Synthesis and solid state structure of oxacalix[4]arenes bearing four nitro groups and four tert-butyl groups at their extra-annular positions

Article abstract of DOI:10.1016/j.tet.2009.09.116

Four oxacalix[4]arene derivatives, in which 1,3-dinitrobenzene units and 1,3-di-tert-butylbenzene units are incorporated in alternating order, were synthesized by aromatic nucleophilic substitution. The introduction of the tert-butyl groups increased the stability of the macrocycles against nucleophilic C-O bond cleavage. X-ray crystal structure analyses reveal that the oxacalixarenes adopt an unsymmetrical 1,3-alternate conformation. The bulky substituents did not disturb the conjugation between the bridging oxygen atoms and the dinitrobenzene rings.

Full text of DOI:10.1016/j.tet.2009.09.116

Tetrahedron 65 (2009) 9983–9988
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Tetrahedron
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Synthesis and solid state structure of oxacalix[4]arenes bearing four nitro
groups and four tert-butyl groups at their extra-annular positions
*
Shuichiro Akagi, Yusuke Yasukawa, Kazuhiro Kobayashi, Hisatoshi Konishi
Department of Chemistry and Biotechnology, Graduate School of Engineering, Tottori University, 4-101 Koyama-minami, Tottori, Tottori 680-8552, Japan
a r t i c l e i n f o
a b s t r a c t
Article history:
Four oxacalix[4]arene derivatives, in which 1,3-dinitrobenzene units and 1,3-di-tert-butylbenzene units
are incorporated in alternating order, were synthesized by aromatic nucleophilic substitution. The in-
troduction of the tert-butyl groups increased the stability of the macrocycles against nucleophilic C–O
bond cleavage. X-ray crystal structure analyses reveal that the oxacalixarenes adopt an unsymmetrical
1,3-alternate conformation. The bulky substituents did not disturb the conjugation between the bridging
oxygen atoms and the dinitrobenzene rings.
Received 23 July 2009
Received in revised form
30 September 2009
Accepted 30 September 2009
Available online 2 October 2009
Ó 2009 Elsevier Ltd. All rights reserved.
1. Introduction
bearing no substituents at the intra-annular positions indicated
that in the crystal the cyclic tetramers adopt a 1,3-alternate (or
Oxacalixarenes are oxygen-atom-bridged metacyclophane
compounds. In contrast to classical calixarenes connected by car-
bon atoms to bridge their aromatic rings, the incorporation of ox-
ygen atoms within the metacyclophane framework is an interesting
method of increasing structural diversity and conferring new
chemical and physical properties upon this class of molecules.1
These macrocycles are usually obtained by base-catalyzed aromatic
nucleophilic substitution of activated dihalogenated aromatic or
heteroaromatic compounds with dihydroxyaromatic compounds.2
The rigid structure makes oxacalixarenes attractive as a building
block for the construction of supramolecular architectures.3
We previously reported2c that CsF-catalyzed aromatic nucleophilic
substitution of 1,3-difluoro-4,6-dinitrobenzene 1 with 2-propylre-
sorcinol 2 initially produced three cyclic products, syn-cyclic tetramer
syn-3, anti-cyclic tetramer anti-3, and cyclic hexamer 4 in moderate
yields (Scheme 1). After longer reaction times, however, the amount of
the anti-3 and 4 decreases. Finally, only syn-3 was obtained in good
yield. These results suggest that the anti-3 and 4 are the kinetic
products and that they convert to syn-3 under the reaction conditions
for their formation. Furthermore, the reversibility of the C–O bond
formationwasconfirmedby reconstructionof bothanti-3and 4to syn-
3 in the presence of CsF.
a boat) conformation with the resorcinol rings oriented nearly
perpendicular to the mean planes defined by the bridging oxygen
atoms. These conformational features are very similar to those of
the oxacalix[4]arenes bearing propyl2c or methyl4 substituents at
the intra-annular positions as schematically shown in Scheme 1.
Comparison of these conformations suggests that there is no severe
steric hindrance between the alkyl substituents at the intra-annu-
lar positions and the neighboring dinitrobenzene rings. Hence, the
syn-cyclic tetramers were obtained as the thermodynamically most
stable products.
In continuation of our interests in the design and synthesis of
oxacalixarenes, we report here the synthesis of oxacalix[4]arene
bearing bulky alkyl substituents at their extra-annular positions.
The present work was conducted to test whether the preference of
an oxacalix[4]arene for the cyclic tetramer formation can be
modified by the presence of substituents at the 4,6-positions of the
resorcinol units. Here we describe the synthesis and solid state
structure of oxacalix[4]arenes 6 bearing four nitro groups and four
tert-butyl groups at their extra-annular positions.
