Selective synthesis and isolation of all possible conformational isomers of proximally para-disubstituted calix[4]arene

Article abstract of DOI:10.1021/jo0267293

All six possible conformational isomers of the proximally p-dibrominated calix[4]arene tetraalkyl ether, 1a-f*, were selectively synthesized by appropriate control of stereochemistry during di-O-alkylation reactions of 5,11-dibromocalix[4]arene syn-dialky

Full text of DOI:10.1021/jo0267293

Selective Syn th esis a n d Isola tion of All P ossible Con for m a tion a l
Isom er s of P r oxim a lly P a r a -Disu bstitu ted Ca lix[4]a r en e
Shoichi Shimizu,* Akihiro Moriyama, Katsuyuki Kito, and Yasuyuki Sasaki
Department of Applied Molecular Chemistry and High Technology Research Center,
College of Industrial Technology, Nihon University, Narashino, Chiba 275-8575, J apan
s5simizu@cit.nihon-u.ac.jp
Received November 17, 2002
All six possible conformational isomers of the proximally p-dibrominated calix[4]arene tetraalkyl
ether, 1a -f*, were selectively synthesized by appropriate control of stereochemistry during di-O-
alkylation reactions of 5,11-dibromocalix[4]arene syn-dialkyl ethers, namely, 5,11-dibromo-27,28-
dihydroxy-25,26-dipropoxy-, 5,11-dibromo-25,26-dihydroxy-27,28-dipropoxy-, 5,11-dibromo-25,28-
dihydroxy-26,27-propoxy-, and 5,11-dibromo-26,28-dihydroxy-25,27-dipropoxycalix[4]arenes. Their
1
conformations were confirmed by H and 13C NMR spectroscopy and are cone for 1a (u BrPr, uBr
,
Pr
uHPr,uHPr), partial cone for 1b* (u BrPr, dBrPr, uHPr,uHPr) and 1d * (u BrPr, uBrPr, uHPr,dHPr), 1,2-alternate
for 1c (u BrPr, uBrPr, dHPr,dHPr) and 1e* (u BrPr, dBrPr, dHPr,uHPr), and 1,3-alternate for 1f* (u BrPr, dBr
,
Pr
uHPr,dHPr). Although both 1c and 1e* are in the 1,2-alternate conformation, the conformation of
1e* was found to be strongly distorted and distinct from that of 1c.
In tr od u ction
the procedures for the stereoselective synthesis of par-
ticular conformers have been well-established.2
A large number of papers have appeared dealing with
calixarenes, the third generation of supramolecules after
cyclodextrins and crown ethers, especially regarding their
structure and functionalization, since they are readily
available from cheap starting materials and represent
very attractive building blocks for the design of more
sophisticated molecules with specific properties.1 Among
the parent compounds, calix[4]arenes have received the
most attention due to their unique cavity-shaped archi-
tecture. A number of synthetic procedures for the selec-
tive functionalization of calix[4]arenes either at the
positions of endo hydroxyl groups (endo positions) or at
the para positions (exo positions) have been developed
during the past two decades, and considerable effort has
been directed toward understanding the factors that
control the conformational outcome under certain reac-
tion conditions. Consequently, a variety of calix[4]arenes
having pair(s) of functional groups on the endo positions
and/or on the exo positions with a distal (1,3- or A,C-)
regiochemistry have become available and, in some cases,
On the contrary, much less attention has been paid to
calix[4]arenes with a proximal (1,2- or A,B-) regio-
chemistry.3-6 In particular, only a limited number of 1,2-
disubstituted and 1,2-bridged calix[4]arenes at the exo
positions have been reported.5,6,10f,i For example, 5,11-
diphenyl- and 5,11-dimethyl-17,23-di-tert-butylcalix[4]-
arenes can be prepared by a multistep process5a and/or
a fragment condensation of suitable dimers.5b On the
other hand, 5,11-dinitrocalix[4]arene tetrapropyl ether,5c
5,11-di-tert-butyl-17,23-dinitrocalix[4]arene tetrapropyl
ether,5d and 5,11-diformylcalix[4]arene tetraoctyl ether5h
are separated from a mixture of their regioisomers. In
addition, 5,11-dibromocalix[4]arene tetrapropyl ether5j
can be prepared by a regioselective bromination, based
on differences in reactivity para to the free phenolic
(2) For 1,3-disubstituted and bridged calix[4]arenes, see ref 1g,
Chapter 5.
(3) For 1,2-disubstituted calix[4]arenes on endo positions, see: (a)
Bottino, F.; Giunta, L.; Pappalardo, S. J . Org. Chem. 1989, 54, 5407-
5409. (b) Groenen, L. C.; Rue¨l, B. H. M.; Casnati, A.; Timmerman, P.;
Verboom, W.; Harkema, S.; Pochini, A.; Ungaro, R.; Reinhoudt, D. N.
Tetrahedron Lett. 1991, 32, 2675-2678. (c) See: K. A.; Fronczek, F.
R.; Waston, W. H.; Kashyap, R. P.; Gutsche, C. D. J . Org. Chem. 1991,
56, 7256-7268. (d) Gutsche, C. D.; Reddy, P. A. J . Org. Chem. 1991,
56, 4783-4791. (e) Araki, K.; Iwamoto, K.; Shigematsu, S.; Shinkai,
S. Chem. Lett. 1992, 1095-1098. (f) Brunink, J . A. J .; Verboom, W.;
Engbersen, J . F. J .; Harkema, S.; Reinhoudt, D. N. Recl. Trav. Chim.
Pays-Bas 1992, 111, 511-516. (g) Pappalardo, S.; Giunta, L.; Foti, M.;
Ferguson, G.; Gallagher, J . F.; Kaitner, B. J . Org. Chem. 1992, 57,
2611-2624. (h) Park, Y. J .; Shin, J . M.; Nam, K. C.; Kim, J . M.; Kook,
S.-K. Bull. Korean Chem. Soc. 1996, 17, 643-647. (i) Shu, C.-m.; Yuan,
T.-s.; Ku, M.-c.; Ho, Z.-c.; Liu, W.-c.; Tang, F.-s.; Lin, L.-g. Tetrahedron
1996, 52, 9805-9818. (j) Pappalardo, S. New. J . Chem. 1996, 20, 465-
472. (k) Markovsky, L. N.; Viscotsky, M. A.; Pirozhenko, V. V.;
Kalchenko, V. I.; Lipkowski, J .; Yu, A. Chem. Commun. 1996, 69-71.
(l) Dieleman, C. B.; Marsol, C.; Matt, D.; Kyritsakas, N.; Harriman,
A.; Kintzinger, J .-P. J . Chem. Soc., Dalton Trans. 1999, 4139-4148.
(m) Bochen˜ska, M.; Banach, R.; Zielin˜ska, A.; Kravtsov, V. Ch. J .
Inclusion Phenom. Macrocycl. Chem. 2001, 39, 219-228.
* To whom correspondence should be addressed. Phone: +81-47-
474-2568. Fax: +81-47-474-2579.
(1) For representative reviews on calixarenes, see: (a) Gutsche, C.
D. Calixarenes; Monographs in Supramolecular Chemistry; Stoddart,
J . F., Ed.; The Royal Society of Chemistry: Cambridge, UK, 1989. (b)
Calixarenes: A Versatile Class of Macrocyclic Compounds; Topics in
Inclusion Science 3; Vicens, J ., Bo¨hmer, V., Eds.; Kluwer: Dordrecht,
The Netherlands, 1991. (c) Shinkai, S. Tetrahedron 1993, 49, 8933-
8968. (d) Takeshita, M.; Shinkai, S. Bull. Chem. Soc. J pn. 1995, 68,
1088-1097. (e) Bo¨hmer, V. Angew. Chem. 1995, 107, 785; Angew.
Chem., Int. Ed. Engl. 1995, 34, 713-745. (f) Pochini, A.; Ungaro, R.
In Comprehensive Supramolecular Chemistry; Vo¨gtle, F., Ed.; Perga-
mon Press: Oxford, UK, 1996; Vol. 2, pp 103-142. (g) Gutsche, C. D.
Caixarenes Revisited; Monographs in Supramolecular Chemistry;
Stoddart, J . F., Ed.; The Royal Society of Chemistry: Cambridge, UK,
1998. (h) Calixarenes in Action; Mandolini, L., Ungaro, R., Eds.;
Imperial College Press: London, UK, 2000. (i) Calixarenes 2001; Asfari,
Z., Bo¨hmer, V., Harrowfield, J ., Vicens, J ., Eds.; Kluwer: Dordrecht,
The Netherlands, 2001.
10.1021/jo0267293 CCC: $25.00 © 2003 American Chemical Society
Published on Web 02/14/2003
J . Org. Chem. 2003, 68, 2187-2194
2187

Shimizu et al.
groups versus ethers.5e,j,7,10f,i However, no conformational
study of calix[4]arenes with a proximal regiochemistry
appears to have been conducted, in contrast to those with
a distal regiochemistry.
CHART 1
We describe herein the selective synthesis and isolation
of all possible conformational isomers of 5,11-dibromocalix-
(4) For 1,2-bridged calix[4]arenes at endo positions, see: (a) Arduini,
A.; Casnati, A.; Dodi, L.; Pochini, A.; Ungaro, R. J . Chem. Soc., Chem.
Commun. 1990, 1597-1598. (b) van Loon, J .-D.; Kraft, D.; Ankone´,
M. J . K.; Verboom, W.; Harkema, S.; Vogt, W.; Bo¨hmer, V.; Reinhoudt,
D. N. J . Org. Chem. 1990, 55, 5176-5179. (c) Yamamoto, H.; Sakaki,
T.; Shinkai, S. Chem. Lett. 1994, 469-472. (d) Arduini, A.; Fabbi, M.;
Mantovani, M.; Mirone, L.; Pochini, A.; Secchi, A.; Ungaro, R. J . Org.
