Reaction of azulenes with 1-trifluoromethanesulfonylpyridinium trifluoromethanesulfonate (TPT) and synthesis of the parent azulene.

Article abstract of DOI:10.1039/b212484j

2-Azulenyl trifluoromethanesulfonate was prepared by the reaction of 2-hydroxyazulene with trifluoromethanesulfonic anhydride in the presence of triethylamine as a base. Under the use of pyridine, 1-trifluoromethanesulfonylpyridinium trifluoromethanesulfonate further reacted with 2-azulenyl trifluoromethanesulfonate to give 1-(1-trifluoromethanesulfonyl-1,4-dihydropyridin-4-yl)azulenyl trifluoromethanesulfonate. Moreover, we found that azulenes also reacted with 1-trifluoromethanesulfonylpyridinium trifluoromethanesulfonate to give 4-(1-azulenyl)-1,4-dihydropyridine derivatives and 6-(1-azulenyl)-1-trifluoromethanesulfonyl-1-aza-hexa-1,3,5-triene depending on the reaction conditions. 2-Azulenyl trifluoromethanesulfonate was converted finally into the parent azulene in excellent yield by palladium-catalyzed reduction using formic acid as a reducing reagent.

Full text of DOI:10.1039/b212484j

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Reaction of azulenes with 1-trifluoromethanesulfonylpyridinium
trifluoromethanesulfonate (TPT) and synthesis of the parent
azulene
a
a
a
a
a
Shunji Ito, Ryuji Yokoyama, Tetsuo Okujima, Tomomi Terazono, Takahiro Kubo,
b
c
a
Akio Tajiri, Masataka Watanabe and Noboru Morita*
a
Department of Chemistry, Graduate School of Science, Tohoku University, Sendai 980-8578,
Japan. E-mail: morita@funorg.chem.tohoku.ac.jp; Fax: ϩ81 22 217 7714;
Tel: ϩ81 22 217 7714
Department of Materials Science, Faculty of Science and Technology, Hirosaki University,
Hirosaki 036-8561, Japan
b
c
Institute of Multidisiplinary Research for Advanced Materials, Tohoku University,
Katahira 2-1-1, Aoba-ku, Sendai 980-8577, Japan
Received 20th December 2002, Accepted 7th April 2003
First published as an Advance Article on the web 23rd April 2003
2
-Azulenyl trifluoromethanesulfonate was prepared by the reaction of 2-hydroxyazulene with trifluoromethane-
sulfonic anhydride in the presence of triethylamine as a base. Under the use of pyridine, 1-trifluoromethane-
sulfonylpyridinium trifluoromethanesulfonate further reacted with 2-azulenyl trifluoromethanesulfonate to give
1
-(1-trifluoromethanesulfonyl-1,4-dihydropyridin-4-yl)azulenyl trifluoromethanesulfonate. Moreover, we found that
azulenes also reacted with 1-trifluoromethanesulfonylpyridinium trifluoromethanesulfonate to give 4-(1-azulenyl)-
,4-dihydropyridine derivatives and 6-(1-azulenyl)-1-trifluoromethanesulfonyl-1-aza-hexa-1,3,5-triene depending on
1
the reaction conditions. 2-Azulenyl trifluoromethanesulfonate was converted finally into the parent azulene in
excellent yield by palladium-catalyzed reduction using formic acid as a reducing reagent.
which employs pyridine and cyclopentadiene as the starting
Introduction
5
6
materials. The Nozoe –Yasunami method is a process via
tropolone and also 2H-cyclohepta[b]furan-2-ones using cyclo-
heptatriene or cyclopentadiene as the starting material. How-
ever, the synthesis of azulenes by way of tropolone needs at
Azulene and its derivatives are important building blocks
for syntheses of medicines
1a,b
and a variety of extended
π-electronic systems such as super-stabilized azulenylmethyl
1c
1d–h
1i,j
6
carbocation, azulenylaromatic compounds,
calixazulene,
least 7 steps. The latest method by Scott consists of diazo-
1k
1l
azuliporphyrin, azulenocoronands, etc. For the purpose of
the preparation of these compounds, azulene remains relatively
difficult to be synthesized. The exploitation of a facile synthetic
method for azulene from cycloheptatriene is of current interest.
methylation and the intramolecular cycloaddition of 3-phenyl-
propanoyl chloride starting from cinnamic acid, followed by
7
dehydration as shown in Scheme 1.