2. Result and discussion
2.1. Synthesis
It is noteworthy that the cyclization reaction is not suppressed
by the introduction of the intra-annular substituents. This fact is
postulated to be a result of the preferred conformation of the syn-
isomers. Thus, X-ray analysis of the tetranitrooxacalix[4]arenes
The resorcinols 5a–d bearing two tert-butyl substituents at their
4,6-positions were used for construction of the oxacalix[4]arenes.
The CsF-catalyzed aromatic nucleophilic substitution of 1,5-difluoro-
2,4-dinitrobenzene 1 with 5a was conducted in DMFat 100 ꢀC for 2 h
(Scheme 2). The crude product was purified by recycling preparative
gel permeation chromatography (GPC) to produce the cyclic
* Corresponding author.
E-mail address: konis@chem.tottori-u.ac.jp (H. Konishi).
0040-4020/$ – see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2009.09.116

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S. Akagi et al. / Tetrahedron 65 (2009) 9983–9988
O2N
O
NO2
NO2
O2N
O
O
NO2
NO2
O
X
X
X
O2N
O
O2N
O
O
O
X
Syn-3
X
Anti-3
O2N
NO2
CsF / DMF
F
F
HO
OH
+
O
O
X
O2N
NO2
2
1
X
O
O
O2N
NO2
X
O
O
NO2
NO2
4
Scheme 1. Synthesis of oxacalix[n]arenes bearing substituents at their intra-annular positions by aromatic nucleophilic substitution.
R
O
O
O
O
O2N
O2N
NO2
NO2
F
F
HO
OH
CsF
R
R
+
Hin
O2N
NO2
100 ºC, 2 h
dry DMF
under Ar
1
6a R = H
5a R = H
6b R = Me
5b R = Me
5c R = OH
6c R = OH
6d R = CO2Me
5d R = CO2Me
Scheme 2. Synthesis of oxacalix[4]arenes 6 from 4,6-di-tert-butylresorcinols 5.
tetramer 6. These structures were confirmed by 1H and 13C NMR
spectroscopies, infrared spectrometry, elemental analysis, and con-
clusively identified by X-ray structure determinations. Their yields
and the chemical shifts of the intra-annular aromatic protons on the
dinitrobenzene rings (Hin, see Scheme 2) are summarized in Table 1.
The chemical shifts of the Hin protons (5.65–6.16 ppm) indicate that
these protons are significantly affected by the ring current of the
neighboring di-tert-butylbenzene rings. Thus, it can be presumed
that the preferred conformations of 6 are estimated to be 1,3-alter-
nate similar to those observed in the crystal structure (vide infra).
that the bulky groups bonded to the 4,6-positions of the resorcinol
units hinder the formation of the oxacalix[6]arene. Meanwhile, it
was reported3b that steric hindrance may also be one of the reasons
for the formation of larger macrocycles in the oxacalix[4]arene
synthesis, where bulky groups were substituted at the 5-positions
of the resorcinol units. The C–O bond of tetranitrooxacalix[4]ar-
enes, for example 7 (Scheme 3), is readily cleaved by the ipso-attack
O
O
O
O
O2N
O2N
NO2
NO2
R
R
Table 1
The yields of oxacalix[4]arenes 6 and the chemical shifts of their Hin protons in CDCl3
Compound
R
Yield (%)
Hin (ppm)
6a
6b
6c
6d
H
Me
OH
CO2Me
74
70
27
49
6.16
5.73
6.00
5.65
7a R = H
7b R = Me
7c R = OH
Despite the presence of bulky tert-butyl groups at the ortho
positions, the cyclic tetramer 6a was synthesized by the reaction of
1 with 5a in 74% yield. Furthermore, no evidence of the presence of
oxacalix[6]arene in the reaction mixture was obtained. It appears
7d R = CO2Me
Scheme 3. Tetranitrooxacalix[4]arenes bearing no bulky substituents at their extra-
annular positions.

S. Akagi et al. / Tetrahedron 65 (2009) 9983–9988
9985
Table 2
MM3 calculated steric energy differences between the syn- and anti-isomer of
oxacalix[4]arenes
The reaction of 1 with 5b also produced the oxacalix[4]arene 6b
(syn-isomer) in good yield (70%), and the corresponding anti-isomer
could not be obtained by GPC separation of the reaction mixture.
