Electrophilc ipso-substltiitlon and some unique reaction behavior of 1,3,6-tri-tri-butylazulene

Article abstract of DOI:10.1002/ejoc.200801078

Electrophilic ipso-substitution reactions between 1,3,6-tritert- butylazulcne (2) and several electrophilic reagents were examined. Friedel-Crafts and Vilsmeier reactions of 2 gave the corresponding ipso-substitution products in moderate to excellent yiel

Full text of DOI:10.1002/ejoc.200801078

FULL PAPER
DOI: 10.1002/ejoc.200801078
Electrophilic ipso-Substitution and Some Unique Reaction Behavior of
1,3,6-Tri-tert-butylazulene
Taku Shoji,*[a] Shunji Ito,[b] Tetsuo Okujima,[c] Junya Higashi,[a] Ryuji Yokoyama,[a]
Kozo Toyota,[a] Masafumi Yasunami,[d] and Noboru Morita*[a]
Keywords: Azulenes / ipso-Substitution / Cycloaddition / Electrochemistry / Aromatic substitution
Electrophilic ipso-substitution reactions between 1,3,6-tri-
tert-butylazulene (2) and several electrophilic reagents were
examined. Friedel–Crafts and Vilsmeier reactions of 2 gave
the corresponding ipso-substitution products in moderate to
excellent yields. One of the ipso-substitution products, 1,6-
di-tert-butyl-3-formylazulene (5), was converted in high
yield into the synthetically more useful azulene derivative
1,6-di-tert-butylazulene (1) by decarbonylation on treatment
with pyrrole in acetic acid. Treatment of 2 with N-[(trifluoro-
methyl)sulfonyl]pyridinium trifluoromethanesulfonate (TPT)
unexpectedly afforded 1-trifluoromethylthioazulene 10 and
1(8H)-azulenone 11. Compound 2 also reacted with tetracy-
anoethylene (TCNE) to give an excellent yield of cycload-
dition product 13, rather than the ipso-substitution reaction
product.
(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2009)
1,3-di-tert-butylazulene is reported to afford the syntheti-
cally useful 1-tert-butyl-3-formylazulene as the sole product
in excellent yield.[3] Still, little is known about the ipso-sub-
stitution reactions of azulene derivatives, although such
azulene derivatives would be expected to show reactivities
higher than those of benzene derivatives toward electro-
philic reagents. Further investigation would thus have im-
portance for evaluation of the reactivities of azulene deriva-
tives toward ipso-substitution. Previously, we had reported
the synthesis of 1,6-di-tert-butylazulene (1; Scheme 2, vide
infra) by Friedel–Crafts alkylation of 6-tert-butylazulene
with tert-butyl chloride in the presence of AlCl3.[4] As
would be expected, the reaction produced significant
amounts of 1,3,6-tri-tert-butylazulene (2; Scheme 1) as a by-
product. We were now able to put our hands on an azulene
derivative suitable for the exploration of electrophilic ipso-
substitution reactions. Electrophilic ipso-substitution of the
unusual compound 2 should provide facile and efficient
synthetic routes to functionalized azulene derivatives.
Moreover, decarbonylation of 1-formylazulene derivatives
should be readily achievable by treatment with pyrrole in
acetic acid.[5] Vilsmeier formylation should therefore be one
of the most promising reactions for exploration, because
azulene derivatives unsubstituted at their 1- and/or 3-posi-
tions should by utilizable for further functionalization reac-
tions.
Introduction
Electrophilic substitution is one of the most powerful
and general methodologies for the functionalization of aro-
matic compounds.[1] Azulene (C10H8) has attracted the
interest of many research groups both because of its un-
usual properties and because of its beautiful blue color.
There are numerous reports of electrophilic substitution re-
actions of azulene derivatives at their 1- and/or 3-posi-
tions.[2] However, difficulties are frequently encountered in
selective functionalization of azulene derivatives by electro-
philic substitution because of their high reactivities toward
electrophilic reagents at these positions. In 1962, Hafner
and Moritz reported that 1,3-dialkylazulenes would un-
dergo electrophilic ipso-substitution reactions such as Frie-
del–Crafts acylation and Vilsmeier formylation at their 1-
and/or 3-positions.[3] In particular, Vilsmeier formylation of
[a] Department of Chemistry, Graduate School of Science, Tohoku
University,
Sendai 980-8578, Japan
Fax: +81-22-795-7714
E-mail: shoji-azulene@m.tains.tohoku.ac.jp
nmorita@m.tains.tohoku.ac.jp
[b] Graduate School of Science and Technology, Hirosaki Univer-
sity,
Hirosaki 036-8561, Japan
[c] Graduate School of Science and Engineering, Ehime Univer-
sity,
Here we report efficient electrophilic ipso-substitution re-
actions between 1,3,6-tri-tert-butylazulene (2) and several
electrophilic reagents, together with some reactivity unique
to 2, including cycloaddition reaction with TCNE.
Matsuyama 790-8577, Japan
[d] Department of Materials Chemistry and Engineering, College
of Engineering, Nihon University,
Koriyama 963-8642, Japan
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ipso-Substitution and Unique Reactions of 1,3,6-Tri-tert-butylazulene
Scheme 1.
Scheme 2)[7] in 98% yield as the sole product. Strikingly, 6-
tert-butyl-1,3-diformylazulene was not produced in this
case, even when the reaction temperature was raised to re-
flux in DMF. It is noteworthy that the yield of the reaction
is comparable to that of the Vilsmeier formylation of 1. This
reactivity should be governed by the electron-withdrawing
nature of the iminium intermediate for the Vilsmeier for-
mylation reaction, which would hamper further ipso-substi-
tution reaction. Although compound 1 could be an impor-
tant synthetic intermediate,[8] the synthesis of 1 from 6-tert-
butylazulene and tert-butyl chloride in the presence of
AlCl3 usually required a tedious separation process because
of the formation of 2 as a by-product.[4] Thus, to evaluate
this ipso-substitution reaction, we attempted the decarbon-
ylation of the product 5 to give the useful compound 1 by
treatment with pyrrole in acetic acid. Conversion of 5 into
1 in 83% yield was observed without any difficulties in the
separation process (Scheme 2).
Results and Discussion
Two electrophilic reactions – Friedel–Crafts acylation
and Vilsmeier formylation – of 2 were investigated as typi-
cal examples of ipso-substitution. Treatment with acetyl
chloride and benzoyl chloride in the presence of aluminium
chloride for Friedel–Crafts acylation was examined
(Scheme 1), and the results are summarized in Table 1.
Treatment of 2 with acetyl chloride (1.5 equiv.) in dichloro-
methane at room temperature gave 1-acetyl-3,6-di-tert-bu-
tylazulene (3a) in 31% yield together with 1,3-diacetyl-6-
tert-butylazulene (3b) in 7% yield (Entry 1). Although the
reaction afforded a mixture of 3a and 3b, these were easily
separated by column chromatography on silica gel. When
excess acetyl chloride was used for the reaction, the reaction
went to completion at room temperature to afford 3b in
77% yield as a sole product (Entry 2).
Table 1. Synthesis of 1-acetylazulene and 1-benzoylazulene deriva-
tives 3a, 3b, 4a, and 4b.
