Unexpected redox processes in the reactions of 1-bromo- and 1,2-epoxy-9-(p-tolylsulfonyl)-1,2,3,4,4a,9a-hexahydrocarbazoles with acetyl bromide

Article abstract of DOI:10.1134/S1070428009040113

1,2-Epoxy-9-(p-tolylsulfonyl)-1,2,3,4,4a,9a-hexahydrocarbazole reacted with acetyl bromide on heating to give 1-acetoxy-2-bromo-9-(p-tolylsulfonyl)-1,2,3, 4,4a,9a-hexahydrocarbazole and 1-acetoxy-9-acetyl-2,6-dibromo-1,2,3,4,4a,9a- hexahydrocarbazole. The structure of the latter was proved by X-ray analysis. Analogous reaction of 1-bromo-9-(p-tolylsulfonyl)-1,2,3,4,4a,9a- hexahydrocarbazole with acetyl bromide led to the formation of 9-acetyl-1,6-dibromo-1,2,3,4,4a,9a-hexahydrocarbazole.

Full text of DOI:10.1134/S1070428009040113

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2009, Vol. 45, No. 4, pp. 536–540. © Pleiades Publishing, Ltd., 2009.
Original Russian Text © N.A. Likhacheva, K.Yu. Suponitskii, R.R. Gataullin, 2009, published in Zhurnal Organicheskoi Khimii, 2009, Vol. 45, No. 4,
pp. 551–554.
Unexpected Redox Processes in the Reactions
of 1-Bromo- and 1,2-Epoxy-9-(p-tolylsulfonyl)-1,2,3,4,4a,9a-
hexahydrocarbazoles with Acetyl Bromide
a
b
c
N. A. Likhacheva , K. Yu. Suponitskii , and R. R. Gataullin
a
Affiliate of Ufa State Petroleum Technical Universitety, ul. Gubkina 67, Salavat, 453250 Bashkortostan, Russia
e-mail: likhacheva_n@mail.ru
b
Nesmeyanov Institute of Organometallic Compounds, Moscow, Russia
c
Institute of Organic Chemistry, Ufa Research Center, Russian Academy of Sciences,
pr. Oktyabrya 71, Ufa, 450054 Bashkortostan, Russia
Received March 14, 2007
Abstract—1,2-Epoxy-9-(p-tolylsulfonyl)-1,2,3,4,4a,9a-hexahydrocarbazole reacted with acetyl bromide on
heating to give 1-acetoxy-2-bromo-9-(p-tolylsulfonyl)-1,2,3,4,4a,9a-hexahydrocarbazole and 1-acetoxy-9-
acetyl-2,6-dibromo-1,2,3,4,4a,9a-hexahydrocarbazole. The structure of the latter was proved by X-ray analysis.
Analogous reaction of 1-bromo-9-(p-tolylsulfonyl)-1,2,3,4,4a,9a-hexahydrocarbazole with acetyl bromide led
to the formation of 9-acetyl-1,6-dibromo-1,2,3,4,4a,9a-hexahydrocarbazole.
DOI: 10.1134/S1070428009040113
Some partially hydrogenated carbazoles have found
application in the synthesis of biologically active com-
pounds and hence attracted researchers’ attention
[5], or DMSO, 160°C [6, 7]) and tetrahydrocarbazole
B via dehydrobromination of the same compound. For
this purpose, we examined opening of the oxirane ring
in epoxide II by the action of acetyl bromide on
heating. When the reaction was carried out for ~4 h
with protection from atmospheric moisture, the only
[1, 2]. Among such carbazole derivatives, those having
functional groups in the cyclohexane ring are also im-
portant. They can be prepared via stereoselective halo-
cyclization of N-alkyl- or N-arylsulfonyl-2-(cyclohex-
product was acetate III whose R value was almost the
f
2
-en-1-yl)anilines, which gives 1-halohexahydrocarba-
same as that of the initial epoxide. The reaction per-
formed without protection from atmospheric moisture
gave 1-acetoxy-9-acetyl-2,6-dibromo derivative IV
(Scheme 1). We tried to improve the yield of IV by
adding several drops of water. In fact, the rate of
formation of compound IV considerably rose, but the
yield did not increase to an appreciable extent, pre-
sumably as a result of tarring due to increased con-
centration of HBr. It is known [6–8] that heating of
some aralkyl halides in dimethyl sulfoxide leads to
reduction of the latter to dimethyl sulfide. In the above
reactions we isolated di-p-tolyl disulfide V which was
formed via reduction of the p-tolylsulfonyl group with
zoles. The latter undergo dehydrohalogenation to the
corresponding tetrahydro derivatives I on heating in
piperidine [3].
