Deeper cavitands

Full text of DOI:10.1021/jo990209z

J . Org. Chem. 1999, 64, 4555-4559
4555
Deep er Ca vita n d s
toluene, and the corresponding phenylenediamine units
were condensed with 1,2-diketones. The resulting fused
pyrazines provide the deepened cavities. Diethyl 2,3-
dioxosuccinate and acenaphthenequinone formed cav-
itands 6 and 7, respectively, as yellow solids in 13 and
Fabio C. Tucci, Dmitry M. Rudkevich, and
J ulius Rebek, J r.*
9
The Skaggs Institute for Chemical Biology and Department
of Chemistry, The Scripps Research Institute, 10550 North
Torrey Pines Road, La J olla, California 92037
4
9% (Scheme 1). Lehn and others utilized a similar
heterocyclization strategy to construct helicates and
extended surfaces.10
Received February 3, 1999
The new cavitands 6 and 7 exist in solution as vase-
like C4v structures, as shown by the H NMR spectra in
1
Cavitands are synthetic structures with curved, open-
ended cavities.1 The earliest cavitands were shallow,
bowl-shaped structures 1a ,b prepared from resorcin-
arenes 2 through alkylation or silylation of the phenolic
hydroxyls (Figure 1).2 These cavitands are limited by
their dimensionssca. 9.0 Å wide and 3.0 Å deepsto
various solvents (Figure 2). Only one set of signals was
found for all groups of protons. However, unlike the rigid
cavitand 3, conformational dynamics were observed, in
a process that is intermediate in rate on the NMR time
,3
1
scale (Figure 3). The H NMR spectrum of cavitand 6 in
CDCl
aromatic ring C-H
warmed to 330 K, the H
3
at 295 K displays sharp resonances except for the
(Figure 2). When the sample is
resonance emerges. Similarly,
interact only with small molecules: CH
and CH
2
Cl
CtCH3 are weakly bound by them in solution.
3
2 3 2
, CHCl , CS ,
c
a-d
c
Subsequently, the rims were built up and the cavities
deepened; 3, for example, offers a depth of ∼8.0 Å. Its
binding properties have been examined under a variety
cavitand 7, with its much deeper cavity, displayed broad
resonances at 295 K in a variety of solvents (p-xylene-
d
6 8 3
10, benzene-d , toluene-d , CDCl ). Again, when the
3
-6
of conditions including on solid surfaces.
Cavitand 3a
samples were heated (>330 K), sharp spectra character-
istic of C4v symmetry arose (Figure 2).
complexed simple aromatic molecules.4 We have now
developed access to even deeper cavitands, capable of
housing more sizable guests, and we communicate our
methods here.
Functional group manipulations on the upper rim of 6
were uneventful. The eight ester groups are moderately
activated and underwent conversion to the octacarbox-
amide 8 on treatment with an excess of n-butylamine in
boiling ethanol. The presence of eight hydrogen bond
donor and acceptor sites (the C(O)-NH functions) of 8
imparted a unique, strongly solvent- and temperature-
dependent folding-unfolding behavior that will be de-
scribed elsewhere. Saponification of 6 with aqueous LiOH
resulted in quantitative conversion to the octaacid 9.
The deeper cavitands 3 are usually prepared by bridg-
ing the resorcinarene hydroxyl groups of 2a with a
preformed heterocycle, e.g., condensation with a 6,7-
disubstituted-2,3-dichloroquinoxaline. The alternative
involves the use of a simpler building block in the
bridging reaction and then extension of the rim through
heterocyclic synthesis. Specifically, the octanitro cavitand
7
4
was obtained by reaction of 2a with 1,2-difluoro-4,5-
a
The NMR chemical shifts of the bridging methines (H ,
8
dinitrobenzene in DMF at 70 °C in the presence of Et
3
N.
Figure 2) in cavitands have been used to estimate the
degree of their conformational mobility.3 Methine chemi-
cal shifts above 5.5 ppm indicate a stable “vase” confor-
mation of C4v symmetry, while shifts below 4.0 ppm are
characteristic of the “kite” conformation. The latter has
the four rim aromatics flipped outward and features C2v
symmetry. The conformational preferences are affected
by solvation, dimerization, and complexation and can be
diagnosed by the shift of the CH triplet resonance.