Chem. 1995, 60, 1454-1457. (e) Pappalardo, S.; Petringa, A.; Parisi,
M. F.; Ferguson, G. Tetrahedron Lett. 1996, 37, 3907-3910. (f) Arduini,
A.; McGregor, W. M.; Paganuzzi, D.; Pochini, A.; Secchi, A.; Ugozzoli,
F.; Ungaro, R. J . Chem. Soc., Perkin Trans. 2 1996, 839-846. (g)
Arnaud-Neu, F.; Caccamese, S.; Fuangswasdi, S.; Pappalardo, S.;
Parisi, M. F.; Petringa, A.; Principato, G. J . Org. Chem. 1997, 62,
8041-8048. (h) Arduini, A.; Domiano, L.; Pochini, A.; Secchi, A.;
Ungaro, R.; Ugozzoli, F.; Struck, O.; Verboom, W.; Reinhoudt, D. N.
Tetrahedron 1997, 53, 3767-3776. (i) Arnaud-Neu, F.; Ferguson, G.;
Fuangswasdi, S.; Notti, A.; Pappalardo, S.; Parisi, M. F.; Petringa, A.
J . Org. Chem. 1998, 63, 7770-7779. (j) Ferguson, G.; Lough, A. J .;
Notti, A.; Pappalardo, S.; Parisi, M. F.; Petringa, A. J . Org. Chem. 1998,
63, 9703-9710. (k) Ozerov, O. V.; Ladipo, F. T.; Patrik, B. O. J . Am.
Chem. Soc. 1999, 121, 7941-7942. (l) Arduini, A.; Bo¨hmer, V.; Delmau,
L.; Desreux, J .-F.; Dozol, J .-F.; Carrera, M. A. G.; Lambert, B.;
Musigmann, C.; Pochini, A.; Shivanyuk, A.; Ugozzoli, F. Chem. Eur.
J . 2000, 6, 2135-2144. (m) Narumi, F.; Morohashi, N.; Matsumura,
N.; Iki, N.; Kameyama, H.; Miyano, S. Tetrahedron Lett. 2002, 43, 621-
625. (n) Mathieu, A.; Asfari, Z.; Vicens, J . Tetrahedron Lett. 2002, 43,
1225-1229.
(5) For 1,2-disubstituted calix[4]arenes on exo positions, see: (a) Ho,
K. H.; Gutsche, C. D. J . Org. Chem. 1982, 47, 2713-2719. (b) Bo¨hmer,
V.; Merkel, L.; Kunz, U. J . Chem. Soc., Chem. Commun. 1987, 896-
897. (c) Kelderman, E.; Derhaeg, L.; Heesink, G. J . T.; Verboom, W.;
Engbersen, J . F. J .; van Hulst, N. F.; Persoons, A.; Reinhoudt, D. N.
Angew. Chem. 1992, 104, 1107; Angew. Chem., Int. Ed. Engl. 1992,
31, 1075-1077. (d) Verboom, W.; Durie, A.; Egberink, R. J . M.; Asfari,
Z.; Reinhoudt, D. N. J . Org. Chem. 1992, 57, 1313-1316. (e) Pappa-
lardo, S.; Giunta, L.; Foti, M.; Ferguson, G.; Gallagher, J . F.; Kaitner,
B. J . Org. Chem. 1992, 57, 2611-2624. (f) Timmerman, P.; Verboom,
W.; van Veggel, F. C. J . M.; van Hoorn, W. P.; Reinhoudt, D. N. Angew.
Chem. 1994, 106, 1313; Angew. Chem., Int. Ed. Engl. 1994, 33, 1292-
1295. (g) Timmerman, P.; Verboom, W.; Reinhoudt, D. N.; Arduini,
A.; Grandi, S.; Sicuri, A. R.; Pochini, A.; Ungaro, R. Synthesis 1994,
185-189. (h) Arduini, A.; Fanni, S.; Manfredi, G.; Pochini, A.; Ungaro,
R.; Sicuri, A. R.; Ugozzoli, F. J . Org. Chem. 1995, 60, 1448-1453. (i)
Caccamese, S.; Bottino, A.; Cunsolo, F.; Parlato, S.; Neri, P. Tetrahe-
dron: Asymmetry 2000, 11, 3103-3112. (j) Gagnon, J .; Ve´zina, M.;
Drouin, M.; Harvey, P. D. Can. J . Chem. 2001, 79, 1439-1446.
(6) For 1,2-bridged calix[4]arenes at exo positions, see: Ikeda, A.;
Yoshimura, M.; Lhotak, P.; Shinkai, S. J . Chem. Soc., Perkin Trans. 1
1996, 1945-1950.
[4]arene tetrapropyl ether with a proximal regiochemis-
try, which are one cone (u BrPr, uBrPr, uHPr,uHPr), two partial
cone ((u BrPr, dBrPr, uHPr,uHPr) and (uBrPr, uBrPr, uHPr,dHPr)),
two 1,2-alternate ((u BrPr, uBrPr, dHPr,dHPr) and (u BrPr, dBr
dHPr,uHPr)), and one 1,3-alternate (u BrPr, dBrPr, uHPr,dH
,
Pr
)
Pr
conformers (Chart 1). It is well-known that p-bromocalix-
[4]arenes are useful intermediates, since bromine-to-
lithium exchange reactions proceed selectively and offer
a simple route to substituted calix[4]arenes with a variety
of functionalities8 and regiocontrol at the para positions.9
In addition, the four conformational isomers of 5,11-
dibromocalix[4]arene tetrapropyl ether, namely two par-
tial, one 1,2-alternate, and one 1,3-alternate conformers,
are inherently chiral.5i,10 The rest, however, can serve as
versatile synthetic precursors to inherently chiral mol-
ecules with specific functionalities. Thus, the conforma-
tional isomers of 5,11-dibromocalix[4]arene tetraalkyl
ether represent very attractive building blocks for the
design of synthetic receptors with chiral discrimination
ability.
(7) van Loon, J .-D.; Arduini, A.; Verboom, W.; Ungaro, R.; van
Hummel, G. J .; Harkema, S.; Reinhoudt, D. N. Tetrahedron Lett. 1989,
30, 2681-2684.
(8) (a) Gutsche, C. D.; Pagoria, P. F. J . Org. Chem. 1985, 50, 5795-
5802. (b) Peak, K.-S.; Kim, H.-J .; Chang, S.-K. Supramol. Chem. 1995,
5, 83-85. (c) Ohseto, F.; Yamamoto, H.; Matsumoto, H.; Shinkai, S.
Tetrahedron Lett. 1995, 36, 6911-6914. (d) Ihm, H.; Paek, K. Bull.
Korean Chem. Soc. 1995, 16, 71-73. (e) Lhota´k, P.; Shinkai, S.
Tetrahedron Lett. 1996, 37, 645-648. (f) Larsen, M.; J ørgensen, M. J .
Org. Chem. 1997, 62, 4171-4173.
(9) (a) Larsen, M.; J ørgensen, M. J . Org. Chem. 1996, 61, 6651-
6655. (b) see ref 1g, pp 106-107.
Resu lts a n d Discu ssion
(10) For inherently chiral calix[4]arenes with dissymmetry or asym-
metry via substitution patters at exo and endo positions, see: (a)
Iwamoto, K.; Shimizu, H.; Araki, K.; Shinkai, S. J . Am. Chem. Soc.
1993, 115, 3997-4006 (Corrigendum 1993, 115, 12228) and references
therein. (b) Bo¨hmer, V.; Kraft, D.; Vogt, W. Supramol. Chem. 1994, 3,
299-301. (c) Ferguson, G.; Gallagher, J . F.; Giunta, L.; Neri, P.;
Pappalardo, S.; Parisi, M. J . Org. Chem. 1994, 59, 42-53. (d) Gonza´lez,
J . J .; Nieto, P. M.; Prados, P.; Echavarren, A. M.; de Mendoza, J . J .
Org. Chem. 1995, 60, 7419-7423. (e) Reference 4g and references
therein. (f) Vysotsky, M. O.; Tairov, M. O.; Pirozhenko, V. V.; Kal-
chenko, V. I. Tetrahedron Lett. 1998, 39, 6057-6060. (g) Shu, C.-M.;
Chung, W.-S.; Wu, S.-H.; Ho, Z.-C.; Lin, L.-G. J . Org. Chem. 1999, 64,
2673-2679. (h) Dieleman, C.; Steyer, S.; J eunesse, C.; Matt, D. J .
Chem. Soc., Dalton Trans. 2001, 2508-2517. (i) Tairov, M. A.;
Vysotsky, M. O.; Kalchenko, O. I.; Pirozhenko, V. V.; Kalchenko, V. I.
J . Chem. Soc., Perkin Trans. 1 2002, 1405-1411.
Syn th esis of P r oxim ally P ar a-Disu bstitu ted Calix-
[4]a r en e Dia lk yl Eth er s. As a working hypothesis, we
assumed that all six possible conformational isomers of
the proximally p-dibrominated calix[4]arene tetraalkyl
ether can be prepared by appropriate stereochemical
control during di-O-alkylation reactions of 5,11-dibromo-
calix[4]arene syn-dialkyl ethers. We thus synthesized all
four possible calix[4]arene syn-dipropyl ethers 5,5j 10,
12*,11 and 13* according to Scheme 1. Initially, 25,26-
(11) Inherently chiral calix[4]arenes are designated with an asterisk
(*).
2188 J . Org. Chem., Vol. 68, No. 6, 2003

Conformers of Proximally Para-Disubstituted Calix[4]arene
SCHEME 1a
by a syn-1,2-diallylation/hydrogenation sequence, af-
forded 9 as a precursor to the regioisomer 10. Treatment
of 9 with AlCl3 in toluene at 0 °C gave 10 in the cone
conformation in 89% yield, which contains two proximally
propylated phenol rings bearing bromine atoms at the
1
para position. The H NMR spectrum of regioisomer 10
was similar to that of 5 except for the inequivalency in
the chemical shift and the signal pattern in the aromatic
region. The 13C NMR spectrum showed peaks at δ 31.93,
31.86, and 29.88 for four methylene bridge carbons, all
of which indicates that 10 is the regioisomer, and is
present in the cone conformation.