When 2-methylresorcinol 2 (X¼Me) was used as a resorcinol unit,
two conformational isomers, syn-3 (X¼Me) and anti-3 (X¼Me),
were obtained.4 Because of these isomers do not practically in-
terconvert with each other at the reaction temperature (100 ꢀC), it is
reasonably concluded that the reaction of 1 with 5b produced only
one stereoisomer, syn-6b. The dihydroxyoxacalix[4]arene 6c was
obtained in a low yield (27%). GPC analysis of the reaction mixture
indicated the formation of a large amount of a complex mixture
with higher molecular weights. 1H NMR analysis of this fraction
indicated the formation of a mixture of the linear and/or branched
higher oligomers. Similar results were obtained in K2CO3/DMSO or
the Et3N/MeCN system. This is in contrast to the facile synthesis of
the dihydroxy derivative, syn-3 (X¼OH), which was prepared in
*
Compound
D
E (kJ molꢁ1
)
Compound
D )
E (kJ molꢁ1
6a
6b
6c
6d
65.98
53.38
61.29
71.61
7a
7b
7c
7d
9.57
6.43
15.06
11.99
of nucleophiles.3c,5 In contrast, 6a is stable to alkaline hydrolysis by
5% KOH in THF/H2O (9:1). We also found that the reconstruction of
oxacalix[4]arene 6a with resorcinol in the presence of CsF in DMF
did not occur. These observations indicate that the C–O bond for-
mation of 6a is irreversible in the present study. Furthermore, it
seems that the bulky tert-groups hinder the approach of nucleo-
philes and destabilize the transition state for ring cleavage.
Figure 1. Molecular structures of 6a–d, top and side views. Thermal ellipsoids are drawn 50% probability level. Atom coloring: O, red; N, blue. Hydrogen atoms are omitted for
clarity. (a) 6a, the DMF molecule is disordered with a ratio 1:1 occupancy; (b) 6b; (c) 6c; (d) 6d, one nitro group is disordered in two parts, solvent molecules are omitted for clarity.

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S. Akagi et al. / Tetrahedron 65 (2009) 9983–9988
K2CO3/DMSO3a in good yield. The low yield of 6c might be due to the
adjacent tert-butyl groups, which reduce the regioselectivity of the
hydroxyl groups at 1- and 3-positions of 5c. The diester derivative
6d was prepared in rather poor yield (49%). In this case, only the syn-
isomer was also separated by GPC. The alkaline hydrolysis of the
ester groups was examined. However, we have found that the ester
groups are stable in 5% KOH in THF/H2O (9:1) under reflux condi-
tions. This low reactivity may be due to protection of the ester
groups by the neighboring aromatic rings at both sides in the 1,3-
alternate conformation.
To assess the stereoselectivities of the syn- and anti-isomers,
molecular mechanics calculations using the Macromodel (Ver. 8.6)
modeling package6 were performed. Conformational searching was
carried out by using the MCMM (torsional sampling Monte Carlo
multiple minimum) option, and each random conformation was
minimized using the Polak-Ribiere Conjugate Gradient method
the mean plane m; the dihedral angles between the aromatic rings
and the mean plane, (a/m), (b/m), (c/m), (d/m); the centroid/cen-
troid distances between the opposite aromatic rings, (a–c), (b–d);
the average bond length between the bridging oxygen atom and
the dinitrobenzene (ln), and the average bond length between the
bridging oxygen atom and the di-tert-butylbenzene ring (lb). These
relevant structural parameters are summarized in Table 3. For
comparison, the parameters for the oxacalix[4]arenes 7b,2b 7c4
bearing no tert-butyl substituents are also listed in this table.