Table 1 records the effect of solvent on this signal for
The NO groups were hydrogenated with Ra/Ni in
2
e
(
1) (a) Cram, D. J . Science 1983, 219, 1177-1183. (b) Cram, D. J .;
Cram, J . M. Container Molecules and their Guests; Royal Society of
Chemistry: Cambridge, 1994; pp 85-130.
(
2) (a) H o¨ gberg, A. G. S. J . Am. Chem. Chem. 1980, 102, 6046-
6
050. (b) H o¨ gberg, A. G. S. J . Org. Chem. 1980, 45, 4498-4500. (c)
Tunstad, L. M.; Tucker, J . A.; Dalcanale, E.; Weiser, J .; Bryant, J . A.;
Sherman, J . C.; Helgeson, R. C.; Knobler, C. B.; Cram, D. J . J . Org.
Chem. 1989, 54, 1305-1312. For a timely review, see: Timmerman,
P.; Verboom, W.; Reinhoudt, D. N. Tetrahedron 1996, 52, 2663-2704.
(3) (a) Cram, D. J .; Karbach, S.; Kim, H.-E.; Knobler, C. B.;
Maverick, E. F.; Ericson, J . L.; Helgeson, R. C. J . Am. Chem. Soc. 1988,
the new cavitands. In contrast to 3a (R ) C11
molecules 6 and 7 exhibit a very solvent-dependent
methine (H ) chemical shift. The CH triplet of 3a is found
at 5.5 ppm at room temperature in CDCl , while for 6
H23),
1
10, 2229-2237. (b) Cram, D. J .; Stewart, K. D.; Goldberg, I.;
Trueblood, K. N. J . Am. Chem. Soc. 1985, 107, 2574-2575. (c) Tucker,
J . A.; Knobler, C. B.; Trueblood, K. N.; Cram, D. J . J . Am. Chem. Soc.
a
1
989, 111, 3688-3699. (d) Moran, J . R.; Karbach, S.; Cram, D. J . J .
3
Am. Chem. Soc. 1982, 104, 5826-5828. (e) Moran, J . R.; Ericson, J .
L.; Dalcanale, E.; Bryant, J . A.; Knobler, C. B.; Cram, D. J . J . Am.
Chem. Soc. 1991, 113, 5707-5714. (f) Cram, D. J .; Choi, H. J .; Bryant,
J . A.; Knobler, C. B. J . Am. Chem. Soc. 1992, 114, 7748-7765.
and 7 it is located upfield 4.6 ppm. In aromatic solvents,
the methine signal for cavitand 3a is found at ca. 6.0
ppm, while for cavitand 6 the CH triplet is detected at
ca. 4.5 ppm and for 7 it is between 5.4 and 6.0 ppm. The
same trend is observed at higher temperatures (>330 K).
These suggest that the cavities of 6 and 7 are quite
conformationally flexible (Figure 3) and prefer aromatic
solvent molecules.
(4) (a) Dalcanale, E.; Soncini, P.; Bacchilega, G.; Ugozzoli, F. J .
Chem. Soc., Chem. Commun. 1989, 500-502. (b) Soncini, P.; Bonsig-
nore, S.; Dalcanale, E.; Ugozzoli, F. J . Org. Chem. 1992, 57, 4608-
4
612. (c) Dalcanale, E.; Costantini, G.; Soncini, P. J . Inclusion Phenom.
Mol. Recognit. Chem. 1992, 13, 87-92.
5) Gas-phase complexation studies: (a) Vincenti, M.; Dalcanale, E.;
Soncini, P.; Guglielmetti, G. J . Am. Chem. Soc.. 1990, 112, 445-447.
b) Vincenti, M.; Minero, C.; Pelizzetti, E.; Secchi, A.; Dalcanale, E.
(
(
Pure Appl. Chem. 1995, 67, 1075-1084. (b) Dickert, F. L.; Baumler,
U. P. A.; Stathopulos, H. Anal. Chem. 1997, 69, 1000-1005.
(8) Kazimierczuk, Z.; Dudycz, L.; Stolarski, R.; Shugar, D. Nucleo-
sides Nucleotides 1981, 8, 101-117.
