Synthesis of Calix[4]arenes with four different "lower rim" substituents

Article abstract of DOI:10.1021/jo981648l

Calix[4]arenes with four different "lower rim" substituents were synthesized following six-step sequences. The first alkyl group (R₁) was introduced using R₁X and CH₃ONa, and then reaction with R₂X and K₂CO₃ led to the introduction of a second alkyl group (R₂) at the 3-position. Benzoate was introduced as a protecting group at the 1,3-O-disubstituent stage and was removed under basic conditions after the incorporation of the third alkyl group (R₃) with R₃X and NaH. The final alkyl group (R₄) was introduced with R₄X and NaH to give the chiral title compounds.

Full text of DOI:10.1021/jo981648l

J . Org. Chem. 1999, 64, 2673-2679
2673
Syn th esis of Ca lix[4]a r en es w ith F ou r Differ en t “Low er Rim ”
Su bstitu en ts
Chun-Mei Shu and Wen-Sheng Chung*
Department of Applied Chemistry, National Chiao Tung University,
Hsinchu, Taiwan 30050, Republic of China
Sing-Ho Wu, Zong-Chia Ho, and Lee-Gin Lin*
Institute of Applied Chemistry, Chinese Culture University, Taipei, Taiwan 11114, Republic of China
Received August 13, 1998
Calix[4]arenes with four different “lower rim” substituents were synthesized following six-step
sequences. The first alkyl group (R1) was introduced using R1X and CH3ONa, and then reaction
with R2X and K2CO3 led to the introduction of a second alkyl group (R2) at the 3-position. Benzoate
was introduced as a protecting group at the 1,3-O-disubstituent stage and was removed under
basic conditions after the incorporation of the third alkyl group (R3) with R3X and NaH. The final
alkyl group (R4) was introduced with R4X and NaH to give the chiral title compounds.
In tr od u ction
previous work on the synthesis of trialkoxycalix[4]-
arenes,6 we demonstrated that alkyl ether linkages can
be introduced at various synthetic stages. We report here
a general synthetic strategy comprised a six-step se-
quence, in which monoalkoxycalix[4]arenes are treated
with different alkyl halides at various alkylation stages,
for the synthesis of calix[4]arenes that are chiral by
virtue of the four different substituents on their “lower
rim”.
Calixarenes, which are cyclic oligomers of phenol-
formaldehyde condensed compounds, are not planar and
possess an inner cavity. This unique structure has
attracted considerable attention in the research area of
enzyme mimics.1 A good enzyme-mimic model requires
not only an appropriate functional group positioned to
display the reactivity and selectivity of the real enzyme
but also the chirality to effect their high stereoselectivity.
To incorporate an appropriate functional group, properly
positioned, onto the calixarene framework was a major
goal of early calixarenes research, and a wide range of
calixarene derivatives were reported.1 However, the
preparation of calixarenes with chirality has been ac-
complished only recently.2
Resu lts a n d Discu ssion
Mon oa lk oxyca lix[4]a r en es. According to the litera-
ture, monoalkoxycalix[4]arenes have usually been pre-
pared either by a multistep process7 or by a one-step
procedure employing a careful separation technique.8
During the synthesis of a series of calix[4]arene allyl
ethers, we were surprised to find that NaOCH3 in
CH3CN would mediate the conversion of calix[4]arene
into monoallyloxycalix[4]arene in good yield.9 Further
investigation proved that calix[4]arene would react with
most of the simple primary alkyl halides in CH3CN in
the presence of NaOCH3 to yield the corresponding
monoalkoxycalix[4]arenes (2a -f) in roughly 75% yield
(Figure 1). This result was quite unexpected, seeming to
violate the notion that more severe reaction conditions
should lead to multiply-substituted products, given that
weaker bases such as Na2CO3 or K2CO3 produced the 1,3-
In the literature, several strategies, including fragment
condensation,3 introduction of chiral substituents,4 and
“lower rim” functionalization,5 have been used for the
preparation of inherently chiral calix[4]arenes. In our
(1) (a) Bo¨hmer, V. Angew. Chem., Int. Ed. Engl. 1995, 34, 713 and
references therein. (b) Gutsche, C. D. In Calixarenes, Monographs in
Supramolecular Chemistry; Stoddart, F. J ., Ed.; Royal Society of
Chemistry: Cambridge, 1989; Vol. 1 and references therein. (c)
Calixarenes, A Versatile Class of Macrocyclic Compounds; Vicens, J .,
Bo¨hmer, V., Eds.; Kluwer: Dordrecht, 1991, and references therein.
(d) Groenen, L. C.; Reinhoudt, D. N. In Supramolecular Chemistry;
Balzani, V., de Cola, L., Eds.; Kluwer: Dordrecht, 1991; pp 51-70 and
references therein.
(2) (a) Shinkai, S. Tetrahedron 1993, 49, 8933-8968 and references
therein. (b) Ferguson, G.; Gallagher, J . F.; Giunta, L.; Neri, P.;
Pappalardo, S.; Paris, M. J . Org. Chem. 1994, 59, 42 and references
therein. (c) Bo¨hmer. V.; Kraft, D.; Tabatabai, M. J . Inclusion Phenom.
1994, 19, 17 and references therein.
(3) (a) Bo¨hmer, V.; Merkel, L.; Kunz, U. J . Chem. Soc., Chem.
Commun. 1987, 896. (b) Bo¨hmer, V.; Marshollek, F.; Zetta, L. J . Org.
Chem. 1987, 52, 3200. (c) Zetta, L.; Wolff, A.; Vogt, W.; Platt, K.-L.;
Bo¨hmer, V. Tetrahedron 1991, 47, 1911. (d) Casabianca, H.; Royer,
A.; Satrallah, A.; Taty-C, A.; Vicens, J . Tetrahedron Lett. 1987, 28,
6595. (e) Shinkai, S.; Arimura, T.; Kawabata, H.; Murakami, H.; Araki,
K.; Iwamoto, K.; Matsuda, T. J . Chem. Soc., Chem. Commun. 1990,
1734. (f) Shinkai, S.; Arimura, T.; Kawabata, H.; Murakami, H.;
Iwamoto, K. J . Chem. Soc., Perkin Trans. 1 1991, 2429.
(5) (a) Iwamoto, K.; Shimizu, H.; Araki, K.; Shinkai, S. J . Am. Chem.
Soc. 1993, 115, 3997 and references therein. (b) Gonzalez, J . J .; Nieto,
P. M.; Prados, P.; Echavarren, A. M.; de Mendoza, J . J . Org. Chem.
1995, 60, 7419-7423. (c) Caccamese, S.; Pappalardo, S. Chirality 1993,
5, 159-163. (d) Iwamoto, K.; Yangagi, A.; Arimura, T.; Matsuda, T.;
Shinkai, S. Chem. Lett. 1990, 1901-1904.
(6) Ho, Z.-C.; Ku, M.-C.; Shu, C.-M.; Lin, L.-G. Tetrahedron 1996,
52, 13189-13200.
(7) (a) Gutsche, C. D.; Lin, L.-G. Tetrahedron 1986, 42, 1633-1640.
(b) Casnati, A.; Arduini, A.; Ghidini, E.; Pochini, A.; Ungaro, R.
Tetrahedron 1991, 47, 2221-2228.
(8) (a) Groenen, L. C.; Ruel, B. H. M.; Casnati, A.; Verboom, W.;
Pochini, A.; Ungaro, R.; Reinhoudt, D. N. Tetrahedron 1991, 47, 8379-
8384. (b) Araki, K.; Iwamoto, K.; Shinkai, S.; Matsuda, T. Bull. Chem.
Soc. J pn. 1990, 63, 3480-3485. (c) Bottino, F.; Giunta, L.; Pappalardo,
S. J . Org. Chem. 1989, 54, 5407-5409.
(4) (a) Arimura, T.; Kawabata, H.; Matsuda, T.; Muramatsu, T.;
Satoh, H.; Fujio, K.; Manabe, O.; Shinkai, S. J . Org. Chem. 1991, 56,
699. (b) Ikeda, A.; Nagasaki, T.; Shinkai, S. J . Phys. Org. Chem. 1992,
5, 699. (c) Matsushita, Y.; Matsui, T. Tetrahedron Lett. 1993, 46, 7433.
(d) Schneider, H.-J .; Schneider, U. J . Inclusion Phenom. 1994, 19, 67.
(9) Ku, M.-C. M.S. Thesis, Institute of Applied Chemistry, Chinese
Culture University, 1994.
10.1021/jo981648l CCC: $18.00 © 1999 American Chemical Society
Published on Web 03/20/1999

2674 J . Org. Chem., Vol. 64, No. 8, 1999
Shu et al.