The subsequent oxidation of tetrahydrocarbazole (I)
with nitrogen(II) oxide [4] or dimethyldioxirane occurs
with complete stereoselectivity and gives the only ep-
oxy derivative II with trans orientation of the oxirane
and pyrrole rings with respect to the cyclohexane ring.
Presumably, in both cases the aromatic ring in mole-
1
2
cule I hampers access to the double C =C bond by
4
a
4b
oxidant due to axial orientation of the C –C bond;
therefore, attack by oxidant is possible only at the side
opposite to the nitrogen atom. As we found previously
+
bromide ion. The latter was oxidized to Br which
replaced the 6-H proton in the aromatic ring of hexa-
hydrocarbazole.
[
4], stereochemistry of the oxirane ring opening is also
controlled by the molecular structure.
We made attempts to synthesize ketone A via
By reaction of 1-bromo-9-(p-tolylsulfonyl)hexahy-
drocarbazole (VI) [3] with acetyl bromide we obtained
2
oxidation of compound III at C (NaIO , DMF, 160°C
4
5
36

UNEXPECTED REDOX PROCESSES IN THE REACTIONS OF 1-BROMO- ...
537
Scheme 1.
Br
H
H
H
H
H O
2
AcBr, 80°C
2
Br
+
Br
O
N
N
N
N
H
H
H
H
Me
Me
Me
OAc
Me
OAc
Ts
Ts
II
Ts
Ac
I
III
IV
S
S
Me
+
Me
V
Br
H
H
Piperidine, 120°C
AcBr, 80°C
I
+ V
N
N
H
H
Me
Br
Me
Br
Ts
VI
Ac
VII
H
H
NaIO , DMF, Δ
or DMSO, 180°C
4
Pyridine, Δ
O
III
N
H
N
H
Me
OAc
Ts
Me
OAc
Ts
A
B
9
-acetyl-1,6-dibromohexahydrocarbazole VII and di-
The structure of the isolated compounds was deter-
sulfide V. Elemental analysis of product VII showed
the absence of anionic bromine; furthermore, good
solubility of VII in chloroform and its spectral param-
eters suggest that the 2-bromine atom in molecule VII
is more stable than iodine in analogous compound to
intramolecular replacement by the oxygen atom of the
acetyl fragment. Therefore, quaternary salt like C is
not formed. However, the existence of equilibrium
mined on the basis of analytical and spectral data. The
1
structure of disulfide V was consistent with its H and
1
3
C NMR spectra. The electron-impact mass spectrum
of V contained the molecular ion peak with m/z 246
+
and fragment ion peaks with m/z 123 [CH
(100%) and 92 [CH
of IV in CDCl
C
H
S]
] . In the H NMR spectrum
, the 5-H and 7-H protons resonated as
3
6
4
+
1
C H
6 5
3
3
two one-proton singlets at δ 7.09 and 7.30 ppm, while
signals from 1-H, 2-H, 4a-H, and 9a-H were poorly
resolved. In the spectrum of IV recorded in acetone-d6,
signals from the aromatic 5-H and 7-H protons coin-
cided (δ 7.15 ppm), and signals from 1-H, 2-H, 4a-H,
and 9a-H were resolved well. The coupling constant
for 1-H (δ 4.70 ppm) and 9a-H (δ 4.55 ppm) was about
V
VII strongly displaced to the right cannot be ruled
out completely [9].
