Synthesis and redox behavior of 1,2-dihydro-1-oxabenz[a]azulen-2-ones

Article abstract of DOI:10.1016/j.tet.2014.02.073

Three new 1,2-dihydro-1-oxabenz[a]azulen-2-one derivatives, 1a (R ¹=H, R²=Me), 1b (R¹=H, R²=Ph), and 1c (R¹=COOEt, R²=Me), have been synthesized by the reaction of 2-hydroxyazulene (2a) and its 1-ethoxycarbonyl derivative 2b with ethyl acetoacetate (3a) or ethyl benzoylacetate (3b) in the presence of aluminum chloride. To our knowledge, these are the first examples of this type of compound, although the yield of the products is low in some cases. Their electronic properties were studied in detail utilizing the analyses of 1,2-dihydro-1-oxabenz[a]azulen-2-one derivative 1a by the spectroscopic and voltammetric analyses. The analyses revealed that the fused α-pyrone system lowers both the HOMO and the LUMO energies, relative to those of parent azulene (10), but has much pronounced effect on the LUMO, consequently, leading to decrease in HOMO-LUMO gap, compared with those of 10. These results should be attracted to the development of amphoteric redox materials. Reactivity toward electrophilic reagents was also examined by bromination and Vilsmeier-Haack formylation reactions of 1a. To evaluate the scope of the reaction products we have examined Sonogashira cross-coupling reaction of the bromination products with trimethylsilylacetylene and conversion of the formylation product to dibromoolefin by the reaction with phosphorous ylide prepared with CBr ₄ and Ph₃P. Effective extension of the π-electron system in the ethynyl products has been revealed by the spectroscopic analysis. These reaction products would be attracted to the application as a terminal group for electronic applications.

Full text of DOI:10.1016/j.tet.2014.02.073

Tetrahedron 70 (2014) 2796e2803
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Synthesis and redox behavior of 1,2-dihydro-1-oxabenz[a]azulen-2-
ones
,
a
a
a
a
Shunji Ito a , Shohei Yamazaki , Shun Kudo , Ryuta Sekiguchi , Jun Kawakami ,
*
Masayuki Takahashi b, Takashi Matsuhashi b, Kozo Toyota b, Noboru Morita b
a Graduate School of Science and Technology, Hirosaki University, Hirosaki 036-8561, Japan
b Department of Chemistry, Graduate School of Science, Tohoku University, Sendai 980-8578, Japan
a r t i c l e i n f o
a b s t r a c t
Three new 1,2-dihydro-1-oxabenz[a]azulen-2-one derivatives, 1a (R1¼H, R2¼Me), 1b (R1¼H, R2¼Ph), and
1c (R1¼COOEt, R2¼Me), have been synthesized by the reaction of 2-hydroxyazulene (2a) and its 1-
ethoxycarbonyl derivative 2b with ethyl acetoacetate (3a) or ethyl benzoylacetate (3b) in the presence
of aluminum chloride. To our knowledge, these are the first examples of this type of compound, although
the yield of the products is low in some cases. Their electronic properties were studied in detail utilizing
the analyses of 1,2-dihydro-1-oxabenz[a]azulen-2-one derivative 1a by the spectroscopic and voltam-
Article history:
Received 20 November 2013
Received in revised form 24 February 2014
Accepted 26 February 2014
Available online 5 March 2014
Keywords:
Coumarin analogues
Azulenes
Amphoteric redox behavior
Electrophilic substitution
metric analyses. The analyses revealed that the fused a-pyrone system lowers both the HOMO and the
LUMO energies, relative to those of parent azulene (10), but has much pronounced effect on the LUMO,
consequently, leading to decrease in HOMOeLUMO gap, compared with those of 10. These results should
be attracted to the development of amphoteric redox materials. Reactivity toward electrophilic reagents
was also examined by bromination and VilsmeiereHaack formylation reactions of 1a. To evaluate the
scope of the reaction products we have examined Sonogashira cross-coupling reaction of the bromi-
nation products with trimethylsilylacetylene and conversion of the formylation product to dibromoolefin
by the reaction with phosphorous ylide prepared with CBr4 and Ph3P. Effective extension of the
p-
electron system in the ethynyl products has been revealed by the spectroscopic analysis. These reaction
products would be attracted to the application as a terminal group for electronic applications.
Ó 2014 Elsevier Ltd. All rights reserved.
1. Introduction
development of advanced materials, such as photosensitizers,3
fluorescent chemosensors,4 organic light-emitting diodes,5 and
Coumarin (2H-1-benzopyran-2-one) and its derivatives are one
of the most important classes of heterocyclic compounds, which
possess a wide range of biological activities, such as anti-clotting,
anti-fungal, and anti-tumor activities (Fig. 1).1,2 They are widely
subsisted in a variety of plants in nature. Sufficient importance of
the coumarin derivatives is attributed to not only their biological
activities, but also their potentials as a useful scaffold for the
organic-based lasers.6 Thus, numerous coumarin derivatives have
been synthesized. Annulated coumarins are also attractive syn-
thetic targets.7e9
Azulene (C10H8) has also attracted the interest of many research
groups because of its unusual properties associated with its re-
markable polarizability and its beautiful blue color owing to its
small HOMOeLUMO gap (Fig. 1).10 Thus, the substitution by azu-
lenyl groups via their 1- and 3-positions promotes extreme stabi-
lization of cationic states, while azulen-4-yl, -6-yl, and -8-yl
substituents strongly stabilize anionic species. The reactivities of
azulenes are also strongly affected by their polarized characters.
Electrophilic substitution reactions of azulene derivatives normally
induce the reaction at the 1- and 3-positions, while the nucleophilic
reagents tend to induce the reaction at 4-, 6-, and 8-positions.
Amphoteric redox properties of the azulene derivatives arising
from their polarized natures are attractive characters that could be
applied to the advanced materials for electronic applications.
During the way to explore the azulene derivatives condensed
with heterocyclic rings, we have recently reported the preparation
8
4
5
8
4
7
5
1
3
6
7
3
2
O
6
2
O
1
Fig. 1. Structure and their numbering schemes of coumarin and azulene.
* 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 2014 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tet.2014.02.073

S. Ito et al. / Tetrahedron 70 (2014) 2796e2803
2797
of stabilized carbocations and biazulene derivative composed with
thiophene-fused azulene and its derivatives.11,12 The redox behav-
ior of these thiophene-fused derivatives was studied in detail by
voltammetric techniques. Our interests broaden the synthetic tar-
gets to the azulene analogues of coumarin derivatives possessed
structural similarity consisted by the replacement of the fused
benzene ring by aromatic azulene derivatives. Previously, only two
reaction of the active methylene compounds with azulene de-
rivatives is one of the useful selections for the construction of
azulene-fused hetelocycles.16 The reaction in the presence of pi-
peridine as a base is utilized to the preparation of azuleno[2,1-b]
pyridine derivatives by way of the example.17 More recently, 2-
amino-3-cyano-4-aryl-10-ethoxycarbonylazuleno[2,1-b]pyran de-
rivatives has been prepared by the three-component condensation
of ethyl 2-hydroxyazulene-1-carboxylate, aldehydes, and malono-
nitrile.18 However, Pechmann condensation that should construct
examples possessing a fused structure of the a-pyrone with azulene
skeleton have been examined, but in different condensation pat-
tern from that of coumarin derivatives.13,14 However, the azulene
analogues of coumarin derivatives possessed similar condensation
a-pyrone skeleton has never been examined by the reaction of 2-
hydroxyazulenes with -carbonyl ester or carboxylic acid to af-
b
pattern in the
a
-pyrone skeleton has never been synthesized up to
ford the novel 1,2-dihydro-1-oxabenz[a]azulen-2-one derivatives
to the best of our knowledge.
now, because of the lack of the useful synthetic accessibility to the
best of our knowledge (Fig. 2).