(6) Schierbaum, K. D.; Weiss, T.; Thoden van Velzen, E. U.;
Engbersen, J . F. J .; Reinhoudt, D. N.; Gopel, W. Science 1994, 265,
413.
7) (a) Rudkevich, D. M.; Hilmersson, G.; Rebek, J ., J r. J . Am. Chem.
(9) Boger, D. L.; Panek, J . S.; Yasuda, M. Org. Synth. 1987, 66, 142-
1
150.
(
(10) (a) W a¨ rnmark, K.; Thomas, J . A.; Heyke, O.; Lehn, J . M. Chem.
Commun. 1996, 701-702. (b) Warrener, R. N.; Butler, D. N.; Russel,
R. A. Synlett 1998, 566-595.
Soc. 1998, 120, 12216-12225. (b) Rudkevich, D. M.; Hilmersson, G.;
Rebek, J ., J r. J . Am. Chem. Soc. 1997, 119, 9911-9912.
1
0.1021/jo990209z CCC: $18.00 © 1999 American Chemical Society
Published on Web 05/12/1999

4
556 J . Org. Chem., Vol. 64, No. 12, 1999
Notes
F igu r e 1. Resorcinarenes 2 and first generation cavitands 1 and 3.
Sch em e 1a
a
(a) diethyl 2,3-dioxosuccinate, benzene, rt, 16 h (13%); (b) acenaphthenequinone, THF, HOAc, reflux, 6 h (49%); (c) n-butylamine,
EtOH, reflux, 19 h (49%); (d) THF, LiOHaq (1 N), reflux, 1 h (100%).
The cavity dimensions of cavitands 6 and 7, estimated
by molecular mechanics,11 are 11 and 14 Å deep, respec-
tively. To our knowledge they are the deepest known
open-ended cavities reported to date,12 and since their
interiors are undoubtedly solvated, an estimate was made
concerning the number and types of solvent that can be
lactam and numerous aromaticsswith 6 and 7 was
attempted, but no binding was detected by H NMR
spectroscopy in either CDCl or toluene-d . Apparently,
3 8
1
(12) For other approaches towards deep cavitands, see: (a) von dem
Bussche-H u¨ nnefeld, C.; B u¨ hring, D.; Knobler, C. B.; Cram, D. J . Chem.
Commun. 1995, 1085-1086. (b) von dem Bussche-H u¨ nnefeld, C.;
Helgeson, R. C.; B u¨ hring, D.; Knobler, C. B.; Cram, D. J . Croat. Chem.
Acta 1996, 69, 1447-458. (c) Ma, S.; Rudkevich, D. M.; Rebek, J ., J r.
J . Am. Chem. Soc. 1998, 120, 4977-4981. For extended calix[4]arene-
resorcinarene-based surfaces, see: (a) Timmerman, P.; Nierop, K. G.
A.; Brinks, E. A.; Verboom, W.; van Veggel, F. C. J . M.; van Hoorn, W.
P.; Reinhoudt, D. N. Chem. Eur. J . 1995, 1, 132-143. (b) Higler, I.;
Timmerman, P.; Verboom, W.; Reinhoudt, D. N. J . Org. Chem. 1996,
accommodated within. Four molecules of CHCl
of benzene are easily modeled within cavitand 6. Cav-
itand 7 can accommodate up to five molecules of CHCl
3
or three
3
or four molecules of either benzene or toluene in its
interior.
The complexation of a number of various guestss
adamantane derivatives, cyclohexane derivatives, capro-
6
1, 5920-5931. (c) Higler, I.; Verboom, W.; van Veggel, F. C. J . M.;
J ong, F. de; Reinhoudt, D. N. Liebigs Ann./ Recl. 1997, 1577-1586.
For deep calix[4]arenes, see: (d) J uneja, R. K.; Robinson, K. D.;
J ohnson, C. P.; Atwood, J . L. J . Am. Chem. Soc. 1993, 115, 3818-
3819 and references therein. (e) Xu, B.; Miao, Y.-J .; Swager, T. M. J .
Org. Chem. 1998, 63, 8561-8564 and references therein.
(11) Mohamadi, F.; Richards, N. G.; Guida, W. C.; Liskamp, R.;
Lipton, M.; Caufield, C.; Chang, G.; Hendrickson, T.; Still, W. C. J .