The partial depropylation of 5 with trimethylsilyl
iodide afforded the inherently chiral 5,11-dibromo-
26,27,28-trihydroxy-25-propoxycalix[4]arene 11* in 94%
yield as a precursor to other remaining syn-dipropyl
ethers 12* and 13*. The 1H NMR spectrum of 11* showed
four doublets at δ 3.51, 3.42, 3.39, and 3.34, correspond-
ing to the equatorial protons of the methylene bridges,
and the 13C NMR spectrum showed peaks at δ 31.71,
31.65, 31.54, and 30.91 for the four pertinent carbons.
1
The values of the 13C NMR chemical shifts12 and H and
13C NMR spectral patterns indicate that 11* is present
in the cone conformation and is inherently chiral. Al-
though treatment of 11* with allyl bromide under 1,2-
di-O-alkylation conditions followed by hydrogenation
gave a mixture of two regioisomers 5 and 12* in the ratio
of 3:7, the desired syn-1,2-dipropyl ether 12* could be
isolated by recrystallization in 20% yield. This ratio
indicates that the acidity of the phenol rings substituted
with a bromine atom on the para position was enhanced
by the inductive effects of the bromine. Treatment of 11*
with propyl bromide under 1,3-di-O-alkylation conditions
selectively gave the syn-1,3-dipropyl ether 13* in 62%
yield. The proximally p-dibrominated calix[4]arene syn-
dipropyl ethers 12* and 13* in the cone conformation
exhibited the expected 1H and 13C NMR spectral patterns.
In particular, a set of four AB systems for ArCH2Ar in
the ratio 1:1:1:1 and four resonances for the pertinent
carbons at δ 32.43, 31.75, 31.33, and 29.95, and at δ
31.58, 31.43, 31.34, and 31.26 were observed for the
inherently chiral regioisomers 12* and 13*, respectively.
Alk yla t ion s of P r oxim a lly P a r a -Disu b st it u t ed
Ca lix[4]a r en e Dia lk yl Eth er s. To selectively prepare
all possible conformational isomers of the 5,11-dibromo-
calix[4]arene tetraalkyl ether, di-O-alkylations of 5,11-
dibromocalix[4]arene dialkyl ethers 5, 10, 12*, and 13*
were conducted under a variety of conditions. The results
of the reaction of calix[4]arene dialkyl ether 5 with propyl
bromide are summarized in Table 1. It is well-known that
the conformational outcome is dependent on reaction
conditions (temperature, solvent, and base), the para-
substituent of calix[4]arene, and the steric demands and
reactivity of the derivatizing reagent.1b,c,e-g The base in
particular can play a pivotal role in the alkylation
process. When NaH was used as a base, the cone
conformer 1a was the major product (86-97%) along with
the minor partial-cone conformer 1b* (14-3%) (entries
1-4). Reinhoudt and co-workers previously reported that
the tetra-O-alkylation of calix[4]arene 2 in DMF using
NaH as a base at room temperature proceeds via the syn-
1,2-dialkylated product,3b affording the tetra-O-alkylated
calix[4]arenes in the cone conformation.5c Our results are
consistent with these findings, because the use of syn-
a
Reagents and conditions: (a) allyl bromide, NaH, MeCN, rt;
(b) H2, Pd/C, THF, rt; (c) NBS, MEK, rt; (d) PrBr, NaH, DMF, 0
°C; (e) PrBr, Cs2CO3, DMF, 80 °C; (f) PrBr, t-BuOK, PhH, reflux;
(g) BnBr, NaH, MeCN, rt; (h) AlCl3, PhMe, 0 °C; (i) Me3SiI, CHCl3,
reflux; (j) PrBr, Ba(OH)2‚8H2O/BaO, DMF, rt; (k) PrBr, Cs2CO3,
acetone, reflux.
dihydroxy-27,28-dipropoxycalix[4]arene 45j in the cone
conformation as a precursor to 5, was obtained in high
purity by hydrogenation of 25,26-diallyloxy-27,28-di-
hydroxycalix[4]arene 3,3b,i prepared according to a modi-
fied literature method3i in 74% yield. Although the
synthetic procedure for the calix[4]arene syn-1,2-dipropyl
ether 4 via the proximal dipropylation of 2 has recently
been described,5j the purification of 4 in the cone confor-
mation could not be accomplished by recrystallization in
our hands. Proximal dibromination at the exo positions
of 4 was achieved through remote control exerted by a
functionality on the endo positions to afford 5 in 83%
yield. The proximally dibrominated calix[4]arene 5 in the
cone conformation exhibited the expected 1H and 13C
NMR spectral patterns for dual proximal fuctionaliza-
tions at the endo and exo positions. In particular, a set
of three AB systems for ArCH2Ar in the ratio 1:2:1 and
three resonances for the pertinent carbons at δ 31.77,
31.26, and 29.90 were observed.12
Regioisomer 10, the calix[4]arene syn-dipropyl ether
containing two adjacent aryl rings with a bromine atom
and an O-propyl group, was synthesized via proximally
dibenzylated calix[4]arene 6 as a key intermediate.
Proximal dibromination at the exo positions of 6, followed
(12) For a single rule in 13C NMR chemical shifts for determination
of calix[4]arene conformations, see: J aime, C.; de Mendoza, J .; Prados,
P.; Nieto, P. M.; Sa´nchez, C. J . Org. Chem. 1991, 56, 3372-3376.
J . Org. Chem, Vol. 68, No. 6, 2003 2189

Shimizu et al.
TABLE 1. P r op yla tion of Ca lix[4]a r en e 5a
rel. conformer distributionc/%
entry
baseb
NaH
NaH
NaH
solvent
time/h
temp/°C
yield/%
cone 1a
paco 1b*
1,2-alt 1c
1
2
DMF
DMF
DMF
CH3CN
DMF
C6H6
DMF
24
6
6
6
15
6
0
rt
reflux
rt
80
96
96
100
90
97
95
86
97
15
3
5
14
3
85
17
0
0
0
0
0
0
3
4d
5
NaH
e
Cs2CO3
99
6
7
t-BuOKf
reflux
80
96
0
83
0
e
Na2CO3
15
92g
(100)g
a
b
7.5 equiv of propyl bromide per OH were used. 7.5 equiv of base per OH were used under standard conditions. c The distribution
percentage was determined by 1H NMR analysis of the product mixture. Allyl bromide was used as an alkylating reagent, and the
d
products were then hydrogenated with Pd/C and H2 in THF. e 15 equiv of base per OH were used. f 2.0 equiv of base per OH were used.
g
Only tri-O-alkylated calix[4]arene was formed as a product.
1,2-dialkylated intermediate, that is, calix[4]arene dialkyl
ether 5, as a starting material led to the selective
formation of the cone conformation.
the di-O-alkylation of calix[4]arene syn-1,3-diethers14b,15
and tetra-O-alkylation of parent calix[4]arenes13,14c are
conducted with Cs2CO3 in THF/DMF, DMF, CH3CN, or
acetone. In the reaction of 13*, a relatively high selectiv-
ity (85%) of the desired 1,3-alternate conformer was
observed. This result is consistent with the generalization
that small para-substituents in the calix[4]arenes favor
1,3-alternate conformers.14c,15a
The alkylation of 5 in the presence of Cs2CO3 selec-
tively gave the partial-cone conformer 1b* (85%) (entry
5) along with cone conformer 1a (15%). It has been
reported that the alkylation of a syn-1,2-diether proceeds
through the intermediacy of the tri-O-alkylated cone
conformer, and that the conformational outcome is
determined in the final alkylation step, and is strongly
dependent on the cation in the base applied.3j Accord-
ingly, the use of Cs2CO3 as a base3j,13 selectively gave the
partial-cone conformer. Under the same conditions, the
reaction of 10 afforded the other partial-cone conformer
1d * (73%) along with cone conformer 1a (27%), for which
the selectivity was lower than that of 1b*. In the final
alkylation step, Cs+-induced inversion of the residual
phenol ring produces a partial cone phenolate, which is
less stable in the latter reaction than in the former
reaction due to steric repulsion between cation and para-
substituents of the three remaining aromatic rings. The
decrease in selectivity is the result of destabilization.
When t-BuOK was used as a base, the alkylation of 5
in benzene at reflux preferentially gave the 1,2-alternate
conformer 1c (83%) along with minor partial-cone con-
former 1b* (17%) (entry 6). Moreover, the reaction of 12*
under the same conditions afforded less selectively the
other 1,2-alternate conformer 1e* (70%) along with two
partial-cone conformers 1b* and 1d * (30%). Although
several studies dealing with fixed 1,2-alternate conform-
ers have appeared,4e,h-k,m,14 only a limited number of
tetra-O-substituted calix[4]arenes in the fixed 1,2-
alternate conformation without intramolecular bridge are
known.14a-d
Con for m a tion a l F ea tu r es of P r oxim a lly P a r a -
Disu bstitu ted Ca lix[4]a r en e Tetr a a lk yl Eth er s. The
conformational isomers of proximally para-disubstituted
5,11-dibromocalix[4]arene tetrapropyl ether, 1a -f*, ex-
1
hibited the expected H and 13C NMR spectral patterns
for proximal fuctionalizations at the exo positions in each
conformation. De Mendoza and co-workers reported that
the resonance arising from the bridge methylene carbon
is near δ 31 when two adjacent aryl groups are in the
syn orientation, and near δ 37 when they are in the anti
orientation.12 Indeed, the resonances for the bridge
methylene carbons are observed at δ 31.11, 31.01, and
30.83 for 1a , at δ 35.48, 35.13, 30.69, and 30.62 for 1b*,
at δ 37.79, 28.95, and 28.81 for 1c, at δ 35.59, 35.33,
30.59, and 30.44 for 1d *, at δ 38.46, 37.22, and 28.91 for
1e*, and at δ 35.45, 35.11, and 34.71 for 1f*. These
findings are in full agreement with those expected on the
basis of symmetry considerations, substantiating each
conformation.
Although the 1H NMR spectrum of the partial-cone
conformer 1d * is very similar to that of partial-cone
conformer 1b*, the resonance for the methyl protons in
the O-propyl groups substituted on the rotated aryl ring
of 1d * appeared at slightly higher field (δ 0.70) than that
(δ 0.83) of 1b*. This indicates that the hydrophobic cavity
contained by the remaining three aryl rings of 1d * is
deeper than that of 1b* due to the two bromine substit-
uents on the para positions, and, as a result, the methyl
group is entrapped in the hydrophobic cavity in solution.