Entry
Reagent
Yield (%)
1
2
3
4
1.5 equiv. CH3COCl
5.0 equiv. CH3COCl
1.5 equiv. PhCOCl
5.0 equiv. PhCOCl
3a (31)
3b (7)
3b (77)
4b (24)
4b (71)
3a (0)
4a (19)
4a (0)
Scheme 2.
Treatment of 2 with benzoyl chloride in the presence of
To examine the reactivity of 1 toward electrophilic rea-
aluminium chloride was also carried out, similarly to the gents, we investigated its reaction with N-[(trifluoromethyl)-
reaction with acetyl chloride. Treatment with benzoyl chlo- sulfonyl]pyridinium trifluoromethanesulfonate (TPT),
ride (1.5 equiv.) at room temperature afforded the presumed which can be easily prepared by treatment of Tf2O with
1-benzoyl-3,6-di-tert-butylazulene (4a) in 19% yield to- pyridine. We have recently reported that treatment of azu-
gether with 1,3-dibenzoyl-6-tert-butylazulene (4b) in 24% lene itself with TPT (prepared from equimolar amounts of
yield; these were also separable by silica gel column Tf2O and pyridine) gives as the main product 6-(azulen-1-
chromatography, similarly to the separation of 3a and 3b yl)-1-[(trifluoromethyl)sulfonyl]-1-azahexa-1,3,5-triene, pro-
(Entry 3).
duced by attack of azulene on TPT at the 2-position. In
Product 4a has also been prepared by us through the contrast, when the reaction was carried out with a large
Vilsmeier–Haack reaction between 1 and N,N-dimethyl- excess of pyridine, it gave 1,3-bis(dihydropyridin-4-yl)azul-
benzamide.[6] We also investigated the similar Vilsmeier– ene, the product of the attack of azulene on TPT selectively
Haack reaction between 2 and N,N-dimethylbenzamide, but at the 4-position.[9] As in the case of the reaction between
that reaction resulted in the complete recovery of the start- azulene and TPT, the proportions of azulene, Tf2O, and
ing compound 2.
pyridine are very important in determining the product dis-
Treatment of 2 with excess benzoyl chloride also gave 4b tribution. Treatment of 1 with TPT in the presence of excess
in 71% yield as the sole product (Entry 4). Friedel–Crafts pyridine gave 6 in 88% yield, along with 7 in 5% yield.
reactions of 2 were thus found to be capable of allowing When equimolar amounts of pyridine and Tf2O were used,
the selective synthesis of 3b and 4b, but the selective synthe- compound 7 was obtained in 92% yield as the main prod-
sis of 3a and 4a through Friedel–Crafts reactions of 2 was uct, along with 8 in 5% yield (Scheme 3). No such dihy-
not straightforward, similarly to the results reported by dropyridinylation of the triene moiety was observed in the
Hafner et al.[3]
case of the reaction between the parent azulene and TPT.
In contrast with the Friedel–Crafts reactions, selective The two tert-butyl groups on the azulene ring might thus
ipso-formylation of 2 was established under normal Vilsme- enhance the reactivity of the triene moiety toward the at-
ier reaction conditions. Treatment of 2 with POCl3 in DMF tack of TPT. Compound 8 was also obtained, in 84% yield,
at 100 °C thus afforded 1,6-di-tert-butyl-3-formylazulene (5; by treatment of 7 with TPT.
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T. Shoji, N. Morita et al.
FULL PAPER
Scheme 3.
Figure 2. UV/Vis spectra of 8 in dichloromethane (black line) and
in hexane (gray line).
Compounds 6, 7, and 8 were fully characterized by their
spectroscopic data, as shown in the Experimental Section.
The mass spectra of 6, 7, and 8 (ionized by ESI) showed the
correct molecular ion peaks. The characteristic stretching
vibration bands of the trifluoromethyl and sulfonyl groups
of 6, 7, and 8 were observed by IR spectroscopy at 1184–
1234 cm–1 and at 1157–1172 cm–1, respectively. These re-
sults are consistent with the structures of these products.
UV/Vis spectra of 7 and 8 in dichloromethane and in hex-
ane are shown in Figures 1 and 2, respectively, whereas the
solvent dependence of the absorption maxima and coeffi-
cients of 7 and 8 are summarized in Table 2. Compound 7
in dichloromethane exhibited strong absorption bands at
560 nm and 610 (sh) nm. These strong absorption bands
should be attributable to CT absorption, as illustrated in
the resonance structure shown in Scheme 4. When the UV/
Vis spectrum of 7 was measured in hexane, compound 7
showed a hypsochromic shift of 34 nm on changing of the
solvent. Compound 8 in dichloromethane showed strong
absorption bands at 572 nm and 612 (sh) nm. The 572 nm
absorption band of 8 exhibited a hypsochromic shift of
24 nm with the change in the solvent from dichloromethane
to hexane.
Table 2. Absorption maxima of 7 and 8 and their coefficients in
dichloromethane and hexane.
Sample
Solvent
λmax [nm] (log ε)
7
CH2Cl2
hexane
CH2Cl2
hexane
560 (4.85), 610 sh (4.71)
526 (4.84)
572 (4.82), 612 sh (4.78)
548 (4.79)
8
Scheme 4. Resonance structure of 7.
Aromatization of the dihydropyridine moiety of 6 to a
pyridine ring system was also investigated. We recently re-
ported base-induced transformations of 1-(dihydrohetero-
aryl)-, 1,3-bis(dihydroheteroaryl)-, and 5-(dihydrohetero-
aryl)azulene derivatives to the corresponding (heteroaryl)-
azulene derivatives, which opened up a new two-step strat-
egy for the heteroarylation of azulene.[10] For the aromatiza-
tion of the dihydropyridine moiety of 6, we investigated two
bases, KOH and tBuOK, similarly to the procedure re-
ported by us previously. Treatment of 6 with KOH in EtOH
afforded 1,6-di-tert-butyl-3-(pyridin-4-yl)azulene (9) in 95%
yield (Scheme 5). On changing the reaction conditions to
tBuOK in DMSO, however, the yield of 9 was significantly
decreased because of the generation of an inseparable com-
plex mixture (Table 3).
The UV/Vis spectrum of 9 in dichloromethane showed a
characteristic weak absorption arising from the azulene sys-
tem at 594 nm (log ε = 2.57) in the visible region. In acetic
acid, compound 9 exhibited a strong absorption at 438 nm
(log ε = 4.40) arising from the development of CT absorp-
tion owing to protonation of the pyridine moiety, as shown
in Scheme 5.
Figure 1. UV/Vis spectra of 7 in dichloromethane (black line) and
in hexane (gray line).
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ipso-Substitution and Unique Reactions of 1,3,6-Tri-tert-butylazulene
of these products. Single crystals of 11 suitable for X-ray
crystallographic analysis were obtained by recrystallization
from methanol, and an ORTEP drawing of the molecular
structure of 11 is shown in Figure 3. These results are also
consistent with the structure of 11.
Scheme 5.
Table 3. Synthesis of 1,6-di-tert-butyl-3-(pyridin-4-yl)azulene (9).