4a -c were produced as racemic mixtures. Due to the lack
of any symmetry in compounds 4a -c, all of the methyl-
ene hydrogens (four calix[4]arene methylenes, benzyloxy
methylene, and alkoxy methylene) reside in different
magnetic environments, and consequently, a total of six
sets of AB quartets were observed in the range of δ 3.50-
5.00 in the proton NMR spectra. By comparing the
spectra of 4a -c and monobenzoated diallyloxycalix[4]-
arene,6 the benzoyloxy moiety of 4a -c was assigned as
anti to the two alkoxy groups.
Compounds 4a -c were further alkylated by treatment
with NaH and large primary alkyl halides in CH3CN to
give 25,26,27-trialkoxy-28-monobenzoyloxycalix[4]arenes
1
(5a -d ). The H NMR spectra of 5a -d displayed pairs of
multiplets corresponding to the newly introduced alkoxy
methylene hydrogens, which indicated that these alkoxy
methylene hydrogens are also located in a distinct
magnetic environment. This phenomena is believed to be
caused by these alkoxy moieties being syn to the two
existing alkoxy moieties, whereas an anti orientation
would result in a set of triplets for the same methylene
hydrogens. The syn orientation of three alkoxy groups
in compounds 5a -d is consistent with our earlier obser-
vation in trialkoxycalix[4]arenes cases,6 and compounds
5a -d are assigned an “up-up-up-down” conformation.
The protecting benzoate moieties were readily removed
under basic hydrolysis to liberate the fourth hydroxy
group for the final alkylation. Basic hydrolysis of com-
pounds 5a -d following a literature procedure6,7a pro-
duced the corresponding hydrolyzed products 6a -d ,
25,26,27-trialkoxy-28-hydroxycalix[4]arenes, in 81-87%
yields.
F igu r e 1. Monoalkoxycalix[4]arenes.
dialkoxy products under the same reaction conditions.
Even after extensive studies, we are still not able to
propose a reasonable explanation for the strange behavior
of NaOCH3 in this monoalkylation reaction. Other bases
such as NaOH or KOH also produced monoalkylated
calix[4]arene, but the composition of the products is
sensitive to the reaction conditions and erratically re-
producible.10
1,3-Dia lk oxyca lix[4]a r en es. When monobenzyloxy-
calix[4]arene (2f) was refluxed with a second alkyl halide
in CH3CN in the presence of K2CO3 by a literature
procedure for synthesis of 1,3-dialkoxycalix[4]arenes,11
corresponding 25-alkoxy-27-benzyloxy-calix[4]arenes (3a-
e) were formed in 88-94% yields (Figure 2). Compound
3e, 25-allyloxy-27-benzyloxy-26,28-dihydroxycalix[4]arene,
could also be prepared by refluxing monoallyloxycalix-
[4]arene (2e) with benzyl bromide in the presence of
K2CO3. It is suspected that all calix[4]arenes with two
different alkoxy substituents at their 1,3-positions can
be synthesized stepwise in either order.
1,2,3-Tr ia lk oxyca lix[4]a r en es. Treatment of 1,3-
dialkoxy compounds 3c-e with benzoyl chloride in py-
ridine at room temperature gave the corresponding mono-
benzoates 4a -c quantitatively. In compounds 4a -c, the
three substituents on the “lower rim” are all larger than
an ethoxy group. Therefore, the “through-the-annulus”
free rotation (i.e., calix[4]arene ring inversion) is re-
stricted.12 The restriction of the calix[4]arene ring inver-
sion yields a pair of enantiomers during the benzoylation
of compounds 3c-e; in other word, a chiral element13 is
created in this benzoylation reaction and compounds
1,2,3,4-Tetr a a lk oxyca lix[4]a r en es. The last alkyl
group was introduced by heating compounds 6a -d , NaH,
and a fourth primary alkyl iodide in refluxing CH3CN to
yield the final product 25,26,27,28-tetraalkoxycalix[4]-
arenes (7a -c), with four different “lower rim” substitu-
ents. The last alkoxy group can in principle be introduced
into compounds 6a -d either in syn or in anti orientation
to the other three alkoxy groups, thus producing products
7a -c in either the “cone” or “partial cone” conformations.
However, the 1H NMR spectra of 7a -c, which were
similar to those of the syn-1,3-dialkoxycalix[4]arenes,
revealed that the four different “lower rim” substituents
were all oriented in the same direction and the products
existed only in “cone” conformation. It is noteworthy that
compound 7b , 25-allyloxy-26-benzyloxy-27-butoxy-28-
propoxycalix[4]arene, was prepared either by allylation
of compound 6b or by introduction of a propoxy group
onto compound 6c. In other words, the allyloxy (the third
alkoxy) and n-propoxy (the fourth alkoxy) groups can be
introduced into products 3d in either order, which is
similar to the previous observation with 1,3-dialkoxycalix-
[4]arenes (3a -e).
The products 5a -d , 6a -d , and 7a -c all inherit the
chirality of compounds 4a -d , and all exist in a racemic
mixture. The optical resolution and X-ray structure
(13) Compounds 4-7 are asymmetric molecules and belong to the
C1 point group. The chiral element of compounds 4-7 can be visualized
either as a chiral axis that goes through the center of the calix[4]arene’s
cavity or as a chiral plane that contains the cavity main axis. Even
though the calixarenes can be classified as meta-cyclophanes, the
chirality of the calix[4]arenes is different from cyclophane systems.
For an excellent review on the specification of molecular chirality,
see: Cahn, R. S.; Ingold, C.; Prelog, V. Angew. Chem., Int. Ed. Engl.
1966, 5, 385.
(10) Unpublished results, Chinese Culture University.
(11) van Loon, J .-D.; Arduini, A.; Coppi, L.; Verboom, W.; Pochini,
A.; Ungaro, R.; Harkema, S.; Reinhoudt, D. N. J . Org. Chem. 1990,
55, 5639-5646.
(12) (a) Araki, K.; Iwamoto, K.; Shinkai, S.; Matsuda, T. Chem. Lett.
1989, 1747. (b) Iwamoto, K.; Araki, K.; Shinkai, S. J . Org. Chem. 1991,
56, 4956. The through-the-annulus free rotation can be inhibited by R
groups larger than the ethyl substituent at room temperature.

Calix[4]arenes with Different “Lower Rim” Substituents
J . Org. Chem., Vol. 64, No. 8, 1999 2675
F igu r e 2. Synthesis of calix[4]arenes with four different “lower rim” substituents.

2676 J . Org. Chem., Vol. 64, No. 8, 1999
Shu et al.
25-Bu toxy-26,27,28-tr ih yd r oxyca lix[4]a r en e (2d ). The
reaction mixture was refluxed with 1.40 mL (2.26 g, 12.3
mmol) of n-butyl iodide for 24 h to afford 1.73 g (72%) of
determination of these compounds (4a -d , 5a -d , 6a -d ,
and 7a -c) is under investigation at present.14
1
colorless crystals: mp 240-241 °C; H NMR (CDCl3) δ 9.73
Exp er im en ta l Section 15
(s, 1 H), 9.41 (s, 2 H), 6.64-7.08 (m, 12 H), 4.36 (d, 2 H, J )
13.2 Hz), 4.28 (d, 2 H, J ) 13.2 Hz), 4.14 (t, 2H, J ) 3.5 Hz),
3.46 (2d, 4 H, J ) 13.2 Hz), 2.13-2.20 (m, 2 H), 1.68-1.76 (m,
2 H), 1.12 (t, 3 H, J ) 7.2 Hz); 13C NMR (CDCl3) δ 151.50 (Cq),
150.80 (Cq), 149.22 (Cq), 134.23 (Cq), 129.31 (CH), 128.84 (CH),
128.80 (CH), 128.75 (CH), 128.41 (CH), 126.05 (CH), 121.95
(CH), 120.90 (CH), 77.32 (CH2), 77.22 (CH2), 31.96 (CH2), 31.91
(CH2), 31.45 (CH2), 19.26 (CH2), 14.01 (CH3); FAB-MS m/z 479
(M+ - 1). Anal. Calcd for C32H32O4: C, 79.97; H, 6.71. Anal.
Calcd for C32H32O4‚1/4H2O: C, 79.23; H, 6.75. Found: C, 78.97;
H, 6.70.
Gen er a l P r oced u r e for 25-Alk oxyca lix[4]a r en es 2a -
f. A sample of 2.12 g (5.00 mmol) of calix[4]arene (1) and 0.32
g (5.9 mmol) of NaOCH3 was refluxed in 150 mL of CH3CN
for 30 min to monodeprotonate the calix[4]arene completely.