Recently, we have reported the synthesis of 2H-cyclo-
2
8
9
Since Plattner’s original synthesis of azulene, a wide variety of
hepta[b]furan-2-ones and 2-hydroxyazulene from the cyclo-
9,10
synthetic methods for azulene and its derivatives have been
adduct of cycloheptatriene with dichloroketene. One target
in our series of these studies is the synthesis of azulene itself
starting from commercially available cycloheptatriene, which
3
reported. There are three efficient approaches to the parent
1j,4
hydrocarbon. One of them is the Ziegler–Hafner method
Scheme 1
T h i s j o u r n a l i s © T h e R o y a l S o c i e t y o f C h e m i s t r y 2 0 0 3
O r g . B i o m o l . C h e m . , 2 0 0 3 , 1, 1 9 4 7 – 1 9 5 2
1947

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could be utilized as a source for the seven-membered ring of
azulenes.
On the other hand, Ortar reported the reduction of naphthyl
triflate 7 into naphthalene 8 in excellent yield using a
11
palladium-catalyzed reaction, as shown in Scheme 2.
Scheme 2
Scheme 4
Therefore, we planned to apply this method to 2-hydroxy-
azulene 9 for the preparation of azulene by way of 2-azulenyl
trifluoromethanesulfonate. We report herein the reaction
of azulenes with trifluoromethanesulfonic anhydride in the
presence of a base and a new synthetic pathway from
cycloheptatriene to azulene.
Results and discussion
Initially, in order to prepare 2-azulenyl trifluoromethane-
sulfonate 10 we examined the reaction of 2-hydroxyazulene 9
with trifluoromethanesulfonic anhydride in the presence of a
base. The reaction of compound 9 with trifluoromethane-
sulfonic anhydride in CH Cl2 at room temperature in the
2
presence of triethylamine gave 2-azulenyl trifluoromethane-
sulfonate 10 in 95% yield. Although triethylamine gave a
satisfactory result, the use of pyridine as a base afforded
1
1
-(1-trifluoromethanesulfonyl-1,4-dihydropyridin-4-yl)azulene
1 in 12% yield in addition to 10 (41%). A plausible reaction
pathway for the formation of compound 11 is assumed to pro-
ceed via compound 10. Indeed, the reaction of compound 10
under the same reaction conditions afforded 1-(1-trifluoro-
methanesulfonyl-1,4-dihydropyridin-4-yl)azulen-2-yl trifluoro-
methanesulfonate 11 in 89% yield (Scheme 3).
The reaction of compound 10 with a large excess of tri-
fluoromethanesulfonic anhydride and pyridine afforded 1,3-
bis(1-trifluoromethanesulfonyl-1,4-dihydropyridin-4-yl)azulen-
Scheme 5
2
-yl trifluoromethanesulfonate 12 in 79% yield (Scheme 4).
In contrast to 2-azulenyl triflate 10, the reaction of the
We investigated the conditions favoring o-attack in the
reaction of azulene with the pyridinium salt. We found
azulene gave preferentially o-addition and ring-opening
product 16 in 67% yield when 1.2 equivalents of trifluoro-
parent azulene with a large excess of trifluoromethanesulfonic
anhydride in the presence of pyridine gave 1,3-bis(1-trifluoro-
methanesulfonyl-1,4-dihydropyridin-4-yl)azulene 13 and 5-
azulenyl-2,4-pentadienal 14
respectively, as shown in Scheme 5.
The configuration of the alkenyl chain moiety in 14 was
deduced to be all trans on the basis of NOE experiments as
shown in Fig. 1 and also by analysis of the H–H spin-coupling
constants. The coupling constants of 2-H with 3-H, 3-H with
12
methanesulfonic anhydride and pyridine were used. A
13,14
in 67% and 29% yields,
plausible mechanism for this reaction would be such as shown
in Scheme 6. The reaction of trifluoromethanesulfonic
anhydride with pyridine forms 1-trifluoromethanesulfonyl-
15
pyridinium trifluoromethanesulfonate (TPT) 15. Compound
15 is attacked by azulene at the o-position of the pyridine, fol-
lowed by ring-opening reaction to give compound 16, which
undergoes easily hydrolysis during the work-up or purification
on silica gel.