Preparation of 1,2-dihydro-1-oxabenz[a]azulen-2-one de-
rivatives 1a, 1b, and 1c was established by the reaction of 2-
hydroxyazulene (2a) and its 1-COOEt derivative 2b with ethyl
acetoacetate (3a) or ethyl benzoylacetate (3b) in the presence of
aluminum chloride; it is outlined in Scheme 1. To our knowledge,
these are the first examples of this type of compound, although the
yield of the products is low in some cases. The starting materials, 2-
hydroxyazulene (2a) and its 1-COOEt derivative 2b, were prepared
according to the literature.19e22 The reaction of 2-hydroxyazulene
(2a) with ethyl acetoacetate (3a) in the presence of aluminum
chloride afforded the presumed 1,2-dihydro-4-methyl-1-oxabenz
[a]azulen-2-one (1a) as brownish orange crystals in 57% yield.
This procedure may have an advantage for the preparation of the
novel 1,2-dihydro-1-oxabenz[a]azulen-2-one skeleton that may
have difficulty in accessing, in one-step reaction. However, the re-
action of 2-hydroxyazulene (2a) with ethyl benzoylacetate (3b)
under the similar reaction conditions afforded 1,2-dihydro-1-oxa-
4-phenylbenz[a]azulen-2-one (1b) as dark violet crystals, but in
relatively low yield (10%). Extension of the procedure to the prep-
aration of 10-COOEt derivative 1c utilizing ethyl 2-hydroxyazulene-
1-carboxylate (2b) also did not afford satisfactory results (12%
yield). Thus, the procedure may have generality for the formation of
1,2-dihydro-1-oxabenz[a]azulen-2-one skeleton, although the
yield of the products is dissatisfied in some cases. The spectral
features of the 4-methyl, 4-phenyl, and 10-COOEt derivatives 1a,
1b, and 1c are in agreement with the structure of the products as
summarized in Experimental section.
R2
4
3
5
6
2O
7
O
1
10
8
9
R1
1a: R1 = H, R2 = Me
1b: R1 = H, R2 = Ph
1c: R1 = COOEt, R2 = Me
Fig. 2. Azulene analogues of coumarin derivatives possessed structural similarity
consisted by the replacement of the fused benzene ring by aromatic azulene
derivatives.
Herein, we report the synthesis of the three new 1,2-dihydro-1-
oxabenz[a]azulen-2-one derivatives, 1a (R1¼H, R2¼Me), 1b (R1¼H,
R2¼Ph), and 1c (R1¼COOEt, R2¼Me), by the reaction of 2-
hydroxyazulene (2a) and its 1-ethoxycarbonyl derivative 2b with
ethyl acetoacetate (3a) or ethyl benzoylacetate (3b) in the presence
of aluminum chloride. Reactivity of 1a toward electrophilic re-
agents was also examined by bromination and VilsmeiereHaack
formylation reactions, which would be attracted to the application
for the further transformation of these molecular materials for
electronic applications. We also report, herein, the redox properties
of 1a examined in detail by voltammetric analyses. Electronic
properties of these compounds are discussed by utilizing time-
dependent density functional theory (TDDFT/TDA) calculations at
the B3LYP/6-31G** level. As the results, amphoteric redox proper-
ties were revealed by the 1,2-dihydro-1-oxabenz[a]azulen-2-one
derivatives. Reactivity toward electrophilic reagents examined by
bromination and VilsmeiereHaack formylation reactions of 1a
revealed the reactive position of the 1,2-dihydro-1-oxabenz[a]
azulene moiety. We have also examined Sonogashira cross-
coupling reaction of the bromination products with trimethylsily-
lacetylene and conversion of the formylation product to dibro-
moolefin by the reaction with phosphorous ylide prepared with
AlCl3
1a; R1 = H, R2 = Me
1b; R1 = H, R2 = Ph
O
O
OH
+
R2
O
1c; R1 = COOEt, R2 = Me
R1
3a; R2 = Me
3b; R2 = Ph
2a; R1 = H
2b; R1 = COOEt
Scheme 1. Preparation of 1,2-dihydro-1-oxabenz[a]azulen-2-ones 1a, 1b, and 1c.
CBr4 and Ph3P. Effective extension of the
p-electron system in the
ethynyl products has been revealed by the spectroscopic analysis.
We have now in hand novel azulene derivatives condensed with
a
heterocyclic ring, 1,2-dihydro-1-oxabenz[a]azulen-2-ones. In
particularly, 4-methyl derivative 1a could be obtained in sufficient
yield for further voltammetric and chemical investigations. To ob-
tain the aspect for the reactivities of the novel 1,2-dihydro-1-
oxabenz[a]azulen-2-one skeleton we have firstly examined the
bromination with N-bromosuccinimide (NBS) utilizing 1a as
a model compound. As the results, we found the two reactive po-
sitions toward the bromination in the novel 1,2-dihydro-1-oxabenz
[a]azulen-2-one skeleton.
2. Results and discussion
2.1. Synthesis
We have applied the Pechmann condensation for the prepara-
tion of the novel 1,2-dihydro-1-oxabenz[a]azulen-2-one de-
rivatives that is a powerful route for the preparation of coumarin
skeleton by the reaction of b-carbonyl ester or carboxylic acid with
As expected by the azulene skeleton in the 1,2-dihydro-1-
oxabenz[a]azulene moiety, bromination of the product 1a utiliz-
ing NBS proceeded not only at the 10-position that corresponds the
most reactive position of the azulene skeleton, but also at the 3-
position. Thus, the reaction produced bromination products, 10-
the corresponding phenol and its derivatives under the acidic
conditions.15 The reaction of active methylene compounds with
troponoid reagents, e.g., diethyl malonate with 2-methoxytropone,
was well known as one of the most powerful synthetic procedures
for the preparation of 2-substituted azulene derivatives.10 The

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S. Ito et al. / Tetrahedron 70 (2014) 2796e2803
bromo-1,2-dihydro-4-methyl-1-oxabenz[a]azulen-2-one (4) as
yellowish brown crystals in 42% yield, along with 3,10-dibromo-
1,2-dihydro-4-methyl-1-oxabenz[a]azulen-2-one (5) as brown
crystals in 31% yield, when the reaction was carried with 1 equiv of
NBS (Scheme 2). The increase of the amount of NBS turned the
major product to 5. Thus, the product 5 was selectively obtained by
the reaction with 2 equiv of NBS in 91% yield. Thus, the reactive
positions of the 1,2-dihydro-1-oxabenz[a]azulene moiety toward
the electrophile should be concluded by the formation of the 3,10-
disubstituted product.
TMSA, Pd(Ph3P)4
CuI, Et3N
O
4
O
TMS
7
TMS
O
TMSA, Pd(Ph3P)4
CuI, Et3N
5
+
+
4
7
O
Br
NBS
TMS
8
O
O
1a
+
O
O
Scheme 4. Sonogashira cross-coupling reaction of 10-bromo- and 3,10-dibromo-1,2-
dihydro-4-methyl-1-oxabenz[a]azulen-2-ones (4 and 5) with trimethylsilylacetylene.
Br
Br
5
4
with trimethylsilylacetylene. One is the presumed cross-coupled
product, 1,2-dihydro-4-methyl-1-oxa-3,10-bis(trimethylsilylethynyl)
benz[a]azulen-2-one (8), in 27% yield and the others are 4 and 7 in 6%
and 53% yields, respectively (Scheme 4). Formation of 4 and 7 is at-
tributed to the debromination at the 3-position under the cross-
coupling conditions probably due to the low reactivity of 5 toward
the palladium-catalyzed cross-coupling reaction.
Although low reactivity of the carbaldehyde function of 6 at the
10-position is expected due to the electron-donating nature of the
azulene skeleton at this position, carbaldehyde 6 was transferred to
dibromoolefin 9 in 48% yield when the reaction was carried out at
50 ꢀC for 30 min with phosphorous ylide prepared with CBr4 and
Ph3P (Scheme 5). The spectral features of the ethynylated products
7 and 8 and the dibromoolefin 9 are in agreement with the struc-
ture of the products as summarized in Experimental section.
Scheme 2. Bromination of 1,2-dihydro-4-methyl-1-oxabenz[a]azulen-2-one (1a) with
NBS.
