Efficient syntheses of 3H-azuleno[8,1-cd]pyridazines and their thermal and photochemical reactions

Article abstract of DOI:10.1016/j.tetlet.2010.07.007

Azulenopyridazines 6 were efficiently synthesized from ethyl 4-hydrazinylazulene-1-carboxylate (2) by p-toluenesulfonic acid-catalyzed imine formation and intramolecular cyclization followed by dehydrogenation using KOH/MeOH in one-pot operation. Thermal

Full text of DOI:10.1016/j.tetlet.2010.07.007

Tetrahedron Letters 51 (2010) 4819–4822
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Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Efficient syntheses of 3H-azuleno[8,1-cd]pyridazines and their thermal and
photochemical reactions
a
a
b,
b
Chi-Phi Wu a, , Rammohan Devulapally , Tsung-Chieh Li , Chien-Kuo Ku , Hsien-Chung Chung
*
*
a Department of Chemistry, Chung Yuan Christian University, Chungli 32023, Taiwan
b Department of Natural Science, Taipei Municipal University of Education, Taipei 10042, Taiwan
a r t i c l e i n f o
a b s t r a c t
Article history:
Azulenopyridazines 6 were efficiently synthesized from ethyl 4-hydrazinylazulene-1-carboxylate (2) by
p-toluenesulfonic acid-catalyzed imine formation and intramolecular cyclization followed by dehydroge-
nation using KOH/MeOH in one-pot operation. Thermal and photochemical reactions of azulenopyrida-
zines 6 afforded 1-vinylazulenes 7 in good yields.
Received 22 April 2010
Revised 29 June 2010
Accepted 2 July 2010
Available online 7 July 2010
Ó 2010 Published by Elsevier Ltd.
Keywords:
Azulene
Azulenopyridazine
p-Toluenesulfonic acid
Thermal reaction
Photochemical reaction
Azulene and substituted azulenes have attracted chemists’
attention for years owing to their specific physical and chemical
properties,1 as well as the potential uses in medicine as anticancer
agents,2 antiulcer drugs,3 antimicrobial agents,4 antioxidant thera-
peutics,5 and anti-inflammatory agents.6 In recent years increasing
interests in this type of compounds have focused on their optical,
electrochemical, and physicochemical properties such as dyes,7a
nonlinear optical,7b,c liquid crystals,7d near-infrared quenchers,7e
and electrochromic materials.7f Previously few synthetic methods
were reported for the syntheses of 1-vinylazulenes; most widely
used methods were the Wittig reactions of 1-azulenecarbaldehy-
des or azulene ylides using strong bases,7c,8a,b the condensation
of the active methylene group with Schiff bases which were gener-
ated from azulene carbaldehydes,8c and the condensation of the
Meldrum’s acid with 1-azulenecarbaldehyde.8d
Owing to our continuing interests related to substituted azu-
lenes,9 we have studied the syntheses of 3H-azuleno[8,1-cd]pyrid-
azines (6) and their thermal10 and photochemical reactions9d,10c,11
leading to the formation of 1-vinylazulenes 7 and report herein our
findings.
We have found that ethyl 4-hydrazinylazulene-1-carboxylate
(2) was readily prepared in 80% yield from ethyl 4-ethoxyazu-
lene-1-carboxylate (1)9a and hydrazine in refluxing ethanol for
1 h. A solution of 2 and acetone in ethanol was refluxed for 1 h
afforded ethyl 4-[2-(propan-2-ylidene)hydrazinyl]azulene-1-car-
boxylate (4a) in 97% yield, which was treated with catalytic
amount of p-toluenesulfonic acid (p-TSA) at reflux temperature
for 1 h undergoing intramolecular Friedel–Crafts type cyclization12
to afford dihydroazulenopyridazine 5a in 87% yield (Scheme 1);
compound 5b was obtained in 94% yield by replacing acetone with
2-butanone (Scheme 1). The structures of the dihydroazulenopy-
ridazines 5a and 5b were confirmed by 1H NMR, 13C NMR, IR,
and MS data analyses.
