Synthesis of 1,6′-Bi- and 1,6′:3,6″-terazulenes from 1-pyridyl- and 1,3-Di(pyridyl)azulenes by the Ziegler-Hafner method

Article abstract of DOI:10.1246/cl.130157

The synthesis of 1,6′-biazulenes 3a and 3b and 1,6′:3,6″- terazulenes 7a and 7b was established by one-pot reactions via the Zincke-type ring-opening of the corresponding pyridinium salts with diethylamine, followed by the reaction with cyclopentadiene in

Full text of DOI:10.1246/cl.130157

doi:10.1246/cl.130157
638
Published on the web May 18, 2013
Synthesis of 1,6¤-Bi- and 1,6¤:3,6¤¤-Terazulenes from 1-Pyridyl- and 1,3-Di(pyridyl)azulenes
by the Ziegler-Hafner Method
Taku Shoji,*1 Atsuyo Yamamoto,1 Erika Shimomura,1 Mitsuhisa Maruyama,1 Shunji Ito,2
Tetsuo Okujima,3 Kozo Toyota,4 and Noboru Morita4
1Department of Chemistry, Faculty of Science, Shinshu University, Matsumoto, Nagano 390-8621
2Graduate School of Science and Technology, Hirosaki University, Hirosaki, Aomori 036-8561
3Department of Chemistry and Biology, Graduate School of Science and Engineering, Ehime University,
Matsuyama, Ehime 790-8577
4Department of Chemistry, Graduate School of Science, Tohoku University, Sendai, Miyagi 980-8578
(Received February 25, 2013; CL-130157; E-mail: tshoji@shinshu-u.ac.jp)
O2N
The synthesis of 1,6¤-biazulenes 3a and 3b and 1,6¤:3,6¤¤-
terazulenes 7a and 7b was established by one-pot reactions via
the Zincke-type ring-opening of the corresponding pyridinium
salts with diethylamine, followed by the reaction with cyclo-
pentadiene in the presence of sodium methoxide. The intra-
molecular charge-transfer characters between azulene rings were
investigated by UV-vis spectroscopy and theoretical calcula-
tions.
Cl
NO2
N
N
NO2
toluene
reflux
O2N Cl
1a: R = H
1b: R = t-Bu
2a: R = H
2b: R = t-Bu
R
R
1) diethylamine, EtOH
2) cyclopentadiene, MeONa
pyridine, reflux
Azulene has attracted the interest of many research groups
owing to its unusual properties as well as its beautiful blue
color.1 Thus, a large variety of synthetic methods for azulene
and its derivatives have been reported by Ziegler-Hafner,2
Nozoe,3 Takase-Yasunami,4 and so on. Among these proce-
dures, Ziegler-Hafner’s method, which employs pyridine and
cyclopentadiene as the starting materials, is the most efficient
procedure for the synthesis of parent azulene itself.
3a: R = H
3b: R = t-Bu
R
Scheme 1. Synthesis of 1,6¤-biazulenes 3a and 3b.
NO2
As well as azulene derivatives, biazulenes have also
attracted much interest due to their characteristic electronic
properties.5 Although the synthesis of symmetric 1,1¤-,5,6 2,2¤-,7
4,4¤-,8 5,5¤-,9 and 6,6¤-biazulenes10 appeared in the literature,
there are few reports for the preparation of unsymmetrical
biazulenes. In 1982, Morita and Takase reported the synthesis of
1,2¤- and 2,6¤-biazulenes by the Ullmann-type cross-coupling
reaction, but the procedure also produced symmetric biazulenes
as by-products.11 Recently, Murafuji et al. have reported the
preparation of 2¤,2¤¤-diamino-1¤,1¤¤,3¤,3¤¤-tetrakis(ethoxycarbon-
yl)-1,6¤:3,6¤¤-terazulene by the Suzuki-Miyaura cross-coupling
reaction of 1,3-dibromoazulene with the corresponding
6-azulenyl borane derivative.12 However, the synthesis of the
parent compounds, unsymmetrically binding bi- and terazulenes,
has never been reported, so far. For better understanding the
nature of these series, preparation of the parent bi- and
terazulenes should be essential.
