Synthesis of azulen-3-ylheterocyclic compounds using 2-(3-methoxycarbonylazulen-1-yl)ethynyltriphenyl-phosphonium bromide

Article abstract of DOI:10.3987/COM-04-S(P)27

3-(3-methoxycarbonylazulen-1-yl)ethynyltriphenylphosphonium bromide was prepared from methyl 3-formylazulenecarboxylate. Its resonance structures were discussed on the basis of the ¹H and ¹³C NMR spectroscopy. Furthermore, its reacti

Full text of DOI:10.3987/COM-04-S(P)27

HETEROCYCLES, Vol. 64, 2004
305
HETEROCYCLES, Vol. 64, 2004 pp. 305 - 316
Received, 27th July, 2004, Accepted, 31st August, 2004, Published online, 3rd September, 2004
SYNTHESIS OF AZULEN-3-YLHETEROCYCLIC COMPOUNDS USING
2-(3-METHOXYCARBONYLAZULEN-1-YL)ETHYNYLTRIPHENYL-
PHOSPHONIUM BROMIDE
Noboru Morita,a)* Shiro Moriyama,a) Taku Shoji,a) Masashi Nakashima,a)
Masataka Watanabe,b) Shigeru Kikuchi,c) Shunji Ito,d) and Kunihide Fujimori.e)
a) Department of Chemistry, Graduate School of Science, Tohoku University,
Sendai 980-8578, Japan
b) Institute of Multidisiplinary Research for Advanced Materials, Tohoku
University, Katahira 2-1-1, Aoba-ku, Sendai 980-8577, Japan
c) Department of Chemistry, Kumamoto University, Kurokami 2-39-1,
Kumamoto 860-8555, Japan
d) Department of Materials Science and Technology, Faculty of Science and
Technology, Hirosaki University, Bunkyocho 3, Hirosaki 036-8561, Japan
e) Department of Chemistry, Faculty of Science, Shinshu University, 3-1-1, Asahi,
Matsumoto, 390-8621, Japan
Abstract
–
3-(3-methoxycarbonylazulen-1-yl)ethynyltriphenylphosphonium
bromide was prepared from methyl 3-formylazulenecarboxylate. Its
1
resonance structures were discussed on the basis of the H and 13C NMR
spectroscopy. Furthermore, its reactivity with o-substituted aniline was
examined. We found that 2-(1-methoxycarbonyl-azulen-3-yl)ethynyltri-
phenylphosphonium bromide reacted with o-substituted aniline except 2-
aminophenol to give corresponding methyl 3-(benzazol-2-yl)azulene-1-
carboxylate.†
INTRODUCTION
The well-known Corey-Fuchs reaction1 originally developed by Makekvie2 has been used
largely for the synthesis of variety of ethynyl derivatives. It is also a convenient method for
preparation of bromoethynyl derivatives which could convert to ethynylphosphonium bromide.3
As part of our effort to design novel scaffolds for polyfunctionalyzed azulenes,4 we have
†
This paper is dedicated to Dr. Pierre Potier on the occasion of his 70th birthday.

306
HETEROCYCLES, Vol. 64, 2004
previously reported the synthesis of 2-(2-azulenyl)ethynyltriphenylphosphonium bromide from
2-formylazulene and its reactivity with o-substituted anilines and relativecompounds.5 We
found that 2-formylazulene could be easily access to 2-(2-azulenyl)ethynyltriphenylphospho-
nium bromide by Corey-Fuchs reaction and subsequent treatment with triphenylphosphine.
Moreover, the phosphonium salt was transformed into azulenylbenzoazoles. However, such
approaches are expected to take more advantage in the synthesis of 2-(1- or 3-azulenyl)-
ethynyltriphenylposponium bromide because 1- or 3-formylazulen is easy to access from
azulene or 1-substituted azulenes by the Vilsmeier reaction. Our focus has been to explore novel
1-azulenylethynyltriphenylposponium bromides and the synthetic routes to heterocyclic
compounds comprised azulene and benzoazol rings with functional properties.
RESULTS AND DISCUSSION
Synthesis of 2-(3-methoxycarbonylazulen-1-yl)ethynyltriphenylphosphonium bromide (4)
X
X
X
CBr , PPh , Zn
DBU
4
3
Y
Y
Y
0°C
a: X=Y=H
b:X=Y=tert-C H
DMSO
40°C
Br
Br
CHO
4
9
H
c:X=CO CH , Y=H
2
3
Br
3c (64%)
2c (92%)
1
Scheme 1.
It was well known that compound (1a) could be easily obtained in high yields by formylation of
parent azulene by Vilsmeier reaction. The reaction of 1a with tetrabromomethane in the
presence of triphenylphosphine seems to give a corresponding bromide (2a), which could not be
isolated due to polymerization during concentration of reaction mixture. Therefore, without
isolation, a solution of reaction mixture of dibromide (2a) was treated with DBU, but 3a could
not be isolated because of complex mixture. Due to decreasing a reaction site and increasing
electron density of azulenyl ring, 1b was use as a 1-formylazulene. Similar results were
obtained. On the other hand, when methyl 3-formylazulene-1-carboxylate (1c) was used as a
substrate, reaction was smoothly proceed to give dibromide (2c) in good yields and
dehydrobromination was also occurred smoothly by treatment of DBU to give a corresponding
bromoethynylazulene derivative (3c). The compound (3c) reacted with triphenylphosphine in