In order to oxidize dihydroazulenopyridazines 5 to azulenopy-
ridazines 6, we found, after several attempts with various reaction
conditions,10a,13 that treatments of dihydroazulenopyridazines 5a
and 5b with KOH/MeOH solution in an open system at room tem-
perature for 1 h afforded the desired dehydrogenated products 6a
and 6b in 96% and 94% yields, respectively (Table 1, entries 1 and
2). When dihydroazulenopyridazine 5a in MeOH was treated with
Br2 at room temperature for 0.3 h, 6a was also obtained in 88%
yield (Table 1, entry 3). The structures of the azulenopyridazines
6a and 6b were confirmed by 1H NMR, 13C NMR, IR, and MS data
analyses. The structure of 6a was further unambiguously con-
firmed by single-crystal X-ray analysis and the ORTEP structure
of 6a is shown in Figure 1.14
In order to improve the efficiency of the synthetic procedure for
the preparation of azulenopyridazines 6, we decided to test one-
pot reaction without purification of 5. A solution of ethyl 4-hydra-
zinylazulene-1-carboxylate (2), acetone (3a), and catalytic amount
of p-TSA was refluxed in ethanol for 1 h afforded the dihydroazu-
lenopyridazine 5a, which was further treated with KOH/MeOH
solution in an open system at room temperature for 1 h afforded
the desired dehydrogenated product 6a in 86% yield (Table 2, entry
* Corresponding authors. Tel.: +886 3 2653333; fax: +886 3 2653399 (C.-P.W.).
E-mail addresses: chiphi@cycu.edu.tw (C.-P. Wu), ramdevula@gmail.com,
ramu_devula@yahoo.com (R. Devulapally), kuo@tmue.edu.tw (C.-K. Ku).
0040-4039/$ - see front matter Ó 2010 Published by Elsevier Ltd.
doi:10.1016/j.tetlet.2010.07.007

4820
C.-P. Wu et al. / Tetrahedron Letters 51 (2010) 4819–4822
EtO2C
R1
EtO2C
EtO2C
EtO2C
O
CH2R2
p-TSA (0.1 equiv.)
NH2NH2
3
R1
CH2R2
NH
EtOH, reflux, 1 h
NH-NH2
R1
EtOH, reflux, 1 h
80%
EtOH, reflux, 1 h
NH-N
OEt
HN
CH2R2
1
2
4
5
4a: R1 = Me, R2 = H, 97%
5a: R1 = Me, R2 = H, 87%
4b
5b:
R1 = Me, R2 = Me, 94%
: R1 = Me, R2 = Me, 95%
Scheme 1. Syntheses of dihydroazulenopyridazines 5a and 5b.
Table 1
Table 2
Dehydrogenation of dihydroazulenopyridazines 5a and 5b
One-pot method for the syntheses of azulenopyridazines 6
EtO2C
EtO2C
EtO2C
R1
EtO2C
HN
O
KOH/MeOH, air, rt
or
p-TSA (0.1 equiv.)
,
3
CH2 R2
EtOH, reflux, 1.0−1.5 h;
R1
CH2R2
R1
CH2R2
R1
CH2R2
NH
KOH/MeOH, air, rt, 1 h
Br2, MeOH, air, rt
N
N
6
N
NHNH2
N
2
5
6
Entry R1
R2
H
Reactant 3
Time (h) p-
TSA
Product 6 yielda
(%)
Entry R1
R2
H
Reactant 5 Reagent Time (h) Product 6 yielda (%)
1
2
3
Me
5a
KOH
KOH
Br2
1.0
1.0
0.3
96 6a
94 6b
88 6a
1
2
3
4
5
6
Me
Me Me
Me CHMe2 3c
Et
3a
3b
1.0
1.0
1.2
1.2
1.5
1.0
86 6a
80 6b
82 6c
85 6d
75 6e
66 6f
Me Me 5b
Me 5a
H
a
Isolated yields after silica gel column chromatography.
