Efficient synthesis and redox behavior of a series of 6-alkyl-2- phenylazulenes

Article abstract of DOI:10.1016/j.tet.2013.03.084

Three new members of 6-alkyl-2-phenylazulene (nPA with n being the number of carbon atoms in the 6-alkyl chain) homologous series, 3a (n=4), 3b (n=6), and 3d (n=10), expected to show smectic E (SmE) phase as a mesophase below fusion, has been synthesized by Pd(PPh₃)₄ catalyzed Suzuki-Miyaura cross-coupling reaction of the corresponding 6-alkyl-2-bromoazulenes. The redox behavior of 3a, 3b, and 3d including that of their 6-octyl and 6-hexadecyl derivatives 3c (n=8) and 3e (n=16), the synthesis was reported previously, was studied in detail by voltammetric and electrochromic analyses. As the results, amphoteric redox properties with a significant color change were revealed by the nPA homologous series 3a-e, which would be attracted to the application for the device fabrication of the molecular materials.

Full text of DOI:10.1016/j.tet.2013.03.084

Tetrahedron 69 (2013) 4259e4269
Contents lists available at SciVerse ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Efficient synthesis and redox behavior of a series of 6-alkyl-2-
phenylazulenes
*
Shunji Ito , Mao Ueda, Ryuta Sekiguchi, Jun Kawakami
Graduate School of Science and Technology, Hirosaki University, Hirosaki 036-8561, Japan
a r t i c l e i n f o
a b s t r a c t
Article history:
Three new members of 6-alkyl-2-phenylazulene (nPA with n being the number of carbon atoms in the 6-
alkyl chain) homologous series, 3a (n¼4), 3b (n¼6), and 3d (n¼10), expected to show smectic E (SmE)
phase as a mesophase below fusion, has been synthesized by Pd(PPh3)4 catalyzed SuzukieMiyaura cross-
coupling reaction of the corresponding 6-alkyl-2-bromoazulenes. The redox behavior of 3a, 3b, and 3d
including that of their 6-octyl and 6-hexadecyl derivatives 3c (n¼8) and 3e (n¼16), the synthesis was
reported previously, was studied in detail by voltammetric and electrochromic analyses. As the results,
amphoteric redox properties with a significant color change were revealed by the nPA homologous series
3aee, which would be attracted to the application for the device fabrication of the molecular materials.
Ó 2013 Elsevier Ltd. All rights reserved.
Received 13 December 2012
Received in revised form 18 March 2013
Accepted 20 March 2013
Available online 25 March 2013
Keywords:
Smectic E mesomorphism
Amphoteric redox behavior
Azulenes
Liquid crystals
1. Introduction
to show nematic or smectic mesomorphisms.6 Recently, we have
also reported the synthesis of the first azulene derivatives (1, 2a,
Azulene (C10H8) has attracted the interest of many research
groups because of its unusual properties and its beautiful blue color.1
Amphoteric redox properties of the azulene derivatives are especially
attractive to construct advanced materials for electronic applications.
However, to date, molecules with potentially useful electronic
properties constructed from azulene derivatives are fairly scarce.
Spontaneous or controllable alignment of molecules on a substrate is
an important factor for device fabrication of molecular materials.2
Smectic mesophases, such as smectic E, B, and H (SmE, SmB, and
SmH) have positional order, and show no fluidity in contrast to the
liquid crystal phase, such as nematic mesophase. Some liquid crys-
talline semiconductors utilizing the ordered smectic mesophase are
recently found to show very fast carrier mobility.3 Thus, the stacking
behavior of the liquid crystal phases may provide opportunities for
materials with one-dimensional transport processes, such as energy
migration, electric conductivity, and photoconductivity.4
The SmE phase has a layered structure with a ‘herring bone’ or-
deringofthe molecules. Oneof themesogenicseries showingtheSmE
phase is a series of 4-alkyl-40-isothiocyanatobiphenyls (nTCB with n
being the numberofcarbonatoms inthe4-alkylchain).5 However, the
highly ordered SmE phase is restricted to a few classes of substances.
Substituted azulene derivatives linked to nematogenic alkylcy-
clohexanes by an ester function have been reported in the literature
and 2b) exhibiting discotic liquid crystalline behavior (Fig. 1).7
Novel hexakis(6-octyl-2-azulenyl)benzene (2a) surrounding six
octyl groups exhibits the columnar mesophases, Colho, with un-
usually large staking distances (h¼5.20e5.52 A), probably due to
ꢀ
the propeller conformation of the molecule.8 Spontaneous uniform
hometropic alignment on non-treated glass substrate is established
in the Colhd phase by the elongation of the six alkyl chains sur-
rounding, hexakis(6-hexadecyl-2-azulenyl)benzene (2b), so far.9
During the way to explore the azulene derivatives with liquid
crystalline behavior, we have recently reported the 6-alkyl-2-
phenylazulene (abbreviated as nPA in this paper with n being the
number of carbon atoms in the 6-alkyl chain) homologous series
(8PA 3c and 16PA 3e) showed only SmE phase as a mesophase
below fusion (Fig. 2).8,9 The nPA molecules have simple structures
composed of azulene core, phenyl group, and alkyl chain. The
molecular difference of the nPA series from nTCB series is in polar
groups. The phase behavior of all hydrocarbon derivatives, nPA
series, will open the possibility to study the nature of SmE phase in
detail over a wide temperature range. Details of the investigation of
the SmE phase in 8PA 3c have been reported, recently.10
Herein, we report efficient synthetic procedure of the three new
members of 6-alkyl-2-phenylazulene homologous series [nPAs 3a
(n¼4), 3b (n¼6), and 3d (n¼10)], which are expected to show SmE
mesomorphism, to investigate the influence of the peripheral
side chains in length, to better understand the SmE phase and the
electrochemical properties in the nPA homologous series.11
The redox properties of 8PA 3c have been examined by cyclic
* Corresponding author. Tel.: þ81 172 39 3568; fax: þ81 172 39 3541; e-mail
address: itsnj@cc.hirosaki-u.ac.jp (S. Ito).
0040-4020/$ e see front matter Ó 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tet.2013.03.084

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S. Ito et al. / Tetrahedron 69 (2013) 4259e4269
8PA 3c and 16PA 3e, reported, previously.8,9 Preparation of 6PA 3b
R
R
and 10PA 3d via 9b and 9c, respectively, commenced with diethyl
6-bromo-2-methoxyazulene-1,3-dicarboxylate (4);8,12 it is outlined
in Schemes 1 and 2. Pd-catalyzed cross-coupling reaction of 4 with
1-hexyne and 1-decyne under SonogashiraeHagihara conditions
afforded diethyl 6-hexynyl- and 6-decynyl-2-methoxyazulene-1,3-
dicarboxylates (5a and 5b) in 85% and 87% yields, respectively.
Catalytic hydrogenation of 5a and 5b utilizing PdeC catalyst pro-
duced reduced products 6b and 6c in 90% and 94% yields, re-
spectively. Two ethyl ester parts of 6b and 6c were hydrolyzed
under basic conditions to give 7b and 7c, following the treatment of
7b and 7c with 100% H3PO4, which was freshly prepared by dis-
solving phosphorous(V) oxide in 85% phosphoric acid, afforded 2-
hydroxy derivatives 8b and 8c in 49% and 58% yields in two steps,
respectively. The products 8b and 8c were transformed into 2-
bromo derivatives 9b and 9c by the treatment with PBr3 in 73%
and 58% yields, respectively.
R
R
R
R
R
R
R
R
R
R
1: R = COOC6H13
6-Hexyl- and 6-decyl-2-phenylazulenes (3b and 3d) were pre-
pared by the Pd-catalyzed SuzukieMiyaura cross-coupling reaction
of 9b and 9c with phenyl boronic acid in 76% and 68% yields, re-
spectively (Scheme 2). The spectral features of 6PA 3b and 10PA 3d
are in agreement with the structure of these products as summa-
rized in the Experimental section.
R
R
R
R
R
Extension of the procedure to the preparation of 6-butyl-2-
phenylazulene (3a) requires 1-butyne (bp¼8 ꢀC) as a reagent for
the starting SonogashiraeHagihara cross-coupling reaction with
bromide 4. However, we found the Pd-catalyzed cross-coupling
reaction of 4 with butylzinc bromide at 50 ꢀC for 30 min under
Negishi cross-coupling conditions to afford diethyl 6-butyl-2-
methoxyazulene-1,3-dicarboxylate (6a) in 71% yield, directly, al-
though it is well known that 2-methoxyazulene derivatives with
1,3-diester functions readily react with organometallic reagents,
such as Grignard and lithium reagents, to afford 2-alkyl azulene
derivatives (Scheme 3).13 The procedure produces the desired 6-
alkyl derivative 6a, efficiently, but the reaction provides a small
amount of undesired diethyl 6-butyl-2-butoxyazulene-1,3-
dicarboxylate (10) in 14% yield. However, the procedure may have
advantage over the SonogashiraeHagihara cross-coupling route for
the preparation as illustrated in Scheme 1, because the present
procedure reduces the catalytic hydrogenation step to obtain the
6-alkyl derivative 6a.
R
2a: R = C8H17
2b: R = C16H33
Fig. 1. Azulene derivatives (1, 2a, and 2b) exhibiting discotic liquid crystalline
behaviors.
R
Formation of the OMeeOBu exchange product 10 by the
Pd-catalyzed Negishi cross-coupling reaction of 4 roused our curi-
osity, although the desired product 6a was obtained in satisfactory
yield for further transformation. To obtain the aspect for the ex-
change reaction we have firstly examined the effect of the amount
of the butylzinc reagent employed. As the results, by increasing the
amount of butylzinc reagent up to 4.4 equiv the reaction at 55 ꢀC for
1 h yielded the exchange product 10 in 46% yield, along with 6a in
32% yield. The starting material 4 was pure enough to exclude the
contamination of the hydroxy compound, diethyl 6-bromo-2-
hydroxyazulene-1,3-dicarboxylate, which may act as the pre-
cursor for the exchange product 10. Thus, the formation of 10 im-
plies the cleavage of the OeMe bond of 4 under the reaction
conditions in any way.
Although the secondary and tertiary alkylzinc reagents are
known to exhibit isomerization during the Negishi cross-coupling
reaction, we anticipated the reaction with the higher zinc re-
agents might produce OeMe bond cleaved products instead of the
exchange product owing to the steric reasons. However, the Pd-
catalyzed cross-coupling reaction of 4 with the secondary alkyl-
zinc reagent, 1-propylbutylzinc bromide, under the Negishi cross-
coupling conditions to afford only an inseparable 77:23 mixture
of diethyl 6-(1-propylbutyl)-2-methoxyazulene-1,3-dicarboxylate
3a: R = C4H9
3b: R = C6H13
3c: R = C8H17
3d: R = C10H21
3e: R = C16H33
Fig. 2. 6-Alkyl-2-phenylazulenes (nPAs 3aee).
voltammetry (CV) in o-dichlorobenzene containing Et4NClO4
(0.1 M) as a supporting electrolyte, however, the comparative study
should clarify the redox behavior of these nPA homologous series
3aee. We also report, herein, the details of the redox behavior of
these nPA homologous series 3aee examined by voltammetric and
electrochromic analyses.