VilsmeiereHaack formylation might become another typical
example to explore the reactivities of the novel 1,2-dihydro-1-
oxabenz[a]azulen-2-one skeleton because of the efficiency of the
reaction in azulene derivatives and also deactivate the azulene
skeleton toward the multiple substitution reactions. Thus, the re-
action of 1a with phosphorous oxychloride in the presence of
dimethylformamide, following the treatment with 0.1 M NaOH,
was employed to obtain further aspect for the reactivity. The re-
action yielded 1,2-dihydro-4-methyl-2-oxo-1-oxabenz[a]azulene-
10-carbaldehyde (6) as reddish orange crystals in 78% yield
(Scheme 3). These results should be concluded that there are cer-
tain differences between the two reactive positions, 3- and 10-
positions. The spectral features of the mono- and dibromides 4
and 5 and carbaldehyde 6 are in agreement with the structure of
the products as summarized in Experimental section.
CBr4, Ph3P
O
6
O
Br
H
Br
9
POCl3, DMF
O
1a
O
Scheme 5. Conversion of 1,2-dihydro-4-methyl-2-oxo-1-oxabenz[a]azulene-10-
carbaldehyde (6) to dibromoolefin 9 by the reaction with phosphorous ylide pre-
pared with CBr4 and Ph3P.
CHO
6
We have recently reported the azulene substitution at its 1-
position act as an efficient terminal group for the acceleration of
the reaction of acetylenes with TCNE (tetracyanoethylene) and
TCNQ (tetracyanoquinodimethane) to afford azulene-substituted
TCBD (tetracyanobutadiene) and DCNQ (dicyanoquinodimethane)
chromophores.23 We have also reported dibromoolefin may be-
come a useful precursor for the enediyne scaffolds that contain
multiple redox-active chromophores.24 These reaction products
may also provide the further transformation as a useful building
block of these molecular materials for electronic applications.
Scheme 3. VilsmeiereHaack formylation of 1,2-dihydro-4-methyl-1-oxabenz[a]azu-
len-2-one (1a).
Reactivity of 1a toward the electrophilic reagents would be
attracted to the application for further transformation of these
molecular materials for electronic applications. To evaluate the
scope of the reaction products 4, 5, and 6 we have examined
Sonogashira cross-coupling reaction of the bromination products 4
and 5 with trimethylsilylacetylene and conversion of carbaldehyde
6 to dibromoolefin by the reaction with phosphorous ylide pre-
pared with CBr4 and Ph3P to accomplish effective extension of the
p-electron system.
2.2. Spectroscopic properties
Sonogashira cross-coupling reaction of bromide 4 with trime-
thylsilylacetylene was established under the palladium-catalyzed
conditions at 90 ꢀC for 24 h in a sealed-tube to afford the cross-
coupled product, 1,2-dihydro-4-methyl-1-oxa-10-(trimethylsilyle-
thynyl)benz[a]azulen-2-one (7) in 47% yield, along with the recovery
of the starting 4 in 9% yield (Scheme 4). The low reactivity to the
palladium-catalyzed reaction may be attributed to the high electron-
density of the azulene skeleton at the 10-position in bromide
4. We found the reaction afforded three products, when the dibro-
Mass spectrum of 1a (R1¼Me, R2¼H), 1b (R1¼Ph, R2¼H), and 1c
(R1¼Me, R2¼COOEt) and the related products measured by ESI-TOF
or MALDI-TOF conditions showed correct MþHþ ion peaks, which
afford a criterion of the structure of these compounds. The NMR
spectra of all of the new products in CDCl3 are summarized
in Supplementary data, which are consisted with the structure of
the products.
The typical examples of the UV and visible spectra of 1a and
the ethynylated products 7 and 8 in dichloromethane are shown in
mide
5
was employed to the cross-coupling reaction

S. Ito et al. / Tetrahedron 70 (2014) 2796e2803
2799
Figs. 3 and 4, respectively, the rest is summarized in Supplementary
data. The absorption spectrum of the compound 1a is quite similar
with those of its 4-phenyl and 10-COOEt derivatives 1b and 1c in
dichloromethane although some shift of the absorption band
was observed in the case of the longest wavelength absorption of
10-COOEt derivative 1c owing to the substituted electron-
withdrawing COOEt group. Compounds 1a and 1b showed the
characteristic weak absorption of the azulene system in the visible
region at lmax¼538 nm (log ε 2.63) and lmax¼531 nm (log ε 2.76),
respectively, that should be consisted with the small HOMOeLUMO
gap. The longest absorption maximum of 10-COOEt derivative 1c in
the visible region [lmax¼509 nm (log ε 2.88)] exhibits a blue shift by
29 nm, relative to that of 10-H derivative 1a.
(log ε 2.54) and 8 at lmax¼564 sh nm (log ε 2.82)] showed a distinct
red shift by 12 nm and 26 nm, respectively, relative to that of 1a that
should be consisted with effective extension of the
p-electron
system by the substituted ethynyl groups. Furthermore, the most
intense peak [7 at lmax¼354 nm (log ε 4.63) and 8 at lmax¼363 sh
nm (log ε 4.54)] and also characteristic absorption bands at around
400e500 nm showed similar spectral shift, compared with those of
1a. Thus, the both trimethylsilylethynyl groups on the azulene and
a-pyrone moieties effectively act as extension of the
p-electron
system (Fig. 4).
In contrast, introduction of the dibromoethenyl group at 10-
position showed little spectral shift in the longest wavelength ab-
sorption band [9 at lmax¼538 nm (log ε 2.60)], relative to that of 1a,
in dichloromethane, probably due to the electron-withdrawing
nature of the substituted two-bromine atoms and the less effec-
tive conjugation come from the twisted conformation of the sub-
stituent. Furthermore, the most intense peak of 9 [lmax¼341 nm
(log ε 4.63)] and also characteristic absorption bands at around
400 nm showed little spectral shift, compared with those of 1a. The
characteristic feature of the UV and visible spectra of 1a and its
related compounds was supported by TDDFT/TDA calculations at
the B3LYP/6-31G** level.
5
4
3
× 50
2
2.3. Redox properties
1
0
To clarify the electrochemical property of the fused system, the
redox behavior of 1a was examined by cyclic voltammetry (CV) and
differential pulse voltammetry (DPV) in benzonitrile containing
tetraethylammonium perchlorate (0.1 M) as a supporting electro-
lyte. Measurements were made by using a standard three electrode
configuration as platinum wire auxiliary and disk working elec-
trodes. 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 ob-
served at þ0.15 V on CV.
200
300
400
500
600
700
800
Wavelength / nm
Fig. 3. UV/Vis spectra of 1,2-dihydro-4-methyl-1-oxabenz[a]azulen-2-one (1a) in
dichloromethane.
5
Redox potentials (in volts vs Ag/AgNO3) of 1a along with those
of azulene (10) itself obtained under our measurement conditions
are summarized in Table 1. The CV waves of 1a are summarized
in Supplementary data. The compound 1a exhibited an irreversible
reduction wave on CV at ꢁ1.70 V. The Er1ed wave should correspond
to the one-electron injection forming a reactive radical anionic
species. The oxidation of 1a showed irreversible oxidation waves on
CV at 0.91 V, 1.30 V, and 2.15 V. The irreversibility should be as-
cribed to the electron removal from the fused system forming
a radical cationic species with high reactivity. The DPV analysis
supported the existence of the three-step oxidation that should
correspond to the formation of higher electronic states. The elec-
trochemical analyses revealed the decrease of both HOMO and
4
3
2
1
0
× 50
× 50
200
300
400
500
600
700
800
Wavelength / nm
Fig. 4. UV/Vis spectra of the ethynyl products 7 (solid line) and 8 (dotted line) in
dichloromethane.