Me
3d
3e
3f
Me CO2Et
Ph
—
H
—
Me
CO2Et
O
7
1.2
N
3g
N
79 6g
a
Isolated yields after silica gel column chromatography.
to know the source of the newly bonded proton in the azulene ring
and to have a better understanding of the plausible mechanism of
the formation of product 7, we envisioned that deuterium-labeling
experiments would give the answer. We synthesized the deute-
rium-labeled azulenopyridazine 8 using a similar condition for 6
except that commercially available acetone-d6 (3a0) was used. A di-
lute solution of deuterium-labeled azulenopyridazine 8 in toluene
when heated at reflux for 2 h gave the deuterium-incorporated
product 9 in 99% yield, whereas 65% yield of 9 was obtained in pho-
tochemical condition (Scheme 2). This result indicates that the
newly bonded proton in the azulene ring of the product 7 came
from the methyl or the methylene group of the reactant 6 through
an intramolecular 1,5-hydrogen shift, not from the solvent or
water during workup (Table 3).
To study the scope of this transformation, various substituted
substrates 6b–6g were examined thermally and photochemically,
and the results are summarized in Table 3. When substituents at
R1 and R2 were methyl groups, there was a possibility of either
the methylene hydrogens (CH2R2) or the methyl hydrogens (R1)
participating in this reaction. When heated at reflux for 2 h, 6b pro-
duced ethyl 3-(but-2-en-2-yl)azulene-1-carboxylate (7b) as a mix-
ture of diastereomers (E/Z = 0.9:1.0) in 96% yield, when irradiated
with light of 350 nm region for 12 h, 6b gave 7b as a mixture of
diastereomers in a slightly different ratio (E/Z = 1.0:0.9) in 73%
yield along with ethyl 3-(but-1-en-2-yl)azulene-1-carboxylate
(7b0) as a minor product in 14% yield (Table 3, entry 2). The forma-
tion of 7b as a major product over 7b0 indicates that the reaction
pathway is favored via methylene hydrogen abstraction (CH2R2)
Figure 1. ORTEP diagram of ethyl 3,3-dimethyl-3H-azuleno[8,1-cd]pyridazine-5-
carboxylate (6a).
1).15 In order to test the compatibility of the one-pot procedure, we
prepared several substituted azulenopyridazines 6b–6g from sub-
strates 2 and various ketones 3 in a similar procedure (Table 2, en-
tries 2–7). 2-Butanone (3b), isobutyl methyl ketone (3c), and
pentan-3-one (3d) gave the 6b–6d, respectively, in excellent yields
(Table 2, entries 1–4); however ethyl 3-oxobutanoate (3e), aceto-
phenone (3f), and 1-cyclohexyl-ethanone (3g) produced 6e–6g in
good (66–79%) yields (Table 2, entries 5–7). These results indicate
the efficiency of the imine formation, intramolecular Friedel–Crafts
reaction, and dehydrogenation in one-pot operation to give 6.
We observed that azulenopyridazine 6a, upon refluxing in tolu-
ene for 2 h gave ethyl 3-(prop-1-en-2-yl)azulene-1-carboxylate
(7a) in 96% yield by elimination of N2.16 We envisioned that 6a
might proceed via a similar reaction under photochemical condi-
tions. Several experiments in various conditions were carried out
with 6a by changing the wavelength of the incident light, the sol-
vents, and the irradiation time period. The best results were ob-
tained when 6a in acetone was irradiated with light of 350 nm
region for 12 h to give 7a in 72% yield (Table 3, entry 1).17 In order

C.-P. Wu et al. / Tetrahedron Letters 51 (2010) 4819–4822
4821
Table 3
The preparation of 1-vinyl azulenes 7 from 3H-azuleno[8,1-cd]pyridazines 6 in thermal and photochemical reaction conditions
EtO2C
EtO2C
Toluene, reflux, 2 h
or
R1
R1
CH2R2
6
hν, acetone, 12 h
N
N
R2
7
Entry
R1
R2
Reactant 6
Product 7 thermal conditions (
D
) Yielda (%)
Product 7 photochemical conditions (hm
) Yielda (%)
1
2
3
4
5
6
Me
Me
Me
Et
Me
Ph
H
Me
CHMe2
Me
CO2Et
H
6a
6b
6c
6d
6e
6f
96 7a
72 7a
96 (E/Z = 0.9:1.0) 7b
91 (E/Z = 1.0:0.8) 7c; 6 7c0
98 (E/Z = 0.4:1.0) 7d
97 (E/Z = 0.8:1.0) 7e
86 7f
73 (E/Z = 1.0:0.9) 7b; 14 7b0
60 (E/Z = 1.0:0.8) 7c; 14 7c0
73 (E/Z = 0.8:1.0) 7d
60 (E/Z = 1.0:0.9) 7e; 18 7e0
74 7f
CO2Et
CO2Et
7
—
—
71 7g
N
N
6g
98 7g
a
Isolated yields after silica gel column chromatography; all compounds were characterized by 1H NMR, 13C NMR, IR, and MS data analyses, 14% yield of ethyl 3-(but-1-en-
2-yl)azulene-1-carboxylate (7b0) was isolated as a minor product; 6% ( ) yields of ethyl 3-(4-methylpent-1-en-2-yl)azulene-1-carboxylate (7c0) were isolated as
D) and 14% (hm
a minor product; 18% yield of ethyl 3-(4-ethoxy-4-oxobut-1-en-2-yl)azulene-1-carboxylate (7e0) was isolated as a minor product; entry 6 (h
m
) reaction completed in 1 h.