HETEROCYCLES, Vol. 64, 2004
307
refluxing ether for 21 h to give 2-(3-methoxycarbonylazulen-1-yl)ethynyltriphenylphospho-
nium bromide (4) in 85% yield.
2
+
-
PPh Br
3
H
Br
PPh
CH
OOC
CH
3
CH
OOC
8
3
OOC
3
! #
"
3
4
7
5
6
3c
4
5
Scheme 2.
Table 1 Chemical shift of 1H NMR spectrum of 3c, 4, and 5
5
3c
4
8.69
9.03
H-2
H-4
H-5
H-6
H-7
H-8
8.45
8.72
7.55
7.86
7.61
9.63
3.95
8.42
8.69
7.55
7.87
7.61
9.62
3.95
7.87-7.97
8.34
8.22
9.78
3.98
OCH3
Ph
≡C-H
7.87-7.93
3.45
Table 2 Chemical shift of 13C NMR spectrum of 3c, 4, and 5
5
3c
4
117.61
144.92(J=2.1)
101.79(J=5.4)
142.96
C-1
C-2
C-3
C-3a
C-4
C-5
C-6
C-7
119.10
140.28
115.97
143.12
137.79
127.79
140.96
129.19
138.61
145.52
81.58
109.72
140.41
115.97
143.03
137.82
127.81
140.85
129.24
138.67
145.58
53.07
139.11
132.52
142.86
132.54
142.85
147.82
C-8
C-8a
C C X
C C X
p-C6H4-
m- C6H4-
o- C6H4-
ipso- C6H4-
CH3-O-
O-CO-
72.93(J=190.95)
116.96(J=33.9)
135.78(J=3.15)
133.07(J=12.75)
130.83(J=14.85)
118.84(J=99.75)
51.49
78.87
75.43
51.28
165.18
51.33
165.15
164.23

308
HETEROCYCLES, Vol. 64, 2004
In order to clarify the substituent effect of triphenylphosphonium group in 4, assignments of the
1
signals in H and 13C-NMR spectra were carried out with aid of HMBC and HMQC NMR
techniques. Phenyl protons and H-5 of azulene ring overlapped as shown in Tables 1. Coupling
constants of phosphorus and carbon decreased according to the increasing distance between
them (JP, C-1sp = 190.95 Hz – JP, C-2Az=2.1 Hz). The signals of azulene protons and carbons linked
to hydrogen in 4 as compared with 5 showed down field shift by 0.24-0.61 ppm and 1.32-4.73
ppm, respectively. Furthermore, the signal at C-2sp showed too much lower field shift by 38.09
ppm. In contrast, the signals of C-1az, C-3az, C-3aaz and C-1sp in 4 as compared with 5 showed
higher field shift by 1.49, 14.18, 2.56 and 9.28 ppm, respectively. These observations suggest
that electron density of each carbon of azulene with hydrogen and C-8aaz decreased by the
combination with triphenylphosphonium group due to contributions of 4a, 4b, and 4c. However,
large down field shift of C-2sp suggested to a possibility of nucleophilic attack at C-2sp of 4.
CO CH
2
CO CH
2
CO CH
2
3
3
3
Br
Br
C
C
C
C
C
C
Br
4a
4b
4c
PPh
PPh
PPh
3
3
3
Synthesis of heterocyclic compounds using 4
As shown in Scheme 3, the reactivity of 4 with the dinuleophilic groups, such as o-phenylenediamine
and related compounds (6a-c), was examined. As a result, a nucleophilic addition of Michael type and
the subsequent of nucleophilic cyclization like 2-(2-azulenyl)ethynyltriphenylphosphonium bromide5 gave
benzazoles such as methyl 3-(1H-benzimidazol-2-yl)azulene-1-carboxylate (7a) and methyl 3-
(benzothiazol-2-yl)azulene-1-carboxylate (7b) in 46 and 71% yields, respectively, except 6c. However,
extremely long reaction time was needed. The reason for its slow reaction rate is the increasing
electron density at acetylenic carbon C-2sp by the contributions of 4a-c. The reaction of 1,8-
diaminonaphthalene with 4 also gave corresponding methyl 3-(1H-perimidin-2-yl)azulene-1-carboxy-
late (8) in 79 % yield.

HETEROCYCLES, Vol. 64, 2004
309
NH2
XH
CH O C
3
Br
PPh3
2
X
N
CH O C
3
2
6
7
a; X = NH
b; X = S
c; X = O
6
4
-CH3P+Ph3Br-
CO CH
2
CO CH
2
3
3
CO CH
2
3
CO CH
2
3
Br
PPh3
Br
PPh3
H
H
H
H
X
H
N
H
Br
PPh3
N
OH
N
HN
XH
CH
3
OH
12
11
9
Scheme 3.
In the case of thereaction of 4 with 6c, only a mixture of 3-[1-(2-hydroxyphenylimino)ethyl]azulene-1-
carboxylate (9) and methyl 3-acetylazulene-1-carboxylate (10)6 was obtained. The imine (9) easily
converted to 10 during purification. Although the reaction mechanism to give 9 is not clear, we think
that N-hydrogen of the first Michael reaction product (11) shits to C-1 to give imine intermediate (12)
and undergoes elimination of the triphenylphosphonium group to give 9, because second Michael
reaction of 11 did not proceed smoothly due to weak nucleophilicity of the hydroxy group. Similar
results have been observed in the reaction of 2-(2-azulenyl)ethynyltriphenylphosphonium bromide with
6c.5
HN
CO2CH3
CH O2C
3
N
COCH3
8
10
Comparing with ring protons of 3-ethynylazulene (5) with azulenylated heterocyclic compounds (7a-b
and 8), by the connecting with these heterocyclic rings at C-3 position of azulene, the ring protons of
azulene shifted to lower field in the order of H-4 > H-2 > H-8 > H-6 > H-5 and 7 (see
EXPERIMENTAL) due to the anisotropy and electron withdrawing character of heterocyclic ring.

