Novel efficient synthesis and properties of 5,6-dihydrocyclohepta[b]indol- 6-one, and its transformation to 6-azolyl-5-azabenz[b]azulenes

Article abstract of DOI:10.3987/COM-12-S(N)60

The title compound, 5,6-dihydrocyclohepta[b]indol-6-one (1), was synthesized from 2-chlorotropone (7) by a two-step sequence involving Pd-catalyzed amination with 2-bromoaniline (15) and subsequent Pd-catalyzed intramolecular Heck reaction. Besides its sy

Full text of DOI:10.3987/COM-12-S(N)60

HETEROCYCLES, Vol. 86, No. 1, 2012
623
HETEROCYCLES, Vol. 86, No. 1, 2012, pp. 623 - 636. © 2012 The Japan Institute of Heterocyclic Chemistry
Received, 26th June, 2012, Accepted, 3rd August, 2012, Published online, 13th August, 2012
DOI: 10.3987/COM-12-S(N)60
NOVEL
EFFICIENT
SYNTHESIS
AND
PROPERTIES
AND
OF
5
,6-DIHYDROCYCLOHEPTA[b]INDOL-6-ONE,
ITS
TRANSFORMATION TO 6-AZOLYL-5-AZABENZ[b]AZULENES
Mitsunori Oda,* Kunihiro Ito, Hiroshi Takagi, and Yurie Fujiwara
Department of Chemistry, Faculty of Science, Shinshu University, Asahi 3-1-1,
Matsumoto, Nagano, 390-8621 Japan, e-mail: mituoda@shinshu-u.ac.jp
Abstract – The title compound, 5,6-dihydrocyclohepta[b]indol-6-one (1), was
synthesized from 2-chlorotropone (7) by a two-step sequence involving
Pd-catalyzed amination with 2-bromoaniline (15) and subsequent Pd-catalyzed
intramolecular Heck reaction. Besides its synthetic detail, some physical
properties of 1, such as acidity, basicity and spectroscopic behavior, were also
reported. Compound 1 was transformed into 6-(1H-pyrazol-1-yl)- and
6
-(1H-1,2,3-triazol-1-yl)-5-azabenz[b]azulenes (13 and 14) as a potential ligand.
This paper is dedicated to Professor Dr. Ei-ichi Negishi on the occasion of his 77th birthday
INTRODUCTION
1
The title compound, 5,6-dihydrocyclohepta[b]indol-6-one (1), has been known since 1972. Boyer et al.
reported the synthesis of 1 by basic hydrolysis of 6-amino-5-azabenz[b]azulene (2), which was obtained
2
in the photochemical intramolecular insertion reaction of 2,2’-diisocyanobiphenyl (3) (Scheme 1).
Almost at the same time, Kaneko et al. reported that 1 formed in the photochemical rearrangement of
3
acridine 10-oxide (4), accompanied with 5 and 6. Later, Nozoe and Yamane et al. applied the Fischer
indole synthesis to substrates containing a seven-membered ring and found two synthetic ways to 1 on a
4
,5
preparative scale.
In one way, 9 was synthesized by the reaction of cyclohexanone and
2
-hydrazinotropone (8), which can be obtained from 2-chlorotropone (7), and, then, dehydrogenation of 9
provided 1. In another way, 11 was synthesized by the Fischer indole synthesis with the phenylhydrazone
of cycloheptane-1,2-dione (10), and 1 was obtained by dehydrogenation of 11 via a brominated
intermediate.
Interestingly, the ca rbon fr amework of1 can be found in a marine bis(indole) alkaloid,

624
HETEROCYCLES, Vol. 86, No. 1, 2012
Boyer et al.
CN
O
NH2
N
H
N
6
5
4
7
NaOH
hv
3
8
9
2
10
1
NC
3
2
1
Kaneko et al.
H
N
hv
1
+
+
N
N+
O–
O
O
4
5
6
Nozoe and Yamane et al.
O
H
N
O
O
H
Cl
NNH2
NH NH
DDQ
2
2
1. cyclohexanone
1
2
. H SO
2
4
7
8
9
O
O
H
N
O
1. PhNHNH2
1. PhNMe Br
3
3
1
2
. H SO
2. LiCl, DMF
2
4
11
Scheme 1. Previously reported synthetic methods for 1
7
caulersin (12), whose synthetic benzo analogs show potent antitumor activity. Meanwhile, 1-azaazulenyl
8
compounds have recently been paid attention to as a ligand, and, hence, we have been interested in 1 as a
bidentate ligand structurally related to 1-azaazulenens and application of its metal complex for
9
functionalized materials, particularly as an electroluminescent compound. Therefore, we have been
curious to know basic properties of 1 for investigation of its metal complexation and also required a more
convenient synthesis
N
O
N
N
H
N
of 1. In this paper, we
N
N
N
N
describe
an
HN
MeO C
alternative efficient
synthesis of 1, and its
properties such as
2
12
13
14
acidity, basicity and Chart 1. Structure of caulersin (12).
Chart 2. Structures of 13 and 14.

