First C3v-symmetrical calix[6](aza)crown

Article abstract of DOI:10.1021/jo026642h

The first C_3v-symmetrical calix[6](aza)crown 8 has been obtained in five steps from X₆H₃Me₃ 3. The key-step introduction of the triple bridge at the small rim has been achieved through reaction of a tris-arylsulfonamide derivative of tren 1 and tris-tosylcalix[6]arene 6. A ¹H NMR study has shown that the tripodal cap rigidifies the whole edifice, preventing ring inversion and constraining the calixarene core in a straight cone conformation.

Full text of DOI:10.1021/jo026642h

F ir st C3v-Sym m etr ica l Ca lix[6](a za )cr ow n
Ivan J abin*,† and Olivia Reinaud*,‡
URCOM, Universite´ du Havre, Faculte´ des Sciences et Techniques, 25 rue Philippe Lebon, BP 540,
76058 Le Havre Cedex, France, and Laboratoire de Chimie et Biochimie Pharmacologiques et
Toxicologiques, UMR CNRS 8601, Universite´ Rene´ Descartes, 45 rue des Saints Pe`res,
75270 Paris Cedex 06, France
ivan.jabin@univ-lehavre.fr
Received November 1, 2002
The first C3v-symmetrical calix[6](aza)crown 8 has been obtained in five steps from X6H3Me3 3.
The key-step introduction of the triple bridge at the small rim has been achieved through reaction
1
of a tris-arylsulfonamide derivative of tren 1 and tris-tosylcalix[6]arene 6. A H NMR study has
shown that the tripodal cap rigidifies the whole edifice, preventing ring inversion and constraining
the calixarene core in a straight cone conformation.
In tr od u ction
by protecting the metal ion from the external medium
while maintaining a large degree of flexibility essential
for the system in order to act as a biomimetic receptor.
The synthesis of calix[4](aza)crowns has already been
explored,4 but only two recent examples of calix[6]arenes
including diamide bridges have been reported.5,6 Fur-
thermore, calix[6]arenes capped with a tripodal bridge
are still rare.7 In this study, we describe the synthesis of
the first C3v-symmetrical calix[6](aza)crown, where the
small rim is capped with the tris(2-aminoethyl)amine
tripodal unit.
Calix[4]arenes have been extensively studied for host-
guest chemistry. However, because of their small size,
they have mostly been used as a platform for the
preorganization of a binding site. The larger calix[6]-
arenes appear more suitable to play the role of a
molecular receptor, yet their higher conformational flex-
ibility, due to facile ring inversion,1 represents an ob-
stacle. We have recently shown that rigidification of the
calix[6]arene core could be achieved through the use of
coordination chemistry.2 Indeed, the binding of a metal
ion to three amino groups that are covalently linked to
the calix[6]arene small rim can constrain the macrocycle
into a cone conformation. The so-called funnel complexes
present a biomimetic environment for Cu or Zn, which
can coordinate a neutral guest inside the hydrophobic
cavity.3 We wanted to extend our supramolecular system
to the use of a ligand consisting of a calix[6]arene capped
with a C3v-symmetrical azacrown bridge. Such a rigidified
ligand should possess a reinforced complexation ability
because the cap should prevent decomplexation processes
Resu lts a n d Discu ssion
A classical route for the synthesis of azacrowns consists
of the use of a poly-toluenesulfonamide salt for the
(4) Bitter, I.; Gru¨n, A.; Toth, G.; Balazs, B.; Toke, L. Tetrahedron
1997, 53, 9799-9812. Tuntulani, T.; Ruangpornvisuti, V.; Tantikun-
watthana, N.; Ngampaiboonsombut, O.; Seangprasertkij-Magee, R.;
Asfari, Z.; Vicens, J . Tetrahedron Lett. 1997, 38, 3985-3988. Oueslati,
I.; Abidi, R.; Thue´ry, P.; Nierlich, M.; Asfari, Z.; Harrowfield, J .; Vicens,
J . Tetrahedron Lett. 2000, 41, 8263-8267. Balazs, B.; Toth, G.;
Horvath, G.; Gru¨n, A.; Csokai, V.; To¨ke, L.; Bitter, I. Eur. J . Org. Chem.
