Unusual photorearrangement of 1,7-disubstituted 7-azabenzonorbornadiene

Article abstract of DOI:10.1134/S107042800904023X

1-(11-Benzoyl-11-azatricyclo[6.2.1.0^2,7]undeca-2,4,6,9-tetraen- 1-yl)ethanone was synthesized by cycloaddition of 2-acetyl-N-benzoylpyrrole to benzyne. Direct photolysis of 1-(11-benzoyl-11-azatricyclo-[6.2.1.0 ^2,7]undeca-2,4,6,9-tet

Full text of DOI:10.1134/S107042800904023X

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2009, Vol. 45, No. 4, pp. 613–616. © Pleiades Publishing, Ltd., 2009.
Published in Russian in Zhurnal Organicheskoi Khimii, 2009, Vol. 45, No. 4, pp. 626–629.
Unusual Photorearrangement of 1,7-Disubstituted
7-Azabenzonorbornadiene*
A. Altundaşa, E. Tepeb, N. Akbulutb, and Y. Karab
a Department of Chemistry, Faculty of Arts and Sciences, Gazi University, Ankara, 06500 Turkey
e-mail: aaltundas@gazi.edu.tr
b Department of Chemistry, Faculty of Arts and Sciences, Atatürk University, Erzurum, 25240 Turkey
Received December 5, 2007
Abstract—1-(11-Benzoyl-11-azatricyclo[6.2.1.02,7]undeca-2,4,6,9-tetraen-1-yl)ethanone was synthesized by
cycloaddition of 2-acetyl-N-benzoylpyrrole to benzyne. Direct photolysis of 1-(11-benzoyl-11-azatricyclo-
[6.2.1.02,7]undeca-2,4,6,9-tetraen-1-yl)ethanone in benzene gave N-(4-acetylnaphthalen-1-yl)benzamide. The
formation of this product is discussed in terms of radical-stabilizing and destabilizing effect of electron-with-
drawing group in the formation of cyclopropane ring.
DOI: 10.1134/S107042800904023X
Fusion of benzene ring to cyclic hydrocarbons was
widely reported in the literature [1–3]. The most
general method for the preparation of such compounds
involves cycloaddition of benzyne to appropriate con-
jugated dienes [4]. Benzyne is known to readily react
with pyrrole derivatives to form 1,4-epimino-1,4-dihy-
dronaphthalene (I, 7-azabenzonorbornadiene) [5, 6].
1,4-Epimino-1,4-dihydronaphthalene (I) attracts much
interest from the synthetic viewpoint due to its ability
to be readily converted into other types of compounds.
For example, Wolthuis et al. [6] studied reactions of
1,4-epimino-1,4-dihydronaphthalene with HCl in
MeOH and showed formation of different naphthalene
derivatives. It is also known that direct photolysis
of 1,4-epimino-1,4-dihydronaphthalenes I produces
3-benzoazepines II [7–9] (Scheme 1). Benzoazepines
and related compounds were found to exhibit impor-
tant pharmacological properties [10].
formation of benzofulvene derivatives via sensitized
irradiation of 7-azabenzonorbornadienes. Motyka [11]
described the conversion of 1,4-epimino-1,4-dihydro-
naphthalene having electron-donating substituents on
the nitrogen atom into indole derivatives by direct
photolysis. The configuration of the nitrogen atom in
7-azabenzonorbornadiene derivatives can be deter-
mined by spectral methods [12, 13]. We previously
studied photochemistry of bicyclic systems having het-
eroatoms and revealed very surprising results [14, 15];
it seemed interesting to examine photochemistry of aza
bicyclic compounds bearing electron-withdrawing sub-
stituents.
In the present article we report on the photolysis
of 7-azabenzonorbornadiene containing two electron-
withdrawing groups, one on the nitrogen atom, and the
other on the bridgehead carbon atom (C1). The sub-
strate structure differed from those reported in [7–9].
Our synthetic strategy was based on the Diels–Alder
reaction of benzyne with 2-acetyl-N-benzoylpyrrole
Scheme 1.
R
N
hν
Scheme 2.
N
R
O
O
Ph
, C2H4Cl2
I
II
N
N
Ph
Swenton et al. [9] reported the details of direct and
photosensitized rearrangements of 7-azabenzonorbor-
nadiene derivatives and proposed a mechanism for the
O
Me
O
Me
* The text was submitted by the authors in English.
III
IV
613