An excess amount of alkyl halides was added, and the reaction
mixture was further refluxed for 8 h (24 h for less reactive
alkyl halides). The reaction mixture was neutralized with a
few drops of acetic acid, and solvent was removed to leave an
off-white residue. The residue was recrystallized from CHCl3
with a slow addition of CH3OH to yield the corresponding
monoalkylated calix[4]arene 2a -f.
25-Meth oxy-26,27,28-tr ih yd r oxyca lix[4]a r en e (2a ). The
reaction mixture was refluxed with 0.80 mL (1.82 g, 12.8
mmol) of methyl iodide for 8 h to afford 1.60 g (73%) of colorless
crystals: mp 273-274 °C; 1H NMR (CDCl3) δ 9.69 (s, 1 H),
9.34 (s, 2 H), 6.67-7.10 (m, 12 H), 4.35 (d, 2 H, J ) 13.0 Hz),
4.26 (d, 2 H, J ) 13.0 Hz), 4.13 (s, 3 H), 3.46 (2d, 4 H, J )
13.0 Hz); 13C NMR (CDCl3) δ 152.54 (Cq), 150.65 (Cq), 149.22
(Cq), 134.04 (Cq), 129.38 (CH), 128.82 (CH), 128.72 (CH), 128.55
(CH), 128.43 (CH), 126.20 (CH), 121.90 (CH), 120.98 (CH),
63.43 (CH3), 31.88 (CH2), 31.30 (CH2); FAB-MS m/z 437 (M+
- 1). Anal. Calcd for C29H26O4: C, 79.43; H, 5.98. Found: C,
79.38; H, 6.03.
25-Eth oxy-26,27,28-tr ih yd r oxyca lix[4]a r en e (2b). The
reaction mixture was refluxed with 1.00 mL (1.95 g, 12.5
mmol) of ethyl iodide for 8 h to afford 1.74 g (77%) of colorless
crystals: mp 292-293 °C; 1H NMR (CDCl3) δ 9.86 (s, 1 H),
9.52 (s, 2 H), 6.68-7.14 (m, 12 H), 4.22-4.42 (m, 6 H), 3.50
(2d, 4 H, J ) 13.4 Hz), 1.77 (t, 3 H, J ) 7.1 Hz); 13C NMR
(CDCl3) δ 151.28 (Cq), 150.62 (Cq), 149.33 (Cq), 134.39 (Cq),
129.56 (CH), 129.22 (CH), 128.76 (CH), 128.69 (CH), 128.56
(CH), 128.50 (CH), 128.41 (CH), 126.10 (CH), 121.85 (CH),
120.98 (CH), 72.60 (CH2), 31.88 (CH2), 31.46 (CH2), 15.17
(CH3); FAB-MS m/z 451 (M+ - 1). Anal. Calcd for C30H28O4:
C, 79.62; H, 6.24. Found: C, 79.60; H, 6.23.
25-Allyloxy-26,27,28-tr ih yd r oxyca lix[4]a r en e (2e). The
reaction mixture was refluxed with 1.00 mL (1.40 g, 11.6
mmol) of allyl bromide for 8 h to afford 1.74 g (75%) of colorless
needlelike crystals: mp 201-202 °C; 1H NMR (CDCl3) δ 9.71
(s, 1 H), 9.31 (s, 2 H), 6.66-7.12 (m, 12 H), 6.42-6.47 (m, 1
H), 5.53-5.65 (m, 2 H), 4.65-4.68 (m, 2 H), 4.37 (d, 2 H, J )
13.2 Hz), 4.27 (d, 2 H, J ) 13.2 Hz), 3.46 (2d, 4 H, J ) 13.2
Hz); 13C NMR (CDCl3) δ 151.24 (Cq), 150.78 (Cq), 149.30 (Cq),
134.35 (Cq), 132.28 (CH), 129.40 (CH), 128.87 (CH), 128.79
(CH), 128.50 (CH), 128.46 (CH), 128.43 (CH), 126.28 (CH),
121.96 (CH), 120.99 (CH), 120.34 (CH2), 77.75 (CH2), 31.94
(CH2), 31.63 (CH2); FAB-MS m/z 463 (M+ - 1). Anal. Calcd
for C31H28O4: C, 80.15; H, 6.08. Anal. Calcd for C31H28O4‚
1/6CHCl3: C, 77.27; H, 5.86. Found: C, 77.22; H, 5.91%.
25-Ben zyloxy-26,27,28-tr ih ydr oxycalix[4]ar en e (2f). The
reaction mixture was refluxed with 1.50 mL (2.16 g, 12.6
mmol) of benzyl bromide for 9 h to afford 2.06 g (80%) of
1
colorless crystals: mp 234-235 °C; H NMR (CDCl3) δ 9.56
(s, 1 H), 9.21 (s, 2 H), 6.66-7.71 (m, 17 H), 5.19 (s, 2 H), 4.34
(d, 2 H, J ) 13.4 Hz), 4.22 (d, 2 H, J ) 13.4 Hz), 3.43 (2d, 4 H,
J ) 13.4 Hz); 13C NMR (CDCl3) δ 151.22 (Cq), 150.79 (Cq),
149.10 (Cq), 135.47 (Cq), 134.29 (Cq), 129.49 (CH), 129.02 (CH),
128.94 (CH), 128.90 (CH), 128.77 (CH), 128.72 (CH), 128.37
(CH), 128.30 (CH), 126.26 (CH), 121.90 (CH), 120.84 (CH),
79.26 (CH2), 31.84(CH2), 31.59(CH2); FAB-MS m/z 513 (M+
-
1). Anal. Calcd for C35H30O4: C, 81.69; H, 5.88. Anal. Calcd
for C35H30O4‚1/4H2O: C, 80.98; H, 5.92. Found: C, 81.08; H,
5.90.
25-P r op oxy-26,27,28-tr ih yd r oxyca lix[4]a r en e (2c). The
reaction mixture was refluxed with 1.20 mL (2.09 g, 12.3
mmol) of n-propyl iodide for 10 h to afford 1.63 g (70%) of
Gen er a l P r oced u r e for 25,27-Dia lk oxyca lix[4]a r en es
3a -e. A sample of 2.57 g (5.00 mmol) of 25-benzyloxy-26,27,-
28-trihydroxycalix[4]arene (2f), 0.82 g (5.9 mmol) of K2O3, and
an excess amount of alkyl halides was refluxed in 50 mL of
CH3CN. The solvent was removed, and the residue was
recrystallized from CHCl3 with a slow addition of CH3OH to
yield the corresponding dialkylated products 3a -e.
25-Be n zyloxy-27-m e t h oxy-26,28-d ih yd r oxyca lix[4]-
a r en e (3a ). The reaction mixture was refluxed with 1.20 mL
(2.74 g, 19.3 mmol) of methyl iodide for 4 h to afford 2.32 g
(88%) of colorless crystals: mp 245-246 °C; 1H NMR (CDCl3)
δ 7.75 (s, 2H), 7.59-7.61 (m, 2 H), 7.39-7.41 (m, 3 H), 6.65-
7.06 (m, 12 H), 5.07 (s, 2 H), 4.24-4.31 (2d, 4 H, J ) 13.1 Hz),
3.93 (s, 3 H), 3.35 (d, 2 H, J ) 13.0 Hz), 3.28 (d, 2 H, J )
13.1 Hz); 13C NMR (CDCl3) δ 153.11 (Cq), 151.69 (Cq), 136.41
(Cq), 133.37 (Cq), 133.01 (Cq), 128.95 (CH), 128.91 (CH), 128.53
(CH), 128.44 (CH), 128.41 (CH), 128.27 (CH), 128.05 (CH),
125.33 (CH), 125.27 (CH), 119.02 (CH), 78.04 (CH2), 63.44
(CH3), 31.34 (CH2), 31.16 (CH2); FAB-MS m/z 529 (M+ + 1).
Anal. Calcd for C36H32O4: C, 81.79; H, 6.10. Found: C, 81.53;
H, 6.01.