From the alkylation of calix[4]arene syn-1,3-dipropyl
ether 13* in the presence of Cs2CO3, the 1,3-alternate
conformer 1f* was obtained as the major product (85%)
along with three other conformers 1a , 1b*, and 1d *
(15%). Often calix[4]arene derivatives in the fixed 1,3-
alternate conformation can be selectively produced, when
In the case of the 1,2-alternate conformers, marked
1
differences were observed between the H NMR signals
of 1c and 1e*. In particular, strong upfield shifts for all
the methyl and methylene protons in the O-propyl groups
were observed for 1c. The reason for this is that all the
protons are exposed to the diamagnetic shielding effects
(13) Iwamoto, K.; Araki, K.; Shinkai, S. J . Org. Chem. 1991, 56,
4955-4962.
(14) For calix[4]arenes in 1,2-alternate conformation, see: (a)
Groenen, L. C.; van Loon, J .-D.; Verboom, W.; Harkema, S.; Casnati,
A.; Ungaro, R.; Pochini, A.; Ugozzoli, F.; Reinhoudt, D. N. J . Am. Chem.
Soc. 1991, 113, 2385-2392. (b) Iwamoto, K.; Araki, K.; Shinkai, S. J .
Chem. Soc., Perkin Trans. 1 1991, 1611-1613. (c) Iwamoto, K.; Shinkai,
S. J . Org. Chem. 1992, 57, 7066-7073. (d) No, K.; Park, Y. J .; Kim, K.
H.; Shin, J . M. Bull. Korean Chem. Soc. 1996, 17, 447-452. (e)
Mathieu, A.; Asfari, Z.; Thuery, P.; Nierlich, M.; Faure, S.; Vicens, J .
J . Inclusion Phenom. Macrocycl. Chem. 2001, 40, 173-181.
(15) (a) Verboom, W.; Datta, S.; Asfari, Z.; Harkema, S.; Reinhoudt,
D. N. J . Org. Chem. 1992, 57, 5394-5398. (b) Fujimoto, K.; Nishiyama,
N.; Tsuzuki, H.; Shinkai, S. J . Chem. Soc., Perkin Trans. 2 1992, 643-
648. (c) Casnati, A.; Pochini, A.; Ungaro, R.; Ugozzoli, F.; Arnaud, F.;
Fanni, S.; Schwing, M.-J .; Egberink, R. J . M.; de J ong, F.; Reinhoudt,
D. N. J . Am. Chem. Soc. 1995, 117, 2767-2777.
2190 J . Org. Chem., Vol. 68, No. 6, 2003

Conformers of Proximally Para-Disubstituted Calix[4]arene
materials and substrates were commercially available materi-
als and were used without further purification.
of the two pairs of aryl rings (one above and one below
the mean plane containing the four bridging meth-
ylenes).4e,j That is to say, two O-propyl groups located
on the same side of the mean plane appear to alternate
in filling the pockets created by the two facing aryl rings,
which takes place on both sides of the mean plane.
Totally, all the protons in the four O-propyl groups of 1c
display strong upfield shifts. On the other hand, no strong
upfield shifts are seen for protons in the two O-propyl
groups of 1e*. This suggests that, in the 1,2-altenate
conformer 1e*, one of the two facing aryl rings is splayed
outward and close to the mean methylene-containing
plane, leading one of the two O-propyl groups located on
the same side to exclusively fill the pocket. For the entire
molecule, only two propyl groups are entrapped in the
hydrophobic pockets. A similar conformational feature
has been reported for 1,2;3,4-calix[4]arene-crown-5;crown-
6, in which the rings closer to the mean plane are
adjacent, and not the alternate ones.14e Consequently, the
conformation of 1e* even in solution appears to be
strongly distorted and distinct from that of 1c, although
both are in the 1,2-alternate conformation.
5,11-Dib r om o-25,26,27,28-t et r a p r op oxyca lix[4]a r en e
(u Br P r , u Br P r , u HP r ,u HP r ) (1a ). To a mixture of 5 (0.50 g, 0.75
mmol) and dry NaH (0.27 g, 11 mmol) in CH3CN (30 mL) was
added allyl bromide (1.36 g, 11.2 mmol), and the reaction
mixture was stirred at room temperature for 6 h. Aqueous HCl
(1 N, 20 mL) was then added dropwise, and most of the organic
solvent was evaporated. The diallylation product was extracted
with CHCl3 (4 × 30 mL). The combined organic layer was dried
over MgSO4 and concentrated. The residue (0.56 g), which
contained the cone and partial cone conformers in a ratio of
97:3, was purified by preparative TLC (SiO2; hexanes/CHCl3
1:1; Rf 0.79) to give the cone conformer (0.43 g) as a white
solid.18 The intermediate product was dissolved in THF (50
mL), and 5% palladium on carbon (0.20 g) was added to the
solution. The mixture was stirred under a hydrogen atmo-
sphere (1 atm), with hydrogen bubbling through the mixture,
at room temperature for 6 h. The catalyst was removed by
filtration and the solution was concentrated under reduced
pressure. The residue was purified by passing it through a
short column (SiO2; CHCl3) to give pure cone conformer 1a
(0.39 g, 0.52 mmol, 69%) as a white solid. Mp 124-125 °C (lit.5j
mp 117-119 °C). Rf 0.77 (CHCl3/hexane 1:1). 1H NMR (CDCl3,
400 MHz) δ 6.76-6.70 (m, 6H), 6.66-6.60 (m, 4H), 4.47 (d, J
) 13.6 Hz, 1H, ArCH2Ar), 4.42 (d, J ) 13.6 Hz, 2H, ArCH2-
Ar), 4.37 (d, J ) 13.6 Hz, 1H, ArCH2Ar), 3.90-3.77 (m, 8H),
3.20 (d, J ) 13.6 Hz, 1H, ArCH2Ar), 3.13 (d, J ) 13.6 Hz, 2H,
ArCH2Ar), 3.06 (d, J ) 13.6 Hz, 1H, ArCH2Ar), 1.908 (sextet,
J ) 7.3 Hz, 4H), 1.890 (sextet, J ) 7.3 Hz, 4H), 1.004 (t, J )
7.5 Hz, 3H), 0.998 (t, J ) 7.4 Hz, 3H). 13C NMR (CDCl3, 100
MHz) δ 156.65, 155.93, 137.79, 136.72, 135.37, 134.35, 131.21,
130.60, 128.63, 128.12, 122.41, 114.82, 76.84, 76.82, 31.11
(ArCH2Ar), 31.01 (ArCH2Ar), 30.83 (ArCH2Ar), 23.36, 23.26,
10.45, 10.39. IR (KBr) ν 3061, 2963, 2933, 2875, 1573, 1450,
1385, 1249, 1210, 1005, 964, 853, 764 cm-1. Anal. Calcd for
Con clu sion
All possible conformational isomers of the proximally
p-dibrominated calix[4]arene tetraalkyl ether, 1a -f*,
could be prepared successfully by using the proper bases
and starting materials, 5,11-dibromocalix[4]arene syn-
dialkyl ethers. Their conformations were confirmed by
1H and 13C NMR spectra to be cone for 1a (u BrPr, uBr
,
Pr
uHPr,uHPr), partial cone for 1b* (u BrPr, dBrPr, uHPr,uHPr) and
C
40H46Br2O4: C, 64.01; H, 6.18. Found: C, 64.04; H, 6.17.
1d * (u BrPr, uBrPr, uHPr,dHPr), 1,2-alternate for 1c (u Br
,
Pr
5,11-Dib r om o-25,26,27,28-t et r a p r op oxyca lix[4]a r en e
uBrPr, dHPr,dHPr) and 1e* (u BrPr, dBrPr, dHPr,uHPr), and 1,3-
alternate for 1f* (u BrPr, dBrPr, uHPr,dHPr). Consequently, it
appears that the hydrophobic cavity produced by the
three aryl rings of the partial-cone conformer 1d * is
deeper than that of the other partial-cone conformer 1b*
due to the two bromine substituents on the para posi-
tions, and that, although both of the conformational
isomers 1c and 1e* are in the 1,2-alternate conformation,
the conformation of 1e* in solution is distinct from that
of 1c. These conformational isomers of 5,11-dibromocalix-
[4]arene tetraalkyl ether represent very attractive build-
ing blocks for the design of synthetic receptors with chiral
discrimination ability, since the bromine substituents are
readily and selectively converted to other substituents.
(u Br P r , d Br P r , u HP r ,u HP r ) (1b*). To a mixture of 5 (0.50 g, 0.75
mmol) and Cs2CO3 (3.67 g, 11.3 mmol) in DMF (30 mL) was
added propyl bromide (1.38 g, 11.2 mmol), and the reaction
mixture was stirred at 80 °C for 15 h. Aqueous HCl (1 N, 20
mL) was then added, and the resulting solution was extracted
with CHCl3 (4 × 30 mL). The combined organic layer was dried
over MgSO4, concentrated, and filtered through a short column
(SiO2; CHCl3). The filtrate was evaporated, and the residue
(0.56 g), which contained the two conformers 1a and 1b* in a
ratio of 15:85, was recrystallized from CHCl3-MeOH to give
the pure partial cone conformer 1b* (0.28 g, 0.37 mmol, 49%)
as a white solid. Mp 175-177 °C. Rf 0.76 (CHCl3/hexane 1:1).