ALTUNDAŞ et al.
614
of 3-benzoazepine VIII, direct photolysis of 1,4-epi-
mino-1,4-dihydronaphthalene IV was performed at
λ 254 nm. Repeated experiments surprisingly showed
the formation of benzamide derivative VI. The product
differed from those obtained by Prinzbach [8] and
Swenton [9]. This can be attributed to the effect of
electron-withdrawing acetyl group at the bridgehead
carbon atom (C1). In keeping with published data,
electron-withdrawing groups destabilize formation of
cyclopropane ring [18]. As shown in Scheme 5, the
transformation of IV through di-π-methane rearrange-
ment or intramolecular [2+2] cycloaddition would
give product VII. Because of destabilizing effect of the
acetyl group, cyclopropane ring is not formed, and the
reaction does not follow path b. Instead, diradical A
undergoes rearrangement into more stable diradical B.
The subsequent hydrogen transfer to the nitrogen atom
from the adjacent carbon atom leads to product VI
through intermediate C (Scheme 5, path a).
(III) which was prepared according to the procedure
reported previously for analogous compounds [16].
New 1,4-epiminonaphthalene derivative (IV) was thus
obtained in 53% yield. Its NMR data indicated that it
exists as a single isomer (Scheme 2). The configura-
tion of IV was determined by further chemical reac-
tions and X-ray analysis of epoxide V. The latter was
synthesized by oxidation of 1-acetyl-N-benzoyl-1,4-
epiminonaphthalene (IV) with m-chloroperoxybenzoic
acid in methylene chloride; according to the X-ray dif-
fraction data, compound V has exo orientation of the
epoxy group [17] (Scheme 3).
Scheme 3.
O
O
Ph
Ph
O
3-ClC6H4CO3H
CH2Cl2
N
N
O
O
Thus we have demonstrated unusual rearrange-
ment of 1,4-epimino-1,4-dihydronaphthalene IV to
N-(4-acetylnaphthalen-1-yl)benzamide (VI) under con-
ditions of direct photolysis. Benzamide derivatives
exhibit various kinds of biological activity such as
antihelminthic, antihistaminic, antifungal, and antibac-
terial properties [19]. We presume that this unexpected
rearrangement takes place because of electron-with-
drawing nature of the carbonyl group at the bridgehead
position, which destabilizes cyclopropane ring. Our
results showed that benzamide derivatives can be syn-
thesized via photochemical transformations which
tolerate several functional groups.
Me
IV
Me
V
A solution of 1,4-epimino-1,4-dihydronaphthalene
IV (0.5 g, 1.73 mmol) in benzene (100 ml) was irra-
diated under nitrogen for 30 h in a quartz tube using
a mercury lamp (λ 240 nm). By thin-layer chromatog-
raphy we isolated N-(4-acetylnaphthalen-1-yl)benz-
amide (VI) in 30% yield (0.15 g, 0.52 mmol), as well
as 55% of unreacted starting compound (Scheme 4).
The structure of VI was determined on the basis of the
1H and C NMR spectra. In the H NMR spectrum of
VI, methyl protons in the acetyl group resonated at
δ 2.69 ppm, and aromatic proton signals appeared in
the region δ 7.27–8.87 ppm. Double resonance experi-
13
1
EXPERIMENTAL
13
ments and C NMR spectrum were also fully consist-
The melting points were determined on a Thomas
Hoover capillary melting apparatus. The IR spectra
were measured in KBr or from neat liquids on a Matt-
ent with the assumed structure.
Scheme 4.
1
son 1000 FT-IR spectrometer. The H and 13C NMR
O
spectra were recorded on a Varian spectrometer at 200
and 50 MHz, respectively. The mass spectra were ob-
tained on a VG Zabspec GC–MS instrument. Column
chromatography was performed on silica gel 60 (70–
230 mesh ATSM). Silica gel 60 F254 on 0.2-mm ana-
lytical aluminum plates (Merck) was used for thin-
layer chromatography.
NHCOPh
Ph
N
hν, PhH
O
COMe
VI
Me
IV
1-(1-Benzoylpyrrol-2-yl)ethanone (III) [16].
A mixture of 1.74 g (22 mmol) of acetyl chloride and
2.1 g (22 mmol) of anhydrous aluminum chloride in
70 ml of 1,2-dichloroethane was stirred for 15 min at
30°C, a solution of 3.44 g (22 mmol) of 1-benzoyl-
1,4-Epimino-1,4-dihydronaphthalenes bearing elec-
tron-withdrawing substituents on the nitrogen atom
were reported to undergo isomerization to benzoazep-
ines upon direct irradiation. Expecting the formation
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 45 No. 4 2009

