Synthesis and stability of 1,1-dialkyl-1H-azulenium cations

Article abstract of DOI:10.1016/j.tet.2006.05.084

Starting from trimethylsilyl enol ether of 1-acetyl-1,3,5-cycloheptatriene, the title 1,1-dimethyl-, 1,1-diethyl-, and 1,1-dipropyl-1H-azulenium cations 6-8 were synthesized in five steps. The order of pK_R+ values of these cations was found to be 7>8>6. A comparison of the values between 1,1-dialkyl- and 1,1-spiroalkylated 1H-azulenium cations with the same number of carbon atoms at the 1-position provided the results of 7>1 and 8<3. The cation 8 shows a relatively lower pK_R+ value to those of 3 and 7 probably due to its slightly bulkier propyl groups from which solvation stabilization of 8 under the conditions suffers. An intermolecular charge-transfer interaction between the cations and dibenzo-24-crown-8 was also studied.

Full text of DOI:10.1016/j.tet.2006.05.084

Tetrahedron 62 (2006) 8177–8183
Synthesis and stability of 1,1-dialkyl-1H-azulenium cations
b
b
b
Mitsunori Oda,a, Nobue Nakajima, Nguyen Chung Thanh, Takanori Kajioka
*
and Shigeyasu Kurodab
aDepartment of Chemistry, Faculty of Science, Shinshu University, Asahi 3-1-1, Matsumoto, Nagano 390-8621, Japan
bDepartment of Applied Chemistry, Faculty of Engineering, University of Toyama, Gofuku 3190, Toyama 930-8555, Japan
Received 6 April 2006; accepted 29 May 2006
Available online 27 June 2006
Abstract—Starting from trimethylsilyl enol ether of 1-acetyl-1,3,5-cycloheptatriene, the title 1,1-dimethyl-, 1,1-diethyl-, and 1,1-dipropyl-
1H-azulenium cations 6–8 were synthesized in five steps. The order of pKR+ values of these cations was found to be 7>8>6. A comparison of
the values between 1,1-dialkyl- and 1,1-spiroalkylated 1H-azulenium cations with the same number of carbon atoms at the 1-position provided
the results of 7>1 and 8<3. The cation 8 shows a relatively lower pKR+ value to those of 3 and 7 probably due to its slightly bulkier propyl
groups from which solvation stabilization of 8 under the conditions suffers. An intermolecular charge-transfer interaction between the cations
and dibenzo-24-crown-8 was also studied.
Ó 2006 Elsevier Ltd. All rights reserved.
1. Introduction
+
+
+
We previously reported the synthesis and some crystal struc-
tures of various 1,1-spiroalkylated 1H-azulenium cations 1–
5.1,2 Their pKR+valueswere in a range of 9.9–13.2, which are
far greater than that of the tropylium cation. The order of the
stability of mono-spiroalkylated cations increases with the
number of carbon atoms of the carbocycle at the 1-position,
as 3>2>1 and the reluctance against electrochemical reduc-
tion showed a similar tendency.1 The enhanced thermo-
dynamic stability is attributed to a hybrid stabilization of
the inductive and s–p conjugation effects of the carbocycle
and the p–p conjugation of the double bond at the 2- and
3-positions. Since the degree of the p–p conjugative effects
is the same in a series of the cations, the order of the stability
of mono-spiroalkylated cations should mainly meet the
degree of the effects of the substituents at the 1-position;
the cation having more carbon atoms in the substituents at
the 1-position should be more stable. Herein, we describe
the synthesis of 1H-azulenium cations 6–8 substituted simply
by linear alkyl groups and also their stability, which does
not come up to the order of the number of carbon atoms in
the alkyl groups.
1
2
3
+
+
+
Tropylium
ion
4
5
4
8
5
7
3
1
3a
2
6
+
+
+
8a
6
7
8
2. Results and discussion
2.1. Synthesis and physical properties of 1,1-dialkyl-1H-
azulenium cations 6–8
The title cations were synthesized by the method, which we
had developed for the spiroalkylated cation 33 (Scheme 1).
The Mukaiyama aldol reaction4 of the trimethylsilyl enol
ether 9 with the ketones in the presence of titanium tetrachlo-
ride and the subsequent Nazarov cyclization5,6 provided
the azulenones 13–15 in moderate yields. Since the yield of
the keto-alcohol 12 was slightly less than those of others, the
Noyori–Mukaiyama aldol reaction7 was also applied for 9
Keywords: Carbocations; pKR+ values; Tropylium ions; Nazarov cycliza-
tions; Intermolecular charge-transfer interaction.