4
1
-H, and 4-H with 5-H were determined to be 14.9, 11.2, and
4.9 Hz, respectively.
Scheme 3
1
948
O r g . B i o m o l . C h e m . , 2 0 0 3 , 1, 1 9 4 7 – 1 9 5 2

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Table 1 Palladium-catalyzed reduction of 10
a
Entry
Pd catalyst
Ligand
Solvent
Time/h
Yield (%)
1
2
3
4
5
6
5% Pd(OAc)2
5% Pd(OAc)2
5% Pd(OAc)2
5% Pd(OAc)2
2% Pd (dba)
10% PPh3
10% PPh3
10% BINAP
10% P(o-tolyl)
5% BINAP
5% P(o-tolyl)
THF
4
4
1
12
2
24
53
63
77
80
89
96
Dioxane
Dioxane
Dioxane
Dioxane
Dioxane
2
3
3
2% Pd (dba)
2
a
Isolated yield.
Scheme 6
examined for the synthesis of the parent azulene. These results
are summarized in Table 1.
A better yield was observed by using dioxane instead of THF
as a solvent (entries 1 and 2). Although a longer reaction time
was required when P(o-tolyl) was used as a phosphine ligand,
3
the yield of the parent hydrocarbon increased (entries 2, 3, and
4
). A higher yield was achieved by the use of Pd (dba) as a
2 3
catalyst (entries 5 and 6), where the parent azulene (1) was
obtained in as high as 96% yield by the combination of
Pd (dba)3 and P(o-tolyl)3 in dioxane. Therefore, 2-hydroxy-
azulene can be converted in excellent yield to the parent azulene
2
Fig. 1 NOE enhancements of 14.
(
Scheme 8).
A similar reaction of azulene with a 1-benzoylpyridinium
salt to give 1,3-bis(1-benzoyl-1,4-dihydropyridin-4-yl)azulene
has been already reported, where formation of a ring-opening
12
product like 14 when the aromatic hydrocarbon compounds
12
react with pyridinium salts was not reported although the
1
6
additions of a number of nucleophiles, such as hydroxide ions,
4,13,16a,17
amines1
and compounds with an active methylene
to pyridinium salts and subsequent ring-opening of
6a,18
group,
pyridine have been reported. The fluorination and pyridinyl-
ation of azulene with several kinds of N-fluoropyridinium salts
19
were also reported. At least, there is no report of the nucleo-
philic addition of azulene to TPT, subsequent ring-opening of
pyridine and hydrolysis to give 5-(azulen-1-yl)penta-2,4-dienal
whose derivatives were considered to play an important role
14
14c
in multistep reversible redox systems, dyes and bacterio-
2
0
rhodopsin so far. Therefore, further investigation on the
reaction of TPT with more reactive azulene derivatives and
other aromatic compounds is now in progress.
Scheme 8
Trifluoromethanesulfonylation of 2-hydroxyazulene 9 with
Finally, the removal of a trifluoromethanesulfonyloxy group
from 10 by a palladium-catalyzed reduction (see Scheme 7) was
trifluoromethanesulfonic anhydride easily proceeded in the
presence of triethylamine as a base to give 2-azulenyl trifluoro-
methanesulfonate 10 in 95% yield. We found that azulene
preferentially attacked the p- and/or o-position of TPT
depending on the amount of pyridine to give 1-(1,4-dihydro-4-
pyridinyl)azulene and/or 6-(1-azulenyl)-1-trifluoromethane-
sulfonyl-1-azahexa-1,3,5-triene, respectively. Moreover, we
found palladium-catalyzed reduction of 2-azulenyl trifluoro-
methanesulfonate to give the parent azulene in excellent yields.