CD3
CO2Et
Toluene, reflux, 2 h, 99%
or
EtO2C
CO2Et
O
3a'
p-TSA (0.1 equiv.)
,
CD3
EtOH, reflux, 1 h;
hν, acetone, 12 h, 65%
1,5-deuterium shift
KOH, MeOH, air, rt, 1 h
94%
CD3
CD3
N
CD3
D
N
NHNH2
D2C
2
8
9
Scheme 2. Deuterium-labeling experiment.
to form more highly substituted product double bond (Table 3, en-
try 2). In the case of substituents at R1 and R2 were methyl and an
isopropyl groups respectively, 7c was produced as a mixture of E/Z
diastereomers (E/Z = 1.0:0.8) in 91% yield along with 3-(4-methyl-
pent-1-en-2-yl)azulene-1-carboxylate (7c0) in 6% yield in thermal
reaction, whereas 60% yield of 7c (E/Z = 1.0:0.8) and 14% yield of
7c0 were obtained under photochemical conditions (Table 3, entry
3). Interestingly, when R1 was an ethyl and R2 was a methyl group,
only the more substituted olefin 7d was generated as a mixture of
E/Z diastereomers in 98% (E/Z = 0.4:1.0) and 73% (E/Z = 0.8:1.0)
yields under the thermal and photochemical conditions, respec-
tively (Table 3, entry 4). Substrate 6e containing R2 as an ethoxy-
carbonyl group, when heated at reflux for 2 h, produced 7e (E/
Z = 0.8:1.0) in 97% yield (Table 3, entry 5), while, under a standard
photochemical conditions, gave 7e (E/Z = 1.0:0.9) in 60% yield
along with 7e0 in 18% yield (Table 3, entry 5). Similarly, substrate
6f (R1 as a phenyl group) produced 7f in 87% yield thermally and
the same in 74% yield photochemically (Table 3, entry 6). Further-
more we extended the thermal and photochemical reactions to spi-
rocyclic azulenopyridazine; thermolysis of 6g produced 7g in 98%
yield, while irradiation (350 nm region, 12 h) of 6g gave 7g in
71% yield (Table 3, entry 7).
Based on the deuterium-labeling studies (Scheme 2) and the
formation of products (Table 3), a plausible mechanism is proposed
CO2Et
CO2Et
CO2Et
Toluene, reflux, 2 h
or
Me
H
H
hν, acetone, 12 h
CH2CHMe2
H
Me
N
6c
N
Me2HCH2C
H
CHMe2
H
7c'
7c
CO2Et
H2
path a H-shift from more
substituted carbon
H-shift from less
path b
substituted carbon
C
H
1,5-hydrogen
shift
N2
Ι
CHMe2
H
Scheme 3. Plausible mechanism for the formation of 1-vinylazulenes 7c and 7c0 from azulenopyridazine 6c in thermal or photochemical conditions.

4822
C.-P. Wu et al. / Tetrahedron Letters 51 (2010) 4819–4822
P.; Jiang, G. J.; Hung, Y.-Y.; Yang, P.-W. J. Chin. Chem. Soc. 1984, 31, 369–375; (d)
Ho, T.-I.; Ku, C.-K.; Liu, R. S. H. Tetrahedron Lett. 2001, 42, 715–717.
