands
were reported,12 host 9a or 9b complexed with pyrazine
or 1,4-dioxane was not detected. It is presumable that
due to the large sulfur or iodide atoms a potential
template should be oriented through the long C4 axis. In
the case of pyrazine or 1,4-dioxane, its lone pair should
be directed toward π-cloud of hemispheres, which sub-
sequently diminishes their templating ability, whereas
when acetonitrile was employed as a solvent, the free
hemicarcerand 9b was isolated in 20% yield. The FAB
mass spectra of 9b, 9a @G, or 9b@G showed their
distinctive molecular ion peaks.
The complexations of free host 9b were tried by heating
(80-170 °C) 9b in methyl ethyl ketone, DMF, DMA,
pyrazine, 1,4-dioxane, N,N-dimethylpropionamide, and
NMP, but no complexation was observed. This might be
due to the larger energy barrier of entrance into the
cavity than that actually anticipated by CPK model.13
sponding tetrabromides (Chart 1). Tetrols 3 and 4 were
treated with TsO(CH2)2Cl/K2CO3/DMF at 55 °C to give
the tetrachlorides 5 (69%) and 6 (65%), respectively.
Tetrachlorides 5 and 6 were refluxed with NaI in methyl
ethyl ketone to give the tetraiodides 7 (87%) and 8 (90%),
respectively.
Both tetraiodides 7 and 8 were used to synthesize
the hemicarcerands because it has been shown that
PhCH2CH2-appended hemicarcerands tend to produce
better crystals for structure determination, whereas those
with CH3(CH2)4-appended groups tend to be soluble in a
greater range of solvents.11
1
Solu tion H NMR Sp ectr a of Hem ica r cep lexes. In
case of 9a @DMA (see Chart 2), its COSY spectrum
showed the cross-peaks between CH2 protons of the R
((CH2)2Ph) group and methine protons (Hg) of the A
moiety and CH2 protons of the R′ ((CH2)2CH3) group and
methine protons (Hh) of the B moiety, respectively.
Therefore, the assignments of Hg and Hh protons were
determined. Its 2D ROESY spectrum also shows the
same cross-peaks (Figure 1). In addition, CH2 protons of
the R and R′ groups show the cross-peaks with the aryl
protons (Hb) of the A moiety and the aryl protons (Ha) of
the B moiety, respectively. This spectrum also shows
connectivities between Hi and Hj protons, Hc and Hd
protons, and He and Hf protons. The assignment of Hc
and He protons was determined from the cross-peaks
between He and Hk protons.
The chemical shifts of hydrogens attached to the
hemisphere parts of hosts changed upon complexation
(Table 1). As expected, the complexed guests generally
affect the ∆δ values of the Hd and Hf protons more than
those of the other protons since these are oriented inward
of the cavity. Especially Hf protons, which are inner
OCH2O protons of the B moiety, show the largest
downfield shifts ranging from 0.08 to 0.25 ppm upon
complexation. The ∆δ values for 9b@DMF range only
Under high dilution conditions, the shell-closing reac-
tion between tetrathiol 2 and tetraiodide 7 or 8 with
Cs2CO3 in an appropriate solvent (G) at 50 °C produced
hemicarceplexes 9a@G or 9b@G in 8-25% yields (Scheme
1
1). All hemicarceplexes were characterized by H NMR,
FAB+ mass, and IR spectra and elemental analyses, and
the spacial arrangements between host and guest were
studied by 2D COSY, NOESY, and ROESY measure-
ments (500 MHz, CD2Cl2, 25 °C).
CPK molecular model studies suggest that hosts 9a
and 9b are hemicarcerands having the cavity large
enough to include 1-methyl-2-piperidone or 1,4-dimethoxy-
benzene. To obtain the various hemicarceplexes, N,N-
dimethylformamide (DMF), N,N-dimethylacetamide
(9) (a) Lee, J .; Choi, K.; Paek, K. Tetrahedron Lett. 1997, 38, 8203.
(b) Ihm, C.; Kim, M.; Ihm, H.; Paek, K. J . Chem. Soc., Perkin Trans.
2 1999, 1569.
(10) Sherman, J . C.; Knobler, C. B.; Cram, D. J . J . Am. Chem. Soc.
1991, 113, 2194.
(11) Cram, D. J .; J aeger, R.; Deshayes, K. J . Am. Chem. Soc. 1993,
115, 10111.
(12) (a) Chapman, R. G.; Chopra, N.; Cochien, E. D.; Sherman, J .
C. J . Am. Chem. Soc. 1994, 116, 369. (b) Nakamura, K.; Sheu, C.;
Keating, A. E.; Houk, K. N. J . Am. Chem. Soc. 1997, 119, 4321. (c)
Chapman, R. G.; Sherman, J . J . Org. Chem. 1998, 63, 4103.
(13) Houk, K. N.; Nakamura, K.; Sheu, C.; Keating, A. E. Science
1996, 273, 627.

5738 J . Org. Chem., Vol. 66, No. 17, 2001
Paek et al.
Ta ble 1. Ch em ica l Sh ifts (in p p m ) of Host 9b’s Gu est-Sen sitive P r oton s a n d th e Differ en ces betw een th e Ch em ica l
Sh ifts of F r ee a n d Com p lexed Hosts (∆δ, in P a r en th esis)a in Th eir 400 MHz 1H NMR Sp ectr a in CDCl3 a t 25 °C
chemical shifts
guest
Ha
Hb
Hc
Hd
He
Hf
Hg
Hh
none
DMF
7.00
7.05
6.75
6.76
5.89
5.79
4.20
4.19
5.93
5.89
3.97
4.14
4.69
4.66
4.74
4.76
(-0.05)
(-0.01)
(0.10)
5.82
(0.07)
5.82
(0.07)
5.85
(0.01)
4.30
(-0.10)
4.24
(-0.04)
4.30b
(0.04)
5.87
(0.06)
5.87
(0.06)
5.87
(-0.08)
(0.03)
4.68
(0.01)
4.69
(0.00)
4.67
(-0.02)
DMA
DMSO
NMP
7.05
6.77
4.22
4.75
(-0.05)
7.03
(-0.03)
7.06
(-0.02)
6.75
(0.00)
6.77
(-0.25)
4.21
(-0.01)
4.76
(-0.02)
4.75
(-0.24)
4.15b
(-0.06)
(-0.02)
(0.04)
∼4.40
(0.06)
∼4.25
(0.02)
(-0.01)
a
b
∆δ ) δfree - δcomplexed
.