HETEROCYCLES, Vol. 86, No. 1, 2012
625
interaction with metal ions. Also, transformation of 1 into azole-substituted 5-azabenz[b]azulenes, 13 and
4, as a potential ligand is described.
1
RESULTS AND DISCUSSION
Development of a new synthetic method for 1
In this study, a short-step strategy for synthesizing 1 from 2-substituted tropones and 2-bromoaniline (15)
by Pd-catalyzed amination and subsequent intramolecular Heck reaction was investigated. Although it
has been known that 2-anilinotropones could be obtained by nucleophilic substitution reaction of various
1
0
tropone derivatives having a leaving group at the 2-position with some unhindered anilines, Brookhart et
al. reported that reaction of sterically hindered aniline with 2-tosyloxytropone (16) gave the
1
1
ring-contraction compound as a major product. They deviced Pd-catalyzed amination using
2
-triflatotropone (17) as an alternative method for synthesizing 2-anilinotropones. Since 15 does not react
with various 2-substituted tropones under conventional conditions, the Pd-catalyzed amination under
reaction conditions reported by Brookhart et al. was applied to preparation of 2-(2-bromoanilino)tropone
(20) in our study. The results are listed in Table 1. 2-Iodotropone (18) and 2-bromotropone (19) were
used in addition to 7, 16, and 17.
Table 1. Palladium-catalyzed amination of 2-substituted tropones with 15
H N
2
O
O
H
N
Y
15
Br
Br
20
Pd (dba) / BINAP
2
3
Cs CO3
2
Y= OTs (16), OTf (17),
I (18), Br (19), Cl (7)
Pd / BINAP a
yield of 20 (%)b
entry
Y
solvent / temp / time
15c
25
52
14
60
80
52
71
60
1
2
3
4
5
6
7
8
9
OTs
OTs
OTf
I
3 mol% Pd (dba) / 6 mol% BINAP
toluene / 80˚C / 6 h
toluene / reflux / 12 h
toluene / 80˚C / 6 h
toluene / reflux / 20 h
toluene / reflux / 15 h
toluene / reflux / 12 h
toluene / reflux / 16 h
toluene / reflux / 4 h
xylene / reflux / 5 h
2
3
3 mol% Pd (dba) / 6 mol% BINAP
2
3
3 mol% Pd (dba) / 6 mol% BINAP
2
3
3 mol% Pd (dba) / 6 mol% BINAP
2
3
Br
3 mol% Pd (dba) / 6 mol% BINAP
2 3
Cl
3 mol% Pd (dba) / 6 mol% BINAP
2 3
Cl
1 mol% Pd (dba) / 2 mol% BINAP
2 3
Cl
5 mol% Pd (dba) / 10 mol% BINAP
2 3
Cl
3 mol% Pd (dba) / 6 mol% BINAP
2 3
a
c
b
1
.2 eq. of 15 and 1.4 eq. of Cs CO were used in all reactions, Isolated yield after chromatography
2
3
Recovery (36%) of 16 was observed.