2001, 61-71. Abidi, R.; Oueslati, I.; Amri, H.; Thue´ry, P.; Nierlich,
M.; Asfari, Z.; Vicens, J . Tetrahedron Lett. 2001, 42, 1685-1689.
Tuntulani, T.; Poompradub, S.; Thavornyutikarn, P.; J aiboon, N.;
Ruangpornvisuti, V.; Chaichit, N.; Asfari, Z.; Vicens, J . Tetrahedron
Lett. 2001, 42, 5541-5544. He, Y.; Xiao, Y.; Meng, L.; Zeng, Z.; Wu,
X.; Wu, C.-T. Tetrahedron Lett. 2002, 43, 6249-6253.
† URCOM, Universite´ du Havre. Tel.: +332 32 74 43 94. Fax: +332
32 74 43 91.
‡ Laboratoire de Chimie et Biochimie Pharmacologiques et Toxi-
cologiques, UMR CNRS 8601. Tel.: +331 42 86 21 83. Fax: +331 42
86 83 87.
(5) Chen, Y.; Chen, Y. Tetrahedron Lett. 2000, 41, 9079-9082. Chen,
Y.-K.; Chen, Y.-Y. Org. Lett. 2000, 2, 743-745.
(1) C. D. Gutsche, Calixarenes Revisited, Monographs in Supramo-
lecular Chemistry; Stoddart, J . F., Ed.; The Royal Society of Chemis-
try: Cambridge, U.K., 1998.
(6) For other examples of covalently bridged calix[6]arenes, see: (a)
Otsuka, H.; Shinkai, S. J . Am. Chem. Soc. 1996, 118, 4271-4275. (b)
Ross, H.; Lu¨ning, U. Tetrahedron Lett. 1997, 38, 4539-4542. (c) Akine,
S.; Goto, K.; Kawashima, T. Tetrahedron Lett. 2000, 41, 897-901. (d)
Lo¨ffler, F.; Lu¨ning, U.; Gohar, G. New J . Chem. 2000, 24, 935-938.
(7) See ref 6a. Grynszpan, F.; Aleksiuk, O.; Biali, S. E. J . Chem.
Soc., Chem. Commun. 1993, 13-16. Takeshita, M.; Nishio, S.; Shinkai,
S. J . Org. Chem. 1994, 59, 4032-4034. Araki, K.; Akao, K.; Otsuka,
H.; Nakashima, K.; Inokuchi, F.; Shinkai, S. Chem. Lett. 1994, 1251-
1254. J ansenn, R. G.; Verboom, W.; van Duynhoven, J . P. M.; van
Velzen, E. J . J .; Reinhoudt, D. N. Tetrahedron Lett. 1994, 35, 6555-
6558. Otsuka, H.; Araki, K.; Matsumoto, H.; Harada, T.; Shinkai, S.
J . Org. Chem. 1995, 60, 4862-4867. Nam, K. C.; Choi, Y. J .; Kim, D.
S.; Kim, J . M.; Chun, J . C. J . Org. Chem. 1997, 62, 6441-6443. Chen,
Y.-Y.; Li, J .-S.; Zhong, Z.-L.; Lu, X.-R. Tetrahedron 1998, 54, 15183-
15188. Li, J .-S.; Chen, Y.-Y.; Lu, X.-R. Eur. J . Org. Chem. 2000, 485-
490. Zhang, Y.; Yuan, H.; Huang, Z.; Zhou, J .; Kawanishi, Y.; Schatz,
J .; Maas, G. Tetrahedron 2001, 57, 4161-4165.