Br
H
H
Br–
N
8
(
.0 Hz. The coupling constant between 1-H and 2-H
J = 12.0 Hz) indicated axial orientation of these pro-
Me
O
3
Me
tons. The 2-H proton (δ 4.07 ppm) showed two large
couplings (J = 12.0 Hz) with the axial 1-H and 3a-H
protons and one small coupling with the equatorial 3-H
proton (J = 3.8 Hz). The 4a-H signal was a multiplet
C
2
Presumably, the axial bromine atom on C in mole-
cule III is stable to oxidation and elimination. Our
attempts to oxidize compound III to ketone A with
4
due to small couplings with protons on C and prob-
ably long-range coupling with 3-H (W-coupling).
eq
NaIO in boiling DMF or with DMSO at 180°C were
4
unsuccessful. Likewise, bromide III remained un-
The above orientations of protons in molecule IV
changed after prolonged heating in boiling pyridine.
was unambiguously proved by X-ray analysis (Fig. 1).
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 45 No. 4 2009

5
38
LIKHACHEVA et al.
interactions conform to the corresponding van der
1
Br
5
H
3
Waals distances.
C
2
4
Br
13
2
5
C
In the C NMR spectra of III and IV, the C signal
2
C
C
6
is located at δ
An appreciably downfield position of the C signal
(δ 31.2 and 31.0 ppm, respectively) is related to
C
48.9 and 49.3 ppm, respectively.
C
4b
2
3
C
4a
H
C
7
1
C
4
a
H
C
H
1
C
α-effect of heavy bromine atom [10], whereas α-effect
9
a
8
a
C
2
7
C
of the oxygen atom on C in analogous compounds is
9
a
H
H
8
1
C
2
O
much weaker [4]. The presence of two one-proton
9
O
1
N
singlets in the aromatic region of the H NMR spec-
1
0
C
1
4
trum of VII, δ 7.02 and 7.20 ppm (5-H, 7-H), indicates
C
12
C
6
the presence of a substituent on C . The substituent on
C occupies equatorial position, as follows from two
1
1
1
3
C
1
3
O
C
large coupling constants for 1-H (J = 13.2, 15.0 Hz;
diaxial interaction) and small coupling with 2-Heq
Fig. 1. Structure of the molecule of 9-acetyl-2,6-dibromo-8-
methyl-1,2,3,4,4a,9a-hexahydrocarbazol-1-yl acetate (IV)
according to the X-ray diffraction data; non-hydrogen atoms
are shown as thermal vibration ellipsoids with a probability
of 50%; some hydrogen atoms are also shown.
(
J = 4.4 Hz) [11].
Thus the reactions of 1-bromo- and 1,2-epoxy-9-
(p-tolylsulfonyl)-1,2,3,4,4a,9a-hexahydrocarbazoles
with acetyl bromide in the presence of moisture lead to
introduction of bromine into the 6-position and are
accompanied by replacement of the p-tolylsulfonyl
group on the nitrogen by acetyl group. The p-tolyl-
sulfonyl group acts as oxidant toward bromide ion and
is reduced to di-p-tolyl disulfide.