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HETEROCYCLES, Vol. 86, No. 1, 2012
Among the 2-substituted tropones used, 7 was surprisingly found to be the most reactive under the
conditions and 20 was obatained in a satisfactory yield (Table 1, entry 6). The order of reactivity of
arylhalides in Pd-catalyzed aminations is usually iodide > bromide > chloride. Therefore, polarizability of
C–X bond has been thought to be important in an oxidative insertion of Pd(0). However, the order of
reactivity of 2-halorotropones in our amination is roughly chloride > bromide > iodide (Table 1, entries 4,
1
2
5
, and 6), as seen in ionic nucleophilic substitution reactions of arylhalides. This reactivity suggests that
charge density at the C-2 atom seems to play an important role in this amination reaction.
Table 2. Palladium-catalyzed intramolecular Heck reaction of 20
O
O
H
N
H
N
Pd/ ligand / additive
Br
1
20
entry
Pd / ligand / additive
3 mol% Pd (dba) / 6 mol% P(t-Bu) / 1.0 eq DABCO
solvent / temp / time
yield of 1 (%) a
1
2
3
4
5
6
7
8
9
CH CN / reflux / 18 h
trace
0
2
3
3
3
5 mol% Pd(OAc) / 20 mol% P(o-tol) / 1.3 eq Et N
dioxane / reflux / 27 h
DMF / reflux / 18 h
HMPA / 80˚C/ 23 h
DMF / reflux / 9 h
DMF / reflux / 23 h
DMF / reflux / 23 h
DMF / reflux / 8 h
DMF / reflux / 8 h
2
3
3
10 mol% Pd(OAc) / 40 mol% P(o-tol) / 1.3 eq Et N
6
2
3
3
29 b
22
2 mol% Pd(PPh ) / 2.0 eq NaHCO
3
3
4
+
–
5 mol% Pd(OAc) / 1.0 eq (Bu) N Br
2
4
10 mol% Pd(OAc) / 10 mol% P(o-tol) / 1.3 eq K CO
3
57
2
3
2
10 mol% Pd(OAc) / 40 mol% P(o-tol) / 1.3 eq K CO
3
54
2
3
2
10 mol% Pd(OAc) / 20 mol% P(o-tol) / 1.0 eq AcOH / 2.0 eq AcONa
79
2
3
40 c
10 mol% Pd(OAc) / 20 mol% P(o-tol) / 3.0 eq AcOH / 0.5 eq AcONa
2
3
1
0
1
10 mol% Pd(OAc) / 20 mol% XPhos / 1.0 eq AcOH / 2.0 eq AcONa
DMF / reflux / 27 h
DMF / reflux / 27 h
90
2
73 c
1
10 mol% Pd(OAc) / 20 mol% XPhos / 2.0 eq AcOH / 2.0 eq AcONa
2
a
Isolated yield after chromatography, b accompanied with 5% yield of cyclohepta[b][1,4]benzoxazine, c accompanied with a
reduction product, 2-anilinotropone.
Next, with a substantial amount of 20 in a hand, its intramolecular Heck reaction was examined to
complete synthesis of the title compound 1. We applied Heck reaction conditions with various palladium
catalysts and phosphine ligands. The results are summarized in Table 2. Under the conditions of entries
1
–5, the yields of 1 were poor or none. Although 1 was obtained under the conditions with
Pd(OAc) /P(o-tol) /K CO /DMF(Table 2, entries 6 and 7), the yields of 1 were still moderate. Addition of
2
3
2
3
weak base and its conjugated acid was found effective to improve the yield (Table 2, entry 8). However,
under acidic conditions with a larger amount of acetic acid the yield of 1 was reduced, accompanied with

HETEROCYCLES, Vol. 86, No. 1, 2012
627
formation of a reduction product (Table 2, entries 9 and 11). The satisfactory yield of 90% was achieved
1
3
under the conditions with sterically hindered ligand, XPhos (Table 2, entry 10). The title compound 1 is
now available in two steps from 7 and 15 in good yields (Scheme 2). Although palladium reagents are
used in these two procedurers, transformation to 1 from 7 in one pot was not achieved yet in spite of
extensive attempts.
H N
2
O
O
O
H
N
H
N
15
Cl
Pd(OAc) / XPhos
2
Br
Br
Pd (dba) / BINAP
AcOH / AcONa
DMF
2
3
Cs CO / toluene
2
3
80%
90%
7
20
1
Scheme 2. Summary of the synthesis of 1
Some physical properties of 1
Compound 1 was isolated as yellow prisms. Although some spectral data were previously reported, those
1
13
were renewed by data measured with high-resolution machines. All H and C NMR signals are assigned
with the aid of HMQC and HMBC spectra (Figure 1). Behavior of 1 in both acidic (CF CO D) and basic
3
2
1
(
NaOD/D O/DMSO-d ) media was also investigated by H NMR analysis. The average chemical shift
2 6
(
8.29 ppm) of hydrogens on the sp2 carbon atoms in CF CO D shows a down-filed shift compared with
3
2
1
0.91
1
77.4
142.6
O
7.72
H
7
.42
O
137.4
H
N
H
N
H
1
12.8
7
.58
134.3
37.0
12.3 Hz
H
1
28.0
22.0
26.4
H
1
7
.55
1
1
24.0
H
130.4
H
.10
H
8.20
7.39
121.0
1
H
7
8.15
122.4
10.8 Hz
1
13
Figure 1. Assigned H (left) and C (right) NMR signals (!ppm) and selected coupling constants of 1.
O–
OH
O
H
N
H
N
H
N
H
11.9 Hz
H+
H+
10.0 Hz
–
H+
+
+
H
H
+
– H+
9.4 Hz
H
H
10.0 Hz
H
H
9.4 Hz
10.0 Hz
1–
1+
1
Scheme 3. Selected coupling constants of protonated and deprotonated spieces of 1