310
HETEROCYCLES, Vol. 64, 2004
CONCLUSION
This study has shown the preparation of 2-(3-methoxycarbonylazulen-1-yl)ethynyltri-
phenylphosphonium bromide (4) and its application to the synthesis of azulenylated benzazoles
at 3-position of azulene ring (7a-b) and a related compound (8) although longer reaction time is
necessary comparing with 2-position of azulene and there is a limitation of this reaction in the
case of o-aminophenol (6c).
EXPERIMENTAL
General Information. Melting points were determined on a Yanaco micro melting point apparatus and
are uncorrected. IR spectra were taken on a Shimazu FTIR-8100M and ES spectra were measured on a
1
Hitachi U-3410 spectrophotometer. H NMR spectra (13C NMR spectra) were recorded on JEOL
LAMBDA 400 (100 MHz) and 600 (125 MHz). MS spectra were measured on a JEOL HX-110 or a
Hitachi M-2500 instrument usually at 70 eV. Elemental analyses were performed at the Instrumental
Analysis Center of Chemistry, Faculty of Science, Tohoku University.
Synthesis of methyl 3-(2,2-dibromovinyl)azulene-1-carboylate (2c)
A suspension of triphenylphosphine (5.16 g, 19.7 mmol), carbon tetrabromide (6.52 g, 19.7 mmol), and
zinc powder (1.28 g, l9.7 mmol) in dry dichloromethane (40 mL) was stirred for 24 h under argon at rt.
A solution of methyl 3-formylazulene-1-carboxylate (526 mg, 2.5 mmol) in dry dichloromethane (10
mL) was added to the suspension at rt and stirred at same temperature for 20 min. The deep brown
reaction mixture was filtered. After the solvent was removed under reduced pressure, the residue was
purified by column chromatography on silica gel using dichloromethane as a solvent to afford methyl
3-(2,2-dibromovinyl)azulene-1-carboxylate (2c) (840 mg, 92.3%). 2c; Green needles (CH2Cl2/hexane),
mp 158.8-160.2 °C; IR (KBr) νmax 3054 (w), 3021 (w), 2996 (w), 2950 (w), 2363 (w), 1688 (s), 1576
(w), 1536 (w), 1509 (w), 1455 (s), 1439 (m), 1424 (m), 1412 (m), 1393 (w), 1375 (w), 1323 (w), 1229
(m), 1213 (s), 1184 (w), 1152 (w), 1053 (w), 1040 (w), 885 (w), 872 (w), 845 (m), 776 (w), 758 (w),
743 (w), 698 (w), 579 (w), 532 (w) cm-1; ES (CH2Cl2) λmax 214.8 (log ε 5.00), 218.6 (5.05), 219.9
(4.94), 226.3 (5.00), 250.0 (4.33) sh, 260.6 (4.29) sh, 300.2 (4.62), 324.6 (4.38), 390.8 (3.97), 408.4
1
(3.81) sh, 564.2 nm (2.69); H NMR (CDCl3, 400 MHz) δ 9.66 (1H, d, J=9.6 Hz, Az-8), 9.01 (1H, s,
Az-2), 8.44 (1H, d, J=9.6 Hz, Az-4), 7.94 (1H, s, -CH=CBr2), 7.83 (1H, dd, J=10.0, 9.6 Hz, Az-6),
13
7.58 (1H, dd, J=10.0, 9.6 Hz, Az-7), 7.50 (1H, dd, J=10.0, 9.6 Hz, Az-5), 3.97 (3H, s, CO2CH3); C