1H NMR (CDCl3, 400 MHz) δ 7.39-7.31 (m, 2H), 7.14-6.91
(m, 5H), 6.59 (t, J ) 5.1 Hz, 1H), 6.31-6.26 (m, 2H), 4.10 (d,
J ) 13.4 Hz, 1H, ArCH2Ar), 4.03 (d, J ) 13.5 Hz, 1H, ArCH2-
Ar), 3.82-3.66 (m, 4H), 3.61 (s, 2H, ArCH2Ar), 3.60-3.54 (m,
2H), 3.53 (s, 2H, ArCH2Ar), 3.37-3.33 (m, 2H), 3.09 (d, J )
13.4 Hz, 1H, ArCH2Ar), 3.01 (d, J ) 13.5 Hz, 1H, ArCH2Ar),
1.98 (sextet, J ) 7.3 Hz, 2H), 1.896 (sextet, J ) 7.2 Hz, 2H),
1.878 (sextet, J ) 7.2 Hz, 2H), 1.54-1.46 (m, 2H), 1.16-1.11
(m, 9H), 0.83 (t, J ) 7.5 Hz, 3H). 13C NMR (CDCl3, 100 MHz)
δ 157.05, 156.60, 155.55, 154.80, 137.39, 136.37, 136.27,
136.22, 135.22, 133.70, 133.33, 133.23, 132.64, 132.05, 131.19,
131.15, 129.52, 129.31, 128.99, 128.92, 122.59, 121.95, 114.92,
114.49, 76.46, 76.26, 75.97, 75.13, 35.48 (ArCH2Ar), 35.13
Exp er im en ta l Section
Gen er a l Rem a r k s. 1H and 13C NMR spectra were obtained
at the indicated frequency as dilute solutions in CDCl3 at room
temperature. Recycling preparative gel-permeation chroma-
tography (GPC) and high-performance liquid chromatography
(HPLC) were performed with a liquid chromatograph, using
J AIGEL-1H and 2H columns and two YMC-pack SIL SH-043-
10 columns, respectively. Analytical thin-layer chromatogra-
phy (TLC) and column chromatography were carried out on
precoated silica gel 60 F254 plastic sheets (E. Merck) and with
silica gel 60 (spherical 0.040-0.100 mm, Kanto), respectively.
Tetrahydrofuran (THF) was freshly distilled from Na-ben-
zophenone. Acetonitrile and chloroform used in reactions as a
solvent were distilled from CaH2 and P2O5, respectively. p-tert-
Butylcalix[4]arene,16 calix[4]arene 2,17 and calix[4]arene 1,2-
diallyl ether 33b,i were prepared according to literature methods
and a modified method. Unless otherwise noted, starting
(16) (a) Gutsche, C. D.; Iqbal, M. Org. Synth. 1989, 68, 234-237.
(b) For spectral data, see: Gutsche, C. D.; Dhawan, B.; No, K. H.;
Muthukrishnan, R. J . Am. Chem. Soc. 1981, 103, 3782-3792.
(17) Gutsche, C. D.; Lin, L.-G. Tetrahedron 1986, 42, 1633-1640.
(18) Isolation of the cone conformer from the conformational mixture
of 5,11-diromono-27,28-diallyloxy-25,26-dipropoxycalix[4]arene was
much easier than that from the mixture of 5,11-diromono-25,26,27,28-
tetrapropoxycalix[4]arene. The route via this diallyl ether intermediate
was therefore adopted for preparing the cone conformer 5 in high
purity.
J . Org. Chem, Vol. 68, No. 6, 2003 2191

Shimizu et al.
(ArCH2Ar), 30.69 (ArCH2Ar), 30.62 (ArCH2Ar), 24.28, 24.02,
23.93, 22.48, 11.11, 11.05, 10.97, 10.09. IR (KBr) ν 3066, 2963,
2932, 2873, 1574, 1453, 1384, 1251, 1195, 1006, 963, 855, 763
cm-1. Anal. Calcd for C40H46Br2O4: C, 64.01; H, 6.18. Found:
C, 64.04; H, 6.14.
combined organic layer was dried over MgSO4, concentrated,
and filtered through a short column (SiO2; CHCl3). The filtrate
was evaporated, and the residue (0.54 g), which contained the
1,2-alternate conformer 1e* (70%) and two other conformers
1b* and 1d *, was subjected to recycling preparative HPLC
(SiO2; CHCl3/hexane 1:5) to give pure 1,2-alternate conformer
1e* (0.28 g, 0.37 mmol, 49%) as a white solid. Mp 123-126
5,11-Dib r om o-25,26,27,28-t et r a p r op oxyca lix[4]a r en e
(u Br P r , u Br P r , d HP r ,d HP r ) (1c). To a solution of 5 (0.50 g, 0.75
mmol) and potassium tert-butoxide (0.34 g, 3.0 mmol) in
benzene (30 mL) was added propyl bromide (1.38 g, 11.2
mmol), and the reaction mixture was heated under reflux for
6 h. Aqueous HCl (1 N, 20 mL) was then added, and the
resulting solution was extracted with CHCl3 (4 × 30 mL). The
combined organic layer was dried over MgSO4, concentrated,
and filtered through a short column (SiO2; CHCl3). The filtrate
was evaporated, and the residue (0.54 g), which contained the
two conformers 1b* and 1c in a ratio of 17:83, was recrystal-
lized from CHCl3-MeOH to give pure 1,2-alternate conformer
1c (0.25 g, 0.33 mmol, 44%) as a white solid. Mp 193-194 °C.
Rf 0.75 (CHCl3/hexane 1:1). 1H NMR (CDCl3, 400 MHz) δ 7.22
(d, J ) 2.5 Hz, 2H), 7.15 (d, J ) 2.5 Hz, 2H), 7.09 (dd, J ) 7.6,
1.5 Hz, 2H), 7.01 (dd, J ) 7.5, 1.4 Hz, 2H), 6.83 (t, J ) 7.5 Hz,
2H), 4.19 (d, J ) 12.6 Hz, 1H, ArCH2Ar), 4.09 (d, J ) 12.8 Hz,
1H, ArCH2Ar), 3.83 (s, 4H, ArCH2Ar), 3.43-3.26 (m, 8H), 3.18
(d, J ) 12.6 Hz, 1H, ArCH2Ar), 3.06 (d, J ) 12.8 Hz, 1H,
ArCH2Ar), 1.41-1.29 (m, 2H), 1.23-1.11 (m, 2H), 1.08-0.96
(m, 2H), 0.95-0.83 (m, 2H), 0.73 (t, J ) 7.5 Hz, 6H), 0.60 (t,
J ) 7.5 Hz, 6H). 13C NMR (CDCl3, 100 MHz) δ: 156.53, 155.82,
136.01, 135.40, 134.75, 132.44, 132.15, 131.25, 129.32, 129.29,
122.19, 114.78, 75.10, 75.08, 37.79 (ArCH2Ar), 28.95 (ArCH2-
Ar), 28.81 (ArCH2Ar), 23.10, 22.79, 10.38, 10.34. IR (KBr) ν
3063, 2962, 2932, 2875, 1575, 1465, 1385, 1251, 1196, 1009,
964, 853, 764 cm-1. Anal. Calcd for C40H46Br2O4: C, 64.01; H,
6.18. Found: C, 64.14; H, 6.19.
1
°C. Rf 0.80 (CHCl3/hexane 1:1). H NMR (CDCl3, 400 MHz) δ
7.21 (d, J ) 2.5 Hz, 2H), 7.16 (dd, J ) 7.4, 1.6 Hz, 2H), 7.06
(d, J ) 2.3 Hz, 2H), 7.01 (dd, J ) 7.5, 1.4 Hz, 2H), 6.93 (t, J )
7.4 Hz, 2H), 4.14 (d, J ) 12.7 Hz, 2H, ArCH2Ar), 3.96 (s, 2H,
ArCH2Ar), 3.70 (s, 2H, ArCH2Ar), 3.68-3.62 (m, 2H), 3.49-
3.43 (m, 2H), 3.25-3.19 (m, 2H), 3.12 (d, J ) 12.7 Hz, 2H,
ArCH2Ar), 3.09-3.03 (m, 2H), 1.73-1.59 (m, 4H), 0.95 (t, J )
7.5 Hz, 6H), 0.92-0.83 (m, 2H), 0.44 (t, J ) 7.5 Hz, 6H), 0.30-
0.17 (m, 2H). 13C NMR (CDCl3, 100 MHz) δ 157.07, 155.24,
136.23, 135.07, 134.66, 132.42, 132.26, 131.88, 129.44, 128.91,
122.58, 114.88, 76.02, 74.17, 38.46 (ArCH2Ar), 37.22 (ArCH2-
Ar), 28.91 (ArCH2Ar), 23.50, 22.45, 10.78, 9.98. IR (KBr) ν
3061, 2962, 2936, 2877, 1573, 1458, 1385, 1250, 1219, 1198,
1010, 956, 856, 767 cm-1. Anal. Calcd for C40H46Br2O4‚0.04
CHCl3: C, 63.27; H, 6.10. Found: C, 63.33; H, 6.00.
5,11-Dib r om o-25,26,27,28-t et r a p r op oxyca lix[4]a r en e
(u Br P r , d Br P r , u HP r ,d HP r ) (1f*). To a mixture of 13* (0.50 g, 0.75
mmol) and Cs2CO3 (3.67 g, 11.3 mmol) in acetone (30 mL) was
added propyl bromide (1.38 g, 11.2 mmol), and the reaction
mixture was heated under reflux for 15 h. Aqueous HCl (1 N,
20 mL) was added, and the resulting solution was extracted
with CHCl3 (4 × 30 mL). The combined organic layer was dried
over MgSO4, concentrated, and filtered through a short column
(SiO2; CHCl3). The filtrate was evaporated, and the residue
(0.53 g), which contained the 1,3-alternate conformer 1f* (85%)
and three other conformers 1a , 1b*, and 1d *, was recrystal-
lized from CHCl3-MeOH to give pure 1,3-alternate conformer
1f* (0.23 g, 0.31 mmol, 41%) as a white solid. Mp 183-185
5,11-Dib r om o-25,26,27,28-t et r a p r op oxyca lix[4]a r en e
(u Br P r , u Br P r , u HP r ,d HP r ) (1d *). To a mixture of 10 (0.50 g, 0.75
mmol) and Cs2CO3 (3.67 g, 11.3 mmol) in DMF (30 mL) was
added propyl bromide (1.38 g, 11.2 mmol), and the reaction
mixture was heated at 80 °C for 15 h. Aqueous HCl (1 N, 20
mL) was then added, and the reaction mixture was extracted
with CHCl3 (4 × 30 mL). The combined organic layer was dried
over MgSO4, concentrated, and filtered through a short column
(SiO2; CHCl3). The filtrate was evaporated, and the residue
(0.56 g), which contained the two conformers 1a and 1d * in a
ratio of 27:73, was subjected to recycling preparative HPLC
(SiO2; CHCl3/hexane 1:5) to give pure partial cone conformer
1d * (0.31 g, 0.41 mmol, 55%) as a white solid. Mp 148-150
1
°C. Rf 0.59 (CHCl3/hexane 1:1). H NMR (CDCl3, 400 MHz) δ
7.17-7.01 (m, 8H), 6.82 (t, J ) 7.5 Hz, 2H), 3.70-3.58 (m, 8H),
3.56 (s, 2H, ArCH2Ar), 3.51 (s, 4H, ArCH2Ar), 3.43 (s, 2H,
ArCH2Ar), 1.85-1.76 (m, 8H), 1.08 (t, J ) 7.4 Hz, 12H). 13C
NMR (CDCl3, 100 MHz) δ 156.08, 155.26, 135.93, 134.96,
133.74, 132.79, 132.44, 131.92, 130.07, 129.54, 122.18, 114.56,
74.84, 74.56, 35.45 (ArCH2Ar), 35.11 (ArCH2Ar), 34.71 (ArCH2-
Ar), 23.96, 10.93. IR (KBr) ν 3070, 2962, 2935, 2867, 1576,
1450, 1383, 1252, 1196, 1067, 1009, 963, 854, 759 cm-1. Anal.