628
HETEROCYCLES, Vol. 86, No. 1, 2012
+
3
that (7.61 ppm) in CDCl , supporting generation of the protonated species 1 . It is worth noting that J
3
H–H
coupling constants between hydrogens on the seven-membered ring are same, evidencing formation of
+
the delocalized tropylium ion structure in 1 (Scheme 3). On the other hand, the average chemical shift in
3
NaOD/D O/DMSO-d (7.64 ppm) shows a very small up-field shift. However, more convergent J
2
6
H–H
–
coupling constants compared with those observed in CDCl suggest generation of deprotonated species 1 .
3
–
Although electron density of the azaazulene ring increases in 1 , a deshielding effect of the ring perimeter
–
may compensate the shielding effect of negative charge in 1 , resulting in the slight up-field shift.
Figure 2. Absorption spectra of 1 in neutral, acidic, and basic media.
Changes of UV-vis spectra in acidic and
basic media (Figure 2) also evidence the
Table 3. Acidity and basicity of 1 and related compounds
compound
pK
pK
a
b
+
–
formation of ionic species, 1 and 1 . While
the spectrum of 1 in EtOH displays mainly
four bands at 224, 276, 307 and 403 nm, the
spectrum in a 50% sulfuric acid solution
shows a slight red-shift of the long-wave
maximum (407 nm) with a hypochromic
effect and also distinct hyperchromic effect
of the maximum around 310 nm. The
spectrum in a 20% NaOH solution shows a
clear red-shift of all bands. Particularly, the
long-wave maximum shifts by 52 nm
compared with that in EtOH. Based on these
1
13.6
12.9
indolea)
pyrrolea)
20.95
23.05
2
-aminotroponeb)
troponec)
11.79
15.02
7.3
2
1 d)
a)
Measured in DMSO. Taken from ref 14. b) Measured in
hydrochloric acid solutions. Taken from ref 15. c) Measured
in sulfuric acid solutions. Taken from ref 16. d) Measured
in 50% aqueous MeOH. Taken from ref 2. See below for
the structure of 21.
N
2
1
spectral changes, values of pK and pK for 1 were determined by a titration method. Table 3 shows the
a
b
1
4
14
15
16
values of 1 and related compounds, indole,
pyrrole,
2-aminotropone,
tropone
and

HETEROCYCLES, Vol. 86, No. 1, 2012
629
2
6
-azabenz[b]azulene (21). The relatively stronger acidity of 1 compared with those of indole and pyrrole
can be attributed to the annelation of an
electron-withdrawing tropone to the indole
skeleton. The basicity of 1 is between those
of tropone and 2-aminotorpone and far lower
than that of 21. These results are consistent to
OH
O
H
N
N
22
4
1
the previously suggested conclusion that 1
Scheme 4. Tautomerism of 1
exist as a tropone-containing structure,
depicted as 1, not as its tautomeric azaazulene structure of 22 (Scheme 4).
In order to investigate interaction between 1 and metal ions, absorption spectra of 1 in the presence of a
large excess (500 eq.) of several metal ions as the perchlorate were measured. Clear spectral change was
+
+
+
2+
2+
not observed in the presence of monovalant ions, such as Li , Na and Ag , and divalent Ca and Mg . In
2
+
the presence of divalent Zn , the long-wave maximum was observed at 439 nm, showing a clear red-shift
2
+
(
Figure 3). Emission upon excitation at 439 nm in the presence of Zn was observed at 497 nm. It is
–
2
2+
worth noting that an emission quantum yield (! = 1.2 x 10 ) in the presence of Zn is 23 times greater
–
4
17
than that (! = 5.3 x 10 ) without metal ion.
Figure 3. Absorption spectra of 1 in the presence of various metal ions.
Synthesis and properties of 6-azolyl-5-azabenz[b]azulenes
Yamane et al. reported the
R
R'
Cl
N
transformation of
various amine-substituted
-azabenz[b]azulenes (24) via
1
into
N
N
HNRR'
EtOH
SOCl2
1
5
6
-chloro-5-azabenz[b]azulene
23
24
4
(
23). Nucleophilic substitution
Scheme 5. Synthesis of 6-amino-5-azabenz[b]azulenes 24 by Yamane et al.