2. Results and discussion
2.1. Synthesis
Preparation of the 6-hexyl and 6-decyl derivatives 6PA 3b and
10PA 3d was easily established by the application of the synthetic
procedure similar to that of 6-octyl and 6-hexadecyl derivatives
(11)
and
diethyl
6-(1-ethylpentyl)-2-methoxyazulene-1,3-
dicarboxylate (12) in 79% yield (Scheme 4). Contrary to the

S. Ito et al. / Tetrahedron 69 (2013) 4259e4269
4261
CO2Et
OMe
CO2Et
OMe
CO2Et
5a: R = C6H9
Pd-C / H2
H
R
Br
R
Pd-catalyst
CO2Et
4
5b: R = C10H17
CO2R2
OMe
100% H3PO4
PBr3
R1
R
OH
R
Br
CO2R2
6b: R1 = C6H13, R2 = Et
6c: R1 = C10H21, R2 = Et
7b: R1 = C6H13, R2 = H
7c: R1 = C10H21, R2 = H
8b: R = C6H13
8c: R = C10H21
9b: R = C6H13
9c: R = C10H21
KOH / H2O
Scheme 1. Preparation of 6-hexyl- and 6-decyl-2-bromoazulenes (9b and 9c).
B(OH)2
9b, 9c
R
Pd-catalyst
3b: R = C6H13
3d: R = C10H21
Scheme 2. Preparation of 6-hexyl- and 6-decyl-2-phenylazulenes (3b and 3d).
CO2Et
CO2Et
OBu
C4H9ZnBr
4
C4H9
OMe
CO2Et
+
C4H9
Pd-catalyst
CO2Et
6a
10
Scheme 3. Negishi cross-coupling reaction of diethyl 6-bromo-2-methoxyazulene-1,3-dicarboxylate (4) with butylzinc bromide.
ZnBr
CO2Et
OMe
CO2Et
CO2Et
OMe
CO2Et
4
+
Pd-catalyst
11
12
Scheme 4. Negishi cross-coupling reaction of diethyl 6-bromo-2-methoxyazulene-1,3-dicarboxylate (4) with 1-propylbutylzinc bromide.
expectation the OeMe bond cleaved products and also the corre-
sponding exchange product were not obtained in this case at all.
Thus, formation of the OMeeOBu exchange product 10 would be
concluded to the participation of some transition-metal catalyzed
reaction. The azulene nuclei with two ester groups may operate as
a good electron-withdrawing group for the Pd-catalyzed oxidative
addition reaction. Thus, there is a possibility that the azulene
functional group will act as an effective functional group for the
transition-metal-catalyzed reaction.
2-bromo derivative 9a by the treatment with PBr3 in 70% yield.
6-Butyl-2-phenylazulene (3a) was obtained by the Pd-catalyzed
SuzukieMiyaura cross-coupling reaction of 9a with phenyl bo-
ronic acid in 79% yield. The spectral features of 4PA 3a are also in
agreement with the structure of the compound as summarized in
the Experimental section.
2.2. Spectroscopic properties
Two ethyl ester parts of 6a was hydrolyzed under basic condi-
tions to give 7a, following the treatment of 7a with freshly prepared
100% H3PO4 afforded 2-hydroxy derivative 8a in 64% yield in
two steps (Scheme 5). The product 8a was also transformed into
Mass spectrum of nPAs 3a (n¼4), 3b (n¼6), and 3d (n¼10)
measured by ESI-TOF conditions showed correct MþHþ ion peaks,
which afford a criterion of the structure of these compounds. The
typical examples of UV and visible spectra of 3d, 8c, and 9c in

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S. Ito et al. / Tetrahedron 69 (2013) 4259e4269
CO2H
KOH / H2O
100% H3PO4
6a
C4H9
OMe
CO2H
7a
B(OH)2
PBr3
C4H9
OH
C4H9
Br
C4H9
Pd-catalyst
8a
9a
3a
Scheme 5. Preparation of 6-butyl-2-phenylazulene (3a).
dichloromethane are shown in Fig. 3, the rest is summarized in the
Supplementary data. The absorption spectra of the newly pre-
pared compounds are quite similar with those of their 6-octyl and
6-hexadecyl derivatives. nPAs 3a (n¼4), 3b (n¼6), and 3d (n¼10)
showed the characteristic weak absorption of the azulene system
in the visible region at 562 nm (log ε 2.58), 562 nm (log ε 2.62),
and 562 nm (log ε 2.56), respectively. The longest absorption
maximum of nPAs 3a (n¼4), 3b (n¼6), and 3d (n¼10) in the visible
region exhibits a slight red shift by 23 nm, 25 nm, and 25 nm,
respectively, relative to those of 2-bromo derivatives 9a
The oxidation of nPAs 3aee showed an irreversible oxidation
wave on CV at 0.72 Ve0.76 V. The irreversibility should be ascribed
to the electron removal from the 2-azulenyl group forming a radical
cationic species with high reactivity. The DPV analysis revealed the
existence of two further oxidation waves that should correspond to
the formation of higher electronic states as summarized in Table 1.
2.4. Electrochromic analysis
To obtain the aspect for the redox species, the electrochemical
reduction and oxidation of nPAs 3aee was conducted by visible
spectral monitoring. Constant-current reduction and oxidation
were applied to the solutions of nPAs 3aee with a platinum mesh as
(lmax¼539 nm), 9b (lmax¼537 nm), and 9c (lmax¼537 nm) prob-
ably because of the electron-withdrawing nature of the
substituted halogen atom. The absorption spectra of 2-hydroxy
derivatives 8a, 8b, and 8c in dichloromethane are quite different
from azulene derivatives because of the ketoeenol tautomerisms
in solution depending on the solvent polarity.14 The NMR spectra
of 8c in CDCl3 represent the existence of their keto forms (keto-
eenol ratio¼92:8) in the solvent, whereas in acetone-d6 the
equilibrium changed to their enol forms as shown the spectra in
the Supplementary data. Therefore, the difference in the absorp-
tion spectra of the hydroxyl derivatives is supposed by their tau-
tomerisms depending on the solvent polarities. We found that the
ketoeenol ratios of these compounds 8a (3:97), 8b (18:82), and
8c (18:82) depends on the length of 6-alkyl chain substituted in
acetone-d6. These changes should be caused by the effect of the
substituted alkyl chains.
2.3. Redox properties
To clarify the electrochemical property, the redox behavior of
nPAs 3aee was examined by CV and differential pulse voltammetry
(DPV) in benzonitrile containing tetraethylammonium perchlorate
(0.1 M) as a supporting electrolyte. Measurements were made by
using a standard three electrode configuration as platinum wire
auxiliary and disk working electrodes. All measurements were
carried out an argon atmosphere and potentials were related to
a standard Ag/AgNO3 reference electrode. Half-wave potential of
ferroceneeferrocenium couple (Fc/Fcþ) under the conditions using
this reference electrode is observed at þ0.15 V on CV.
Redox potentials (in volts vs Ag/AgNO3) of nPAs 3aee are
summarized in Table 1. The typical CV waves of nPA 3d are shown in
Fig. 4 and the other data for the nPAs 3aee are summarized in the
Supplementary data. The redox properties essentially did not de-
pend on the length of the 6-alkyl chain substituted. These com-
pounds exhibited a reversible reduction wave on CV at ꢁ1.91 V
to ꢁ1.94 V. The Er1ed wave should correspond to the one-electron
injection forming a radical anionic species. The reversibility on
the CV wave should be attributed to the stabilization of the radical
anionic species by the 2-azulenyl substituent.
Fig. 3. UV/vis spectra of 10PA 3d (solid line), 8c (broken line), and 9c (dotted line) in
dichloromethane: (a) visible and (b) UVevis regions.

S. Ito et al. / Tetrahedron 69 (2013) 4259e4269
4263
Table 1
Redox potentials of the nPA homologous series 3aee measured by CV and DPVa
Sample
E1red [V]
E1ox [V]
E2ox [V]
E3ox [V]
4PA 3a
DPVb
ꢁ1.92
ꢁ1.90
ꢁ1.93
ꢁ1.90
ꢁ1.91
ꢁ1.90
ꢁ1.94
ꢁ1.91
ꢁ1.92
ꢁ1.91
(þ0.75)
þ0.64
þ0.84
þ0.83
þ0.82
þ0.82
þ0.81
þ1.78
þ1.77
þ1.79
þ1.76
þ1.79
6PA 3b
(þ0.72)
þ0.63
DPVb
8PA 3c
DPVb
(þ0.76)
þ0.65
10PA 3d
(þ0.72)
þ0.64
DPVb
16PA 3e
DPVb
(þ0.74)
þ0.67
a
The redox potentials were measured by CV and DPV [V versus Ag/AgNO3, 1 mM
in benzonitrile containing Et4NClO4 (0.1 M), Pt electrode (i.d., 1.6 mm), scan rate
100 mV sꢁ1 and Fc/Fcþ¼þ0.15 V]. In the case of irreversible waves, which are given
in parentheses, Eox and Ered were calculated as Epa (anodic peak potential)ꢁ0.03 V
and Epc (cathodic peak potential)þ0.03 V, respectively.
b
The values are peak potentials measured by DPV.
the working electrode and a wire counter electrode, and visible
spectra were measured in benzonitrile containing Et4NCO4 (0.1 M)
as a supporting electrolyte at room temperature under the elec-
trochemical redox conditions. The visible spectral changes of 10PA
3d under electrochemical redox conditions are shown in Fig. 5. The
other data for the visible spectral changes of nPAs 3aee are sum-
marized in the Supplementary data. The blue color of the solution
of 10PA 3d gradually changed to yellow during the electrochemical
reduction. Accordingly, a new absorption band in the visible region
gradually developed during the electrochemical reduction (Fig. 5a).
Observed color change should be ascribed to the formation of
Fig. 5. Continuous change in visible spectra of 10PA 3d: (a) constant-current electro-
chemical reduction (100 mA, 1 min intervals) and (b) constant-current electrochemical
(a)
6
oxidation (100
m
A, 1 min intervals) in benzonitrile (2 mL; 2.9ꢂ10ꢁ3 M) containing
Et4NClO4 (0.1 M).
4
2
a radical anionic species in one-electron reduction. Reverse oxi-
dation of the intermediary yellow colored solution regenerated the
spectrum of 10PA 3d with good reversibility as suggested by the
reversibility upon CV under the electrochemical reduction
conditions.
0
When the visible spectra of 10PA 3d were measured under
electrochemical oxidation conditions, a new absorption band also
gradually developed in the visible region (Fig. 5b). The blue color of
the solution also changed to yellow during the electrochemical
oxidation. Reverse reduction of the intermediary yellow colored
solution regenerated the spectrum of 10PA 3d with good re-
versibility in contrast to the expectation. The radical cationic spe-
cies produced by the electrochemical oxidation should be unstable
under the condition of the spectral measurements as suggested by
the irreversible CV wave under the oxidation conditions. The re-
versibility for the spectral measurements may be ascribed to the
reproduction of the neutral species by the electrochemical reaction
of the oxidized species.