HETEROCYCLES, Vol. 64, 2004
311
NMR (CDCl3, 100 MHz) δ 165.46 (CO2Me), 141.33 (Az-8a), 141.22 (Az-3a), 140.08 (Az-6), 139.09
(Az-2), 138.44 (Az-8), 134.88 (Az-4), 129.32 (CH=CBr2), 129.0 (Az-7), 127.22 (Az-5), 122.51 (Az-1
or 3), 116.63 (Az-1 or 3), 88.44 (CH=CBr2), 51.33 (CO2CH3); MS (EI, 70eV) m/z 371.9 (M++2,
50.24%), 370.9 (M++1, 15.41), 369.8 (M+, 100), 368.8 (8.71), 367.9 (51.34), 340.8 (16.51), 338.8
(35.3), 336.8 (17.19), 231.9 (11.66), 229.9 (14.15), 210.0 (44.76), 179.0 (33.83), 166.1 (10.42), 152.1
(10.93), 151.1 (29.34), 150.0 (25.86), 89.5 (24.25), 75.5 (14.76), 75.0 (14.59); Anal. Calcd for
C14H10O2Br2: C, 45.44; H, 2.72; Br, 43.19. Found: C, 45.38; H, 2.84; Br, 43.38.
Synthesis of methyl 3-(2-bromoethynyl)azulene -1-carboylate (3c)
To a stirred solution of 2c (740 mg, 2.0 mmol) in DMSO (40 mL), DBU (3.04 g, 20.0 mmol) in
DMSO (20 mL) was added dropwise over a period of 7 min under argon at 40°C. After stirring
for 23 min at 40°C, the reaction mixture was quenched with water, neutralized with 2N HCl and
extracted with toluene. The extract was washed with brine, dried over anhydrous MgSO4. After
the solvent was removed under reduced pressure, the resulting residue was purified by column
chromatography (silica gel, toluene) to afford methyl 3-(2-bromoethynyl)azulene-1-carboxylate
(3c) (370.5 mg, 64.1%). 3c; Deep green needles (CH2Cl2 / hexane); mp 142.3-144.1 °C; IR
(KBr) νmax 2998 (w), 2953 (w), 1684 (s), 1636 (w), 1580 (w), 1536 (w), 1514 (w), 1455 (s),
1443 (s), 1424 (m), 1410 (m), 1393 (w), 1372 (w), 1293 (w), 1231 (s), 1219 (s), 1181 (w), 1163
(w), 1142 (w), 1053 (m), 893 (w), 876 (w), 779 (m), 747 (m), 602 (w), 575 (w), 471 (w) cm-1;
ES (CH2Cl2) λmax 221.8 (logε4.72), 226.3 (4.84)、243.6 (4.54) sh, 276.6 (4.47), 296.4 (4.44) sh,
303.1 (4.49), 315.6 (4.58), 381.2 (3.91), 397.2 (3.93), 558.8 (2.71), 600.7 (2.62) sh, 655.1 nm
1
(2.17) sh; H NMR (400 MHz, CDCl3) δ 9.62 (1H, d, J=10.0 Hz, Az-8), 8.69 (1H, d, J=10.0 Hz,
Az-4), 8.42 (1H, s Az-2), 7.87 (1H, t, J=9.6 Hz, Az-6), 7.61 (1H, dd, J=10.0, 9.6 Hz, Az-7), 7.55
(1H, dd, J=10.0, 9.6 Hz, Az-5), 3.95 (3H, s, CO2CH3); 13C NMR (100 MHz, CDCl3) δ 165.15
(CO2Me), 145.58 (Az-8a), 143.03 (Az-3a), 140.85 (Az-6), 140.41 (Az-2), 138.67 (Az-8), 137.82
(Az-4), 129.24 (Az-7), 127.81 (Az-5), 115.97 (Az-1), 109.72 (Az-3), 75.43 (Az-C≡CBr), 53.07
(Az-C≡CBr), 51.33 (CO2CH3); MS (EI, 70eV) m/z 289.9 (M++2, 99.15%), 288.9 (M++1, 15.15),
287.9 (M+, 100), 259.8 (9.64), 258.8 (70.39), 257.8 (10.41), 256.9 (72.55), 230.9 (8.18), 229.9
(5.92), 228.9 (7.95), 151.1 (13.03), 150.0 (78.2), 149.0 (7.18), 129.4 (6.78), 128.4 (7.53), 98.0
(7.07), 74.9 (32.21), 73.9 (8.64), 61.9 (5.26); Anal. Calcd for C14H9O2Br: C, 58.16; H, 3.14; Br,
27.64. Found: C, 58.25; H, 3.24; Br, 28.12.
Synthesis of 2-(3-methoxycarbonylazulen-1-yl)ethynyltriphenylphosphonium bromide (4)