(2) For leading references, see: Blanchard, S.; Le Clainche, L.;
Rager, M.-N.; Chansou, B.; Tuchagues, J .-P.; Duprat, A. F.; Le Mest,
Y.; Reinaud, O. Angew. Chem., Int. Ed. 1998, 37, 2732-2735. Se´ne`que,
O.; Rager, M.-N.; Giorgi, M.; Reinaud, O. J . Am. Chem. Soc. 2000, 122,
6183-6189. Le Clainche, L.; Rondelez, Y.; Se´ne`que, O.; Blanchard, S.;
Campion, M.; Giorgi, M.; Duprat, A. F.; Le Mest, Y.; Reinaud, O. C. R.
Acad. Sci. Paris, Se´rie IIc: Chem. 2000, 3, 811-819. Rondelez, Y.;
Se´ne`que, O.; Rager, M.-N.; Duprat, A. F.; Reinaud, O. Chem. Eur. J .
2000, 6, 4218-4226. Le Clainche, L.; Giorgi, M.; Reinaud, O. Inorg.
Chem. 2000, 39, 3436-3437. Rondelez, Y.; Rager, M.-N.; Duprat, A.
F.; Reinaud O. J . Am. Chem. Soc. 2002, 124, 1334-1340.
(3) Se´ne`que, O.; Giorgi, M.; Reinaud, O. Chem. Commun. 2001, 984-
985. Se´ne`que, O.; Rager, M.-N.; Giorgi, M.; Reinaud, O. J . Am. Chem.
Soc. 2001, 123, 8442-8443. Rondelez, Y.; Bertho, G.; Reinaud, O.;
Angew. Chem., Int. Ed. 2002, 41, 1044-1046.
10.1021/jo026642h CCC: $25.00 © 2003 American Chemical Society
Published on Web 03/29/2003
3416
J . Org. Chem. 2003, 68, 3416-3419

First C3v-Symmetrical Calix[6](aza)crown
SCHEME 1a
field shift of the methoxy protons of compounds 4 and 6
(δOMe ) 2.27 and 2.07, respectively) indicates that these
groups are included inside the cavity, projecting the bulky
ethyl ester or tosyl groups outside. In the case of calix-
[6]arene 5, the methoxy groups present a quasi-normal
resonance (δOMe ) 3.47) suggesting that they are involved
in an intramolecular hydrogen bonding network with the
hydroxylated arms. This was confirmed by the high-field
shift observed for these groups (δOMe ) 3.01) when a
protic solvent (CD3OD) was added. It is also noteworthy
that, in contrast to compounds 4 and 5, sharp signals
are observed for the ArCH2Ar methylene protons of tris-
tosyl calix[6]arene 6 (two doublets at 3.29 and 4.40 ppm).
It shows that, with these bulky tosyl arms, the cone-cone
interconversion of 6 is slower than the NMR time scale.
a
(i) (o)NO2BsCl, TEA, THF, 0 °C then rt, 76%.
alkylation reaction.8 Thus, to obtain the desired triply
bridged calix[6]arene, we chose to attempt the tris-
alkylation reaction between the trianion of a tris-aryl-
sulfonamide derivative of tris(2-aminoethyl)amine (tren)
1 and a tris-tosylcalix[6]arene derivative. For this pur-
pose, we first prepared the tris-protected tren 2 by the
reaction between tren 1 and 3.4 equiv of 2-nitrobenze-
nesulfonyl chloride in the presence of triethylamine (76%
yield) (Scheme 1). The 2-nitrobenzenesulfonyl-protected
group [(o)NO2Bs] was chosen instead of the more classical
tosyl one because it can be removed under milder
conditions. It is noteworthy that compound 2 is an
amorphous and hygroscopic solid that we were unable
to recrystallize; consequently it was only purified by flash
chromatography on silica gel.