-2
-4
0
-0.5
-1
-1.5
-2
-2.5
Potential / V
(b)
1
0
-1
-2
-3
-4
2.5. Theoretical calculations
To better understand the electronic properties of the 6-alkyl-2-
phenylazulene homologous series [nPA, 3a (n¼4), 3b (n¼6), 3c
(n¼8), 3d (n¼10), and 3e (n¼16)], we have also performed time-
dependent density functional theory (TDDFT/TDA) calculations at
the B3LYP/6-31G** level15 of 2-phenylazulene along with its radical
cationic and anionic species. The results on the calculations are
summarized in the Supplementary data. As shown in the
Supplementary data, the HOMOs, SOMO, and LUMOs of these
1
0.8
0.6
Potential / V
0.4
0.2
0
Fig. 4. CV waves of 10PA 3d (1 mM) in benzonitrile containing Et4NClO4 (0.1 M) as
a supporting electrolyte: (a) reduction wave and (b) oxidation wave.

4264
S. Ito et al. / Tetrahedron 69 (2013) 4259e4269
compounds showed symmetrical orbitals with respect to the
symmetrical structure of these species. Judging from a comparison
between the experimental and the theoretical UV/vis spectra, the
longest wavelength absorption maxima of the neutral species could
be assigned to HOMO/LUMO transition as characteristics for
azulene derivatives.
using a quarts cell (1ꢂ10ꢂ35 mm) equipped with a Pt mesh and
a wire as the working and counter electrodes, respectively, which
were separated by a glass filter. A constant-current reduction and
oxidation were applied to the sample solution. The electrical cur-
rent was monitored by a microampere meter. The potential values
are automatically increased by the resistance of the sample solution
from 0 V up to ꢃ12 V by our constant-current apparatus. Spec-
troelectrograms were monitored on an Ocean Optics USB2000
spectrophotometer.
Density potential analysis of the radical ionic species repre-
sented to the localization of the most of charges on the azulene
part. Therefore, the amphoteric redox behaviors of these 6-alkyl-2-
phenylazulene homologous series are responsible to the stabiliza-
tion by the substituted 2-azulenyl group. Spin density distributes
on the whole molecule in the radical anionic state, whereas that of
the radical cationic state localizes on the azulene moiety. In addi-
tion, the radical anion had been characterized by ESR spectroscopy,
previously, although the radical cation has never examined spec-
troscopically.16 Therefore, the spectral changes under electro-
chemical conditions to develop the new absorption band in the
visible region are presumably due to the generation of these radical
ionic states, although the experimental absorption maxima of these
species could not be reproduced by the TDDFT/TDA calculations at
the B3LYP/6-31G** level.
4.1.1. 6-Butyl-2-phenylazulene (3a). A solution of 2-bromo-6-
butylazulene (9a) (467 mg, 1.77 mmol), phenyl boronic acid
(401 mg, 3.29 mmol), CsCO3 (1.55 g, 4.76 mmol), Pd(PPh3)4 (91 mg,
0.079 mmol) in dioxane (39 mL) was heated at 100 ꢀC for 2 h under
an Ar atmosphere. The reaction mixture was poured into water and
extracted with CH2Cl2. The organic layer was washed with brine,
dried over MgSO4, and concentrated under reduced pressure. The
residue was purified by column chromatography on silica gel with
toluene to afford 3a (367 mg, 79%). Blue plates; mp 191.8e192.7 ꢀC
(hexane); 1H NMR (500 MHz, CDCl3):
d
¼8.17 (d, 3JH,H¼10.4 Hz, 2H,
4,8-H), 7.93 (d, 3JH,H¼8.2 Hz, 2H, 20,60-H), 7.59 (s, 2H,1,3-H), 7.44 (dd,
3JH,H¼8.2, 7.3 Hz, 2H, 30,50-H), 7.32 (tt, 3JH,H¼7.3 Hz,1H, 40-H), 7.05 (d,
3
3. Conclusions
3JH,H¼10.4 Hz, 2H, 5,7-H), 2.77 (t, JH,H¼7.8 Hz, 2H, 100-H), 1.69 (tt,
3JH,H¼7.8, 7.5 Hz, 2H, 200-H),1.40 (tq, 3JH,H¼7.5, 7.4 Hz, 2H, 300-H), 0.95
Three new members of 6-alkyl-2-phenylazulene homologous
series [nPA, 3a (n¼4), 3b (n¼6), and 3d (n¼10)] have been suc-
cessfully synthesized by Pd(PPh3)4 catalyzed SuzukieMiyaura
cross-coupling reaction of 6-alkyl-2-bromoazulenes (9a, 9b, and
9c). The efficient preparation of the 6-alkyl-2-bromoazulene ho-
mologous (9a, 9b, and 9c) are established by the introduction of
6-alkyl substituent via SonogashiraeHagihara and Negishi cross-
coupling reactions. The spectroscopic properties of nPA series 3a
(n¼4), 3b (n¼6), and 3d (n¼10) have been clarified and were
compared with those of 6-octyl and 6-hexadecyl derivatives 3c
(n¼8) and 3e (n¼12). Amphoteric redox behavior of 3aee with
a significant color change under electrochemical conditions was
revealed by voltammetric and electrochromic analyses. The num-
ber of carbon atoms in the peripheral side chain does not affect
significantly the redox behaviors of 3aee. Introduction of 6-alkyl
chain in 2-phenylazulene should induce SmE mesomorphism that
is closest to an ordered crystal among orthorhombic structures
exhibited by the calamitic mesogens. Therefore, the present com-
pounds might exhibit excellent paths for charge carrier trans-
portation and may become an intrinsic candidate for the future
applications to a semiconductor owing the amphoteric redox
properties of the azulene derivatives.11
(t, 3JH,H¼7.4 Hz, 3H, 400-H); 13C NMR (125 MHz, CDCl3):
¼153.03 (C-
d
6), 148.58 (C-2), 139.93 (C-3a,8a), 136.72 (C-10), 135.41 (C-4,8),
128.85 (C-30,50), 127.88 (C-40), 127.45 (C-20,60), 124.96 (C-5,7), 114.26
(C-1,3), 42.07 (C-100), 34.74 (C-200), 22.40 (C-300), 13.96 (C-400); IR (KBr
disk): nmax¼2970 (w), 2927 (m), 2857 (w), 1577 (m), 1546 (w), 1464
(m),1440 (m),1413 (m),1381 (w),1335 (w),1297 (w),1232 (w),1023
(w), 965 (w), 908 (w), 834 (s), 760 (s), 687 (m), 640 (w), 497 (w)
cmꢁ1; UVevis (CH2Cl2): lmax (log ε)¼240 (4.15), 287 sh (4.55), 301
(4.82), 311 (4.86), 343 sh (3.71), 359 sh (3.89), 378 (4.16), 396 (4.22),
525 sh (2.44), 562 (2.58), 601 (2.57), 660 sh (2.21) nm; HRMS (ESI
positive): calcd for C20H20þHþ 261.1638; found 261.1640. Anal. Calcd
for C20H20: C, 92.26; H, 7.74; found: C, 92.58; H, 7.47.
4.1.2. 6-Hexyl-2-phenylazulene (3b). A solution of 2-bromo-6-
hexylazulene (9b) (196 mg, 0.673 mmol), phenyl boronic acid
(153 mg, 1.25 mmol), CsCO3 (575 mg, 1.76 mmol), Pd(PPh3)4 (34 mg,
0.029 mmol) in dioxane (12 mL) was heated at 100 ꢀC for 2 h under
an Ar atmosphere. The reaction mixture was poured into water and
extracted with CH2Cl2. The organic layer was washed with brine,
dried over MgSO4, and concentrated under reduced pressure. The
residue was purified by column chromatography on silica gel with
toluene to afford 3b (148 mg, 76%). Blue plates; mp 180.6e181.3 ꢀC
(hexane); 1H NMR (500 MHz, CDCl3):
d
¼8.17 (d, 3JH,H¼10.4 Hz, 2H,
4. Experimental section
4.1. General
4,8-H), 7.94 (d, 3JH,H¼8.1 Hz, 2H, 20,60-H), 7.60 (s, 2H,1,3-H), 7.45 (dd,
3JH,H¼8.1, 7.3 Hz, 2H, 30,50-H), 7.32 (t, 3JH,H¼7.3 Hz, 1H, 40-H), 7.05 (d,
3
3JH,H¼10.4 Hz, 2H, 5,7-H), 2.76 (t, JH,H¼7.8 Hz, 2H, 100-H), 1.70 (tt,
3JH,H¼7.8, 7.4 Hz, 2H, 200-H), 1.40e1.27 (m, 6H, 300,400,500-H), 0.89 (t,
Melting points were determined on a Stuart Scientific melting
point apparatus SMP3 and are uncorrected. Mass spectra were
obtained with a Hitachi NanoFrontier LD instrument. IR and UV/vis
spectra were measured on a JUSCO FT/IR-6100 infrared spectro-
photometer, and a JUSCO V-670 spectrophotometer, respectively.
1H NMR spectra (13C NMR spectra) were recorded on a JEOL ECA500
at 500 MHz (125 MHz). 1H NMR chemical shifts in CDCl3 and
DMSO-d6 are reported in parts per million (ppm) downfield from
tetramethylsilane. 13C NMR chemical shifts in CDCl3 are referred by
3JH,H¼7.1 Hz, 3H, 600-H); 13C NMR (125 MHz, CDCl3):
¼153.09 (C-6),
d
148.54 (C-2), 139.90 (C-3a,8a), 136.69 (C-10), 135.42 (C-4,8), 128.84
(C-30,50), 127.88 (C-40),127.44 (C-20,60),124.97 (C-5,7), 114.23 (C-1,3),
42.38 (C-100), 32.59 (C-200), 31.72 (C-400), 28.99 (C-300), 22.58 (C-500),
14.08 (C-600); IR (KBr disk): nmax¼2954 (w), 2927 (m), 2855 (m),
1577 (m), 1465 (m), 1443 (w), 1418 (w), 836 (m), 757 (s), 688 (m),
508 (w) cmꢁ1; UVevis (CH2Cl2): lmax (log ε)¼240 (4.17), 280 sh
(4.40), 301 (4.81), 310 (4.84), 343 sh (3.76), 360 sh (3.92), 378 (4.16),
396 (4.21), 447 (2.32), 527 sh (2.50), 562 (2.62), 598 (2.60), 659 sh
(2.26) nm; HRMS (ESI positive): calcd for C22H24þHþ 289.1951;
the solvent signals as 77.0 ppm. The peak assignment of 1H and 13
C
NMR spectra reported was accomplished by HH COSY, DEPT, HMQC,
and HMBC experiments. Gel permeation chromatography (GPC)
was performed on a TOSOH TSKgel G2000H6 with CHCl3 as an
eluent. Spectroelectrogram measurements were accomplished in
benzonitrile containing Et4NClO4 (0.1 M) as a supporting electrolyte
found 289.1947. Anal. Calcd for C22
found: C, 90.93; H, 8.66.