25-B e n zy lo x y -27-e t h o x y -26,28-d ih y d r o x y c a lix [4]-
a r en e (3b). The reaction mixture was refluxed with 1.50 mL
(2.93 g, 18.8 mmol) of ethyl iodide for 4 h to afford 2.41 g (89%)
of colorless crystals: mp 258-259 °C; 1H NMR (CDCl3) δ 8.19
(s, 2 H), 7.74-7.76 (m, 2 H), 7.43-7.45 (m, 3 H), 6.61-7.05
(m, 12 H), 5.08 (s, 2 H), 4.34 (d, 2 H, J ) 12.9 Hz), 4.28 (d, 2
H, J ) 12.9 Hz), 4.09 (q, 2 H, J ) 7.0 Hz), 3.37 (2d, 4 H, J )
12.9 Hz), 1.65 (t, 3 H, J ) 7.0 Hz); 13C NMR (CDCl3) δ 153.25
(Cq), 151.79 (Cq), 151.59 (Cq), 136.75 (Cq), 133.54 (Cq), 133.50
(Cq), 129.02 (CH), 128.86 (CH), 128.53 (CH), 128.44 (CH),
128.37 (CH), 128.12 (CH), 128.08 (CH), 127.51 (CH), 125.58
1
colorless crystals: mp 262-263 °C; H NMR (CDCl3) δ 9.62
(s, 1 H), 9.31 (s, 2 H,), 6.52-6.97 (m, 12 H), 4.24 (d, 2 H, J )
13.3 Hz), 4.16 (d, 2 H, J ) 13.3 Hz), 3.99 (t, 2 H, J ) 6.9 Hz),
3.42 (2d, 4 H, J ) 13.3 Hz), 2.03-2.11 (m, 2 H), 1.15 (t, 3 H,
J ) 7.4 Hz); 13C NMR (CDCl3) δ 151.40 (Cq), 150.77 (Cq), 149.17
(Cq), 134.19 (Cq), 129.28 (CH), 128.79 (CH), 128.76 (CH), 128.70
(CH), 128.41(CH), 128.38 (CH), 126.02 (CH), 121.91 (CH),
120.87 (CH), 78.96 (CH2), 31.87 (CH2), 31.41 (CH2), 23.22
(CH2), 10.56 (CH3); FAB-MS m/z 465 (M+ - 1). Anal. Calcd
for C31H30O4: C, 79.80; H, 6.48. Anal. Calcd for C31H30O4‚
H2O: C, 76.84; H, 6.66. Found: C, 76.91; H, 6.31.
(14) Single-crystal X-ray crystallography of the tetraalkoxy calix-
[4]arenes indicated that it is in a “cone” conformation. The author has
deposited atomic coordinates for 7c with the Cambridge Crystal-
lographic Data Center. The coordinates can be obtained, on request,
from the Director, Cambridge Crystallographic Data Center, 12 Union
Road, Cambridge, CB2 1EZ, U.K. We are indebted to Mr. J .-H. Lee
(NTU) and Prof. S.-M. Peng for the single-crystal X-ray analyses.
(15) All reagents were obtained from Merck Chemical Co. and used
without further purification. Melting points were taken in capillary
tubes on a Mel-Temp apparatus (Laboratory Devices Cambridge, MA)
and are uncorrected. 1H NMR spectra were recorded on either a Varian
Gemini 200 or Unity-300 spectrometer. Chemical shifts are reported
as δ values in ppm relative to TMS (δ ) 0.0) as an internal standard.
DEPT program of the 13C NMR was used to determine the Cq, CH,
CH2, and CH3 of each carbon. FAB-MS spectra were taken on a J EOL
J MS-HX 110 spectrometer, and elemental analyses were taken on a
Perkin-Elmer 240C analyzer. MMCALC program in ChemWindow 3
computer software package was used to calculate the theoretical EA
values. Chromatographic separations were performed with Merck silica
gel (230-400 mesh ASTM) on columns of 25 mm diameter filled to a
height of 150 mm. TLC analyses were carried out on Merck aluminum
sheets silica gel 60 F254 plates (absorbant thickness 0.2 mm).

Calix[4]arenes with Different “Lower Rim” Substituents
J . Org. Chem., Vol. 64, No. 8, 1999 2677
(CH), 125.29 (CH), 119.01 (CH), 78.18 (CH2), 72.11 (CH2), 31.51
(CH2), 31.43 (CH2), 15.29 (CH3); FAB-MS m/z 541 (M+ - 1).
Anal. Calcd for C37H34O4: C, 81.89; H, 6.32. Found: C, 81.75;
H, 6.35.
benzoated and yielded 0.63 g (95%) of colorless needlelike
crystals: mp 179-181 °C; 1H NMR (CDCl3) δ 7.80 (s, 1 H),
6.12-7.33 (m, 22 H), 5.05, 4.83 (AB, 2 H, J ) 12.1 Hz), 4.26
(d, 1 H, J ) 13.0 Hz), 4.12 (d, 1 H, J ) 13.0 Hz), 3.72-4.05
(m, 6 H), 3.38 (d, 1 H, J ) 13.0 Hz), 3.24 (d, 1 H, J ) 13.0 Hz),
1.77-1.83 (m, 2 H), 1.04 (t, 3 H, J ) 7.4 Hz); 13C NMR (CDCl3)
δ 163.46 (Cq), 154.47 (Cq), 153.43 (Cq), 153.21 (Cq), 147.96 (Cq),
137.61 (Cq), 133.14 (Cq), 133.04 (Cq), 132.49 (Cq), 132.39 (CH),
130.10 (CH), 129.73 (CH), 129.55 (CH), 129.17 (CH), 128.83
(CH), 128.16 (CH), 128.03 (CH), 127.90 (CH), 127.46 (CH),
127.14 (CH), 127.07 (CH), 126.75 (CH), 123.57 (CH), 118.75
(CH), 75.20 (CH2), 74.50 (CH2), 37.94 (CH2), 31.37 (CH2), 30.91
(CH2), 23.03 (CH2), 10.61 (CH3); FAB-MS m/z 661 (M+ + 1).
Anal. Calcd for C45H40O5: C, 81.79; H, 6.10. Anal. Calcd for
C45H40O5‚1/4H2O: C, 81.24; H, 6.14. Found: C, 81.31; H, 6.13.
25-Ben zyloxy-26-b en zoyloxy-27-b u t oxy-28-h yd r oxy-
ca lix[4]a r en e (4b). A sample of 0.57 g (1.0 mmol) of 25-
benzyloxy-27-butoxy-26,28-dihydroxy-calix[4]arene (3d ) was
benzoated and yielded 0.62 g (93%) of colorless crystals: mp
25-Be n zyloxy-27-p r op oxy-26,28-d ih yd r oxyca lix[4]-
a r en e (3c). The reaction mixture was refluxed with 1.50 mL
(2.61 g, 15.4 mmol) of n-propyl iodide for 3 h to afford 2.61 g
(94%) of colorless needlelike crystals: mp 234-235 °C; 1H
NMR (CDCl3) δ 8.14 (s, 2 H), 7.74-7.76 (m, 2 H), 7.43-7.45
(m, 3 H), 6.62-7.06 (m, 12 H), 5.07 (s, 2 H), 4.36 (d, 2 H, J )
13.0 Hz), 4.29 (d, 2 H, J ) 13.0 Hz), 3.95 (t, 2 H, J ) 6.1 Hz),
3.37 (2d, 4 H, J ) 13.0 Hz), 2.03-2.06 (m, 2 H), 1.24 (t, 3 H,
J ) 7.2 Hz); 13C NMR (CDCl3) δ 153.37 (Cq), 151.82 (Cq), 151.65
(Cq), 136.77 (Cq), 133.38 (Cq), 133.33 (Cq), 129.04 (CH), 128.91
(CH), 128.54 (CH), 128.49 (CH), 128.42 (CH), 128.05 (CH),
128.02 (CH), 127.47 (CH), 125.56 (CH), 125.26 (CH), 118.94
(CH), 78.33 (CH2), 78.25 (CH2), 31.43 (CH2), 23.47 (CH2), 11.02
(CH3); FAB-MS m/z 555 (M+ - 1). Anal. Calcd for C38H36O4:
C, 81.99; H, 6.52. Found: C, 82.01; H, 6.55.
25-B e n zy lo x y -27-b u t o x y -26,28-d ih y d r o x y c a lix [4]-
a r en e (3d ). The reaction mixture was refluxed with 1.70 mL
(2.75 g, 14.9 mmol) of n-butyl iodide for 4 h to afford 2.59 g
(91%) of colorless needlelike crystals: mp 196-197 °C; 1H
NMR (CDCl3) δ 8.06 (s, 2 H), 7.73-7.74 (m, 2 H), 7.43-7.46
(m, 3 H), 6.60-7.06 (m, 12 H), 5.07 (s, 2 H), 4.34 (d, 2 H, J )
13.0 Hz), 4.29 (d, 2 H, J ) 13.0 Hz), 3.96 (t, 2 H, J ) 6.1 Hz),
3.36 (2d, 4 H, J ) 13.0 Hz), 1.92-2.02 (m, 2 H), 1.60-1.70 (m,
2 H), 1.06 (t, 3 H, J ) 7.4 Hz); 13C NMR (CDCl3) δ 153.33 (Cq),
151.92 (Cq), 151.69 (Cq), 136.74 (Cq), 133.30 (Cq), 133.23 (Cq),
129.56 (CH), 128.99 (CH), 128.86 (CH), 128.53 (CH), 128.45
(CH), 128.40 (CH), 128.00 (CH), 127.46 (CH), 125.48 (CH),
125.18 (CH), 118.89 (CH), 78.26 (CH2), 76.45 (CH2), 32.05
(CH2), 31.40 (CH2), 19.23 (CH2), 14.03 (CH3); FAB-MS m/z 569
(M+ - 1). Anal. Calcd for C39H38O4: C, 82.08; H, 6.71. Found:
C, 82.06; H, 6.74.