NO2
N
N
O2N
Cl
NO2
R
2Cl
R
EtOH
reflux
6a: R = H
6b: R = t-Bu
4a: R = H
4b: R = t-Bu
N
N
NO2
O2N
Cl
NO2
NO2
1) diethylamine, EtOH
2) cyclopentadiene,
MeONa, pyridine, reflux
toluene
reflux
O2N
NO2
N
N
Herein, we describe the first synthesis of 1,6¤-biazulenes 3a
and 3b and 1,6¤:3,6¤¤-terazulenes 7a and 8b by the Ziegler-
Hafner’s method, i.e., ring-opening reaction of pyridinium salts
2a, 2b, 6a, and 6b with diethylamine, followed by the reaction
with cyclopentadienide (CPD) ion. The reactivity of 3a toward
an electrophile was also investigated. The electronic properties
of the new bi- and terazulenes obtained by this investigation
were characterized by absorption spectroscopy and theoretical
calculations.
Cl
5a: R = H
5b: R = t-Bu
7a: R = H
7b: R = t-Bu
R
R
Scheme 2. Synthesis of 1,6¤;3,6¤¤-terazulenes 7a and 7b.
respectively. For the preparation of 1,6¤-biazulenes 3a and 3b
by Ziegler-Hafner’s method, generation of pyridinium salts 2a
and 2b is required. Preparation of 2a has already been reported
by us.13 Similar to the preparation of 2a, tert-butyl derivative 1b
An overview of the synthetic path for the 1,6¤-bi- and
1,6¤:3,6¤¤-terazulenes are summarized in Schemes 1 and 2,
Chem. Lett. 2013, 42, 638-640
© 2013 The Chemical Society of Japan
www.csj.jp/journals/chem-lett/

639
Tf
N
was transformed into pyridinium salt 2b in 97% yield by the
reaction with 1-chloro-2,4-dinitrobenzene in toluene at refluxing
temperature. The synthesis of 1,6¤-biazulenes 3a and 3b was
established by the Zincke-type ring-opening reaction of the
pyridinium moiety of 2a and 2b with diethylamine,14 following
the reaction with CPD ion. The reaction of 2a and 2b with
diethylamine in EtOH at room temperature gave the correspond-
ing Zincke-type intermediates as brown oil. The crude products
were directly treated with cyclopentadiene in the presence of
sodium methoxide (MeONa) as a base in pyridine to yield the
presumed 1,6¤-biazulenes 3a and 3b in 56% and 91% yields,
respectively, as two-step yields based on 2a and 2b, respectively
(Scheme 1).15
TfN
pyridine, Tf2O
CH2Cl2
3a
8
N
Tf
KOH
EtOH, reflux
N
N
For the synthesis of 1,6¤:3,6¤¤-terazulenes 7a and 7b,
preparation of pyridinium salts 6a and 6b is necessary, prior
to the one-pot reactions involving the Zincke-type reaction
with diethylamine, followed by the reaction with CPD ion
(Scheme 2). However, the reaction of 4a and 4b, which could be
obtained by a procedure reported by us,16 with 1-chloro-2,4-
dinitrobenzene in toluene at refluxing temperature afforded 5a
and 5b in 97% and 94% yield, respectively, instead of 6a and
6b.17 We found the desired products 6a and 6b were obtained in
99% and 99% yields, respectively, when the solvent was
changed to ethanol from toluene. The ring-opening reaction of
6a with diethylamine, followed by the reaction with CPD ion
afforded the desired terazulene 7a in 10% yield. The 6-tert-butyl
derivative 7b was also prepared by the similar ring-opening of
the pyridinium moiety and nucleophilic reaction with CPD ion
in 17% yield. The low yield of the products should be
attributable to a significant decomposition of the compounds
under the reaction conditions. These novel 1,6¤-biazulenes 3a
and 3b and 1,6¤:3,6¤¤-terazulenes 7a and 7b were stable green
crystals and could be storable in the crystalline state under
ordinary conditions.
