Synthesis and studies of 1,4,5,8,9,12,13,16-octamethoxytetraphenylene

Article abstract of DOI:10.1021/ol020253s

(Matrix presented) The synthesis of 1,4,5,8,9,12,13,16-octamethoxytetraphenylene (6) is accomplished in five steps from 3,6-dimethoxy-2-nitroaniline (8). Its inclusion property and the electrochemical data of the corresponding tetraquinone 7 are presented

Full text of DOI:10.1021/ol020253s

ORGANIC
LETTERS
2003
Vol. 5, No. 6
823-826
Synthesis and Studies of
1,4,5,8,9,12,13,16-Octamethoxytetraphenylene†
Chun Wing Lai,‡,§ Chi Keung Lam,‡ Hung Kay Lee,‡ Thomas C. W. Mak,‡ and
,‡,§
Henry N. C. Wong*
Department of Chemistry and Central Laboratory of the Institute of Molecular
Technology for Drug DiscoVery and Synthesis, The Chinese UniVersity of Hong Kong,
Shatin, New Territories, Hong Kong SAR, China
hncwong@cuhk.edu.hk
Received December 20, 2002
ABSTRACT
The synthesis of 1,4,5,8,9,12,13,16-octamethoxytetraphenylene (6) is accomplished in five steps from 3,6-dimethoxy-2-nitroaniline (8). Its inclusion
property and the electrochemical data of the corresponding tetraquinone 7 are presented.
Since the first successful synthesis of tetraphenylene by
Rapson, Shuttleworth, and Niekerk in 1943,1 extensive efforts
have been made to explore its chemistry as well as that of
its derivatives. Their inclusion properties toward solvent
molecules2 as well as their electronic and physical properties3
have been carefully studied. Recently, 2,3,6,7,10,11,14,15-
octamethoxytetraphenylene has been suggested to be a
potential redox indicator on the basis of its redox-controlled
reversible C-C bond formation.4
ecules consisting of tetraphenylene derivatives as building
blocks is still not known. Triggered by the aforementioned
reasons, we have started a research project with the eventual
aim to construct three-dimensional molecular scaffolds using
tetraphenylenols or their derivatives as building blocks. In
our project, we would like to prepare all five tetraphenylenols
1-5 as shown in Figure 1.
Although many aspects concerning the chemistry of
tetraphenylene were studied, the construction of supermol-
† Dedicated to Professor Tze-Lock Chan (The Chinese University of
Hong Kong) on the occasion of his retirement.
‡ Department of Chemistry, The Chinese University of Hong Kong.
§ Central Laboratory of the Institute of Molecular Technology for Drug
Discovery and Synthesis, The Chinese University of Hong Kong.
(1) Rapson, W. S.; Shuttleworth, R. G.; Niekerk, J. N. J. Chem. Soc.
1943, 326.
(2) (a) Mak, T. C. W.; Wong, H. N. C. In ComprehensiVe Supramolecular
Chemistry; MacNicol, D. D., Toda, F., Bishop, P., Eds.; Pergamon Press:
Oxford, 1996; Vol. 6, pp 351-369. (b) Mak, T. C. W.; Wong, H. N. C.
Top. Curr. Chem. 1987, 140, 141. (c) Huang, N. Z.; Mak, T. C. W. Chem.
Commun. 1982, 543.
(3) (a) Salem, L. The Molecular Orbital Theory of Conjugated Systems;
W. A. Benjamin: New York, 1966; pp 122-125, 468-470. (b) Rashidi-
Ranjbar, P.; Man, Y. M.; Sandstro¨m, J.; Wong, H. N. C. J. Org. Chem.
1989, 54, 4888.
(4) Rathore, R.; Le Magueres, P.; Lindeman, S. V.; Kochi, J. K. Angew.
Chem., Int. Ed. 2000, 39, 809.
Figure 1. Five tetraphenylenols 1-5 for the construction of
molecular scaffolds.
10.1021/ol020253s CCC: $25.00 © 2003 American Chemical Society
Published on Web 02/22/2003