Comput. Chem. 1990, 11, 440-467.

Notes
J . Org. Chem., Vol. 64, No. 12, 1999 4557
openings with guest/solvent exchange fast on the NMR
time scale. The uptake and release of guests involves the
folding and unfolding of the host walls, motions that are
influenced by solvent size and polarity. Cavitand 7
complexes C60 but not C70, a behavior that augurs well
for the use of these containers as selective reaction
vessels, possibly even catalysts. These applications are
the focus of current investigations.
Exp er im en ta l Section
Gen er a l. Melting points are uncorrected. 1H NMR and 13
C
NMR spectra were recorded on a 600 MHz spectrometer. The
chemical shifts were measured relative to residual nondeuter-
ated solvent resonances. Fast atom bombardment (FAB) mass
spectra were obtained with a VG ZAB-VSE double-focusing high-
resolution mass spectrometer equipped with a cesium ion gun;
m-nitrobenzyl alcohol (NBA) was used as a matrix. For high-
resolution mass spectral data (HRMS-FAB), for compounds
with molecular weight e 500, the measured masses always
agreed to e 5 ppm with the calculated values. For compounds
with significantly higher molecular weight (g2000), slightly
lower resolution (e10 ppm) was achieved.16 Matrix-assisted laser
desorption/ionization (MALDI) mass spectrometry experiments
were performed using 2,5-dihydroxybenzoic acid (DHB) as a
matrix. Silica gel chromatography was performed with silica gel
6
0 (230-400 mesh). All experiments with moisture- or air-
sensitive compounds were performed in anhydrous solvents
under a nitrogen atmosphere. 1,2-Difluoro-4,5-dinitrobenzene,
diethyl 2,3-dioxosuccinate, resorcinarene 2a , and cavitand 3a
8
9
2c
4b
were synthesized in accordance with literature protocols. Mo-
lecular modeling was performed using the Amber* force field in
the MacroModel 5.5 program.11
Op tim ized P r oced u r e for Octa n itr o Ca vita n d 4. Resor-
cinarene 1a (1.10 g, 1.0 mmol) and 1,2-difluoro-3,4-dinitroben-
zene (0.90 g, 4.4 mmol) were suspended in anhydrous DMF (50
3
mL), and then Et N (2.23 mL, 16.0 mmol) was added dropwise
via syringe. The resulting tan solution was slowly warmed to
70 °C and stirred at that temperature for 16 h. After cooling to
F igu r e 2. Downfield section of the 1H NMR spectra of
room temperature, the mixture was poured onto acidic H
1) and the bright yellow precipitate was filtered. The solids
were dried under vacuum and then chromatographed on silica
gel with CH Cl as the eluent. The product obtained from the
column was then triturated with MeOH (100 mL) and dried
2
O (pH
cavitands 6 and 7 (600 MHz). The solvent signals and the
corresponding satellites are marked with “b” and “*”, respec-
tively. The letters on top of the peaks (a, b, c, and d) represent
assignments made on the basis of COSY and ROESY spectra
of analogues.
∼
2
2
(
13) For C60/C70 complexations with calixarenes in solution, see: (a)
these solvents can fill the required space well enough and
enjoy a high concentration advantage over the intended
guest solutes. Modeling suggested that 7 can accom-
modate C60 (Figure 4) even though the round C60 is not
well complemented by the square hole. The electron-rich
walls of 7 and their considerable contact with incumbent
Haino, T.; Yanase, M.; Fukazawa, Y. Angew. Chem., Int. Ed. Engl.
1997, 36, 259-260. (b) Raston, C. L.; Atwood, J . L.; Nichols, P. J .;
Sudria, I. B. N. Chem. Commun. 1996, 2615-2616. (c) Araki, K.; Akao,
K.; Ikeda, A.; Suzuki, T.; Shinkai, S. Tetrahedron Lett. 1996, 37, 73-
7
6. (d) Ikeda, A.; Yoshimura, M.; Shinkai, S. Tetrahedron Lett. 1997,
38, 2107-2110. (e) Ikeda, A.; Suzuki, Y.; Yoshimura, M.; Shinkai, S.
