An Alternative Synthesis of Bipyrenol: A High-Yield Oxidative Coupling Reaction of a Pyrene Derivative with Cu(BF 4) 2 ·nH 2 O

Article abstract of DOI:10.1055/s-0036-1588819

An alternative synthesis has been developed with the objective of extending the applications of bipyrenol in mind. The key reaction involves the oxidative coupling of 2-hydroxypyrene menthyl carbonate to afford the corresponding pyrene dimer. In marked contrast to our previous method, i.e., the oxidation of 2-hydroxypyrene, the revised method is a clean and high-yielding reaction. By optimizing the reaction conditions, the yield of the alternative synthesis is increased to 88%.

Full text of DOI:10.1055/s-0036-1588819

SYNTHESIS
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Georg Thieme Verlag Stuttgart · New York
2017, 49, A–D
paper
A
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Synthesis
S. Rajbangshi, K.-i. Sugiura
Paper
An Alternative Synthesis of Bipyrenol: A High-Yield Oxidative Cou-
pling Reaction of a Pyrene Derivative with Cu(BF ) ·nH O
4
2
2
Subas Rajbangshi
Ken-ichi Sugiura*
Ment
Ment
Ment
O
O
O
Cu(BF4)2
MeCN
simple
optical
resolution
Department of Chemistry, Graduate School of Science
and Engineering, Tokyo Metropolitan University, 1-1
Minami-Osawa, Hachi-Oji, Tokyo 192-0397, Japan
sugiura@porphyrin.jp
tBu
tBu
tBu
Ment = menthyl carbonate
88%
Received: 04.03.2017
HO OH
HO OH
Accepted after revision: 02.04.2017
Published online: 09.05.2017
DOI: 10.1055/s-0036-1588819; Art ID: ss-2017-f0139-op
Abstract An alternative synthesis has been developed with the objec-
tive of extending the applications of bipyrenol in mind. The key reaction
involves the oxidative coupling of 2-hydroxypyrene menthyl carbonate
to afford the corresponding pyrene dimer. In marked contrast to our
previous method, i.e., the oxidation of 2-hydroxypyrene, the revised
method is a clean and high-yielding reaction. By optimizing the reac-
tion conditions, the yield of the alternative synthesis is increased to
(
R)-1
(S)-1
1,1'-bi-2-naphthol (BINOL)
HO OH
HO OH
88%.
Key words BINOL, bipyrenol, copper(II) tetrafluoroborate, oxidative
coupling, pyrene
1
,1′-Bi-2-naphthol 1 (BINOL) (Figure 1) and structurally
tBu
tBu tBu
tBu
similar axially chiral molecules have opened new doors in
chemistry. Many chemical modifications aimed at enhanc-
(R)-2
(S)-2
1
1
,1'-bi-2-pyrenol (bipyrenol)
ing the properties of BINOLs, which are dependent on their
chiral structures, have been reported. Among them, the ex-
pansion of the π-system of BINOL is frequently used be-
cause large polycyclic aromatic hydrocarbons (PAHs) in-
crease the chiral space of a molecule, i.e., replacing the
naphthalene of 1 with π-expanded PAHs such as phenan-
threne, anthracene, and chrysene. Along with these ad-
vances, we are interested in the photophysical properties of
chiral molecules, i.e., emission from chiral molecules,
Figure 1 Chiral molecular structures of 1,1′-bi-2-naphthol (BINOL) 1
and 1,1′-bi-2-pyrenol (bipyrenol)
6
with FeCl in MeNO /EtOH. One of the advantages of our
synthetic strategy and/or the chemistry of 2 is the simple
optical resolution, i.e., the diastereomixture of the corre-
sponding menthyl carbonate is easily separated by SiO col-
3
2
2
3
4
2
5
known as circularly polarized luminescence (CPL). Howev-
umn chromatography.