Table 3
Structural parameters of oxacalix[4]arenes 6 and 7
6a
6b
6c
6d
7b
7c
0.038
Deviation of the bridging oxygen atoms from the mean plane (Å)
0.305
ꢁ0.307
0.304
ꢁ0.306
0.019
ꢁ0.019
0.020
ꢁ0.020
0.020
ꢁ0.020
0.020
ꢁ0.020
0.108
ꢁ0.108
ꢁ0.108
ꢁ0.108
0.095
ꢁ0.096
0.095
ꢁ0.095
ꢁ0.038
0.038
(PRCG) with the MM3 force field. The minimization convergence
*
ꢁ0.038
criteria were considered to be complete when the gradient was less
than 0.005. For each compound the conformational analyses always
found both 1,3-alternate conformation (syn-isomer) and chair con-
formation (anti-isomer) among the output structure collected within
Dihedral angles between the di-tert-butylbenzene rings and the mean plane (ꢀ)
a/m
c/m
57.9
57.9
77.2
77.5
77.4
73.3
76.6
74.3
87.7
88.2
81.7
87.8
Dihedral angles between the dinitrobenzene rings and the mean plane (ꢀ)
80 kJ molꢁ1. The calculated steric energy differences ( E kJ molꢁ1
D )
b/m
d/m
64.9
64.4
35.2
38.9
35.3
39.0
37.5
47.7
17.0
28.1
18.8
36.1
between the anti- and syn-isomer of 6 are reported in Table 2. For
comparison, the E values for the corresponding oxacalix[4]arenes 7
D
Centroid/centroid distances (Å)
bearing no tert-butyl substituents are also included in this table. In all
cases, the syn-isomers are more stable than the anti-isomers. In the
series of 6, the anti-isomers have energy higher by 53–72 kJ molꢁ1
than the corresponding syn-isomers. Thus, it is reasonable to pos-
tulate that the preferred formation of syn-isomers is accounted for by
a–c
b–d
6.081
5.676
5.333
6.808
5.339
6.782
5.324
6.712
4.755
7.317
4.905
7.108
Average bond lengths (Å)
ln
lb
1.360
1.401
1.353
1.408
1.356
1.405
1.356
1.400
1.358
1.414
1.356
1.398
these energy differences. On the other hand, in the series of 7, the DE
values are in the range of 6–15 kJ molꢁ1. In the case of compounds 7a
and 7c, only the syn-isomers were isolated in the K2CO3/DMSO, CsF/
DMF or Et3N/MeCN system; whereas the base-catalyzed synthesis of
7b and 7d produced a mixture of the two isomers, and the anti-
isomers readily converted to the thermodynamically more stable
syn-isomers in the presence of K2CO3 or CsF. The reason for the syn-
preference in the synthesis of 6 is that the energy gap between the
syn-isomer and anti-isomer much increased by introducing tert-
butyl groups at the extra-annular ortho positions relative to the
bridging oxygen atoms.
In the crystal of compound 6a, there is one DMF molecule be-
tween the opposite di-tert-butylbenzene rings. One of the methyl
groups of the DMF molecule is pointing toward the mean plane m
and is located nearly above the centroid of the nearer di-tert-
butylbenzene ring. The inclusion of the DMF molecule probably
forces the macrocycle 6a to bend and to open the cavity. Indeed, the
deviation of the bridging oxygen atoms from the mean plan m is
0.30 Å. This value is much larger than that of 6b (0.02 Å), 6c (0.02 Å)
and 6d (0.11 Å). Furthermore, 6a has the longest centroid/centroid
distance (a–c) and the shortest centroid/centroid distance (b–d)
among the oxacalix[4]arenes investigated. The distance between
the carbon of the methyl group and the aromatic ring is 3.64 Å,
2.2. X-ray crystal structures
indicating some C–H/p interactions.
The crystal structures of 6b, 6c, and 6d resemble each other. The
four bridging oxygen atoms are located nearly in the mean plane m
described as above. The dihedral angles a/m and c/m are in the range
of 73.3–77.5ꢀ, and the dihedral angles b/m and d/m are in the range of
35.2–47.7ꢀ. The centroid/centroid distances a–c, b–d are in the
range of 5.32–5.34 Å and 6.71–6.81 Å, respectively. The substituents
(Me, OH, COOMe) at the intra-annular positions have little effect on
the conformational preference of the oxacalix[4]arenes. For com-
pound 6c, there is no hydrogen bonding between the distal OH
groups, because the O/O distance of 4.25 Å is much longer than that
of usual hydrogen bonded O/O distance (ca. 2.85 Å). For compound
6d, the ester groups are arranged in antiparallel fashion with respect
to each other, and the oxygen atoms of the carbonyl groups point
inward of the cavity. The torsion angles between the planes of the
ester groups and the aromatic ring bearing the substituent are 40.8ꢀ
and 37.6ꢀ. This torsion of the ester groups is apparently due to steric
interaction with the dinitrobenzene rings. For the oxacalix[4]arenes
7b and 7c, bearing no tert-butyl substituents, the dihedral angles a/m
and c/m are in the range of 81.7–88.9ꢀ, the dihedral angles b/m and d/
m are in the range of 17.0–36.1ꢀ, and the centroid/centroid distances
a–c, b–d are in the range of 4.76–4.91 Å and 7.11–7.32 Å, respectively.
