Preparation of 4,13,19,28-tetrahydroxy-9,9,24,24-tetramethyl[2.1.2.1]metacyclophane, a novel exo-hydroxycalixarene analogue

Article abstract of DOI:10.1039/a901502g

A novel 4,13,19,28-tetrahydroxy-9,9,24,24-tetramethyl[2.1.2.1]metacyclophane is prepared from bisphenol A in six steps and found to have a saddle structure in solid state.

Full text of DOI:10.1039/a901502g

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4
26 J. CHEM. RESEARCH (S), 1999
J. Chem. Research (S),
Preparation of 4,13,19,28-Tetrahydroxy-9,9,24,24-
tetramethyl[2.1.2.1]metacyclophane, a Novel
exo-Hydroxycalixarene Analoguey
1
999, 426^427y
a
a
b
Akira Miyazawa,* Yasuzo Suzuki, Tsuyoshi Sawada,
b
c
Shuntaro Mataka and Masashi Tashiro
a
Department of Polymer Chemistry, National Institute of Materials and Chemical Research, 1-1
higashi, Tsukuba, Ibaraki 305-3565, Japan
b
Institute of Advanced Material Study, Kyushu University, 6-1 Kasuga-kohen, Kasuga,
Fukuoka 816-8580, Japan
c
Tohwa Institute for Science, Tohwa University, 1-1-1, Chikushigaoka, Minami-ku, Fukuoka,
Fukuoka 815-0032, Japan
A novel 4,13,19,28-tetrahydroxy-9,9,24,24-tetramethyl[2.1.2.1]metacyclophane is prepared from bisphenol A in six
steps and found to have a saddle structure in solid state.
We have reported that a series of [2.n.2.n]metacyclophanes
(
n ˆ 1; 2) are useful building blocks for supramolecular
assemblies by fuctionalization of hydroxy groups intro-
duced at internal positions.
1� 3
Recently, exo-calixarene
derivatives containing hydroxy groups at the outer pos-
itions have been central for novel supramolecular
4� 7
assemblies.
Here, we report the preparation of
exo-tetrahydroxy[2.1.2.1]metacyclophane and the crystal
structure of its tetramethylated derivative.
Me Me
R2
R2
1
OR1
Fig. 1 Top view of the molecular structure of 6 showing the atom
numbering scheme (hydrogen atoms are omitted for clarity).
Selected atom distances in Ð: C(5)^C(20), 10.655, C(8)^C(23),
5.668, C(12)^C(27), 3.710, C(15)^C(30) 5.833.
R O
R1 = R2 = H
1
2
3
i
R1 = Me, R2 = H
ii
R1 = Me, R2 = CH2Cl
iii
Me Me
Me Me
9,9,24,24-tetramethyl[2.1.2.1]metacyclophane 6 in 14% yield.
Demethylation leading to the desired 4,13,19,28-tetra-
hydroxy-9,9,24,24-tetramethyl[2.1.2.1]metacyclophane 7 in
66% yield was carried out by reaction with BBr3. According
1
OR1
R O
1
OR1
R O
1
to H NMR spectroscopy, compound 7 is conformationally
v
1
X
X
£exible in solution. The H NMR spectrum of 7 shows
two singlets assigned to four methyl groups (d 1.49, 12H)
1
OR1
R O
1
OR1
R O
and eight protons (d 2.87, 8H) of bridging CH at 273 K.
2
1
No signi¢cant change in the H NMR spectrum was
observed in the temperature range 173ö273 K.
Me Me
6 R1 = Me
7 R1 = H
The molecular structure of 6 (satisfactory crystals of 7
could not be obtained) was determined by single crystal
X-ray crystallographic analysis (Fig. 1). Two phenyl rings
which face each other incline into the cavity whereas the
other two phenyl rings point outwards and the con-
formation of 6 can be described as saddle like in the solid
state. Bond distances and angles are unexceptional.
Functionalization of the hydroxy groups leading to
supramolecular assemblies is in progress.
Me Me
R1 = Me, X = S
4
5
iv
vi
R1 = Me, X = SO2
Scheme 1 Reagants and conditions: i, Mel, K2CO3 (72%); ii,
HCHO)x, HCl, AcOH, H3PO4 (56%); iii, Na2S (62%), iv,
m-CPBA (82%); v, 450 8C (1 Torr) 44%; vi, BBr3 (66%)
(
exo-Tetrahydroxy[2.1.2.1]metacyclophane 7 was prepared
from bisphenol
A 1 in six steps (Scheme 1). The
bis-(chloromethyl) derivative 3 was prepared according to
the method reported previously.8 Cyclization of 3 with
sodium sul¢de under high-dilution conditions a¡orded
Experimental
1
All melting points are uncorrected. H NMR spectra were recorded
on a Nippon Denshi JEOL GSX-270 spectrometer in CDCl3 with
Me4Si as internal reference. IR spectra were measured for KBr pellets
on a Perkin Elmer Paragon1000 spectrometer. Mass spectra were
obtained on a Hitachi M-80B spectrometer utilizing a 75 eV direct
inlet system. X-Ray crystallographic analysis was performed on an
Enraf-Nonius CAD4 di¡ractometer. Column chromatography was
carried on silica gel (Wako gel, C300).
the corresponding dithiacyclophane
4
in 62% yield.
Oxidation of 4 with m-CPBA, followed by £ash vacuum
pyrolysis (450 8C, 1 Torr) gave 4,13,19,28-tetramethoxy-
*
To receive any correspondence (e-mail: amiya@nimc.go.jp).
y This is a Short Paper as de¢ned in the Instructions for Authors,
Section 5.0 [see J. Chem. Research (S), 1999, Issue 1]; there is
therefore no corresponding material in J. Chem. Research (M).
Cyclization of 3 with Na2S.öA solution of 4.0 g (11.3 mmol) of
dichloride 3 in 300 mL of benzene was added dropwise over a period
12 h to a solution of 5.43 g (22.6 mmol) of sodium sul¢de nonahydrate