Tetrahedron 1998, 54, 2497-2508. (f) Atwood, J . L.; Barbour, L. J .;
Raston, C. L.; Sudria, I. B. N. Angew. Chem., Int. Ed. Engl. 1998, 37,
C
C
60 encouraged experiments, and strong complexation of
60 by 7 was indeed detected in the toluene solution.
9
81-983. (g) Haino, T.; Yanase, M.; Fukazawa, Y. Angew. Chem., Int.
Ed. Engl. 1998, 37, 997-998. (h) Wang, J .; Gutsche, C. D. J . Am. Chem.
Soc. 1998, 120, 12226-12231. (i) Georghiou, P. E.; Mizyed, S.;
Chowdhury, S. Tetrahedron Lett. 1999, 40, 611-614. For C60/C70
complexations with cyclotriveratrylene (CTV), see: (j) Steed, J . W.;
J unk, P. C.; Atwood, J . L.; Barnes, M. J .; Raston, C. L.; Burkhalter,
R. S. J . Am. Chem. Soc. 1994, 116, 10346-10347. (k) Atwood, J . L.;
Barnes, M. J .; Gardiner, M. G.; Raston, C. L. Chem Commun. 1996,
Specifically, addition of 7 to a toluene solution of C60 (1.0-
-
5
2
.0 × 10 M) led to an increase in the absorption of the
band at 430 nm, characteristic of complexation (Figure
1
3
5
). Treatment of the titration data with the Benesi-
14,15
Hildebrand equation
gave a value for the association
1
449-1450. For a preliminary study of C70 complexation by other
resorcinarene-based cavitands, see ref 7a.
14) Connors, K. A. Binding Constants; J ohn Wiley and Sons: New
constant, K
) 900 ( 250 M- at 293 ( 1 K, or a ∆G )
1
a
(
-
4.0 ( 0.2 kcal/mol. The binding isotherm provides a
1
York, 1987. No significant changes in the H NMR spectra were
detected in 7 upon C60 or C70 addition. Mass spectrometry measure-
ments (MALDI and ESI) of 1:1 mixtures of 7 and C60 or C70 did not
show the molecular ions for the complexes.
good fit to a 1:1 stoichiometry. Control experiments with
model compound 10 and the “shallow” cavitand 3a
-
1
showed only very weak interactions (K < 10 M ).
a
(
15) The results obtained through the Benesi-Hildebrand equation
Unexpectedly, the UV/vis spectra showed no apparent
binding of the slightly larger C70 in 7. Accordingly, this
example of selective complexation of fullerenes by resor-
cinarene-based compounds is one of the first reported.13
In summary, deeper cavitands of nanometric dimen-
sions are now available for use as open-ended molecular
containers. The cavities reported here feature wide
were confirmed by the use of a nonlinear regression analysis curve-
fitting software developed in the laboratories of Prof. Fran c¸ ois N.
Diederich at ETH, Z u¨ rich.
(16) For details on high-resolution mass spectrometry, see: (a) Rose,
M. E.; J ohnstone, R. A. W. Mass Spectrometry for Chemists and
Biochemists; Cambridge University Press: Cambridge, 1982. (b) J en-
nings, K. R.; Dolnikowsi, G. G. Methods in Enzymology; McCloskey,
J . A., Ed.; Academic Press: New York, 1990; p 37 and references
therein.

4
558 J . Org. Chem., Vol. 64, No. 12, 1999
Notes
F igu r e 3. Proposed conformational dynamics for deep cavitands 6 and 7.
Ta ble 1. Ch em ica l Sh ifts of Meth in e Tr ip lets (Ha , F igu r e
2
) in Ca vita n d s 3a , 6, a n d 7 in Differ en t Solven ts
compd
solvent
CDCl3
benzene-d6
p-xylene-d10
toluene-d8
CDCl3
temp (K)
chem shift (δ, ppm)a,b,c
3
6
7
a 4
295
295
295
295
295
330
295
295
295
330
295
350
295
380
295
380
5.52
6.06
6.00
6.05
4.04
4.12
4.47
4.45
4.57 (b)
4.55
5.87 (b)
5.60
6.04 (b)
5.56
5.44 (b)
5.18
CDCl3
benzene-d6
p-xylene-d10
CDCl3
CDCl3
benzene-d6
benzene-d6
toluene-d8
toluene-d8
p-xylene-d10
p-xylene-d10
a
b, broad. b At 0.5 mM. c error, ( 0.05 ppm.