312
HETEROCYCLES, Vol. 64, 2004
To a suspension of 3c (370.5 mg, 1.28 mmol) in abs. ether (20 mL), triphenylphosphine (403.3 mg,
1.54 mmol) was added. It was refluxed for 21 days under argon. The red precipitate was collected by
filtration, washed with ether and dried thoroughly in vacuo to give 2-(3-methoxycarbonylazulen-1-
yl)ethynyltriphenylphosphonium bromide (4) (600.4 mg, 85%). 4; Red powder; mp 219.6-221.4 °C
(decomp.); IR (KBr) νmax 3049 (w), 2947 (w), 2139 (s), 1695 (s), 1583 (w), 1514 (w), 1441 (s), 1412
(m), 1390 (w), 1371 (m), 1294 (w), 1215 (s), 1178 (w), 1111 (m), 1057 (m), 997 (w), 787 (m), 752 (w),
725 (m), 688 (m), 530 (m), 520 (s), 484 (w) cm-1; ES (CH2Cl2) λmax 227.9 nm (log ε 4.89), 262.5 (4.13)
sh, 270.5 (4.20) sh, 294.8 (4.56), 310.8 (4.45) sh, 315.6 (4.46), 324.9 (4.38) sh, 379.3 (4.19), 394.3
1
(4.19), 511.8 (2.93), 549.2 (2.83) sh, 597.2 nm (2.37) sh; H NMR (400M Hz, CDCl3) δ 9.78 (1H, d,
J=10.0 Hz, Az-4), 9.03 (1H, d, J=10.0 Hz, Az-8), 8.69 (1H, s, Az-2), 8.34 (1H, t, J=8.8 Hz, Az-6), 8.22
13
(1H, dd, J=10.0, 8.8 Hz, Az-5), 7.87-7.93 (16H, m, Ph-H and Az-7), 3.98 (3H, s, CO2Me); C NMR
(100MHz, CDCl3) δ 164.23 (CO2Me), 147.82 (Az-4a), 144.92 (Az-2, d, J=2.1 Hz), 142.96 (Az-8a),
142.86 (Az-6), 142.85 (Az-4), 139.11 (Az-8), 135.78 (Ph-p, d, J=3.15 Hz), 133.07 (Ph-m, d, J=12.75
Hz), 132.52 (Az-7), 132.54 (Az-5), 130.83 (Ph-o, d, J=14.85 Hz), 118.84 (Ph-ipso, d, J=99.75 Hz),
117.61 (Az-3), 116.96 (Az-C≡C-P, d, J=33.9 Hz), 101.79 (Az-1, d, J=5.4 Hz), 72.93 (Az-C≡C-P, d,
J=190.95 Hz), 51.49 (CO2Me); Anal. Calcd for C32H24O2BrP·1/5H2O: C, 69.25; H, 4.43. Found: C,
69.20; H, 4.54.
Synthesis of methyl 3-ethynylazulene-1-carboxylate (5)
2-(1-Methoxycarbonylazulen-3-yl)ethynyltriphenylphosphonium bromide (4) (106.3 mg, 0.192 mmol)
was dissolved in a mixture of 0.4 M of aqueous sodium hydroxide (10 mL) and methanol (10 mL). It
was stirring at rt for 15 min. The occurring solid product was collected by filtration. From the filtrate,
the product was also obtained by extraction with ethyl acetate. The combined product was purified by
column chromatography (silica gel, hexane and ethyl acetate (4:1)) to give methyl 3-ethynylazulene-1-
carbonylate (5) (37.9 mg, 93.8%). 5; Dark violet plates (EtOH); mp 105–106°C; IR (KBr) νmax 3546
(m), 3467 (m), 3416 (m), 3243 (s), 2091 (w), 1696 (s), 1686 (s), 1458 (s), 1439 (s), 1422 (s), 1412 (s),
1393 (m), 1314 (m), 1226 (s), 1210 (s), 1048 (s), 774 (m), 772 (m), 742 (s), 712 (m), 702 (m), 660 (m),
579 (m) cm-1; ES (EtOH) λmax 240.4 nm (log ε 4.58), 270.2 (4.48), 298.3 (4.51), 310.8 (4.59), 376.1
1
(3.90), 391.8 (3.92), 555.9 (2.75), 595.0 sh (2.68), 637.2 sh (2.40), 749.5 (1.90), 814.8 (1.91); H NMR
(400 MHz, CDCl3) δ 9.63 (1H, d, J=10.0 Hz, Az-8), 8.72 (1H, d, J=10.0 Hz, Az-4), 8.45 (1H, s, Az-2),
7.86 (1H, t, J=10.0 Hz, Az-6), 7.61 (1H, t, J= 10.0 Hz, Az-7), 7.55 (1H, t, J=10.0 Hz, Az-5), 3.95 (3H,
13
s, CO2CH3), 3.45 (1H, s, Az-C≡C-H); C NMR (100 MHz, CDCl3) δ 165.18 (CO2CH3), 145.52 (C-