er, the quantum yields (Φ) of reported axially chiral mole-
As far as we know, the same procedure was not applica-
ble to the optical resolution of 1. We speculated that an ex-
panded π-system would enhance the differences in physical
properties attributable to the differences in stereochemis-
try. In the case of 1, the revised reaction scheme Route B of
Scheme 1, namely, carbonate formation and the subsequent
coupling reaction, seemed convenient. We adopted this
strategy in our previous report. However, the oxidation of
cules are not sufficient for inducing CPL in advanced mate-
6
rials, e.g., the Φ of 1 is merely 0.04. With these findings as
background, we previously reported pyrene-based axially
chiral molecules, 1,1′-bi-2-pyrenols 2 (bipyrenols) (Figure
1
), and their enhanced photophysical properties.6
In our previous report, we adopted a classic synthetic
method, i.e., the oxidative coupling reaction of 2-pyrenol
the carbonate with FeCl was unsuccessful. Considering the
3
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Georg Thieme Verlag Stuttgart · New York — Synthesis 2017, 49, A–D

B
Synthesis
S. Rajbangshi, K.-i. Sugiura
Paper
wide application of bipyrenol 2, in this study, we have de-
Table 1 Oxidative Coupling Reaction of 5 Affording dia-6
veloped a simple and high-yielding alternative synthesis of
2
.
Entry
Reagent
Equiv
Solvent
Yield of
dia-6 (%)
Although many revised synthetic methods were report-
ed after the first synthesis of 1 by oxidative coupling using
II
6a
1
2
3
4
5
6
7
8
9
Cu (BF
CuCl
CuBr
Cu(OAc)
4
)
2
·nH
2
O
butyronitrile
butyronitrile
butyronitrile
butyronitrile
butyronitrile
butyronitrile
butyronitrile
butyronitrile
MeCN
64
7
metals such as FeCl , including a solid-state reaction with
dec.b
3
2
6
6
6
6
8
FeCl known as the Toda reaction, the revised Toda reac-
tion using microwave irradiation,
3
dec.b
9
10
2
CuCl /amine,
2
dec.b
11
2 2
·H O
H O /Au/SrTiO , and phenyliodine(III) bis(trifluoroace-
2
2
3
1
2
CuSO ·5H O
dec.
b
tate) (PIFA)/BF ·Et O, and an organometallic method using
4
2
3
2
the Suzuki–Miyaura coupling,1 our synthetic study on
3
FeCl3
6
dec.b
85
structurally well-defined oligopyrenes, in which the syn-
II
5a
Cu (BF
4
4
4
4
)
)
)
)
2
2
2
2
·nH
·nH
·nH
·nH
2
2
2
2
O
O
O
O
II
14
theses were carried out with Cu (BF ) ·nH O, gave us a
4
2
2
II
4a
Cu (BF
90
hint toward the alternative synthesis of 2. This oligomeriza-
tion proceeded smoothly under mild conditions to give
higher oligomers of 1,3-pyrenylenes, and the reaction mix-
ture was clean and not contaminated with tarry products
often found in oxidation reactions.
II
4a
4a
Cu (BF
88
II
–c
10
Cu (BF
EtOH
a
Because of the high hygroscopicity of commercially available
·nH O, it was too difficult to weigh the reagent accurately.
Decomposition occurred and dia-6 was not available in any quantity.
Cu(BF
4
)
2
2
b
c
Substrate 5, used as reference compound in our previ-
ous photochemistry, was prepared by the carbonate reac-
No reaction occurred.
6
tion of 2-pyrenol 4 with (–)-menthyl chloroformate. The
oxidation reaction of 5 was carried out under various con-
ditions, as listed in Table 1. First, an oxidation reaction used
for the synthesis of pyrene oligomers was employed (Table
ined the FeIII salt used in our previous study for the prepara-
tion of rac-2 (Table 1, entry 6). However, decomposition
was also observed.
14
1
, entry 1), i.e., treatment of an excess amount of
II
Cu (BF ) ·nH O in boiling butyronitrile afforded the desired
In the experiments in Table 1 (entries 7 and 8), the stoi-
4
2
2
II
dimerized diastereomixture, dia-6, in 64% yield. As was
chiometry of Cu (BF ) ·nH O was examined. We found that
4
2
2
II
II
mentioned in the Introduction, many Cu salts have been
approximately four equivalents of Cu (BF ) ·nH O were
suitable for the reaction.