The required tris-tosyl calix[6]arene was prepared from
the known X6H3Me3 39 [obtained by selective 1,3,5-
trimethylation of p-tBu-calix[6]arene (X6H6)10] in an
efficient three-step sequence (54% overall yield). First,
X6H3Me3 3 was converted into the triester derivative 4
by alkylation with an excess of ethylbromoacetate in the
presence of NaH in 77% yield.11 A subsequent reduction
by LAH afforded the tris-hydroxy derivative 5 in 82%
yield. The latter was reacted at low temperature with
an excess of TsCl in a mixture of anhydrous pyridine and
chloroform, giving the tris-tosyl calix[6]arene 6 in 86%
yield (Scheme 2). This reaction necessitated careful
attention to the reaction conditions (essentially the low
temperature and reaction time), otherwise unidentified
calixarene-type byproducts were formed, lowering the
yield. The 1H NMR spectra of compounds 4, 5, and 6,
recorded at 298 K in CDCl3, are characteristic of a major
flattened cone conformation of C3v symmetry.12 The high-
Key-step formation of the triply bridged calix[6]arene
was conducted under standard conditions, reacting 6 and
2 in the presence of Cs2CO3 as a base in DMF. After flash
chromatography on silica gel, the expected capped calix-
[6]arene 7 was isolated in 31% yield. Finally, deprotection
of the amino groups was performed by SNAr substitution
of the (o)NO2Bs groups by thiophenate, giving rise to the
desired calix[6]azacrown 8 (X6Me3tren) with a 75% yield
(Scheme 2).
The 1H NMR spectra of capped calixarenes 7 and 8 are
displayed in Figure 1. Their profiles are remarkably
simple, attesting to a major C3v-symmetrical rigid cone
conformation. Evidence for the rigidification of the cone
conformation due to the capping is given by the sharp
and well-defined signals corresponding to the ArCH2Ar
methylene protons. Some unusual features, however, are
specifically observed for compound 8. Its methoxy groups
are less high-field shifted than for compound 7 (δOMe
)
3.05 instead of 2.40 ppm), suggesting that they are more
distant from the C3 axis. The very small difference of
resonance between the two tBu signals of 8 (∆δtBu ) 0.02
ppm) also indicates that all tBu groups have similar
orientations. This stands in contrast to the classical
alternate in and out positions adopted by the tBu groups
SCHEME 2a
a
(i) Ethylbromoacetate, NaH, THF, reflux, 77%. (ii) LAH, ether, reflux, 82%. (iii) TsCl, pyridine, CHCl3, -20 °C, 86%. (iv) 2, Cs2CO3,
DMF, rt then 90 °C, 31%. (v) PhSH, Na2CO3, DMF, 50 °C, 75%.
J . Org. Chem, Vol. 68, No. 9, 2003 3417

J abin and Reinaud
F IGURE 1. 1H NMR spectra of compounds 7 (R ) (o)NO2Bs, top) and 8 (R ) H, bottom) in CDCl3 at 298 K: (+) residual water
or solvent peaks (CHCl3 and CH3CN; this latter was present in elemental analysis characterization of compound 8).
of calixarenes with the same symmetry13 (for example,
∆δtBu ) 0.51, 0.37, 0.63, and 0.47 ppm for calixarenes 4,
5, 6 and 7, respectively). This shows that the skeleton of
calix[6]azacrown 8 has a more straight and regular cone
conformation. As in the case of compound 5, these
features might well be due to the establishment of
hydrogen bonds between the anisole units and their
neighboring phenoxy protic substituents, namely, the
tren-NH groups in the case of 8. Indeed, addition of CD3-
OD induced a split of the tBu resonances attesting to a
conformational change. Finally, a variable temperature
1H NMR study showed some broadening of the spectra
at low temperature. However, the axial and equatorial
ArCH2Ar methylene protons were differentiated over the
whole temperature range (240-330 K), indicating that
the cone-cone inversion did not occur on the NMR time
scale.