Peak is overlapped with Hi proton peak.
Ta ble 2. .1H NMR Sp ectr a l Ch em ica l Sh ifts of F r ee a n d
Com p lexed Gu ests in Hosts 9a a n d 9b in Th eir 400 MHz
1H NMR Sp ectr a in CDCl3 a t 25 °C
host
guest
DMF
H
free δ
compl δ
∆δ
9a
a
b
c
a
b
c
a
b
c
a
b
c
a
a
b
c
d
7.99
2.94
2.86
2.09
3.02
2.94
7.99
2.94
2.86
2.09
3.02
2.94
2.61
2.85
3.40
2.05
2.35
6.24
1.53
-0.08
-1.33
-0.31
1.69
1.75
1.41
2.94
3.42
3.33
1.25
1.76
1.19
2.94
3.43
3.34
1.29
2.95
3.50
1.55
2.89
2.93
9a
9b
9b
DMA
DMF
DMA
6.23
1.75
-0.08
-1.34
-0.32
1.65
-0.34
-0.65
1.85
9b
9b
DMSO
NMPa
-0.84
-0.58
F igu r e 1. Part of the 2D ROESY spectrum (500 MHz) of
9a @DMA at 25 °C in CD2Cl2.
a
Major confomer.
Ta ble 3. Ha lf-Lives a n d Activa tion F r ee En er gies for
Decom p lexa tion of 9B@DMF a n d 9B@DMA in C6D5NO2
from 0.01 to 0.10 ppm. It is likely that complexed DMF
is more conformationally mobile in its cavity than com-
plexed DMA, DMSO, and NMP due to its relatively small
size. The chemical shift change of Hi cannot be identified
due to its multiplicity as well as overlapping. Also,
chemical shifts of feet hydrogens (2-phenylethyl or pentyl)
do not change upon complexation.
t1/2 (h)
150
°C
160
°C
170
°C
180
°C
200 220
°C
∆Gq
complex
°C (kJ mol-1
)
9b@DMF 116.0 57.8
9b@DMA
28.9
16.5
104 ( 4
73 ( 9
231.0 116.0 57.8 28.9
The guest signals were much more sensitive than the
host signals to incarceration. Table 2 records the chemical
shifts in the 400 MHz 1H NMR spectra of complexed and
free guests as well as their differences (∆δ) in host 9a
and 9b in CDCl3 at 25 °C.
Contrary to this, Ha and Hb of DMA in 9b showed the
similar chemical shift changes (3.43, 3.34 ppm, respec-
tively) owing to their similar steric circumstances.
Decom p lexa tion Kin etics of th e Hem ica r cep lex-
es. The first-order rate constants for decomplexation of
hemicarceplexes 9b@DMF and 9b@DMA were deter-
mined in C6D5NO2 at various temperatures in the range
of 150-220 °C by watching the decreasing signals of the
complexed guest protons and/or the appearance of the
free guest proton’s signals.5 Interestingly, complexed
DMA gave doublets (or two singlets) for each hydrogen,
which is totally unexpected because DMA can freely
rotate through the long C4 axis as well as the short
equatorial axis at least at 220 °C.
1
Upon complexation, the H NMR spectra show large
upfield shifts of the guests ranging from 1.19 to 3.50 ppm
due to the shielding effect of the two hemispheres of host.
As the size of guests increases, the chemical shifts of
complexed guests become more upfield shifted because
the larger guest approaches more closely to the shielding
zone of hemispheres. The similar chemical shifts of DMF
or DMA in 9a and 9b within the experimental error
manifests the magnetic independence between guest and
feet (R). Ha of NMP in 9b showed the largest upfield shift
(3.50 ppm), but Hc and Hd of NMP in 9b showed rather
small chemical shift changes (2.89, 2.93 ppm, respec-
tively), which implies that due to the steric effect Hc and
Hd cannot get in close to hemisphere’s shielding zone.
The decomplexations exhibited good first-order behav-
ior. Table 3 records the half-lives for decomplexations at
various temperatures and the derived free energies of
activation for decomplexation. The decomplexation half-

Molecular Engineering
J . Org. Chem., Vol. 66, No. 17, 2001 5739
life for 9b@DMA is about seven times longer than that
for 9b@DMF at the same temperature. This is possibly
due to the fact that the longer DMA guest should pass
from occupying the host’s axial bowls to being aligned
with the equatorially disposed portals. But free energy
of activation for decomplexation of 9b@DMF is 31 kJ
mol-1 higher than that for 9b@DMA. Presumably, the
steric compression in 9b@DMA is greater than that in
9b@DMF , and therefore, 9b@DMA reaches more easily
to transition states for decomplexation.
En er gy Ba r r ier s for F r ee Rota tion a r ou n d th e
C(dO)-N Am id e Bon d s of Com p lexed DMA a n d
DMF . The rotational barrier to amide bonds has been
extensively studied in solution and in the gas phase,
experimentally and theoretically.14 The energy barriers
decrease in the order of polar solvents > nonpolar
solvents > gas phase. Generally, the energy barrier for
DMF is larger than for DMA. This difference is mainly
caused by destabilization of the ground state in DMA due
to steric repulsion rather than by a difference in the
energy of the transition state.