H24$1/6H2O: C, 90.67; H, 8.42;
4.1.3. 6-Decyl-2-phenylazulene (3d). A solution of 2-bromo-6-
decylazulene (9c) (441 mg, 1.27 mmol), phenyl boronic acid

S. Ito et al. / Tetrahedron 69 (2013) 4259e4269
4265
(324 mg, 2.66 mmol), CsCO3 (1.21 g, 3.71 mmol), Pd(PPh3)4 (56 mg,
0.048 mmol) in dioxane (31 mL) was heated at 100 ꢀC for 2 h under
an Ar atmosphere. The reaction mixture was poured into water and
extracted with CH2Cl2. The organic layer was washed with brine,
dried over MgSO4, and concentrated under reduced pressure. The
residue was purified by column chromatography on silica gel with
toluene to afford 3d (297 mg, 68%). Blue plates; mp 171.2e172.3 ꢀC
pressure. The residue was purified by column chromatography on
silica gel with 5% ethyl acetate/CH2Cl2 to afford 5b (2.87 g, 87%). Red
crystals; mp 49.2e50.9 ꢀC (H2O/methanol); 1H NMR (500 MHz,
CDCl3):
d
¼9.31 (d, 3JH,H¼11.2 Hz, 2H, 4,8-H), 7.73 (d, 3JH,H¼11.2 Hz,
2H, 5,7-H), 4.46 (q, 3JH,H¼7.1 Hz, 4H,1,3-COOEt), 4.14 (s, 3H, 2-OMe),
3
3
2.49 (t, JH,H¼7.1 Hz, 2H, 30-H), 1.66 (tt, JH,H¼7.6, 7.1 Hz, 2H, 40-H),
3
1.47 (m, 2H, 50-H), 1.46 (t, JH,H¼7.1 Hz, 6H, 1,3-COOEt), 1.35e1.30
3
(hexane); 1H NMR (500 MHz, CDCl3):
d
¼8.17 (d, 3JH,H¼10.3 Hz, 2H,
(m, 8H, 60e90-H), 0.89 (t, JH,H¼6.9 Hz, 3H, 100-H); 13C NMR
4,8-H), 7.94 (d, 3JH,H¼8.1 Hz, 2H, 20,60-H), 7.60 (s, 2H,1,3-H), 7.45 (dd,
3JH,H¼8.1, 7.4 Hz, 2H, 30,50-H), 7.32 (t, 3JH,H¼7.4 Hz, 1H, 40-H), 7.05 (d,
(125 MHz, CDCl3):
d
¼170.29 (C-2), 164.65 (1,3-COOEt), 141.47 (C-
3a,8a), 134.83 (C-4,8), 134.69 (C-6), 133.97 (C-5,7), 108.07 (C-1,3),
96.51 (C-20), 84.30 (C-10), 63.00 (2-OMe), 60.22 (1,3-COOEt), 31.81
(t), 29.16 (t), 29.07 (t), 28.98 (t), 28.43 (C-40), 22.63 (t), 19.75 (C-30),
14.44 (1,3-COOEt),14.09 (C-100); IR (KBr disk): nmax¼2990 (m), 2979
(m), 2935 (m), 2913 (m), 2855 (m), 2224 (w, C^C), 1682 (s, C]O),
1587 (w), 1567 (m), 1541 (m), 1490 (s), 1469 (m), 1438 (s), 1394 (m),
1383 (m), 1354 (w), 1333 (w), 1278 (s), 1224 (m), 1195 (s), 1116 (m),
1107 (m), 1078 (m), 1038 (m), 1003 (m), 851 (m), 794 (w), 716 (w),
704 (w) cmꢁ1; UVevis (CH2Cl2): lmax (log ε)¼239 (4.39), 271 sh
(4.13), 318 sh (4.72), 329 (4.82), 372 (4.19), 383 sh (4.06), 398 sh
(3.83), 467 sh (2.65), 494 (2.71), 534 sh (2.57), 593 sh (2.01) nm;
HRMS (ESI positive): calcd for C27H34O5þNaþ 461.2298; found
461.2301. HRMS (ESI positive): calcd for C27H34O5þHþ 439.2479;
found 439.2477. Anal. Calcd for C27H34O5: C, 73.94; H, 7.81; found:
C, 73.83; H, 7.75.
3
3JH,H¼10.3 Hz, 2H, 5,7-H), 2.76 (t, JH,H¼7.8 Hz, 2H, 100-H), 1.70 (tt,
3JH,H¼7.8, 7.3 Hz, 2H, 200-H), 1.40e1.26 (m, 14H, 300e900-H), 0.88 (t,
3JH,H¼7.0 Hz, 3H, 1000-H); 13C NMR (125 MHz, CDCl3):
¼153.10 (C-
d
6), 148.55 (C-2), 139.92 (C-3a,8a), 136.71 (C-10), 135.42 (C-4,8),
128.84 (C-30,50), 127.87 (C-40), 127.45 (C-20,60), 124.97 (C-5,7), 114.23
(C-1,3), 42.39 (C-100), 32.63 (C-200), 31.88 (t), 29.60 (t), 29.56 (t),
29.52 (t), 29.33 (t), 29.31 (t), 22.67 (t), 14.11 (C-1000); IR (KBr disk):
nmax¼3045 (w), 2917 (s), 2849 (s), 1577 (m), 1548 (w), 1468 (m),
1440 (m), 1414 (m), 1295 (w), 1127 (w), 1024 (w), 966 (w), 907 (w),
834 (s), 757 (s), 720 (w), 687 (m), 653 (w), 497 (w) cmꢁ1; UVevis
(CH2Cl2): lmax (log ε)¼240 (4.14), 301 (4.79), 310 (4.82), 345 sh
(3.74), 360 sh (3.89), 378 (4.14), 396 (4.19), 429 sh (2.19), 523 sh
(2.40), 562 (2.56), 598 (2.54), 655 sh (2.20) nm; HRMS (ESI posi-
tive): calcd for C26H32þHþ 345.2577; found 345.2566. Anal. Calcd
for C26H32: C, 90.64; H, 9.36; found: C, 90.86; H, 9.46.
4.1.6. Diethyl 6-butyl-2-methoxyazulene-1,3-dicarboxylate (6a). To
a degassed solution of diethyl 6-bromo-2-methoxyazulene-1,3-
dicarboxylate (4) (2.12 g, 5.56 mmol) and butylzinc bromide
(0.5 M, 33 mL) in dry THF (18 mL) was added PdCl2[dppf]$CH2Cl2
(186 mg, 0.228 mmol). The resulting mixture was stirred at 50 ꢀC
for 30 min under an Ar atmosphere. The reaction mixture was
washed successively with 5% NH4Cl solution and water, dried over
MgSO4, and concentrated under reduced pressure. The residue was
purified by column chromatography on silica gel with 20% ethyl
acetate/hexane to afford 6a (1.41 g, 71%) and diethyl 2-butoxy-6-
butylazulene-1,3-dicarboxylate (10) (303 mg, 14%).
4.1.4. Diethyl 6-(1-hexynyl)-2-methoxyazulene-1,3-dicarboxylate
(5a). To
a
degassed solution of diethyl 6-bromo-2-
methoxyazulene-1,3-dicarboxylate (4) (1.96 g, 5.14 mmol), 1-
hexyne (1.30 g, 15.8 mmol), CuI (113 mg, 0.590 mmol), triethyl-
amine (130 mL) in dry toluene (130 mL) was added Pd(PPh3)4
(315 mg, 0.273 mmol). The resulting mixture was stirred at room
temperature for 2.5 h under an Ar atmosphere. The reaction mix-
ture was washed successively with 5% NH4Cl solution and water,
dried over MgSO4, and concentrated under reduced pressure. The
residue was purified by column chromatography on silica gel with
5% ethyl acetate/CH2Cl2 to afford 5a (1.67 g, 85%). Reddish purple
crystals; mp 50.2e51.2 ꢀC (hexane); 1H NMR (500 MHz, CDCl3):
Compound 6a: Orange prisms; mp 59.0e60.5 ꢀC (hexane); 1H
NMR (500 MHz, CDCl3):
d
¼9.42 (d, 3JH,H¼11.1 Hz, 2H, 4,8-H), 7.59 (d,
d
¼9.31 (d, 3JH,H¼11.4 Hz, 2H, 4,8-H), 7.73 (d, 3JH,H¼11.4 Hz, 2H, 5,7-
3JH,H¼11.1 Hz, 2H, 5,7-H), 4.46 (q, 3JH,H¼7.1 Hz, 4H, 1,3-COOEt), 4.13
3
3
H), 4.46 (q, 3JH,H¼7.1 Hz, 4H, 1,3-COOEt), 4.14 (s, 3H, 2-OMe), 2.50 (t,
3JH,H¼7.1 Hz, 2H, 30-H), 1.65 (tt, 3JH,H¼7.5, 7.1 Hz, 2H, 40-H), 1.51 (tq,
3JH,H¼7.5, 7.3 Hz, 2H, 50-H),1.46 (t, 3JH,H¼7.1 Hz, 6H,1,3-COOEt), 0.98
(s, 3H, 2-OMe), 2.89 (t, JH,H¼7.7 Hz, 2H, 10-H), 1.71 (tt, JH,H¼7.7,
3
7.6 Hz, 2H, 20-H), 1.46 (t, JH,H¼7.1 Hz, 6H, 1,3-COOEt), 1.39 (tq,
3JH,H¼7.6, 7.3 Hz, 2H, 30-H), 0.95 (t, 3JH,H¼7.3 Hz, 3H, 40-H); 13C NMR
(t, 3JH,H¼7.3 Hz, 3H, 60-H); 13C NMR (125 MHz, CDCl3):
d
¼170.28 (C-
(125 MHz, CDCl3):
d
¼169.77 (C-2), 164.83 (1,3-COOEt), 155.43 (C-6),
2),164.65 (1,3-COOEt),141.46 (C-3a,8a),134.83 (C-4,8),134.67 (C-6),
133.96 (C-5,7), 108.06 (C-1,3), 96.41 (C-20), 84.28 (C-10), 62.99 (2-
OMe), 60.22 (1,3-COOEt), 30.48 (C-40), 22.06 (C-50), 19.43 (C-30),
14.43 (1,3-COOEt), 13.60 (C-60); IR (KBr disk): nmax¼2935 (m), 2864
(w), 2219 (w, C^C), 1674 (s, C]O), 1580 (w), 1568 (m), 1534 (w),
1485 (s), 1433 (s), 1390 (m), 1330 (w), 1285 (m), 1249 (m), 1223 (m),
1197 (m), 1126 (w), 1109 (w), 1077 (w), 1036 (m), 996 (m), 877 (w),
852 (w), 794 (w) cmꢁ1; UVevis (CH2Cl2): lmax (log ε)¼239 (4.27),
270 (4.00), 318 sh (4.64), 329 (4.75), 372 (4.07), 397 sh (3.69), 466
sh (2.49), 494 (2.58), 534 sh (2.42), 588 sh (1.67) nm; HRMS (ESI
positive): calcd for C23H26O5þNaþ 405.1672; found 405.1651. HRMS
(ESI positive): calcd for C23H26O5þHþ 383.1853; found 383.1833.