Exp er im en ta l Section
Gen er a l P r oced u r es. THF and ether were distilled over
sodium/benzophenone under argon. Pyridine was distilled over
KOH under argon. Chloroform was distilled over P2O5 under
argon. DMF was distilled over MgSO4 and stored over 4 Å
molecular sieves under argon. TsCl was recrystallized (dichlo-
romethane/pentane) before use. 1H and 13C NMR spectra were
recorded at, respectively, 200 and 50 MHz. Thin-layer chro-
matographies (TLC) were performed with aluminum plates
(0.20 mm) precoated with fluorescent silica gel. Reaction
components were then visualized under UV light and dipped
in a Dragendorff solution. Silica gel (230-400 mesh) was used
for flash chromatography separations. All reactions were
performed under an inert atmosphere. Elemental analyses
were performed at the Laboratoire de Microanalyse Organique,
IRCOF, France.
N,N′,N′′-Tr i-2-n it r ob en zen esu lfon yl-2,2′,2′′-n it r ilot r i-
eth yla m in e 2. At 0 °C, TEA (3.9 mL, 27.75 mmol) was added
to a solution of tren (1.0 mL, 6.68 mmol) in 20 mL of anhydrous
THF. (o)NO2BsCl (5.03 g, 22.7 mmol) was added by small
portions over the course of 20 min time, and then the reaction
mixture was stirred for 16 h at room temperature. After
removal of the solvent under reduced pressure, addition of
water, and extraction with dichloromethane, the resulting
crude residue was purified by flash chromatography, yielding
2 (3.56 g, 76%) as an amorphous yellow solid that we were
unable to recrystallize. Mp: 85-88 °C (decomp). IR (CHCl3):
In conclusion, we have described the synthesis of the
1
first C3v-symmetrical calix[6](aza)crown 8. A H NMR
study has shown that the alternate 1,3,5-azabridge at the
small rim rigidifies the whole edifice, preventing ring
inversion and constraining the calixarene core in a
straight cone conformation. The ability of this novel
ligand to coordinate a metal ion together with its host-
guest properties (neutral or charged molecules recogni-
tion) are under intense investigation.
1
ν 3340, 1542, 1362 cm-1. H NMR (CDCl3): δ 2.63 (t, J ) 5.5
Hz, 6H), 3.10 (q, J ) 5.5 Hz, 6H), 5.76 (t, J ) 5.5 Hz, 3H),
7.69-7.87 (m, 9H), 8.04-8.13 (m, 3H). 13C NMR (CDCl3): δ
41.77, 54.78, 125.7, 131.0, 133.1, 133.2, 133.9, 148.2. MS (FAB)
m/z: 702.4 (M - H+, calcd 702.1).
(8) Macrocycle Synthesis, a Practical Approach; Parker, D., Ed.;
Oxford University Press: New York, 1996.
(9) J anssen, R. G.; Verboom, W.; Reinhoudt, D. N.; Casnati, A.;
Freriks, M.; Pochini, A.; Uggozoli, F.; Ungaro, R.; Nieto, P. M.;
Carramolino, M.; Cuevas, F.; Prados, P.; de Mendoza, J . Synthesis
1993, 380-385.
(10) Gutsche, C. D.; Dhawan, B.; Leonis, M.; Stewart, D. Org. Synth.
1990, 68, 238-242.
(11) Takeshita, M.; Shinkai, S. Chem. Lett. 1994, 1349.
(12) The 1H NMR spectrum of 6 revealed the presence of minor
conformational isomers.
(13) Se´ne`que, O.; Rondelez, Y.; Le Clainche, L.; Inisan, C.; Rager,
M.-N.; Giorgi, M.; Reinaud, O. Eur. J . Inorg. Chem. 2001, 2597-2604.
