Study of pinacol coupling reaction to synthesize functional macrocyclic molecules

Article abstract of DOI:10.1080/15421400701503659

[2.1.2.1]Metacyclophane ([2.1.2.1]MCP) 3 containing hydroxyl groups at the bridge is obtained by a pinacol coupling reaction using aluminum powder. The Albright-Gordman oxidation of [2.1.2.1]MCP 3 yielded tetracarbonyl derivative 4, and the following cond

Full text of DOI:10.1080/15421400701503659

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Study of Pinacol Coupling
Reaction to Synthesize
Functional Macrocyclic
Molecules
Yousuke Nishiyama a , Tsuyoshi Sawada a , Kazufumi
Chifuku a , Aiko Sato a , Yutaka Kuwahara a & Hideto
Shosenji a
a Department of Science and Technology for
Chemistry and Physics, Graduate School of Science
and Technology , Kumamoto University , Kurokami,
Kumamoto, Japan
Published online: 22 Sep 2010.
To cite this article: Yousuke Nishiyama , Tsuyoshi Sawada , Kazufumi Chifuku ,
Aiko Sato , Yutaka Kuwahara & Hideto Shosenji (2007) Study of Pinacol Coupling
Reaction to Synthesize Functional Macrocyclic Molecules, Molecular Crystals and
Liquid Crystals, 470:1, 359-368, DOI: 10.1080/15421400701503659
To link to this article: http://dx.doi.org/10.1080/15421400701503659
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Mol. Cryst. Liq. Cryst., Vol. 470, pp. 359–368, 2007
Copyright # Taylor & Francis Group, LLC
ISSN: 1542-1406 print=1563-5287 online
DOI: 10.1080/15421400701503659
Study of Pinacol Coupling Reaction to Synthesize
Functional Macrocyclic Molecules
Yousuke Nishiyama
Tsuyoshi Sawada
Kazufumi Chifuku
Aiko Sato
Yutaka Kuwahara
Hideto Shosenji
Department of Science and Technology for Chemistry and Physics,
Graduate School of Science and Technology, Kumamoto University,
Kurokami, Kumamoto, Japan
[2.1.2.1]Metacyclophane ([2.1.2.1]MCP) 3 containing hydroxyl groups at the bridge
is obtained by a pinacol coupling reaction using aluminum powder. The Albright-
Gordman oxidation of [2.1.2.1]MCP 3 yielded tetracarbonyl derivative 4, and the
following condensation reaction of 1,2-phenylenediamine yielded quinoxaline-
annulated [2.1.2.1]MCP 5. The UV and fluorescence spectra as well as the influ-
ences of an alkali metal ion on the fluorescence spectra of quinoxaline-annulated
[2.1.2.1]MCP 5 were reported
Keywords: calixarene; fluorescence; metacyclophane; pinacol coupling; quinoxaline;
UV-Vis absorption spectrum
INTRODUCTION
The pinacol coupling reaction is one of the effective reactions for
preparing a 1,2-diol in which a carbon-carbon covalent bond is formed
between the carbonyl groups of an aldehyde or a ketone in the
presence of an electron donor in a free radical process (Scheme 1) [1].
This work was supported by the Department of Applied Chemistry and Biochemistry,
Faculty of Engineering, and Department of Science and Technology for Chemistry and
Physics, Graduate School of Science and Technology, Kumamoto University.
Address Correspondence to Dr. Tsuyoshi Sawada, Science and Technology for Chem-
istry and Physics, Graduate School of Science and Technology, Kumamoto University,
2-39-1 Kurokami, Kumamoto 860–8555, Japan. E-mail: sawada@kumamoto-u.ac.jp
359