Entry
Base
Solvent
Yield (%)
1
2
KOH
tBuOK
EtOH
DMSO
95
57
We extended the reaction with TPT to compound 2. As
with our results on the Friedel–Crafts and Vilsmeier reac-
tions of 2, we expected the formation of 6, 7, and 8 through
ipso-substitution reactions. Contrarily to expectations, how-
ever, 1,6-di-tert-butyl-3-[(trifluoromethyl)thio]azulene (10)
and 3,6,8a-tri-tert-butyl-(8aH)-azulen-1-one (11) were ob-
tained in 51% and 38% yields, respectively (Scheme 6). The
trifluoromethyl moiety appears widely in medicinal and ag-
rochemical science.[11] Treatment of azulene with trifluoro-
acetic anhydride has already been reported to give 1-(tri-
fluoroacetyl)azulene,[12] which exhibits tumor-specific cyto-
toxicity and apoptosis-inducing activity toward human
cells.[13] Recently, we reported a facile and efficient synthetic
route to several 1-azulenyl methyl and phenyl sulfides and
1,3-bis(methylthio and phenylthio)azulenes via 1-azulenyl-
sulfonium and 1,3-azulenediylsulfonium ion intermedi-
ates.[14] However, this is the first example of a (trifluoro-
methyl)thio derivative of azulene. This procedure could pro-
vide a useful methodology for the synthesis of 1-[(trifluoro-
methyl)thio]azulene derivatives.
Figure 3. ORTEP drawing of the molecular structure of 11.[15] Tri-
clinic, a = 6.7426(19), b = 12.461(4), c = 12.566(4) Å, α =
73.681(11), β = 71.971(12), γ = 76.620(14)°, V = 951.4(5) Å3, Z =
2, Dcalcd. = 1.091 gcm–3, µ(Mo-Kα) = 0.641 cm–1, R = 0.0595, Rw
= 0.1348, R1 = 0.0468.
Unique reactivity of 2 was also observed in its reaction
with tetracyanoethylene (TCNE). TCNE is known as a
strong organic electron acceptor, and the high reactivity of
TCNE toward nucleophiles or electron-rich reagents is fre-
quently used to introduce strong acceptor moieties into or-
ganic molecules.[16] In the early days of azulene chemistry,
Hafner et al. reported the reaction between azulene and
TCNE, giving 1-(1,2,2-tricyanoethenyl)azulene via CT
complex between azulene and TCNE.[17] As in the literature
reported by Hafner et al., treatment of 1 with TCNE gave
1,6-di-tert-butyl-3-(1,2,2-tricyanoethenyl)azulene (12) in
94% yield (Scheme 7).
Scheme 7.
Scheme 6.
In contrast with the reaction behavior of 1, treatment of
2 with TCNE in ethyl acetate afforded a quantitative yield
Compounds 10 and 11 were characterized by their spec- of the unique cycloaddition product 13 (Scheme 8), rather
troscopic data as shown in the Experimental Section. As- than the ipso-substitution product. A retrocycloaddition re-
1
signment of peaks in the H NMR spectra of 10 and 11 action was also observed when the cycloadduct 13 was
was accomplished by decoupling, NOE, and 2D COSY ex- heated at reflux in ethyl acetate, giving the initial compound
periments. The mass spectra of 10 and 11, ionized by EI 2 quantitatively. Takekuma et al. recently reported that
and ESI, respectively, showed the correct molecular ion 1,2-bis(3-guaiazulenyl)ethylene and 2-(3-guaiazulenyl)-1,1-
peaks. The characteristic stretching vibration band of the bis(4-methoxyphenyl)ethylene reacted with TCNE to give
carbonyl group of 11 was observed at 1701 cm–1 in the IR 1:2 cycloaddition products.[18] The reactions are believed to
spectrum. These results are consistent with the structures proceed via CT complexes of azulene and TCNE. The CT
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T. Shoji, N. Morita et al.
FULL PAPER
complex is presumed to react with 2 equiv. TCNE at azul-
ene and ethylene moieties to form 1:2 cycloaddition prod-
ucts. The reaction between 2 and TCNE should also pro-
ceed through the formation of CT complexes as illustrated
in Scheme 9. However, compound 13, to the best of our
knowledge, would be the first example of a cycloaddition
product of TCNE directly reacting with an azulene moiety.
Scheme 8.
Figure 4. ORTEP drawing of the molecular structure of 13.[20] Mo-
noclinic, a = 11.7998(3), b = 22.7898(6), c = 19.3162(5) Å, β =
104.026(1)°, V = 5039.5(2) Å3, Z = 8, Dcalcd. = 1.119 gcm–3, µ(Mo-
Kα) = 0.67 cm–1, R = 0.049, Rw = 0.061, R1 = 0.049.
tion maxima and coefficients of 12 are summarized in
Table 4. In its UV/Vis spectrum in dichloromethane, 12
showed strong absorption at 544 nm. The strong absorption
might be attributable to CT absorption, depending on the
contribution of the resonance structure as illustrated in
Scheme 10. The largest solvent effect was observed when
the solvent was changed from CH2Cl2 (λmax = 544 nm) to
hexane (λmax = 508 nm). The UV/Vis spectrum of 13 in
Scheme 9. Proposed reaction mechanism for the cycloaddition re- dichloromethane showed a characteristic absorption attrib-
action between 2 and TCNE.
utable to its fulvene-like structure in the visible region at
412 nm (log ε = 2.84).
Mass spectra of 12 and 13, ionized by ESI, showed the
correct molecular ion peaks. The characteristic stretching
vibration bands of the cyano groups of 12 and 13 were ob-
served at 2210 and 2201 cm–1, respectively, in their IR spec-
1
tra. Neuenschwander and co-workers have reported the H
and 13C NMR shifts of fulvene, and chemical shifts were
observed in the olefinic region.[19] 1H and 13C NMR signals
for 13 were also observed in the olefinic region, as with
fulvene, so product 13 has the fused-ring structure between
fulvene and seven-membered ring moieties. Single crystals
of 13 suitable for X-ray crystallographic analysis were ob-
tained by recrystallization from ethanol, and an ORTEP
drawing of the molecular structure of 13 is shown in Fig-
ure 4. The C1–C10, C2–C3, and C4–C5 bond lengths are
1.358, 1.345, and 1.341 Å, respectively, which demonstrate
the fulvene-like structure of 13. The C11–C12 bond
(1.605 Å) is relatively longer than the general single bond.
The thermodynamic instability of 13 might be attributable
to the strain in the molecule.
Figure 5. UV/Vis spectra of 12 in dichloromethane (black line) and
in hexane (gray line).
UV/Vis spectra of 12 in dichloromethane and in hexane
To clarify the electrochemical properties of 2, 6, 7, 8, 9,
are shown in Figure 5. Cyanovinyl compounds are well 12, and 13, the redox potentials of these products were mea-
known to exhibit solvatochromic[21] and vapochromic sured by CV and DPV. The measurements were carried out
behavior.[22] In the case of azulene derivatives, we have with a standard three-electrode configuration. Tetraethyl-
also reported that 1,1,4,4-tetracyano-2,3-bis[5-isopropyl-3- ammonium perchlorate (0.1 ) in benzonitrile was used as
(methoxycarbonyl)-1-azulenyl]butadiene showed solvato- a supporting electrolyte with platinum wire auxiliary and
chromism.[23] We examined the solvatochromic effect of 12 working electrodes. All measurements were run under ar-
in eight solvents, and the solvent dependence of the absorp- gon, and potentials were related to the reference electrode
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ipso-Substitution and Unique Reactions of 1,3,6-Tri-tert-butylazulene
Table 4. Solvatochromic data for the longest-wavelength absorp-
tions of 12.