* Corresponding author. Tel./fax: +81 263 37 3343; e-mail: mituoda@
shinshu-u.ac.jp
0040–4020/$ - see front matter Ó 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2006.05.084

8178
M. Oda et al. / Tetrahedron 62 (2006) 8177–8183
O
O
R
R
OTMS
O
R
HCO2H, H3PO4
R
OH
TiCl4
R
R
9
10 (R=Me, 59%)
11 (R=Et, 72%)
12 (R=Pr, 41%)
13 (R=Me, 68%)
14 (R=Et, 58%)
15 (R=Pr, 69%)
NNHTs
Ph3C+ClO4
–
6 (60%)
7 (61%)
8 (56%)
H2NNHTs
THF
MeLi
ether
R
R
R
R
16 (R=Me)
17 (R=Et)
18 (R=Pr)
19 (R=Me, 33% based on 13)
20 (R=Et, 39% based on 14)
21 (R=Pr, 20% based on 15)
Scheme 1.
with 4,4-dimethoxyheptane. The reaction gave a mixture of
two products, 22 and 23 (Scheme 2). Separation of the prod-
ucts by column chromatography resulted in isolation of only
23. So far, 22 has not been isolated, though its existence in the
mixture was confirmed by its NMR spectrum. Without puri-
fication, this mixture was converted by the Nazarov cycliza-
tion into 15 in 78% yield based on 9. The azulenones 13–15
were transformed into the 1,4-dihydroazulenes 19–21 via the
tosylhydrazone 16–18 by the Shapiro reaction.8 The final
hydride abstraction with trityl perchlorate (Ph3C+ClO4ꢀ) pro-
duced the desired cations 6–8. Their structures were fully
characterized by spectroscopic and combustion analyses.
The results of H–H COSY, HMQC, and HMBC experiments
covered the assignments of both proton and carbon signals
indicated in Section 5 except the carbon signals for the 6-
and 7-positions of 6. Their UV spectra showed three bands
at 224–231, 264–271, and 358–363 nm as seen in the spectra
of 1–3 (Table 1; Figs. 1 and 2).
Figure 1. UV spectra of the cations 1–3 in acetonitrile.
MeO OMe
O
O
Pr
Pr
HCO2H
H3PO4
Pr
TMSOTf
Pr
Pr
+
15
9
Pr
OMe
(78% based on 9)
22
23
Scheme 2.
Table 1. UV absorption maxima in acetonitrile of 1, 2, 3, 6, 7, and 8
Compounds
lmax in nm (log 3)
Figure 2. UV spectra of the cations 6–8 in acetonitrile.
1
2
3
6
7
8
230 (4.31), 272 (4.44), 364 (4.00)
230 (4.26), 272 (4.33), 367 (4.07)
227 (4.29), 268 (4.34), 362 (4.03)
222 (4.33), 264 (4.43), 358 (4.09)
228 (4.15), 268 (4.18), 362 (3.94)
231 (4.29), 271 (4.35), 363 (4.08)
determined,9 which indicates thermodynamic stability for
the carbocation.
Rþ þ H2O#ROH þ Hþ
ð1Þ
2.2. Thermodynamic stability and reduction potentials
of 1,1-dialkyl-1H-azulenium cations
The pKR+ values of 6, 7, and 8 obtained by the UV method in
50% aqueous acetonitrile solutions were 8.6, 10.1, and 9.2,
respectively (Table 2). The thermodynamic stability of these
cations is comparable to those of the cations 1–3 and
Assuming equilibrium between a carbocation and its
corresponding alcohol (Eq. 1), the pKR+ value can be

M. Oda et al. / Tetrahedron 62 (2006) 8177–8183
Table 2. The pKR+ values and reduction potentials of 1, 2, 3, 6, 7, and 8
8179
Although the potentials of 6–8 decreasewith increasing num-
ber of carbon atoms in the substituents, the value of 8 is com-
parable to that of 7, suggesting that stabilization by inductive
and s–p conjugative effects of the propyl groups in 8 is the
same as that of the ethyl groups in 7. This is in contrast to
the result in the case of 1,1-spiroalkyl-1H-azulenium cations
1–3. Specially, it is most clear when the cations with the same
number of carbon atoms in the substituents at the 1-position
between two series of 1,1-dialkyl- and 1,1-spiroalkyl cations
are compared; 7 shows slightly greater stability than 1 based
not only on the pKR+ values but also on reduction potentials,
though stability of 8 is less than that of 3. Therefore, it is
apparent that stabilization by inductive and s–p conjugative
effects of the alkyl group in the 1,1-dialkyl system is almost
saturated up to the number of six carbon atoms.
Compounds
pKR+ valuesa
Reduction potentials
(V vs SCE)b
1
2
3
6
7
8
9.9
10.0
10.4
8.6
10.1
9.2
ꢀ0.41
ꢀ0.46
ꢀ0.54
ꢀ0.38
ꢀ0.45
ꢀ0.46
a
For measurements, see Section 5.
Irreversible.
b
1,2-bicyclo[2.2.2]octanotropylium cation (24, pKR+ 8.8)10
and is greater than that (pKR+ 3.88)11 of the tropylium cat-
ions. The order of the stability (7>8>6) is not that expected
from the number of carbon atoms in the alkyl groups. Since
two propyl groups located at the 1-position of the cation 8
are slightly hydrophobic and bulky to show steric hindrance,
the solvation stabilization in the aqueous acetonitrile solu-
tion of the cation 8 must suffer.12 In other words, the degree
of the inductive and conjugative effects of the propyl group
in 8 cannot be adequately evaluated from this pKR+ value.
On the other hand, tropylium ions in general show
irreversible potentials by electrochemical reduction (Fig. 3).
The reduction potentials of tropylium ions indicate their
reluctance for the reduction and provide another empirical
stability parameter for carbocations.13 Reduction potentials
for 6–8 measured by cyclic voltammetry in an acetonitrile
solution with tetrabutylammonium perchlorate as a support-
ing electrolyte are shown in Table 2.