Obviously, the centroid/centroid distances a–c are elongated by the
introduction of the four tert-butyl substituents at the extra-annular
All oxacalix[4]arenes 6a–d adopt unsymmetrical 1,3-alternate
conformations. Figure 1 shows the ORTEP drawing of their crystal
structures. Their conformational features are characterized by the
following structural parameters. As shown in Scheme 4, four ben-
zene rings are designated as a, b, c and d and the mean plane de-
fined by the bridging four oxygen atoms is designated as m. The
parameters are: the deviation of the bridging oxygen atoms from
R
O
R
lb
a
ln
O
O2N
O2N
NO2
X
(a-c)
d
b
m
X
NO2
O
R
O
c
R
(b-d)
Scheme 4. Structural parameters for 6 (R¼tert-Bu) and 7 (R¼H).

S. Akagi et al. / Tetrahedron 65 (2009) 9983–9988
9987
1
positions. Concurrently, the centroid/centroid distances b–d are
shortened by this modification.
Found: C, 62.03; H, 5.85; N, 7.09. 400 MHz H NMR (CDCl3, 30 ꢀC)
1.31 (s, 36H, t-Bu), 6.16 (s, 2H, meta to NO2) 6.48 (s, 2H, meta to t-
Bu), 7.53 (s, 2H, ortho to t-Bu), 8.83 (s, 2H, ortho to NO2). 125 MHz
d
In these compounds, the bonds between the bridging oxygen
atom and the dinitrobenzene ring are shorter than the bond be-
tween the bridging heteroatom and the di-tert-butylbenzene rings.
The significant shortening of the former bonds indicate that the
bridging oxygen atoms strongly conjugate with the dinitrobenzene
rings. For all compounds, these bond lengths and the differences
(lnꢁlb) are similar. Hence it is considered that the tert-butyl sub-
stituents do not influence the conjugation between the bridging
oxygen atoms with the dinitrobenzene rings.
13C NMR (CDCl3, 30 ꢀC)
d 30.1, 35.0, 105.6, 114.6, 126.0, 128.0, 133.3,
140.3, 150.5, 156.0. IR (KBr) cmꢁ1 2965, 1618, 1597, 1533, 1350, 1296.
4.2.2. 12,52-Dimethyl-14,16,54,56-tetra-tert-butyl-34,36,74,76-tetrani-
tro-2,4,6,8-tetraoxa-1,3,5,7(1,3)-tetrabenzenacyclooctaphane
(6b). GPC separation and recrystallization from CHCl3/hexane
yielded 6b as a colorless solid (70%); mp 250 ꢀC (dec). Rf¼0.8
(hexane/EtOAc 3:1). Anal. Calcd for C42H48N4O12: C, 62.99; H, 6.04;
N, 7.00. Found: C, 63.00; H, 6.09; N, 6.96. FABMS m/z 800 (Mþ).
1
3. Conclusion
400 MHz H NMR (CDCl3, 30 ꢀC)
d
1.26 (s, 36H, t-Bu), 1.72 (s, 6H,
Me), 5.73 (s, 2H, meta to NO2), 7.41 (s, 2H, ortho to t-Bu), 8.91 (s, 2H,
13
In the present study, we accomplished the preparation of oxa-
calix[4]arenes 6 by aromatic nucleophilic substitution of 1,5-
difluoro-2,4-dinitrobenzene with 4,6-di-tert-butylresorcinols. 1H
NMR and X-ray crystallographic analysis demonstrated that the
oxacalix[4]arenes adopt 1,3-alternate conformations both in solu-
tion and in the solid state. Introduction of four tert-butyl groups at
the ortho position to the bridging oxygen atoms inhibits the C–O
bond cleavage via ipso-attack of nucleophiles. Furthermore, the
substituents enhance the solubility of the macrocycles in common
organic solvents. The presence of nitro functions will allow the
design of novel building blocks for host molecules. Preparation of
derivatives of this type is the subject of our investigation.
ortho to NO2). 125 MHz C NMR (CDCl3, 30 ꢀC)
d 11.5, 30.5, 35.3,
102.2, 123.3, 125.3, 126.5, 131.8, 140.8, 148.2, 156.0. IR (KBr) cmꢁ1
2967, 1614, 1599, 1532, 1478, 1348, 1298.