9
N
Scheme 3. Synthesis of 3,1¤,3¤-tripyridyl-1,6¤-biazulene (9).
To examine the reactivity of 3a toward an electrophilic
reagent, we have investigated the reaction of 3a with
1-trifluoromethanesulfonylpyridinium trifluoromethanesulfonate
(TPT), which can be easily prepared by the treatment of Tf2O
with pyridine and also the expected 4-pyridyl product can be
utilized for further transformation, e.g., as reported in this
communication (Scheme 3).16,18 The reaction of 3a with TPT
in the presence of excess pyridine gave 8 in 71% yield.
Aromatization of the three dihydropyridine moieties of 8 was
accomplished by the treatment of 8 with KOH in ethanol to
afford 3,1¤,3¤-tripyridyl-1,6¤-biazulene (9) in 85% yield. Pyridine
moieties act as a highly versatile functional group in organic
synthesis. Thus, further functionalization of 1,6¤-biazulene 3a
should be full of promise.
These new azulene derivatives 3a, 3b, 7a, 7b, and 9 were
fully characterized by spectral data. Mass spectra of 3a, 3b, 7a,
7b, and 9 ionized by EI or FAB showed the correct molecular
ion peaks. UV-vis spectra of 1,6¤-biazulene 3a and 1,6¤;3,6¤¤-
terazulene 7a showed characteristic weak absorption bands
arising from the azulene system in the visible region (Figure 1).
Although the extinction coefficients increased with the number
of azulene rings substituted, the absorption maxima of 3a
(-max = 583 nm) and 7a (-max = 576 nm) were almost equal to
that of the parent azulene (-max = 576 nm). Compounds 3a and
7a also exhibited relatively strong absorptions at -max = 430 nm
and -max = 436 nm, respectively, which may be attributable to
Figure 1. UV-vis spectra of 3a (blue line), 7a (red line), and
azulene (green line) in dichloromethane.
intramolecular charge transfer (ICT) between the two azulene
rings of the molecules, because these bands could not be
observed in that of the parent azulene.
To examine the theoretical aspects of the spectroscopic
properties, molecular orbital calculations were performed on 3a
by using B3LYP/6-31G** density functional theory.19 The
frontier Kohn-Sham orbitals of 3a are shown in Figure 2. The
strong absorption band at -max = 430 nm of 3a should be
considered as the transition from the HOMO¹1, that is mainly
located on the 1-azulenyl group, to the LUMO+1, that is located
on the azulene ring substituted by 6-position. The shape of
HOMO¹1 and LUMO+1 resemble the HOMO and LUMO
of the parent azulene itself in 1- and 6-azulenyl moieties,
respectively. Thus, the absorption band could be assumed as the
ICT from 1-azulenyl to 6-azulenyl groups. The relatively weak
absorption band at -max = 583 nm was confirmed to arise from
the overlap of the ³-³* transitions of substituted azulene-rings
as shown in Table 1. The calculations also revealed the ICT
contribution of 3a from 6-azulenyl to 1-azulenyl group
(HOMO ¼ LUMO) is negligibly small (Table 1).
In conclusion, 1,6¤-biazulenes 3a and 3b and 1,6¤:3,6¤¤-
terazulenes 7a and 7b were synthesized by Ziegler-Hafner’s
Chem. Lett. 2013, 42, 638-640
© 2013 The Chemical Society of Japan
www.csj.jp/journals/chem-lett/

640
Yamazaki, I. Shimao, M. Yasunami, Tetrahedron Lett. 1989, 30, 1557.
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LUMO
5
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LUMO+1
7
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Figure 2. Frontier Kohn-Sham orbitals of 3a at the B3LYP/
6-31G** level.