-
5
F igu r e 5. Absorption spectra of C60 (1.0 × 10 M) in the
presence of 7 in toluene at 293 ( 1 K. The concentrations for
-
5
7
2
for the ascending curves are 0.0, 5.0 × 10 , 1.0, 1.5, 2.0,
-4
.5, 3.0 and 3.5 × 10 M, respectively.
, 330 K) δ 7.95 (s, 8 H), 7.15 (s, 4 H), 6.76 (s, 4
H), 4.53 (q, J ) 7.0 Hz, 16 H), 4.12 (t, J ) 7.5 Hz, 4 H), 2.03-
.99 (m, 8 H), 1.46 (t, J ) 7.0 Hz, 24 H), 1.32-1.20 (m, 72 H),
, 330 K) δ 164.97,
1H NMR (CDCl
3
1
0
.89 (t, J ) 7.2 Hz, 12 H); 13C NMR (CDCl
3
F igu r e 4. Side and top views of the energy-minimized11 CPK
models of C60‚cavitand 7 complex. The long alkyl “feet” are
omitted for clarity.
154.17, 152.55, 144.13, 139.55, 132.33, 124.50, 119.24, 113.64,
62.89, 36.49, 32.18, 31.95, 29.84 (br), 29.76, 29.58, 27.34, 22.91,
-
1
14.36, 14.24; IR (CDCl
98, 737; HRMS-FAB m/z 2317.9846 ([M + Cs] , calcd for
24Cs ) 2317.9974, error 5.5 ppm).
Ca vita n d 7. To a solution of crude octaamine 5 (248 mg, 0.16
3
, cm ) ν 2926, 2854, 1729, 1478, 1416,
+
8
under vacuum. The product was obtained as a pale yellow solid
128 152 8
C H N O
(
1.40 g, 0.8 mmol; 80%). The spectral and analytical data agreed
7
with the literature values.
mmol) in anhydrous THF (27 mL) and glacial HOAc (1 mL) was
added acenaphthenequinone (372 mg, 2.04 mmol). The initial
suspension was refluxed under an N atmosphere for 6 h. The
2
Op tim ized P r oced u r e for Octa a m in o Ca vita n d 5. Oc-
tanitro cavitand 4 (704 mg; 0.40 mmol) was dissolved in toluene
(
150 mL), and to this solution was added a catalytic amount of
solvents were removed under vacuum, and the remaining solid
was suspended in acetone (70 mL) with stirring for 30 min. The
remaining solids were filtered, rinsed with acetone, and then
dried under vacuum to give the title compound as a tan solid
Ra/Ni, prewashed with EtOH (2 × 5 mL) and toluene (2 × 5
mL). The resulting mixture was evacuated, and the reaction
flask was filled with H
times, and the mixture was stirred for 12 h at 45 °C under an
atmosphere. After cooling, the catalyst was filtered through
2
. This operation was repeated three
(214 mg, 0.10 mmol; 49% from octanitro cavitand 4): mp > 270
1
H
2
°C; H NMR (CDCl
3
, 330 K) δ 8.41 (d, J ) 6.8 Hz, 8 H), 8.06 (d,
a pad of CELITE and then rinsed with toluene (50 mL) and
MeOH (2 × 50 mL). The filtrates were combined and evaporated
under vacuum to give a brown solid (563 mg, 0.37 mmol; 93%)
that was taken directly to the coupling step.