25-Allyloxy-27-b e n zyloxy-26,28-d ih yd r oxyca lix[4]-
a r en e (3e). Meth od A. F r om 25-Ben zyloxyca lix[4]a r en e
(2f). A sample of 2.57 g (5.00 mmol) of 25-benzyloxy-26,27,-
28-trihydroxycalix[4]arene (2f), 0.82 g (5.9 mmol) of K2CO3,
and 1.30 mL (1.82 g, 15.0 mmol) of allyl bromide was refluxed
in 50 mL of CH3CN for 4 h. The solvent was removed, and the
residue was recrystallized from CHCl3 and CH3OH to yield
2.55 g (92%) of colorless crystals: mp 213-214 °C; 1H NMR
(CDCl3) δ 7.98 (s, 2 H), 7.70-7.72 (m, 2 H), 7.31-7.46 (m, 3
H), 6.63-7.06 (m, 12 H), 6.10-6.25 (m, 1 H), 5.69-5.75 (d, 1
H, J ) 18.5 Hz), 5.30 (d, 1 H, J ) 10.3 Hz), 5.07 (s, 2 H), 4.53
(s, 2 H), 4.26-4.37 (2d, 4 H, J ) 12.9 Hz), 3.37 (2d, 4 H, J )
12.9 Hz); 13C NMR (CDCl3) δ 153.28 (Cq), 151.59 (Cq), 136.60
(Cq), 133.19 (Cq), 133.13 (CH), 132.62 (CH), 129.50 (CH), 128.98
(CH), 128.88 (CH), 128.55 (CH), 128.46 (CH), 128.44 (CH),
128.03 (CH), 127.92 (CH), 127.90 (CH), 127.58 (CH), 125.48
(CH), 125.36 (CH), 118.90 (CH), 117.54 (CH2), 78.26 (CH2),
76.66 (CH2), 31.38 (CH2); FAB-MS m/z 553 (M+ - 1). Anal.
Calcd for C38H34O4: C, 82.28; H, 6.18. Anal. Calcd for C38H34O4‚
1/4H2O: C, 81.62; H, 6.22. Found: C, 81.80; H, 6.20.
Meth od B. Fr om 25-Allyloxycalix[4]ar en e (2e). A sample
of 2.32 g (5.00 mmol) of 25-allyloxy-26,27,28-trihydroxy-
calix[4]arene (2e), 0.82 g (5.9 mmol) of K2CO3, and 1.50 mL
(2.16 g, 12.6 mmol) of benzyl bromide was refluxed in 50 mL
of CH3CN for 4 h. The solvent was removed, and the residue
was recrystallized from CHCl3 and CH3OH to yield 2.50 g
(90%) of colorless crystals that were identical in physical and
spectral properties with compound 3e obtained by method A.
Gen er a l P r oced u r e for 25,27-Dia lk oxy-26-ben zoyl-
oxyca lix[4]a r en es 4a -c. A sample of 1.00 mmol of 25,27-
dialkoxycalix[4]arenes (3c-e) was dissolved in 10 mL of
pyridine, and 2.00 mL (3.14 g, 17.0 mmol) of benzoyl chloride
was added. The mixture was stirred at room temperature for
48 h and was then treated with 100 mL of diluted HCl to
induce a white solid. The white solid was recrystallized from
CHCl3 with a slow addition of CH3OH to yield the correspond-
ing benzoate products 4a -c.
1
161-162 °C; H NMR (CDCl3) δ 7.63 (s, 2 H), 6.01-7.23 (m,
17 H), 4.94, 4.74 (AB, 2 H, J ) 12.1 Hz), 3.61-4.17 (m, 8 H),
3.28 (d, 1 H, J ) 12.7 Hz), 3.24 (d, 1 H, J ) 12.7 Hz), 1.39-
1.80 (m, 4 H), 0.92 (t, 3 H, J ) 7.3 Hz); 13C NMR (CDCl3) δ
163.60 (Cq), 154.60 (Cq), 153.59 (Cq), 153.28 (Cq), 148.04 (Cq),
137.70 (Cq), 133.24 (Cq), 132.55 (Cq), 132.46 (CH), 130.23 (CH),
129.89 (CH), 129.36 (CH), 129.29 (CH), 129.25 (CH), 128.93
(CH), 128.24 (CH), 128.09 (CH), 128.02 (CH), 127.53 (CH),
127.24 (CH), 127.16 (CH), 126.86 (CH), 125.08 (CH), 118.79
(CH), 74.68 (CH2), 73.63 (CH2), 37.98 (CH2), 37.92 (CH2),
31.73 (CH2), 31.44 (CH2), 30.98 (CH2), 19.09 (CH2), 14.15(CH3);
FAB-MS m/z 675 (M+ + 1). Anal. Calcd for C46H42O5: C, 81.87;
H, 6.27. Anal. Calcd for C46H42O5‚1/4H2O: C, 81.33; H, 6.31.
Found: C, 81.24; H, 6.26.
25-Allyloxy-26-b en zoyloxy-27-b en zyloxy-28-h yd r oxy-
ca lix[4]a r en e (4c). A sample of 0.55 g (1.0 mmol) of 25-
allyloxy-27-benzyloxy-26,28-dihydroxycalix[4]arene (3e) was
benzoated and yielded 0.64 g (98%) of colorless needlelike
crystals: mp 162-163 °C; 1H NMR (CDCl3) δ 7.57 (s, 1 H),
6.18-7.36 (m, 22 H), 5.95-6.10 (m, 1 H), 5.34-5.37 (m, 2 H),
5.08, 4.84 (AB, 2 H, J ) 11.9 Hz), 4.60-4.68 (m, 1 H), 4.26-
4.36 (m, 1 H), 4.17 (d, 1 H, J ) 13.1 Hz), 4.11 (d, 1 H, J ) 13.1
Hz), 3.62-4.17 (m, 4 H), 3.37 (d, 1 H, J ) 13.1 Hz), 3.27 (d, 1
H, J ) 13.1 Hz); 13C NMR (CDCl3) δ 163.60 (Cq), 154.20 (Cq),
153.49 (Cq), 153.18 (Cq), 147.95 (Cq), 137.25 (Cq), 133.59 (Cq),
133.32 (Cq), 132.65 (Cq), 132.62 (Cq), 132.56 (Cq), 132.53 (CH),
132.35 (CH), 130.27 (CH), 129.41 (CH), 128.21 (CH), 128.18
(CH), 128.10 (CH), 127.81 (CH), 127.42 (CH), 127.19 (CH),
127.11 (CH), 125.16 (CH), 118.77 (CH), 117.27(CH2), 74.87
(CH2), 73.87 (CH2), 37.89 (CH2), 37.86 (CH2), 31.22 (CH2), 31.02
(CH2); FAB-MS m/z 659 (M+ + 1). Anal. Calcd for C45H38O5:
C, 82.04; H, 5.81. Anal. Calcd for C46H38O5‚1/4H2O: C, 81.49;
H, 5.85. Found: C, 81.30; H, 5.80.
Gen er a l P r oced u r e for 25,26,27-Tr ia lk oxy-28-ben -
zoyloxyca lix[4]a r en es 5a -d . A sample of 1.0 mmol of 25,-
27-dialkoxy-26-benzoyloxycalix[4]arene (4a -c), 0.12 g (5.0
mmol) of NaH, and an excess amount of alkyl halides was
refluxed in 50 mL of CH3CN for 1 h. The solvent was removed,
and the crude product was recrystallized from CHCl3 with a
slow addition of CH3OH to yield the corresponding trialkoxy
products 5a -d .