630
HETEROCYCLES, Vol. 86, No. 1, 2012
reactions of 23 with amines and hydrazines provide various 6-substituted derivatives in good yields by
simply heating in EtOH (Scheme 5). However, less nucleophilic azoles react with 23 neither in refluxing
Table 4. Palladium-catalyzed amination of 23 with pyrazole and triazole
Y
Y
N
Cl
N
N
N
N
H
N
Pd (dba) / ligand
2
3
Cs CO3
2
23
13 (Y=CH), 14 (Y=N)
azolea
b
c
entry
Pd (dba) / ligand
solvent / temp / time
yield [%] (product)
2
3
1
2
3
4
pyrazole
pyrazole
triazole
triazole
a
2.5 mol% Pd (dba) / 5 mol% XPhos
dioxane / reflux / 6 h
toluene / reflux / 9 h
toluene / 80˚C / 14 h
toluene / 90˚C / 20 h
9 (13)
77 (13)
69 (14)
72 (14)
2
3
3 mol% Pd (dba) / 6 mol% BINAP
2
3
6 mol% Pd (dba) / 12 mol% BINAP
2
3
10 mol% Pd (dba) / 20 mol% BINAP
2
3
2
.0 eq. of azole was used in all reactions, b 2.0 eq. of Cs CO were used in all reactions,
Isolated yield after chromatography.
2
3
c
EtOH nor under base-assisted conditions. Hence, Pd-catalyzed amination was
examined. The results are shown in Table 4. The desired products 13 and 14
were obtained in good yields under the conditions Pd (dba) /BINAP/Cs CO in
N
N
N
N
2
3
2
3
refluxing toluene (entries 2–4). In the reaction with 1,2,3-triazole, a small
1
amount of the 2-triazolyl isomer 24 was observed as another product by H
24
NMR analysis of the crude reaction mixture. However, 24 was not isolated
because of its facile hydrolysis to 1 during chromatographic purification, as Chart 3. Structure of 24.
seen in hydrolysis of 2. Compound 14 is more sensitive to acid and base than 13. Compounds 13 and 14
were isolated as violet crystals, having weak visible absorptions at 510 and 496 nm in EtOH, respectively
(Figure 4). While no emission was observed upon excitation at those long-wave maxima, emissions at
1
8
4
35 nm were observed upon excitation at 383 for 13 and 385 nm for 14. This emission behavior is
resemble to that seen in azulenes. A pK value of 13 was determined to be 8.4 by a UV-vis titration
b
method, though basicity of 14 could not be determined because of its instability in acid and basic aqueous
solutions, The value shows that 13 is less basic by 1.1 pK unit than the parent 6-azabenz[b]azulene (21),
b
indicating that the pyrazole moiety shows electron-withdrawing functionality. Absorption spectra of 13
and 14 in the presence of a large excess (500 eq.) of metal ions are also examined. The results are shown
in Figures. 5 and 6. A blue-shifts of the long-wave absorption maxima with a hyperchromic effect for

HETEROCYCLES, Vol. 86, No. 1, 2012
631
Figure 4. Absorption spectra of 13 and 14 in EtOH.
Figure 5. Absorption spectra of 13 in the presence of various metal ions.
Figure 6. Absorption spectra of 14 in the presence of various metal ions.
2
+
2+
Mg and Zn was observed for 13 and 14, suggesting that coordination of metal ions with their nitrogen
on the 6 position occurs, though it is not clear whether azole nitrogens participate in the coordination or

632
HETEROCYCLES, Vol. 86, No. 1, 2012
2
+
2+
not so far. Interestingly, 13 interacts much strongly with Mg , while 14 dose with Zn . However, clear
change of their emission spectra in the presence of metal ions was not observed.
CONCLUSION
It has been demonstrated that the title compound 1 can be efficiently synthesized from 2-chrorotropone
(7) by Pd-catalyzed amination with 2-bromoamniline (15) and subsequent by Pd-catalyzed intramolecular
Heck reaction. Various 2-substituted tropones were subjected to the amination and it was revealed that,
among the tropones used, 2-chlorotropones (7) reacts most effectively. In the intramolecular Heck
reaction, it was found that addition of weak acid and its conjugated base and use of a sterically hindered
ligand was valid to improve the yield. Basicity and acidity of 1 were disclosed and its interaction with
metal ions in solution was studied. The Pd-catalyzed amination of 23, derived from 1, with azoles gave
the azolyl products 13 and 14. Some spectroscopic properties of these compounds were also clarified.
EXPERIMENTAL
Melting points were measured on a Yanaco MP-3. IR spectra were recorded on a JEOL Diamond-20
spectrometer. UV-vis spectra were measured on a Shimadzu UV-2550 spectrometer. Emission spectra
1
13
were recorded on a Shimadzu RF-5300PC spectrometer. H and C-NMR spectra were recorded with
tetramethylsilane as internal standard on a JEOL "400 NMR instruments. Mass spectra were measured on
a JMS-700 mass spectrometer. Column chromatography was done with Silica gel 60N from Kanto Chem.,
Inc. X-Phos, Pd
tri-o-tolylphosphine and 2-bromoaniline were purchased from Tokyo Kasei Industrial Co. Pd(OAc)
purchased from Wako Chem. 2-Holotropones were prepared according to the literature method of
2
(dba)
3
, Pd(PPh
3
)
4
, and Cs
2
CO
3
were purchased from Sigma-Aldrich Japan, Inc. BINAP,
2
was
1
9
Doering. 6-Chloro-5-azabenz[b]azulene (23) was prepared from 1 according to the literature method of
4
Nozoe. Emission quantum yields were determined by comparison of a total emission area with that of
anthracene (! = 0.27, upon excitation at 356 nm in ethanol).
2
-(2-Bromoanilino)tropone (20)
A mixture of 7 (281 mg, 2.00 mM), 2-bromoaniline (413 mg, 2.40 mM), Pd
BINAP (75 mg, 0.12 mM), and Cs CO (912 mg, 2.80 mM) in 5 mL of toluene was refluxed on an oil
2
3
(dba) (55 mg, 0.060 mM),
2
3
bath for 12 h. The resulted reaction mixture was passed through a Celite pad and washed with toluene.
After evaporation of the filtrate, the residue was purified by silica gel column chromatography with
1
AcOEt/Hexane (30/70) to give 444 mg (80% yield) of 20 as slightly brown needles. Mp 84–85 ˚C. H
NMR (CDCl ) # = 6.82 (td, J = 8.4, 0.8 Hz, 1H), 6.98 (d, J = 10.4 Hz, 1H), 7.12 (m, 2H), 7.30–7.35 (m,
3
1
3
2
H), 7.38 (t, J = 8.4 Hz, 1H), 7.46 (d, J = 8.4 Hz, 1H), 7.70 (d, J = 10.8 Hz, 1H), 8.75 (brs, 1H) ppm; C