Table 1
Redox potentialsa of 1a and parent azulene (10)b measured by CV and DPV
Sample
Er1ed [V]
Eo1x [V]
Eo2x [V]
Eo3x [V]
Relative to that of parent azulene (10) [lmax¼576 nm (log ε
2.51)], the longest wavelength absorption band of 1a exhibits a blue
shift by 38 nm in the same solvent.25 The most intense band of 1a
1a
(ꢁ1.70)
ꢁ1.67
dd
(þ0.91)
þ0.85
(þ1.30)
þ1.22
(þ2.15)
þ2.03
DPVc
10
(þ0.63)
þ0.59
(þ1.17)
þ1.11
DPVc
ꢁ1.95
[
lmax¼339 nm (log ε 4.66)] shows a red shift by 63 nm, compared
with that of 10 [lmax¼276 nm (log ε 4.66)]. The 1,2-dihydro-1-
oxabenz[a]azulen-2-one series also exhibited characteristic ab-
sorption bands at around 400 nm, e.g., lmax¼392 nm (log ε 4.06)
and lmax¼414 nm (log ε 4.08) in compound 1a.
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 on CV, which are
given in parentheses, Eox and Ered were calculated as Epa (anodic peak potential)
e0.03 V and Epc (cathodic peak potential) þ0.03 V, respectively.
Effective extension of the
p-electron system in the ethynyl
b
The redox potentials of 10 were measured under the same conditions.
The values indicated by italics are peak potentials measured by DPV.
The clear reduction wave could not obtained under the conditions of CV
products 7 and 8 has been revealed by the UV/Vis spectroscopic
analysis. Characteristic weak absorption of the azulene system in
the compounds 7 and 8 in the visible region [7 at lmax¼550 nm
c
d
measurement.

2800
S. Ito et al. / Tetrahedron 70 (2014) 2796e2803
LUMO energy levels compared with those of parent azulene (10),
which should be attributable to the fused heterocyclic systems.
Two-distinct conformations were optimized with the respect
to the dibromoethenyl group at 10-position. Within the structures
the conformer that lean the dibromoethenyl group to the seven-
membered ring side was the predominant (Fig. S-38
in Supplementary data). The twisted conformation with the di-
hedral angle 40ꢀ leads to the less effective conjugation between the
dibromoethenyl group and the 1,2-dihydro-1-oxabenz[a]azulen-2-
one core. The HOMO of 9 spread into the dibromoethenyl group as
shown in Supplementary data that accord with the extension of the
2.4. Theoretical calculations
To better understanding the electronic properties of the 1,2-
dihydro-1-oxabenz[a]azulen-2-one series, we have also per-
formed TDDFT/TDA calculations at the B3LYP/6-31G** level of 1,2-
dihydro-4-methyl-1-oxabenz[a]azulen-2-one (1a) and its 10-
COOMe derivative for simplification of 1c including radical cat-
ionic and anionic species of 1a as model compounds along with
azulene (10) for comparative studies.26 We have also examined the
p-electron system, but less effective effect in HOMO energy in 9,
probably due to the electron-withdrawing nature of the substituted
two-bromine atoms and the less effective conjugation come from
the twisted conformation of the substituent, consequently, resulted
to slight decrease in the HOMOeLUMO gap. The little spectral
shifts in 9, compared with those of 1a, should be concluded to the
little effect in the HOMOeLUMO gap by the dibromoethenyl
substituent.
effect of the extension of the
p-electron system by ethynyl and
dibromoethenyl substituents on the 1,2-dihydro-1-oxabenz[a]
azulen-2-one core utilizing the calculations at the B3LYP/6-31G**
level. The results on the calculations are summarized
in Supplementary data.
The calculations revealed that the fused a-pyrone system lowers
both the HOMO and the LUMO energies, relative to those of parent
azulene (10), but has much pronounced effect on the LUMO, con-
sequently leading to slight decrease in HOMOeLUMO gap (Fig. S-26
in Supplementary data). This is affected to the amphoteric redox
properties of the new system as observed by the voltammetric
analyses. The TDDFT/TDA calculations reproduced the blue shift in
the longest wavelength absorption band of 1a, relative to that of
parent azulene (10), which should be ascribed by the HOMO-
eLUMOþ1 character in the longest wavelength absorption in ad-
dition to the HOMOeLUMO transition. Characteristic absorption
bands at around 400 nm in the 1,2-dihydro-1-oxabenz[a]azulen-2-
one series is ascribed by the theoretical calculations to be HOMO-
eLUMOþ1 and HOMOe1ꢁLUMO transitions, in which the molec-
ular orbitals are also spread into the whole molecule. The blue shift
in the 10-COOEt derivative 1c should be explained by the electron-
withdrawing nature of the COOEt group that should lower the
HOMO energy but has less pronounced effect on the LUMO as
similar with the azulene derivatives, consequently, leading to an
increased HOMOeLUMO gap.
3. Conclusions
Three new members of 1,2-dihydro-1-oxabenz[a]azulen-2-one
derivatives, 1a (R1¼H, R2¼Me), 1b (R1¼H, R2¼Ph), and 1c
(R1¼COOEt, R2¼Me) have been successfully synthesized by Lewis
acid catalyzed condensation reaction of 2-hydroxyazulenes 2a and
2b with ethyl acetoacetate (3a) or ethyl benzoylacetate (3b). Thus,
the present procedure may have generality for the formation of 1,2-
dihydro-1-oxabenz[a]azulen-2-one skeleton, but in some cases the
yield of the products is relatively low. However, 1,2-dihydro-4-
methyl-1-oxabenz[a]azulen-2-one (1a) was obtained by the re-
action of 2-hydroxyazulene (2a) with ethyl acetoacetate (3a) in the
presence of aluminum chloride in satisfactory yield for further
transformations. Thus, the reactivities of the new 1,2-dihydro-1-
oxabenz[a]azulen-2-one derivative 1a are revealed by the bromi-
nation utilizing NBS and VilsmeiereHaack formylation reactions.
The reactive positions of the 1,2-dihydro-1-oxabenz[a]azulene
moiety toward the electrophiles were revealed as the 10-position
that correspond to the most reactive position of azulene nucleus
along with 3-position of the heterocyclic moiety that match with
the reactive position of coumarin derivatives.27 To evaluate the
scope of the reaction products we have examined Sonogashira
cross-coupling reaction of the bromination products 4 and 5 with
trimethylsilylacetylene and conversion of the formylation product
6 to dibromoolefin 9 by the reaction with phosphorous ylide pre-
pared with CBr4 and Ph3P. Thus, these reaction products would be
attracted to the application as a terminal group for electronic
applications.
The spectroscopic properties of 1,2-dihydro-1-oxabenz[a]azu-
len-2-one derivatives, 1a (R1¼H, R2¼Me), 1b (R1¼H, R2¼Ph), and 1c
(R1¼COOEt, R2¼Me) have been clarified and were compared with
those of azulene (10) itself. As suggested by the DFT calculations,
the absorption spectrum of the new members of 1,2-dihydro-1-
oxabenz[a]azulen-2-one derivatives revealed the small HOMO-
eLUMO gap as similar with that of azulene (10) itself. The analyses
revealed the decrease of both HOMO and LUMO energy levels,
which should be attributable to the fused heterocyclic systems. The
amphoteric redox properties observed by the electrochemical
analysis of 1a is also reflected by the small HOMOeLUMO gap of the
product as similar with that of azulene (10) itself. Distinct red shift
in the characteristic absorption bands in the visible region of the
ethynyl derivatives 7 and 8, relative to that of 1a, is consisted with
As shown in Supplementary data, the HOMO of 1a spread into
the whole molecule with the respect to the azulene nucleus and
fused a-pyrone moiety, while the most of the LUMO of 1a localized
on the azulene part. Electrostatic potential map of the radical cat-
ionic species of 1a represented to the delocalization of the most of
charges on the whole molecule, while in the radical anionic species
of 1a localized the most of charges on the azulene part. Spin density
also distributes on the whole molecule in the radical cationic state,
whereas that of the radical anionic state mainly localizes on the
azulene part. Therefore, the amphoteric redox behaviors of 1,2-
dihydro-4-methyl-1-oxabenz[a]azulen-2-one (1a) are responsible
to the stabilization by the fused azulene moiety.
