Electrochemical reactions of dihydroazaazulanones possessing a spirocyclic moiety: Ring cleavages of the spiro-rings, hydrogen migrations and formations of azaazulanones

Article abstract of DOI:10.3987/COM-01-9382

Electrochemical oxidations of dihydroazaazulanones possessing a spirocyclic moiety afforded two types of dibydroazaazulanones and one type of azaazulanones. The reaction is considered to proceed via a ring cleavage of the spiro-three membered ring followed by a hydrogen migration.

Full text of DOI:10.3987/COM-01-9382

HETEROCYCLES, Vol. 57, No. 2, 2002, pp. 219-222, Received, 1st November, 2001
ELECTROCHEMICAL REACTIONS OF DIHYDROAZAAZULAN-
ONES POSSESSING A SPIROCYCLIC MOIETY: RING CLEAVAGES
OF
THE
SPIRO-RINGS, HYDROGEN MIGRATIONS AND
FORMATIONS OF AZAAZULANONES
Katsuhiro Saito* and Ryosuke Ueno
Department of Applied Chemistry, Nagoya Institute of Technology,
Gokiso-cho, Showa-ku, Nagoya 466-8555, J apan
Abstract – Electrochemical oxidations of dihydroazaazulanones
possessing a spirocyclic moiety afforded two types of dihydroaza-
azulanones and one type of azaazulanones. The reaction is considered
to proceed via a ring cleavage of the spiro-three membered ring
followed by a hydrogen migration.
As a member of nonbenzenoid aromatic compounds, the chemistry of bicyclo[5.3]deca-
3,4,6,8-tetraen-2-ones (azulanones) has been researched extensively.1 The aza-analogs of
the azulanones, cyclohepta[b]pyrrol-2(1H)-one (azaazulanone) derivatives and its dihydro
isomer, 1,2,3,3a-tetrahydrocyclohepta[b]pyrrol-2-one (dihydroazaazulanone) derivatives
have attracted attention of chemists not only from view points of their physical and
chemical properties but also from their pharmacologocal activities.2
The dihydroazaazulanone skeleton contains a cycloheptatriene and a carbonyl group
connected by a sp2 hybridized nitrogen atom constructing a 10π-electrons conjugated
system containing two hetero atoms. The authors have researched on the chemistry of
these compounds,3 and reported on the synthesis of dihydroazaazulanone derivatives (1)
possessing a norcaradiene system as a spirocyclic moiety by cycloaddition reactions of
iminotropones with 8-oxoheptafulvene.4 As a series of our researches on the reactivities of
dihydroazaazulanone derivatives, we studied the electrochemistry of the title compounds.
Here the results are reported.
The following Figure presents cyclic voltammograms of the dihydroazaazulanones (1a and
1b) possessing a spirocyclic moiety.5 Both of them show oxidation peaks at ca. +1.1 V vs.
Ag/AgCl.

6
5
1a
1b
4
3
2
1
0
-1
-2
-1
0
1
2
potential / V
Electrochemical reductions of 1a or 1b at –1.4 V vs. Ag/AgCl in methylene chloride failed to
give any isolable products and the starting materials were mostly recovered.6 On the
other hand, electrochemical oxidation of 1a at +1.3 V vs. Ag/AgCl in methylene chloride
afforded three kinds of products (2a, 3a, and 4a) in 47, 25, and 17 % yields, respectively.
The analogous result was obtained in the reaction with 1b to form 2b, 3b, and 4b in the
yields of 42, 42, and 15 %, respectively.
No mutual conversions between 2, 3, and 4 were observed under the reaction conditions.
X
N
X
N
X
N
X
N
H
H
H
-e
O
+
O
O
+
O
H
H
H
a X=Br
b X=OMe
3
4
2
1
+e
No Reaction
The structures of azaazulanone derivatives (4) were determined on the basis of the
coincidences of their spectral properties with those of the authentic samples.7 The
structures of 2 and 3 were established on the basis of their spectral properties,8 and
further supported by their almost quantitative formation of 4 by oxidation reactions with
DDQ.