HETEROCYCLES, Vol. 64, 2004
313
3a), 143.12 (C-8a), 140.96 (C-6), 140.28 (C-2), 138.61 (C-4), 137.79 (C-8), 129.19 (C-5), 127.79 (C-7),
119.10 (C-1), 115.97 (C-3), 81.58 (-C≡C-H), 78.87 (-C≡C-H), 51.28 (CH3O-); MS (EI, 70eV) m/
210 (M+, 100 %), 180 (11), 179 (74.6), 152 (7.6), 151 (24.7), 150 (19.7), 90 (4), 75 (5.8); Anal. Calcd
for C14H10O2·3/4H2O: C, 75.15; H, 5.18. Found: C, 74.99; H, 4.96.
Synthesis of methyl 3-(1H-benzimidazol-2-yl)azulene-1-carboxylate (7a)
To a stirred solution of 4 (100 mg, 0.18 mmol) in CHCl3 (10 mL), o-phenylenediamine (6a) (23.5 mg,
0.22 mmol) was added. The mixture was refluxed for 11 days under argon. The solvent was removed
under reduced pressure. The residue was purified by column chromatography (silica gel, ethyl acetate)
and GPC (CHCl3) to give methyl 3-(1H-benzimidazol-2-yl)azulene-1-carboxylate (7a) (25 mg, 45.7%).
7a; Deep purple needles (toluene); mp 121.7 – 123.9°C; IR (KBr) νmax 3135 (w), 3058 (w), 3002 (w),
2903 (w), 2857 (w), 2795 (w), 1694 (s), 1622 (w), 1593 (w), 1580 (w), 1559 (s), 1539 (w), 1507 (w),
1485 (w), 1458 (m), 1439 (s), 1426 (m), 1414 (s), 1401 (s), 1341 (m), 1316 (w), 1306 (w), 1293 (w),
1271 (m), 1242 (m), 455* (m), 1204 (s), 1129 (w), 1113 (w), 1055 (m), 1036 (w), 1013 (w), 932 (w),
889 (w), 880 (w), 781 (m), 764 (w), 745 (s), 563 (w) cm-1; ES (THF) λmax 230.8 nm (log ε 4.57) sh,
271.4 (4.52), 282.0 (4.48) sh, 313.0 (4.65), 331.0 (4.41) sh, 397.8 (4.11), 416.7 (4.00) sh, 561.4 (2.80)
1
sh, 599.4 (2.71) sh, 667.61 nm (2.12) sh; H NMR (400 MHz, DMSO-d6) δ 12.92 (1H, s, NH), 10.39
(1H, d, J=10.0 Hz, Az- 8), 9.65 (1H, d, J=10.0, Az-4), 9.08 (1H, s, Az-2), 8.14 (1H, dd, J=10.0, 9.6 Hz,
Az-6), 7.92 (1H, dd, J=10.4, 9.2 Hz, Az-7), 7.85 (1H, dd, J=9.6, 10.0 Hz, Az-5), 7.62-7.72 (1H, m,
13
Benzo-Ha), 7.50-7.53 (1H, m, Benzo-Ha), 7.25-7.35 (2H, m, Benzo-Hb), 3.94 (3H, s, CO2CH3); C
NMR (100 MHz, DMSO-d6) δ 164.54 (CO2Me), 149.10 (Az-C=N), 144.14 (Az-8a), 142.17 (Az-3a),
141.94 (Az-6), 140.39 (Az-8), 140.37 (Benzo), 138.98 (Az-2), 138.32 (Az-4), 133.99 (Benzo), 130.01
(Az-7), 129.93 (Az-5), 122.23 (Benzo), 121.47 (Benzo), 118.43 (Benzo), 116.63 (Benzo), 115.24 (Az-
3 or 1), 110.81 (Az-1 or 3), 51.23 (CO2CH3); MS (EI, 70eV) m/z 302.1 (M+, 100%), 301.1 (39.6),
287.1 (25.8), 271.0 (10.4), 244.1 (14.2), 243.1 (71.5), 242.1 (30.5), 241.1 (7.0), 151.1 (5.1), 135.1
(11.1); Anal. Calcd for C19H14N2O2·1/5H2O: C, 74.59; H, 4.74; N, 9.16. Found: C, 74.53; H, 4.77; N,
8.94.
Synthesis of methyl 3-(benzothiazol-2-yl)azulene-1-carboxylate (7b)
To a stirred solution of 4 (100 mg, 0.181 mmol) in CHCl3 (10 mL), o-aminobenzenethiol (6b) (27.24
mg, 0.218 mmol) was added. The reaction mixture was refluxed for 14 days under Ar． The solvent
was removed under reduced pressure. The residue was purified by column chromatography (silica gel,