25-Ally lo x y -26-b e n z y lo x y -27-b e n z o y lo x y -28-p r o -
p oxyca lix[4]a r en e (5a ). A sample of 0.66 g (1.0 mmol) of 25-
ben zyloxy-26-ben zoyloxy-28-h ydr oxy-27-pr opoxyca lix[4]-
arene (4a ) was alkylated with 0.43 mL (0.60 g, 5.0 mmol) of
allyl bromide and yielded 0.60 g (86%) of colorless crystals:
mp 155-156 °C; 1H NMR (CDCl3) δ 6.39-7.74 (m, 22 H), 5.48-
5.62 (m, 1 H), 4.71-4.89 (m, 4 H), 4.03-4.20 (m, 4 H), 3.47-
3.85 (m, 6 H), 3.17 (d, 1 H, J ) 13.2 Hz), 2.99 (d, 1 H, J ) 13.2
Hz), 1.84-1.91 (m, 2 H), 1.04 (t, 3 H, J ) 7.5 Hz); 13C NMR
(CDCl3) δ 166.12 (Cq), 157.70 (Cq), 157.45 (Cq), 157.21 (Cq),
150.07 (Cq), 139.60 (CH), 139.11 (Cq), 138.60 (Cq), 135.57 (Cq),
135.27 (CH), 134.88 (Cq), 133.80 (CH), 133.55 (CH), 133.42
(CH), 132.34 (CH), 130.63 (CH), 130.58 (CH), 130.49 (CH),
130.39 (CH), 129.89 (CH), 129.55 (CH), 129.41 (CH), 124.54
(CH), 123.42 (CH), 114.91 (CH2), 78.29 (CH2), 75.36 (CH2),
25-B e n z y lo x y -26-b e n z o y lo x y -28-h y d r o x y -27-p r o -
p oxyca lix[4]a r en e (4a ). A sample of 0.56 g (1.0 mmol) of
25-benzyloxy-27-propoxy-26,28-dihydroxycalix[4]arene (3c) was

2678 J . Org. Chem., Vol. 64, No. 8, 1999
Shu et al.
38.65 (CH2), 32.73 (CH2), 32.65 (CH2), 25.28 (CH2), 12.42 (CH3);
FAB-MS m/z 701 (M+ + 1). Anal. Calcd for C48H44O5: C, 82.26;
H, 6.33. Anal. Calcd for C48H44O5‚1/2H2O: C, 81.21; H, 6.39.
Found: C, 81.40; H, 6.29.
25-Allyloxy-26-ben zyloxy-27-h yd r oxy-28-p r op oxyca lix-
[4]a r en e (6a ). A sample of 0.50 g (0.71 mmol) of 25-allyloxy-
26-benzyloxy-27-benzoyloxy-28-propoxycalix[4]arene (5a ) was
subjected to hydrolysis and yielded 0.35 g (81%) of color-
1
25-Ben zyloxy-26-b en zoyloxy-27-b u t oxy-28-p r op oxy-
ca lix[4]a r en e (5b). A sample of 0.67 g (1.0 mmol) of 25-
benzyloxy-26-benzoyloxy-27-butoxy-28-hydroxy-calix[4]arene
(4b) was alkylated with 0.48 mL (0.84 g, 4.9 mmol) of n-propyl
iodide and yielded 0.58 g (82%) of colorless crystals: mp 158-
159 °C; 1H NMR (CDCl3) δ 6.40-7.80 (m, 22 H), 4.84, 4.66
(AB, 2 H, J ) 10.9 Hz), 4.12-4.19 (m, 2 H), 3.82 (bd, 3 H, J )
12.3 Hz), 3.25-3.58 (m, 5 H), 3.10 (t, 2 H, J ) 13.5 Hz), 1.74-
1.84 (m, 2 H), 1.51-1.56 (m, 2 H), 1.10-1.45 (m, 2 H), 1.02 (t,
3 H, J ) 7.3 Hz), 0.53 (t, 3 H, J ) 7.6 Hz); 13C NMR (CDCl3)
δ 164.52 (Cq), 156.72 (Cq), 155.85 (Cq), 155.51 (Cq), 148.47 (Cq),
137.39 (Cq), 136.78 (Cq), 136.69 (Cq), 133.94 (Cq), 133.72 (Cq),
133.41(CH), 133.31 (Cq), 133.21 (Cq), 132.03 (CH), 131.86 (CH),
130.69 (CH), 130.08 (CH), 129.94 (CH), 129.04 (CH), 128.92
(CH), 128.82 (CH), 128.75 (CH), 128.36 (CH), 127.97 (CH),
127.75 (CH), 124.28 (CH), 122.65 (CH), 122.04 (CH), 121.66
(CH), 76.73 (CH2), 75.37 (CH2), 74.28 (CH2), 36.96 (CH2), 32.55
(CH2), 30.50 (CH2), 30.35 (CH2), 21.56 (CH2), 19.50 (CH2), 14.04
(CH3), 8.98(CH3); FAB-Ms m/z 717 (M+ + 1). Anal. Calcd for
less crystals: mp 106-107 °C; H NMR (CDCl3) δ 7.45-7.48
(m, 2 H), 7.32-7.38 (m, 3 H), 6.38-7.30 (m, 12 H), 5.09
(s, 1 H), 4.78-4.99 (m, 4 H), 4.54-4.58 (m, 2 H), 4.31-4.44
(m, 4 H), 3.72-3.78 (m, 2 H), 3.07-3.33 (m, 4 H), 1.83-
1.91 (m, 2 H), 1.18 (t, 3 H, J ) 7.5 Hz); 13C NMR (CDCl3) δ
155.85 (Cq), 154.20 (Cq), 154.07 (Cq), 153.27 (Cq), 137.29
(Cq), 137.15 (Cq), 136.23 (CH), 133.43 (Cq), 133.34 (Cq),
132.87 (Cq), 132.49 (Cq), 131.01 (Cq), 130.67 (Cq), 129.01 (CH),
128.58 (CH), 128.41 (CH), 128.31 (CH), 127.92 (CH), 127.85
(CH), 123.26 (CH), 123.21 (CH), 123.09 (CH), 119.20 (CH),
116.12 (CH2), 77.44 (CH2), 75.11 (CH2), 31.35 (CH2), 31.18
(CH2), 30.86 (CH2), 23.31 (CH2), 10.76 (CH3); FAB-MS m/z 597
(M+ + 1). Anal. Calcd for C41H40O4: C, 82.52; H, 6.76. Anal.
Calcd for C41H40O4‚1/4H2O: C, 81.90; H, 6.79. Found: C, 82.08;
H, 6.79.
25-Ben zyloxy-27-bu toxy-26-h yd r oxy-28-p r op oxyca lix-
[4]a r en e (6b). A sample of 0.40 g (0.56 mmol) of 25-benzyloxy-
26-benzoyloxy-27-butoxy-28-propoxycalix[4]arene (5b) was sub-
jected to hydrolysis and yielded 0.29 g (85%) of colorless
crystals: mp 117-118 °C; 1H NMR (CDCl3) δ 7.50-7.52 (m, 2
H), 7.35-7.38 (m, 2 H), 6.36-7.17 (m, 12 H), 4.86, 4.74 (AB, 2
H, J ) 10.9 Hz), 4.71 (s, 1 H), 4.32-4.45 (m, 4 H), 3.72-3.75
(m, 4 H), 3.17-3.30 (m, 4 H), 1.78-1.81 (m, 2 H), 1.52-1.63
(m, 2H), 1.41-1.49 (m, 2 H), 0.98 (t, 3 H, J ) 7.3 Hz), 0.64 (t,
3 H, J ) 7.5 Hz); 13C NMR (CDCl3) δ 156.83 (Cq), 154.18 (Cq),
154.08 (Cq), 153.24 (Cq), 137.08 (Cq), 137.07 (Cq), 133.48 (Cq),
132.88 (Cq), 132.46 (Cq), 131.26 (Cq), 130.99 (Cq), 129.14 (Cq),
129.12 (Cq), 128.60 (CH), 128.43 (CH), 128.37 (CH), 128.00
(CH), 127.95 (CH), 127.89 (CH), 127.83 (CH), 127.80 (CH),
122.94 (CH), 119.31 (CH), 77.76 (CH2), 76.59 (CH2), 75.69
(CH2), 32.35 (CH2), 30.87 (CH2), 30.79 (CH2), 30.68 (CH2), 22.31
(CH2), 19.59 (CH2), 14.04 (CH3), 9.39 (CH3); FAB-MS m/z 613
(M+ + 1). Anal. Calcd for C42H44O4: C, 82.32; H, 7.24. Found:
C, 82.00; H, 7.44.