The five-membered nitrogen-containing ring has an
9
a
envelope conformation with the C atom deviating by
.565 Å from the plane formed by the four remaining
atoms. The saturated six-membered ring adopts a chair
0
1
2
conformation, and the substituents on C and C occu-
1
py equatorial positions, in keeping with the H NMR
EXPERIMENTAL
data. Molecules IV in crystal give rise to chains along
the b crystallographic axis via slightly shortened
A single crystal of compound IV was obtained by
slow crystallization from 95% ethanol. Monoclinic
crystal system with the following unit cell parameters
1
2c
intermolecular contacts Br ···Br (2 – x, –y, –z),
1
2a
3
1
.8696(5) Å, and shortened contacts Br ···Br (x, y –
, z), 3.6384(5) Å (Fig. 2). The other intermolecular
(
1
100 K): a = 8.5214(6), b = 11.0319(7), c =
3
8.6968(12) Å; β = 90.6910(10)°; V = 1757.5(2) Å ;
3
–1
Z = 4; dcalc = 1.682 g/cm ; μ = 4.626 mm ; space
group P2 /n. Intensities of 22262 reflections were
measured at 100 K on a Smart Apex2 CCD diffrac-
1
2
d
Br
2c
2e
Br
1
c
Br
1
d
Br
Br
tometer [λ(MoK ) = 0.71073 Å, graphite monochro-
α
1
e
2
b
a
Br
Br
2a
mator, 2θ < 60°]. The initial array of experimental
reflection intensities was processed by SAINT and
SADABS programs incorporated into APEX2 software
Br
1a
1
b
1
Br
Br
Br
2
Br
[12] with account taken of correction for absorption
b
0
(
Tmin = 0.474, Tmax = 0.630). The structure was solved
by the direct method and was refined with respect to
2
hkl
F
by the full-matrix least-squares procedure in
anisotropic approximation for non-hydrogen atoms.
The positions of hydrogen atoms were set on the basis
of geometry considerations and were refined using the
riding model [U (H) = nU (C); n was assumed equal
iso
eq
c
to 1.5 for methyl carbon atoms and to 1.2 for the other
carbon atoms]. The final divergence factors were
Fig. 2. A fragment of crystal packing of 9-acetyl-2,6-di-
bromo-8-methyl-1,2,3,4,4a,9a-hexahydrocarbazol-1-yl
acetate (IV).
R = 0.0395 [for 4175 reflections with I > 2σ(I)] and
1
wR = 0.0909 (for all 5108 independent reflections,
2
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 45 No. 4 2009

UNEXPECTED REDOX PROCESSES IN THE REACTIONS OF 1-BROMO- ...
539
Rint = 0.0402); goodness of fit 0.984. All calculations
were performed using SHELXTL-97 software [13].
trum (CDCl
3
), δ
C
, ppm: 19.4, 20.8, 21.5 (CH
3
); 24.3
4
3
4a
2
9a
(C ), 31.2 (C ), 40.1 (C ), 49.3 (C ), 69.8 (C ), 74.3
1
5
6
7
o
(
C ); 119.5, 127.1, 127.3, 129.6, 130.9 (C , C , C , C ,
The IR spectra were recorded on a UR-20 spec-
m
4b
8
8a
i
1
13
C ); 134.4, 135.9, 137.6, 140.7, 144.1 (C , C , C , C ,
trometer. The H and C NMR spectra were measured
on a Bruker AM-300 instrument at 300.13 and
p
C ); 169.8 (C=O). Found, %: C 55.06; H 4.81;
Br 16.48; N 2.67; S 6.46. C H BrNO S. Calculated,
2
2
24
4
7
5.47 MHz, respectively, using tetramethylsilane as
%: C 55.23; H 5.06; Br 16.70; N 2.93; S 6.70.
internal reference. The elemental compositions were
determined on an M-185B CHN analyzer. The mass
spectra (electron impact, 70 eV) were obtained on
an MKh-1320 instrument. Silica gel LS (40–100 μm,
Lancaster) was used for column chromatography.
Qualitative TLC analysis was performed on Sorbfil
plates (Sorbpolimer Ltd., Krasnodar, Russia); spots
were visualized by treatment with iodine vapor.