3. Intermolecular charge-transfer interaction of the
1,1-substituted 1H-azulenium cations with dibenzo-
24-crown-8
The tropylium cation as an acceptor shows intermolecular
charge-transfer (ICT) interactions with n-donors of halide
anions14 and p-donors of aromatic hydrocarbons.15 Benz-
ene-substituted crown ethers are known to serve also as
a p-donor and show ICT absorptions with tropylium cat-
ions.16 As a typical example, the tropylium cation and
dibenzo-24-crown-8 yielded the 1:1 inclusion complex 25.17
We also are interested in whether the 1,1-substituted 1H-
azulenium cations interact with dibenzo-24-crown-8 or
not. In order to examine such possibility, measurements of
1H NMR and UV–vis spectra in the presence of the crown
ether were carried out. The difference between the average
chemical shifts of the cationic protons in the presence and
absence of the crown ether is quite small as shown in Table 3.
The acetonitrile solutions containing a 1:1 mixture of the
cation and the crown ether indicated clear ICT bands around
500–700 nm. However, attempts to isolate inclusion com-
plexes have met with little success so far. These results sug-
gest that the interaction between the azulenium cations
and the benzene ring of the crown ether occurs not in the
way of the cationic part sandwiched between two benzene
rings of the crown ether like 25 but the cationic part with
one benzene ring at the outside of the crown molecule, prob-
ably due to larger molecular sizes of these azulenium cations
than that of the tropylium cation. Further study for evaluating
the associate constant for complexes and interaction using
+
24
Table 3. The change of average chemical shifts of the cations 1, 2, 3, 6, 7,
and 8 in the presence of dibenzo-24-crown-8 and ICT absorption bands
Compounds
Change of the shifta
d (ppm)
ICT absorption
wavelength (nm)b
1
2
3
6
+0.031
+0.025
+0.016
+0.04
599, 646
650, 715sh
554, 667
655
7
+0.01
+0.006
+0.11
520sh
509sh
8
Tropylium ion
425c
a
The average shifts of the seven-membered ring protons of a 1:1 mixture in
CDCl3 solutions.
Measured in acetonitrile.
Taken from Ref. 16.
b
c
Figure 3. Cyclic voltammograms of the cations 6–8 in an acetonitrile solu-
tion containing 0.1 M tetrabutylammonium perchlorate.

8180
M. Oda et al. / Tetrahedron 62 (2006) 8177–8183
crown ethers with a larger core size is the focus of current
investigations.
anhydrous MgSO4. The solvent was removed under reduced
pressure and the residue was purified by column chromato-
graphy (SiO2, hexane–ethyl acetate (9:1) as eluent) to give
1
O
O
1.58 g (72% yield) of 11 as a pale yellow oil. H NMR
(CDCl3) d 0.86 (t, J¼7.6 Hz, 6H), 1.53 (m, 4H), 2.63
(d, J¼7.1 Hz, 2H), 2.83 (s, 2H), 4.15 (br s, 1H), 5.58 (dt,
J¼9.4, 7.1 Hz, 1H), 6.29 (dd, J¼9.4, 5.6 Hz, 1H), 6.71 (dd,
J¼11.2, 5.9 Hz, 1H), 6.88 (dd, J¼11.2, 5.9 Hz, 1H), 7.12
(d, J¼5.9 Hz, 1H) ppm; 13C NMR (CDCl3) d 8.1, 25.2,
31.3, 43.6, 74.4, 125.8, 127.3, 129.1, 131.9, 133.1, 136.5,
201.8 ppm; IR (KBr) nmax¼1647s, 732s cmꢀ1; MS (20 eV)
m/z (rel int) 220 (M+, 2), 202 (18), 134 (18), 119 (93), 91
(100), 65 (25), 57 (28). Found: 220.1463. Calcd for
C14H20O2: M, 220.1445.
O
O
O
O
+
O
O
25
4. Summary
We have synthesized and characterized the 1,1-dialkyl-1H-
azulenium cations 6–8 whose stability was discussed based
on their pKR+ values and reduction potentials. The pKR+
value of the cation 8 is smaller relative to those of 1, 2, 3,
and 7. This can be ascribed to its restrained solvation stabi-
lization due to its slightly bulkier substituents. Comparison
of reduction potentials of various 1H-azulenium cations sug-
gests that stabilization by inductive and s–p conjugative
effects shows saturation up to the number of six carbon atoms
in the alkyl group in the 1,1-dialkyl-1H-azulenium cations.
A mixture of 1.35 g (6.52 mmol) of 11 in formic acid (7.5 ml)
and phosphoric acid (7.5 ml) was heated at 90 ꢁC for 4 h.