4 2 2
II
15
used for the synthesis of 1. Hence, Cu salts including CuCl ,
2
CuBr , Cu(OAc) ·H O, and CuSO ·5H O were examined for
the synthesis of dia-6. However, all of these Cu salts in-
duced decomposition (Table 1, entries 2–5). We also exam-
Because of the limited solubility of the pyrene oligo-
mers, we used butyronitrile, the best solvent in our previ-
ous study,14 because this coordinative solvent has unique
polarity attributable to the lipophilic propyl group and the
2
2
2
4
2
II
HO OH
Route A
b
c
e
(R)-2
Ment
Ment
OH
O O
tBu
tBu
rac-2
a
d
Ment
O
tBu
tBu
tBu
3
4
dia-6
(S)-2
c
f
e
Route B
Me
tBu
Me
Me
5
Ment =
O
O
Scheme 1 Two synthetic routes for 2. Route A: previously reported route; Route B: an alternative route introduced in this study. Reagents and conditions:
(
a) (i) tert-butyl chloride, AlCl , CH Cl ; (ii) [IrI(OMe)cod] , 4,4′-di-tert-butyl-2,2′-bipyridyl, bis(pinacolato)diboron, cyclohexane; (iii) H O , KOH;
3
2
2
2
2
2
(
b) FeCl /EtOH, reflux; (c) (–)-menthyl chloroformate, Et N, toluene, r.t.; (d) SiO flash chromatography; (e) KOH, EtOH/H O (4:1), reflux; (f) oxidative
3
3
2
2
coupling reaction. The conditions are summarized in Table 1.
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C
Synthesis
S. Rajbangshi, K.-i. Sugiura
Paper
polar/coordinative nitrile group. However, the high cost of
butyronitrile forced us to explore more cost-efficient sol-
vents. EtOH, as used in the synthesis of rac-2, did not in-
duce the reaction. Acetonitrile gave the best result, i.e., dia-
The synthesis of the menthyl carbonate of 4-tert-butylpyrene-2-ol 5
was conducted in accordance with a reported method. The following
6
reagents were used as received: Cu(BF ) ·nH O (Sigma-Aldrich Co.)
4
2
2
and EtOH (Wako Pure Chemical Industries, Ltd.). The following re-
agents were used after purification: butyronitrile (Tokyo Chemical In-
dustry Co., Ltd., distilled over CaH under N ) and MeCN (Wako Pure
6
was obtained in 88% yield. Currently, the conditions listed
2
2
in entry 9 (Table 1) are the best. The obtained dia-6 was
separated into the corresponding diastereomers and subse-
quent hydrolysis afforded optically pure 2.
Chemical Industries, Ltd., distilled over CaH under N ). Silica gel thin
2
2
layer chromatography (Merck & Co., Inc.) was performed using Silica Gel
60 F254 Aluminium Sheet from Merck Co. Ltd. Column chromatography
was performed using Neutral Silica Gel 60N (spherical, 40-50 mm) from
II
In all the reactions using Cu (BF ) ·nH O, the reaction
4
2
2
1
Kanto Chemical Co., Inc as the silica gel. The H NMR spectra were record-
mixtures contained dark yellow products that could be eas-
1
ed on a Bruker Avance III 500 (500 MHz for H) spectrometer in CDCl3
ily separated from dia-6 by SiO column chromatography.
2
(Acros Organics Co., Inc.) with TMS as the internal standard. Infrared spec-
Although these colored materials were trace products,
tra were recorded on a Shimadzu FTIR-8400 instrument using KBr pellet
16
our interest in π-expanded quinoidal molecules prompted
us to perform careful isolation and analysis of these prod-
ucts. The colored products were further separated into sev-
eral products and two of them were characterized as com-
pounds 7 and 8 (Figure 2), i.e., 7 and 8 were formed by the
direct oxidation of substrate 5. This quinone formation
might reflect the high reactivity of pyrene. In the synthesis
of bianthracenol, the formation of quinone was also report-
ed, however, the origin of the quinoidal oxygen is the
–1
and/or liquid film techniques in the range of 500 to 4000 cm . The ab-
sorption spectra were recorded on a Shimadzu UV-3600 using spectro-
photometric-grade CH2Cl2 (reagent grade, treated with sulfuric acid). At-
mospheric pressure chemical ionization (APCI) mass spectra were record-
ed on a Bruker micrOTOF II SDT1. Other experimental details, including
18
spectroscopic studies, were reported previously.