F igu r e 2. Partial 1H NMR spectra (500 MHz) of (a) 9a @DMA
and (b) 9b@NMP (in C6D5NO2 at 63 and 141 °C) in CD2Cl2 at
various temperatures.
Dynamic 1H NMR experiments were performed to
compare the energy barrier for free rotation around the
amide bond of complexed and free amide guests in
DMSO-d6 or C6D5NO2 as a solvent. The coalescence tem-
perature for two NCH3 groups of 9a @DMA in C6D5NO2
was 151 °C with ∆Gq424K ) 18.6 kcal mol-1 for complexed
amide rotation around its C(dO)-N bond. In DMSO-d6,
the same coalescence temperature was observed. For
DMA simply dissolved in C6D5NO2, the reported coales-
cence temperature was 63 °C and ∆Gq
) 18.0 kcal
336K
mol-1 10
.
When 9b@DMF was submitted to the same experi-
ment in C6D5NO2, the coalescence temperature was
assumed to be over 161 °C. The coalescence of DMF
dissolved directly in C6D5NO2 was reported to be 120 °C
with ∆Gq
) 20.2 kcal mol-1 10
. In aggrement with
393K
known results, the barrier of complexed DMF was
observed to be higher than that for complexed DMA.
Incarceration of DMA or DMF raises the rotational
barrier compared to its simple dissolution. This behavior
is probably a result of steric constriction on guest by
incarceration. Also the energy barrier of complexed DMA
was not affected by the polarity change of solvent within
experimental error because DMA is enclosed by the shell
of the host.
Or ien ta tion s of Gu ests In sid e Hem ica r cer a n d s:
Ca r cer oisom er ism . Interestingly, the acetyl peaks
(MeCdO) of DMA and the aldehydic peaks (HCdO) of
DMF did not change their doublet pattern in 1H NMR
spectra even though the temperature was increased to
187 °C. Essentially, the peaks should coalesce into
singlets on the increase of the temperature allowing rapid
isomerization if each of doublet were caused by the
different orientation (carceroisomers) of the guests in the
shell.7a
F igu r e 3. Part of the 2D NOESY spectrum (500 MHz) at -90
°C in CD2Cl2 of 9a @DMA.
major) for the N-methyl group cis to the carbonyl of DMA
and at δ ) -1.26 (doublet, major) and -1.83 (singlet,
minor) for the acetyl group of DMA, respectively. The
integration ratio of major to minor signal is 3:1.
2D NOESY spectrum (Figure 3) of 9a @DMA showed
that the major doublet signal at δ ) -1.26 corresponds
to the isomer in which the acetyl group is positioned close
to the B moiety (Chart 2) from its cross-peaks with the
resonances of the aryl protons (Ha), the methine CH
protons (Hh) and the R′ groups (propyl groups) of the B
moiety, whereas the major singlet signal at δ ) -0.72
showed cross-peaks with the resonances of the aryl
protons (Hb), the methine CH protons (Hg), and the R
groups (2-phenylethyl group) of the A moiety, which
means the N-methyl group cis to the carbonyl is oriented
toward the A moiety. Accordingly, the minor signals at
δ ) -0.83 and -0.24 are from the opposite orientation
of DMA relative to the major conformer, which gave too
weak NOEs. These results support that two carcero-
isomers exist in a 3:1 ratio and the acetyl group of DMA
is mainly oriented toward the B moiety as shown in
The dynamic behavior of complexed guest was studied
1
by variable-temperature H NMR experiments, and the
orientations of the guests of major isomers were deter-
mined by 2D NOESY and ROESY measurements.
As shown in Figure 2a, at a temperature below -90
°C, 1H NMR spectra of 9a @DMA show two new reso-
nances at δ ) -0.24 (doublet, minor) and -0.72 (singlet,
(14) Wiberg, K. B.; Rablen, P. R.; Rush, D. J .; Keith, T. A. J . Am.
Chem. Soc. 1995, 117, 4261.

5740 J . Org. Chem., Vol. 66, No. 17, 2001
Paek et al.
F igu r e 5. Observed orientation of NMP in the major (left)
and minor isomer (right) of 9b@NMP (R ) (CH2)4CH3).
F igu r e 4. Observed orientation of DMA in the major isomer
(left) and in the minor isomer (right) of 9a @DMA (R )
(CH2)2Ph).
Figure 4 below -90 °C in CD2Cl2. 9b@DMA gave the
same results showing that the behavior of the guest
inside the host is not affected by feet of the host.
When the temperature of 9b@DMF is lowered to -81
°C its 1H NMR spectra show that each guest’s signal
changes into doublets for the CHO proton at δ ) 6.21
and for the N-methyl group trans to the carbonyl at δ )
-0.31 and -1.04 at 1:1 integration ratios. NOESY
experiments at a temperature below -81 °C revealed
both doublets of the N-methyl protons show cross-peaks
with the resonances of the B moiety. Therefore, it is
assumed that two doublet signals of DMF were caused
by an unusual circumstance of the host B moiety and
not by carceroisomerism of DMF even though the struc-
tural elucidation of two isomers was not confirmed due
to weak NOE connectivities.
F igu r e 6. Energy-minimized structures of hemicarceplexes
9b@DMA (left) and 9b@NMP (right).
When 9b@DMSO was subjected to the similar 1H
NMR experiment, their end-to-end rotation inside the
host was too fast to observe two carceroisomers in 1H
NMR time scale even at a temperature below -116 °C.
Interestingly, VT NMR experiment of 9b@NMP showed
the presence of unequal populations of two carcero-
isomers even at 141 °C (Figure 2b). At a temperature
below -21 °C, the spectrum of 9b@NMP showed clearly
that the N-methyl group of incarcerated NMP exists in
major (the singlet at δ ) -0.89) and minor (two unequal
singlets at δ-0.63 and -0.70) isomers. The multiplets
(actually two kinds of multiplet) at δ ) -0.86 and -1.12
is assigned to the 3-CH2 and 4-CH2 groups, respectively.