Then the resulted dark brown mixture was poured into water
and extracted with ether (50 mlꢂ3). The combined organic
layer was washed with a saturated NaHCO3 aqueous solution
and brine, and then dried over anhydrous MgSO4. The sol-
vent was removed under reduced pressure and the residue
was purified by column chromatography (SiO2, hexane–ethyl
acetate (9:1) as eluent) to give 700 mg (58% yield) of 14 as
a pale yellow oil. 1H NMR (CDCl3) d 0.68 (t, J¼6.1 Hz, 6H),
1.61 (m, 4H), 2.29 (s, 2H), 2.68 (d, J¼6.5 Hz, 2H), 5.65 (dt,
J¼9.9, 6.5 Hz, 1H), 6.13 (dd, J¼9.9, 5.9 Hz, 1H), 6.63 (d,
J¼11.3 Hz, 1H), 6.80 (dd, J¼11.3, 5.9 Hz, 1H) ppm; 13C
NMR (CDCl3) d 8.5, 21.5, 31.4, 44.3, 46.6, 125.4, 127.2,
5. Experimental
5.1. General
127.9, 133.5, 136.7, 168.5, 206.0 ppm; IR (KBr) nmax
¼
Melting points were measured on a Yanaco MP-3 and are
uncorrected. IR spectra were recorded on a Perkin–Elmer
Spectrum RX I spectrometer. UV spectra were measured
2963s, 1692s cmꢀ1; MS (70 eV) m/z (rel int) 202 (M+, 80),
173 (32), 145 (100), 131 (39), 118 (58), 105 (22), 91 (45).
Found: 202.1358. Calcd for C14H18O: M, 202.1373.
1
on a Shimadzu UV-1600 spectrometer. H and 13C NMR
were recorded with tetramethylsilane as an internal standard
on JEOL a400 spectrometer. Mass spectra were measured on
a JMS-700 mass spectrometer. Cyclic voltammograms were
recorded on a Yanako P1100 instrument. Column chromato-
graphy was done with either Merck Kieselgel 60 Art 7734 or
Wako activated alumina. Ether and THF were purified by
distillation from sodium and benzophenone under argon
atmosphere. An ether solution of methyl lithium was
purchased from Kanto Chem. Co. and was titrated before
use. Titanium tetrachloride was purchased from Wako
Chem. and was used without purification. Dibenzo-24-
crown-8 was purchased from Tokyo Kasei Industry. The syn-
theses of 1-(trimethylsiloxyvinyl)-1,3,5-cycloheptatriene 9
from 1-acetyl-1,3,5-cycloheptatriene and 3,3-dimethyl-
1,2,3,8-tetrahydroazulenone 14 via 10 from 9 were previ-
ously reported.3 Trityl perchlorate was prepared by the
method of Dauben et al.18
Similarly 15 was obtained via 12. Compound 12: a pale
yellow oil. H NMR (CDCl3) d 0.89 (t, J¼7.2 Hz, 6H),
1
1.23–1.52 (m, 8H), 2.64 (d, J¼7.3 Hz, 2H), 2.83 (s, 2H),
5.59 (dt, J¼9.3, 7.2 Hz, 1H), 6.29 (dd, J¼9.3, 5.6 Hz, 1H),
6.70 (dd, J¼11.2, 6.0 Hz, 1H), 6.89 (dd, J¼11.2, 5.6 Hz,
1H), 7.10 (d, J¼6.0 Hz, 1H) ppm; 13C NMR (CDCl3)
d 14.6, 17.1, 25.2, 41.9, 44.4, 74.1, 125.8, 127.3, 129.0,
131.9, 133.0, 136.5, 201.8 ppm; IR (KBr) nmax¼3480br m,
2933s, 1650s, 1603s, 1408s, 1384s, 1200s, 1170s,
717s cmꢀ1; MS (20 eV) m/z (rel int) 230 (M+ꢀH2O, 19),
205 (5), 134 (19), 133 (22), 119 (28), 118 (18), 115 (14),
105 (10), 103 (7), 92 (13), 91 (100), 90 (30), 89 (27).19 Found:
230.1636. Calcd for C16H22O: M, 230.1671. Compound 15:
a pale yellow oil. 1H NMR (CDCl3) d 0.83–0.91 (m, 2H), 0.85
(t, J¼7.2 Hz, 6H), 1.09–1.19 (m, 2H), 1.44 (td, J¼12.8,
4.1 Hz, 2H), 1.57 (td, J¼12.8, 4.1 Hz, 2H), 2.32 (s, 2H),
2.66 (d, J¼6.5 Hz, 2H), 5.65 (dt, J¼9.9, 7.2 Hz, 1H), 6.13
(dd, J¼9.9, 6.0 Hz, 1H), 6.64 (d, J¼11.4 Hz, 1H), 6.78 (dd,
J¼11.4, 6.0 Hz, 1H) ppm; 13C NMR (CDCl3) d 14.6, 17.7,
21.6, 41.7, 45.7, 46.1, 125.6, 127.4, 128.1, 133.0, 136.8,
169.4, 206.4 ppm; IR (KBr) nmax¼2957s, 2929s, 1692s,
1272s cmꢀ1; MS (70 eV) m/z (rel int) 231 (M++1, 19), 230
(M+, 100), 224 (21), 188 (31), 187 (40), 167 (15), 159 (81),
149 (50), 145 (84). Found: 230.1674. Calcd for C16H22O:
M, 230.1671.
5.1.1. Synthesis of 3,3-diethyl- and 3,3-dipropyl-1,2,3,8-
tetrahydroazulenones (14 and 15) by the Mukaiyama
aldol method. A solution of 2.06 g (10.0 mmol) of the silyl
enol ether 9 in 30 ml of dichloromethanewas added dropwise
to a solution of 1.30 ml (11.0 mmol) of titanium chloride and
3.20 ml (30.0 mmol) of 3-pentanone in 20 ml of dichloro-
methane at 0 ꢁC under nitrogen atmosphere. After being stirred
for 3 h, the reaction mixturewas poured intowater. The aque-
ous layer was extracted with dichloromethane (50 mlꢂ2).