5,11,17,23,29,35-H exa -ter t-b u t yl-37,39,41-t r im et h oxy-
38,40,42-tr is(2-h yd r oxyeth oxy)ca lix[6]a r en e 5. To a solu-
tion of 4 (4.15 g, 3.26 mmol) in 350 mL of anhydrous Et2O
was added LAH (1.43 g, 37.6 mmol) at -4 °C. After 16 h of
refluxing, the reaction mixture was cooled to 0 °C and 50 mL
of an aqueous solution of HCl (4 M) was added slowly. After
dichloromethane (500 mL) extraction, the organic layer was
washed twice with 50 mL of an aqueous solution of HCl (4
M). The solvent was removed under reduced pressure, and the
resulting residue was dissolved in 200 mL of chloroform. The
3418 J . Org. Chem., Vol. 68, No. 9, 2003

First C3v-Symmetrical Calix[6](aza)crown
insoluble material was removed by filtration and the chloro-
form was removed under reduced pressure, giving a white solid
that was purified by recrystallization in ethanol. Thus, pure
compound 5 (3.06 g, 82%) was obtained as a white solid. Mp:
CHCl3. Mp: 264 °C (decomp). IR (CHCl3): ν 1546, 1481, 1372,
1167 cm-1 1H NMR (CDCl3): δ 0.87 (s, 27H), 1.34 (s, 27H),
.
2.40 (s, 9H), 2.88-3.05 (m, 6H), 3.06 (d, J ) 14.1 Hz, 6H),
3.89-4.10 (m, 12H), 4.11-4.20 (m, 6H), 4.37 (d, J ) 14.1 Hz,
6H), 6.88 (s, 6H), 7.20 (s, 6H), 7.22-7.50 (m, 9H), 8.27 (d, J )
7.8 Hz, 3H). 13C NMR (CDCl3): δ 28.73, 31.08, 31.76, 34.22,
34.37, 48.67, 49.10, 54.69, 61.20, 73.48, 115.4, 123.8, 124.0,
127.7, 131.3, 132.4, 133.1, 133.3, 133.6, 133.9, 146.3, 146.5,
147.8, 150.0, 154.5. Anal. Calcd for C99H123N7O18S3, H2O: C,
65.58; H, 6.95; N, 5.41. Found: C, 65.82; H, 7.18; N, 5.88.
X6Me3tr en 8. Na2CO3 (0.604 g, 5.70 mmol) was added to a
solution of 7 (0.641 g, 0.357 mmol) in 30 mL of anhydrous DMF
at room temperature. The reaction mixture was vigorously
stirred, and thiophenol (0.293 mL, 2.85 mmol) was added,
leading to a greenish coloration. After 24 h at 50 °C, the DMF
was removed under reduced pressure and 50 mL of an aqueous
solution of NaOH (1 M) was added. After dichloromethane
extraction and concentration, the resulting residue was dis-
solved in 3 mL of dichloromethane, and 5 mL of acetonitrile
was added. The resulting precipitate was isolated by suction
filtration and washed twice with acetonitrile giving 8 (0.330
g, 75%) as a white solid. Mp: 251-252 °C (decomp). IR
(CHCl3): ν 3660 to 3110, 1480 cm-1. 1H NMR (CDCl3): δ 1.06
(s, 27H), 1.08 (s, 27H), 2.58 (m, 6H), 2.82 (m, 6H), 2.92 (m,
6H), 3.05 (s, 9H), 3.41 (d, J ) 14.9 Hz, 6H), 3.92 (m, 6H), 4.49
(d, J ) 14.9 Hz, 6H), 6.93 (s, 6H), 7.04 (s, 6H). 13C NMR
(CDCl3): δ 30.08, 31.44, 31.49, 34.17, 34.24, 48.80, 49.79, 55.25,
61.00, 73.54, 125.6, 126.2, 133.2, 133.4, 145.7, 145.9, 152.4,
154.2. Anal. Calcd for C81H114N4O6, 2.5 H2O, 0.5 CH3CN: C,
75.45; H, 9.30; N, 4.83. Found: C, 75.34; H, 9.17; N, 4.78.
1
227 °C (decomp). IR (CHCl3): ν 3660 to 3120, 1480 cm-1. H
NMR (CDCl3): δ 0.91 (s, 27H), 1.28 (s, 27H), 3.30 (sl, 6H), 3.43
(sl, 6H), 3.47 (s, 9H), 3.92 (sl, 12H), 6.65 (s, 6H), 7.13 (s, 6H).