Calcd for C40H46Br2O4: C, 64.01; H, 6.18. Found: C, 63.79; H,
6.13.
1
°C. Rf 0.78 (CHCl3/hexane 1:1). H NMR (CDCl3, 400 MHz) δ
25,26-Dih yd r oxy-27,28-d ip r op oxyca lix[4]a r en e (4). To
a solution of calix[4]arene 1,2-diallyl ether 3 (5.00 g, 9.90
mmol) in THF (200 mL) was added 5% palladium on carbon
(1.00 g). The mixture was stirred under a hydrogen atmo-
sphere (1 atm), with hydrogen bubbling through the mixture,
at room temperature for 12 h. After filtration and evaporation
of the solvent, the residue was recrystallized from CHCl3-
MeOH to give 4 (4.99 g, 9.81 mmol, 99%) as a white solid. Mp
190-191 °C (lit.5j mp 195-196 °C). Rf 0.47 (CHCl3/hexane 4:1).
1H NMR (CDCl3, 400 MHz) δ 8.99 (s, 2H), 7.06 (dd, J ) 7.6,
1.5 Hz, 2H), 6.99-6.97 (m, 6H), 6.79 (t, J ) 7.6 Hz, 2H), 6.63
(t, J ) 7.5 Hz, 2H), 4.55 (d, J ) 12.4 Hz, 1H, ArCH2Ar), 4.34
(d, J ) 13.0 Hz, 2H, ArCH2Ar), 4.34 (d, J ) 13.5 Hz, 1H,
ArCH2Ar), 4.12-4.06 (m, 2H), 3.93-3.86 (m, 2H), 3.41 (d, J )
12.4 Hz, 1H, ArCH2Ar), 3.39 (d, J ) 13.0 Hz, 2H, ArCH2Ar),
3.35 (d, J ) 13.5 Hz, 1H, ArCH2Ar), 2.20-2.07 (m, 4H), 1.16
(t, J ) 7.5 Hz, 6H). 13C NMR (CDCl3, 100 MHz) δ 153.46,
151.19, 134.66, 134.12, 129.42, 129.11, 129.05, 128.78, 128.77,
128.02, 124.71, 120.53, 78.29, 31.91 (ArCH2Ar), 31.78 (ArCH2-
Ar), 29.98 (ArCH2Ar), 23.27, 10.34. IR (KBr) ν 3323, 3081,
2927, 1591, 1465, 1246, 1197, 1094, 980, 756 cm-1. Anal. Calcd
for C34H36O4: C, 80.28; H, 7.13. Found: C, 79.88; H, 7.16.
7.27-7.15 (m, 5H), 7.06 (dd, J ) 7.4, 1.3 Hz, 1H), 6.87 (t, J )
7.5 Hz, 1H), 6.66 (t, J ) 7.6 Hz, 1H), 6.30-6.26 (m, 2H), 4.06
(d, J ) 13.6 Hz, 1H, ArCH2Ar), 3.99 (d, J ) 13.7 Hz, 1H,
ArCH2Ar), 3.86-3.70 (m, 4H), 3.68 (s, 2H, ArCH2Ar), 3.60 (s,
2H, ArCH2Ar), 3.58-3.49 (m, 2H), 3.27-3.22 (m, 2H), 3.04 (d,
J ) 13.6 Hz, 1H, ArCH2Ar), 2.96 (d, J ) 13.7 Hz, 1H, ArCH2-
Ar), 2.02 (sextet, J ) 7.4 Hz, 2H), 1.91-1.82 (m, 4H), 1.40-
1.28 (m, 2H), 1.17 (t, J ) 7.4 Hz, 3H), 1.11 (t, J ) 7.4 Hz, 3H),
1.10 (t, J ) 7.4 Hz, 3H), 0.70 (t, J ) 7.5 Hz, 3H). 13C NMR
(CDCl3, 100 MHz) δ 157.52, 156.42, 155.58, 154.85, 139.49,
138.41, 135.16, 134.34, 134.25, 133.30, 132.67, 132.57, 132.11,
131.97, 131.40, 130.73, 130.58, 130.16, 129.77, 128.44, 122.06,
121.94, 114.74, 114.60, 76.45, 76.26, 75.69, 75.01, 35.59
(ArCH2Ar), 35.33 (ArCH2Ar), 30.59 (ArCH2Ar), 30.44 (ArCH2-
Ar), 24.34, 23.99, 23.90, 22.38, 11.08, 11.05, 11.02, 9.40. IR
(KBr) ν 3070, 2962, 2932, 2874, 1576, 1456, 1386, 1250, 1195,
1002, 965, 854, 761 cm-1. Anal. Calcd for C40H46Br2O4: C,
64.01; H, 6.18. Found: C, 64.08; H, 6.21.
5,11-Dib r om o-25,26,27,28-t et r a p r op oxyca lix[4]a r en e
(u Br P r , d Br P r , d HP r ,u HP r ) (1e*). To a solution of 12* (0.50 g,
0.75 mmol) and potassium tert-butoxide (0.34 g, 3.0 mmol) in
benzene (30 mL) was added propyl bromide (1.38 g, 11.2
mmol), and the reaction mixture was heated under reflux for
6 h. Aqueous HCl (1 N, 20 mL) was then added, and the
resulting solution was extracted with CHCl3 (4 × 30 mL). The
5,11-Dib r om o-27,28-d ih yd r oxy-25,26-d ip r op oxyca lix-
[4]a r en e (5). To a solution of 4 (7.95 g, 15.6 mmol) in
2-butanone (250 mL) was added N-bromosuccinimide (5.56 g,
31.2 mmol), and the yellow solution was stirred at room
2192 J . Org. Chem., Vol. 68, No. 6, 2003

Conformers of Proximally Para-Disubstituted Calix[4]arene
temperature for 24 h. After evaporation of the solvent, tritu-
ration of the solid residue with MeOH gave 5 (8.60 g, 12.9
mmol, 83%) as a white solid. Mp 260-262 °C dec (lit.5j mp
>200 °C dec). Rf 0.29 (CHCl3/hexane 1:1). 1H NMR (CDCl3,
400 MHz) δ 8.89 (s, 2H), 7.11-7.06 (m, 6H), 6.98 (dd, J ) 7.6,
1.5 Hz, 2H), 6.84 (t, J ) 7.6 Hz, 2H), 4.51 (d, J ) 12.4 Hz, 1H,
ArCH2Ar), 4.30 (d, J ) 13.4 Hz, 1H, ArCH2Ar), 4.27 (d, J )
13.1 Hz, 2H, ArCH2Ar), 4.11-4.05 (m, 2H), 3.91-3.84 (m, 2H),
3.43 (d, J ) 12.4 Hz, 1H, ArCH2Ar), 3.36 (d, J ) 13.1 Hz, 2H,
ArCH2Ar), 3.22 (d, J ) 13.4 Hz, 1H, ArCH2Ar), 2.18-2.06 (m,
4H), 1.15 (t, J ) 7.5 Hz, 6H). 13C NMR (CDCl3, 100 MHz) δ
153.26, 150.52, 134.64, 133.17, 131.55, 131.22, 130.74, 130.52,
129.22, 129.17, 125.09, 112.18, 78.45, 31.77 (ArCH2Ar), 31.26
(ArCH2Ar), 29.90 (ArCH2Ar), 23.23, 10.29. IR (KBr) ν 3449,
3073, 2966, 2929, 2874, 1586, 1467, 1211, 1193, 1088, 997, 769
cm-1. Anal. Calcd for C34H34Br2O4: C, 61.28; H, 5.14. Found:
C, 60.91; H, 5.17.
25,26-Diben zyloxy-27,28-d ih yd r oxyca lix[4]a r en e (6).