The combined organic layer was washed with a saturated
NaHCO3 aqueous solution and brine, and then dried over
5.1.2. Synthesis of 3,3-dipropyl-1,2,3,8-tetrahydroazule-
none (21) by the Noyori–Mukaiyama aldol method. To
a solution of 5.15 g (25.0 mmol) of the silyl enol ether 9

M. Oda et al. / Tetrahedron 62 (2006) 8177–8183
8181
and 4.41 g (27.5 mmol) of 4,4-dimethoxyheptane in 125 ml
of dichloromethane at ꢀ78 ꢁC under nitrogen atmosphere
was added 0.45 ml (2.5 mmol) of trimethylsilyl triflate. After
being stirred at the same temperature for 19 h, the reaction
mixture was poured into water. The aqueous layer was
extracted with dichloromethane (50 mlꢂ2). The combined
organic layer was washed with a saturated NaHCO3 aqueous
solution and brine, and then dried over anhydrous MgSO4.
The solvent was removed under reduced pressure and the resi-
due was purified by column chromatography (SiO2, hexane–
ethyl acetate (96:4) as eluent) to give 5.98 g of a mixture of
22 and 23 as a pale yellow oil. This mixture was dissolved in
formic acid (40 ml) and phosphoric acid (40 ml) and was
heated at 90 ꢁC for 4 h. The resulted dark brown mixture
was poured into ice-water (100 ml) and extracted with ether
(100 mlꢂ3). The combined organic layer was washed with
a saturated NaHCO3 aqueous solution and brine, and then
dried over anhydrous MgSO4. The solvent was removed under
reduced pressure and the residue was purified by column chro-
matography (SiO2, hexane–ethyl acetate (9:1) as eluent) to
give 4.48 g (78% yield based on 9) of 15 as a pale yellow oil.
J¼9.6, 6.8 Hz, 1H), 6.08 (dd, J¼9.6, 6.0 Hz, 1H), 6.08 (d,
J¼5.6 Hz, 1H), 6.37 (d, J¼5.6 Hz, 1H), 6.39 (dd, J¼10.8,
6.0 Hz, 1H), 6.56 (d, J¼10.8 Hz, 1H) ppm; 13C NMR
(CDCl3) d 22.6, 27.9, 51.8, 120.7, 125.2, 127.37, 127.40,
130.6, 132.8, 148.6, 149.2 ppm; IR (KBr) nmax¼2925s,
732s cmꢀ1; MS (70 eV) m/z (rel int) 158 (M+, 35), 143
(100), 128 (74), 115 (18), 91 (23), 77 (21), 58 (22). Found:
158.1049. Calcd for C12H14: M, 158.0960.
Similarly, 14 and 15 were transformed to 20 without iso-
lating 17 in 31% yield based on 14 and to 21.
1
Compound 20: a pale yellow oil. H NMR (CDCl3) d 0.51
(t, J¼7.3 Hz, 6H), 1.52 (dq, J¼11.4, 7.3 Hz, 2H), 1.73 (dq,
J¼11.4, 7.3 Hz, 2H), 2.68 (d, J¼6.6 Hz, 2H), 5.34 (dt,
J¼9.6, 6.6 Hz, 1H), 6.06 (dd, J¼9.8, 5.9 Hz, 1H), 6.17
(d, J¼5.4 Hz, 1H), 6.22 (d, J¼5.4 Hz, 1H), 6.38 (dd,
J¼11.0, 5.6 Hz, 1H), 6.46 (d, J¼11.0 Hz, 1H) ppm; 13C
NMR (CDCl3) d 8.7, 27.8, 29.0, 60.4, 120.4, 125.5, 127.1,
128.7, 133.0, 135.0, 144.9, 145.4 ppm; IR (KBr)
nmax¼2964s, 2931s, 729s cmꢀ1; MS (70 eV) m/z (rel int)
186 (M+, 19), 171 (27), 157 (69), 141 (55), 129 (100), 115
(43), 105 (24), 91 (46), 77 (23), 57 (63). Found: 186.1437.
Calcd for C14H18: M, 186.1409.
Purification of a mixture of 22 and 23 by column chromato-
graphy gave 23 as a pale yellow oil. 1H NMR (CDCl3) d 0.94
(t, J¼7.3 Hz, 6H), 1.45–1.55 (m, 4H), 2.14 (t, J¼7.6 Hz, 2H),
2.42 (t, J¼7.9 Hz, 2H), 2.67 (d, J¼7.2 Hz, 2H), 5.59 (dt,
J¼8.9, 7.2 Hz, 1H), 6.26 (dd, J¼9.3, 5.6 Hz, 1H), 6.41 (s,
1H), 6.68 (dd, J¼11.1, 6.0 Hz, 1H), 6.81 (dd, J¼11.1,
5.6 Hz, 1H), 7.05 (d, J¼6.0 Hz, 1H) ppm; 13C NMR
(CDCl3) d 13.9, 14.4, 21.0, 21.9, 25.9, 34.7, 40.5, 120.8,
125.4, 127.0, 129.3, 131.3, 139.9, 135.2, 161.4, 191.5 ppm;
UV (CH3OH) lmax¼291 (log 3¼3.91), 318sh (3.78) nm; IR
(KBr) nmax¼2957s, 2929s, 1692s, 1272s cmꢀ1; MS (70 eV)
m/z (rel int) 230 (M+, 100), 201 (29), 187 (45), 159 (22),
145 (78), 139 (48), 119 (26), 91 (78). Found: 230.1670. Calcd
for C16H22O: M, 230.1671.