25-Allyloxy-26-ben zyloxy-28-bu toxy-27-h yd r oxyca lix-
[4]a r en e (6c). A sample of 0.30 g (0.42 mmol) of 25-allyloxy-
26-benzyloxy-27-benzoyloxy-28-butoxycalix[4]arene (5c) was
subjected to hydrolysis and yielded 0.21 g (81%) of colorless
crystals: mp 114-116 °C; 1H NMR (CDCl3) δ 4.46-7.48 (m, 2
H), 7.34-7.39 (m, 3 H), 6.39-7.25 (m, 13 H), 5.05 (s, 1 H),
4.95-4.99 (m 2 H), 4.88, 4.82 (AB, 2 H, J ) 11.3 Hz), 4.54-
4.60 (m, 2 H), 4.32-4.44 (m, 4 H), 3.77-3.79 (m, 2 H), 3.08-
3.33 (m, 4 H), 1.92-2.02 (m, 2 H), 1.52-1.54 (m, 2 H), 0.98 (t,
3 H, J ) 7.4 Hz); 13C NMR (CDCl3) δ 155.89 (Cq), 154.25 (Cq),
154.07 (Cq), 153.29 (Cq), 137.31 (CH), 137.28 (Cq), 137.16 (Cq),
136.29 (Cq), 133.43 (Cq), 133.35 (Cq), 132.89 (Cq), 132.51 (Cq),
131.01 (Cq), 130.65 (Cq), 129.03 (CH), 129.00 (CH), 128.60 (CH),
128.34 (CH), 127.95 (CH), 127.89 (CH), 127.87 (CH), 127.84
(CH), 123.12 (CH), 119.22 (CH), 116.02 (CH2), 77.59 (CH2),
75.84 (CH2), 75.13 (CH2), 32.22 (CH2), 31.34 (CH2), 31.16 (CH2),
30.86 (CH2), 19.50 (CH2), 14.03 (CH3); FAB-MS m/z 611 (M+
+ 1). Anal. Calcd for C42H42O4: C, 82.59; H, 6.93. Found: C,
82.27; H, 6.93.
25-Allyloxy-27-ben zyloxy-26-h yd r oxy-28-p r op oxyca lix-
[4]a r en e (6d ). A sample of 0.61 g (0.87 mmol) of 25-allyloxy-
26-benzoyloxy-27-benzyloxy-28-propoxycalix[4]arene (5d ) was
subjected to hydrolysis and yielded 0.45 g (87%) of colorless
crystals: mp 142-143 °C; 1H NMR (CDCl3) δ 7.52-7.54 (m, 2
H), 7.38-7.40 (m, 3 H), 6.41-7.18 (m, 12 H), 6.08-6.22 (m, 1
H), 5.20-5.46 (m, 2 H), 4.87 (s, 1 H), 4.86, 4.76 (AB, 2 H, J )
14.1 Hz), 4.32-4.45 (m, 6 H), 3.75 (t, 2 H, J ) 8.5 Hz), 3.20-
3.34 (m, 4 H), 1.86-2.14 (m, 2 H), 0.64 (t, 3 H, J ) 7.5 Hz);
13C NMR (CDCl3) δ 156.82 (Cq), 154.03 (Cq), 153.83 (Cq), 153.25
(Cq), 137.27 (Cq), 137.00 (Cq), 136.95 (Cq), 133.97 (CH), 133.53
(Cq), 132.83 (Cq), 132.66 (Cq), 131.10 (Cq), 130.88 (Cq), 129.11
(CH), 128.60 (CH), 128.43 (CH), 128.24 (CH), 128.02 (CH),
127.97 (CH), 127.90 (CH), 127.85 (CH), 123.33 (CH), 122.92
(CH), 119.30 (CH), 117.72 (CH2), 77.44 (CH2), 76.59 (CH2),
76.39 (CH2), 30.98 (CH2), 30.84 (CH2), 22.32 (CH2), 9.42 (CH3);
FAB-MS m/z 597 (M+ + 1). Anal. Calcd for C41H40O4: C, 82.52;
H, 6.76. Found: C, 82.57; H, 6.92.
C
49H48O5: C, 82.09; H, 6.75. Anal. Calcd for C49H48O5‚1/4H2O:
C, 81.58; H, 6.78. Found: C, 81.70; H, 6.67.
25-Allyloxy-26-ben zyloxy-27-ben zoyloxy-28-bu toxycalix-
[4]a r en e (5c). A sample of 0.67 g (1.0 mmol) of 25-benzyloxy-
26-benzoyloxy-27-butoxy-28-hydroxy-calix[4]arene (4b) was
alkylated with 0.43 mL (0.60 g, 5.0 mmol) of allyl bromide and
yielded 0.61 g (86%) of colorless crystals: mp 152-153 °C; 1H
NMR (CDCl3) δ 6.37-7.72 (m, 17 H), 5.42-5.58 (m, 1 H), 4.69-
4.88 (m, 4 H), 4.00-4.17 (m, 4 H), 3.71-3.87 (m, 3 H), 3.56-
3.62 (m, 1H), 3.38-3.49 (m, 2 H), 3.14 (d, 1 H, J ) 13.2 Hz),
2.98 (d, 1 H, J ) 13.2 Hz), 1.79-1.81 (m, 2 H), 1.46-1.56 (m,
2 H), 0.99 (t, 3 H, J ) 7.4 Hz); 13C NMR (CDCl3) δ 164.52 (Cq),
156.11 (Cq), 155.82 (Cq), 155.58 (Cq), 148.42 (Cq), 137.97 (Cq),
137.49 (CH), 136.98 (Cq), 133.94 (Cq), 133.65 (Cq), 133.38 (Cq),
133.24 (CH), 132.17 (Cq), 131.93 (CH), 131.78 (CH), 130.76
(CH), 130.69 (CH), 129.89 (CH), 129.82 (CH), 128.99 (CH),
128.87 (CH), 128.77 (CH), 128.26 (CH), 127.92 (CH), 127.78
(CH), 124.13 (CH), 122.87 (CH), 122.12 (CH), 121.75 (CH),
113.23 (CH2), 76.25 (CH2), 74.35 (CH2), 73.72 (CH2), 37.01
(CH2), 32.51 (CH2), 31.11 (CH2), 31.01 (CH2), 29.70 (CH2), 19.47
(CH2), 14.01(CH3); FAB-MS m/z 715 (M+ + 1). Anal. Calcd for
C
49H46O5: C, 82.32; H, 6.49. Anal. Calcd for C49H46O5‚1/4H2O:
C, 81.81; H, 6.51. Found: C, 81.82; H, 6.54.
25-Allyloxy-26-b en zoyloxy-27-b en zyloxy-28-p r op oxy-
ca lix[4]a r en e (5d ). A sample of 0.66 g (1.0 mmol) of 25-allyl-
oxy-26-benzoyloxy-27-benzyloxy-28-hydroxycalix[4]arene (4c)
was alkylated with 0.48 mL (0.84 g, 4.9 mmol) of n-propyl
iodide and yielded 0.59 g (84%) of colorless crystals: mp 156-
158 °C; 1H NMR (CDCl3) δ 6.40-7.76 (m, 22 H), 6.08-6.20
(m, 1 H), 5.29-5.39 (m, 2 H), 4.84, 4.66 (AB, 2 H, J ) 10.9
Hz), 4.19-4.21 (m, 1 H), 4.13-4.17 (3d, 3 H), 3.81 (bd, 2 H, J
) 14.1 Hz), 3.45 (bd, 2 H, J ) 13.8 Hz), 3.31-3.33 (m, 2 H),
3.04-3.14 (m, 2 H), 1.26-1.30 (m, 2 H), 0.52 (t, 3H, J ) 7.6
Hz); 13C NMR (CDCl3) δ 164.29 (Cq), 156.44 (Cq), 155.24 (Cq),
154.98 (Cq), 148.15 (Cq), 137.13 (Cq), 136.42 (Cq), 134.23 (CH),
133.69 (Cq), 133.57 (CH), 133.18 (Cq), 132.92 (Cq), 131.81 (Cq),
131.56 (CH), 128.79 (CH), 128.71 (CH), 128.52 (CH), 128.44
(CH), 128.09 (CH), 127.71 (CH), 127.52 (CH), 122.39 (CH),
121.76 (CH), 116.99 (CH2), 76.43 (CH2), 75.06 (CH2), 75.01
(CH2), 36.70 (CH2), 30.30 (CH2), 30.27 (CH2), 21.34 (CH2), 8.81
(CH3); FAB-MS m/z 701 (M+ + 1). Anal. Calcd for C48H44O5:
C, 82.26; H, 6.33. Anal. Calcd for C48H44O5‚1/4H2O: C, 81.73;
H, 6.36. Found: C, 81.87; H, 6.36.
Gen er a l P r oced u r e for 25,26,27-Tr ia lk oxy-28-h yd r oxy-
ca lix[4]a r en es 6a -d . A solution of 0.71 mmol of 25,26,27-
trialkoxy-28-benzoyloxycalix[4]arene (5a -d ) in 10 mL of THF
was added to a solution of 1.25 g of KOH in 5 mL of H2O and
10 mL of EtOH, and the mixture was then refluxed for 4 h.
The solvent was removed, and the residue was treated with
CH3OH to induce an off-white solid. Further recrystallization
from CHCl3 and CH3OH afforded the corresponding hydrolysis
products 6a -d .