10. (a) Dervan, P. B.; Santilli, D. S. J. Am. Chem. Soc. 1980, 102, 3863–3870; (b)
Santilli, D. S.; Dervan, P. B. J. Am. Chem. Soc. 1979, 101, 3663–3664; (c) Levek, T.
J.; Kiefer, E. F. J. Am. Chem. Soc. 1976, 98, 1875–1879; (d) Novák, Z.; Vincze, Z.;
Czégény, Z.; Magyarfalvi, G.; Smith, D. M.; Kotschy, A. Eur. J. Org. Chem. 2006,
3358–3363; (e) Simoni, D.; Rondanin, R.; Furnò, G.; Aiello, E.; Invidiata, F. P.
Tetrahedron Lett. 2000, 41, 2699–2703.
in Scheme 3. Azulenopyridazine 6c decomposes under thermal or
photochemical condition with elimination of N2 to give biradical
I, which subsequently undergoes 1,5-hydrogen shifts from the
more substituted carbon (path a) or less substituted carbon (path
b) via six-membered ring transition structures leading to the for-
mation of 7c or 7c0, respectively.
11. (a) Selco, J. I.; Brooks, T.; Chang, M.; Trieu, M. T. J. Org. Chem. 1994, 59, 429–433;
(b) Fox, M. A.; Lemal, D. M.; Johnson, D. W.; Hohman, J. R. J. Org. Chem. 1982, 47,
398–404; (c) Payne, A. D.; Wege, D. J. Chem. Soc., Perkin Trans. 1 2001, 1579–
1580; (d) Heath, R. B.; Bush, L. C.; Feng, X.-W.; Berson, J. A.; Scaiano, J. C.;
Berinsta, A. B. J. Phys. Chem. 1993, 97, 13355–13357; (e) Blay, G.; Garcia, B.;
Molina, E.; Pedro, J. R. Org. Lett. 2005, 7, 3291–3294; (f) Hsu, D.-S.; Chou, Y. Y.;
Tung, Y. S.; Liao, C.-C. Chem. Eur. J. 2010, 16, 3121–3131.
In summary, azulenopyridazines 6, which can be synthesized
efficiently in a one-pot operation from ethyl 4-hydrazinylazu-
lene-1-carboxylate (2), undergoes thermal as well as photochemi-
cal reaction with elimination of N2 followed by a 1,5-hydrogen
shift to give 1-vinylazulenes 7 in good yields.
12. Kametani, T.; Kigasawa, K.; Hiiragi, M.; Ishimaru, H.; Uryu, T.; Haga, S. J. Chem.
Soc., Perkin Trans. 1 1973, 471–472.
Acknowledgments
13. (a) Hoogesteger, F. J.; Havenith, R. W. A.; Zwikker, J. W.; Jenneskens, L. W.;
Kooijman, H.; Veldman, N.; Spek, A. L. J. Org. Chem. 1995, 60, 4375–4384. and
references cited therein; (b) Overberger, C. G.; O’shaughnessy, M. T.; Shalit, H. J.
Am. Chem. Soc. 1949, 71, 2661–2666.
14. Crystallographic data for the structure 6a in this paper have been deposited
with the Cambridge Crystallographic Data Center as supplementary
publication no. CCDC 770915. Copies of the data can be obtained, free of
charge, on application to CCDC, 12 Union Road, Cambridge CB2 1EZ, UK, (fax:
We gratefully acknowledge Professor Chun-Chen Liao for helpful
discussions. This research project was funded by the CYCU distinc-
tive research area project as grant CYCU-98-CR-CH and National Sci-
ence Council (NSC) of Taiwan(Grant Nos.: NSC98-2119-M-007-006,
98-2119-M-033-003). R.D. thanks NSC of Taiwan (Grant Nos.: NSC
+44
(0)
1223
336033
or
e-mail:
deposit@ccdc.cam.ac.uk
or
98-2811-M-033-016, 99-2811-M-033-009) for
fellowship.
a postdoctoral
www.ccdc.cam.ac.uk/data_request/cif).