13C NMR (CDCl3): δ 30.90, 31.36, 31.64, 34.12, 34.15, 34.31,
60.33, 61.73, 75.23, 124.4, 127.2, 133.1, 133.2, 145.8, 146.2,
153.2, 153.4. Anal. Calcd for C75H102O9, 2 EtOH: C, 76.54; H,
9.27. Found: C, 76.74; H, 9.04.
5,11,17,23,29,35-H exa -ter t-b u t yl-37,39,41-t r im et h oxy-
38,40,42-tr is(2-tosyleth oxy)ca lix[6]a r en e 6. TsCl (0.997 g,
5.23 mmol) was added to a solution of 5 (1.00 g, 0.87 mmol) in
1 mL of anhydrous CHCl3, and then, at -10 °C, anhydrous
pyridine (3.0 mL, 36.79 mmol) was slowly added under
vigorous stirring. The flask containing the reaction mixture
was placed in a freezer at -20 °C for 16 h. The solvents were
removed under high vacuum, and 10 mL of ethanol was added
to the crude residue. The resulting solid was isolated by
filtration and washed twice with cold ethanol, yielding com-
pound 6 (1.20 g, 86%) as a white solid. Mp: 153-154 °C. IR
1
(CHCl3): ν 1598, 1482, 1361, 1175 cm-1. H NMR (CDCl3): δ
0.74 (s, 27H), 1.37 (s, 27H), 2.07 (s, 9H), 2.37 (s, 9H), 3.29 (d,
J ) 15.6 Hz, 6H), 4.11 (t, J ) 4.7 Hz, 6H), 4.40 (d, J ) 14.9
Hz, 6H), 4.42 (t, J ) 4.7 Hz, 6H), 6.58 (s, 6H), 7.21 (s, 6H),
7.28 (d, J ) 7.8 Hz, 6H), 7.82 (d, J ) 7.8 Hz, 6H). 13C NMR
(CDCl3): δ 21.77, 29.67, 31.18, 31.76, 34.06, 34.36, 60.05, 68.97,
70.16, 123.7, 128.1, 130.1, 132.9, 133.5, 145.2, 146.0, 146.3,
151.1, 154.4. Anal. Calcd for C96H120O15S3, 2 H2O: C, 70.04;
H, 7.59. Found: C, 70.37; H, 7.22.
Ca p p ed Ca lix[6]a r en e 7. Cs2CO3 (0.815 g, 2.50 mmol) was
added to a solution of 6 (1.152 g, 0.715 mmol) in 25 mL of
anhydrous DMF at room temperature. The reaction mixture
was vigorously stirred, and a solution of 2 (0.506 g, 0.721
mmol) in 25 mL of anhydrous DMF was slowly added (for 1 h)
at room temperature. After 2 h at room temperature the
reaction mixture was heated at 90 °C for 16 h. The DMF was
removed under reduced pressure, and 50 mL of water was
added. After dichloromethane extraction and concentration,
flash chromatography (dichloromethane/EtOAc, 99:1 then 98:
2) afforded 7 (0.398 g, 31%) as a yellow solid. An analytical
sample was obtained by recrystallization in a mixture of EtOH/
Ack n ow led gm en t. We thank Marie-Noe¨lle Rager
(Ecole Nationale Supe´rieure de Chimie de Paris) for the
variable temperature NMR experiments and the Labo-
ratoire de Spectrome´trie de Masse, (Universite´ de
Rouen, IRCOF) for the FAB mass spectrum.
Su p p or t in g In for m a t ion Ava ila b le: 1H and 13C NMR
spectra of compounds 2, 5, and 6 and 13C NMR spectra of
compounds 7 and 8. This material is available free of charge
via the Internet at http://pubs.acs.org.
J O026642H
J . Org. Chem, Vol. 68, No. 9, 2003 3419