Calix[4]arenes with Different “Lower Rim” Substituents
J . Org. Chem., Vol. 64, No. 8, 1999 2679
Gen er a l P r oced u r e for 25,26,27,28-Tetr a a lk oxyca lix-
[4]a r en es 7a -c. A sample of 0.65 mmol of 25,26,27-trialkoxy-
calix[4]arene (6a -c), 0.06 g (2.5 mmol) of NaH, and an ex-
cess amount of alkyl halides was refluxed in 30 mL of CH3CN
for 1 h. The solvent was removed, and the crude product
was recrystallized from CHCl3 with a slow addition of CH3-
OH or n-hexane to yield the corresponding tetraalkoxy prod-
ucts 7a -c.
If the recrystallization of compound 7b was carried out in
CHCl3 and n-hexane, the resulting crystals melted at 88-89
°C and the elemental analysis had a value of C, 82.78 and H,
7.81. (Anal. Calcd for C45H48O4‚1/4C6H14: C, 82.81; H, 7.70.)16
Meth od B. F r om 25-a llyloxy-26-ben zyloxy-28-bu toxy-
27-h yd r oxyca lix[4]a r en e (6c). A sample of 0.10 g (0.16
mmol) of 25-allyloxy-26-benzyloxy-28-butoxy-27-hydroxy-calix-
[4]arene (6c) was alkylated with 0.11 mL (0.20 g, 1.6 mmol)
of n-propyl iodide and yielded 0.06 g (54%) of colorless crystals,
which were identical in physical and spectral properties with
the product 7b afforded in method A.
25-Allyloxy-26-ben zyloxy-27-bu toxy-28-p r op oxyca lix-
[4]a r en e (7a ). A sample of 0.19 g (0.32 mmol) of 25-allyloxy-
26-benzyloxy-27-hydroxy-28-propoxycalix[4]arene (6a) was alky-
lated with 0.18 mL (0.29 g, 1.6 mmol) of n-butyl iodide and
yielded 0.16 g (76%) of colorless crystals: mp 90-91 °C; 1H
NMR (CDCl3) δ 7.38-7.39 (m, 2 H), 7.24-7.26 (m, 3 H), 6.26-
6.82 (m, 13 H), 4.93-5.02 (m, 2 H), 4.75 (s, 2 H), 4.26, 4.44
(m, 6 H), 3.86 (t, 2 H, J ) 8.0 Hz), 3.68 (t, 2 H, J ) 7.1 Hz),
2.99-3.09 (m, 4 H), 1.74-1.87 (m, 4 H), 1.15-1.18 (m, 2 H),
0.97 (t, 3 H, J ) 7.4 Hz), 0.79 (t, 3 H, J ) 7.3 Hz); 13C NMR
(CDCl3) δ 157.28 (Cq), 156.50 (Cq), 155.70 (Cq), 154.90 (Cq),
137.79 (Cq), 136.50 (Cq), 136.45 (Cq), 136.23 (Cq), 136.12 (CH),
134.20 (Cq), 134.09 (Cq), 133.92 (Cq), 129.09 (CH), 128.53 (CH),
128.41 (CH), 128.12 (CH), 127.84 (CH), 127.75 (CH), 127.72
(CH), 127.64 (CH), 127.61 (CH), 122.15 (CH), 121.82 (CH),
116.31 (CH2), 76.79 (CH2), 75.58 (CH2), 74.73 (CH2), 31.93
(CH2), 31.21 (CH2), 31.16 (CH2), 31.05 (CH2), 30.94 (CH2), 23.44
(CH2), 19.01 (CH2), 14.03 (CH3), 10.70 (CH3); FAB-MS m/z 653
(M+ + 1). Anal. Calcd for C45H48O4: C, 82.79; H, 7.41. Anal.
Calcd for C45H48O4‚1/2H2O: C, 81.66; H, 7.46. Found: C, 81.34;
H, 7.56.
25-Allyloxy-26-ben zyloxy-28-bu toxy-27-p r op oxyca lix-
[4]a r en e (7b). Meth od A. F r om 25-Ben zyloxy-27-bu toxy-
26-h yd r oxy-28-p r op oxyca lix[4]a r en e (6b). A sample of 0.40
g (0.65 mmol) of 25-benzyloxy-27-butoxy-26-hydroxy-28-
propoxycalix[4]arene (6b) was alkylated with 0.17 mL (0.24
g, 2.0 mmol) of allyl bromide and yielded 0.29 g (67%) of
colorless crystals: mp 62-63 °C; 1H NMR (CDCl3) δ 7.45-
7.46 (m, 2 H), 7.34-7.37 (m, 3 H), 6.31-6.89 (m, 13 H), 4.96-
5.08 (m, 2 H), 4.83 (bd, 2 H), 4.32-4.45 (m, 6 H), 3.78-3.92
(m, 4 H), 3.10-3.17 (m, 4 H), 1.81-1.88 (m, 4 H), 1.49-1.51
(m, 2 H), 0.98 (t, 3 H, J ) 7.4 Hz), 0.81 (t, 3 H, J ) 7.4 Hz);
13C NMR (CDCl3) δ 156.97 (Cq), 156.28 (Cq), 155.51 (Cq), 154.58
(Cq), 137.49 (CH), 136.19 (Cq), 136.14 (Cq), 135.93 (Cq), 135.87
(Cq), 134.02 (Cq), 133.90 (Cq), 133.73 (Cq), 128.92 (CH), 128.28
(CH), 128.22 (CH), 128.15 (CH), 127.84 (CH), 127.59 (CH),
127.52 (CH), 127.45 (CH), 127.40 (CH), 121.90 (CH), 121.67
(CH), 116.05 (CH2), 76.32 (CH2), 76.20 (CH2), 75.37 (CH2),
74.62 (CH2), 32.10 (CH2), 30.93 (CH2), 30.87 (CH2), 30.81 (CH2),
30.68 (CH2), 22.77 (CH2), 19.17 (CH2), 13.79 (CH3), 9.65 (CH3);
FAB-MS m/z 653 (M+ + 1). Anal. Calcd for C45H48O4: C, 82.79;
H, 7.41. Anal. Calcd for C45H48O4‚1/4CH3OH: C, 82.27; H, 7.42.
Found: C, 82.46; H, 7.53.
25-Allyloxy-27-ben zyloxy-26-bu toxy-28-p r op oxyca lix-
[4]a r en e (7c).14 A sample of 0.30 g (0.50 mmol) of 25-allyloxy-
27-benzyloxy-26-hydroxy-28-propoxycalix[4]arene (6d) was alky-
lated with 0.28 mL (0.49 g, 2.9 mmol) of n-propyl iodide and
yielded 0.28 g (85%) of colorless crystals: mp 82-83 °C; 1H
NMR (CDCl3) δ 7.37-7.39 (m, 2 H), 7.33-7.34 (m, 3 H), 6.32-
6.70 (m, 13 H), 5.12-5.24 (m, 2 H), 4.99 (s, 2 H), 4.30, 4.53
(m, 6 H), 3.74-3.79 (m, 4 H), 3.06-3.18 (m, 4 H), 1.81-1.84
(m, 4 H), 1.32-1.40 (m, 2 H), 0.90-0.96 (m, 6 H); 13C NMR
(CDCl3) δ 156.87 (Cq), 156.81 (Cq), 156.44 (Cq), 155.96 (Cq),
138.39 (Cq), 136.38 (Cq), 136.19 (CH), 136.15 (Cq), 136.12 (Cq),
135.31 (Cq), 135.13 (Cq), 130.12 (CH), 128.77 (CH), 128.66 (CH),
128.46 (CH), 128.43 (CH), 128.40 (CH), 128.38 (CH), 128.36
(CH), 128.27 (CH), 122.66 (CH), 122.62 (CH), 122.38 (CH),
117.04 (CH2), 77.17 (CH2), 76.89 (CH2), 76.10 (CH2), 75.39
(CH2), 32.51 (CH2), 31.67 (CH2), 31.54 (CH2), 23.60 (CH2), 19.69
(CH2), 14.51 (CH3), 10.73 (CH3); FAB-MS m/z 653 (M+ + 1).
Anal. Calcd for C45H48O4: C, 82.79; H, 7.41. Found: C, 82.77;
H, 7.59.
Ack n ow led gm en t. Financial support of this work
from the National Science Council of the Republic of
China (Grant NSC-86-2113-M034-002 and NSC-87-
2113-M-009-002) is gratefully acknowledged.
Su p p or tin g In for m a tion Ava ila ble: NMR spectra for 2f,
3e, 4c, 5d , 6d , and 7c and an ORTEP diagram. This material
is available free of charge via the Internet at http://pubs.acs.org.
J O981648L
(16) A different crystal structure was formed when compound 7b
was crystallized from different solvent-pair systems (e.g., CHCl3 and
CH3OH, or CHCl3 and n-hexane); consequently, a different melting
point was also observed. We speculated that the different crystal
structures of compound 7b was caused by the inclusion of different
solvent molecules such as CH3OH or n-hexane into the same cavity.