The 5-CH2 group of NMP resonates at much lower field
of δ ) 1.85, since it is far away from the aromatic cavity.
The integration ratio of major to minor signal is 2:1.
2D NOESY experiments of 9b @NMP at -21 °C
revealed that the 4-CH2 group of NMP shows strong
cross-peaks with Hf and Hk, which means these protons
are mainly oriented toward the B moiety although it is
difficult to discriminate between the major and minor
isomer (Figure 5). The major singlet signal of the N-
methyl group at δ ) -0.89 and the 3-CH2 group of NMP
at -0.86 show cross-peaks with the resonances of the
protons of the bridging unit near the A moiety (Hi) and
of the inner OCH2O protons (Hf) of the B moiety, but
these protons cannot be discriminated due to overlapped
peaks, whereas the minor doublet signal of the N-methyl
group at δ ) -0.66 shows a cross-peak with Hj, which
means that this methyl group in the minor isomer is
located in the B moiety. This suggests that N-methyl
group is mainly oriented toward the A moiety in the
major isomer (Figure 5).
Id en tifica tion of Ha lf-Tw istom er s. Figure 6 shows
the energy-minimized structures of 9b @DMA and
9b@NMP calculated with MM+ force-field using Hyper-
Chem. The results correspond closely to the structure of
1
the major isomers observed in their H NMR spectra.
As shown in Figure 2a, 1H NMR chemical shifts of
DMA in host 9a appeared as two equal singlets at room
temperature, which remained up to 187 °C. As the tem-
perature of 9a @DMA in CD2Cl2 decreased, two singlets
were broadened, and then below -90 °C, the chemical
shifts of incarcerated DMA were split into two new
resonances indicating the existence of carceroisomers.
But the interesting point is the presence of two singlets
at -0.24 and -1.26 ppm for the thiahemisphere-directing
trans N-methyl of minor carceroisomer and for the
thiahemisphere-directing acetyl group of major carcero-
isomers, respectively, which, we assumed, is due to the
stable twistomerism at thiahemisphere moiety (B). These
half-twistomers did not coalesce each other, but two
carceroisomers coalesced each other by the rapid end-to-
end rotation of DMA vertical to C4 axis to give two sets
of two singlets at -0.31 ppm for trans N-methyl and at
-1.33 ppm for acetyl at high temperature.
The simultaneous observation of twistomers and car-
ceroisomers of 9b@NMP under the same conditios was
possible even at 25 °C (Figure 2b). At a temperature
1
below -21 °C, the H NMR chemical shifts of N-methyl
group of 9b @NMP clearly showed that carceplex
9b@NMP exists in the major (the singlet at δ-0.89) and
minor (two unequal singlets at δ-0.63 and -0.70) car-
ceroisomers at 2:1. The two unequal singlets of minor
isomer implies that the stabilities of two twistomers are

Molecular Engineering
J . Org. Chem., Vol. 66, No. 17, 2001 5741
9b@DMF is 31 kJ mol-1 higher than that for 9b@DMA.
The dynamic NMR experiments of hemicarceplexes re-
vealed that the energy barriers for rotation around the
amide bonds of complexed DMA and DMF are higher
than those of free DMA and DMF.
Ta ble 4. Ra te Con sta n t (k), Coa lescen ce Tem p er a tu r e
(Tc), a n d Rota tion a l Ba r r ier (∆Gcq) for Isom eiza tion of
Tw o Ca r cer oisom er sa
host
guest
k (Hz)
Tc (°C)
∆Gcq (kcal mol-1
)
9a
9b
9b
9b
9b
DMA
DMA
DMF
DMSO
NMP
5592
6002
773
-61
-61
9.6 ( 1
9.6 ( 1
Orientations of the guests inside the hosts were studied
by 2D NOESY and ROESY NMR experiments. Two
carcerostereoisomers of 9a @DMA or 9b@DMA appeared
as 3:1 ratio at -90 °C in CD2Cl2, and they coalesced at
-61 °C, which gave the isomerization barrier of ∆Gq )
9.6 ( 1 kcal mol-1. 9b@NMP showed two carcerostereo-
isomers (2:1 ratio) at -21 °C in CD2Cl2 that are coalesced
at 50 °C to show the higher isomerization barrier (∆Gq)
15.4 ( 1 kcal mol-1). The acetyl group of DMA or 3- and
4-CH2 units of NMP in 9b are mainly directed toward
the B moiety surrounded by sulfur atoms at low tem-
peratures at which the acetyl group of major 9b@DMA
or NCH3 of minor 9b@NMP gave doublets on 1H NMR
spectra due to their half-twistomerism. These doublets
were coalesced with their counterparts to give new
doublets at high temperature, which means these half-
twistomers induced by incorporating unsymmetrical thia
bridges between two hemispheres are unexpectedly
stable even at substantially high temperature.
-39
10.5 ( 1
<-116
50
255
15.4 ( 1
a
Determined by variable-temperature 1H NMR (500 MHz,
CD2Cl2) experiments.
different each other due to the prochirality of NMP. Its
NOESY experiments in CD2Cl2 at -21 °C showed that
N-methyl group of the major isomer is directing the A
moiety (Figure 5).
A CPK molecular model shows that the cavity of the
B moiety is smaller than that of the A moiety due to the
inward-directing sulfur atoms. 1H NMR spectra in Figure
4 show that the guest’s peaks located in the B moiety
are split into the doublet, slightly downfield shifted,
whereas the peaks located in the A moiety are not split
and more upfield shifted. It is probable that the twist-
1
omer isomerization at A moiety is faster on an H NMR
time scale but that at the B moiety is slower on an 1H
NMR time scale due to the large rotational barrier of thia
bonds, which results in the unprecedented half-twistom-
erism.