Scheme 7
O r g . B i o m o l . C h e m . , 2 0 0 3 , 1, 1 9 4 7 – 1 9 5 2
1949

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Experimental
125.73 (C-5), 124.83 (C-7), 120.85 (C-2Ј and C-6Ј), 119.79
(
(
q, J 324.0, OTf or Tf ), 118.76 (q, J 321.0, OTf or Tf ), 117.96
C-1), 111.40 (C-3Ј and C-5Ј), 105.14 (C-3), and 28.59 (C-4Ј);
General
ϩ
ϩ
MS (70 eV) m/z (EI) 487 (M , 56%), 354 (M Ϫ CF SO , 47),
Melting points were determined on a Yanagimoto micro melt-
ing point apparatus MP-S3 and are uncorrected. Mass spectra
were obtained with a JEOL HX-110 or a Hitachi M-2500
instrument usually at 70 eV. IR and UV spectra were measured
on a Shimadzu FTIR-8100M and a Hitachi U-3410 spectro-
3
2
2
21 (100), 204 (15), 192 (18), 165 (11), and 69 (5).
Synthesis of 1-(1-trifluoromethanesulfonyl-1,4-dihydropyridin-4-
yl)-2-azulenyl trifluoromethanesulfonate 11 in the presence of
pyridine
1
13
photometer, respectively. H NMR spectra ( C NMR spectra)
were recorded on JEOL LAMBDA 400 (100 MHz) and 600
A solution of trifluoromethanesulfonic anhydride (80 mg) in
(
150 MHz) spectrometers. J Values are given in Hz. Elemental
dry CH Cl (10 mL) was added dropwise at room temperature
2
2
analyses were performed at the Instrumental Analysis Center of
Chemistry, Faculty of Science, Tohoku University.
to a mixture of 10 (53.6 mg) and pyridine (43.5 mg) in the same
solvent (10 mL) over a period of 15 min, and the mixture was
stirred at room temperature for another 4.5 h. A solution of
trifluoromethanesulfonic anhydride (195 mg) and pyridine
(54.8 mg) in CH Cl (10 mL) was added to the reaction mixture
Synthesis of 2-azulenyl trifluoromethanesulfonate 10 in the
presence of triethylamine
2
2
9
and stirred for another 2 h. After the reaction mixture was
washed with water, 2 M HCl and saturated aqueous NaCl, the
To a solution of 2-hydroxyazulene 9 (220 mg) and triethyl-
amine (306 mg) in dry CH Cl (10 mL), a solution of trifluoro-
methanesulfonic anhydride (630 mg) in dry CH Cl (10 mL)
was added dropwise over the period of 30 min at room temper-
ature. After 30 minutes stirring, the reaction mixture was
poured into water. The organic layer was washed with 2 M HCl
2
2
organic layer was dried over anhydrous MgSO and concen-
4
2
2
trated under reduced pressure. The residue was purified by
column chromatography on silica gel with CH Cl to afford 11
2
2
(
84.5 mg, 89%).
and water, dried with anhydrous MgSO , and concentrated
4
Reaction of 10 with a large excess of trifluoromethanesulfonic
anhydride
under reduced pressure. The residue was purified by column
chromatography on silica gel with CH Cl to afford 2-azulenyl
2
2
trifluoromethanesulfonate 10 (402 mg, 95%).
0: Purple needles, mp 58.0 ЊC; Found: C, 47.94; H, 2.67; S,
1.75. Calc. for C H F O S: C, 47.83; H, 2.55; S, 11.6%;
Pyridine (90 mg, 1.1 mmol) was added to a solution of
1
trifluoromethanesulfonic anhydride (277 mg) in dry CH Cl2
2
1
11
7
3
3
(10 mL), followed by addition of 10 (50 mg) at room temper-
ature. After heating at reflux temperature for 1 h, trifluoro-
methanesulfonic anhydride (271 mg) and pyridine (133 mg)
were added to the reaction mixture and stirred for another 6 h.