UNUSUAL PHOTOREARRANGEMENT OF 1,7-DISUBSTITUTED 7-AZABENZO...
615
Scheme 5.
O
O
O
·
N
Ph
HN
Ph
H
Ph
N
·
hν
·
·
VI
·
Path a
·
O
Me
Me
O
Me
O
A
B
C
IV
O
Ph
O
N
hν
N
Ph
Path b
[2+2]
O
O
Me
VII
Me
D
pyrrole in 10 ml of dichloroethane was added, and the
mixture was stirred for 5 h at 30°C. The mixture was
cooled to 0°C, quenched with cold water, and extract-
ed with methylene chloride. The organic layer was
separated, washed with water (2×100 ml), and dried
over Na2SO4. The solvent was removed, and the
residue was purified by chromatography on silica gel
using hexane–ethyl acetate (9:1) as eluent. The prod-
uct was additionally recrystallized from diethyl ether–
hexane. Yield 3.10 g (70%), colorless crystals, mp 65–
66°C. IR spectrum (KBr), ν, cm–1: 3113, 3080, 2936,
2953, 2876, 1727, 1676, 1600, 1548, 1446, 1421, 1344,
raphy on silica gel using hexane–ethyl acetate (9:1) as
eluent. The product was additionally recrystallized
from diethyl ether–hexane. Yield 2.30 g (53%), color-
less crystals, mp 135–136°C. IR spectrum (KBr), ν,
cm–1: 3438, 3310, 3106, 3080, 3029, 2927, 1727, 1676,
1600, 1472, 1370, 1344, 1268, 1242, 1140, 1114,
1
1063, 961. H NMR spectrum (CDCl3), δ, ppm: 7.66–
7.26 m (8H, Harom), 7.09–7.04 quasi d.d (2H, 10-H,
H
arom, J = 5.5, 1.2 Hz), 6.25 d.d (1H, 9-H, J = 5.5,
2.2 Hz), 5.66 d (1H, 8-H, J = 2.2 Hz), 2.41 s (3H,
13
CH3). C NMR spectrum (CDCl3), δC, ppm: 201.32,
172.76, 148.04, 147.17, 144.58, 142.22, 133.67, 132.28,
128.93, 128.72, 126.00, 125.97, 121.07, 120.82, 82.91
(C1), 70.65 (C8), 29.99. High-resolution mass spec-
trum: m/z 289.1111 [M]+. Calculated: M 289.1102.
1
1319, 1268, 1217, 1191, 1089, 1038, 936. H NMR
spectrum (CDCl3), δ, ppm: 7.86 d.d (1H, 5-H, J = 2.0,
1.6 Hz), 7.77–7.60 m (5H, Ph), 7.27 d.d (1H, 3-H,
J = 3.4, 1.6 Hz), 7.27 d.d (1H, 4-H, J = 3.4, 2.0 Hz).
13C NMR spectrum (CDCl3), δC, ppm: 189.03, 171.31,
135.68 (2C), 135.56, 131.61, 130.81, 130.59, 123.03,
112.59, 28.34.
1-(11-Benzoyl-11-azatricyclo[6.2.1.02,7]undeca-
2,4,6,9-tetraen-1-yl)ethanone (IV) was prepared by
reaction of benzyne [20] with pyrrole III. 2-Carboxy-
benzenediazonium hydrochloride, 2.60 g (17 mmol),
and 2-methyloxirane, 1.7 g (40 mmol), were added
under stirring to a solution of 3.10 g (15.00 mmol) of
compound III in 70 ml of dichloroethane. The mixture
was heated for 3.5 h under reflux, cooled to room
temperature, and evaporated. The residue was treated
with 100 ml of diethyl ether, and the extract was
washed with 10% aqueous NaHCO3 (2×100 ml) and
water (100 ml) and dried over Na2SO4. After removal
of the solvent, the residue was subjected to chromatog-
Epoxidation of 1-(11-benzoyl-11-azatricyclo-
[6.2.1.02,7]undeca-2,4,6,9-tetraen-1-yl)ethanone (IV)
[17]. A solution of 0.5 g (1.74 mmol) of compound IV
and 0.36 g (2.09 mmol) of m-chloroperoxybenzoic
acid in 30 ml of methylene chloride was stirred for
20 h at room temperature in the presence of 1 g of
solid NaHCO3. The mixture was then filtered and
washed with 10% aqueous NaHCO3 (2×20 ml). The
organic layer was dried over sodium sulfate and evap-
orated under reduced pressure, and the residue was
recrystallized from methylene chloride–hexane to
obtain 0.48 g (78%) of 1-(11-benzoyl-9,10-epoxy-11-
azatricyclo[6.2.1.02,7]undeca-2,4,6-trien-1-yl)ethanone
(V) as colorless crystals with mp 208–209°C. IR spec-
trum (KBr), ν, cm–1: 3027, 2931, 2858, 1708, 1631,
1581, 1457, 1427, 1373, 1276, 1130, 1064, 1025, 944,
1
887, 848, 755,698. H NMR spectrum (CDCl3), δ,
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 45 No. 4 2009