View Article Online
J. CHEM. RESEARCH (S), 1999 427
in 1 l of EtOH with stirring at room temperature under an N2
atmosphere. After addition was complete, the reaction mixture
was evaporated to leave a residue from which organic materials were
extracted with chloroform. The chloroform solution was washed with
water and brine, dried with Na2SO4, and evaporated to leave a residue
which was chromatographed on SiO2 with hexane^AcOEt (9:1 v/v) as
eluent to give a colorless solid, which was recrystalized from
hexane^chloroform to yield 2.20 g (62%) of 2,18-dithia-
Data Collection and Processing.öCAD4 FR590 di¡ractometer,
o� 2y mode with o scan width ˆ 0:8 ‡ 0:360 tan y, scan speed
�
1
2^20 8 min , graphite-monochromated Cu-Ka radiation; 5714 ref-
lections were measured ꢀ2:98 ꢁ y ꢁ 64:94, ‡h, Æk, Æ1). 5401 unique
[merging R ˆ 0:0235 after absorption correction (max, min. trans-
mission factor ˆ 0:9663, 0.9990)], linear and approximately isotopic
crystal decay, ca. � 0:0% corrected during procedure.
Structure Analysis and Re¢nement.öThe structure was solved by
1
0
5
,14,21,30-tetramethoxy-10,10,26,26-tetramethyl[3.1.3.1]metacyclo-
direct methods (SIR92). Full-matrix least-squares re¢nement on
�
1
2
phane 4 as colorless prisms; mp 237^238 8C; nmax/cm 811, 1031,
F with all non-hydrogen atoms anisotropic and hydrogens in calcul-
1
3
249, 1503, 1606, 2917, 2963, 2996; dH 1.55 (12H, s), 3.25 (8H, s),
ated positions with Uiso ˆ 1:3 times of U (bonded atoms). The
2
2
2
.81 (12H, s), 6.56 (4H, d, J ˆ 2:4 Hz), 6.80 (4H, d, J ˆ 8:6 Hz), 7.28
weighting scheme w ˆ 1=‰s ꢀF † ‡ ꢀ0:1687P† ‡ 26:0206PŠ where
0
‡
2
2
(
4H, dd, J ˆ 2:4, 8.6 Hz); m/z 628 (M ) (Found: C, 72.33; H, 7.12.
P ˆ ꢀF ‡ 2F †=3. Final R and Rw values are 0.0477, 0.1269 (re¢ned
0
c
2
C38H44O4S2 requires C, 72.59; H, 7.05%).
on F ). All calculations were performed on a MicroVAX3100 and
IBM RISC System/6000 3100 using MolEN11 and SHELXL-93.
Full crystallographic details, excluding structure factors, have been
deposited at the Cambridge Crystallographic Data Centre (CCDC).
See Instructions for Authors, J. Chem. Research (S), 1998 Issue 1.
Any request to the CCDC for this material should quote the full litera-
ture citation and the reference number 423/23.
12
Oxidation and Flash Vacuum Pyrolysis.öTo 3.66 g (5.82 mmol) of
in 90 mL of dry chloroform was added 5.52 g (25.6 mmol) of
4
m-CPBA and the solution stirred for 1 h under an N2 atmosphere.
The reaction mixture was poured into 100 mL of aqueous NaOH,
1
0%. The organic phase separated, dried with Na2SO4 and evaporated
to give the disulfone 5 (3.30 g, 82%) as a white powder; mp > 300 8C;
�
1
nmax/cm 822, 1026, 1119, 1253, 1304, 1503, 1612, 2935, 2968, 3009;
dH 1.60 (12H, s), 3.85 (12H, s), 4.12 (8H, s), 6.85 (4H, d, J ˆ 8:6 Hz),
See http://www.rsc.org/suppdata/jc/1999/426 for crystallo-
graphic ¢les in .cif format.
6
.95 (4H, d, J ˆ 2:4 Hz), 7.33 (4H, dd, J ˆ 2:4, 8.6 Hz).
Without further puri¢cation, sulfone 5 (3.5 g, 5.05 mmol) was
pyrolyzed at 450 8C (1 Torr) according to the literature.9 The