After the reaction mixture was washed with water, the organic
Ϫ1
νmax(KBr)/cm 1576 (m), 1536 (m), 1474 (m), 1456 (s), 1426 (s),
399 (s), 1316 (m), 1296 (m), 1246 (s), 1215 (s), 1132 (s), 1105
s), 972 (s), 932 (s), 897 (m), 855 (s), 841 (s), 808 (m), 797 (m),
1
(
7
5
39 (m), 718 (m), 669 (w), 604 (s), 592 (m), 581 (m), 576 (m),
67 (w), and 513 (m); λmax(CH Cl )/nm (log ε) 627 sh (2.20), 574
2
2
layer was dried over anhydrous MgSO and concentrated under
4
sh (2.62), 539 (2.67), 335 (3.75), 322 (3.65), 315 sh (3.55), 280
reduced pressure. The residue was purified by column chrom-
atography on silica gel with ethyl acetate–hexane (1 : 4) to afford
(
4.76), 273 (4.76), and 232 (4.26); δ (400 MHz; CDCl ; Me Si)
H 3 4
8
.37 (d, J 9.8, H-4 and H-8), 7.71 (t, J 10.3, H-6), 7.35 (dd,
1
,3-bis(1-trifluoromethanesulfonyloxy-1,4-dihydropyridin-4-
J 10.3, 9.8, 5-H and 7-H), and 7.19 (s, 1-H and 3-H); δ (100
C
yl)-3-(trifluoromethanesulfonyloxy)azulene 12 (100 mg, 79%).
MHz, CDCl ) 153.78 (C-2), 138.32 (C-4 and C-8), 138.30
3
12: Blue crystals, mp 170.0 ЊC (decomp); Found: C, 39.83; H,
(
C-6), 137.83 (C-3a and C-8a), 125.32 (C-5 and C-7), 118.84 (q,
2
.33; S, 13.75. Calc. for C H F N O S : C, 39.56; H, 2.16; S,
23 16 9 2 7 3
Ϫ1
J = 321.2, OSO CF ), and 106.24 (C-1 and C-3); m/z (EI) 276
2
3
13.77%; νmax(KBr)/cm 3117 (w), 1684 (m), 1429 (s), 1416 (s),
ϩ
ϩ
(
M , 62%), 143 (M Ϫ CF SO , 7), and 115 (100).
3 2
1387 (m), 1348 (m), 1289 (m), 1233 (s), 1196 (s), 1161 (s), 1142
(
(
(
(
(
8
s), 1103 (m), 1073 (m), 1073 (m), 947 (m), 932 (m), 920 (m), 909
m), 826 (s), 770 (m), 756 (m), 743 (m), 696 (m), 683 (m), 656
Synthesis of triflate 10 in the presence of pyridine
Ϫ1
m), 592 (s), and 519 (m) cm ; λ (CH Cl )/nm (log ε) 662 sh
max
2
2
A solution of trifluoromethanesulfonic anhydride (342 mg)
2.71), 600 sh (2.26), 564 (2.76), 359 (3.59), 342 (3.67), 293
in dry CH Cl (10 mL) was added dropwise at room temper-
2
2
4.68), 283 (4.62), and 234 (4.55); δ (400 MHz; CDCl ; Me Si)
H
3
4
ature to a mixture of 2-hydroxyazulene 9 (135 mg) and pyridine
.71 (d, J 10.0, 4-H and 8-H), 7.82 (t, J 9.8, 6-H), 7.35 (dd,
(
246 mg) in the same solvent (10 mL) over a period of 30 min,
J 10.0, 9.8, 5-H and 7-H), 6.64 (dd, J 8.6, 0.8, 2Ј-H, 2Љ-H, 6Ј-H,
and 6Љ-H), 5.21 (dd, J 8.6, 3.2, 3Ј-H, 3Љ-H, 5Ј-H, and 5Љ-H), and
and stirring the mixture at room temperature for another 30
min. After the reaction mixture was washed with water, 2 M
HCl and saturated aqueous NaCl, the organic layer was dried
over anhydrous MgSO4 and concentrated under reduced
pressure. The residue was purified by column chromatography
on silica gel with CH Cl to afford 10 (106 mg, 41%) and 1-(1-
4
.85 (2H, m, 4Ј-H); δ (100 MHz; CDCl ) 145.92 (C-2), 140.18
C
3
(
(
C-6), 137.19 (C-4 and C-8), 135.62 (C-3a and C-8a), 125.11
C-5 and C-7), 120.70 (C-2Ј, C-2Љ, C-6Ј, and C-6Љ), 117.82 (C-1
and C-3), 119.79 (q, J 324.0, OTf or Tf ), 118.81 (q, J 320.0,
Tf or OTf ), 111.65 (C-3Ј, C-3Љ, C-5Ј, and C-5Љ), and 82.92
2
2
trifluoromethanesulfonyl-1,4-dihydropyridin-4-yl)-2-azulenyl
trifluoromethanesulfonate 11 (53 mg, 12%).