Anal. Calcd for C23H26O5: C, 72.23; H, 6.85; found: C, 72.12; H, 6.76.
140.88 (C-3a,8a), 136.13 (C-4,8), 132.30 (C-5,7), 107.34 (C-1,3), 62.96
(2-OMe), 60.04 (1,3-COOEt), 41.39 (C-10), 34.64 (C-20), 22.26 (C-30),
14.46 (1,3-COOEt), 13.86 (C-40); IR (KBr disk): nmax¼2936 (m), 1673
(s, C]O), 1577 (w), 1545 (w), 1482 (m), 1427 (s), 1389 (m), 1278 (m),
1232 (m), 1187 (s), 1102 (m), 1034 (m), 994 (m), 869 (w), 807 (w),
707 (w), 563 (w) cmꢁ1; UVevis (CH2Cl2): lmax (log ε)¼235 (4.48),
263 sh (4.30), 270 (4.36), 304 sh (4.70), 314 (4.80), 348 (3.98), 358
sh (3.94), 374 sh (3.71), 444 sh (2.67), 462 (2.73), 494 sh (2.61), 545
sh (1.85) nm; HRMS (ESI positive): calcd for C21H26O5þKþ 397.1412;
found 397.1438. HRMS (ESI positive): calcd for C21H26O5þNaþ
381.1672; found 381.1693. HRMS (ESI positive): calcd for
C21H26O5þHþ 359.1853; found 359.1869. Anal. Calcd for C21H26O5:
C, 70.37; H, 7.31; found: C, 70.33; H, 7.24.
Compound 10: Red oil; 1H NMR (500 MHz, CDCl3):
d
¼9.40 (d,
4.1.5. Diethyl 6-(1-decynyl)-2-methoxyazulene-1,3-dicarboxylate
3JH,H¼11.1 Hz, 2H, 4,8-H), 7.57 (d, 3JH,H¼11.1 Hz, 2H, 5,7-H), 4.45 (q,
3JH,H¼7.1 Hz, 4H, 1,3-COOEt), 4.28 (t, 3JH,H¼6.6 Hz, 2H, 10-H), 2.88 (t,
3JH,H¼7.7 Hz, 2H, 100-H), 1.88 (tt, 3JH,H¼7.7, 6.6 Hz, 2H, 20-H), 1.70 (tt,
3JH,H¼7.7, 7.6 Hz, 2H, 200-H), 1.54 (tq, 3JH,H¼7.7, 7.4 Hz, 2H, 30-H), 1.45
(t, 3JH,H¼7.1 Hz, 6H, 1,3-COOEt), 1.39 (tq, 3JH,H¼7.4, 7.4 Hz, 2H, 300-H),
0.99 (t, 3JH,H¼7.4 Hz, 3H, 40-H), 0.94 (t, 3JH,H¼7.4 Hz, 3H, 400-H); 13C
(5b). To
a
degassed solution of diethyl 6-bromo-2-
methoxyazulene-1,3-dicarboxylate (4) (2.88 g, 7.55 mmol), 1-
decyne (3.14 g, 22.7 mmol), CuI (159 mg, 0.835 mmol), triethyl-
amine (80 mL) in dry toluene (190 mL) was added Pd(PPh3)4
(352 mg, 0.305 mmol). The resulting mixture was stirred at room
temperature for 2.5 h under an Ar atmosphere. The reaction mix-
ture was washed successively with 5% NH4Cl solution and
water, dried over MgSO4, and concentrated under reduced
NMR (125 MHz, CDCl3):
(C-6), 141.05 (C-3a,8a), 135.76 (C-4,8), 132.23 (C-5,7), 107.29 (C-1,3),
76.18 (C-10), 59.98 (1,3-COOEt), 41.34 (C-100), 34.62 (C-200), 32.44
d
¼168.88 (C-2), 164.99 (1,3-COOEt), 155.03

4266
S. Ito et al. / Tetrahedron 69 (2013) 4259e4269
(C-20), 22.23 (C-300), 19.14 (C-30), 14.50 (1,3-COOEt), 13.93 (C-40),
13.84 (C-400); IR (KBr disk): nmax¼2958 (s), 2933 (s), 2872 (m), 1683
(s, C]O), 1578 (m), 1545 (m), 1478 (s), 1458 (s), 1431 (s), 1383 (s),
1274 (s), 1235 (s), 1180 (s), 1102 (m), 1063 (m), 1032 (s), 994 (m), 962
(m), 932 (w), 896 (w), 847 (m), 813 (w), 797 (w), 717 (w), 684 (w),
647 (w), 611 (w) cmꢁ1; UVevis (CH2Cl2): lmax (log ε)¼236 (4.40),
269 (4.28), 305 sh (4.64), 315 (4.73), 348 (3.93), 368 sh (3.83), 460
(2.69), 495 (2.54), 547 (1.75) nm; HRMS (ESI positive): calcd for
C24H32O5þNaþ 423.2142; found 423.2164. HRMS (ESI positive):
calcd for C24H32O5þHþ 401.2323; found 401.2340.
(t, 3JH,H¼7.1 Hz, 3H, 60-H); 13C NMR (125 MHz, CDCl3):
¼169.78 (C-
d
2),164.85 (1,3-COOEt),155.48 (C-6),140.90 (C-3a,8a),136.14 (C-4,8),
132.31 (C-5,7), 107.34 (C-1,3), 62.97 (2-OMe), 60.06 (1,3-COOEt),
41.70 (C-10), 32.52 (C-20), 31.61 (C-40), 28.83 (C-30), 22.51 (C-50),
14.47 (1,3-COOEt), 14.02 (C-60); IR (KBr disk): nmax¼2943 (w), 2923
(m), 2875 (w), 2852 (w), 1677 (s, C]O),1580 (w), 1545 (w),1491 (s),
1430 (s), 1415 (s), 1391 (s), 1335 (w), 1276 (s), 1240 (m), 1203 (s),
1156 (m), 1109 (m), 1038 (s), 1001 (m), 923 (w), 898 (w), 838 (m),
735 (w), 710 (w), 568 (w) cmꢁ1; UVevis (CH2Cl2): lmax (log ε)¼236
(4.43), 263 sh (4.26), 270 (4.31), 304 sh (4.65), 314 (4.74), 347 (3.98),
359 sh (3.93), 374 sh (3.74), 438 sh (2.60), 464 (2.70), 496 sh (2.56),
545 sh (1.80) nm; HRMS (ESI positive): calcd for C23H30O5þNaþ
409.1985; found 409.2032. HRMS (ESI positive): calcd for
C23H30O5þHþ 387.2166; found 387.2213. Anal. Calcd for C23H30O5:
C, 71.48; H, 7.82; found: C, 71.39; H, 7.76.
4.1.7. Diethyl 2-methoxy-6-(1-propylbutyl)azulene-1,3-dicarboxylate
(11). To a degassed solution of diethyl 6-bromo-2-methoxyazulene-
1,3-dicarboxylate (4) (509 mg, 1.34 mmol) and 1-propylbutylzinc
bromide (0.5 M, 8 mL) in dry THF (15 mL) was added PdCl2[dppf]$
CH2Cl2 (57 mg, 0.070 mmol). The resulting mixture was stirred at
50 ꢀC for 1 h under an Ar atmosphere. The reaction mixture was
washed successively with 5% NH4Cl solution and water, dried over
MgSO4, and concentrated under reduced pressure. The residue was
purified by column chromatography on silica gel with 20% ethyl
acetate/hexane to afford a 77:23 mixture of 11 and diethyl 6-(1-
ethylpentyl)-2-methoxyazulene-1,3-dicarboxylate (12) (421 mg,
4.1.9. Diethyl 6-decyl-2-methoxyazulene-1,3-dicarboxylate (6c). A
mixture
of
diethyl
6-(1-decynyl)-2-methoxyazulene-1,3-
dicarboxylate (5b) (2.87 g, 6.54 mmol), 10% PdeC (691 mg) in
ethanol (305 mL) was stirred at room temperature for 1 day under
an H2 atmosphere. After the Pd catalyst was removed by filtration,
the solvent was removed under reduced pressure. The residue was
purified by column chromatography on silica gel with 20% ethyl
79%). Red oil; 1H NMR (500 MHz, CDCl3):
d
¼9.44 (d, 3JH,H¼11.2 Hz,
3
2H, minor-4,8-H), 9.43 (d, JH,H¼11.1 Hz, 2H, 4,8-H), 7.563 (d,
3JH,H¼11.1 Hz, 2H, 5,7-H), 7.559 (d, 3JH,H¼11.2 Hz, 2H, minor-5,7-H),
4.46 (q, 3JH,H¼7.1 Hz, 4H,1,3-COOEt and 4H, minor-1,3-COOEt), 4.133
acetate/hexane to afford 6c (2.71 g, 94%). Red oil; 1H NMR
3
(500 MHz, CDCl3):
d
¼9.42 (d, JH,H¼11.1 Hz, 2H, 4,8-H), 7.59 (d,
3JH,H¼11.1 Hz, 2H, 5,7-H), 4.46 (q, 3JH,H¼7.1 Hz, 4H, 1,3-COOEt), 4.13
3
3
3
(s, 3H, minor-2-OMe), 4.131 (s, 3H, 2-OMe), 2.80 (dddd, JH,H¼9.8,
(s, 3H, 2-OMe), 2.88 (t, JH,H¼7.7 Hz, 2H, 10-H), 1.72 (tt, JH,H¼7.7,
7.3 Hz, 2H, 20-H), 1.46 (t, 3JH,H¼7.1 Hz, 6H, 1,3-COOEt), 1.38e1.25 (m,
14H, 30e90-H), 0.87 (t, 3JH,H¼7.0 Hz, 3H, 100-H); 13C NMR (125 MHz,
9.8, 4.9, 4.9 Hz, 1H, 10-H), 2.67 (dddd, 3JH,H¼9.8, 9.8, 4.9, 4.9 Hz, 1H,
minor-10-H), 1.86e1.62 (m, 4H, 20-H and 4H, minor-20-H and -100-H),
3
1.47 (t, JH,H¼7.1 Hz, 6H, 1,3-COOEt and 6H, minor-1,3-COOEt),
CDCl3):
d
¼169.77 (C-2), 164.84 (1,3-COOEt), 155.49 (C-6), 140.89 (C-
1.31e1.00 (m, 4H, 30-H and 4H, minor-30-H and -40-H), 0.85 (t,
3JH,H¼7.3 Hz, 6H, 40-H), 0.81 (t, 3JH,H¼7.2 Hz, 3H, minor-50-H), 0.78 (t,
3a,8a), 136.14 (C-4,8), 132.32 (C-5,7), 107.34 (C-1,3), 62.97 (2-OMe),
60.05 (1,3-COOEt), 41.70 (C-10), 32.57 (C-20), 31.84 (t), 29.53 (t),
29.48 (t), 29.42 (t), 29.27 (t), 29.17 (t), 22.64 (t), 14.47 (1,3-COOEt),
14.08 (C-100); IR (KBr disk): nmax¼2920 (s), 2851 (m), 1683 (s, C]O),
1580 (w), 1546 (w), 1493 (s), 1484 (m), 1431 (s), 1415 (s), 1392 (s),
1277 (s), 1241 (m), 1203 (s), 1153 (m), 1109 (m), 1034 (s), 1001 (m),
857 (w), 823 (w), 718 (w) cmꢁ1; UVevis (CH2Cl2): lmax (log ε)¼236
(4.46), 270 (4.34), 304 sh (4.68), 314 (4.77), 348 (4.00), 359 sh
(3.95), 373 sh (3.78), 440 sh (2.69), 464 (2.75), 496 sh (2.63), 544 sh
(2.08) nm; HRMS (ESI positive): calcd for C27H38O5þNaþ 465.2611;
found 465.2604. HRMS (ESI positive): calcd for C27H38O5þHþ
443.2792; found 443.2784.