4.2.3. 12,52-Dihydroxy-14,16,54,56-tetra-tert-butyl-34,36,74,76-tetra-
nitro-2,4,6,8-tetraoxa-1,3,5,7(1,3)-tetrabenzenacyclooctaphane
(6c). GPC separation and recrystallization from CHCl3/hexane
yielded 6c as a colorless solid (27%); mp 305 ꢀC (dec). Rf¼0.6
(hexane/EtOAc 3:1). Anal. Calcd for C40H44N4O14$2H2O: C, 57.14; H,
5.75; N, 6.66. Found: C, 57.22; H, 5.82; N, 6.57. 500 MHz 1H NMR
(CDCl3, 30 ꢀC)
meta to NO2), 7.05 (s, 2H, ortho to t-Bu), 8.83 (s, 2H, ortho to NO2).
d 1.38 (s, 36H, t-Bu), 5.24 (br, 2H, OH), 6.00 (s, 2H,
13
125 MHz C NMR (CDCl3, 30 ꢀC)
132.3, 138.9, 139.8, 141.0, 155.9. IR (KBr) 3524, 2963, 1618, 1597,
1529, 1354, 1298 cmꢁ1
d 30.3, 35.4, 103.2, 117.3, 125.6,
4. Experimental section
4.1. General
.
4.2.4. Dimethyl-14,16,54,56-tetra-tert-butyl-34,36,74,76-tetranitro-
2,4,6,8-tetraoxa-1,3,5,7(1,3)-tetrabenzenacyclooctaphane-12,52-di-
carboxylate (6d). GPC separation and recrystallization from CHCl3/
hexane yielded 6d as a colorless solid (49%); mp 255 ꢀC (dec).
Rf¼0.6 (hexane/EtOAc 3:1). Anal. Calcd for C44H48N4O16: C, 59.45;
H, 5.44; N, 6.30. Found; C, 59.50; H, 5.36; N, 6.32. 400 MHz 1H NMR
Melting points were determined with a Laboratory Devices Mel-
Temp II capillary melting point apparatus and are uncorrected. Ele-
mental analyses were performed at the Division of Instrumental
Analysis, Research Center for Bioscience and Technology, Tottori
University. Preparative gelpermeation liquid chromatography (GPLC)
was performed on a Japan Analytical Industry LC-918 instrument
equipped with refractive index detector RI-50, using chloroform as
(CDCl3, 30 ꢀC)
meta to NO2), 7.70 (s, 2H, ortho to t-Bu), 8.82 (s, 2H, ortho to NO2).
d 1.31 (s, 36H, t-Bu), 3.43 (s, 6H, CH3), 5.65 (s, 2H,
13
a mobile phase on JAI gel 1Hþ2H columns (20ꢂ600 mm). 1H and 13
C
125 MHz C NMR (CDCl3, 30 ꢀC)
125.1, 130.4, 132.3, 141.8, 148.9, 157.1, 161.5. IR (KBr) 2965, 2876,
1734, 1616, 1530, 1352, 1304 cmꢁ1
d 30.5, 35.7, 52.7, 104.3, 119.6,
NMR spectrawere recorded in CDCl3 or DMSO-d6 solutionwitha JEOL
JNM LA400 or a JEOL JNM ECP500 spectrometer. All chemical shifts
.
are quoted in parts per million on the
d scale with TMS or residual
solvent signal as an internal standard. Fast atom bombardment mass
spectra were recorded using xenon ionization techniques with m-
nitrobenzyl alcohol (MNBA) as the matrix on a JEOL AX-505 spec-
trometer at the Faculty of Agriculture, Tottori University. Infrared
spectra were recorded with KBr discs using a Perkin Elmer FT-IR 1600
spectrometer.
4.3. Crystal structure determination
Intensity data and cell parameters were recorded on a Rigaku
RAXIS RAPID imaging plate area detector with graphite mono-
chromated Mo K
a
radiation (
l
¼0.7107 Å). Calculations were per-
formed using the WinGX7 (for 6a and 7d) or the CrystalStructure8
(for 6b, 6c, and 6d). The structure was solved by direct methods and
refined by full-matrix, least-squares procedures (based on Fo2),
using of theSHELXL-97 program.9 Crystallographic data in cif for-
mat can be obtained free of charge from The Cambridge Crystal-
lographic Data Centre via www.ccdc.cam.ac.uk/data_request/cif.
4.2. Synthesis of oxacalix[4]arenes
1,5-Difluoro-2,4-dinitrobenzene
1 (1 mmol), the appropriate
resorcinol (1 mmol), and CsF (2 mmol) were combined in a round-
bottomed flask under an argon atmosphere. Dry DMF (2.5 ml) was
added, and the reaction mixture was then stirred for 2 h at 100 ꢀC.
After cooling, dilution of the mixture with methanol/water (1:1 v/v)
produced light tan precipitates, which were collected by filtration,
washed with water, then methanol, and finally dried under reduced
pressure. The crude product was purified by GPC and recrystallization
from appropriate solvents.