The calculations of 7 and 8 also reproduced the extension of the
p-electron system by both ethynyl groups at 3- and 10-positions,
which possess large coefficient in HOMO of 1a, but little contri-
bution in LUMO of 1a. The calculations revealed that the HOMO of 7
and 8 spread into both ethynyl groups at 3- and 10-positions, while
the most of the LUMO of 7 and 8 localized on the 1,2-dihydro-1-
oxabenz[a]azulen-2-one core. Thus, the
p-electron system effec-
tively extended by the both ethynyl groups at 3- and 10-positions,
which lower both the HOMO and the LUMO energies, relative to
those of parent 1a, but has much pronounced effect on the HOMO,
consequently, leading to decrease in HOMOeLUMO gap (Fig. S-27
in Supplementary data). The TDDFT/TDA calculations reproduced
the distinct red shift in the longest wavelength absorption band of 7
and 8, relative to that of 1a, which should be ascribed by the
HOMOeLUMO transition and also the HOMOeLUMOþ1 character
the effective extension of the p-electron system by the substituted
ethynyl groups at both 3- and 10-positions.
Reactivity of 1a toward electrophilic reagents would be attrac-
ted to the application for further transformation of these molecular
materials for electronic applications. The investigation of biological
activities of the new systems is a task for the future, in relation to
in 8 that should be consisted with effective extension of the
p-
electron system by the substituted ethynyl groups.

S. Ito et al. / Tetrahedron 70 (2014) 2796e2803
2801
a wide range of biological activities of the coumarin derivatives. The
synthesis of novel -electron systems by the fusion of azulene
derivatives with other heterocyclic systems are currently under
investigation in our laboratory.
under reduced pressure. The residue was purified by column
chromatography on silica gel with ethyl acetate/hexane (1:4) to
afford 1b (29 mg, 10%). Dark purple crystals; mp 158.0e159.4 ꢀC
p
(toluene); 1H NMR (500 MHz, CDCl3):
d¼8.38 (d, 1H, J¼10.0 Hz, 9-
H), 7.89 (d, 1H, J¼9.7 Hz, 5-H), 7.61 (dd, 1H, J¼10.2, 9.4 Hz, 7-H),
7.58e7.51 (m, 5H, 4-Ph), 7.40 (dd, 1H, J¼10.0, 9.4 Hz, 8-H), 7.17 (s,
1H, 10-H), 7.14 (dd, 1H, J¼10.2, 9.7 Hz, 6-H), 6.08 (s, 1H, 3-H); 13C
4. Experimental section
4.1. General
NMR (125 MHz, CDCl3):
d¼162.88 (C-10a), 162.37 (C-2), 154.82 (C-
4), 142.84 (C-9a), 137.17 (s, 4-Ph), 136.96 (C-9), 136.82 (C-7), 134.20
(C-5), 134.09 (C-4b), 129.43 (d, 4-Ph), 128.88 (d, 4-Ph), 127.83 (d, 4-
Ph), 127.49 (C-8), 126.94 (C-6), 108.79 (C-3), 107.84 (C-4a), 103.88
(C-10); IR (KBr disk): nmax¼3049 (w), 1723 (s), 1593 (w), 1578 (w),
1561 (m), 1514 (s), 1475 (m), 1450 (m), 1435 (w), 1399 (m), 1363 (w),
1304 (w), 1272 (w), 1222 (w), 1174 (w), 1071 (w), 972 (w), 931 (w),
875 (w), 852 (w), 829 (m), 787 (w), 769 (m), 705 (w), 684 (w), 639
(w), 624 (w) cmꢁ1; UV/Vis (CH2Cl2): lmax (log ε)¼278 sh (4.10), 295
(4.22), 330 sh (4.42), 344 (4.52), 358 sh (4.27), 373 sh (3.96), 397
(4.06), 418 (4.05), 501 sh (2.75), 531 (2.76), 582 sh (2.62), 638 sh
(2.23) nm; HRMS (ESI positive) calcd for C19H12O2þHþ 273.0911;
found 273.0902. Anal. Calcd for C19H12O2$1/3H2O: C, 82.00; H, 4.59;
found: C, 82.35; H, 5.01.
Melting points were determined on a Stuart Scientific melting
point apparatus SMP3 or a Yanagimoto micro melting point appa-
ratus MP-S3 and are uncorrected. Mass spectra were obtained with
a Hitachi NanoFrontier LD instrument under ESI conditions or
a Bruker Daltonics autoflex III TOF/TOF instrument under MALDI-
TOF conditions. IR and UV spectra were measured on a JUSCO FT/
IR-6100 or a Varian 670-IR and a JASCO V-670 spectrophotome-
ters, respectively. 1H NMR spectra (13C NMR spectra) were recorded
on a JEOL ECA500 spectrometer at 500 MHz (125 MHz). 1H NMR
chemical shifts in CDCl3 are reported in parts per million (ppm)
downfield from tetramethylsilane. 13C NMR chemical shifts in CDCl3
are referred by the solvent signals as 77.0 ppm. The peak assignment
of 1H and 13C NMR spectra reported was accomplished by HH COSY,
DEPT, HMQC, and HMBC experiments. Elemental analyses were
performed at the Instrumental Analysis Center of Hirosaki Univer-
sity. The voltammetry measurements were carried out in benzoni-
trile containing Et4NClO4 (0.1 M) as a supporting electrolyte utilizing
Pt working and auxiliary electrodes, and a reference electrode
formed from Ag/AgNO3 (0.01 M) in acetonitrile containing n-
Bu4NClO4 (0.1 M) at the scan rate of 100 mV sꢁ1. The internal ref-
erence Fc/Fcþ discharges at þ0.15 V under these conditions.
4.1.3. Ethyl 1,2-dihydro-4-methyl-1-oxa-2-oxobenz[a]azulene-10-
carboxylate (1c). A solution of ethyl 2-hydroxyazulene-1-
carboxylate (2b) (219 mg, 1.01 mmol), ethyl acetoacetate (3a)
(172 mg,1.32 mmol), and aluminum chloride (281 mg, 2.11 mmol) in
1,2-dichloroethane (15 mL) was refluxed for 15 h. The reaction
mixture was poured into 2 M HCl solution and extracted with
dichloromethane. 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 ethyl
acetate/hexane (1:2) to afford 1c (33 mg, 12%). Reddish orange
crystals; mp 219.4e222.9 ꢀC (toluene); 1H NMR (500 MHz, CDCl3):
4.1.1. 1,2-Dihydro-4-methyl-1-oxabenz[a]azulen-2-one (1a). A solu-
tion of 2-hydroxyazulene (2a) (502 mg, 3.48 mmol) and ethyl
acetoacetate (3a) (491 mg, 3.77 mmol) in 1,2-dichloroethane
(50 mL) was refluxed for 15 h in the presence of aluminum chlo-
ride (1.00 g, 7.50 mmol). The reaction mixture was poured into 2 M
HCl solution and extracted with dichloromethane. The organic layer
was washed with brine, dried over MgSO4, and concentrated under
reduced pressure. The residue was purified by column chroma-
tography on silica gel with ethyl acetate/hexane (1:4) to afford 1a
(419 mg, 57%). Brownish orange crystals; mp 168.0e170.0 ꢀC (tol-
d
¼9.75 (d, 1H, J¼10.2 Hz, 9-H), 8.83 (d, 1H, J¼10.0 Hz, 5-H), 7.87 (dd,
1H, J¼9.8, 9.6 Hz, 7-H), 7.72 (dd,1H, J¼10.2, 9.6 Hz, 8-H), 7.65 (dd,1H,
J¼10.0, 9.8 Hz, 6-H), 6.06 (s, 1H, 3-H), 4.50 (q, 2H, J¼7.1 Hz, 10-
COOEt), 2.76 (s, 3H, 4-Me), 1.50 (t, 3H, J¼7.1 Hz, 10-COOEt); 13C
NMR (125 MHz, CDCl3):
d¼163.99 (10-COOEt),161.86 (C-10a),161.30
(C-2), 151.53 (C-4), 143.27 (C-9a), 138.46 (C-7), 137.71 (C-9), 136.77
(C-4b), 134.93 (C-5), 131.44 (C-8), 129.85 (C-6), 110.09 (C-3), 108.68
(C-4a), 103.13 (C-10), 60.43 (10-COOEt), 22.29 (4-Me), 14.53 (10-
COOEt); IR (KBr disk): nmax¼2921 (w), 1729 (s), 1715 (s), 1683 (w),
1663 (m), 1586 (m), 1556 (w), 1523 (s), 1457 (s), 1414 (w), 1296 (w),
1253 (m), 1202 (m), 1172 (w), 1089 (m), 1034 (m), 932 (w), 892 (w),
861 (w), 785 (w) cmꢁ1; UV/Vis (CH2Cl2): lmax (log ε)¼252 sh (4.10),
262 sh (3.98), 273 sh (3.85), 298 sh (4.34), 313 (4.57), 327 (4.64), 336
sh (4.63), 341 (4.67), 374 (3.92), 394 (3.96), 413 (4.64), 482 sh (2.83),
509 (2.88), 551 sh (2.74), 604 sh (2.17) nm; HRMS (ESI positive) calcd
for C17H14O4þKþ 321.0524; found 321.0483; HRMS (ESI positive)
calcd for C17H14O4þNaþ 305.0784; found 305.0753; HRMS (ESI
positive) calcd for C17H14O4þHþ 283.0965; found 283.0951. Anal.