3JH,H¼7.3 Hz, 3H, minor-200-H); 13C NMR (125 MHz, CDCl3):
¼169.87
d
(C-2 and minor-C-2),164.83 (minor-1,3-COOEt),164.82 (1,3-COOEt),
158.77 (C-6),158.57 (minor-C-6),140.89 (minor-C-3a,8a),140.86 (C-
3a,8a), 136.07 (C-4,8 and minor-C-4,8), 131.52 (minor-C-5,7), 131.46
(C-5,7), 107.25 (C-1,3 and minor-C1,3), 62.95 (2-OMe and minor-2-
OMe), 60.05 (1,3-COOEt and minor-1,3-COOEt), 52.91 (minor-C-10),
50.54 (C-10), 39.61 (C-20), 36.81 (minor-C-20), 30.30 (minor-C-100),
29.84 (minor-C-30), 22.69 (minor-C-40), 20.74 (C-30), 14.47 (1,3-
COOEt and minor-1,3-COOEt), 14.04 (C-40), 13.88 (minor-C-50),
12.21 (minor-C-200); IR (neat): nmax¼2957 (m), 2930 (m), 2871 (m),
1682 (s, C]O), 1579 (m), 1544 (m), 1487 (s), 1433 (s), 1390 (s), 1276
(s),1238 (s),1185 (s),1107 (m),1090 (m),1070 (m),1033 (s),1000 (s),
925 (w), 850 (m), 796 (w), 714 (w), 572 (w) cmꢁ1; UVevis (CH2Cl2):
lmax (log ε)¼229 sh (4.40), 236 (4.45), 264 sh (4.28), 270 (4.33), 304
sh (4.68), 314 (4.79), 348 (3.96), 358 sh (3.92), 374 sh (3.68), 438 sh
(2.63), 463 (2.73), 491 sh (2.63), 537 sh (1.99) nm; HRMS (ESI posi-
tive): calcd for C24H32O5þKþ 439.1881; found 439.1875. HRMS (ESI
positive): calcd for C24H32O5þNaþ 423.2142; found 423.2122.
HRMS (ESI positive): calcd for C24H32O5þHþ 401.2323; found
401.2321.
4.1.10. 6-Butyl-2-hydroxyazulene (8a). To a solution of diethyl 6-
butyl-2-methoxyazulene-1,3-dicarboxylate
(6a)
(426
mg,
1.19 mmol) was dissolved in ethanol (6 mL) was added 2 M KOH
(4 mL). The resulting mixture was refluxed for 4 h. After cooling the
reaction mixture, the mixture was acidified with 2 M HCl (7 mL).
The precipitated crystals were collected by filtration, washed with
water, and dried in vacuo to afford 6-butyl-2-methoxyazulene-1,3-
dicarboxylic acid (7a) (357 mg, 99%), which was utilized to the next
reaction without further purification.
A mixture of 7a (1.10 g, 3.64 mmol) and freshly prepared 100%
phosphoric acid, which was prepared by 85% phosphoric acid
(64.0 g) and phosphorous(V) oxide (25.4 g), was heated at 130 ꢀC
for 20 min with occasional stirring with a glass rod. After cooling
the reaction mixture, the mixture was poured into ice-water and
extracted with toluene. The organic layer was washed with water,
dried over MgSO4, and concentrated under reduced pressure. The
residue was purified by column chromatography on silica gel with
20% ethyl acetate/hexane to afford 8a (476 mg, 65%).
4.1.8. Diethyl 6-hexyl-2-methoxyazulene-1,3-dicarboxylate (6b). A
mixture
of
diethyl
6-(1-hexynyl)-2-methoxyazulene-1,3-
dicarboxylate (5a) (1.67 g, 4.37 mmol), 10% PdeC (466 mg) in eth-
anol (255 mL) was stirred at room temperature for 1 day under an
H2 atmosphere. After the Pd catalyst was removed by filtration, the
solvent was removed under reduced pressure. The residue was
purified by column chromatography on silica gel with 20% ethyl
acetate/hexane to afford 6b (1.52 g, 90%). Orange prisms; mp
45.3e47.5 ꢀC (hexane); 1H NMR (500 MHz, CDCl3):
d
¼9.42 (d,
Compound 7a: Yellow crystals; mp 148.2e149.3 ꢀC (hexane); 1H
3JH,H¼11.1 Hz, 2H, 4,8-H), 7.59 (d, 3JH,H¼11.1 Hz, 2H, 5,7-H), 4.46 (q,
NMR (500 MHz, DMSO-d6):
d¼12.57 (s, 2H, 1,3-COOH), 9.33 (d,
3JH,H¼7.2 Hz, 4H, 1,3-COOEt), 4.13 (s, 3H, 2-OMe), 2.88 (t,
3JH,H¼11.1 Hz, 2H, 4,8-H), 7.75 (d, 3JH,H¼11.1 Hz, 2H, 5,7-H), 4.06 (s,
3H, 2-OMe), 2.89 (t, 3JH,H¼7.7 Hz, 2H,10-H),1.67 (tt, 3JH,H¼7.7, 7.5 Hz,
2H, 20-H), 1.34 (tq, 3JH,H¼7.5, 7.3 Hz, 2H, 30-H), 0.91 (t, 3JH,H¼7.3 Hz,
3
3JH,H¼7.7 Hz, 2H, 10-H), 1.72 (tt, JH,H¼7.7, 7.4 Hz, 2H, 20-H), 1.46 (t,
3JH,H¼7.2 Hz, 6H, 1,3-COOEt), 1.38e1.29 (m, 6H, 30,40,50-H), 0.88

S. Ito et al. / Tetrahedron 69 (2013) 4259e4269
4267
3
3H, 40-H); 13C NMR (125 MHz, DMSO-d6¼39.5 ppm):
d
¼169.08 (C-
d
¼9.51 (s, 1H, 2-OH), 7.93 (d, JH,H¼10.6 Hz, 2H, 4,8-H), 7.09 (d,
2), 165.43 (1,3-COOH), 155.16 (C-6), 139.76 (C-3a,8a), 135.45 (C-4,8),
132.12 (C-5,7), 107.12 (C-1,3), 62.26 (2-OMe), 40.30 (C-10), 34.10 (C-
20), 21.73 (C-30), 13.75 (C-40); IR (KBr disk): nmax¼2956 (m), 2868
(w), 1658 (s, C]O), 1577 (m), 1547 (w), 1493 (s), 1444 (s), 1401 (m),
1271 (w), 1226 (m), 1104 (w), 1004 (w), 843 (w) cmꢁ1; UVevis
(CH2Cl2): lmax (log ε)¼235 (4.50), 263 sh (4.24), 271 (4.34), 302 sh
(4.63), 312 (4.74), 342 (3.99), 371 sh (3.72), 426 sh (2.78), 450 (2.87),
477 sh (2.78), 521 sh (2.18) nm; HRMS (ESI positive): calcd for
C17H18O5þHþ 303.1227; found 303.1234.
3JH,H¼10.6 Hz, 2H, 5,7-H), 6.85 (d, 3JH,H¼11.9 Hz, 1H, mior-8-H), 6.70
(s, 2H, 1,3-H), 6.51 (dd, 3JH,H¼11.9 Hz, 4JH,H¼1.2 Hz, 1H, minor-7-H),
3
4
6.37 (dd, JH,H¼8.4 Hz, JH,H¼1.2 Hz, 1H, minor-5-H), 6.30 (dd,
3JH,H¼8.4 Hz, 4JH,H¼1.2 Hz,1H, minor-4-H), 5.65 (d, 4JH,H¼1.2 Hz, 1H,
minor-1-H), 2.97 (s, 2H, minor-3-H), 2.75 (t, 3JH,H¼7.7 Hz, 2H, 10-H),
2.26 (t, 3JH,H¼7.7 Hz, 2H, minor-10-H), 1.67 (tt, 3JH,H¼7.7, 7.4 Hz, 2H,
20-H), 1.50 (tt, 3JH,H¼7.7, 7.3 Hz, 2H, minor-20-H), 1.40e1.26 (m, 6H,
30,40,50-H and 6H, minor-30,40,50-H), 0.87 (t, 3JH,H¼7.0 Hz, 3H, minor-
60-H), 0.86 (t, 3JH,H¼7.1 Hz, 3H, 60-H); 13C NMR (125 MHz, acetone-
Compound 8a: Red needles; mp 75.7e76.6 ꢀC (hexane); 1H NMR
d6¼29.8 ppm) of major tautomer: ¼167.51 (C-2), 148.05 (C-6),
d
(500 MHz, acetone-d6¼2.04 ppm) of major tautomer:
d
¼9.49 (s,1H,
140.09 (C-3a,8a), 131.08 (C-4,8), 125.94 (C-5,7), 103.73 (C-1,3), 42.37
(C-10), 33.65 (C-20), 32.43 (C-40), 29.66 (C-30), 23.23 (C-50), 14.30 (C-
60); IR (KBr disk): nmax¼2955 (m), 2927 (m), 2854 (m), 1646 (m),
1631 (m), 1580 (w), 1534 (s), 1499 (s), 1437 (m), 1404 (m), 1261 (w),
2-OH), 7.93 (d, 3JH,H¼10.5 Hz, 2H, 4,8-H), 7.09 (d, 3JH,H¼10.5 Hz, 2H,
3
5,7-H), 6.70 (s, 2H, 1,3-H), 2.75 (t, JH,H¼7.8 Hz, 2H, 10-H), 1.66 (tt,
3JH,H¼7.8, 7.5 Hz, 2H, 20-H), 1.37 (tq, 3JH,H¼7.5, 7.4 Hz, 2H, 30-H), 0.92
(t, JH,H¼7.4 Hz, 3H, 40-H); 13C NMR (125 MHz, acetone-
1236 (m), 1158 (w), 1136 (w), 841 (w), 832 (w), 787 (w) cmꢁ1
;
3
d6¼29.8 ppm) of major tautomer:
d
¼167.51 (C-2), 148.02 (C-6),
UVevis (CH2Cl2): lmax (log ε)¼241 (4.07), 268 (3.93), 280 (3.93),
289 (3.92), 318 sh (3.62), 357 sh (4.15), 373 (4.21), 397 sh (4.01), 425
sh (3.27), 448 sh (3.05), 480 sh (2.84), 519 sh (2.49), 569 sh (1.96)
nm; HRMS (ESI positive): calcd for C16H20OþHþ 229.1587; found
229.1585. Anal. Calcd for C16H20O: C, 84.16; H, 8.83; found: C, 84.10;
H, 8.79.