Table 1. Electronic transitions for 3a derived from the
computed values based on the B3LYP/6-31G** method and
experimental values
8
9
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Experimental
max/nm
Computed
max/nm
(strength)
Composition of banda,b
/CI coefficientsc
-
-
(log ¾)
583 (2.95)
531 (0.0078)
519 (0.0086)
497 (0.0001)
403 (0.4482)
c
H¹1 ¼ L/0.97
H ¼ L+1/0.95
H ¼ L/0.99
430 (4.32)
H¹1 ¼ L+1/0.94
aH: HOMO. L: LUMO. CI: configuration interaction.
b
15 Typical procedure: Diethylamine (16 mL) was added to a solution
of 2a (1.71 g, 4.2 mmol) in ethanol (36 mL). The resulting solution
was stirred at room temperature for 5 h. The reaction mixture was
concentrated under reduced pressure. To the residue was added
cyclopentadiene (333 mg, 5.0 mmol), 2.5 M MeONa (2 mL), and
pyridine (50 mL) and the mixture was refluxed for 1 day. Precipitate
was separated by filtration and the solvent was removed under
reduced pressure. The residue was purified by column chromatog-
raphy on silica gel with CH2Cl2 as an eluent to give 3a (593 mg, 56%
based on 2a) as green crystals. Mp 135.0-137.0 °C (CH2Cl2/MeOH);
1H NMR (500 MHz, CDCl3): ¤H 8.66 (d, 1H, J = 10.0 Hz, H8), 8.41
(d, 2H, J = 10.5 Hz, H4¤,8¤), 8.40 (d, 1H, J = 10.0 Hz, H4), 8.13 (d,
1H, J = 4.0 Hz, H2), 7.88 (t, 1H, J = 3.5 Hz, H2¤), 7.65 (t, 1H,
J = 10.0 Hz, H6), 7.51 (d, 2H, J = 10.5 Hz, H5¤,7¤), 7.47 (d, 1H,
J = 4.0 Hz, H3), 7.41 (d, 2H, J = 3.5 Hz, H1¤,3¤), 7.23 (t, 2H,
method, which consisting of the Zincke-type ring-opening of
pyridinium salts 2a, 2b and 6a, 6b, respectively, with diethyl-
amine, followed by the reaction with CPD ion. The ICT nature
of 1,6¤-biazulene 3a and 1,6¤:3,6¤¤-terazulene 7a was charac-
terized by UV-vis spectroscopy, which was evaluated by TD-
DFT calculations. Previously, we have reported the 6-aryl- and
6-ethynylazulene derivatives exhibiting significant electrochro-
mic properties with multiple electron transfers under the
electrochemical reaction conditions.20 Thus, 1,6¤-bi- and
1,6¤:3,6¤¤-terazulenes that possess 6-azulenyl group should
exhibit redox stability in their electrochemical reactions.
To evaluate the scope of this class of molecules investigated
by this research, reactivity, electrochemical and optical proper-
ties of the reported 1,6¤-biazulenes and 1,6¤:3,6¤¤-terazulenes are
currently under investigation in our laboratory.
J = 10.5 Hz, H5,7); 13C NMR (125 MHz, CDCl3):
¤
C
147.10
(C3a¤,8a¤), 142.51 (C8a), 138.60 (C6), 138.44 (C2), 138.00 (C4),
137.70 (C3a), 136.06 (C8), 135.93 (C2¤), 135.86 (C6¤), 135.64 (C4¤,8¤),
134.79 (C1), 125.55 (C5¤,7¤), 124.34 (C5 or 7), 123.99 (C5 or 7), 118.12
(C1¤,3¤), 117.89 (C3).
16 a) T. Shoji, R. Yokoyama, S. Ito, M. Watanabe, K. Toyota, M.
Yasunami, N. Morita, Tetrahedron Lett. 2007, 48, 1099. b) T. Shoji, S.
Ito, J. Higashi, N. Morita, Eur. J. Org. Chem. 2011, 5311.
17 Pyridinium salts 5a and 5b were precipitated in toluene under the
reaction conditions. Thus, further reaction should be hampered due to
the insolubility of 5a and 5b.
Dedicated to the late Professor Masafumi Yasunami for his
long-termed contribution to azulene chemistry.
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3
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Chem. Lett. 2013, 42, 638-640
© 2013 The Chemical Society of Japan
www.csj.jp/journals/chem-lett/