4.3.1. Crystallographic data for compound 6a. Diffraction-quality
crystals were obtained by slow vapor diffusion of water to DMF:
C40H44N4O12$C3H7NO, M¼845.89, crystal size: 0.3ꢂ0.3ꢂ0.3 mm3,
crystal system: monoclinic, space group: Cc, a¼21.798(15),
b¼9.700(9), c¼20.683(8) Å,
a
¼90ꢀ,
b
¼94.99(2)ꢀ,
g
¼90ꢀ, volume:
F(000)¼1792,
4356(5) Å3, Z¼4, T¼173 K,
r
(calcd)¼1.29 g$cmꢁ3
,
34,254 reflections collected, 9017 unique (Rint¼0.030). A DMF mol-
ecule is disordered in a ratio of 0.5 to 0.5 about the twofold axes
perpendicular to the mean plane of the macrocycle. All heavy atoms
were refined anisotropically. Hydrogen atoms were placed from
expected geometry and refined isotropically. This model converged
to the final R1¼0.0365, wR2¼0.0993 and GOF¼0.922 with 595
4.2.1. 14,16,54,56-Tetra-tert-butyl-34,36,74,76-tetranitro-2,4,6,8-tet-
raoxa-1,3,5,7(1,3)-tetrabenzenacyclooctaphane (6a). The crude
product was purified by recrystallization from CHCl3/hexane to
produce a tan powder. (74%); mp 310 ꢀC (dec). Rf¼0.8 (hexane/
EtOAc 3:1). Anal. Calcd for C40H44N4O12: C, 62.17; H, 5.74; N, 7.25.

9988
S. Akagi et al. / Tetrahedron 65 (2009) 9983–9988
parameters. Residual peaks in final difference map were 0.21 e Åꢁ3
Hydrogen atoms of eight methyl groups in four tert-butyl groups
were placed using an idealized disordered CH3 model and other
hydrogen atoms were placed from expected geometry and were
refined isotropically. Disorder of one nitro group was modeled.
This model converged to the final R1¼0.0726, wR2¼0.2389 and
GOF¼0.929 with 637 parameters. Residual peaks in final differ-
ence map were 0.30 e Åꢁ3 and ꢁ0.33 e Åꢁ3. CCDC reference
number 740948.
and ꢁ0.21 e Åꢁ3. CCDC reference number 740949.
4.3.2. Crystallographic data for compound 6b. Single crystals were
obtained by vapor diffusion of hexane in a CHCl3 solution at room
temperature: C42H48N4O12, M¼808.86, crystal size: 0.5ꢂ0.5ꢂ0.2 mm3,
crystal system: triclinic, space group: P-1, a¼11.449(1), b¼13.687(1),
c¼13.873(1) Å,
a
¼74.55(1)ꢀ,
b
¼79.70(1)ꢀ,
g
¼87.71(1)ꢀ, volume:
2062(1) Å3, Z¼2, T¼173 K,
r
(calcd)¼1.290 g cmꢁ3
,
F(000)¼848,
19,964 reflections collected, 9339 unique (Rint¼0.019). All heavy
atoms were refined anisotropically. Hydrogen atoms were placed
from expected geometry and refined isotropically. This model
converged to the final R1¼0.0435, wR2¼0.1414 and GOF¼1.026
with 548 parameters. Residual peaks in final difference map were
0.53 e Åꢁ3 and ꢁ0.41 e Åꢁ3. CCDC reference number 740950.
Supplementary data
Supplementary data associated with this article can be found in
online version at doi:10.1016/j.tet.2009.09.116.
References and notes
4.3.3. Crystallographic data for compound 6c. Single crystals were
obtained by vapor diffusion of hexane in a CHCl3 solution at room
temperature: C40H44N4O14, M¼804.81, crystal size: 0.5ꢂ0.2ꢂ0.1 mm3,
crystal system: triclinic, space group: P-1, a¼11.432(3), b¼13.655(5),
1. (a) Vysotsky, M.; Saadioui, M.; Bo¨hmer, V. In Calixarenes 2001; Asfari, Z., Bo¨hmer,
V., Harrowfield, J., Vicens, J., Eds.; Kluwer: Dordrecht, 2001; Chapter 13, pp. 250–
265; (b) Maes, W.; Dehaen, W. Chem. Soc. Rev. 2008, 37, 2393–2402; (c) Wang,
M. X. Chem. Commun. 2008, 4541–4551.
2. (a) Wang, M. X.; Yang, H. B. J. Am. Chem. Soc. 2004, 126, 15412–15422; (b) Katz, J.