Calcd for C17H14O4: C, 72.33; H, 5.00; found: C, 72.16; H, 4.96.
uene); 1H NMR (500 MHz, CDCl3):
8.35 (d,1H, J¼9.7 Hz, 9-H), 7.69 (dd,1H, J¼9.6, 9.3 Hz, 7-H), 7.45 (dd,
1H, J¼9.6, 9.3 Hz, 6-H), 7.41 (dd, 1H, J¼9.7, 9.3 Hz, 8-H), 7.08 (s, 1H,
10-H), 6.03 (s, 1H, 3-H), 2.77 (s, 3H, 4-Me); 13C NMR (125 MHz,
d
¼8.70 (d, 1H, J¼9.3 Hz, 5-H),
CDCl3):
d¼162.65 (C-10a), 162.32 (C-2), 152.21 (C-4), 142.41 (C-9a),
136.80 (C-9), 136.59 (C-7), 134.66 (C-4b), 133.69 (C-5), 127.25 (C-8),
126.86 (C-6), 109.12 (C-4a), 108.90 (C-3), 103.81 (C-10), 21.88 (4-
Me); IR (KBr disk): nmax¼3102 (w), 2972 (w), 1699 (s), 1593 (w),
1569 (m), 1517 (s), 1481 (w), 1450 (m), 1397 (m), 1368 (w), 1308 (w),
1280 (w), 1204 (w), 1173 (w), 1058 (w), 1043 (w), 1020 (w), 935 (w),
914 (w), 878 (m), 820 (w), 787 (m), 752 (w), 729 (m), 675 (w), 621
(w), 599 (w), 576 (w), 537 (w) cmꢁ1; UV/Vis (CH2Cl2): lmax (log ε)¼
253 (3.85), 274 (3.96), 288 (4.08), 300 (4.17), 326 (4.61), 336 sh
(4.65), 339 (4.66), 353 sh (4.21), 372 sh (3.92), 392 (4.06), 414 (4.08),
504 sh (2.57), 538 (2.63), 583 sh (2.48), 643 sh (1.91) nm; HRMS (ESI
positive) calcd for C14H10O2þHþ 211.0754; found 211.0736. Anal.
Calcd for C14H10O2: C, 79.98; H, 4.79; found: C, 80.04; H, 4.92.
4.1.4. 10-Bromo-1,2-dihydro-4-methyl-1-oxabenz[a]azulen-2-one
(4). To a solution of 1,2-dihydro-4-methyl-1-oxabenz[a]azulen-2-
one (1a) (40 mg, 0.19 mmol) in dichloromethane (2 mL) was
added N-bromosuccinimide (NBS) (36 mg, 0.20 mmol) at room
temperature. After the solution was stirred at the same tempera-
ture for 2.5 h, the reaction mixture was concentrated under re-
duced pressure. The residue was purified by column
chromatography on silica gel with ethyl acetate/dichloromethane
(1:2) to afford 4 (23 mg, 42%), 3,10-dibromo-1,2-dihydro-4-methyl-
1-oxabenz[a]azulen-2-one (5) (22 mg, 31%), and the recovered 1a
(8.6 mg, 22%).
4.1.2. 1,2-Dihydro-1-oxa-4-phenylbenz[a]azulen-2-one (1b). A so-
lution of 2-hydroxyazulene (2a) (148 mg, 1.03 mmol) and ethyl
benzoylacetate (2b) (267 mg, 1.39 mmol) in 1,2-dichloroethane
(15 mL) was refluxed for 15 h in the presence of aluminum chlo-
ride (296 mg, 2.22 mmol). The reaction mixture was poured into
2 M HCl solution and extracted with dichloromethane. The organic
layer was washed with brine, dried over MgSO4, and concentrated
Compound 4: Yellowish brown crystals; mp 189.1e189.4 ꢀC
(toluene); 1H NMR (500 MHz, CDCl3):
d
¼8.68 (d, 1H, J¼9.7 Hz, 5-H),

2802
S. Ito et al. / Tetrahedron 70 (2014) 2796e2803
8.45 (d, 1H, J¼10.1 Hz, 9-H), 7.75 (dd, 1H, J¼9.7, 9.7 Hz, 7-H), 7.52
(dd, 1H, J¼10.1, 9.7 Hz, 8-H), 7.50 (dd, 1H, J¼9.7, 9.7 Hz, 6-H), 6.05 (s,
(4.59), 380 sh (3.83), 404 (3.93), 422 (3.95), 483 sh (2.97), 504
(2.99), 545 sh (2.83), 599 sh (2.21) nm; HRMS (ESI positive) calcd
for C15H10O3þNaþ 261.0522; found 261.0535; HRMS (ESI positive)
calcd for C15H10O3þHþ 239.0703; found 239.0702. Anal. Calcd for
1H, 3-H), 2.78 (s, 3H, 4-Me); 13C NMR (125 MHz, CDCl3):
d¼161.21
(C-2), 158.92 (C-10a), 151.66 (C-4), 138.04 (C-9a), 137.55 (C-7),
135.35 (C-9), 134.08 (C-4b), 133.93 (C-5), 127.81 (C-8), 127.41 (C-6),
109.62 (C-3), 108.42 (C-4a), 91.22 (C-10), 21.88 (4-Me); IR (KBr
disk): nmax¼3062 (w), 2910 (w), 1733 (w), 1597 (m), 1579 (m), 1520
(s), 1486 (w), 1456 (m), 1444 (w), 1392 (m), 1374 (w), 1306 (w), 1283
(w), 1072 (w), 921 (w), 878 (m), 828 (w), 747 (m), 727 (w), 664 (w),
603 (w) cmꢁ1; UV/Vis (CH2Cl2): lmax (log ε)¼260 (3.75), 276 (3.78),
293 sh (4.02), 306 sh (4.18), 330 (4.52), 342 sh (4.55), 343 (4.56),
359 sh (4.07), 382 (3.77), 402 (3.94), 423 (3.90), 517 sh (2.39), 546
(2.42), 593 sh (2.24), 652 sh (1.39) nm; HRMS (ESI positive) calcd for
C15H10O3: C, 75.62; H, 4.23; found: C, 75.37; H, 4.23.
4.1.7. 1,2-Dihydro-4-methyl-1-oxa-10-(trimethylsilylethynyl)benz[a]
azulen-2-one (7). To a solution of 10-bromo-1,2-dihydro-4-methyl-
1-oxabenz[a]azulen-2-one (4) (16 mg, 0.055 mmol), trimethylsily-
lacetylene (315 ml, 2.23 mmol), CuI (5.1 mg, 0.027 mmol), and trie-
thylamine (5 mL) in THF (10 mL) was added Pd(Ph3P)4 (14 mg,
0.012 mmol). The resulting mixture was stirred at 90 ꢀC for 24 h in
an autoclave. The reaction mixture was washed with 5% NH4Cl so-
lution, dried over MgSO4, and concentrated under reduced pressure.