314
HETEROCYCLES, Vol. 64, 2004
CH2Cl2) to give methyl 3-(benzothiazol-2-yl)azulene-1-carboxylate (7b) (41.1 mg, 71%).
7b; Brown needles (CH2Cl2/hexane); mp 178.2-179.9 °C; IR (KBr) νmax 3054 (w), 2994 (w), 2950 (w),
1701 (s), 1578 (w), 1530 (s), 1505 (w), 1456 (m), 1441 (s), 1418 (m), 1402 (s), 1358 (m), 1304 (w),
1275 (w), 1225 (m), 1210 (s), 1193 (m), 1175 (m), 1159 (w), 1152 (w), 1053 (m), 1013 (w), 922 (m),
887 (w), 880 (w), 777 (m), 762 (w), 747 (s), 722 (m), 706 (w), 691 (w), 577 (w), 444 (w) cm-1; ES
(CH2Cl2) λmax 217.4 nm (log ε 4.88), 220.0 (4.77), 222.8 (4.80), 226.6 (4.91), 275.3 (4.35), 313.7 (4.53),
330.0 (4.43) sh, 345.4 (4.29) sh, 397.8 (4.16), 420.6 (3.97) sh, 545.0 (2.80), 584.4 (2.69) sh, 634.6 nm
1
(2.19) sh; H NMR (CDCl3, 400 MHz) δ 10.20 (1H, d, J=10.0 Hz, Az-8), 9.77 (1H, d, J=10.0 Hz, Az-
4), 8.80 (1H, s, Az-2), 8.12 (1H, dd, J=7.6, 0.8 Hz, Benzo-Ha), 7.97 (1H, dd, J=9.6, 9.2 Hz, Az-6), 7.92
(1H, dd, J=8.0, 0.8 Hz, Benzo-Ha), 7.79 (1H, dd, J=10.0, 9.2 Hz, Az-7), 7.71 (1H. dd, J=10.0, 9.6 Hz,
13
Az-5), 7.50 (1H, ddd, J=8.4, 7.2, 1.2 Hz, Benzo-Hb), 7.38 (1H, ddd, J=8.0, 7.2, 1.2 Hz, Benzo-Hb); C
NMR (CDCl3, 100 MHz) δ 165.3 (CO2Me), 164.3 (Az-C=N), 154.2 (Az-3a), 143.8 (Az-8a), 141.5
(Az-2), 141.2 (Az-6), 140.6 (Benzo), 140.2 (Az-8), 139.3 (Az-4), 134.0 (Benzo), 130.4 (Az-7), 130.0
(Az-5), 126.2 (Benzo), 124.8 (Benzo), 122.6 (Benzo), 121.3 (Benzo), 120.3 (Az-1 or 3), 116.7 (Az-1
or 3), 51.4 (CO2CH3); MS (EI, 70eV) m/z 319.0 (M+, 100%), 318.0 (34.2), 304.1 (21.4), 288.1 (17.7),
260.9 (13.8), 260.0 (64.8), 259.0 (25.2), 143.6 (11.6), 130.1 (11.3); Anal. Calcd for C19H13NO2S: C,
71.45; H, 4.10; N, 4.39; S, 10.04. Found: C, 71.15; H, 4.19; N, 4.30; S, 10.07.
Synthesis of methyl 3-(1H-perimidin-2-yl)azulene-1-carboxylate (8)
To a stirred solution of 4 (100 mg, 0.181 mmol) in CHCl3 (10 mL), 1,8-diaminonaphyhalene (34.4 mg,
0.217 mmol) was added and refluxed for 23 h under argon. The solvent was removed under reduced
pressure and the resulting residue was purified by column chromatography (silica gel, CH2Cl2 / ethyl
acetate) to give methyl 3-(1H-perimidin-2-yl)azulene-1-carboxylate (8) (50.7 mg, 79.4 %). 8: Reddish
brown crystals (CH2Cl2 / hexane); mp 114.4-117.0 °C; IR (KBr) νmax 3594 (w), 3586 (w), 3565 (w),
3551 (w), 3544 (w), 3046 (w), 2946 (m), 1696 (s), 1674 (m), 1634 (s), 1590 (s), 1536 (m), 1520 (m),
1449 (s), 1441 (s), 1418 (s), 1372 (s), 1337 (m), 1285 (w), 1238 (s), 1225 (s), 1204 (s), 1177 (m), 1163
(m), 1132 (w), 1051 (m), 1034 (w), 907 (w), 876 (w), 824 (m), 770 (s), 750 (s), 629 (w), 571 (w), 532
(w) cm-1; ES (THF) λmax 236.2 nm (log ε 4.71), 289.7 (4.59), 301.8 (4.55), 307.9 (4.54) sh, 345.0 (4.28),
1
357.5 (4.26) nm sh; H NMR (400 MHz, DMSO-d6) δ 10.66 (1H, s, NH), 10.17 (1H, d, J=10.0 Hz, Az-
8), 9.71 (1H, d, J=10.0 Hz, Az-4), 8.95 (1H, s, Az-2), 8.18 (1H, t, J=9.6 Hz, Az-6), 7.92 (1H, dd,
J=10.0, 9.6, Az-7 or 5), 7.91 (1H, dd, J=10.0, 9.6 Hz, Az-5 or 7), 7.20-7.00 (4H, m, perimidine-H),
13
6.76 (1H, d, J=6.8 Hz, perimidine-H), 6.56 (1H, d, J=7.2 Hz, perimidine-H), 3.93 (3H, s, CO2CH3); C