Table 5. Redox potentials[a] of 2, 6, 7, 8, 9, 12, and 13.
Sam- E1red [V]
E2red [V]
E3red [V]
E1ox [V]
E2ox[V]
Solvent
λmax [nm] (logε)
Solvent
λmax [nm] (logε)
ple
CH2Cl2
CH3CN
CHCl3
MeOH
544 (4.46)
535 (4.47)
527 (4.48)
520 (4.47)
EtOH
THF
AcOEt
hexane
519 (4.48)
515 (4.49)
513 (4.51)
508 (4.52)
2
6
7
8
9
(–2.14)
(–2.00)
(–0.95)
(–0.90)
–1.94
(–1.92)
–0.94
(+0.46)
(+0.54)
(+0.55)
(+0.64)
(–2.14)
(–1.99)
(–1.96)
(+0.64)
(–2.14)
(–2.12)
(–2.14)
(+0.59)
(+0.84)
12
13
(–0.92)
(–1.70)
(–2.00)
(–1.90)
(–2.14)
(–2.17)
(+1.10)
(+1.24)
[a] Redox potentials were measured by CV and DPV [V vs. Ag/
AgNO3, 1 m in benzonitrile containing Et4NClO4 (0.1 ), Pt elec-
trode (1.6 mm i.d.), scan rate = 100 mVs–1, and Fc/Fc+ = +0.15 V].
In the case of reversible waves, redox potentials measured by CV
are presented. The peak potentials measured by DPV are shown in
parentheses.
Scheme 10. Presumed electrochemical behavior of 12.
of 12 and 13 showed irreversible oxidation waves at +1.10
to +1.24 V, respectively, by DPV. These results indicate in-
stability of the radical cation species of these compounds.
formed from Ag/AgNO3 (0.01 ) in acetonitrile containing
nBu4NClO4 (0.1 ) with Fc/Fc+, which discharges at
+0.15 V under these conditions, as internal reference.
The redox potentials are summarized in Table 5. The
electrochemical reduction of 2, 6, 7, and 8 showed irrevers-
ible reduction waves at –0.90 to –2.14 V upon DPV. These
results indicate instability of the radical anionic states of
these compounds. Compounds 7 and 8 showed less negative
first reduction potentials (7: –0.95 V; 8: –0.90 V) than 2
(–2.14 V) and 6 (–2.00 V), which indicates that the substitu-
tion of electron-withdrawing triene moieties increased the
π-accepting properties. A reversible reduction wave was ob-
served in 9 at –1.96 V by CV. We have recently reported the
redox behavior of 1-(methylthio)-3-(pyridin-4-yl)azulene,
which shows an irreversible first reduction wave at –1.70 V
by DPV.[10c] These results indicate that the tert-butyl groups
on the azulene ring stabilize the radical anionic states of
azulene derivatives relative to the methylthio group, al-
though 9 shows a slightly more negative first reduction po-
Figure 6. Cyclic voltammogram for the reduction of 12 (1 m) in
tential. The electrochemical reduction of 2, 6, 7, 8, and 9 benzonitrile containing Et4NClO4 (0.1 ) as a supporting electro-
lyte; scan rate = 100 mV s–1.
showed irreversible oxidation waves at +0.46 to +0.64 V by
DPV. These results indicate instability of radical cationic
species of these compounds. Compounds 6, 7, 8, and 9
showed slightly more positive oxidation potentials (6:
+0.54 V; 7: +0.55 V; 8: +0.64 V; 9: +0.59 V) than 2
Conclusions
(+0.46 V), which indicates the dihydropyridine or triene
We report ipso-substitution (i.e., by Friedel–Crafts reac-
moieties acting as π-accepting substituents.
tions and Vilsmeier formylations) and some unique reactiv-
A cyclic voltammogram of 12 is shown in Figure 6. Elec- ity characteristics of 1 and 2. Friedel–Crafts reactions be-
trochemical reduction showed a reversible reduction wave tween 2 and acetyl chloride and benzoyl chloride in the
at the halfwave potential of –0.94 V by CV, probably due presence of aluminium chloride gave the corresponding
to the formation of a stabilized radical anion species. The ipso-substitution products, although selective monosubsti-
electrochemical behavior of 12 could thus be explained as tution was not established. In contrast, Vismeier for-
shown in Scheme 10. The electrochemical reduction also ex- mylation of 2 with POCl3 in DMF afforded 5 in excellent
hibited irreversible waves at –2.00 and –2.14 V by DPV, yield. Compound 5 was readily converted into 1 by decar-
probably due to the reduction of the substituted azulene bonylation with pyrrole in acetic acid. We also examined
ring. The reduction of 13 showed three irreversible re- the reactivity of 1 toward some electrophiles. Treatment of
duction waves at –1.70, –1.90, and –2.17 V by DPV. The 1 with TPT gave 6, 7, and 8, depending on the proportions
first reduction wave of 13 is slightly less negative than that of the amounts of reagents used. The preparation of 8 by
of 2, which indicates that the fulvene derivative 13 has a treatment of 7 with TPT was also established. In contrast,
lower LUMO level than 2. The electrochemical oxidation the reaction between 2 and TPT unexpectedly afforded
Eur. J. Org. Chem. 2009, 1554–1563
© 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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1559

T. Shoji, N. Morita et al.
FULL PAPER
The resulting mixture was stirred at the same temperature for 2 h.
The reaction mixture was poured into water and extracted with
toluene. The organic layer was washed with brine, dried with
MgSO4, and concentrated under reduced pressure. The residue was
purified by column chromatography on silica gel with toluene/Ac-
OEt (4:1) to give 3b (413 mg, 77%).
compounds 10 and 11. Although 1 reacted with TCNE to
give the substitution reaction product 12, compound 2 af-
forded the fulvene-like 1:1 cycloaddition product 13 in ex-
cellent yield on treatment with TCNE.
1-Benzoyl-3,6-di-tert-butylazulene (4a) and 1,3-Dibenzoyl-6-tert-bu-
tylazulene (4b):[6] Benzoyl chloride (422 mg, 3.00 mmol) and AlCl3
(800 mg, 6.00 mmol) were added at room temperature to a solution
of 2 (592 mg, 2.00 mmol) in CH2Cl2 (20 mL). The resulting mixture
was stirred at the same temperature for 2 h. The reaction mixture
was poured into water and extracted with toluene. The organic
layer was washed with brine, dried with MgSO4, and concentrated
under reduced pressure. The residue was purified by column
chromatography on silica gel with toluene/AcOEt (4:1) to give 4a
(130 mg, 19%) as purple crystals and 4b (188 mg, 24%) as red
needles.
Experimental Section
General: Melting points were determined with a Yanagimoto MP-
S3 micro melting apparatus and are uncorrected. Mass spectra were
obtained with a Hitachi M-2500 or a Bruker APEX II instrument.
IR and UV/Vis spectra were measured with a Shimadzu FTIR-
1
8100M and a Hitachi U-3410 spectrophotometer, respectively. H
NMR spectra (13C NMR spectra) were recorded with a JEOL
GSX 400 instrument at 400 MHz (100 MHz) or
a Bruker
AVANCE 400 instrument at 400 MHz (100 MHz). Gel permeation
chromatography (GPC) purification was performed with a TSKgel
G2000H6 instrument. Elemental analyses were performed at the
Research and Analytical Center for Giant Molecules, Graduate
School of Science, Tohoku University.