Compound 18: creamy white solids, mp 139–141 ꢁC. Found:
C, 69.32; H, 7.71; N, 6.92%. Calcd for C23H30N2O2S: C,
69.31; H, 7.59; N, 7.03%.
Compound 21: a pale yellow oil. 1H NMR (CDCl3) d 0.75 (t,
J¼6.8 Hz, 6H), 0.78–0.89 (m, 2H), 0.90–1.05 (m, 2H), 1.44
(m, 2H), 1.66 (m, 2H), 2.67 (d, J¼6.4 Hz, 2H), 5.33 (dt,
J¼9.8, 6.4 Hz, 1H), 6.06 (dd, J¼9.8, 6.0 Hz, 1H), 6.13 (d,
J¼5.4 Hz, 1H), 6.27 (d, J¼5.4 Hz, 1H), 6.36 (dd, J¼11.0,
6.0 Hz, 1H), 6.49 (d, J¼11.0 Hz, 1H) ppm; 13C NMR
(CDCl3) d 14.7, 17.4, 27.8, 38.7, 59.8, 120.4, 125.6, 127.1,
127.2, 132.4, 134.5, 145.8, 146.3 ppm; IR (KBr) nmax
¼
5.1.3. Synthesis of 1,1-dimethyl-, 1,1-diethyl-, and 1,1-
dipropyl-1,4-dihydroazulenes (19, 20, and 21). A suspen-
sion of 14 (0.895 g, 4.43 mmol) of tosylhydrazide in 5 ml of
dry THF was stirred at 40 ꢁC for 72 h. The solids formed
were collected by filtration and washed well with ether to
give 0.848 g of 16 (56% yield) as a white powder. Analytical
samples of 16 were obtained by recrystallization from
hexane–dichloromethane.
2955s, 2929s, 2870s, 731s cmꢀ1; MS (70 eV) m/z (rel int)
214 (M+, 32), 213 (53), 185 (32), 171 (39), 155 (31), 143
(49), 142 (32), 131 (21), 129 (100), 128 (60), 117 (36), 115
(49). Found: 214.1650. Calcd for C16H22: M, 214.1721.
5.1.4. Synthesis of 1,1-dimethyl-, 1,1-diethyl-, and 1,1-di-
propyl-1H-azulenium perchlorates (6, 7, and 8). To a solu-
tion of the precursor hydrocarbon (1.00 mmol) in 10 ml of
acetonitrile at 0 ꢁC under nitrogen atmosphere was added
trityl perchlorate (1.00 mmol) in one portion. The mixture
was stirred at room temperature for 1 h. The solvent was
removed under reduced pressure and the residue was
dissolved in the least amount of dichloromethane. Ether
was added to the solution and solids formed were collected
and washed well with cold ether.
Compound 16: colorless microcrystals, mp 197–198 ꢁC.
Found: C, 66.39; H, 6.48; N, 8.25%. Calcd for
C19H22N2O2S: C, 66.64; H, 6.47; N, 8.18%.
To a suspension of 1.00 g (2.92 mmol) of 16 in 20 ml of dry
ether at 0 ꢁC under nitrogen atmosphere was added 50 ml of
methyl lithium solution (0.8 M ether solution, 40 mmol)
slowly through a syringe. After the addition, the mixture
was stirred for 12 h. The mixture was quenched by adding
water carefully and was poured into a mixture of ether and
ice-water. The aqueous layer was extracted with ether
(50 mlꢂ2). The combined organic layer was washed with
brine and dried over anhydrous MgSO4. The solvent was
removed under reduced pressure and the residue was purified
by column chromatography (SiO2, hexane as eluent) to give
Compound 6: yellow microcrystals, mp 99–100 ꢁC. 1H
NMR (CD3CN) d 1.55 (s, Me), 7.37 (d, J¼5.2 Hz, H-3),
7.73 (d, J¼5.2 Hz, H-2), 8.76 (tt, J¼9.7, 1.4 Hz, H-6),
8.83 (td, J¼9.7, 1.4 Hz, H-7), 8.91 (td, J¼9.7, 1.4 Hz, H-
5), 9.00 (dd, J¼9.7, 1.4 Hz, H-4), 9.02 (dd, J¼9.7, 1.4 Hz,
H-8) ppm; 13C NMR (CD3CN) d 21.6 (Me), 57.8 (C-1),
133.4 (C-3), 145.6 (C-4), 146.1 (C-8), 149.7 (C-6 or 7),
149.8 (C-7 or 6), 153.1 (C-5), 167.8 (C-2), 171.0 (C-3a),
180.0 (C-8a) ppm; IR (KBr) nmax¼1087s, 626s cmꢀ1; MS
(70 eV) m/z (rel int) 157 (C12H+13, 17), 156 (68), 141 (100),
1
273 mg (59% yield) of 19 as a pale yellow oil. H NMR
(CDCl3) d 1.14 (s, 6H), 2.69 (d, J¼6.4 Hz, 2H), 5.35 (dt,

8182
M. Oda et al. / Tetrahedron 62 (2006) 8177–8183
128 (23), 115 (28). Found: C, 56.20; H, 5.18%. Calcd for
C12H13ClO4: C, 56.15; H, 5.10%.