HETEROCYCLES, Vol. 86, No. 1, 2012
633
NMR (CDCl ) # = 110.8, 120.0, 125.2, 125.4, 127.2, 128.3, 131.4, 133.9, 135.7, 137.0, 137.5, 152.7,
3
–
1
1
77.2 ppm; IR (KBr) $max = 3427brm, 3236m, 1547vs cm ; UV-vis (EtOH) " = 236 (log % = 4.25), 341
max
+
+
(
3.99), 400 (4.10) nm; MS (70 eV) m/z (rel int) = 277 (M , 12), 275 (M , 11), 276 (19), 197 (38), 196
(
100), 168 (17), 167 (53), 98 (15), 77 (15). Anal. Calcd for C H BrNO: C, 56.55; H, 3.65; N, 5.07%.
1
3
10
Found: C, 56.76; H, 3.77; N, 5.15%.
5
,6-Dihydrocyclohepta[b]indol-6-one (1)
A mixture of 20 (215 mg, 0.779 mM), XPhos (74 mg, 0.16 mM), Pd(OAc)
128 mg, 1.56 mM), and AcOH (47 µL, 0.78 mM) in 5 mL of DMF was refluxed on an oil bath for 27 h.
The resulted reaction mixture was passed through a Celite pad and washed with CH Cl . After
2
(18 mg, 0.080 mM), NaOAc
(
2
2
evaporation of the filtrate, the residue was purified by silica gel column chromatography with
AcOEt/Hexane (40/60) to give 137 mg (90% yield) of 1 as yellow prisms. Mp 255–256 ˚C [lit.
1
2
3a
1
2
49.5–250.5, 250–252, 245–246˚C ]. H NMR (CDCl ) # = 7.10 (ddd, J = 10.8, 8.8, 1.0 Hz, H-9), 7.39
3
(tt, J = 8.0. 1.2 Hz, H-2), 7.42 (dt, J = 12.3, 1.0 Hz, H-7), 7.55 (ddd, J = 12.3, 8.8, 1.0 Hz, H-8), 7.58 (tt, J
=
8.0, 1.2 Hz, H-3), 7.72 (dm, J = 8.0 Hz, H-4), 8.15 (dm, J = 8.0 Hz, H-1), 8.20 (dm, J = 10.8 Hz, H-10),
1
1
0.91 (brs, N-H) ppm; H NMR (CF CO D) # = 7.69 (m, H-2), 7.90–7.95 (m, H-3,4), 8.19 (t, J = 10.0 Hz,
3
2
H-9), 8.25 (d, J = 10.0 Hz, H-7), 8.42 (t, J = 8.4 Hz, H-8), 8.48 (d, J = 8.4 Hz, H-1), 9.35 (d, J = 10.0 Hz,
1
3
H-10) ppm; C NMR (CF CO D) # = 115.3, 123.4, 126.6, 127.1, 128.1, 134.1, 135.7, 138.2, 139.9, 141.8,
3
2
1
1
42.5, 144.8, 183.1 ppm; H NMR (NaOD/D O/DMSO-d ) # = 6.95 (t, J = 9.4 Hz, H-9), 7.18 (d, J = 11.9
2 6
Hz, H-7), 7.27 (t, J = 8.2 Hz, H-2), 7.46 (t, J = 8.2 Hz, H-3), 7.52 (dd, J = 11.9, 9.4 Hz, H-8), 7.83 (d, J =
1
3
8
.2 Hz, H-4), 8.21 (d, J = 8.2 Hz, H-1), 8.43 (d, J = 9.4 Hz, H-10) ppm; C NMR (NaOD/D O/DMSO-d )
2
6
#
= 119.4, 120.7, 121.3, 121.9, 127.4, 128.5, 129.6, 130.6, 132.4, 137.8, 152.3, 155.8, 182.2 ppm;
6
-(1H-Pyrazol-1-yl)-5-azabenz[b]azulene (13)
A mixture of 23 (45 mg, 0.21 mM), pyrazole (29 mg, 0.42 mM), Pd (dba) (9 mg, 7 µM), BINAP (6 mg,
2
3
1
2 3
4 µM), and Cs CO (137 mg, 0.420 mM) in 5 mL of toluene was refluxed on an oil bath for 9 h. The
resulted reaction mixture was passed through a Celite pad and washed with toluene. After evaporation of
3
the filtrate, the residue was purified by silica gel column chromatography with AcOEt/CHCl (30/70) to
1
give 40 mg (77% yield) of 13 as violet needles. Mp 135–136 ˚C. H NMR (CDCl ) # = 6.64 (dd, J = 2.7,
3
1
.3 Hz, pyrazolyl-H), 7.54 (ddd, J = 8.1, 7.7, 1.0 Hz, H-2), 7.69 (ddd, J = 10.3, 8.9, 0.5 Hz, H-9), 7.80
ddd, J = 8.1, 7.7, 1.0 Hz, H-3), 7.89 (dd, J = 1.3, 0.5 Hz, pyrazolyl-H), 7.94 (ddd, J = 10.6, 10.3, 1.0 Hz,
H-8), 8.13 (dt, J = 8.1, 1.0 Hz, H-4), 8.38 (dt, J = 8.1, 1.0 Hz, H-1), 8.82 (dd, J = 10.6, 1.1 Hz, H-7), 8.88
(
1
3
(
ddd, J = 8.9, 1.1, 0.5 Hz, H-10), 9.65 (dd, J = 2.7, 0.5 Hz, pyrazolyl-H), ppm; C NMR (CDCl ) # =
3
1
07.8 (pyrazole C-4), 120.8 (C-4), 120.9 (C-1), 122.9 (C-2), 125.9 (C-7), 127.5 (C-9), 127.8 (C-10b),