Ar
N
Ar
N
-e
O
O
1
H
H
6
5
-H+
Ar
N
Ar
H
H
Ar
N
N
O
O
O
H
H
7
4
10
8
-H+
-H
Ar
N
H
H
Ar
N
O
O
-H+
+H
+H
3
2
H
11
9
The reaction mechanism is considered to be as follows. An electrochemical one-electron
oxidation at the lone pair electrons of the nitrogen atom of 1 generates a cationic
intermediate (5). An elimination of a proton from the canonical formula (6) of 5 forms a
radical intermediate (7). A successive elimination of a hydrogen radical concerted with a
ring opening process at the spiro-three membered ring in 7 can form the final product,
azaazulanone derivative (4).
On the other hand, a 1,3-hydrogen migration process in a cationic intermediate (6)
generates an another type of a cationic intermediate (8), which then affords 2 via a ring
opening process of the spiro-three membered ring accompanied by an elimination of a
proton.
A
molecular orbital calculation with a PM 3 method showed the heat of
formation of 8 (1314 kJ ) to be lower than that of 6 (1494 kJ ) supporting the appropriateness
of the molecular rearrangement of 6 to 8.
A ring opening process of the spiro-three membered ring in the canonical formula (10) of 5
forms an enole radical type intermediate (11), which can afford 3 through an elimination of
a proton and abstraction of a hydrogen radical.

REFERENCES AND NOTES
1. D. J . Bertelli and P. Crews, Tetrahedron, 1970, 26, 4717; H. Takeshita, A. Chisaka, and H.
Mametsuka, Bull. Chem. Soc. J pn., 1980, 53, 3373; L. T. Scott, and C. M. Adnams, J . Am.
Chem. Soc., 1984, 106, 4857.
2. T. Nishiwaki and T. Fukui, J . Chem. Res. Synop., 1986, 288; N. Abe, N. Ishikawa, T.
Hayashi, and Y. Miura, Bull. Chem. Soc. J pn., 1990, 63, 1617; H. Takeshita, A. Mori, Y.
Ikeda, and N. Kato, Chem. Lett., 1990, 2199; S. Suzuki, Y. Fukui, T. Tsuchinaga, H.
Tsunekawa, and K. Saito, Heterocycles, 1997, 45, 1787.
3. K. Ito, K. Saito, S. Takeuchi, and K. Takahashi, Heterocycles, 1992, 34, 1415; T. Ido, S.
Kondo, and K. Saito, ibid., 1999, 50, 63; T. Doi, H. Ishiguro, M. Sato, and K. Saito, ibid.,
1999, 51, 1775; K. Saito, T. Ido, Y. Awadu, T. Kanie, and S. Kondo, ibid., 2000, 53, 519.
4. Y. Saito, M. Tomita, H. Taniguchi, H. Okabayashi, and K. Saito, Heterocycles, 1995, 41,
2181.
5. The cyclic voltammograms of 1a and 1b (0.5 mM) were performed with a platinum
electrode in acetonitrile in the presence of 0.1 M TBAP (tetra-n-butylammonium
perchlorate) with a scan rate ν = 200 mV s-1.
6. The electrochemical reactions were performed in dichloromethane or acetonitrile
(200 mL) with dihydroazaazulanones (1a or 1b, 0.5 mmol), TBAP (17.5 mmol) as a
supporting electrolyte, a platinum gauze as a working electrode, and a platinum rod as a
counter electrode in a divided-cell at 0 ℃ under a nitrogen atmosphere.
7. K. Ito, K. Saito, and K. Takahashi, Bull. Chem. Soc. J pn., 1992, 65, 812.
8. The NMR spectra of the selected products are as follows.
2a:1HNMR (CDCl3) δ: 2.48 (m, 1 H), 2.82 (ddd, 1 H, J = 17.3, 8.0 and 3.0 Hz), 4.94 (dd, 1
H, J = 13.5 and 2.9 Hz), 6.10 (m, 3 H), 6.65 (d, 1 H, J = 11.3 Hz), 7.36-7.62 (m, 9 H).
13CNMR (CDCl3) δ: 29.7, 58.3, 117.7, 122.5, 123.5, 127.8, 128.0, 128.2, 128.4, 129.5,
129.8, 130.1, 130.4, 130.6, 131.9, 135.6, 149.7.
3a:1HNMR (CDCl3) δ: 3.11 (m, 1 H), 4.01 (d, 1 H, J = 4.9 Hz), 5.38 (dd, 1 H, J = 8.9 and
3.5 Hz), 5.47 (dd, 1 H, J = 6.6 and 1.4 Hz), 6.25 (m, 2 H), 6.41 (dd, 1 H, J = 10.4 and 6.6
Hz), 7.20-7.60 (m, 9 H). 13CNMR (CDCl3) δ: 44.6, 54.6, 100.2, 122.2, 122.8, 125.9,
127.5, 127.6, 127.9, 128.4, 128.9, 129.1, 129.2, 132.4, 132.8, 138.2, 175.3.