140.09 (C-3a,8a), 131.08 (C-4,8), 125.94 (C-5,7), 103.73 (C-1,3), 42.07
(C-10), 35.85 (C-20), 22.98 (C-30), 14.20 (C-40); IR (KBr disk):
nmax¼2966 (m), 2928 (m),1644 (s),1627 (s),1580 (m),1531 (s),1498
(s), 1436 (m), 1403 (m), 1260 (m), 1234 (m), 1158 (m), 1142 (w), 841
(m), 786 (w), 759 (w), 716 (w), 667 (w), 597 (w) cmꢁ1; UVevis
(CH2Cl2): lmax (log ε)¼237 (4.12), 243 sh (4.11), 269 (3.98), 281
(3.99), 290 (3.99), 319 (3.67), 357 sh (4.19), 372 (4.25), 397 sh (4.04),
448 sh (3.07), 481 sh (2.85), 520 (2.48), 570 (1.87) nm; HRMS (ESI
positive): calcd for C14H16OþKþ 239.0833; found 239.0917. HRMS
(ESI positive): calcd for C14H16OþNaþ 223.1093; found 223.1093.
Anal. Calcd for C14H16O: C, 83.96; H, 8.05; found: C, 83.95; H, 7.97.
4.1.12. 6-Decyl-2-hydroxyazulene (8c). To a solution of diethyl 6-
decyl-2-methoxyazulene-1,3-dicarboxylate (6c) (2.65 g, 5.99 mmol)
was dissolved in ethanol (32 mL) was added 2 M KOH (24 mL). The
resulting mixture was refluxed for 4 h. After cooling the reaction
mixture, the mixture was acidified with 2 M HCl (39 mL). The pre-
cipitated crystals were collected by filtration, washed with water, and
dried in vacuo to afford 6-decyl-2-methoxyazulene-1,3-dicarboxylic
acid (7c) (2.23 g, 96%), which was utilized to the next reaction
without further purification.
4.1.11. 6-Hexyl-2-hydroxyazulene (8b). To a solution of diethyl 6-
hexyl-2-methoxyazulene-1,3-dicarboxylate (6b) (1.50 g, 3.88 mmol)
was dissolved in ethanol (20 mL) was added 2 M KOH (14 mL). The
resulting mixture was refluxed for 4 h. After cooling the reaction
mixture, the mixture was acidified with 2 M HCl (23 mL). The pre-
cipitated crystals were collected by filtration, washed with water, and
dried in vacuo to afford 6-hexyl-2-methoxyazulene-1,3-dicarboxylic
acid (7b) (1.23 g, 96%), which was utilized to the next reaction
without further purification.
A mixture of 7c (260 mg, 0.673 mmol) and freshly prepared
100% phosphoric acid, which was prepared by 85% phosphoric acid
(11.9 g) and phosphorous(V) oxide (4.86 g), was heated at 130 ꢀC for
20 min with occasional stirring with a glass rod. After cooling the
reaction mixture, the mixture was poured into ice-water and
extracted with toluene. The organic layer was washed with water,
dried over MgSO4, and concentrated under reduced pressure. The
residue was purified by column chromatography on silica gel with
20% ethyl acetate/hexane to afford 8c (114 mg, 60%).
A mixture of 7b (1.13 g, 3.42 mmol) and freshly prepared 100%
phosphoric acid, which was prepared by 85% phosphoric acid
(59.7 g) and phosphorous(V) oxide (24.4 g), was heated at 130 ꢀC
for 20 min with occasional stirring with a glass rod. After cooling
the reaction mixture, the mixture was poured into ice-water and
extracted with toluene. The organic layer was washed with water,
dried over MgSO4, and concentrated under reduced pressure. The
residue was purified by column chromatography on silica gel with
20% ethyl acetate/hexane to afford 8b (401 mg, 51%).
Compound 7c: Yellow crystals; mp 124.3e126.9 ꢀC (hexane); 1H
NMR (500 MHz, CDCl3):
d
¼11.84 (br, 2H, 1,3-COOH), 9.75 (d,
3JH,H¼11.1 Hz, 2H, 4,8-H), 7.78 (d, 3JH,H¼11.1 Hz, 2H, 5,7-H), 4.40 (s,
3H, 2-OMe), 2.96 (t, 3JH,H¼7.7 Hz, 2H, 10-H),1.76 (tt, 3JH,H¼7.7, 7.3 Hz,
2H, 20-H), 1.41e1.26 (m, 14H, 30e90-H), 0.88 (t, 3JH,H¼6.9 Hz, 3H, 100-
H); 13C NMR (125 MHz, CDCl3):
d
¼169.02 (C-2), 166.95 (1,3-COOH),
Compound 7b: Yellow crystals; mp 136.4e137.4 ꢀC (hexane); 1H
157.90 (C-6), 141.99 (C-3a,8a), 138.03 (C-4,8), 134.37 (C-5,7), 104.67
(C-1,3), 64.48 (2-OMe), 41.85 (C-10), 32.56 (C-20), 31.85 (t), 29.54 (t),
29.48 (t), 29.40 (t), 29.27 (t), 29.18 (t), 22.65 (t), 14.09 (C-100); IR
(KBr disk): nmax¼2925 (s), 2854 (m), 1645 (s, C]O), 1575 (m), 1545
(w), 1492 (s), 1449 (s), 1398 (m), 1284 (m), 1226 (s), 1008 (m), 677
(w) cmꢁ1; UVevis (CH2Cl2): lmax (log ε)¼236 (4.45), 271 (4.32), 303
sh (4.60), 312 (4.69), 346 sh (3.98), 371 sh (3.71), 426 sh (2.82), 450
(2.89), 496 sh (2.58), 544 sh (1.95) nm; HRMS (ESI positive): calcd
for C23H30O5þHþ 387.2166; found 387.2151. Anal. Calcd for
C23H30O5: C, 71.48; H, 7.82; found: C, 71.83; H, 7.62.
NMR (500 MHz, DMSO-d6):
d
¼12.58 (s, 2H, 1,3-COOEt), 9.34 (d,
3JH,H¼11.1 Hz, 2H, 4,8-H), 7.75 (d, 3JH,H¼11.1 Hz, 2H, 5,7-H), 4.08 (s,
3H, 2-OMe), 2.88 (t, 3JH,H¼7.6 Hz, 2H,10-H),1.67 (tt, 3JH,H¼7.6, 7.1 Hz,
2H, 20-H), 1.31e1.25 (m, 6H, 30,40,50-H), 0.84 (t, 3JH,H¼7.0 Hz, 3H, 60-
H); 13C NMR (125 MHz, DMSO-d6¼39.5 ppm):
d
¼169.11 (C-2),
165.44 (1,3-COOH), 155.17 (C-6), 139.78 (C-3a,8a), 135.47 (C-4,8),
132.12 (C-5,7), 107.14 (C-1,3), 62.27 (2-OMe), 40.60 (C-10), 31.95 (C-
20), 31.07 (C-40), 28.25 (C-30), 22.00 (C-50),13.91 (C-60); IR (KBr disk):
nmax¼2928 (s), 2864 (m), 2580 (m), 1653 (s, C]O), 1576 (m), 1545
(m), 1491 (s), 1449 (s), 1399 (s), 1281 (m), 1227 (s), 1126 (w), 1097
(w), 1006 (m), 926 (w), 892 (w), 860 (w), 736 (w), 676 (w), 420 (w)
cmꢁ1; UVevis (CH2Cl2): lmax (log ε)¼236 (4.31), 263 sh (4.07), 271
(4.17), 302 sh (4.43), 312 (4.55), 345 sh (3.89), 370 sh (3.66), 426 sh
(2.71), 450 (2.78), 476 sh (2.70), 521 sh (2.20) nm; HRMS (ESI
positive): calcd for C19H22O5þNaþ 353.1359; found 353.1351. HRMS
(ESI positive): calcd for C19H22O5þHþ 331.1540; found 331.1529.
Compound 8b: Red needles; mp 90.8e91.2 ꢀC (hexane); 1H NMR
(500 MHz, acetone-d6¼2.04 ppm) of ketoeenol ratio¼18:82:
Compound 8c: Red plates; mp 90.4e91.3 ꢀC (hexane); 1H NMR
(500 MHz, CDCl3) of ketoeenol ratio¼92:8: ¼9.02 (br, 1H, minor-
d
3
2-OH), 7.93 (d, JH,H¼10.5 Hz, 2H, minor-4,8-H), 7.05 (d,
3JH,H¼10.5 Hz, 2H, minor-5,7-H), 6.78 (d, JH,H¼11.8 Hz, 1H, 8-H),
3
3
4
6.75 (s, 2H, minor-1,3-H), 6.45 (dd, JH,H¼11.8 Hz, JH,H¼1.1 Hz, 1H,
3
4
7-H), 6.32 (dd, JH,H¼8.5 Hz, JH,H¼1.1 Hz, 1H, 5-H), 6.28 (dd,
3JH,H¼8.5 Hz, 4JH,H¼1.1 Hz, 1H, 4-H), 5.75 (d, 4JH,H¼1.1 Hz, 1H, 1-H),
3
3.06 (s, 2H, 3-H), 2.74 (t, JH,H¼7.7 Hz, 2H, minor-10-H), 2.26 (t,
3
3JH,H¼7.6 Hz, 2H, 10-H), 1.67 (tt, JH,H¼7.7, 7.3 Hz, 2H, minor-20-H),

4268
S. Ito et al. / Tetrahedron 69 (2013) 4259e4269
1.50 (tt, 3JH,H¼7.6, 7.0 Hz, 2H, 20-H), 1.30e1.26 (m, 14H, 30e90-H and
pressure. The residue was purified by column chromatography on
silica gel with 20% ethyl acetate/hexane to afford 9b (286 mg, 73%).