360
Y. Nishiyama et al.
On the other hand, calixarenes, namely, [1n] metacyclophanes
(MCPs), have been investigated as a valuable host molecules for
metal cations [2] and neutral molecules [3], since they are produced
by a one step reaction and can be functionalized at lower and upper
rims [4].
We have previously reported the novel single-step synthesis of
[2.2]MCPs via the pinacol coupling of dialdehyde derivatives [5]. The
synthesized MCPs had four hydroxyl groups at the exo-position of
bridge moiety. Further, we have been investigating an application of
the pinacol coupling reaction for preparing calixarene analogs [6].
Here, we have investigated the preparation of tetrahydroxy
[2.1.2.1]MCP by the pinacol coupling method and its oxidation;
further, the annulation of a quinoxaline moiety at the bridge position
has also been investigated. The quinoxalin-annulated[2.1.2.1]MCP
have two fluorescent heterocycles in a ring skeleton and a calixarene-
like cavity that could form a complex with an alkali metal cation. There-
fore, it is interesting to note the resulting properties of the complexation
with the alkali metal cation and its influence on the fluorescence
spectra. In this article, we describe the synthesis, structure, and photo-
chemical properties of [2.1.2.1]MCPs and their derivatives.
EXPERIMENTAL
Materials
2,20-Bischlorometyl-4,40-bis(tert-butyl)-1,10-dimethoxybiphenylmethane 1
was prepared as reported method [7]. Other chemicals and solvents
were obtained commercially.
Synthesis
Synthesis of 4,40-Bis(tert-butyl)-1,10-dimethoxy-
2,20-biphenylmethanedialdehyde (2)
2,20-Bischlorometyl-4,40-bis(tert-butyl)-1,10-dimethoxybiphenylmethane 1
(22 g, 90 mmol) was dissolved in pyridine (540 mL, 6.84 mol), and
refluxed for 2 h. Then, white powder separated out and washed with

Pinacol Synthesis of Functional Metacyclophane
361
hexane gave pyridinium salt (30 g, 57%). Secondly, pyridinium salt
(30 g, 50 mmol) and N,N0-Dimethyl-p-nitroso anilinium chloride (22 g,
18 mmol) was dissolved in ethanol (241 mL), and aqueous 20% sodium
hydroxide solution (102 mL) was dropping to this solution slowly at rt.
After stirred for 90 min, 5 N hydrochloric acid (292 mL) was added at
rt. The mixture was stirred for 30 min, then water (365 mL) was added
and filtrated deposit. After drying, this deposit was dissolved in heated
hexane and filtrated. Then, colorless needles were obtained in filtrate
and recrystallized with hexane yield 2 (14 g, 63%).
2: colorless needles; mp 118–120ꢀC; IR (KBr) 1000, 1100, 1200,
1255, 1480, 1670, 2925 cmꢁ1
;
1H-NMR (400 MHz, CDCl3) d1.26
2
(s, 18H), 3.84 (s, 6H), 4.13 (s, 2H), 7.38 (d, JHH ¼ 2.44 Hz, 2H), 7.76
2
(d, JHH ¼ 2.44 Hz, 2H), 10.38 (s, 2H). Anal. Calcd for C25H32O4:
C, 75.73; H, 8.13. Found: C, 75.51; H, 8.33.
Preparation of 5,12,20-tetra-tert-butyl-1,2,16,17-tetrahydroxyl-
8,15,23,30-tetramethoxyl-[2.1.2.1]metacyclophane (3) by using
Aluminum Powder
To a mixture of 2 (1.0 g, 2.5 mmol), methanol (330 mL), and aluminum
powder (150 mesh, 4.1 g, 15 mmol), aqueous 20% sodium hydroxide sol-
ution (150 mL) was added dropwise during a period of 2 h at rt under mech-
anical stirring. After 30 min, the mixture was filtered and the filtrate was
extracted with chloroform (60 mL ꢂ 4). The extract was washed with
water, dried over MgSO4 and evaporated in vacuo, leaving a residue,
which was subjected to column chromatographed on silica gel (Waco-gel,
C-300, eluent; hexane=ethyl acetate, 3=1), to afford 3 (0.58 g, 29%).
3: white powder; mp 259–261ꢀC ; m=z (FAB) 796 (Mþ) for C50H68O8;
1H NMR (400 MHz, [D6]DMSO, 100ꢀC, TMS): d ¼ 1.01–1.40 (brm,
36H), 2.82–3.05 (brm, 12H), 3.40–5.30 (brm, 12H), 7.00–7.34 (brm,
8H); Anal. Calcd for C50H68O8: C, 75.34; H, 8.60. Found: C, 75.53; H,
8.47%.
Synthesis of 5,12,20-tetra-tert-butyl-1,2,16,17-tetracarbonyl-
8,15,23,30-tetramethoxyl- [2.1.2.1]metacyclophane (4)
To a solution of 3 (50 mg, 0.063 mmol) in dry dimethyl sulfoxide
(7.0 mL, 97 mmol) was added acetic anhydride (1.0 mL, 9.7 mmol).
After the mixture was stirred for 24 h at 80ꢀC under nitrogen, cold
water (20 mL) and ammonia solution (1.0 mL) was added to it and
the mixture was extracted with chloroform (60 mL ꢂ 4). The extract
was washed with water, dried over MgSO4 and evaporated in vacuo,
leaving a residue, which was subjected to column chromatographed
on silica gel (Waco-gel, C-300, eluent; hexane=ethyl acetate, 3=1) and
recrystalized with hexane, to afford 4 (0.42 g, 18%).