Such high isomerization energy barriers for supra-
molecular carceroisomers or twistomers may present an
opportunity for the development of unprecedented mo-
lecular devices. For example, if methods could be found
to control the supramolecular isomerization, then such
materials could be used to re-align guests by acting as
switchable matrixes.
Isom er iza tion En er gy Ba r r ier s for Ca r cer oiso-
m er s. Table 4 records the isomerization energy barriers
of carceroisomers determined by variable-temperature
NMR experiments. In the case of 9a @DMA, the two
carceroisomers coalesced at -61 °C and the rotational
barrier (∆Gq212K) for isomerization was calculated to be
9.6 ( 1 kcal mol-1. For 9a and 9b, having different feet,
the activation energies for interconversion of complexed
DMA are consistent with each other.
Exp er im en ta l Section
Gen er a l P r oced u r es. All chemicals were reagent grades
and used directly unless otherwise specified. THF was stored
over calcium hydride for 1 week and was freshly distilled under
N2 from sodium benzophenone ketyl just prior to use. All
anhydrous reactions were conducted under an argon atmo-
sphere. Melting points were measured on an Electrothermal
9100 apparatus and were uncorrected. IR spectra were taken
with a Mattson 3000 FT-IR spectrometer. The 1H NMR spectra
were recorded on a Bruker Avance DPX300 (300 MHz), J EOL
lambda-400 (400 MHz), or Bruker Avance DPX500 (500 MHz)
in CDCl3 unless stated otherwise, and residual solvent protons
were used as internal standard. FAB(+) mass spectra were
run on a HR MS (VG70-VSEQ) at Korea Basic Science
Institute using m-nitrobenzyl alcohol as a matrix. Gravity
column chromatography was performed on silica gel 60 (E.
Merck, 70-230 mesh ASTM). Flash chromatography was
performed on silica gel 60 (E. Merck, 230-400 mesh ASTM).
Thin-layer chromatography was done on silica plastic sheets
(E. Merck, silica gel 60 F254, 0.2 mm). Elemental analyses
were performed at the Korea Basic Science Institute.
2,20:3,19-Dim et h en o-1H ,21H ,23H ,25H -b is[1,3]d ioxo-
cin o[5,4-i:5′,4′-i′]ben zo[1,2-d :5,4-d ′]bis[1,3]ben zod ioxocin ,
7,11,15,28-Tetr a k is(2-ch lor oeth oxy)-1,21,23,25-ter a k is(2-
p h en yleth yl)-, Ster eoisom er (5). To a solution of tetrol 3
(0.51 g, 0.50 mmol) and potassium carbonate (0.69 g, 5.0 mmol)
in DMF (30 mL) was added 2-chloroethane tosylate (0.71 g,
3.0 mmol), and the reaction mixture was stirred for 3 d at 55-
60 °C. After being cooled to room temperature, the mixture
was partitioned between CH2Cl2 (250 mL) and 2 N HCl (2 ×
100 mL). The organic phase was separated, washed with water
and brine, and subsequently dried over MgSO4. After evapora-
tion of CH2Cl2, the residue was chromatographed on a silica
gel gravity column using CH2Cl2-hexane (3:1, v/v) and then
hexanes-EtOAc (3:1, v/v). The recrystallization from CH2Cl2-
MeOH gave the product 5 (0.43 g, 69%): mp 269.7 °C; 1H NMR
(CDCl3, 400 MHz) δ 7.21-7.13 (m, ArH, 20H), 6.85 (s, ArH,
q
The ∆Gc of 9b@DMF is rather higher than that of
9b@DMA. It means DMF inside the host exists in two
types of substantially stable isomers. If not, the coales-
cence temperature of DMF should be lower than for DMA
due to its smaller size.
The coalescence temperature of 9b@DMSO is below
-116 °C, which suggests that end-to-end rotation of the
1
DMSO molecule inside the host is fast in H NMR time
scale even at a temperature below -116 °C.
Upon warming to 50 °C, the N-methyl proton peaks of
NMP were coalesced to give ∆Gc ) 15.4 ( 1 kcal mol-1
q
for the rotational barrier of interconversion of NMP
inside the cavity, which is 5.8 kcal mol-1 higher than that
for 9b@DMA primarily due to its larger size and rigidity.
When the temperature of 9b@NMP was increased
until 141 °C in C6D5NO2, the N-methyl proton peak of
NMP still remained as two singlets, which is similar to
those of 9b@DMA and 9b@DMF .
Con clu sion s
Resorcin[4]arene-based
tetraoxatetrathiahemicar-
ceplexes were synthesized by shell closure of a tetrathio-
cavitand and a tetraiodocavitand, which possess a non-
centrosymmetric C4v cavity, and therefore, different
orientations of incarcerated unsymmetric guest could give
different stereoisomers.
The first-order rate for decomplexation of hemicar-
1
ceplexes was determined by H NMR experiments, and
the free energy of activation for decomplexation of

5742 J . Org. Chem., Vol. 66, No. 17, 2001
Paek et al.
4H), 5.85 (d, OCH2O, J ) 7.1 Hz, 4H), 4.83 (t, ArCH, 4H), 4.43
(d, OCH2O, J ) 7.1 Hz, 4H), 4.18 (t, OCH2, 8H), 3.71 (t, CH2Cl,
8H), 2.68 (m, PhCH2, 8H), 2.48 (m, PhCH2CH2, 8H).
CH3OH‚4H2O: C, 68.19; H, 6.46; N, 0.64. Found: C, 68.18;
H, 6.32; N, 0.64.