ϩ
(
C-4Јand C-4Љ); m/z (FAB) 698 (M , 100%), 629 (5), 565 (80),
5
60 (15), and 501 (21).
1
1: Purple needles, mp 65.0–65.5 ЊC; Found: C, 42.08; H,
2
1
1
.40; S, 13.41. Calc. for C H F NO S : C, 41.89; H, 2.27; S,
3.16%; νmax(KBr)/cm 3130 (w), 1449 (m), 1435 (s), 1420 (s),
397 (m), 1289 (m), 1248 (s), 1238 (s), 1225 (s), 1204 (s), 1192
17
11
6
5 2
Reaction of parent azulene with trifluoromethanesulfonic
anhydride in the presence of pyridine
Ϫ1
(
(
(
(
(
m), 1163 (s), 1140 (s), 1082 (m), 951 (m), 920 (m), 835 (s), 739
Pyridine (1.56 g) was added to a solution of trifluoromethane-
m), 718 (w), 698 (m), 613 (m), and 583 (m); λmax(CH Cl )/nm
sulfonic anhydride (588 mg) in dry CH Cl (20 mL), followed by
2
2
2
2
log ε) 641 sh (2.22), 589 (2.63), 339 (3.73), 288 (4.74), and 279
4.72); δH (400 MHz; CDCl ; Me Si) 8.71 (d, J 9.8, 8-H), 8.56
addition of parent azulene 1 (256 mg) at room temperature.
After 10 min and 30 min, trifluoromethanesulfonic anhydride
(153 mg and 424 mg, respectively) was added to the reaction
mixture. After stirring for another 16 h, DMSO (20 mL) was
added to the reaction mixture, and stirred for another 30 min.
The reaction mixture was washed with water and saturated
aqueous NaCl. The organic layer was dried over anhydrous
3
4
d, J 9.5, 4-H), 7.76 (dd, J 10.0, 9.5, 6-H), 7.37 (t, J 9.5, 5-H),
.35 (dd, J 10.0, 9.8, 7-H), 7.26 (s, 3-H), 6.62 (dd, J 8.6, 3.4, 2Ј-
H and 6Ј-H), 5.19 (dd, J 8.6, 3.4, 3Ј-H and 5Ј-H), and 4.91
7
(
(
broad s, 4Ј-H); δC (100 MHz; CDCl ) 151.18 (C-2), 139.04
3
C-6), 138.93 (C-4), 137.88 (C-8a), 135.91 (C-8), 134.55 (C-3a),
1
950
O r g . B i o m o l . C h e m . , 2 0 0 3 , 1, 1 9 4 7 – 1 9 5 2

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ϩ
MgSO and concentrated under reduced pressure. The residue
5), 121.8 (C-3Ј); m/z (EI) 339 (M , 33%), 206 (100), 191 (7), 178
4
was purified by column chromatography on silica gel with
CH Cl to afford 1,3-bis(trifluoromethanesulfonyl-1,4-dihydro-
(30), 165 (5), 152 (12), and 127 (9).
2
2
pyridin-4-yl)azulene 13 (738 mg, 67%) and 5-(azulenyl)penta-
Preparation of 14 from 16 on silica gel
2
,4-dienal 14 (122 mg, 29%).
3: Blue crystals, mp 133.5–134.0 ЊC; Found: C, 48.08; H,
.83; S, 11.63. Calc. for C H F N O S : C, 48.00; H, 2.93; S,
A solution of 16 (13 mg) in a small amount of CH Cl was
2
2
1
placed on the silica gel with CH Cl for 12 h at room temper-
2
2
2
1
1
22
16
6
2
4 2
Ϫ1
ature. The solution was passed through the column chromato-
graphy to afford 14 (8 mg).