ALTUNDAŞ et al.
616
3. Paquette, L.A., Kukla, M.J., and Stowell, J.C., J. Am.
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and 3.39 d (1H each, 9-H, 10-H, J = 3.5 Hz), 2.42 s
(3H, CH3). 13C NMR spectrum (CDCl3), δC, ppm:
201.20, 175.78, 145.79, 145.33, 136.07, 132.97, 130.47,
130.16, 129.64, 129.57, 123.49, 123.02, 82.11 (C1),
67.91 (C8), 58.54, 54.52, 29.77.
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A solution of 0.50 g (1.73 mmol) of compound IV in
100 ml of benzene was placed into a quartz tube,
flushed with nitrogen under stirring with a magnetic
stirrer, and irradiated at λ 254 nm for 30 h. The solvent
was removed under reduced pressure, and the residue
was purified by thin-layer chromatography on silica
gel using hexane–ethyl acetate (4:1) as eluent. The
product was recrystallized from methylene chloride–
hexane. Yield 0.15 g (30%), yellow crystals, mp 156–
158°C. IR spectrum (KBr), ν, cm–1: 3285, 3080, 3004,
2927, 2851, 1702, 1651, 1600, 1523, 1497, 1446, 1370,
1293, 1242, 1191, 1114, 1012, 910. 1H NMR spectrum
(CDCl3), δ, ppm: 8.87 br.d (1H, 5-H, J = 8.1 Hz),
8.61 br.s (1H, NH), 8.10 (1H, 3-H) and 7.85 (1H, 2-H)
(AB system, J = 8.1 Hz), 7.97 d (2H, o-H, J = 7.4 Hz),
7.84 d (1H, 8-H, J = 8.6 Hz), 7.58-7.27 m (5H, 6-H,
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16. Kakushima, M., Hamel, P., Frenette, R., and Rokach, J.,
13
7-H, m-H, p-H), 2.69 s (3H, CH3). C NMR spectrum
(CDCl3), δC, ppm: 201.77, 167.39, 138.56, 136.67,
133.99, 133.77, 133.26, 131.55, 130.78, 129.82, 129.4,
129.28, 128.49, 121.93, 119.72, 31.52. High-resolution
mass spectrum: m/z 289.1098 [M]+. Calculated:
M 289.1102.
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The authors thank Atatürk University for financial
support of this work. We also thank Dr. R. Altundaş
and Dr. H. Seçen (Atatürk University) for helpful dis-
cussion and critical reading of the manuscript.
18. Altundaş, R., Dastan, A., Ünaldi, N.S., Güven, K.,
Uzun, O., and Balci, M., Eur. J. Org. Chem., 2002,
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