362
Y. Nishiyama et al.
4: colorless prisms; mp > 300; FT-IR 1003, 1214, 1480, 1651, 1660,
2958 cmꢁ1; UV-Vis (methanol) 259 (e1125), 313 (e3056); 1H-NMR
(500 MHz, Toluene-d8) d1.15 (s, 36H), 3.20 (s, 12H), 3.56 (br, 4H),
2
2
7.35 (d, JHH ¼ 2.44 Hz, 4H), 8.01 (d, JHH ¼ 2.44 Hz, 4H); MS (TOF)
m=z 815 (Mþ þ Al). Found: C, 74.55; H, 7.85%. Calcd for
C50H60O8 þ H2O: C, 74.44; H, 7.69%.
Synthesis of 13,20,36,43-tetra-tert-butyl-16,23,39,46-
tetramethoxy[1.1](2,3)(2,3-diphenyl)quinoxalinophane (5)
To a solution of 4 (25 mg, 0.03 mmol) in acetic acid (15 mL) was
added 1,2-phenylenediamine (150 mg, 0.92 mmol). After the mixture
was refluxed for 48 h under nitrogen, cold water (10 mL) was added
to it and the mixture was extracted with chloroform (60 mL ꢂ 4). The
extract was washed with water, dried over MgSO4 and evaporated
in vacuo, leaving a residue, which was subjected to column chromato-
graphed on silica gel (Waco-gel, C-300, eluent; hexane=ethyl acetate,
5=1) and recrystalized with the mixture of methanol and chloroform,
to afford 5 (7.0 mg, 25%).
5: colorless prisms; mp > 300; FT-IR 1010, 1217, 1363, 1479,
1743, 2959 cmꢁ1; UV-Vis (methanol) 299 (e3194), 307 (e3333), 332
(e2917); 1H-NMR (500 MHz, Toluene-d8) d1.22 (s, 36H), 3.24
2
2
(d, JHH ¼ 14.04 Hz, 2H), 3.62 (s, 12H), 4.47 (d, JHH ¼ 13.41 Hz,
2
2
2H), 7.25 (d, JHH ¼ 2.44 Hz, 4H), 7.26 (d, JHH ¼ 2.44 Hz, 4H), 7.36
(m, 4H), 8.13 (m, 4H); MS (TOF) m=z 938 (Mþ þ 5H); MS (FABþ)
m=z 933 (Mþ). HRMS Found: 933.52218. Calcd for C62H67N3O5:
933.50803.
Measurements
1H-NMR and IR spectra of synthesized compounds were taken on
a JEOL EX400 and Shimadzu IR-408 spectrometer, respectively.
UV-visible absorption and Fluorescence spectra were obtained from
Hitachi U 3210 spectrophotometer and Shimadzu RF-540 spectro-
fluorophotometer. X-ray crystallography was determined by Rigaku
AFC 7 R radiation diffractmeter.
X-Ray Structure Determination
Crystal Data of 4:. colorless prism, C50H60O8, M ¼ 788.98,
˚
˚
Monoclinic, space group P 21=n,a ¼ 14.354(5) A, b ¼ 14.965(5) A,
ꢀ
3
˚
˚
c ¼ 10.866(5) A, b ¼ 91.042(5 ), V ¼ 2333.7(16) A , Z ¼ 2, Dcalc
¼
1.123 Mg=m3, crystal dimension 0.25 ꢂ 0.20 ꢂ 0.20 mm. Data were
measured on a Rigaku AFC 7 R radiation diffractmeter with