1.65%; νmax(KBr)/cm 3114 (w), 3025 (w), 1686 (s), 1638 (m),
578 (m), 1559 (m), 1429 (m), 1412 (s), 1370 (m), 1350 (m), 1287
(
1
7
s), 1233 (s), 1202 (s), 1159 (s), 1138 (m), 1125 (m), 1076 (s),
036 (m), 951 (s), 941 (s), 855 (m), 783 (m), 768 (m), 735 (m),
08 (m), 695 (s), 594 (s), 579 (s), 571 (m), and 525 (m); λmax
Preparation of parent azulene using palladium-catalyzed
reduction of 2-azulenyl trifluoromethanesulfonate 10
(
(
CH Cl )/nm (log ε) 722 sh (2.00), 652 sh (2.46), 601 (2.54), 368
3.88), 351 (3.85), 336 sh (3.59), 296 (4.76), 290 (4.73), and 287
2 2
A mixture of 10 (275 mg), Pd (dba)3 (19 mg, 2.1 mol%),
2
P(o-tolyl) (16 mg), HCOOH (467 mg), and n-Bu N (1.85 g) in
3
3
sh (4.73); δ (400 MHz; CDCl ; Me Si) 8.32 (d, J 9.5, 4-H and
8
5
H
3
4
dioxane (100 mL) was heated at reflux temperature. After stir-
ring at the same temperature for 24 h, the reaction mixture was
poured into water and extracted with hexane. The organic layer
-H), 7.71 (s, 2-H), 7.64 (t, J 10.3, 6-H), 7.17 (dd, J 10.3, 9.5,
-H and 7-H), 6.57 (dd, J 8.3, 1.2, 2Ј, 2Љ, 6Ј and 6Љ-H), 5.270
(
dd, J 8.3, 3.7, 3Ј, 3Љ, 5Ј and 5Љ-H), and 4.81 (broad s); δ (100
C
was dried over MgSO , and concentrated under reduced pres-
4
MHz; CDCl ) 138.60 (C-6), 137.39 (C-2), 135.31 (C-3a and
C-8a), 133.35 (C-4 and C-8), 130.86 (C-1 and C-3), 122.84 (C-5
and C-7), 120.34 (C-2Ј, C-2Љ, C-6Ј and C-6Љ), 119.78 (q, J 325.0,
CF ), 112.94 (C-3Ј, C-3Љ, C-5Ј, and C-5Љ), and 30.53 (C-4Ј and
3
sure. The residue was purified by column chromatography on
alumina with hexane to afford parent azulene 1 (122 mg, 96%)
and recovered 10 (4 mg, 1%).
3
ϩ
C-4Љ); m/z (EI) 550 (M , 40%), 417 (21), 283 (64), 212 (100), 176
(
9), 148 (15), and 69 (13).
4: Green plates, mp 92.5–93.5 ЊC (lit. 94–95 ЊC); Found: C,
3.07; H, 6.01. Calc. for C H O 1/2H O: C, 82.92; H, 6.03%;
References
1
1
1
1
(a) T. Yanagisawa, S. Wakabayashi, T. Tomiyama, M. Yasunami
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8
15
12
2
Ϫ1
νmax(KBr)/cm 3034 (w), 2816 (w), 2739 (w), 1669 (s), 1599 (s),
590 (s), 1580 (s), 1489 (m), 1456 (m), 1418 (m), 1401 (m), 1389
m), 1283 (m), 1167 (m), 1127 (s), 1013 (m), 982 (m), 793 (m),
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1
(
5
821; (d ) S. Ito, H. Inabe, T. Okujima, N. Morita, M. Watanabe,
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2
2
(
(
9
8
7
7
2.74), 570 (2.79), 426 (4.32), 328 (4.29), 315 sh (4.21), 301 sh
(
4.09), 260 (4.20), and 228 (4.32); δ (400 MHz; CDCl ; Me Si)
H
3
4
.61 (d, J 8.1, CHO), 8.46 (d, J 9.8, 8Ј-H), 8.27 (d, J 9.8, 4Ј-H),
.21 (d, J 4.2, 2Ј-H), 7.64 (t, J 9.8, 6Ј-H), 7.60 (d, J 14.9, 5-H),
.42 (d, J 4.2, 3Ј-H), 7.39 (dd, J 14.9, 11.2, 3-H), 7.27 (t, J 9.8,
Ј-H), 7.23 (t, J 9.8, 5Ј-H), 7.07 (dd, J 14.9, 11.2, 4-H), 6.25 (dd,
7
Perkin Trans. 1, 2002, 1896–1905; (g) K. Kurotobi, H. Tabata,
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016; (h) S. Ito, H. Inabe, N. Morita, K. Ohta, T. Kitamura and
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J 14.9, 8.1, 2-H); δ (100 MHz, CDCl ) 193.49 (CHO), 153.66
C
3
(
C-3Ј), 144.33 (C-3a or C-8a), 138.98 (C-6), 137.82 (C-8a or
C-3a), 137.56 (C-4), 134.42 (C-5Ј), 134.34 (C-2), 133.68 (C-8),
29.08 (C-2Ј), 126.09 (C-1), 125.74 (C-5), 124.73 (C-7), 123.75
(
(
j) D. A. Colby and T. D. Lash, J. Org. Chem., 2002, 67, 1031–1033;
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1
(l ) H. Wakabayashi, T. Kurihara and T. Nozoe, Heterocycles, 2001,
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ϩ
(
(
C-4Ј), and 120.28 (C-3); m/z (EI) 208 (M , 63%), 179 (100), 165
2
3
P. A. Plattner and A. S. Pfau, Helv. Chim. Acta, 1937, 20, 224–
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2
32.