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HETEROCYCLES, Vol. 86, No. 1, 2012
1
31.0 (C-3), 131.2 (C-10), 135.0 (C-8), 135.5 (pyrazole C-5), 142.1 (pyrazole C-3), 142.6 (C-6), 143.8
(C-10a), 152.1 (C-5a), 156.3 (C-4a) ppm; IR (KBr) $max = 1454s, 1382s, 1334s, 1203s, 1041s, 654s, 755s,
–
1
7
30s cm ; UV-vis (EtOH) " = 271 (log% = 4.29), 311 (4.48), 350 (4.12), 383 (3.92), 510 (3.04) nm;
max
+
+
MS (70 eV) m/z (rel int) =246 (M +1, 21), 245 (M , 100), 244 (27), 218 (83), 217 (30), 192 (22), 190 (15),
+
1
77 (14), 151 (12). HRMS m/z Calcd for C H N (M ) 245.0953, found: 245.0915. Anal. Calcd for
1
6
11
3
C H N : C, 78.35; H, 4.52; N, 17.13%. Found: C, 78.26; H, 4.79; N, 16.97%.
1
6
11
3
6
-(1H-1,2,3-Triazol-1-yl)-5-azabenz[b]azulene (14)
A mixture of 23 (45 mg, 0.21 mM), 1,2,3-triazole (29 mg, 0.42 mM), Pd (dba) (19 mg, 0.021 mM),
2
3
2 3
BINAP (26 mg, 0.042 mM), and Cs CO (137 mg, 0.420 mM) in 5 mL of toluene was heated at 90 ˚C on
an oil bath for 20 h. The resulted reaction mixture was passed through a Celite pad and washed with
toluene. After evaporation of the filtrate, the residue was purified by silica gel column chromatography
1
with AcOEt/CH
2
Cl
2
(40/60) to give 37 mg (72% yield) of 14 as violet needles. Mp 189–191 ˚C. H NMR
(
CDCl ) # = 7.60 (td, J = 8.0, 0.8 Hz, H-2), 7.86 (m, H-3,9), 7.98 (d, J = 1.2 Hz, triazolyl-H), 7.99 (td, J =
3
1
0.2, 1.0 Hz, H-8), 8.13 (dt, J = 8.0, 0.8 Hz, H-4), 8.43 (dt, J = 8.0, 0.9 Hz, H-1), 8.79 (d, J = 10.2 Hz,
1
3
H-7), 8.94 (dd, J = 8.6, 1.0 Hz, H-10), 9.51 (d, J = 1.2 Hz, triazolyl-H), ppm; C NMR (CDCl ) # =
3
1
20.8(C-4), 121.2 (C-1), 123.1 (C-2), 127.4 (C-7), 128.1 (C-9), 129.0 (C-10b), 130.0 (C-3), 130.8 (C-10),
32.2 (C-8), 134.4 (triazole C-4), 134.9 (triazole C-5), 139.3 (C-6), 145.1 (C-10a), 151.7 (C-5a), 156.9
1
(C-4a) ppm; IR (KBr) $max = 3348m, 3168m, 3109s, 3047m, 1616w, 1604m, 1517w, 1475w, 1458s,
–
1
1
437w, 1394s, 1357m, 1330m, 1321w, 1236s, 1070s, 1016s, 789m, 758s, 727s cm ; UV-vis (EtOH) "
max
=
245 (log% = 4.18), 258sh (4.17), 274 (4.12), 300sh (4.38), 317 (4.48), 368 (3.55), 385 (3.70), 401sh
+
(
3.39), 514 (2.78) nm; MS (70 eV) m/z (rel int) = 246 (M , 3), 218 (100), 217 (27), 190 (18), 177 (12),
+
1
67 (9), 151 (9), 150 (6), 108 (8), 106 (7), 77 (7), 57 (8). HRMS m/z Calcd for C H N (M ) 246.0911,
1
6
11
4
found: 246.0904.
Determination of acidity and basicity for 1 and 13
The acidity of 1 and basicity of 13 were determined from titration curves based on pH-dependent
absorption spectra in 50% aqueous ethanol solutions by a curve fitting method using KaleidaGraph
program. The absorption peak at 455 nm for acidity of 1 and the absorption peak at 383 nm for basicity of
1
3 were used. Buffer solutions used for measurements of basicity of 13 are as follows; AcOH/AcONa at a
range of pH 4.35~7.40 and KH PO /Na HPO at a range of pH 6.97~8.92. Instead buffer solutions, NaOH
2
4
2
4
solutions were used a range of pH 10.50~14.00 for measurements of acidity of 1. The basicity of 1 was
determined from titration curves based on Hammet acitity function (H )-dependent absorption spectra.
0
The absorption peak at 402 nm was used and solutions used are as follows; H PO solutions at a range of
3
4