Pinacol Synthesis of Functional Metacyclophane
363
graphite-monochromated Mo-Ka radiation. Total 6442 refrections
(5349 unique) were collected using w-2q scan technique with in a 2q
range of 55.0ꢀ. The structure was solved by direct methods (SIR92),
and refined a full-matrix least squares methods using CrystalStruc-
ture analysis software with 5349 observed refrections [I > 2s(I)].
The final refinement converged to R ¼ 0.073 and Rw ¼ 0.13. CCDC
298137 contains the supplementary crystallographic data for this
article. These data can be obtained free of charge from The
Cambridge Crystallographic Data Center via www.ccdc.cam.ac.uk/
data_request/cif.
RESULTS AND DISCUSSION
The preparation of [2.1.2.1]MCP 3 is shown in Scheme 2.
Diphenylmethane dialdehyde 2 was prepared from bis(chloro-
methyl) diphenyl methane 1. The pinacol coupling reaction of 2 was
carried out with aluminum powder, titanium chloride, or samarium
diiodide. Attempting the pinacol coupling reaction with samarium
iodide yielded a complex mixture of linear chain polymers. By using
titanium tetrachloride, 1:2 mixture of a 1,2-alternate and a partial-cone
structure of [2.1.2.1]MCP 3 were obtained. The pinacol coupling with
aluminum powder yielded a 1,2-alternate structure of [2.1.2.1]MCP 3
as a single isomer [6].
Oxidation and the subsequent condensation reaction of [2.1.2.1]MCP
3 are shown in Scheme 3.

364
Y. Nishiyama et al.
The oxidation of [2.1.2.1]MCP 3 was performed by the Albright-
Goldman oxidation [8] using dimethylsulfoxide with acetic anhydride.
The X-ray crystallographic structure of [2.1.2.1]MCP-tetraone 4 is
shown in Figure 1.
The conformation of tetracarbonyl[2.1.2.1]MCP 4 was determined
as a 1,2-alternate type with oppositely located diphenylmethane units.
The carbonyl groups of tetracarbonyl[2.1.2.1]MCP 4 were directed
perpendicular to each other (94.4ꢀ). These results indicated that the
p-conjugated system of [2.1.2.1]MCP did not continue at a periphery
of a macrocycle. The diameter of the molecular cavity between the
˚
bridges carbon was measured as 7.4 A. The dihedral angle of the benzene
rings were determined as 177.9ꢀ. The tetracarbonyl[2.1.2.1]MCP 4
exhibit a flipping motion at rt and its dynamic NMR spectra indicated
the activation energy D G# of the conformational mobility as
45.9 kJ=mol. This value was a little higher than that of tetramethoxy
[2.1.2.1]MCP (43.6 kJ=mol) [7].
The condensation of tetracarbonyl[2.1.2.1]MCP 4 with o-phenylene-
diamine [9] in the presence of acetic acid yielded a [1.1]diphenyl-
quinoxalinophane ([1.1]DPQP) 5 possessing two quinoxaline rings at
the bridge moieties.
The UV-Vis absorption spectra and the fluorescence spectra of
[1.1]DPQP 5 and parent quinoxaline, as the reference compound, are
shown in Figure 2 and Figure 3.
UV-Vis absorption maximums (kmax,UV) of [1.1]DPQP 5 were
observed at 298 nm and 307 nm and those of quinoxaline were mea-
sured to be at 304 nm and 315 nm. In the case of [1.1]DPQP 5, the
decreasing intensity, blue shift, and shoulder peaks were observed
at the long-wavelength region and were compared with those of
the quinoxaline. The shoulder peaks appear to be influenced by the
extension caused by the p-conjugated system.
FIGURE 1 X-ray crystallographic structure of tetracarbonyl[2.1.2.1]MCP 4

Pinacol Synthesis of Functional Metacyclophane
365
FIGURE 2 UV-Vis absorption spectra of [1.1]DPQP 5 and quinoxaline in
CH3CN at rt.
The relative emission intensity of [1.1]DPQP 5 was higher than
that of the parent quinoxaline. In the case of the parent quinoxaline,
the emission maxium was observed at 350 nm in 2.0 ꢂ 10ꢁ5 mol=L.
However, in higher concentration (2.0 10ꢁ3 mol=L), its excimer emission
peaks were detected at 430, 390, 360 nm. The excimer is a short-lived
dimeric molecule formed from two species, at least one of which is in
an electronic excited state. The excimer of the fluorescent molecules
is expected to be observed at a longer wavelength than that of the
monomer emission. The emission maximum of the monomeric diphe-
nylquinoxaline and its intramolecular excimer was detected at
350 nm and 480 nm, respectively. In this case, the two quinoxaline
moieties of a [1.1]DPQP 5 could form a intramolecular excimer due
to its conformational flexibility.
The change in the relative emission intensity of [1.1]DPQP 5 in
the presence of sodium perchlorate or litium perchlorate are shown
in Figure 4.
The measurements were performed in acetonitrile at 7.5 ꢂ 10ꢁ5
M
[1.1]DPQP 5 in the presence of alkali perchlorate from 10ꢁ6 to 10ꢁ1 M.
Since attempting titration with potassium perchlorate caused the