Octa ester Ca vita n d 6. The crude octaamine 5 (563 mg; 0.37
mmol) was dissolved in anhydrous benzene (40 mL) and kept
J ) 8.1 Hz, 8 H), 8.02 (s, 8 H), 7.82 (t, J ) 7.5 Hz, 8 H), 7.29 (s,
4 H), 6.89 (s, 4 H), 4.55 (t, J ) 7.2 Hz, 4 H), 2.06 (q, J ) 7.2 Hz,
1
8 H), 1.31-1.17 (m, 72 H), 0.83 (t, J ) 7.1 Hz, 12 H); H NMR
(benzene-d , 350 K) δ 8.13 (s, 8 H), 8.07 (d, J ) 6.7 Hz), 7.51 (d,
6
J ) 8.4 Hz), 7.46 (s, 4 H), 7.43 (s, 4 H), 7.13 (t, J ) 7.5 Hz, 8 H),
5.60 (t, J ) 7.2 Hz, 4 H), 2.36 (q, J ) 7.2 Hz, 8 H), 1.56-1.51
(m, 8 H), 1.45-1.42 (m, 8 H), 1.36-1.29 (m, 56 H), 0.90 (t, J )
2
under N . Diethyl 2,3-dioxosuccinate (606 mg; 3.00 mmol) was
1
added dropwise through a syringe, and the resulting solution
was stirred at room temperature for 16 h. The solvent was
removed under vacuum, and the remaining residue was chro-
matographed on silica gel eluting with a 7:3 mixture of hexanes
and EtOAc. The product was obtained as a yellow solid (109 mg,
6.8 Hz, 12 H); H NMR (p-xylene-d10, 380 K) δ 8.07 (d, J ) 6.7
Hz, 8 H), 8.03 (s, 8 H), 7.61 (d, J ) 8.2 Hz, 8 H), 7.37 (s, 4 H),
7.35 (t, J ) 7.5 Hz, 8 H), 7.26 (s, 4 H), 5.18 (t, J ) 7.7 Hz, 4 H),
2.30 (q, J ) 7.4 Hz, 8 H), 1.54-1.49 (m, 8 H), 1.41-1.37 (m, 8
1
3
H), 1.31-1.25 (m, 56 H), 0.86 (t, J ) 7.0 Hz, 12 H); C NMR
(CDCl , 330 K) δ 154.43, 153.57, 149.99, 138.65, 136.30, 132.16,
0
.05 mmol; 13% from octanitro cavitand 4): mp ) 139-141 °C;
3

Notes
J . Org. Chem., Vol. 64, No. 12, 1999 4559
1
3
30.05, 129.14, 128.55, 124.19, 121.69, 119.70, 113.80, 35.61,
1.85, 29.62 (br), 29.33, 29.27, 27.20, 22.56, 13.91; IR (CDCl
solved in benzene (5 mL), and acenaphthenequinone (273 mg;
1.5 mmol) was added. The heterogeneous mixture was heated
under reflux for 8 h. After cooling, the solvent was removed
under vacuum and the residue was chromatographed on silica
gel (95:5 hexanes/EtOAc). The product was obtained as a white
3
,
-1
cm ) ν 2927, 2854, 1601, 1485, 1429; HRMS-FAB m/z 2237.9717
+
(
[M + Cs] , calcd for C144
136 8 8
H N O Cs ) 2237.9535, error 8.1
ppm).
1
n -Bu tyl Octa ca r boxa m id e Ca vita n d 8. A 25 mL round-
bottomed flask, equipped with a reflux condenser and a magnetic
stirring bar, was charged with octaester 6 (50 mg, 23.0 µmol),
absolute EtOH (10 mL), and n-butylamine (1 mL, 10.0 mmol).
The resulting mixture was heated under reflux, and the con-
sumption of the starting material was followed by TLC (3:2
hexanes/EtOAc). After 19 h the volatiles were removed under
vacuum and the residue was chromatographed on silica gel,
eluting with a 3:2 mixture of hexanes and EtOAc (R ) 0.31).
The product was obtained as a yellowish solid (27 mg, 11.3 µmol;
4
d
solid (169 mg, 0.6 mmol; 60%): mp > 270 °C; H NMR (CDCl )
3
δ 8.39 (d, J ) 6.9 Hz, 2 H), 8.07 (d, J ) 8.4 Hz, 2 H), 7.96 (s, 2
H), 7.82 (t, J ) 7.6 Hz, 2 H), 2.52 (s, 6 H); 13C NMR (CDCl ) δ
3
153.34, 140.02, 139.59, 136.07, 132.18, 129.97, 129.15, 128.92,
-
1
128.61, 121.52, 20.32; IR (CH Cl , cm ) ν 3054, 2986, 1421, 896;
2
2
+
HRMS-FAB m/z 283.1235 ([M + H]
, calcd for C20H14N H )
2
283.1235, error 0.0 ppm).