HETEROCYCLES, Vol. 86, No. 1, 2012
635
H –0.37~1.45 and H SO solutions at a range of H –2.06~0.02.
0
2
4
0
ACKNOWLEDGEMENTS
We deeply thank emeritus Prof. Kunihide Fujimori at Shinshu University for giving us an authentic
sample of 1. We also thank Mr Hiroki Okamoto and Ms Yuko Yamaga for their technical assistance to
prepare compound 14.
REFERENCES AND NOTES
1
2
3
.
.
.
The compound has also been called as indolo[2,3-b]tropone.
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1
975, 23, 2818.
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5
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2
-(2-phenylhydrzino)tropone; T. Nozoe, K. Takase, H. Saito, H. Yamamoto, and K. Imafuku, Chem.
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6
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7
8
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B. Joseph, D. Alagille, J.-Y. Mérour, and S. Léonce, Chem. Pharm. Bull., 2000, 48, 1872.
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Ariyoshi, K. Umeda, N. Yamauchi, S. Tagashira, Y. Murakami, H. Fujii, and N. Abe, Heterocycles,
2
007, 73, 325; e) M. Oda, K. Ogura, N. C. Thanh, S. Kishi, S. Kuroda, K. Fujimori, T. Noda, and N.
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9
.
A part of this study, development of the novel synthetic procedure of 1, has been briefly reported; J.
Jin, K. Ito, F. Takahashi, and M. Oda, Chem. Lett., 2010, 39, 861.

636
HETEROCYCLES, Vol. 86, No. 1, 2012
1
0. a) S. Iseda, Bull. Chem. Soc. Jpn., 1955, 28, 617; b) S. Iseda, Bull. Chem. Soc. Jpn., 1957, 30, 694; c)
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6
654.
1
1
1
1. F. A. Hicks and M. Brookhart, Org. Lett., 2000, 2, 219.
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3. XPhos is a trivial name of 2-dicyclohexylphosphino- 2’,4’,6’-triisopropylbiphenyl; X. Huang, K. W.
Anderson, D. Zim, L. Jiang, A. Klapars, and S. L. Buchwald, J. Am. Chem. Soc., 2003, 125, 10767.
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1
1
1
1
6. H. Hosoya and S. Nagakura, Bull. Chem. Soc. Jpn., 1966, 39, 1414.
7. Upon excitation at 403 nm in EtOH, 1 emits light with a maximum at 439 nm. The quantum yield
–
5
was obtained in a molar concentration of 1 less than 10 mol/L.
–
4
–4
1
8. Emission quauntum yields for 13 and 14 are 7.4 x 10 and 3.8 x 10 , respectively. Quantum yields
–
4
were obtained in molar concentrations of these substrates less than 10 mol/L.
1
9. W. v. E. Doering and L. H. Knox, J. Am. Chem. Soc., 1952, 74, 5683.