Compound 4a: M.p. 78.0–81.0 °C (ref.[6] 80.9–81.9 °C).
Compound 4b: M.p. 168.0–169.0 °C (AcOEt). 1H NMR (400 MHz,
CDCl3): δ = 9.81 (d, J = 10.4 Hz, 2 H, 4,8-H), 8.17 (s, 1 H, 2-H),
8.08 (d, J = 10.4 Hz, 2 H, 5,7-H), 7.48 (dd, J = 6.8, 1.6 Hz, 4 H,
o-Ph), 7.52 (ddd, J = 6.8, 1.6, 1.6 Hz, 2 H, p-Ph), 7.46 (ddd, J =
6.8, 1.6, 1.6 Hz, 4 H, m-Ph), 1.53 (s, 9 H, tBu) ppm. 13C NMR
(100 MHz, CDCl3): δ = 192.67, 167.14, 146.12, 143.88, 140.44,
139.62, 131.51, 130.64, 129.43, 128.12, 123.45, 39.14, 31.71 ppm.
UV/Vis (CH2Cl2): λmax (log ε) = 237 (4.47), 309 (4.69), 322 (4.64),
386 (sh) (4.15), 399 (4.17), 487 (3.02) nm. HRMS (ESI): calcd. for
1-Acetyl-3,6-di-tert-butylazulene (3a) and 1,3-Diacetyl-6-tert-butyl-
azulene (3b): Acetyl chloride (236 mg, 3.00 mmol) and AlCl3
(800 mg, 6.00 mmol) were added at room temperature to a solution
of 2 (592 mg, 2.00 mmol) in CH2Cl2 (20 mL). The resulting mixture
was stirred at the same temperature for 30 min. The reaction mix-
ture was poured into water and extracted with toluene. The organic
layer was washed with brine, dried with MgSO4, and concentrated
under reduced pressure. The residue was purified by column
chromatography on silica gel with hexane/AcOEt (4:1) to give 3a
(175 mg, 31%) as purple crystals and 3b (38 mg, 7%) as red crys-
tals.
C28H24O2
+ +
Na+ [M Na]+ 415.1674; found 415.1669.
C28H24O2·0.25H2O (392.49): calcd. C 84.71, H 6.22; found C 84.75,
H 6.31.
Compound 3a: M.p. 119.0–120.0 °C. 1H NMR (400 MHz, CDCl3):
δ = 9.82 (d, J = 10.8 Hz, 1 H, 8-H), 8.78 (d, J = 10.8 Hz, 1 H, 4-
H), 8.10 (s, 1 H, 2-H), 7.70 (dd, J = 10.8, 1.6 Hz, 1 H, 7-H), 7.61
(dd, J = 10.8, 1.6 Hz, 1 H, 5-H), 2.69 (s, 3 H, 1-COMe), 1.59 (s, 9
H, t-Bu), 1.46 (s, 9 H, tBu) ppm. 13C NMR (100 MHz, CDCl3): δ
= 194.99, 163.46, 140.44, 139.03, 138.13, 137.98, 137.81, 136.41,
126.82, 123.95, 122.19, 38.47, 32.85, 31.69, 29.07 ppm. IR (KBr
1,3-Dibenzoyl-6-tert-butylazulene (4b): Benzoyl chloride (1.40 g,
10.0 mmol) and AlCl3 (2.67 g, 20.0 mmol) were added at room tem-
perature to a solution of 2 (592 mg, 2.00 mmol) in CH2Cl2 (20 mL).
The resulting mixture was stirred at the same temperature for 2 h.
The reaction mixture was poured into water and extracted with
toluene. The organic layer was washed with brine, dried with
MgSO4, and concentrated under reduced pressure. The residue was
purified by column chromatography on silica gel with toluene/Ac-
OEt (4:1) to give 4b (557 mg, 71%).
disk): ν
= 2961 (s), 2868 (m), 1636 (s), 1578 (s), 1475 (m), 1460
˜
max
(m), 1437 (s), 1398 (m), 1381 (s), 1364 (m), 1350 (m), 1232 (s), 1209
(m), 1182 (m), 949 (m), 847 (m), 602 (m) cm–1. UV/Vis (CH2Cl2):
λmax (log ε) = 229 (4.28), 240 (4.28), 272 (4.15), 309 sh (4.53), 318
(4.62), 388 (sh) (3.97), 401 (4.00), 546 (2.76), 588 (sh) (2.66), 652
(sh) (2.10) nm. HRMS (ESI): calcd. for C20H26O + Na+ [M +
Na]+ 305.1876; found 305.1875. C20H26O·0.1H2O (282.42): calcd.
C 84.52, H 9.29; found C 84.58, H 9.25.
Compound 3b: M.p. 190.5–195.5 °C. 1H NMR (400 MHz, CDCl3):
δ = 9.97 (d, J = 11.6 Hz, 2 H, 4,8-H), 8.59 (s, 1 H, 2-H), 8.04 (d,
J = 11.6 Hz, 2 H, 5,7-H), 2.73 (s, 6 H, 1,3-COMe), 1.51 (s, 9 H,
tBu) ppm. 13C NMR (100 MHz, CDCl3): δ = 195.26, 167.03,
143.07, 142.61, 140.10, 131.01, 123.44, 39.07, 31.73, 28.86 ppm. IR
1,6-Di-tert-Butyl-3-formylazulene (5):[7] POCl3 (613 mg, 4.00 mmol)
was added at room temperature to a solution of 2 (296 mg,
1.00 mmol) in DMF (20 mL). The resulting mixture was stirred at
100 °C for 12 h. The reaction mixture was poured into NaOH (1 )
and extracted with toluene. The organic layer was washed with
brine, dried with MgSO4, and concentrated under reduced pressure.
The residue was purified by column chromatography on silica gel
with toluene/AcOEt (1:1) to give 5 (262 mg, 98%) as purple crys-
1
tals. M.p. 95.0–99.0 °C (ref.[7] 96.0–99.0 °C). H NMR (400 MHz,
CDCl3): δ = 10.33 (s, 1 H, 3-CHO), 9.44 (d, J = 10.8 Hz, 1 H, 4-
H), 8.80 (d, J = 10.8 Hz, 1 H, 8-H), 8.12 (s, 1 H, 2-H), 7.75–7.66
(m, 2 H, 5,7-H), 1.59 (s, 9 H, tBu), 1.48 (s, 9 H, tBu) ppm.
(KBr disk): ν
= 1649 (m), 1632 (s), 1583 (m), 1574 (m), 1508
˜
max
(m), 1427 (s), 1400 (s), 1364 (m), 1221 (s), 1192 (m), 976 (m), 924
(m), 874 (m), 596 (m) cm–1. UV/Vis (CH2Cl2): λmax (log ε) = 242
(4.49), 292 (4.70), 313 (4.57), 378 (sh) (4.02), 391 (4.04), 491 (2.97),
515 (sh) (2.92), 571 (sh) (2.33) nm. HRMS (ESI): calcd. for
1,6-Di-tert-butylazulene (1):[4] Pyrrole (10 mL) was added to a solu-
tion of 5 (2.68 g, 10.0 mmol) in acetic acid (50 mL). The mixture
was stirred at room temperature for 24 h. The reaction mixture was
poured into water and extracted with hexane. The organic layer
was dried with MgSO4 and concentrated under reduced pressure.