Violet plates; mp 87.8e89.0 ꢀC (hexane); 1H NMR (500 MHz,
3
14H, minor-30e90-H), 0.88 (t, JH,H¼7.0 Hz, 3H, 100-H), 0.87 (t,
3JH,H¼7.0 Hz, 3H, minor-100-H); 13C NMR (125 MHz, CDCl3) of
ketoeenol ratio¼92:8:
d¼202.49 (C-2), 167.86 (C-8a), 165.94 (mi-
CDCl3):
d
¼8.13 (d, 3JH,H¼10.4 Hz, 2H, 4,8-H), 7.26 (s, 2H, 1,3-H), 7.12
nor-C-2), 147.88 (C-3a), 147.67 (minor-C-6), 145.62 (C-6), 139.23 (C-
7), 138.93 (minor-C-3a,8a), 131.27 (C-5), 130.60 (minor-C-4,8),
130.33 (C-8), 125.60 (C-4), 125.22 (minor-C-5,7), 122.03 (C-1),
102.87 (minor-C-1,3), 43.85 (C-3), 41.92 (minor-C-10), 40.32 (C-10),
32.86 (minor-C-20), 31.85 (C-20), 30.26 (t), 29.57 (t), 29.54 (t), 29.51
(t), 29.49 (t), 29.39 (t), 29.29 (t, 2C-minor), 29.27 (t), 28.98 (t), 22.64
(t), 14.07 (C-100 and minor-C-100); 1H NMR (500 MHz, acetone-
(d, 3JH,H¼10.4 Hz, 2H, 5,7-H), 2.77 (t, 3JH,H¼7.8 Hz, 2H, 10-H), 1.69 (tt,
3JH,H¼7.8, 7.3 Hz, 2H, 20-H), 1.39e1.28 (m, 6H, 30,40,50-H), 0.88 (t,
3JH,H¼7.1 Hz, 3H, 60-H); 13C NMR (125 MHz, CDCl3):
¼154.18 (C-6),
d
138.52 (C-3a,8a), 134.67 (C-4,8), 125.77 (C-5,7), 125.74 (C-2), 118.40
(C-1,3), 42.42 (C-10), 32.52 (C-20), 31.67 (C-40), 28.96 (C-30), 22.55 (C-
50), 14.06 (C-60); IR (KBr disk): nmax¼2961 (m), 2927 (s), 2855 (m),
1581 (m), 1557 (w), 1545 (w), 1465 (w), 1438 (m), 1402 (s), 1286 (w),
1232 (w), 1072 (w), 973 (w), 917 (w), 861 (w), 838 (s), 791 (m), 596
(m, CeBr) cmꢁ1; UVevis (CH2Cl2): lmax (log ε)¼234 (4.23), 286
(4.87), 293 (4.87), 325 sh (3.76), 337 (3.86), 350 (3.90), 364 (3.88),
502 sh (2.58), 537 (2.71), 575 sh (2.65), 629 sh (2.26) nm; HRMS (ESI
positive): calcd for C16H19BrþHþ 291.0743; found 291.0744. Anal.
Calcd for C16H19Br: C, 65.99; H, 6.58; found: C, 66.37; H, 6.54.
d6¼2.04 ppm) of ketoeenol ratio¼18:82: ¼9.49 (s, 1H, 2-OH), 7.93
d
(d, 3JH,H¼10.5 Hz, 2H, 4,8-H), 7.10 (d, 3JH,H¼10.5 Hz, 2H, 5,7-H), 6.84
3
(d, JH,H¼11.9 Hz, 1H, minor-8-H), 6.69 (s, 2H, 1,3-H), 6.50 (dd,
3JH,H¼11.9 Hz, 4JH,H¼1.4 Hz, 1H, minor-7-H), 6.32 (dd, 3JH,H¼8.4 Hz,
3
4
4JH,H¼1.0 Hz, 1H, minor-5-H), 6.30 (dd, JH,H¼8.4 Hz, JH,H¼1.0 Hz,
4
1H, minor-4-H), 5.65 (d, JH,H¼1.0 Hz, 1H, minor-1-H), 2.99 (s, 2H,
minor-3-H), 2.75 (t, 3JH,H¼7.7 Hz, 2H, 10-H), 2.27 (t, 3JH,H¼7.6 Hz, 2H,
minor-10-H), 1.68 (tt, JH,H¼7.7, 7.2 Hz, 2H, 20-H), 1.50 (tt, 3JH,H¼7.6,
4.1.15. 2-Bromo-6-decylazulene (9c). To a solution of 6-decyl-2-
hydroxyazulene (8c) (776 mg, 2.73 mmol) in dry toluene
(100 mL) was added PBr3 (2.44 g, 9.01 mmol). The resulting mixture
was heated at 100 ꢀC for 1 h. The reaction mixture was poured into
water and extracted with toluene. The organic layer was washed
with water, dried over MgSO4, and concentrated under reduced
pressure. The residue was purified by column chromatography on
silica gel with 20% ethyl acetate/hexane to afford 9c (550 mg, 58%).
3
7.1 Hz, 2H, minor-20-H),1.40e1.26 (m,14H, 30e90-H and 14H, minor-
3
30e90-H), 0.87 (t, JH,H¼7.0 Hz, 3H, minor-100-H), 0.86 (t,
3JH,H¼7.0 Hz, 3H,100-H); 13C NMR (125 MHz, acetone-d6¼29.8 ppm)
of major tautomer:
d
¼167.52 (C-2), 148.06 (C-6), 140.10 (C-3a,8a),
131.08 (C-4,8), 125.94 (C-5,7), 103.73 (C-1,3), 42.38 (C-10), 33.69 (C-
20), 32.59 (t), 30.29 (t, 3C), 30.21 (t), 30.02 (t), 29.98 (t), 29.34 (t),
23.29 (t), 14.32 (C-100); IR (KBr disk): nmax¼2921 (s), 2851 (s), 1645
(m), 1629 (m), 1583 (w), 1535 (s), 1500 (s), 1465 (m), 1439 (m), 1404
(m), 1261 (w), 1236 (m), 1139 (w), 876 (w), 831 (m), 787 (w), 719
(w), 650 (w), 411 (w) cmꢁ1; UVevis (CH2Cl2): lmax (log ε)¼239
(4.05), 271 (3.92), 280 (3.95), 289 (3.94), 319 (3.70), 356 sh (4.09),
372 (4.15), 398 sh (3.93), 424 sh (3.26), 448 sh (2.97), 481 sh (2.75),
519 sh (2.41), 570 sh (1.84) nm; HRMS (ESI positive): calcd for
C20H28OþHþ 285.2213; found 285.2228. Anal. Calcd for C20H28O: C,
84.45; H, 9.92; found: C, 84.76; H, 9.75.
Violet plates; mp 76.1e77.1 ꢀC (hexane); 1H NMR (500 MHz, CDCl3):
3
d
¼8.13 (d, JH,H¼10.5 Hz, 2H, 4,8-H), 7.26 (s, 2H, 1,3-H), 7.12 (d,
3JH,H¼10.5 Hz, 2H, 5,7-H), 2.77 (t, JH,H¼7.0 Hz, 2H, 10-H), 1.69 (tt,
3
3JH,H¼8.1, 7.0 Hz, 2H, 20-H), 1.39e1.25 (m, 14H, 30e90-H), 0.87 (t,
3JH,H¼7.0 Hz, 3H,100-H); 13C NMR (125 MHz, CDCl3):
¼154.18 (C-6),
d
138.54 (C-3a,8a), 134.66 (C-4,8), 125.77 (C-5,7 and C-2), 118.41 (C-
1,3), 42.42 (C-10), 32.56 (C-20), 31.87 (t), 29.57 (t), 29.52 (t), 29.47 (t),
29.29 (t, 2C), 22.66 (t), 14.10 (C-100); IR (KBr disk): nmax¼2917 (s),
2850 (s),1582 (m),1532 (w),1467 (m),1440 (w),1402 (m),1290 (w),
1234 (w), 1218 (w), 1156 (w), 1070 (w), 1031 (w), 969 (w), 916 (w),
4.1.13. 2-Bromo-6-butylazulene (9a). To a solution of 6-butyl-2-
hydroxyazulene (8a) (615 mg, 3.07 mmol) in dry toluene
(115 mL) was added PBr3 (2.26 g, 8.35 mmol). The resulting mixture
was heated at 100 ꢀC for 1 h. The reaction mixture was poured into
water and extracted with toluene. The organic layer was washed
with water, dried over MgSO4, and concentrated under reduced
pressure. The residue was purified by column chromatography on
silica gel with 20% ethyl acetate/hexane to afford 9a (562 mg, 70%).
Violet plates; mp 103.2e103.9 ꢀC (hexane); 1H NMR (500 MHz,
862 (w), 831 (m), 787 (w), 768 (w), 720 (w), 594 (m, CeBr) cmꢁ1
;
UVevis (CH2Cl2): lmax (log ε)¼235 (4.11), 255 sh (3.82), 286 (4.77),
294 (4.78), 325 sh (3.69), 337 (3.78), 350 (3.80), 364 (3.78), 395 sh
(2.26), 503 sh (2.48), 537 (2.60), 573 sh (2.55), 627 sh (2.17) nm;
HRMS (ESI positive): calcd for C20H27BrþHþ 347.1369; found
347.1353. Anal. Calcd for C20H27Br: C, 69.16; H, 7.84; found: C, 69.47;
H, 7.77.
CDCl3):
d
¼8.13 (d, 3JH,H¼10.5 Hz, 2H, 4,8-H), 7.26 (s, 2H, 1,3-H), 7.12
Acknowledgements
(d, 3JH,H¼10.5 Hz, 2H, 5,7-H), 2.77 (t, 3JH,H¼7.8 Hz, 2H, 10-H), 1.68 (tt,
3JH,H¼7.8, 7.5 Hz, 2H, 20-H), 1.39 (tq, 3JH,H¼7.5, 7.4 Hz, 2H, 30-H), 0.94
This work was supported by JSPS KAKENHI Grant Numbers
21550031, 24550037 to S.I.
(t, 3JH,H¼7.4 Hz, 3H, 40-H); 13C NMR (125 MHz, CDCl3):
¼154.13 (C-
d
6), 138.53 (C-3a,8a), 134.66 (C-4,8), 125.77 (C-5,7), 125.76 (C-2),
118.41 (C-1,3), 42.11 (C-10), 34.67 (C-20), 22.38 (C-30), 13.93 (C-40); IR
(KBr disk): nmax¼2954 (m), 2920 (m), 2855 (m), 1579 (m), 1464 (m),
1438 (m), 1401 (m), 1284 (w), 1232 (m), 1102 (w), 1068 (w), 1027
(w), 980 (w), 916 (m), 859 (m), 834 (s), 788 (m), 722 (w), 693 (w),
596 (m, CeBr) cmꢁ1; UVevis (CH2Cl2): lmax (log ε)¼233 (4.16), 256
sh (3.82), 275 sh (4.52), 285 (4.82), 293 (4.81), 325 sh (3.65), 336
(3.76), 350 (3.81), 364 (3.81), 497 sh (2.45), 539 (2.61), 574 sh (2.56),
631 sh (2.12) nm; HRMS (ESI positive): calcd for C14H15BrþHþ
263.0430; found 263.0461. Anal. Calcd for C14H15Br: C, 63.89; H,
5.74; found: C, 64.03; H, 5.85.
Supplementary data
General and experimental details for the electrochemical mea-
surements; cyclic voltammograms of nPAs 3aee; spectroelectro-
grams of nPAs 3aee; UV/vis spectra of 4PA 3a, 6PA 3b, and 10PA 3d
and related compounds; Copies of 1H and 13C NMR spectra of the
reported compounds; DFT calculation results based on B3LYP/6-
31G** method. Supplementary data associated with this article can
be found in the online version, at http://dx.doi.org/10.1016/
j.tet.2013.03.084. These data include MOL files and InChiKeys of the
most important compounds described in this article.
4.1.14. 2-Bromo-6-hexylazulene (9b). To a solution of 6-hexyl-2-
hydroxyazulene (8b) (308 mg, 1.35 mmol) in dry toluene (50 mL)
was added PBr3 (2.02 g, 7.46 mmol). The resulting mixture was
heated at 100 ꢀC for 1 h. The reaction mixture was poured into
water and extracted with toluene. The organic layer was washed
with water, dried over MgSO4, and concentrated under reduced
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