sublimed product was collected and chromatographed on SiO2 with
hexane±CHCl3 (1/1, v/v) as eluent to give 4,13,19,28-
tetrahydroxy-9,9,24,24-tetramethyl[2.1.2.1]metacyclophane 6 (1.26 g,
4
1
Received, 23rd February 1999; Accepted, 26th March 1999
Paper E/9/01502G
�
1
4%) as colorless prisms (hexane); mp 213^214 8C; nmax/cm 803,
035, 1243, 1257, 1502, 1605, 2926, 2956; dH 1.47 (12H, s), 2.84 (8H,
References
s), 3.60 (12H, s), 6.56 (4H, d, J ˆ 2:3 Hz), 6.61 (4H, d, J ˆ 8:6 Hz),
‡
6
7
.88 (4H, dd, J ˆ 2:3, 8.6 Hz); m/z 564 (M ) (Found: C, 80.77; H,
1
M. Tashiro, A. Tsuge, T. Sawada, T. Makishima, S. Horie, T.
Arimura, S. Mataka and T. Yamato, J. Org. Chem., 1990,
55, 2404.
.79. C38H44O4 requires C, 80.81; H, 7.85%).
Demethylation of 6.öTo a solution of 400 mg (0.71 mmol) of 6 in
0 mL of dry CH2Cl2 was added dropwise 4.25 mL (4.25 mmol) of
5
2
3
A. Tsuge, T. Sawada, S. Mataka, N. Nishiyama, H. Sakashita
and M. Tashiro, J. Chem. Soc., Perkin Trans. 1, 1992, 1489.
T. Sawada, A. Tsuge, T. Thieman, S. Mataka and M. Tashiro,
J. Inclusion Phenom. Mol. Recognit. Chem., 1994, 19, 301.
D. W. Chaser, J. Org. Chem., 1985, 50, 545.
G. Sartori, R. Maggi, F. Bigi, A. Arduini, A. Pastorio and C.
Porta, J. Chem. Soc., Perkin Trans. 1, 1994, 1657.
«
V. Bohmer, R. Dorrenbacher, M. Frings, M. Heydenreich, D.
BBr3 with stirring at 0 8C under an N2 atmosphere. After addition
was complete, the reaction mixture was poured into a large volume
of ice/water. The organic layer was washed with water and brine,
dried with Na2SO4, and evaporated to leave a residue. The resulting
residue was chromatographed on SiO2 with CHCl3 as eluent to give
the 4,13,19,28-tetrahydroxy-9,9,24,24-tetramethyl[2.1.2.1]metacyclo-
phane 7 (238 mg, 66%) as colorless prisms from hexane; mp
4
5
6
�
1
2
2
38^240 8C; nmax/cm
820, 1100, 1157, 1255, 1416, 1503, 1611,
de Paoli, W. Vogt, G. Fergunson and I. Thondorf, J. Org.
Chem., 1996, 61, 549.
T. N. Sorrell and H. Yuan, J. Org. Chem., 1997, 62, 1899.
US Pat. 2884462, 1956 (Chem. Abstr., 1956, 74, 87599).
M. Tashiro and T. Yamato, J. Org. Chem., 1985, 50, 2939.
930, 2960, 3017, 3420; dH 1.49 (12H, s), 2.87 (8H, s), 4.23 (4H, s,
D2O exchangeable), 6.55 (4H, d, J ˆ 2:3 Hz), 6.61 (4H, d,
7
8
9
‡
J ˆ 8:6 Hz), 6.87 (4H, dd, J ˆ 2:3, 8.6 Hz); m/z 508 (M ) (Found:
C, 80.15; H, 7.25. C34H36O4 requires C, 80.28; H, 7.13%).
X-Ray Crystal Structure Determination of 6. Crystal
Data.öC38H44O4, M ˆ 564:77, triclinic, space group P-1 (no. 2),
10 SIR92: M. C. Altmare, M. Burla, G. Camalli, C. Cacarano, A.
Giacovazzo, G. Guagliardi and J. Polidori, J. Appl.
Crystallogr., 1994, 27, 435.
a ˆ 11:066ꢀ2†,
b ˆ 14:832ꢀ1†,
c ˆ 9:690ꢀ1† Ð,
a ˆ 91:71ꢀ1†,
3
b ˆ 93:15ꢀ1†, g ˆ 90:38ꢀ1†, V ˆ 1587:1ꢀ4† Ð , (by least-squares
11 MolEN: An Interactive Structure Solution Procedure,
Enraf-Nonius, Delft, The Netherlands, 1990.
re¢nement on di¡ractometer angles for 23 automatically centered
�
3
re£ections, l ˆ 1:541 84 Ð), Z ˆ 2, Dc ˆ 1:1817 g cm , colorless
12 SHEXL-93: G. M. Sheldrick, University of Go
«
ttingen,
�
1
prism, crystal size 0:10  0:15  0:17 mm. mꢀCu-Ka† ˆ 0:587 mm
.
Germany, 1993.