Hem ica r cep lex (9b@DMF ): yield 13%; mp > 267 °C dec;
1
2,20:3,19-Dim et h en o-1H ,21H ,23H ,25H -b is[1,3]d ioxo-
cin o[5,4-i:5′,4′-i′]b en zo[1,2-d :5,4-d ′]b is[1,3]b en zod ioxo-
cin , 7,11,15,28-Tetr a k is(2-ch lor oeth oxy)-1,21,23,25-ter a -
p en tyl-, Ster eoisom er (6). The procedure for compound 5
was followed with tetrol 4 (0.50 g, 0.57 mmol), potassium
carbonate (0.79 g, 5.7 mmol) in DMF (30 mL) and 2-chloroet-
hane tosylate (1.1 g, 4.5 mmol) to obtain product 6 (0.42 g,
65%): mp 255.6-257.6 °C; 1H NMR (CDCl3, 300 MHz) δ 6.80
(s, ArH, 4H), 5.82 (d, OCH2O, J ) 7.2 Hz, 4H), 4.70 (t, ArCH,
4H), 4.39 (d, OCH2O, J ) 7.2 Hz, 4H), 4.16 (t, OCH2, 8H), 3.69
(t, CH2Cl, 8H), 2.17 (m, CH2, 8H), 1.40-1.23 (m, CH2, 24H),
0.92 (t, CH3, 12H).
2,20:3,19-Dim et h en o-1H ,21H ,23H ,25H -b is[1,3]d ioxo-
cin o[5,4-i:5′,4′-i′]b en zo[1,2-d :5,4-d ′]b is[1,3]b en zod ioxo-
cin , 7,11,15,28-Tetr a k is(2-iod oeth oxy)-1,21,23,25-ter a k is-
(2-p h en yleth yl)-, Ster eoisom er (7). A solution of sodium
iodide (118 mg, 0.79 mmol) in MEK (30 mL) was refluxed for
1 h. To a refluxing solution was added tetrachloride 5 (100
mg, 0.079 mmol) and the mixture refluxed for 3 d. After
evaporation of MEK, the crude mixture was taken up in CH2-
Cl2 (100 mL), washed with water (2 × 100 mL) and brine (25
mL), and subsequently dried over MgSO4. After evaporation
of CH2Cl2, the crude product was recrystallized from CH2Cl2-
MeOH to give the product 7 (112 mg, 87%) as a white powder:
mp 279.5 °C; 1H NMR (CDCl3, 400 MHz) δ 7.28-7.16 (m, ArH,
20H), 6.86 (s, ArH, 4H), 5.92 (d, OCH2O, J ) 7.1 Hz, 4H), 4.83
(t, ArCH, 4H), 4.44 (d, OCH2O, J ) 7.1 Hz, 4H), 4.19 (t, OCH2,
8H), 3.37 (t, CH2I, 8H), 2.70 (m, PhCH2, 8H), 2.49 (m,
PhCH2CH2, 8H).
FT-IR (KBr) 1682 cm-1 (νCdO); H NMR (CDCl3, 400 MHz) δ
7.05 (s, ArHa, 4H), 6.76 (s, ArHb, 4H), 6.23 (d, COH, 1H), 5.89
(d, OCH2,eO, J ) 7.3 Hz, 4H), 5.79 (d, OCH2,cO, J ) 7.3 Hz,
4H), 4.76 (t, ArCHh, 4H), 4.66 (t, ArCHg, 4H), 4.25 (s, OCH2,i
,
8H), 4.19 (d, OCH2,d O, J ) 7.3 Hz, 4H), 4.14 (d, OCH2,fO, J )
7.3 Hz, 4H), 3.67 (s, ArCH2,kS, 8H), 3.06 (s, SCH2,j, 8H), 2.16
(m, CH2, 16H), 1.75 (d, NCH3, 3H), 1.37-1.23 (m, CH2, 32H),
0.99-0.89 (m, CH3, 24H), -0.08 (d, NCH3, 3H); FAB(+) MS
m/z 1948 (9b@DMF +, 100), 1875 (9b+, 8). Anal. Calcd for
C111H135O21N1S4‚5H2O: C, 65.43; H, 7.17. Found: C, 65.56; H,
6.93.
Hem ica r cep lex (9b@DMA): yield 25%; mp > 259 °C dec;
1
FT-IR (KBr) 1658 cm-1 (νCdO); H NMR (CDCl3, 400 MHz) δ
7.05 (s, ArHa, 4H), 6.77 (s, ArHb, 4H), 5.87 (d, OCH2,eO, J )
7.3 Hz, 4H), 5.82 (d, OCH2,cO, J ) 7.3 Hz, 4H), 4.75 (t, ArCHh,
4H), 4.68 (t, ArCHg, 4H), 4.30 (d, OCH2,dO, J ) 7.3 Hz, 4H),
4.27 (s, OCH2,i, 8H), 4.22 (d, OCH2,fO, J ) 7.3 Hz, 4H), 3.69
(s, ArCH2,kS, 8H), 3.06 (s, SCH2,j, 8H), 2.17 (m, CH2, 16H), 1.65
(d, NCH3, 3H), 1.37-1.23 (m, CH2, 32H), 1.00-0.84 (m, CH3,
24H), -0.32 (d, NCH3, 3H), -1.34 (d, COCH3, 3H); FAB(+)
MS m/z 1962 (9b@DMA+, 82), 1874 (9b+, 23). Anal. Calcd for
C
112H137O21N1S4‚CH3OH‚3H2O: C, 66.28; H, 7.24; N, 0.68.
Found: C, 66.25; H, 7.16; N, 0.52.