9-Acetyl-2,6-dibromo-8-methyl-1,2,3,4,4a,9a-
hexahydrocarbazol-1-yl acetate (IV). Yield 0.258 g
(37%), mp 189–191°C (from EtOH). H NMR spec-
trum (acetone-d ), δ, ppm: 1.60 d.q (1H, 4-H , J = 3.6,
1
6
ax
13.0 Hz), 1.83–2.19 m (2H, 3-H , 4-H ), 1.96 s (3H,
ax
eq
CH ), 2.05 s (3H, CH ), 2.11 s (3H, CH ), 2.38 d (1H,
3
3
3
2
3-H , J = 13.0 Hz), 3.77 m (1H, 4a-H), 4.07 d.t (1H,
eq
2
4
7
-H, J = 3.8, 12.0 Hz), 4.55 t (1H, 9a-H, J = 8.0 Hz),
.70 d.d (1H, 1-H, J = 8.0, 12.0 Hz), 7.15 s (2H, 5-H,
-H). Found, %: C 45.58; H 4.09; Br 35.71; N 2.89.
(
1S,2R,4aS,9aR)-1,2-Epoxy-8-methyl-9-(p-tolyl-
sulfonyl)-1,2,3,4,4a,9a-hexahydrocarbazole (II) was
synthesized by oxidation of 0.034 g (0.1 mmol) of
compound I with dimethyldioxirane according to the
procedure described in [14]. After removal of the
solvent, the residue was subjected to chromatography
using a 1×15-cm column charged with 0.1 g of silica
gel (eluent benzene). Yield 0.028 g (80%). The physi-
cal constants and spectral parameters of compound II
were consistent with those reported in [4].
C H Br NO . Calculated, %: C 45.87; H 4.30;
Br 35.90; N 3.15.
1
7
19
2
3
9-Acetyl-1,6-dibromo-8-methyl-1,2,3,4,4a,9a-
hexahydrocarbazole (VII). Acetyl bromide, 4.9 g
(39.83 mmol), was added to a solution of 1 g
(2.38 mmol) of hexahydrocarbazole VI in 40 ml of
chloroform. The mixture was heated for 10 h under
reflux, diluted with 50 ml of chloroform, and washed
with a 10% aqueous solution of sodium hydrogen car-
bonate and with water. The organic phase was separat-
Reaction of compound II with acetyl bromide.
Acetyl bromide, 15.5 mmol, was added to a solution of
.55 g (1.55 mmol) of compound II in 20 ml of
benzene. The mixture was heated for 70 h at 80°C,
diluted with 150 ml of methylene chloride, and washed
with a 10% aqueous solution of sodium hydrogen car-
bonate and with water. The organic phase was separat-
0
ed and dried over MgSO , the solvent was removed
under reduced pressure, and the residue was subjected
to column chromatography on silica gel using benzene
4
1
as eluent. Yield 0.24 g (26%), mp 164–166°C. H NMR
ed, dried over MgSO , and evaporated under reduced
pressure, and the residue was subjected to chromatog-
raphy on silica gel using benzene as eluent.
spectrum (CDCl
2.25 s (3H, CH ), 2.50 s (3H, CH
4a-H), 3.77 d.d.d (1H, 1-H, J = 4.4, 13.2, 15.0 Hz),
.45–4.51 m (1H, 9a-H), 7.02 s (1H, Harom), 7.20 s
arom). Found, %: C 46.33; H 4.19; Br 41.03;
3
), δ, ppm: 1.40–2.30 m (6H, CH
2
),
4
), 3.64–3.68 m (1H,
3
3
4
Di-p-tolyl disulfide (V). Yield 0.088 g (46%).
1
(
1H, H
H NMR spectrum (CCl –C D ), δ, ppm: 2.22 s (CH ),
4
6
6
3
N 3.40. C H Br NO. Calculated, %: C 46.54; H 4.43;
1
5
17
2
6
.94 d and 7.28 d (4H each, Harom, J = 8.0 Hz).
C NMR spectrum (CDCl ), δ , ppm: 21.4 (CH );
1
3
Br 41.28; N 3.62.
3
C
3
o
m
i
p
1
28.9, 129.9 (C , C ); 134.5, 137.0 (C , C ). Mass
+
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