We herein report the synthesis of 1,4,5,8,9,12,13,16-
octamethoxytetraphenylene (6). The inclusion property of 6
and the electrochemical data of its corresponding tet-
raquinone 7 will also be delineated.
Table 1. Attempted Conditions for the Conversion of 11 to 6
isol isol
metal yield of yield of
type of
lithiation
The synthesis of 6 is described in Figure 2. Sandmeyer
alkyllithium temp (°C)
solvent
salt
6 (%) 12 (%)
n-BuLi
(2.1 equiv)
-78
0
rt
0
0
-78
0
-78
Et2O
CuCl2
CuCl2
CuCl2
CuCl2
10
31
16
3
5
3
4
8
7
21
13
2
Et2O
Et2O
THF
Et2O/THF (1/1) CuCl2
t-BuLi
(2.1 equiv)
t-BuLi
Et2O
Et2O
Et2O
CuCl2
CuCl2
CuCl2
1
4
4
2
(4.5 equiv)
n-BuLi
(2.1 equiv)
0
0
Et2O
Et2O
CuBr2
ZnCl2
0
0
10
5
prolonged treatment, and prominent deterioration of the
lithiated species was observed at room temperature. With
the exception of CuCl2, both CuBr2 and ZnCl2 gave
exclusively 12 as the only product. The optimum conditions
for the realization of 6 in 31% yield are therefore n-BuLi,
Et2O, 0 °C with CuCl2.
It was found that 6 formed a 1:2 clathrate inclusion
compound with dichloromethane. Many attempts have been
made to examine the inclusion properties of 6 toward other
organic solvents to no avail. However, in mixed solvent
systems, the host-guest selectivity between 6 and dichlo-
romethane is remarkable: for example, in CH2Cl2/C6H5Me/
C6H6/C6H14 (1:1:1:1), CH2Cl2/C5H5N/p-C6H4Me2 (1:1:1),
CH2Cl2/C6H5OMe/p-C6H4Me2 (1:1:1), CH2Cl2/CH2Br2/CH2I2/
p-C6H4Me2 (1:1:1:1), CH2Cl2/CHCl3/CCl4/p-C6H4Me2 (1:1:
1:1), and CH2Cl2/MeCOMe/H2O (1:1:1) solvent systems,
only the 2:1 complex of dichloromethane and 6 was formed,
which was confirmed by an X-ray crystallographic analysis9
(Figures 3 and 4) and NMR spectroscopic data.
Figure 2. Synthesis of 1,4,5,8,9,12,13,16-octamethoxytetraphen-
ylene (6) from 3,6-dimethoxy-2-nitroaniline (8).
reaction between diazotized 3,6-dimethoxy-2-nitroaniline (8)5
and potassium iodide gave 2-iodo-3,6-dimethoxy-1-nitroben-
zene (9) in 80% yield. Ullmann coupling reaction6 of 9
afforded the symmetrical 3,3′,6,6′-tetramethoxy-2,2′-di-
nitrobiphenyl (10) in 51% yield. The two nitro groups in 10
were reduced to amino groups in 71% yield by hydrazine
reduction in the presence of palladium on charcoal in
refluxing methanol.6
Another Sandmeyer reaction between diazotized 2,2′-
diamino-3,3′,6,6′-tetramethoxybiphenyl and potassium iodide
completed the synthesis of 2,2′-diiodo-3,3′,6,6′-tetramethoxy-
biphenyl (11) in 67% yield.6
The results in Table 1 show the reaction conditions for
the conversion of 11 to 6. In agreement with the literature,7
treatment of 11 with n-BuLi in diethyl ether as solvent led
to 6 as the major product, whereas the use of tetrahydrofuran
only gave 1,4,5,8-tetramethoxybiphenylene (12)5 as the major
product. The use of n-BuLi at 0 °C resulted in smooth
lithiation of 11 after 8 h. From thin-layer chromatographic
studies, lithiation at -78 °C remained incomplete after
Figure 3. Molecular structure and atom labeling of 6‚2CH2Cl2.
Thermal ellipsoids are drawn at 50% probability level. Hydrogen
atoms are omitted for clarity. The average formal single and double
bonds in the central ring are 1.495(5) and 1.390(4) Å, respectively.
(5) Rees, C. W.; West, D. E. J. Chem. Soc. C 1970, 583.
(6) Hine, J.; Hahn, S.; Miles, D. E.; Ahn, K. J. Org. Chem. 1985, 50,
5092.
Figure 5 shows the conversion of 6 to its corresponding
tetraphenylenol and quinone derivatives. Deprotection of the
(7) Kabir, S. M. H.; Iyoda, M Synthesis 2000, 13, 1839.
824
Org. Lett., Vol. 5, No. 6, 2003