The residue was purified by column chromatography on silica gel
with dichloromethane/hexane (3:1) and GPC with chloroform to
afford 7 (8.0 mg, 47%) and the recovered 4 (1.4 mg, 9%). Brown
crystals; mp 238.9e241.0 ꢀC decomp. (CH2Cl2/hexane); 1H NMR
C
C
14H9BrO2þHþ 288.9859; found 288.9852. Anal. Calcd for
14H9BrO2: C, 58.16; H, 3.14; found: C, 58.35; H, 3.44.
4.1.5. 3,10-Dibromo-1,2-dihydro-4-methyl-1-oxabenz[a]azulen-2-
one (5). To a solution of 1,2-dihydro-4-methyl-1-oxabenz[a]azu-
len-2-one (1a) (100 mg, 0.476 mmol) in dichloromethane (2.5 mL)
was added N-bromosuccinimide (NBS) (175 mg, 0.983 mmol) at
room temperature. After the solution was stirred at the same
temperature for 1 h, the reaction mixture was poured into water
and extracted with dichloromethane. 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 dichloromethane to afford 5 (159 mg, 91%). Brown
crystals; mp 193.4e194.3 ꢀC (toluene); 1H NMR (500 MHz, CDCl3):
(500 MHz, CDCl3):
d
¼8.71 (d, 1H, J¼9.7 Hz, 5-H), 8.64 (d, 1H,
J¼10.2 Hz, 9-H), 7.76 (dd, 1H, J¼10.0, 9.7 Hz, 7-H), 7.53 (dd, 1H,
J¼10.2, 9.7 Hz, 8-H), 7.51 (dd, 1H, J¼10.0, 9.7 Hz, 6-H), 6.09 (d, 1H,
J¼1.0 Hz, 3-H), 2.79 (d, 3H, J¼1.0 Hz, 4-Me), 0.35 (s, 9H, TMS); 13C
NMR (125 MHz, CDCl3):
d
¼162.09 (C-10a),161.66 (C-2),151.73 (C-4),
143.62 (C-9a),137.77 (C-7),136.42 (C-9), 134.70 (C-4b),134.23 (C-5),
128.36 (C-6 or C-8), 128.34 (C-6 or C-8), 119.06 (C-3), 108.35 (C-4a),
103.95 (C^C), 98.30 (C-10), 95.24 (C^C), 21.93 (4-Me), 0.22 (TMS);
IR (KBr disk): nmax¼2960 (m), 2901 (m), 2869 (w), 2142 (s, C^C),
1735 (s, C]O), 1732 (s, C]O), 1637 (w), 1600 (s), 1583 (s), 1531 (s),
1471 (s), 1457 (s), 1452 (s), 1410 (s), 1401 (m), 1381 (w), 1325 (w),
1288 (m), 1246 (s), 1217 (w), 1179 (w), 1103 (m), 1022 (m), 991 (w),
930 (m), 926 (w), 883 (m), 856 (s), 841 (s), 821 (m), 765 (m), 755 (m),
733 (w), 718 (w), 695 (w), 653 (m), 603 (w), 575 (w), 557 (w), 502
(w) cmꢁ1; UV/Vis (CH2Cl2): lmax (log ε)¼251 sh (4.24), 256 (4.24),
267 sh (4.14), 323 (4.57), 339 (4.62), 351 sh (4.62), 354 (4.63), 367 sh
(4.09), 393 (3.85), 414 (3.99), 438 (3.91), 526 (2.54), 550 (2.54), 608
sh (2.28), 670 sh (1.50) nm; HRMS (MALDI-TOF, dithranol) calcd for
d¼8.80 (d, 1H, J¼9.7 Hz, 5-H), 8.51 (d, 1H, J¼10.3 Hz, 9-H), 7.80 (dd,
1H, J¼10.2, 9.5 Hz, 7-H), 7.58 (dd, 1H, J¼10.3, 9.5 Hz, 8-H), 7.56 (dd,
1H, J¼10.2, 9.7 Hz, 6-H), 3.02 (s, 3H, 4-Me); IR (KBr disk):
nmax¼2921 (w), 1733 (s), 1599 (w), 1576 (m),1546 (w),1523 (s), 1473
(w), 1458 (w), 1438 (m), 1389 (m), 1371 (w), 1301 (w), 1252 (w),
1226 (w), 1076 (w), 1023 (w), 945 (m), 913 (w), 831 (w), 746 (m),
700 (w), 650 (w) cmꢁ1; UV/Vis (CH2Cl2): lmax (log ε)¼267 (3.93),
281 (3.96), 299 sh (4.12), 312 (4.21), 339 (4.51), 349 sh (4.54), 352
(4.54), 366 sh (4.20), 391 sh (3.93), 411 (4.13), 434 (4.12), 519 sh
(2.59), 542 (2.60), 599 sh (2.38), 661 sh (1.50) nm; HRMS (ESI
positive) calcd for C14H8Br2O2þHþ 366.8964; found 366.8937. Anal.
Calcd for C14H8Br2O2: C, 45.69; H, 2.19; found: C, 45.96; H, 2.53. Low
solubility hampered the measurement of 13C NMR.
C
19H18O2SiþHþ 307.1149, found 307.1149; HRMS (MALDI-TOF,
dithranol) calcd for C19H18O2Siþ 306.1071, found 306.1033. Anal.
Calcd for C19H18O2Si: C, 74.47; H, 5.92; found: C, 74.34; H, 5.78.
4.1.8. 1,2-Dihydro-4-methyl-1-oxa-3,10-bis(trimethylsilylethynyl)
4.1.6. 1,2-Dihydro-4-methyl-1-oxa-2-oxobenz[a]azulene-10-
carbaldehyde (6). To a solution of 1,2-dihydro-4-methyl-1-oxabenz
[a]azulen-2-one (1a) (108 mg, 0.514 mmol) in dimethylformamide
(10 mL) was added phosphorus oxychloride (250 ml, 2.68 mmol) at
room temperature. The resulting mixture was stirred at room
temperature for 2 h. The reaction mixture was poured into water,
benz[a]azulen-2-one (8). To
dihydro-4-methyl-1-oxabenz[a]azulen-2-one
a
solution of 3,10-dibromo-1,2-
(5) (99 mg,
0.27 mmol), trimethylsilylacetylene (1.91 mL, 13.5 mmol), CuI
(11 mg, 0.058 mmol), and triethylamine (10 mL) in THF (25 mL) was
added Pd(Ph3P)4 (32 mg, 0.028 mmol). The resulting mixture was
stirred at 90 ꢀC for 24 h in an autoclave. The reaction mixture was
washed with 5% NH4Cl solution, dried over MgSO4, and concen-
trated under reduced pressure. The residue was purified by column
chromatography on silica gel with dichloromethane/hexane (3:1)
and GPC with chloroform to afford 8 (29 mg, 27%), 10-bromo-1,2-
dihydro-4-methyl-1-oxabenz[a]azulen-2-one (4) (4.9 mg, 6%),
and 1,2-dihydro-4-methyl-1-oxa-10-(trimethylsilylethynyl)benz[a]
azulen-2-one (7) (44 mg, 53%).