HETEROCYCLES, Vol. 64, 2004
315
NMR (100 MHz, DMSO-d6) δ 164.5 (CO2Me), 150.50 (Az-C=N), 144.96 (Az-8a), 142.57 (Az-3a),
142.03 (Az-6), 141.56 (perimidine), 140.65 (Az-8), 139.14 (Az-2), 138.68 (perimidine), 138.41 (Az-4),
135.01 (perimidine), 130.43 (Az-5 and 7), 128.90 (perimidine), 127.99 (perimidine), 120.99
(perimidine), 119.11 (Az-1 or 3), 118.92 (perimidine), 117.40 (perimidine), 114.36 (Az-3 or 1), 113.71
(perimidine), 102.42 (perimidine), 51.20 (CO2CH3); MS (EI, 70eV) m/z 352.1 (M+, 100%), 351.1
(20.3), 337.1 (9.9), 321.0 (7.1), 320.0 (12.1), 294.1 (7.9), 293.1 (34.3), 292.1 (29.0), 291.1 (9.9), 290.1
(5.7), 176.0 (6.5), 160.5 (21.1), 146.0 (15.5); Anal. Calcd for C23H16N2O2 ·1/4H2O: C, 77.40; H, 4.66; N,
7.85. Found: C, 77.46; H, 4.96; N, 7.71.
Reaction of 4 with o-aminophenol (6c)
To a stirred solution of 2-(3-methoxycarbonylazulen-1-yl)ethynyltriphenylphosphonium bromide (4)
(100 mg, 0.181 mmol) in CHCl3 (10 mL), o-aminophenol (23.7 mg, 0.218 mmol) was added. The
reaction mixture was refluxed for 3 days under Ar． The solvent was removed under reduced pressure.
The residue was purified by GPC (CHCl3), to give a mixture of methyl 3-[1-(2-
hydroxyphenylimino)ethyl]azulene-1-carboxylate (9) (27.0 mg, 46.7%) and a small amount of methyl
3-acetylazulene-1-carboxylate (10)6 (detected on 1H NMR). Because the imine (9) easily converted to 10
during purification, we could not obtain analytically pure 9. 9; Brown needles (CH2Cl2/hexane); 1H NMR
(CDCl3, 400 MHz) δ 10.19 (1H, d, J=10.0 Hz, Az-8), 9.80 (1H, d, J=10.0 Hz, Az-4), 8.74 (1H, s, Az-2),
7.95 (1H, t, J=9.8 Hz, Az-6), 7.72 (1H, dd, J= 10.0, 9.8 Hz, Az-7), 7.69 (1H, dd, J=10.0, 9.8 Hz, Az-5),
6.87-7.14 (4H, m, Ph-H), 3.99 (3H, s, CO2CH3), 2.61 (3H, s, CH3C=N); MS (EI, 70eV) m/z 319.1 (M+,
100%), 318.1 (45.4), 305.0 (20.6), 304.0 (97.6), 288.1 (8.1), 261.1 (11.4), 260.1 (54.3), 245.1 (5.4),
244.0 (11.2), 212.0 (12.2), 211.1 (26.0), 186.0 (19.4), 180.0 (8.4), 155.0 (9.8), 153.1 (5.6), 152.1 (14.2),
136.5 (10.1), 133.1 (5.0), 126.0 (5.1), 65.0 (5.3). 10;6 Brown crystals (CH2Cl2 / hexane); mp 115.0-
1
116.8 °C; H NMR (CDCl3, 400 MHz) δ 10.04 (1H, d, J=10.0 Hz, Az-4 or 8), 9.82 (1H, d, J= 10.0 Hz,
Az-4 or 8), 8.79 (1H, t, J = 9.8 Hz, Az-6), 7.78-7.85 (2H, m, Az-5, 7), 3.98 (3H, s, CO2CH3), 2.73 (3H,
s, COCH3); MS (EI, 70eV) m/z 228.1 (M+, 44.4%), 214.0 (13.6), 213.1 (100), 197.0 (11.5), 127.0 (5.0),
126.0 (6.0), 91.0 (8.8).
REFERENCES
1. E. J. Corey and P. L. Fuchs, Tetrahedron Lett., 1972, 3769.
2. F. Ramirez, N. B. Desai, and N. J. McKelvie, J. Am. Chem. Soc., 1962, 84, 1745.

316
HETEROCYCLES, Vol. 64, 2004
3. (a) S. I. Miller and J. I. Dickstein, Acc. Chem. Res., 1976, 9, 358; (b) N. Morita and S.I. Miller, J.
Org. Chem., 1977, 42, 4245; (c) N. Morita, D. I. Dickstein, and S. I. Miller, J. Chem. Soc., Perkin
Trans. 1, 1979, 2103.
4. S. Ito, H. Inabe, T. Okujima, N. Morita, M. Watanabe, N. Harade, and K. Imafuku. J. Org. Chem.,
2001, 66, 7090; (b) S. Ito, A. Nomura, N. Morita, C. Kabuto, H. Kobayashi, S. Maejima, K.
Fujimori, and M. Yasunami J. Org. Chem., 2002, 67, 7295; (c) S. Ito, T. Okujima, and N. Morita, J.
Chem. Soc., Perkin Trans. 1, 2002, 1896; (d) S. Ito, H. Inabe, N. Morita, K. Ohta, T. Kitamura, and
K. Imafuku, J. Am. Chem. Soc., 2003, 125, 1669; (e) S. Ito, R. Yokoyama, T. Okujima, T. Terazono,
T. Kubo, A. Tajiri, M. Watanabe, and N. Morita, Org. Biomol. Chem., 2003, 1, 1947; (f) S. Ito, T.
Okujima, C. Kabuto, and N. Morita Tetrahedron, 2003, 59, 4651; (g) R. Yokoyama, S. Ito, T.
Okujima, T. Kubo, M. Yasunami, A. Tajiri, and N, Morita, Tetrahedron, 2003, 59, 8191; (h) S. Ito,
T. Kubo, N. Morita, T. Ikoma, S. Tero-Kubota, and A. Tajiri, J. Org. Chem., 2003, 68, 9753; (i) T.
Makinoshima, M. Fujituka, M. Sasaki, Y. Araki, O. Ito, S. Ito, and N. Morita, J. Phys. Chem. A,
2004, 108, 368; (j) S. Ito, H. Inabe, N. Moria, and A. Tajiri, Eur. J. Org. Chem., 2004, 1774; (k) S.
Ito, T. Terazono, T. Kubo, T. Okujima, N. Morita, T. Murafuji, Y. Sugihara, K. Fujimori, J.
Kawakami, and A. Tajiri, Tetrahedron, 2004, 60, 5357.
5. S. Ito, S. Moriyama, M. Nakashima, M. Watanabe, T. Kubo, M. Yasunami, K. Fujimori, and N.
Morita, Heterocycles, 2003, 61, 339.
6. (a) A. G. Anderson Jr, R. Scotoni Jr, E. J. Cowles, and C. G. Fritz, J. Org. Chem., 1957, 22, 1193;
(b) K. Sato, S. Yamashiro, K. Imafuku, S. Ito, N. Morita, and K. Fujimori, J. Chem. Res. (S), 2000,
334.