Hem ica r cep lex (9b@DMSO): yield 10%; mp > 248 °C dec;
1H NMR (CDCl3, 400 MHz) δ 7.03 (s, ArHa, 4H), 6.75 (s, ArHb,
4H), 5.87 (d, OCH2,eO, J ) 7.3 Hz, 4H), 5.82 (d, OCH2,cO, J )
7.3 Hz, 4H), 4.76 (t, ArCHh, 4H), 4.69 (t, ArCHg, 4H), 4.27 (s,
OCH2,i, 8H), 4.24 (d, OCH2,dO, J ) 7.3 Hz, 4H), 4.21 (d,
OCH2,fO, J ) 7.3 Hz, 4H), 3.70 (s, ArCH2,kS, 8H), 3.06 (s,
SCH2,j, 8H), 2.15 (m, CH2, 16H), 1.37-1.23 (m, CH2, 32H),
1.01-0.88 (m, CH3, 24H), -0.34 (d, SCH3, 6H); FAB(+) MS
m/z 1953 (9b@DMSO+, 100). Anal. Calcd for C110H134O21S5:
C, 67.67; H, 6.92. Found: C, 67.43; H, 7.09.
2,20:3,19-Dim et h en o-1H ,21H ,23H ,25H -b is[1,3]d ioxo-
cin o[5,4-i:5′,4′-i′]b en zo[1,2-d :5,4-d ′]b is[1,3]b en zod ioxo-
cin , 7,11,15,28-Tet r a k is(2-iod oet h oxy)-1,21,23,25-t er a -
p en tyl-, Ster eoisom er (8). The procedure for compound 7
was followed with sodium iodide (0.79 g, 5.3 mmol) in MEK
(40 mL) and tetrachloride 6 (0.18 g, 0.53 mmol) to obtain
product 8 (0.76 g, 90%) as a white powder: mp 213.1-216.4
Hem ica r cep lex (9b@NMP ): yield 13%; mp > 263 °C dec;
1H NMR (CDCl3, 400 MHz) δ 7.06 (s, ArHa, 4H), 6.77 (s, ArHb,
4H), 5.87 (d, OCH2,eO, 4H), 5.85 (d, OCH2,cO, 4H), 4.75 (t,
ArCHh, 4H), 4.67 (t, ArCHg, 4H), 4.26-4.09 (m, OCH2,i,
OCH2,d,fO, 16H), 3.71 (s, ArCH2,kS, 8H), 3.06 (s, SCH2,j, 8H),
2.15 (m, CH2, 16H), 1.85 (m, NCH2, 2H), 1.35-1.23 (m, CH2,
32H), 1.01-0.86 (m, CH3, 24H), -0.58 (m, COCH2, 2H), -0.65
(s, NCH3, 3H), -0.84 (m, NCH2CH2, 2H); FAB(+) MS, m/z 1974
1
°C; H NMR (CDCl3, 300 MHz) δ 6.82 (s, ArH, 4H), 5.87 (d,
OCH2O, J ) 7.2 Hz, 4H), 4.69 (t, ArCH, 4H), 4.39 (d, OCH2O,
J ) 7.2 Hz, 4H), 4.15 (t, OCH2, 8H), 3.34 (t, CH2I, 8H), 2.17
(m, CH2, 8H), 1.40-1.14 (m, CH2, 24H), 0.93 (t, CH3, 12H).
Gen er a l P r oced u r e of Hem ica r cep lexes (9@G). Under
argon atmosphere, a solution of tetraiodide 7 or 8 (0.25 g, 0.17
mmol) and tetrathiol 2 (0.18 g, 0.20 mmol) in solvent G (60
mL) was added dropwise to a suspension of Cs2CO3 (0.55 g,
1.7 mmol) in solvent G (100 mL) for 8 h at 50 °C. The mixture
was stirred for another 12 h, and then the temperature was
increased into 80 °C followed by stirring for 3 h. After being
cooled to room temperature, the solvent was taken up in
CH2Cl2 (300 mL), washed with 2 N HCl (80 mL), H2O (3 ×
200 mL), and brine (50 mL), and dried over MgSO4. After
evaporation of the solvent, the crude mixture was purified by
flash column chromatography (SiO2, EtOAc/hexane ) 1/9).
Hem ica r cep lex (9a @DMF ): yield 8%; mp >266 °C dec;
(9b @NMP +, 100), 1874 (9b+, 18). Anal. Calcd for C113H137
21N1S4‚CH2Cl2: C, 66.52; H, 6.81. Found: C, 66.30; H, 6.98.