References and notes
1. Oda, M.; Sakamoto, A.; Uchiyama, T.; Kajioka, T.; Miyatake,
R.; Kuroda, S. Tetrahedron Lett. 1999, 40, 3595–3596; Oda,
M.; Fukuta, A.; Kajioka, T.; Uchiyama, T.; Miyatake, R.;
Kuroda, S. Tetrahedron 2000, 56, 9917–9925; Oda, M.;
Fukuta, A.; Uchiyama, T.; Kajioka, T.; Kuroda, S. Recent
Research Developments in Organic Chemistry; Transworld
Research Network: Trivandrum, 2002; Vol. 6; pp 543–563;
For our related carbocations with smaller rings, see: Oda, M.;
Kajioka, T.; Okujima, T.; Itoh, S.; Morita, N.; Miyatake, R.;
Kuroda, S. Chem. Lett. 1997, 1011–1012; Oda, M.; Kajioka,
T.; Okujima, T.; Uchiyama, T.; Nagara, K.; Itoh, S.; Morita,
N.; Sato, T.; Miyatake, R.; Kuroda, S. Tetrahedron 1999, 55,
6081–6096; Oda, M.; Kajioka, T.; Kawamori, Y.; Uchiyama,
T.; Kuroda, S.; Morita, N. Recent Research Developments in
Organic and Bioorganic Chemistry; Transworld Research
Network: Trivandrum, 2001; Vol. 4; pp 133–149; Oda, M.;
Sakamoto, A.; Miyatake, R.; Kuroda, S. Tetrahedron Lett.
1998, 39, 6195–6198; Oda, M.; Sakamoto, A.; Kajioka, T.;
Miyatake, R.; Kuroda, S. Tetrahedron 1999, 55, 12479–12492.
2. Oda, M.; Kainuma, H.; Miyatake, R.; Kuroda, S. Tetrahedron
Lett. 2002, 43, 3485–3488; Oda, M.; Kainuma, H.; Uchiyama,
T.; Miyatake, R.; Kuroda, S. Tetrahedron 2003, 59, 2831–2841.
3. Oda, M.; Kajioka, T.; Ikeshima, K.; Miyatake, R.; Kuroda, S.
Synth. Commun. 2000, 30, 2335–2343; We had already
reported the synthesis of the azulenone 13 from 9.
Compound 7: faintly greenish microcrystals, mp 97–99 ꢁC.
1H NMR (CD3CN) d 0.50 (t, J¼7.4 Hz, Me), 2.17 (dq,
J¼14.4, 7.4 Hz, one of CH2), 2.32 (dq, J¼14.4, 7.4 Hz, one
of CH2), 7.52 (d, J¼5.6 Hz, H-3), 7.71 (d, J¼5.2 Hz, H-2),
8.80 (tt, J¼10.0, 1.3 Hz, H-6), 8.85 (td, J¼10.0, 1.3 Hz,
H-5), 8.95 (td, J¼10.0, 1.3 Hz, H-5), 8.99 (dd, J¼10.0,
1.3 Hz, H-4), 9.02 (dd, J¼10.0, 1.3 Hz, H-8) ppm; 13C
NMR (CD3CN) d 9.0 (Me), 29.7 (CH2), 67.3 (C-1), 136.0
(C-3), 144.6 (C-4), 145.3 (C-8), 149.5 (C-7), 149.7 (C-6),
153.0 (C-5), 165.7 (C-2), 172.5 (C-3a), 178.5 (C-8a) ppm;
IR (KBr) nmax¼1449s, 1095s, 623s cmꢀ1; MS (70 eV) m/z
(rel int) 185 (C14H+17, 88), 171 (21), 169 (30), 157 (78), 141
(100), 129 (95), 128 (56), 115 (41). Found: C, 58.88; H,
5.97%. Calcd for C12H13ClO4: C, 59.06; H, 6.02%.
Compound 8: faintly brownish microcrystals, mp 148–
1
150 ꢁC. H NMR (CD3CN) d 0.55–0.66 (m, one of H-20,
2H), 0.73 (t, J¼7.1 Hz, Me, 6H), 0.96–1.07 (m, one of H-
20, 2H), 2.07 (m, one of H-10, 2H), 2.32 (m, one of H-10,
2H), 7.45 (d, J¼5.4 Hz, H-3), 7.73 (d, J¼5.4 Hz, H-2),
8.75 (tt, J¼10.0, 1.5 Hz, H-6), 8.79 (td, J¼10.0, 1.5 Hz, H-
5), 8.90 (td, J¼10.0, 1.5 Hz, H-5), 8.96 (d-like, H-4 and H-
13
8) ppm; C NMR (CD3CN) d 14.4 (C-30, Me), 18.3 (C-20,
CH2), 38.9 (C-10, CH2), 66.5 (C-1), 135.3 (C-3), 144.5 (C-
4), 145.2 (C-8), 149.3 (C-7), 149.5 (C-6), 152.7 (C-5),
166.1 (C-2), 172.1 (C-3a), 178.9 (C-8a) ppm; IR (KBr)
nmax¼1490s, 1450s, 1095s, 831s, 623s cmꢀ1; MS (70 eV)
m/z (rel int) 213 (C16H+21, 4), 212 (21), 184 (16), 183 (100),
165 (16), 155 (16), 154 (28), 153 (21), 152 (20), 141 (13),
128 (10). Found: C, 61.86; H, 6.81%. Calcd for
C16H21ClO4: C, 61.44; H, 6.77%.