Deter m in a tion of th e Associa tion Con sta n t. Binding
studies were performed in toluene solution at 293 ( 1 K. A 1
mL volume of toluene was placed in both the sample cell and
f
1
9%): mp ) > 270 °C; H NMR (p-xylene-d10 + 20% v/v DMSO-
) δ 8.74 (s, 8 H), 8.51 (t, J ) 5.2 Hz, 8 H), 8.06 (s, 4 H), 7.79
-3
the reference cell, and 14 µL of a 1.0 × 10 M C60 (or C70) stock
6
solution was added to the sample cell, giving a final concentra-
(
1
0
s, 4 H), 5.59 (m, 4 H), 3.49-3.46 (m, 16 H), 2.53-2.48 (m, 8 H),
-5
-2
tion of 2.0 × 10 M. An aliquot from the 1.0 × 10 M stock
solution of compounds 3a , 7, or 10 was added to the sample cell
and to the reference cell, and after homogenization, the absorp-
tion spectrum was recorded. Additional aliquots of 3a , 7, or 10
were added to both cells, and the spectrum was recorded after
each addition. The association constant was calculated from the
.70-1.66 (m, 16 H), 1.48-1.44 (m, 32 H), 1.29-1.25 (m, 56 H),
.99 (t, J ) 7.3 Hz, 24 H), 0.90 (t, J ) 6.8 Hz, 12 H); IR (CDCl
3
,
-
1
cm ) ν 3427, 3304, 2959, 2929, 2856, 1671; HRMS-FAB m/z
2
error 5.7 ppm); MALDI-MS m/z 2405 ([M + H] , calcd for
C
N
+
534.3612 ([M + Cs] , calcd for C144
H
192
N
16
O
16Cs ) 2534.3757,
+
+
144
H
O
192
N
16
O
16H ) 2404.2), 4811 ([M
32H ) 4807.5).
Octa a cid Ca vita n d 9. Cavitand 6 (109 mg; 0.05 mmol) was
2
384
+ H] , calcd for C288H -
absorption intensities changes at 430 nm for C60 and 420 nm
32
for C70 using the Benesi-Hildebrand equation.1
ments were performed at least in triplicate.
4,15
All experi-
dissolved in THF (2 mL), and to the resulting solution was added
aqueous LiOH (8 mL of a 1 N solution) slowly. The mixture was
heated under reflux for 1 h; after that time the reaction was
complete by TLC (2:1 hexane/ethyl acetate). The mixture was
cooled to 0 °C and acidified with 1 N HCl. The solids were filtered
and washed with cold water (20 mL). The product was obtained
Ack n ow led gm en t. We are grateful to the Skaggs
Research Foundation and the National Institutes of
Health for support. We thank Prof. Fran c¸ ois N. Dieder-
ich for helpful discussions and for providing us with a
copy of his curve-fitting program. We also thank Dr.
Shihong Ma for experimental advice.
as a tan solid after drying in high vacuum overnight (98 mg,
0
1
.05 mmol; ∼100%): mp > 270 °C; H NMR (DMSO-d
6
) δ 14.05
(br, 8H), 8.55 (s, 8H), 7.69 (s, 4H), 7.30 (s, 4H), 4.76 (br, 4H),
1
2
.26 (br, 8H), 1.21-1.14 (m, 72H), 0.82 (t, J ) 6.8 Hz, 12H); H
NMR (acetone-d ) δ 12.32 (br, 8H), 8.08 (s, 8H), 7.46 (s, 4H),
6
1
Su p p or tin g In for m a tion Ava ila ble: Representative H
7
1
2
.21 (s, 4H), 4.31 (t, J ) 7.4 Hz, 4H), 2.18-2.15 (m, 8H), 1.28-
13
and C NMR, UV/vis spectra, and binding isotherm. This
-
1
.16 (m, 72H), 0.86 (t, J ) 6.9 Hz, 12H); IR (THF, cm ) ν 3463,
material is available free of charge via the Internet at
http://pubs.acs.org.
920, 2851, 1728, 1478, 1209, 1068, 905.
9
,10-Dim eth yla cen a p h th o[1,2-b]qu in oxa lin e (10). 3,4-
Dimethyl-1,2-phenylenediamine (136 mg; 1.0 mmol) was dis-
J O990209Z