The crude product was purified by column chromatography on sil-
ica gel with hexane to afford 1 (1.99 g, 83%) as blue crystals. M.p.
C18H20O2
+ +
Na+ [M Na]+ 291.1356; found 291.1355.
C18H20O2·0.2H2O (268.35): calcd. C 79.50, H 7.56; found C 79.50,
H 7.56.
1
1,3-Diacetyl-6-tert-butylazulene (3b): Acetyl chloride (785 mg,
40.5–45.0 °C (ref.[4] 42.0–44.0 °C). H NMR (500 MHz, CDCl3): δ
10.0 mmol) and AlCl3 (2.67 g, 20.0 mmol) were added at room tem-
= 8.61 (d, J = 10.5 Hz, 1 H, 8-H), 8.19 (d, J = 10.5 Hz, 1 H, 4-H),
perature to a solution of 2 (592 mg, 2.00 mmol) in CH2Cl2 (20 mL). 7.74 (d, J = 4.0 Hz, 1 H, 2-H), 7.25 (dd, J = 10.5, 2.0 Hz, 1 H, 7-
1560 Eur. J. Org. Chem. 2009, 1554–1563
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© 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

ipso-Substitution and Unique Reactions of 1,3,6-Tri-tert-butylazulene
H), 7.22 (dd, J = 10.5, 2.0 Hz, 1 H, 5-H), 7.19 (d, J = 4.0 Hz, 1 H,
3-H), 1.59 (s, 9 H, tBu), 1.44 (s, 9 H, tBu) ppm.
13.6 Hz, 1 H, 6Ј-H), 7.66–7.51 (m, 4 H, 5,7,4Ј,5Ј-H), 6.65 (d, J =
6.8 Hz, 2 H, 2ЈЈ,6ЈЈ-H), 5.12 (dd, J = 6.8, 3.2 Hz, 2 H, 3ЈЈ,5ЈЈ-H),
4.85 (s, 1 H, 4ЈЈ-H), 1.58 (s, 9 H, tBu), 1.49 (s, 9 H, tBu) ppm. 13C
NMR (100 MHz, CDCl3): δ = 143.92, 142.85, 142.63, 142.35,
136.96, 132.97, 132.60, 126.64, 125.81, 124.98, 124.56, 121.86,
121.56, 119.12, 111.83, 111.55, 38.86, 33.25, 31.67, 31.42 ppm. IR
1,6-Di-tert-butyl-3-{1-[(trifluoromethyl)sulfonyl]-1,4-dihydropyridin-
4-yl}azulene (6): Tf2O (339 mg, 1.20 mmol) and pyridine (396 mg,
5.00 mmol) in CH2Cl2 (10 mL) were added at room temperature to
a solution of 1 (240 mg, 1.00 mmol) in CH2Cl2 (10 mL). The re-
sulting mixture was stirred at the same temperature for 30 min. The
solvent was removed under reduced pressure, and the residue was
purified by column chromatography on silica gel with CH2Cl2 to
give 6 (379 mg, 88 %) as blue crystals. M.p. 128.0–130.0 °C. 1H
NMR (400 MHz, CDCl3): δ = 8.60 (d, J = 10.8 Hz, 1 H, 4-H), 8.17
(d, J = 10.8 Hz, 1 H, 8-H), 7.62 (s, 1 H, 2-H), 8.02 (s, 1 H, 2-H),
7.24 (d, J = 10.8 Hz, 1 H, 7-H), 7.22 (d, J = 10.8 Hz, 1 H, 5-H),
6.55 (d, J = 8.4 Hz, 2 H, 2Ј,4Ј-H), 5.28 (dd, J = 8.4, 3.2 Hz, 2 H,
5Ј-H), 4.78 (s, 1 H, 4Ј-H), 1.57 (s, 9 H, tBu), 1.45 (s, 9 H, tBu)
ppm. 13C NMR (100 MHz, CDCl3): δ = 138.45, 135.34, 134.84,
(KBr disk): ν
= 1573 (m), 1494 (s), 1436 (m), 1413 (m), 1394
˜
max
(m), 1371 (m), 1223 (m), 1172 (s), 1116 (s), 1072 (m), 887 (m), 839
(s), 796 (m), 769 (m), 705 (m), 680 (m), 617 (m), 590 (m), 578 (m),
447 (m) cm–1. UV/Vis (CH2Cl2): λmax (log ε) = 238 (4.36), 288
(4.40), 360 (sh) (4.09), 378 (sh) (4.07), 548 (4.79) nm. UV/Vis (hex-
ane): λmax (log ε) = 236 (4.35), 258 (sh) (4.22), 286 (4.33), 302 (sh)
(4.18), 362 (4.18), 526 (4.84) nm. HRMS (ESI): calcd. for
C
30H32F6N2O4S2 + Na+ [M + Na]+ 685.1605; found 685.1600.
C30H32F6N2O4S2 (662.71): calcd. C 54.37, H 4.87, N 4.23; found
C 54.34, H 5.02, N 4.26.
134.53, 133.82, 131.34, 129.02, 128.21, 125.28, 119.88, 119.86, 6Ј-(1,6-Di-tert-butylazulen-3-yl)-3Ј-{1ЈЈ-[(trifluoromethyl)sulfonyl]-
119.82 (q, JC,F = 323.9 Hz), 119.07, 113.63, 38.32, 33.30, 32.13,
1ЈЈ,4ЈЈ-dihydropyridin-4ЈЈ-yl}-1Ј-[(trifluoromethyl)sulfonyl]-1Ј-aza-
hexa-1Ј,3Ј,5Ј-triene (8): Tf2O (282 mg, 1.00 mmol) and pyridine
31.78 ppm. IR (KBr disk): ν = 2965 (m), 2957 (m), 2907 (m),
˜
max
2872 (m), 1580 (m), 1410 (s), 1368 (m), 1285 (m), 1233 (s), 1196 (95 mg, 1.2 mmol) in CH2Cl2 (5 mL) were added at room tempera-
(s), 1159 (s), 1076 (m), 949 (s), 810 (m), 696 (s), 594 (s), 569 (m),
ture to a solution of 7 (227 mg, 0.503 mmol) in CH2Cl2 (5 mL).
525 (m) cm–1. UV/Vis (CH2Cl2): λmax (log ε) = 243 (4.20), 261 The resulting mixture was stirred at the same temperature for
(4.02), 293 (4.70), 303 (4.75), 345 (sh) (3.64), 355 (3.78), 367 (3.49),
372 (3.64), 458 (sh) (1.87), 598 (2.53), 648 (sh) (2.42) nm. HRMS
30 min. The solvent was removed under reduced pressure, and the
residue was purified by column chromatography on silica gel with
(ESI): calcd. for C24H28F3NO2S + Na+ [M + Na]+ 474.1690; found CH2Cl2 to give 8 (278 mg, 84%).
474.1685. C24H28F3NO2S (451.55): calcd. C 63.84, H 6.25, N 3.10;
found C 63.77, H 6.15, N 3.14.