15. General one-pot procedure for the preparation of pyperazine 6a: To a solution
of ethyl 4-hydrazinylazulene-1-carboxylate (2) (300 mg, 1.3 mmol) in 4 mL
ethanol, acetone (110 mg, 2 mmol) and p-toluenesulfonic acid (23 mg,
0.1 mmol) were added and refluxed for 1 h. The reaction mixture was cooled
to room temperature; 1 mL of 1% KOH/MeOH solution was added and stirred
for 1 h. The reaction was quenched with distilled water and the reaction
mixture was extracted with EtOAc. The organic layer was dried over MgSO4,
concentrated, and chromatographed on silica gel column (Hexane/EtOAc = 4:1)
to give 6a (300.6 mg, 1.12 mmol) as a yellow-green solid (mp: 127 °C) in 86%
yield. 1H NMR (CDCl3, 300 MHz) d 1.41–1.46 (t, J = 7.2 Hz, 3H), 1.76 (s, 6H),
4.38–4.45 (q, J = 7.2 Hz, 2H), 7.45–7.51 (t, J = 9.9 Hz, 1H), 7.89–7.96 (t,
J = 9.9 Hz, 1H), 8.15 (d, J = 9.9 Hz, 1H) 8.39 (s, 1H), 9.43 (d, J = 9.6 Hz); 13C
NMR (CDCl3, 75 MHz) d 14.5 (1°), 31.5 (1°), 60.1 (2°), 69.8 (4°), 116. 3 (4°),
121.1 (4°), 124.6 (4°), 128.0 (3°), 129.1 (3°), 138.0 (4°), 138.9 (3°), 139.7 (3°),
140.0 (3°), 143.5 (4°), 165.1 (4°); IR (KBr, neat) 1677, 1602, 1031 cmꢀ1; MS
(ESI) relative intensity: 291 (M++23, 100), 269 (12), 254 (15), 195 (5); MS (EI)
relative intensity: 240 (M+ꢀ28, 54), 195 (27), 167 (100), 152 (55).
References and notes
1. (a) Chen, S. L.; Klein, R.; Hafner, K. Eur. J. Org. Chem. 1998, 423–433; (b) Nozoe,
T.; Takeshita, H. Bull. Chem. Soc. Jpn. 1996, 69, 1149–1178; (c) Salman, H.;
Abraham, Y.; Tal, S.; Meltzman, S.; Kapon, M.; Tessler, N.; Speiser, S.; Eichen, Y.
Eur. J. Org. Chem. 2005, 2207–2212.
2. (a) Asato, A. E.; Peng, A.; Hossain, M. Z.; Mirzadegan, T.; Bertram, J. S. J. Med.
Chem. 1993, 36, 3137–3147; (b) Hong, B.-C.; Jiang, Y.-F.; Kumar, E. S. Bioorg.
Med. Chem. Lett. 2001, 11, 1981–1984; (c) Hidetsugu, W.; Kana, H.; Keiko, Y.;
Ken, H.; Hirotaka, K.; Hirofumi, N.; Teruo, K.; Kazue, S.; Seiji, S.; Susumu, S.;
Shuichi, K.; Hidecki, N.; Noboru, M.; Hiroshi, S. Anticancer Res. 2003, 23, 4747–
4755.
3. Yanagisawa, T.; Wakabayashi, S.; Tomiyama, T.; Yasunami, M.; Takase, K. Chem.
Pharm. Bull. 1988, 36, 641–647.
4. (a) Sullivan, B. W.; Faulkner, D. J. J. Org. Chem. 1986, 51, 5134–5136; (b) Bozin,
B.; Mimica-Dukic, N.; Bogavac, M.; Suvajdzic, L.; Simin, N.; Samojlik, I.;
Couladis, M. Molecules 2008, 13, 2058–2068; (c) Wang, D.-L.; Xu, J.; Han, S.; Gu,
Z. Chin. J. Org. Chem. 2008, 28, 2016–2019.
16. General procedure for the preparation of 1-vinylazulene 7a in thermal
condition: To a solution of 6a (268 mg, 1.0 mmol) in 10 mL of toluene was
refluxed for 2 h. The reaction mixture was concentrated to give the crude
residue which was purified by silica gel column chromatography (Hexane/
EtOAc = 8:1) to give the 7a (230.4 mg, 0.96 mmol) as a purple color solid (mp:
44–44.5 °C) in 96% yield.