made alkaline with 0.1
M NaOH, and then extracted with
dichloromethane. The organic layer was washed with brine, dried
with MgSO4, and concentrated under reduced pressure. Hexane
was added to the residue. The precipitated crystals were collected
by filtration, washed with hexane, and dried in vacuo to afford 6
(96 mg, 78%). Reddish orange crystals; mp >350 ꢀC (toluene); 1H
NMR (500 MHz, CDCl3):
d
¼10.60 (s, 1H, 10-CHO), 9.92 (d, 1H,
J¼10.3 Hz, 9-H), 8.96 (d, 1H, J¼10.0 Hz, 5-H), 7.98 (dd, 1H, J¼9.7,
9.7 Hz, 7-H), 7.87 (dd, 1H, J¼10.3, 9.7 Hz, 8-H), 7.79 (dd, 1H, J¼10.0,
9.7 Hz, 6-H), 6.16 (d, 1H, J¼1.1 Hz, 3-H), 2.83 (d, 3H, J¼1.1 Hz, 4-Me);
Compound 8: Yellowish brown crystals; mp 271.5e275.7 ꢀC
decomp. (CH2Cl2/hexane); 1H NMR (500 MHz, CDCl3):
d
¼8.78 (d,
1H, J¼9.7 Hz, 5-H), 8.62 (d, 1H, J¼10.1 Hz, 9-H), 7.78 (dd, 1H, J¼10.2,
9.5 Hz, 7-H), 7.56 (dd, 1H, J¼10.1, 9.5 Hz, 8-H), 7.54 (dd, 1H, J¼10.2,
9.7 Hz, 6-H), 3.01 (s, 3H, 4-Me), 0.35 (s, 9H TMS), 0.31 (s, 9H, TMS);
13C NMR (125 MHz, CDCl3):
d¼184.62 (10-CHO), 165.01 (C-10a),
160.70 (C-2), 152.01 (C-4), 141.96 (C-9a), 139.51 (C-7), 139.03 (C-9),
138.51 (C-4b), 135.94 (C-5), 134.02 (C-8), 131.45 (C-6), 110.36 (C-3),
110.07 (C-10),108.75 (C-4a), 22.23 (4-Me); IR (KBr disk): nmax¼2927
(w), 1733 (s), 1718 (w), 1650 (s), 1583 (m), 1524 (s), 1476 (w), 1455
(s), 1420 (w), 1399 (w), 1372 (m), 1314 (w), 1289 (w), 1197 (w), 1025
(m), 946 (w), 922 (w), 881 (m), 775 (w), 763 (w), 683 (w), 649 (w),
606 (w), 552 (w) cmꢁ1; UV/Vis (CH2Cl2): lmax (log ε)¼253 sh (4.00),
259 (4.03), 270 (4.00), 324 sh (4.65), 330 (4.66), 341 sh (4.60), 345
13C NMR (125 MHz, CDCl3):
d
¼160.19 (C-2 or C-10a), 160.04 (C-2 or
C-10a), 153.91 (C-4), 144.56 (C-9a), 138.34 (C-7), 136.43 (C-9),
134.95 (C-4b), 134.59 (C-5), 129.14 (C-6 or C-8), 129.08 (C-6 or C-8),
108.14 (C-4a), 105.27 (C-3), 104.44 (C^C), 104.38 (C^C), 98.98
(C^C), 98.42 (C-10), 94.95 (C^C), 19.98 (4-Me), 0.22 (TMS), 0.06
(TMS); IR (KBr disk): nmax¼2959 (m), 2899 (m), 2871 (w), 2146 (s,
C^C), 1733 (s, C]O), 1628 (w), 1601 (m), 1581 (w), 1532 (s), 1487

S. Ito et al. / Tetrahedron 70 (2014) 2796e2803
2803
(m), 1447 (s), 1405 (m), 1373 (w), 1325 (w), 1306 (w), 1284 (w), 1249
(s), 1211 (w), 1183 (w), 1132 (w), 1086 (m), 1008 (m), 946 (w), 930
(w), 858 (s), 843 (s), 763 (m), 706 (w), 668 (w), 618 (w), 567 (w)
cmꢁ1; UV/Vis (CH2Cl2): lmax (log ε)¼248 (4.51), 265 sh (4.33), 293
(4.23), 318 sh (4.28), 337 (4.45), 339 (4.45), 356 sh (4.51), 363 (4.54),
373 (4.54), 379 (4.54), 413 sh (4.08), 436 (4.25), 464 (4.27), 528 sh
(2.88), 564 sh (2.82), 618 sh (2.54), 691 sh (1.68) nm; HRMS
31G** method. Supplementary data related to this article can be
found at http://dx.doi.org/10.1016/j.tet.2014.02.073.
References and notes
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(MALDI-TOF, dithranol) calcd for
C
24H26O2Si2þHþ 403.1544,
found 403.1544; HRMS (MALDI-TOF, dithranol) calcd for
C
24H26O2Siþ2 402.1466, found 402.1469. Anal. Calcd for C24H26O2Si2:
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azulen-2-one (9). A mixture of 1,2-dihydro-4-methyl-1-oxabenz[a]
azulen-2-one-10-carbaldehyde (6) (15 mg, 0.063 mmol), CBr4
(218 mg, 0.657 mmol), and Ph3P (280 mg, 1.07 mmol) in 1,2-
dichloroethane (10 mL) was stirred at 50 ꢀC for 30 min under an
Ar atmosphere. The reaction mixture was concentrated under re-
duced pressure. The residue was purified by column chromatog-
raphy on silica gel with ethyl acetate/hexane (2:3) to afford 9
(12 mg, 48%). Reddish brown crystals; mp 170.4e173.7 ꢀC decomp.
ꢀ
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(CH2Cl2/hexane); 1H NMR (500 MHz, CDCl3):
d
¼8.79 (d, 1H,
J¼9.5 Hz, 5-H), 8.31 (d, 1H, J¼10.2 Hz, 9-H), 7.82 (s, 1H, 10-H), 7.79
(dd, 1H, J¼10.1, 9.3 Hz, 7-H), 7.55 (dd, 1H, J¼10.2, 9.3 Hz, 8-H), 7.54
(dd, 1H, J¼10.1, 9.5 Hz, 6-H), 6.10 (d, 1H, J¼1.0 Hz, 3-H), 2.82 (d, 3H,
J¼1.0 Hz, 4-Me); 13C NMR (125 MHz, CDCl3):
¼161.74 (C-2), 159.42
d
(C-10a), 152.06 (C-4), 137.46 (C-7), 137.43 (C-9a), 135.86 (C-9),
135.19 (C-4b), 134.21 (C-5), 128.60 (C-10), 127.89 (C-6), 127.83 (C-8),
110.96 (C-10), 109.42 (C-3), 108.52 (C-4a), 94.79 (C-20), 22.04 (4-
Me); IR (KBr disk): nmax¼2924 (s), 2852 (m), 1732 (s, C]O), 1715 (s,
C]O), 1628 (m), 1597 (m), 1583 (m), 1524 (s), 1479 (m), 1450 (s),
1406 (m),1387 (w), 1372 (w), 1316 (w), 1292 (w), 1185 (w), 1106 (w),
1021 (w), 926 (w), 892 (w), 874 (w), 836 (m), 792 (w), 755 (m), 737
(w), 693 (w), 604 (w), 564 (w) cmꢁ1; UV/Vis (CH2Cl2): lmax (log ε)¼
265 (4.10), 277 sh (4.03), 334 (4.63), 341 (4.63), 401 (3.98), 420
(3.96), 508 sh (2.58), 538 (2.60), 591 sh (2.41), 651 sh (1.85) nm;
HRMS (MALDI-TOF, dithranol) calcd for C16H10Br2O2þHþ 392.9120,
found 392.9129. Anal. Calcd for C16H10Br2O2: C, 48.77; H, 2.56;
found: C, 48.91; H, 2.75.
Acknowledgements
This work was supported by JSPS KAKENHI Grant Numbers
21550031, 24550037 to S.I.
Supplementary data
25. Ito, S.; Okujima, T.; Kabuto, C.; Morita, N. Tetrahedron 2003, 59, 4651e4659.
26. The B3LYP/6-31G** density functional calculations were performed by Spar-
tan’10, Wavefunction: Irvine, CA.
27. Reddy, C. R.; Srikanth, B.; Rao, N. N.; Shin, D.-S. Tetrahedron 2008, 64,
11666e11672.
UV/Vis spectra of 1b and 1c and related compounds; cyclic
voltammograms of 1a; Copies of 1H and 13C NMR spectra of the
reported compounds; DFT calculation results based on B3LYP/6-