1,6-Di-tert-butyl-3-(pyridin-4-yl)azulene (9)
Treatment of 6 with KOH in EtOH: KOH (561 mg, 10.0 mmol) was
6Ј-(1,6-Di-tert-butylazulen-3-yl)-1Ј-[(trifluoromethyl)sulfonyl]-1Ј-
azahexa-1Ј,3Ј,5Ј-triene (7) and 6Ј-(1,6-Di-tert-butylazulen-3-yl)-3Ј-
{1ЈЈ-[(trifluoromethyl)sulfonyl]-1ЈЈ,4ЈЈ-dihydropyridin-4ЈЈ-yl}-1Ј-[(tri-
fluoromethyl)sulfonyl]-1Ј-azahexa-1Ј,3Ј,5Ј-triene (8): Tf2O (339 mg,
1.20 mmol) and pyridine (119 mg, 1.50 mmol) in CH2Cl2 (10 mL)
were added at room temperature to a solution of 1 (240 mg,
1.00 mmol) in CH2Cl2 (10 mL). The resulting mixture was stirred at
the same temperature for 10 min. The solvent was removed under
reduced pressure, and the residue was purified by column
chromatography on silica gel with CH2Cl2 to give 7 (415 mg, 92%)
as metallic-green needles and 8 (33 mg, 5%) as metallic-green need-
les.
added at room temperature to a solution of 6 (451 mg, 1.00 mmol)
in EtOH (20 mL). The resulting mixture was heated at reflux for
30 min, poured into water, extracted with CH2Cl2, and dried with
MgSO4. The solvent was removed under reduced pressure, and the
residue was purified by column chromatography on silica gel with
AcOEt to give 9 (323 mg, 95%) as blue crystals.
Treatment of 6 with tBuOK in DMSO: tBuOK (336 mg, 3.00 mmol)
was added at room temperature to a solution of 6 (451 mg,
1.00 mmol) in DMSO (20 mL). The resulting mixture was stirred
at the same temperature for 10 min, poured into water, extracted
with toluene, and dried with MgSO4. The solvent was removed
under reduced pressure, and the residue was purified by column
chromatography on silica gel with AcOEt and by GPC with CHCl3
to give 9 (194 mg, 57%).
1
Compound 7: M.p. 210.0–218.0 °C (hexane). H NMR (500 MHz,
CDCl3): δ = 8.66 (d, J = 10.5 Hz, 1 H, 4-H), 8.63 (d, J = 10.5 Hz,
1 H, 2Ј-H), 8.46 (d, J = 10.5 Hz, 1 H, 8-H), 8.04 (s, 1 H, 2-H), 7.81
(d, J = 14.5 Hz, 1 H, 6Ј-H), 7.66 (t, J = 10.5 Hz, 1 H, 4Ј-H), 7.58
(d, J = 10.5, 2.0 Hz, 1 H, 5-H), 7.55 (d, J = 10.5, 2.0 Hz, 1 H, 7-
H), 7.13 (dd, J = 14.5, 10.5 Hz, 1 H, 5Ј-H), 6.57 (dd, J = 14.5,
1
Compound 9: M.p. 126.0–127.0 °C. H NMR (400 MHz, CDCl3):
δ = 8.68 (d, J = 10.8 Hz, 1 H, 8-H), 8.64 (d, J = 5.6 Hz, 2 H, 2Ј,6Ј-
H), 8.50 (d, J = 10.8 Hz, 1 H, 4-H), 7.89 (s, 1 H, 2-H), 7.52 (d, J
= 5.6 Hz, 2 H, 3Ј,5Ј-H), 7.35 (dd, J = 10.8, 2.0 Hz, 1 H, 7-H), 7.33
(dd, J = 10.8, 2.0 Hz, 1 H, 5-H), 1.62 (s, 9 H, tBu), 1.46 (s, 9 H,
tBu) ppm. 13C NMR (100 MHz, CDCl3): δ = 162.36, 149.68,
145.14, 138.92, 136.16, 135.75, 135.44, 134.60, 133.82, 124.95,
123.93, 122.08, 120.28, 38.31, 33.13, 31.99, 31.67 ppm. IR (KBr
10.5 Hz, 1 H, 3Ј-H), 1.59 (s, 9 H, tBu), 1.48 (s, 9 H, tBu) ppm. 13
C
NMR (100 MHz, CDCl3): δ = 177.90, 164.45, 143.62, 141.75,
141.51, 141.03, 136.67, 132.86, 132.18, 125.85, 124.97, 124.16,
122.79, 122.49, 121.13, 119.47 (q, JC,F = 310.2 Hz), 38.76, 33.27,
31.65, 31.50 ppm. IR (KBr disk): ν
= 2964 (m), 1570 (s), 1498
˜
max
disk): ν
= = 3067 (s), 3030 (s), 2963 (s), 2905 (s), 1593 (s), 1578
(s), 1439 (m), 1394 (m), 1338 (m), 1184 (s), 1157 (s), 1115 (s), 1070
(m), 1022 (m), 831 (s), 796 (m), 769 (m), 758 (m), 630 (m), 571 (m)
cm–1. UV/Vis (CH2Cl2): λmax (log ε) = 236 (4.35), 258 (sh) (4.22),
286 (4.32), 372 (4.13), 394 (sh) (3.64), 355 (3.78), 367 (3.49), 372
(3.64), 560 (4.85), 610 (sh) (4.71) nm. UV/Vis (hexane): λmax (log ε)
= 236 (4.35), 258 (sh) (4.22), 286 (4.33), 302 (sh) (4.18), 362 (4.18),
526 (4.84) nm. HRMS (ESI): calcd. for C24H28F3NO2S + Na+ [M
+ Na]+ 474.1690; found 474.1685. C24H28F3NO2S (451.55): calcd.
C 63.84, H 6.25, N 3.10; found C 64.11, H 6.44, N 3.09.
˜
max
(s), 1545 (m), 1518 (m), 1495 (m), 1460 (m), 1427 (m), 1390 (m),
1365 (m), 1240 (m), 1217 (m), 1199 (m), 835 (s), 825 (s), 692 (m),
617 (m), 557 (m), 416 (m) cm–1. UV/Vis (CH2Cl2): λmax (log ε) =
246 (4.30), 263 (4.10), 289 (4.40), 317 (4.49), 347 (3.79), 358 (sh)
(3.83), 389 (4.04), 473 (1.96), 594 (2.57), 641 (2.47), 715 (1.93) nm.
UV/Vis (AcOH): λmax (log ε) = 292 (4.48), 338 (sh) (4.24), 350
(4.31), 438 (4.40) nm. HRMS (ESI): calcd. for C23H27N + H+ [M
+ H]+ 318.2222; found 318.2216. C23H27N (317.47): calcd. C 87.02,
H 8.57, N 4.41; found C 86.86, H 8.46, N 4.40.
1
Compound 8: M.p. 171.0–176.0 °C (AcOEt). H NMR (400 MHz,
CDCl3): δ = 8.68 (d, J = 10.4 Hz, 1 H, 4-H), 8.49 (d, J = 10.4 Hz,
1 H, 8-H), 8.48 (s, 1 H, 2Ј-H), 7.96 (s, 1 H, 2-H), 7.76 (d, J =
Treatment of 2 with TPT: Tf2O (677 mg, 2.40 mmol) and pyridine
(791 mg, 10.0 mmol) in CH2Cl2 (10 mL) were added at room tem-
Eur. J. Org. Chem. 2009, 1554–1563
© 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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1561

T. Shoji, N. Morita et al.
perature to a solution of 2 (296 mg, 1.00 mmol) in CH2Cl2 (10 mL). 3,5,9-Tri-tert-butyltricyclo[6.2.2.02,6]dodeca-2,4,6,9-tetraene-
FULL PAPER
The resulting mixture was stirred at the same temperature for 12 h.