Figure 6. Cyclic voltammogram of 7: CH2Cl2, 0.12 M [Bu4N]+-
[BF4]-, scan rate ) 100 mV s-1
.
gives the reduction potentials for other p-quinones as well
as those of tetraquinone 7.7 The E° values were taken from
cyclic voltammetry peak potentials as (Ea + Ec)/2. The data
show that the potential difference between the addition of
the first and second electron is exceptionally small in 7 (∆E°
) 0.2 V). One of the likely explanations is that charge
transfer occurs between the semi-quinone and the opposite
p-benzoquinone unit. Owing to the characteristic saddle shape
of tetraphenylene, face-to-face interaction may occur between
two opposite p-benzoquinone units that facilitate the distribu-
tion of charge. It is therefore likely that the second electron
requires less energy to overcome the repulsive force inside
the semi-quinone. However, the actual cause of the small
∆E° is still unclear to us. In addition, a cyclic voltammetric
method was also applied to 6. Although the anodic peak
corresponding to the oxidation of 6 to 62+ is ill defined, on
the return scan the cathodic peak at Ered ) 0.172 V
representing the reduction of 62+ to 6 is clear.4
Figure 4. Stereoview of 6‚2CH2Cl2. In the crystal structure,
molecules of 6 are arranged in a layer matching the plane (020),
and between such adjacent layers lie the CH2Cl2 solvate molecules.
methoxy groups of 6 employing boron tribromide at ambient
temperature afforded 1,4,5,8,9,12,13,16-octahydroxytetraphen-
ylene (5) in quantitative yield. Phenol 5 was oxidized to its
corresponding tetraquinone 7 in 67% yield by the use of lead
tetraacetate.
Insummary,thesynthesisof1,4,5,8,9,12,13,16-octamethoxy-
tetraphenylene 6 has been accomplished. A 1:2 clathrate
inclusion compound was obtained between 6 and dichlo-
romethane. In addition, the cyclic voltammogram of tet-
raquinone 7 shows extraordinarily small ∆E° between two
Table 2. Electrochemical Data of p-Quinones and
Tetraquinone 7a
Figure 5. Synthesis of 1,4,5,8,9,12,13,16-octahydroxytetraphen-
ylene (5) and its corresponding quinone 7.
To examine the electrochemical property of 7, a cyclic
voltammetric method was employed. As shown in Figure 6,
the cyclic voltammogram of 7 indicates three reversible
couples at E° ) -0.597, -0.813, and - 1.296 V, respec-
tively (see footnote b of Table 2).
In the first two couples, both reversible processes exhibit
an equal peak separation of 116 mV and nearly equal anodic
and cathodic peak currents at cathodic potentials. Table 2
(8) Almlof, J. E.; Feyereisen, M. W.; Jozefiak, T. H.; Miller, L. L. J.
Am. Chem. Soc. 1990, 112, 1206.
(9) Crystal data for 6‚2CH2Cl2: C34H36Cl4O8, Mw ) 714.43, triclinic,
P1h (No. 2), with a ) 9.460(2) Å, b ) 12.892(3) Å, c ) 15.324(3) Å, R )
90.929(5)°, â ) 104.420(5)°, γ ) 110.950(4)°, V ) 1678.8(6) Å3, and Dc
) 1.413 g cm-3 for Z ) 2. The structure was solved by direct methods and
refined to R1 ) 0.0488 and wR2 ) 0.0887 for 5279 observed data. In the
crystal structure, molecules of 1 are arranged in a layer matching the plane
(020) and between such adjacent layers lie the CH2Cl2 solvate molecules.
CCDC reference no. 189269.
a Compound 7 shows exceptionally small ∆E° values as compared with
that of p-benzoquinone. b All potentials are referenced to the ferrocenium/
ferrocene couple. The E° values were taken from cyclic voltammetry peak
potentials as (Ea + Ec)/2.
Org. Lett., Vol. 5, No. 6, 2003
825

reduction potentials. It is believed that charge transfer may
occur intramolecularly between a semi-quinone and the
opposite p-benzoquinone unit in 7. Further investigation of
the electrochemical properties of 7 and inclusion properties
of 5 are in progress.
University Grants Committee of the Hong Kong Special
Administrative Region, China (Project No. AoE/P-10/01).
Supporting Information Available: Experimental pro-
cedures and full characterization for compounds 5-7 and
9-11. The X-ray crystallographic data of 1:2 clathrate
inclusion compound between 6 and dichloromethane in CIF
format. This material is available free of charge via the
Internet at http://pubs.acs.org.
Acknowledgment. This work was supported by a grant
from the Research Grants Council of the Hong Kong SAR,
China (Project No. CUHK 4264/00P), as well as partially
by the Area of Excellence Scheme established under the
OL020253S
826
Org. Lett., Vol. 5, No. 6, 2003