F r ee Hem ica r cer a n d (9b). Under argon atmosphere, a
-
O
solution of tetrathiol 2 (0.29 g, 0.32 mmol) in acetonitrile (60
mL) was added dropwise to a refluxing solution of tetraiodide
8 (0.40 g, 0.27 mmol) and Cs2CO3 (0.87 g, 2.7 mmol) in
acetonitrile (120 mL) for 12 h. The mixture was refluxed for
another 1 d. After evaporation of acetonitrile, the crude
mixture was taken up in CH2Cl2 (300 mL), washed with 2 N
HCl (80 mL), H2O (3 × 200 mL), and brine (50 mL), and dried
over MgSO4. After evaporation of CH2Cl2, the residue was
chromatographed on a silica gel column using hexanes-EtOAc
(9:1, v/v) and the recrystallization from CH2Cl2-MeOH gave
the product 9b as a white powder (98 mg, 20%): mp > 258 °C
1
FT-IR (KBr) 1682 cm-1 (νCdO); H NMR (CDCl3, 400 MHz) δ
1
7.08 (s, ArHa, 4H), 6.82 (s, ArHb, 4H), 6.24 (d, COH, H), 5.86
1
(d, OCH2,eO, J ) 7.1 Hz, 4H), 5.77 (d, OCH2,cO, J ) 7.1 Hz,
dec; H NMR (CDCl3, 400 MHz) δ 7.00 (s, ArHa, 4H), 6.75 (s,
4H), 4.74 (t, ArCHg, 4H), 4.73 (t, ArCHh, 4H), 4.22 (s, OCH2,i
,
ArHb, 4H), 5.93 (d, OCH2,eO, 4H), 5.89 (d, OCH2,cO, 4H), 4.74
(t, ArCHh, 4H), 4.69 (t, ArCHg, 4H), 4.25 (s, OCH2,i, 8H), 4.20
(d, OCH2,dO, 4H), 3.97 (d, OCH2,fO, 4H), 3.61 (s, ArCH2,kS,
8H), 3.07 (s, SCH2,j, 8H), 2.09 (m, CH2, 16H), 1.34-1.23 (m,
CH2, 32H), 1.00-0.85 (m, CH3, 24H); FAB(+) MS m/z 1874
(M+, 5). Anal. Calcd for C108H128O20S4‚3CH2Cl2: C, 62.62; H,
6.34. Found: C, 62.33; H, 6.48.
8H), 4.14 (d, OCH2,dO, J ) 7.1 Hz, 4H), 4.11 (d, OCH2,fO, J )
7.1 Hz, 4H), 3.64 (s, ArCH2,kS, 8H), 3.03 (s, SCH2,j, 8H), 2.60
(m, PhCH2, 8H), 2.40 (m, PhCH2CH2, 8H), 2.10 (m, CH2, 8H),
1.53 (d, NCH3, 3H), 1.19 (m, CH2, 8H), 0.95 (t, CH3, 12H),
-0.08 (d, NCH3, 3H).
Hem ica r cep lex (9a @DMA): yield 11%; mp >274 °C dec;
1
FT-IR (KBr) 1658 cm-1 (νCdO); H NMR (CDCl3, 400 MHz) δ
Kin etics of Decom p lexa tion of 9b@DMF a n d 9b@DMA.
Decomplexation kinetics were conducted on 0.5 mL samples
of 2 mM solutions of complexes in degassed C6D5NO2 in sealed
1H NMR tubes in a temperature-controlled (( 1 °C), insulated
oil bath. Each tubes were removed at timed intervals and
detected by a 400 MHz 1H NMR spectrometer. About eight
spectra were collected for each temperature. Plots of -ln(A/
A0) vs time gave good straight lines that provided first-order
rate constants (k) for decomplexation (eq 1). The activation
7.13 (s, ArHa, 4H), 6.82 (s, ArHb, 4H), 5.89 (d, OCH2,eO, J )
7.1 Hz, 4H), 5.85 (d, OCH2,cO, J ) 7.1 Hz, 4H), 4.81 (t, ArCHg,
4H), 4.76 (t, ArCHh, 4H), 4.34 (d, OCH2,dO, J ) 7.1 Hz, 4H),
4.30 (s, OCH2,i, 8H), 4.23 (d, OCH2,fO, J ) 7.1 Hz, 4H), 3.70
(s, ArCH2,kS, 8H), 3.08 (s, SCH2,j, 8H), 2.65 (m, PhCH2, 8H),
2.44 (m, PhCH2CH2, 8H), 2.16 (m, CH2, 8H), 1.69 (d, NCH3,
3H), 1.23 (m, CH2, 8H), 0.99 (t, CH3, 12H), -0.31 (d, NCH3,
3H), -1.33 (d, COCH3, 3H). Anal. Calcd for C120H129O21N1S4‚

Molecular Engineering
J . Org. Chem., Vol. 66, No. 17, 2001 5743
free energies of decomplexation (∆Gq) were obtained from the
slope of the linear plot of ln k vs 1/T (eq 2).
∆Gqc ) 4.58Tc[9.972 + log(Tc/∆ν)] × 10-3 kcal mol-1 (3)
where ∆ν is the separation in Hz between the two signals.
Deter m in a tion of En er gy Ba r r ier s for In ter con ver -
sion of Ca r cer oisom er s. The energy barriers for intercon-
version between the different orientations of 9a @DMA,
9b@DMA, 9b@DMF , 9b@DMSO, and 9b@NMP were deter-
mined by measuring the dynamic 1H NMR at various tem-
peratures from +27 to -98 °C in CD2Cl2. For 9b@NMP ,
additional spectra were taken from 27 to 141 °C in C6D5NO2.
ln(A/A0) ) -kt
(1)
(2)
ln k ) ln A - ∆Gq/RT
NMR Mea su r em en ts. Str u ctu r e Deter m in a tion . All
dynamic NMR measurements were performed on a Bruker
Avance DPX300 (300 MHz) or Bruker Avance DPX500 (500
MHz) spectrometer. NOESY, ROESY, and COSY measure-
ments were carried out with 5 mm QNP 1H probehead. All
NOESY experiments were performed with mixing times
between 250 and 650 ms. The probe temperatures were
calibrated against 80% ethylene glycol in DMSO-d6 (for high
temperature) and 4% methanol in methanol-d4 (for low tem-
perature) as standard.
From the coalescence temperatures ∆Gq values (kcal mol-1
)
c
were calculated with eq 3 above. Also, the first-order rate
constants (k) were calculated with eq 4. The orientation of
incarcerated DMA in the major carceroisomer was determined
by NOESY and ROESY measurements at -90 °C. The
orientation of NMP in the major carceroisomer was determined
at -21 °C.
Deter m in a tion of Rota tion a l Ba r r ier s a r ou n d th e
Am id e Bon d of In ca r cer a ted DMF a n d DMA. The rota-
tional energy barriers around the amide bonds of 9a @DMA
and 9b@DMF were determined by measuring dynamic 1H
NMR at different temperatures from 25 to 187 °C in C6D5NO2
k ) π∆ν/1.414
(4)
Ack n ow led gm en t . Financial support from the
Korea Science and Engineering Foundation (No. 1999-
2-123-001-3) and the Korea Research Foundation (KRF-
2000-015-DP0196) is gratefully acknowledged.
or DMSO-d6. From the coalescence temperature, ∆Gq values
c
(kcal mol-1) were calculated with eq 315
(15) Friebolin, H. Basic One- and Two-Dimensional NMR Spectros-
copy; Wille, E. E., Ed.; VCH verlagsgesellschaft mbH Press: Weinheim,
1991.
J O015594I