The solvent was removed under reduced pressure, and the residue
was purified by column chromatography on silica gel with hexane/
AcOEt (4:1) to give 1,6-di-tert-butyl-3-[(trifluoromethyl)thio]azu-
lene (10, 174 mg, 51%) as purple crystals and 3,6,8a-tri-tert-butyl-
1(8aH)-azulenone (11, 119 mg, 38%) as yellow prisms.
11,11,12,12-tetracarbonitrile (13): TCNE (384 mg, 3.00 mmol) was
added at room temperature to a solution of 2 (593 mg, 2.00 mmol)
in AcOEt (10 mL). The resulting mixture was stirred at the same
temperature for 15 h. The solvent was removed under reduced pres-
sure, and the residue was purified by column chromatography on
silica gel with CH2Cl2 to give 13 (837 mg, 100%) as orange prisms.
1
M.p. 151.0–152.0 °C (decomp.). H NMR (600 MHz, CDCl3): δ =
Compound 10: M.p. 104.0–105.0 °C (CH2Cl2). 1H NMR (400 MHz,
CDCl3): δ = 8.72 (d, J = 10.4 Hz, 1 H, 8-H), 8.66 (d, J = 10.4 Hz,
1 H, 4-H), 7.87 (s, 1 H, 2-H), 7.57 (dd, J = 10.4, 2.0 Hz, 1 H, 7-
H), 7.50 (dd, J = 10.4, 2.0 Hz, 1 H, 5-H), 1.60 (s, 9 H, tBu), 1.48
(s, 9 H, tBu) ppm. 13C NMR (100 MHz, CDCl3): δ = 162.87,
6.87 (d, J = 8.8 Hz, 1 H, 7-H), 6.20 (dd, J = 7.9, 1.4 Hz, 1 H, 10-
H), 6.13 (s, 1 H, 4-H), 4.97 (d, J = 7.9 Hz, 1 H, 1-H), 4.10 (dd, J
= 8.8, 1.4 Hz, 1 H, 8-H), 1.34 (s, 9 H, tBu), 1.23 (s, 9 H, tBu), 1.16
(s, 9 H, tBu) ppm. 13C NMR (150 MHz, CDCl3): δ = 156.15 (3-
C), 155.65 (9-C), 148.16 (2-C), 145.80 (5-C), 129.75 (7-C), 128.83
(4-C), 120.22 (10-C), 115.94 (2-C), 112.98 (CN), 112.53 (CN),
111.44 (CN), 111.13 (CN), 46.27 (12-C), 45.30 (11-C), 44.82 (1-C),
43.51 (8-C), 35.10 (tBu), 34.38 (tBu), 32.86 (tBu), 31.52 (tBu), 30.91
143.18, 141.67, 138.95, 136.90, 135.97, 134.65, 129.40 (q, JC,F
=
308.6 Hz), 123.27, 122.01, 103.03, 38.65, 33.27, 31.98, 31.83 ppm.
IR (KBr disk): νmax = = 2907 (s), 2872 (s), 1587 (s), 1578 (m), 1549
˜
(m), 1500 (m), 1475 (m), 1460 (m), 1410 (m), 1392 (m), 1379 (m),
1363 (m), 1261 (m), 1244 (m), 1217 (m), 1201 (m), 1068 (m), 978
(m), 873 (m), 841 (m), 750 (m), 677 (m), 636 (m), 478 (m), 451 (m)
cm–1. UV/Vis (CH2Cl2): λmax (log ε) = 239 (4.32), 262 (3.97), 296
(4.74), 304 (4.79), 323 (3.65), 350 sh (3.83), 354 (3.82), 363 (3.68),
372 (3.79), 561 (2.66), 598 (sh) (2.60), 663 (2.11) nm. HRMS (EI):
calcd. for C19H23F3S+ [M]+ 340.1473; found 340.1469. C19H23F3S
(340.45): calcd. C 67.03, H 6.81; found C 67.14, H 6.94.
(tBu), 27.54 (tBu) ppm. IR (KBr disk): ν
= 2968 (s), 2907 (m),
˜
max
2872 (m), 2201 (m, CϵN), 1632 (m), 1479 (m), 1466 (m), 1394 (m),
1365 (m), 1252 (m), 1199 (m), 852 (m) cm–1. UV/Vis (CH2Cl2): λmax
(log ε) = 250 (4.04), 277 (3.89), 412 (2.84) nm. HRMS (ESI): calcd.
for C28H32N4 + Na+ [M + Na]+ 447.2525; found 447.2519.
C28H32N4 (424.58): calcd. C 79.21, H 7.60, N 13.20; found C 79.33,
H 7.69, N 13.19.
Compound 11: M.p. 109.0–110.0 °C (MeOH). 1H NMR (600 MHz,
CDCl3): δ = 6.69 (d, J = 7.7 Hz, 1 H, 4-H), 6.33 (dd, J = 11.7,
1.6 Hz, 1 H, 7-H), 6.15 (dd, J = 7.7, 1.6 Hz, 1 H, 5-H), 5.82 (d, J
= 11.7 Hz, 1 H, 8-H), 5.71 (s, 1 H, 2-H), 1.38 (s, 9 H, tBu), 1.16
(s, 9 H, tBu), 0.80 (s, 9 H, tBu) ppm. 13C NMR (150 MHz, CDCl3):
δ = 209.17 (1-C), 180.61 (3-C), 153.02 (6-C), 136.06 (3a-C), 128.78
(8-C), 127.31 (7-C), 124.43 (2-C), 123.46 (4-C), 121.19 (5-C), 63.58
(8a-C), 42.84 (tBu), 36.44 (tBu), 34.71 (tBu), 30.28 (tBu), 29.76
Acknowledgments
This work was partially supported by the Global Center of Excel-
lence (GCOE) project, the International Center of Research &
Education for Molecular Complex Chemistry, of the Ministry of
Education, Culture, Sports, Science, and Technology, Japan.
(tBu), 25.76 (tBu) ppm. IR (KBr disk): ν
= 2872 (s), 1701 (s,
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C=O), 1394 (m), 1363 (m), 1315 (m), 1246 (m), 1196 (m), 1159 (m),
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of 1 (240 mg, 1.00 mmol) in AcOEt (5 mL). The resulting mixture
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column chromatography on silica gel with toluene/AcOEt (4:1) to
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115.04, 114.23, 39.23, 33.32, 31.63, 31.11 ppm. IR (KBr disk): ν
˜
max
= 2970 (m), 2210 (m, CϵN), 1581 (m), 1491 (s), 1466 (m), 1444
(m), 1400 (m), 1383 (m), 1361 (m), 1107 (m), 557 (m) cm–1. UV/
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(sh) (4.16), 363 (sh) (3.86), 388 (sh) (3.85), 405 (3.87), 524 (sh)
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Received: November 2, 2008
Published Online: February 11, 2009
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