4. Mukaiyama, K.; Narasaka, K. Org. Synth. 1987, 65, 6–11.
5. For our recent results for preparing tetrahydroazulen-1-ones by
the Nazarov cyclization, see: Oda, M.; Yamazaki, T.; Kajioka,
T.; Miyatake, R.; Kuroda, S. Liebigs Ann. Recl. 1997, 2563–
2566; Kajioka, T.; Oda, M.; Yamada, S.; Miyatake, R.;
Kuroda, S. Synthesis 1999, 184–187; Oda, M.; Kajioka, T.;
Haramoto, K.; Miyatake, R.; Kuroda, S. Synthesis 1999,
1349–1353.
5.2. Determination of pKRD values
6. For recent reviews of the Nazarov cyclizations, see: Tius, M. A.
Eur. J. Org. Chem. 2005, 2193–2206; Pellissier, H. Tetrahedron
2005, 61, 6479–6517.
7. Murata, S.; Suzuki, M.; Noyori, R. Tetrahedron Lett. 1980, 21,
2527–2528.
8. Shapiro, R. H. Org. React. 1976, 23, 405–507.
9. Doering, W. v. E.; Knox, L. H. J. Am. Chem. Soc. 1954, 76,
3203–3206; Doering, W. v. E.; Knox, L. H. J. Am. Chem.
Soc. 1957, 79, 3203–3206.
The UV spectra in various pH of 50% aqueous acetonitrile
solutions were measured by exactly the same method of
Komatsu et al.11 Observedabsorbanceatthelongestabsorption
maxima at 358–363 nm was plotted against pH to give a clas-
sical titration curve, whose midpoint was taken as the pKR+.
5.3. Cyclic voltammetry
10. Nakazawa, T.; Niimoto, Y.; Kubo, K.; Murata, I. Angew. Chem.
1980, 92, 566–567; Angew. Chem., Int. Ed. Engl. 1980, 19,
545–546.
11. Komatsu, K.; Akamatsu, H.; Jinbu, Y.; Okamoto, K. J. Am.
Chem. Soc. 1988, 110, 633–634; Komatsu, K.; Akamatsu, H.;
Aonuma, S.; Jinbu, Y.; Maekawa, N.; Takeuchi, K.
Tetrahedron 1991, 47, 6951–6966.
12. For clusters of solvated tropylium cations, see: Kinoshita, T.;
Wakisaka, A.; Yasumoto, C.; Takeuchi, K.; Yoshizawa, K.;
Suzuki, A.; Yamabe, T. Chem. Commun. 2001, 1768–1769.
13. Forlinear relationships between thermodynamic and kinetic pa-
rameters of aromatic carbocations, see: Okamoto, K.; Takeuchi,
K.; Kouichi, K.; Kubota, Y.; Ohara, R.; Arima, M.; Takahashi,
K.; Waki, Y.; Shirai, S. Tetrahedron 1983, 39, 4011–4024.
14. Harmon, K. M.; Cummings, F. E.; Davis, D. A.; Diestler, D.
J. Am. Chem. Soc. 1962, 84, 3349–3355.
A standard three-electrode cell configuration was employed
using a glassy carbon disk working electrode, a Pt wire aux-
iliary electrode, and an Ag wire as an Ag/Ag+ quasi-refer-
ence electrode. The reference electrode was calibrated at
the completion of each measurement on a saturated calomel
electrode (SCE). Cyclic voltammetry was measured in an
acetonitrile solution with tetrabutylammonium perchlorate
as a supporting electrolyte and a scan rate of 0.1 V sꢀ1 at
25 ꢁC. Under these conditions, ferrocene showed a half
wave oxidation potential of +0.40 V versus SCE.
Acknowledgements
We gratefully thank Mr. Takuya Uchiyama and Mr. Hitoshi
Kainuma at University of Toyama for their preliminary syn-
thetic efforts.
15. Feldman, M.; Winstein, S. J. Am. Chem. Soc. 1961, 83, 3338–
3339.

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8183
€
16. Lamsa, M.; Kuokkanen, T.; Jalonen, J.; Virtanen, O. J. Phys.
Org. Chem. 1995, 8, 377–384; Lamsa, M.; Kuokkanen, T.
€
18. Dauben, H. J., Jr.; Lewis, R.; Honnen, R.; Harman, K. M.
J. Org. Chem. 1960, 25, 1442–1445.
€
€
J. Phys. Org. Chem. 1996, 9, 21–28.
€
19. No molecular ion peak was observed even with low ionization
energy of 20 eV presumably because elimination of water
should benefit from relief of steric strain.
€
17. Lamsa, M.; Suorsa, T.; Pursiainen, J.; Kuokkanen, T.;
Rissanen, K. Chem. Commun. 1996, 1443–1445.