To a slurry of calix[4]arene 2 (5.00 g, 11.8 mmol) and NaH
(2.83 g of a 60% dispersion in paraffin liquid, 71 mmol) in CH3-
CN (250 mL) was added benzyl bromide (3.08 mL, 25.9 mmol),
and the reaction mixture was stirred at room temperature for
30 min to produce a light purple solution. Aqueous HCl (1 N,
30 mL) was then added dropwise, and most of the organic
solvent was evaporated. After addition of water (40 mL), the
product was extracted with CHCl3 (80 mL). The combined
organic layer was dried over MgSO4 and concentrated. The
residue was purified by passing it through a short column
(SiO2; hexane, then CHCl3) to give 6 (4.29 g, 7.09 mmol, 60%)
as a white solid. Mp 224-227 °C. Rf 0.75 (CHCl3). 1H NMR
(CDCl3, 270 MHz) δ 8.97 (s, 2H), 7.53-7.35 (m, 10H), 7.09-
6.93 (m, 8H), 6.81 (t, J ) 7.6 Hz, 2H), 6.59 (t, J ) 7.6 Hz, 2H),
5.06 (d, J ) 11.2 Hz, 2H), 4.88 (d, J ) 11.2 Hz, 2H), 4.47 (d,
J ) 12.4 Hz, 1H, ArCH2Ar), 4.24 (d, J ) 13.5 Hz, 1H, ArCH2-
Ar), 4.10 (d, J ) 12.7 Hz, 2H, ArCH2Ar), 3.33 (d, J ) 13.2 Hz,
2H, ArCH2Ar), 3.22 (d, J ) 13.0 Hz, 2H, ArCH2Ar). 13C NMR
(CDCl3, 67.9 MHz) δ 153.31, 151.23, 136.71, 134.81, 134.54,
129.32, 129.09, 129.00, 128.84, 128.75, 128.70, 128.62, 128.16,
125.05, 120.57, 78.56, 31.99 (ArCH2Ar), 30.66 (ArCH2Ar). IR
(KBr) ν 3404, 3332, 3035, 2934, 2857, 1591, 1465, 1215, 1182,
1092, 973, 915, 759, 698 cm-1. Anal. Calcd for C42H36O4: C,
83.42; H, 6.00. Found: C, 82.95; H, 6.18.
as a plate-shaped crystal. Mp 155-158 °C. Rf 0.67 (CHCl3/
hexane 1:1). 1H NMR (CDCl3, 270 MHz) δ 7.32-7.23 (m, 10H),
6.74-6.54 (m, 10H), 6.29-6.14 (m, 2H), 5.20-5.12 (m, 4H),
4.92 (d, J ) 11.6 Hz, 2H), 4.83 (d, J ) 11.6 Hz, 2H), 4.38 (d,
J ) 6.5 Hz, 4H), 4.30 (d, J ) 13.9 Hz, 1H, ArCH2Ar), 4.25 (d,
J ) 13.5 Hz, 1H, ArCH2Ar), 4.18 (d, J ) 13.9 Hz, 2H, ArCH2-
Ar), 3.05 (d, J ) 13.9 Hz, 1H, ArCH2Ar), 3.04 (d, J ) 13.5 Hz,
1H, ArCH2Ar), 2.96 (d, J ) 13.9 Hz, 2H, ArCH2Ar). 13C NMR
(CDCl3, 126 MHz) δ 155.45, 155.14, 137.99, 137.64, 137.06,
135.48, 135.01, 134.76, 131.28, 130.62, 129.68, 128.80, 128.21,
128.16, 128.10, 122.85, 117.86, 115.25, 76.80, 76.00, 31.34
(ArCH2Ar), 31.29 (ArCH2Ar), 31.25 (ArCH2Ar). IR (KBr) ν
3062, 3039, 2922, 2859, 1572, 1459, 1196, 992, 754, 699 cm-1
.
Anal. Calcd for C48H42Br2O4: C, 68.42; H, 5.02. Found: C,
68.73; H, 5.20.
5,11-Dibr om o-25,26-d iben zyloxy-27,28-d ip r op oxyca lix-
[4]a r en e (9). To a solution of 8 (3.70 g, 4.39 mmol) in THF
(200 mL) was added 5% palladium on carbon (0.70 g). The
mixture was stirred under a hydrogen atmosphere (1 atm),
with hydrogen bubbling through the mixture, at room tem-
perature for 3 h. After filtration and evaporation of the solvent,
the residue was purified by passing it through a short column
(SiO2; CHCl3) to give 9 (3.50 g, 4.13 mmol, 94%) as a white
solid. Mp 140-143 °C. Rf 0.67 (CHCl3/hexane 1:1). 1H NMR
(CDCl3, 270 MHz) δ 7.40-7.22 (m, 10H), 6.77-6.68 (m, 6H),
6.61-6.54 (m, 4H), 4.88 (d, J ) 11.5 Hz, 2H), 4.83 (d, J ) 11.5
Hz, 2H), 4.36 (d, J ) 13.8 Hz, 1H, ArCH2Ar), 4.25 (d, J ) 13.5
Hz, 2H, ArCH2Ar), 4.17 (d, J ) 13.5 Hz, 1H, ArCH2Ar), 3.89-
3.74 (m, 4H), 3.05 (d, J ) 14.3 Hz, 1H, ArCH2Ar), 2.99 (d, J )
14.0 Hz, 3H, ArCH2Ar), 1.85 (sextet, J ) 7.5 Hz, 4H), 0.92 (t,
J ) 7.5 Hz, 6H). 13C NMR (CDCl3, 22.5 MHz) δ 156.20, 155.71,
138.12, 138.05, 137.14, 135.88, 134.97, 131.63, 130.98, 129.84,
129.08, 128.48, 128.32, 123.16, 115.18, 78.91, 76.06, 31.58
(ArCH2Ar), 31.47 (ArCH2Ar), 31.31 (ArCH2Ar), 23.60, 10.69.
IR (KBr) ν 3030, 2924, 2874, 1572, 1457, 1210, 1194, 966, 764,
699 cm-1. Anal. Calcd for C48H46Br2O4: C, 68.09; H, 5.48.
Found: C, 68.23; H, 5.54.
5,11-Dib r om o-25,26-d ih yd r oxy-27,28-d ip r op oxyca lix-
[4]a r en e (10). To a stirred solution of 9 (2.74 g, 3.24 mmol)
in toluene (300 mL) at 0 °C was added anhydrous AlCl3 (0.86
g, 6.4 mmol), and the reaction mixture was stirred at 0 °C for
1 h. The reaction was then quenched with diluted HCl (50 mL).
The organic layer was separated, dried over MgSO4, and
concentrated. The residue was purified by column chromatog-
raphy (SiO2; CHCl3/hexane 4:1) to give 10 (1.92 g, 2.88 mmol,
89%) as a white solid. Mp 266-269 °C. Rf 0.58 (CHCl3/hexane
5,11-Dibr om o-25,26-d iben zyloxy-27,28-d ih yd r oxyca lix-
[4]a r en e (7). To a solution of 6 (3.80 g, 6.28 mmol) in
2-butanone (100 mL) was added N-bromosuccinimide (2.24 g,
12.6 mmol), and the yellow solution was stirred at room
temperature for 24 h. After evaporation of the solvent, the
residue was recrystallized from CHCl3-MeOH to give 7 (4.31
g, 5.65 mmol, 90%) as a white solid. Mp 113-116 °C. Rf 0.74
(CHCl3). 1H NMR (CDCl3, 270 MHz) δ 8.90 (s, 2H), 7.49-7.37
(m, 10H), 7.13-6.96 (m, 8H), 6.86 (t, J ) 7.6 Hz, 2H), 5.05 (d,
J ) 11.3 Hz, 2H), 4.85 (d, J ) 11.3 Hz, 2H), 4.45 (d, J ) 12.6
Hz, 1H, ArCH2Ar), 4.16 (d, J ) 13.8 Hz, 1H, ArCH2Ar), 4.02
(d, J ) 13.0 Hz, 2H, ArCH2Ar), 3.35 (d, J ) 12.6 Hz, 1H,
ArCH2Ar), 3.19 (d, J ) 13.8 Hz, 1H, ArCH2Ar), 3.17 (d, J )
13.0 Hz, 2H, ArCH2Ar). 13C NMR (CDCl3, 67.9 MHz) δ 153.21,
150.53, 136.42, 134.84, 133.64, 131.55, 131.28, 130.92, 130.10,
129.45, 129.36, 129.15, 128.86, 125.39, 112.24, 78.76, 31.84
(ArCH2Ar), 31.52 (ArCH2Ar), 30.64 (ArCH2Ar). IR (KBr) ν
1
4:1). H NMR (CDCl3, 400 MHz) δ 8.87 (s, 2H), 7.13 (s, 4H),
7.02 (dd, J ) 7.5, 1.3 Hz, 2H), 6.98 (dd, J ) 7.5, 1.3 Hz, 2H),
6.68 (t, J ) 7.5 Hz, 2H), 4.46 (d, J ) 12.5 Hz, 1H, ArCH2Ar),
4.30 (d, J ) 13.0 Hz, 2H, ArCH2Ar), 4.28 (d, J ) 13.5 Hz, 1H,
ArCH2Ar), 4.06-4.00 (m, 2H), 3.89-3.83 (m, 2H), 3.39 (d, J )
13.5 Hz, 1H, ArCH2Ar), 3.35 (d, J ) 13.0 Hz, 2H, ArCH2Ar),
3.30 (d, J ) 12.5 Hz, 1H, ArCH2Ar), 2.17-2.05 (m, 4H), 1.15
(t, J ) 7.4 Hz, 6H). 13C NMR (CDCl3, 67.9 MHz) δ 153.03,
151.18, 136.66, 136.14, 132.42, 131.54, 129.29, 129.00, 128.55,
128.28, 121.04, 117.32, 78.65, 31.93 (ArCH2Ar), 31.86 (ArCH2-
Ar), 29.88 (ArCH2Ar), 23.36, 10.42. IR (KBr) ν 3301, 2964,
2936, 2878, 1572, 1466, 1197, 979, 755 cm-1. Anal. Calcd for
C
34H34Br2O4: C, 61.28; H, 5.14. Found: C, 60.89; H, 5.15.
3312, 3063, 2929, 2876, 1458, 1219, 1186, 975, 764, 700 cm-1
.