Synthesis of the Diastereomixture of 6 (dia-6) (Table 1, Entry 9)
Dry MeCN (200 mL) was introduced into a 300 mL three-necked flask
and purged with N . Against the stream of N , compound 5 (1.00 g, 2.2
2
2
17
hydroxy group of anthracenol.
mmol) and Cu(BF ) ·nH O (2.07 g, 8.77 mmol) were added. The reac-
4
2
2
tion mixture was refluxed under an inert atmosphere. After 3 h, TLC
analysis showed the disappearance of 5 and the formation of new
Ment
Ment
O
O
products attributable to 6 [R = 0.45 and 0.40 for the two diastereo-
O
f
mers; SiO2 eluted with a mixed solvent of n-hexane/toluene (2:3)].
The mixture was cooled and the solvent was removed under reduced
pressure. The residue was suspended in CHCl3 and this mixture was
passed through a short SiO column eluted with CHCl to remove in-
O
O
2
3
organic salts. The obtained crude product was further purified
O
tBu
tBu
through another SiO column with a mixed solvent of n-hexane/tolu-
2
ene (2:3) as eluent to give diastereomixture dia-6 (0.88 g, 88%). The
eluent was exchanged with a mixed solvent of n-hexane/toluene (1:4)
to give trace amounts of colored products (vide infra).
7
8
Figure 2 Molecular structures of quinoidal molecules 7 and 8 formed
in the oxidation reactions
The obtained dia-6 was separated by SiO2 column chromatography
again. As reported in our previous study, the product having a high Rf
value is the (R)-isomer of menthyl carbonate and the product having
In conclusion, upon rearranging the order of the reac-
tion in the synthesis of 2, we found an easy synthesis of dia-
a low R value is the (S)-isomer. The yields of both isomers were 44%
f
(
0.40 g, each). All of the spectroscopic data were identical with those
6
. The availability of stable carbonate 5 under the ambient
reported previously.
the products was easily determined by H NMR measurements be-
cause these diastereomers showed completely different spectra.
6
It should be emphasized again that the purity of
1
conditions spared us the trouble of handling unstable π-ex-
panded phenol 4. This could induce the clean and high-yield
formation of dia-6. We were also interested in the forma-
tion of pyrene-based quinones, such as 7 and 8. Because the
π-expanded quinones showed potential as component mol-
ecules for advanced materials, exploration of the selective
synthesis of quinones from 5 and/or dia-6 should be inter-
esting. Our revised synthetic method may well contribute
to the application of bipyrenol 2 in various fields of chemis-
try, including asymmetric synthesis, molecular recognition,
and advanced materials, and could be used in the synthesis
of new π-expanded axially chiral molecules.
The collected colored compounds were separated by preparative
thin-layer chromatography [SiO2 eluted with a mixed solvent of
n-hexane/CHCl (1:20)]. We isolated two trace products 7 and 8 hav-
3
ing R values of 0.25 and 0.28, respectively [SiO , n-hexane/toluene
f
2
(2:3)]. Spectroscopic data are as follows.
Compound 7
1
H NMR (500 MHz, CDCl , TMS): δ = 8.51 (d, J = 7.3 Hz, 1 H), 8.43 (d,
3
J = 7.3 Hz, 1 H), 7.81 (d, J = 7.3 Hz, 1 H), 7.77 (d, J = 7.3 Hz, 1 H), 7.51 (s,
1
H), 7.47 (s, 1 H), 4.65 (ddd, J = 10.7, 10.7, 4.4 Hz, 1 H), 2.24 (d, m, J =
12.0 Hz, 1 H), 2.13 (sept d, J = 6.9, 4.4 Hz, 1 H), 1.77–1.68 (m, 2 H),
1
1
.55–1.50 (m, 1 H), 1.43 (s, 9 H), 1.21 (ddd, J = 12.0, 12.0, 12.0 Hz, 1 H),
.10 (ddd, J = 12.0, 12.0, 3.5 Hz, 1 H), 0.975 (d, J = 6.3 Hz, 3 H), 0.973
(d, J = 6.3 Hz, 3 H), 0.95–0.85 (m, 2 H), 0.89 (d, J = 6.3 Hz, 3 H).