5. Becker, D. A.; Ley, J. J.; Echegoyen, L.; Alvarado, R. J. Am. Chem. Soc. 2002, 124,
4678–4684.
6. Rekka, E.; Chrysselis, M.; Siskou, I.; Kourounakis, A. Chem. Pharm. Bull. 2002, 50,
904–907.
17. General procedure for the preparation of 1-vinylazulene 7a in photochemical
condition: To a solution of 6a (268 mg, 1.0 mmol) in 10 mL of acetone in a
pyrex vessel was degassed with Argon. The solution was irradiated with
350 nm UV light in a Rayonet reactor for 12 h. The reaction mixture was
concentrated to give the crude residue which was purified by silica gel column
chromatography (Hexane/EtOAc = 8:1) to give the 7a (172.8 mg, 0.72 mmol) in
72% yield. 1H NMR (CDCl3, 300 MHz) d 1.40–1.45 (t, J = 7.2 Hz, 3H), 2.27 (s, 3H),
4.37–4.45 (q, J = 7.2 Hz, 2H), 5.15 (s, 1H), 5.38 (s, 1H), 7.35–7.41 (t, J = 9.9 Hz,
1H), 7.43–7.49 (t, J = 9.9 Hz, 1H), 7.70–7.77 (t, J = 9.6 Hz, 1H), 8.31 (s, 1H), 8.74
(d, J = 9.6 Hz, 1H), 9.60 (d, J = 9.3 Hz, 1H); 13C NMR (CDCl3, 75 MHz) d 14.6 (1°),
24.8 (1°), 59.8 (2°), 114.9 (2°), 115.5 (4°), 126.6 (3°), 127.4 (3°), 131.6 (4°),
137.1 (3°), 137.8 (3°), 138.3 (3°), 139.3 (3°), 139.4 (4°), 140.0 (4°) 141.1 (4°),
165.5 (4°); IR (KBr, neat) 1687, 1042 cmꢀ1; MS (ESI) relative intensity: 263
(M++23, 100), 241 (11), 195 (4); MS (EI) relative intensity: 240 (M+ꢀ28, 56),
195 (26), 167 (100), 152 (56).
7. (a) Razus, A. C.; Birzan, L.; Nae, S.; Cristian, L.; Chiraleu, F.; Cimpeanu, V. Dyes
Pigm. 2003, 57, 223–233; (b) Lacroix, P. G.; Malfant, I.; Iftime, G.; Razus, A. C.;
Nakatani, K.; Delaire, J. A. Chem. Eur. J. 2000, 6, 2599–2608; (c) Iftime, G.;
Lacroix, P. G.; Nakatani, K.; Razus, A. C. Tetrahedron Lett. 1998, 39, 6853–6856;
(d) Estdale, S. E.; Brettle, R.; Dunmur, D. A.; Marson, C. M. J. Mater. Chem. 1997,
7, 391–401; (e) Pham, W.; Weissleder, R.; Tung, C.-H. Angew. Chem., Int. Ed.
2002, 41, 3659–3662; (f) Ito, S.; Morita, N. Eur. J. Org. Chem. 2009, 4567–4579.
8. (a) McDonald, R. N.; Stewart, W. S. J. Org. Chem. 1965, 30, 270–273; (b) Currie, J.
O., Jr.; Labar, R. A.; Breazeale, R. D.; Anderson, A. G., Jr. Justus Liebigs Ann. Chem.
1973, 166–180; (c) Razus, A. C.; Nitu, C.; Tecuceanu, V.; Cimpeanu, V. Eur. J. Org.
Chem. 2003, 4601–4610. and references cited therein; (d) Razus, A. C.; Birzan,
L.; Cristian, L.; Tecuceanu, V. ARKIVOC 2009, xi, 31–34.
9. (a) Wu, C.-P.; Cheng, L.-Y.; Wen, Y.-S.; Hsiao, C.-D. J. Chin. Chem. Soc. 1997, 44,
265–269; (b) Yang, P.-W.; Chen, J.-A.; Wakabayashi, H.; Shindo, K.; Kurihara, T.;
Wu, C.-P.; Yasunami, M.; Nozoe, T. J. Chin. Chem. Soc. 1997, 44, 5–7; (c) Wu, C.-