366
Y. Nishiyama et al.
FIGURE 3 Emission fluorescence spectra of [1.1]DPQP 5 and quinoxaline in
˚
CH3CN at 20 C.
FIGURE 4 Relative intensity change in emission maximum of [1.1]DPQP 5 in
the presence of NaClO4 or LiClO4.

Pinacol Synthesis of Functional Metacyclophane
367
acetonitrile solvent to saturate, the titration of lithium and sodium
perchlorate was investigated and the intensity change is shown in
Figure 4.
As compared to the case of lithium perchlorate, an increase in the
amount of sodium perchlorate, decreases the relative emission inten-
sity of the monomer (350 nm) and the excimer (480 nm). In the case
of titration with sodium cations, small amount of red shifts were
observed in monomeric and excimeric emissions; these shifts were
identical-5nm. On the other hand, the titration with lithium perchlor-
ate does not indicate any shift in the emission maximum although
there is a small change in the relative intensity. Increasing the
radiationless deactivaton and the red shift of the emission maximum
by complexation of [1.1]DPQP 5 with sodium ion may be possible;
however this hypothesis lacks substantial evidence with regard to
complexation.
CONCLUSIONS
By the pinacol coupling reaction with aluminum powder, we have pre-
pared the novel macrocyclic tetrahydroxy[2.1.2.1]MCP 3 as a single
isomer. This compound 3 is regarded as a calixarene analog and it also
comprises tetrahydroxyl groups that are functionalized at the bridge
position. The oxidation and the subsequent annulation produced fluor-
escence macrocycle 5. This [1.1]DPQP 5 indicated intramolecular exci-
mer and monomer emissions, and the influenced of titration with
sodium perchlorate on them. These results suggested that the pinacol
coupling reaction could be a useful method to produce a novel macro-
cyclic calixarene analog.
REFERENCES
[1] Fittig, R. (1859). Justus Liebigs Ann. Chem., 110, 23.
[2] (a) Ziegler, I. M., Hamdi, A., Abidi, R., & Vincens, J. (2006). Supramolecular Chem.,
18, 219.
(b) Hamada, F., Masuda, T., & Kondo, Y. (1995). J. Supramolecular Chem., 5, 129.
[3] Garrier, E., Gac, S. L., & Jabin, I. (2005). Tetrahedron: Asymmetry, 16, 3767.
[4] (a) Rao, C. P. & Dey, M. (2004). Calixarene in Encyclopedia of Nanoscience and
Nanotechnology, 1, 475–497.
(b) Gutsche, C. D. (1998). Calixarene Revisited, The Royal Society of Chemistry:
Cambridge.
(c) Vicens, J. & Bo¨hmer, V. (1991). ‘Calixarene: A Versatile Class of Macrocyclic Com-
pounds, Kluwer Academic Publishers: Dordrecht.
[5] (a) Sahade, D. A., Mataka, S., Sawada, T., Tsukinoki, T., & Tashiro, M. (1997). Tetra-
hedron Lett., 38, 3745.
(b) Sahade, D. A., Tsukamoto, K., Thiemann, T., Sawada, T., & Mataka, S. (1999).
Tetrahedron, 55, 2573.

368
Y. Nishiyama et al.
[6] Sawada, T., Nishiyama, Y., Tabuchi, W., Ishikawa, M., Tsutsumi, E., Kuwahara, Y.,
& Shosenji, H. (2006). Org. Lett., 8, 10995.
[7] Sawada, T., Tsuge, A., Thiemann, T., Mataka, S., & Tashiro M. J. (1994). Inclusion
Phenomenon Mol. Recognition Chem., 19, 301.
[8] Albright, J. D. & Goldman, L. (1965). J. Am. Chem. Soc., 87, 4214.
[9] Clemo, G. R. & McIlwain, H. (1934). J. Chem. Soc., 1935, 1991.