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Synthesis
S. Rajbangshi, K.-i. Sugiura
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To confirm this compound consists of 1,6-pyrenequinone, not 1,8-
pyrenequinone, differential NOE and 1H– H COSY experiments were
carried out (see the Supporting Information).
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2
5
867.
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447 (0.21) nm.
(
MS (APCI): m/z [M + H]+ calcd for C31H35O : 487.24; found: 487.3
5
7
(70%).
(
(
c) Riehl, J. P.; Richardson, F. S. Chem. Rev. 1986, 86, 1.
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1
H NMR (500 MHz, CDCl , TMS): δ = 8.31 (d, J = 2.3 Hz, 1 H), 8.25 (d,
Moreno, F.; Maroto, B. L.; Muller, G.; Ortiz, M. J.; de la Moya, S.
3
J = 8.6 Hz, 1 H), 8.05 (d, J = 8.6 Hz, 1 H), 7.98 (d, J = 2.3 Hz, 1 H), 7.30 (s,
Chem. Eur. J. 2015, 13488.
1
1
1
1
H), 6.81 (s, 1 H), 4.67 (ddd, J = 10.7, 10.7, 4.4 Hz, 1 H), 2.21 (d, m, J =
2.0 Hz, 1 H), 2.07 (sept d, J = 6.9, 4.4 Hz, 1 H), 1.77–1.70 (m, 2 H),
.55–1.50 (m, 1 H), 1.43 (s, 9 H), 1.20 (ddd, J = 12.0, 12.0, 12.0 Hz, 1 H),
.10 (ddd, J = 12.0, 12.0, 3.5 Hz, 1 H), 0.980 (d, J = 6.3 Hz, 3 H), 0.978
(6) Hassan, K.; Yamashita, K.-i.; Hirabayashi, K.; Shimizu, T.;
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(d, J = 6.3 Hz, 3 H), 0.95–0.85 (m, 2 H), 0.88 (d, J = 6.3 Hz, 3 H).
(
8) Toda, F.; Tanaka, K.; Iwata, S. J. Org. Chem. 1989, 54, 3007.
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2
2
max
(9) Ji, S.-J.; Lu, J.; Zhu, X.; Yang, J.; Lang, J.-P.; Wu, L. Synth. Commun.
(
2
shoulder, s, 0.07), 364 (0.20), 347 (0.17), 330 (s, 0.08), 300 (s, 0.22),
89 (0.24) nm.
MS (APCI): m/z [M + H]+ calcd for C31H35O : 487.24; found: 487.3
2002, 32, 3069.
(
10) (a) Bandin, M.; Casolari, S.; Cozzi, P. G.; Proni, G.; Schmohel, E.;
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(
(
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(
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Acknowledgment
2015, 51, 17669.
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hedron 2001, 57, 345.
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This work was supported in part by the Tokyo Kasei Chemical Promo-
tion Foundation, the Cooperative Research Program of ‘Network Joint
Research Center for Materials and Devices: Dynamic Alliance for Open
Innovation Bridging Human, Environment and Materials’, and the Pri-
ority Research Program sponsored by the Asian Human Resources
Fund of Tokyo Metropolitan Government (TMG).
44, 303.
15) The stoichiometry of this hygroscopic reagent was regarded to
be Cu(BF ) ·6H O as the idealized hexahydrate salt. However, it
4
2
2
was too difficult to weigh the reagent accurately because of the
high hygroscopicity of commercially available Cu(BF ) ·nH O.
Supporting Information
4
2
2
(
16) (a) Sugiura, K.-i.; Mikami, S.; Iwasaki, K.; Hino, S.; Asato, E.;
Sakata, Y. J. Mater. Chem. 2000, 10, 315. (b) Hossain, M. A.;
Akiyama, K.; Goto, K.; Sugiura, K.-i. ChemistrySelect 2016, 1,
Supporting information for this article is available online at
https://doi.org/10.1055/s-0036-1588819.
S
u
p
p
ortioIgnfrm oaitn
S
u
p
p
ortioIgnfrm oaitn
3784. (c) Hossain, M. A.; Akiyama, K.; Sugiura, K.-i. ChemistrySe-
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©
Georg Thieme Verlag Stuttgart · New York — Synthesis 2017, 49, A–D