L.; Feldman, M. B.; Conry, R. R. Org. Lett. 2005, 7, 91–94; (c) Konishi, H.; Tanaka,
K.; Teshima, Y.; Mita, T.; Morikawa, O.; Kobayashi, K. Tetrahedron Lett. 2006, 47,
4041–4044; (d) Katz, J. L.; Feldman, M. N.; Conry, R. R. Org. Lett. 2006, 8, 2755–
2758; (e) Maes, W.; Van Rossom, W.; Van Hecke, K.; Van Meervelt, L.; Debaen, W.
Org. Lett. 2006, 8, 4161–4164; (f) Wang, Q. Q.; Wang, D. X.; Zhang, Q. Y.; Wang,
M. X. Org. Lett. 2007, 9, 2847–2850.
3. (a) Katz, J. L.; Selby, K. J.; Conry, R. R. Org. Lett. 2005, 7, 3505–3507; (b) Hao, E.;
Fronczek, F. R.; Graça, M.; Vicente, H. J. Org. Chem. 2006, 71, 1233–1236; (c)
Csokal, V.; Kulik, B.; Bitter, I. Supramol. Chem. 2006, 18, 111–115; (d) Jiao, L.; Hao,
E.; Fronczek, F. R.; Smith, K. M.; Graça, M.; Vicente, H. Tetrahedron 2007, 63,
4011–4017; (e) Hou, B. Y.; Zheng, Q. Y.; Wang, D. X.; Wang, M. X. Tetrahedron
2007, 63, 10801–10808; (f) Hou, B. Y.; Wang, D. X.; Yang, H. B.; Zheng, Q. Y.;
Wang, M. X. J. Org. Chem. 2007, 72, 5218–5226; (g) Ferrini, S.; Fusi, S.; Giorgi, G.;
Ponticelli, F. Eur. J. Org. Chem. 2008, 5407–5413; (h) Van Rossom, W.; Maes, W.;
Kishore, L.; Ovaere, L.; Van Meervelt, L.; Debaen, W. Org. Lett. 2008, 10, 585–588;
(i) Hou, B. Y.; Zheng, Q. Y.; Wang, D. X.; Huang, Z. T.; Wang, M. X. Chem. Commun.
2008, 3864–3866.
c¼13.883(5) Å,
a
¼74.69(1)ꢀ,
b
¼79.56(1)ꢀ,
g
¼87.49(1)ꢀ, volume:
2056(1) Å3, Z¼2, T¼173 K,
r
(calcd)¼1.300 g$cmꢁ3
,
F(000)¼848,
19,962 reflections collected, 9273 unique (Rint¼0.058). All heavy
atoms were refined anisotropically. Positions of the OH hydrogen
were located by the direct method. Hydrogen atoms of eight methyl
groups in four tert-butyl groups were placed using an idealized dis-
ordered CH3 model. Other hydrogen atoms were placed from expec-
ted geometry. All hydrogen atoms were refined isotropically. This
model converged tothe finalR1¼0.0754, wR2¼0.2096and GOF¼1.063
with 524 parameters. Residual peaks in final difference map were
0.47 e Åꢁ3 and ꢁ0.67 e Åꢁ3. CCDC reference number 740951.
4.3.4. Crystallographic data for compound 6d. Single crystals were
obtained by vapor diffusion of hexane in an acetone solution at room
temperature: C44H48N4O16$C3H6O, M¼946.96, crystal size: 0.4ꢂ0.4ꢂ
0.3 mm3, crystal system: triclinic, space group: P-1, a¼13.011(5),
4. Konishi, H.; Mita, T.; Yasukawa, Y.; Morikawa, O.; Kobayashi, K. Tetrahedron Lett.
2008, 49, 6831–6834.
5. Konishi, H.; Mita, T.; Morikawa, O.; Kobayashi, K. Tetrahedron Lett. 2007, 48,
3029–3032.
6. MacroModel, Version 8.6; Schro¨dinger, LLC: New York, NY, 2004.
7. Farrugia, L. J. J. Appl. Crystallogr. 1999, 32, 837–838.
8. CrystalStructure, Version 3.8.2; Rigaku and Rigaku/MSC: The Woodlands, TX,
2007.
b¼13.967(6), c¼14.257(5) Å,
a
¼71.28(2)ꢀ,
b
¼75.58(2)ꢀ,
g
¼79.18(1)ꢀ,
volume: 2360(2) Å3, Z¼2, T¼173 K,
r
(calcd)¼1.332 g$cmꢁ3
,
F(000)¼1000, 20,924 reflections collected, 10,464 unique
(Rint¼0.065). All heavy atoms were refined anisotropically.
9. Sheldrick, G. M. Acta Crystallogr., Sect. A 2008, 64, 112–122.