5,11-Dibr om o-26,27,28-tr ih yd r oxy-25-p r op oxyca lix[4]-
Anal. Calcd for C42H34Br2O4: C, 66.16; H, 4.49. Found: C,
66.04; H, 4.69.
a r en e (11*). To a stirred solution of 5 (5.00 g, 7.50 mmol) in
CHCl3 (250 mL) was added dropwise trimethylsilyl iodide (3.04
mL, 21.4 mmol), and the mixture was heated under reflux for
24 h. After addition of water (100 mL), the organic layer was
separated, washed with water, dried over MgSO4, and con-
centrated. The residue was purified through a short column
(SiO2; CHCl3) to give 11* (4.40 g, 7.05 mmol, 94%). Mp 164-
166 °C. Rf 0.49 (CHCl3/hexane 1:1). 1H NMR (CDCl3, 400 MHz)
δ 9.69 (s, 1H), 9.46 (s, 1H), 9.18 (s, 1H), 7.20 (d, J ) 2.4 Hz,
1H), 7.12-7.07 (m, 6H), 7.03 (dd, J ) 7.5, 1.4 Hz, 1H), 6.92 (t,
J ) 7.6 Hz, 1H), 6.73 (t, J ) 7.5 Hz, 1H), 4.41 (d, J ) 12.8 Hz,
1H, ArCH2Ar), 4.23 (d, J ) 13.4 Hz, 1H, ArCH2Ar), 4.20 (d, J
5,11-Dibr om o-27,28-d ia llyloxy-25,26-d iben zyloxyca lix-
[4]a r en e (8). To a mixture of 7 (3.00 g, 3.93 mmol) and NaH
(2.36 g of a 60% dispersion in paraffin liquid, 59 mmol) in CH3-
CN (100 mL) was added allyl bromide (5.1 mL, 59 mmol), and
the reaction mixture was stirred at room temperature for 6 h.
Aqueous HCl (1 N, 60 mL) was then added dropwise, and most
of the organic solvent was evaporated. The product was
extracted with CHCl3 (100 mL), and the organic layer was
dried over MgSO4 and concentrated. The residue was recrys-
tallized from CHCl3-MeOH to give 8 (2.78 g, 3.30 mmol, 84%)
J . Org. Chem, Vol. 68, No. 6, 2003 2193

Shimizu et al.
) 13.9 Hz, 2H, ArCH2Ar), 4.16-4.05 (m, 2H), 3.51 (d, J ) 13.4
Hz, 1H, ArCH2Ar), 3.42 (d, J ) 13.9 Hz, 1H, ArCH2Ar), 3.39
(d, J ) 12.8 Hz, 1H, ArCH2Ar), 3.34 (d, J ) 13.9 Hz, 1H,
ArCH2Ar), 2.24-2.11 (m, 2H), 1.27 (t, J ) 7.4 Hz, 3H). 13C
NMR (CDCl3, 100 MHz) δ 151.34, 150.41, 150.32, 148.52,
133.77, 133.73, 131.58, 131.29, 131.13, 131.07, 131.06, 130.78,
130.42, 129.66, 129.42, 129.05, 128.90, 127.92, 127.42, 126.39,
121.46, 113.69, 112.23, 79.18, 31.71 (ArCH2Ar), 31.65 (ArCH2-
Ar), 31.54 (ArCH2Ar), 30.91 (ArCH2Ar), 23.26, 10.65. IR (KBr)
2967, 2928, 2875, 1574, 1468, 1205, 979, 859, 762 cm-1. Anal.
Calcd for C34H34Br2O4: C, 61.28; H, 5.14. Found: C, 60.90; H,
5.15.
5,11-Dib r om o-26,28-d ih yd r oxy-25,27-d ip r op oxyca lix-
[4]a r en e (13*). To a mixture of 11* (1.00 g, 1.60 mmol), BaO
(1.43 g, 9.33 mmol), and Ba(OH)2‚8H2O (1.51 g, 4.79 mmol) in
DMF (50 mL) was added propyl bromide (0.72 mL, 7.9 mmol),
and the reaction mixture was stirred at room temperature for
24 h. Aqueous HCl (1 N, 50 mL) was then added, and the
resulting solution was extracted with CHCl3 (3 × 50 mL). The
combined organic layer was washed with 10% aqueous Na2S2O3
(50 mL), dried over MgSO4, and concentrated. The residue was
recrystallized from CHCl3-MeOH to give 13* (0.66 g, 0.99
mmol, 62%) as a white solid. Mp 315-317 °C. Rf 0.65 (CHCl3/
hexane 2:1). 1H NMR (CDCl3, 400 MHz) δ 8.37 (s, 1H), 8.17
(s, 1H), 7.19 (d, J ) 2.4 Hz, 1H), 7.13 (d, J ) 2.4 Hz, 1H),
7.09-6.93 (m, 6H), 6.82 (t, J ) 7.5 Hz, 1H), 6.66 (t, J ) 7.5
Hz, 1H), 4.28 (d, J ) 13.1 Hz, 1H, ArCH2Ar), 4.27 (d, J ) 12.9
Hz, 1H, ArCH2Ar), 4.25 (d, J ) 13.1 Hz, 1H, ArCH2Ar), 4.21
(d, J ) 13.0 Hz, 1H, ArCH2Ar), 3.98-3.91 (m, 4H), 3.40 (d, J
) 13.1 Hz, 1H, ArCH2Ar), 3.34 (d, J ) 12.9 Hz, 1H, ArCH2-
Ar), 3.33 (d, J ) 13.1 Hz, 1H, ArCH2Ar), 3.29 (d, J ) 13.1 Hz,
1H, ArCH2Ar), 2.08-2.00 (m, 4H), 1.301 (t, J ) 7.4 Hz, 3H),
1.296 (t, J ) 7.4 Hz, 3H). 13C NMR (CDCl3, 100 MHz) δ 153.43,
152.79, 151.97, 151.37, 135.96, 134.90, 133.59, 132.63, 132.38,
131.89, 131.19, 130.88, 130.37, 129.53, 129.29, 129.16, 128.91,
128.67, 128.10, 127.22, 125.69, 119.43, 117.91, 110.63, 78.76,
78.56, 31.58 (ArCH2Ar), 31.43 (ArCH2Ar), 31.34 (ArCH2Ar),
31.26 (ArCH2Ar), 23.62, 23.58, 11.04, 11.00. IR (KBr) ν 3275,
ν 3334, 2936, 2875, 1591, 1466, 1216, 1083, 956, 758 cm-1
.
Anal. Calcd for C31H28Br2O4: C, 59.63; H, 4.52. Found: C,
59.42; H, 4.63.
5,11-Dibr om o-25,28-d ih yd r oxy-26,27-d ip r op oxyca lix[4]-
a r en e (12*). To a mixture of 11* (1.47 g, 2.35 mmol) and NaH
(0.28 g of a 60% dispersion in paraffin liquid, 7.0 mmol) in
CH3CN (50 mL) was added allyl bromide (0.23 mL, 2.7 mmol),
and the reaction mixture was stirred at room temperature for
20 min to produce a light purple solution. Aqueous HCl (1 N,
30 mL) was then added dropwise, and most of the organic
solvent was evaporated. The allylation product was extracted
with CHCl3 (3 × 40 mL). The combined organic layer was dried
over MgSO4 and concentrated. The residue was purified by
passing it through a short column (SiO2; hexane, then CHCl3).
The intermediate product was dissolved in THF (50 mL), and
5% palladium on carbon (0.30 g) was added to the solution.
The mixture was stirred under a hydrogen atmosphere (1 atm),
with hydrogen bubbling through the mixture, at room tem-
perature for 1 h. After filtration and evaporation of the solvent,
the residue (1.42 g) was subjected to recycling preparative GPC
(CHCl3). The first eluate was concentrated, and the residue
that contained the two isomers 5 and 12* in a ratio of 3:7 (0.92
g) was recrystallized from CHCl3-MeOH to give 12* (0.32 g,
0.48 mmol, 20%) as a white solid. Mp 250-252 °C. Rf 0.64
(CHCl3/hexane 4:1). 1H NMR (CDCl3, 400 MHz) δ 9.31 (s, 1H),
8.76 (s, 1H), 7.14-7.00 (m, 8H), 6.92 (t, J ) 7.5 Hz, 1H), 6.70
(t, J ) 7.5 Hz, 1H), 4.49 (d, J ) 12.5 Hz, 1H, ArCH2Ar), 4.43
(d, J ) 12.6 Hz, 1H, ArCH2Ar), 4.27 (d, J ) 13.5 Hz, 1H,
ArCH2Ar), 4.21-4.15 (m, 1H), 4.16 (d, J ) 13.5 Hz, 1H, ArCH2-
Ar), 3.97-3.89 (m, 2H), 3.85-3.79 (m, 1H), 3.50 (d, J ) 13.5
Hz, 1H, ArCH2Ar), 3.37 (d, J ) 12.5 Hz, 1H, ArCH2Ar), 3.32
(d, J ) 13.6 Hz, 1H, ArCH2Ar), 3.22 (d, J ) 12.6 Hz, 1H,
ArCH2Ar), 2.27-1.96 (m, 4H), 1.17 (t, J ) 7.4 Hz, 3H), 1.14
(t, J ) 7.4 Hz, 3H). 13C NMR (CDCl3, 100 MHz) δ 153.75,
152.77, 151.39, 150.46, 136.38, 136.05, 134.68, 133.78, 132.13,
131.81, 131.51, 131.35, 130.82, 130.49, 129.55, 129.48, 129.30,
128.76, 128.53, 128.37, 125.89, 121.43, 116.61, 111.91, 78.78,
78.43, 32.43 (ArCH2Ar), 31.75 (ArCH2Ar), 31.33 (ArCH2Ar),
29.95 (ArCH2Ar), 23.51, 23.22, 10.56, 10.35. IR (KBr) ν 3235,
2960, 2932, 2875, 1575, 1467, 1219, 1197, 1061, 957, 760 cm-1
.
Anal. Calcd for C34H34Br2O4: C, 61.28; H, 5.14. Found: C,
61.04; H, 5.20.
Ack n ow led gm en t . We thank Takako Okazaki,
Nobuyuki Kobayashi, Hisae Yoneyama, and Masahiro
Kamatani for their assistance in this study. We also
thank Professor P. D. Harvey for kindly providing us
with the Supporting Information for his paper.5j This
work was partially supported by a Grant from the
Ministry of Education, Culture, Sports, Science, and
Technology to promote advanced scientific research.
Su p p or tin g In for m a tion Ava ila ble: Copies of 1H and 13C
NMR spectra of conformational isomers 1a -f. This material
is available free of charge via the Internet at http://pubs.acs.org.
J O0267293
2194 J . Org. Chem., Vol. 68, No. 6, 2003