K.-P. Zeller, Azulene, in Houben-Weyl; Methoden der Organischen
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Isolation of intermediate 6-(1-azulenyl)-1-trifluoromethane-
sulfonyl-1-azahexa-1,3,5-triene 16
4
5
(a) K. Ziegler and K. Hafner, Angew. Chem., 1955, 67, 301–
A solution of pyridine (95 mg) in CH Cl (5 mL) was added to a
solution of trifluoromethanesulfonic anhydride (340 mg) in dry
CH Cl (10 mL) to give a white precipitate (TPT). A solution of
azulene 1 (128 mg) in dry CH Cl (15 mL) was added dropwise
over a period of 10 min with stirring to the dispersed TPT
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302; (b) K. Hafner, Liebigs Ann. Chem., 1957, 606, 79–89;
2
2
(
c) K. Hafner and K.-P. Meinhardt, Org. Synth., 1990, Coll. Vol. 7,
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1
2
2
2
2
(
Ed. M. Kotake, Asakura Shoten, Tokyo, 1960, Vol. 13, pp. 439–
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2
2
3
46–363.
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7%).
6: Silver metallic colored crystals, mp 223.0 ЊC (decomp);
Found: C, 56.41; H, 3.71; S, 9.54. Calc. for C H F NO S: C,
6
6
1
1
K. Takase, Chem. Lett, 1980, 579–582; M. Yasunami, S. Miyoshi,
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1
6
12
3
2
Ϫ1
5
1
6.63; H, 3.56; S, 9.45%; νmax(KBr)/cm 1578 (s), 1538 (m),
7
8
L. T. Scott, M. A. Minton and M. A. Kirms, J. Am. Chem. Soc.,
509 (s), 1487 (s), 1406 (m), 1343 (m), 1283 (m), 1209 (m), 1171
1
980, 102, 6311–6314.
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4, 679–689.
(
s), 1119 (s), 1017 (m), 849 (s), and 776 (m); λmax (CH Cl )/nm
2 2
(
log ε) 529 (5.80), 350 (5.09), 278 (5.24), and 231 (5.41); δ (600
H
5
MHz; CDCl ; Me Si) 8.69 (d, J 10.1, 2-H), 8.56 (d, J 9.9, 8Ј-H),
8
7
3
4
9 R. Yokoyama, S. Ito, M. Watanabe, N. Harada, C. Kabuto and
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1
359–1363; (b) M. Zengin, A. Dastan and M. Balci, Synth.
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Ј-H), 7.18 (dd, J 14.7, 11.7, 5-H), 6.63 (dd, J 14.1, 10.1, 3-H);
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5
3
2
002, 648, 164–175.
1
1
40.3 (C-6), 140.2, 139.8 (C-6Ј), 138.2 (C-4Ј), 135.2 (C-2Ј),
34.1 (C-8Ј), 127.8 (C-5Ј), 126.8 (C-7Ј), 126.2, 123.8 (C-3 and
1
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952
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