Furan ring opening-indole ring closure: Synthesis of furo[2′, 3′:3,4]-cycloheota[1,2-b]indolium chlorides

Article abstract of DOI:10.1002/jhet.5570430315

A new synthetic approach to furo[2′,3′:3,4]cyclohepta[1,2-b] indolium chlorides is elaborated starting from 2-acetylaminoaryldifurylmethanes or 2-aminoaryldifurylmethanes under treatment with methanolic HCl solution. The reaction proceeds in three steps: recyclization, intramolecular cyclization, and disproportionation. In this case the furan ring takes part in building up both pyrrole and seven-membered rings. The same salts can be obtained directly from 2-acetylaminobenzaldehydes and 2-methylfuran under similar conditions without isolation of corresponding 2-acetylaminoaryldifurylmethanes.

Full text of DOI:10.1002/jhet.5570430315

May-Jun 2006
623
Furan Ring Opening – Indole Ring Closure: Synthesis of Furo[2',3':3,4]-
cyclohepta[1,2-b]indolium Chlorides
Alexander V. Butin*, Sergey K. Smirnov and Tatyana A. Stroganova
Kuban State University of Technology, Moskovskaya st. 2, Krasnodar, 350072, Russia.
E-mail: alexander_butin@mail.ru
Received August 15, 2005
X
Ac
H
N
R
R
NH
R
R
Cl-
NH
HCl
R
R
HCl
R
+
+
O
R
O
O
R
O
O
R
R
X = H, Ac; R3 = Me, Et
A new synthetic approach to furo[2',3':3,4]cyclohepta[1,2-b]indolium chlorides is elaborated starting
from 2-acetylaminoaryldifurylmethanes or 2-aminoaryldifurylmethanes under treatment with methanolic
HCl solution. The reaction proceeds in three steps: recyclization, intramolecular cyclization, and
disproportionation. In this case the furan ring takes part in building up both pyrrole and seven-membered
rings. The same salts can be obtained directly from 2-acetylaminobenzaldehydes and 2-methylfuran under
similar conditions without isolation of corresponding 2-acetylaminoaryldifurylmethanes.
J. Heterocyclic Chem., 43, 623 (2006).
Introduction.
the interaction of nitroarenes with an excess of the
corresponding Grignard reagent [11].
A great number of indole derivatives possessing diverse
biological and pharmaceutical activities are annulated
with five-, six, and seven-membered carbocycles. Among
the 2,3-condensed derivatives a remarkable amount of
attention is devoted to azaazulenes (cyclohepta[b]indoles)
which are constituents of some alkaloids [1] and pigments
[2]. These compounds show a wide range of biological
activity including anti-inflammatory [3], anticancer [4],
antitumor [5] and are affecting central nervous system [6].
The biological activity of cyclohepta[b]indoles contributed
to the development of plenty of synthetic approaches to their
synthesis. There are two main approaches among them: 1)
formation of pyrrole part of indole; 2) formation of
carbocyclic fragment. For a long time one of the most
popular approaches to the pyrrole ring construction of
indoles has been provided by the Fischer synthesis based on
transformation of corresponding phenylhydrazones [7].
Another one applied to the synthesis of fused indole
derivatives is the Bischler method [8].
The indoles condensed with seven-membered cycle are
usually obtained by reaction of ꢀ-iodoanilines with
cycloheptanone in the presence of palladium acetate [9] or
by palladium-mediated cross-coupling of 2-functionalized
nitroarenes with ꢀ-halo-enones followed by the reductive
N-heteroannelation [10]. An interesting example of the
pyrrole ring formation is the synthesis of indole tricyclic
derivative under the modified Bartoli reaction conditions:
In recent years the second approach to the fused
indoloazulenes has been rapidly developing. It involves
the annelation of carbocyclic fragment to the preformed
indole moiety [12].
Thus inter- and intramolecular cyclizations catalyzed by
transition metals (palladium, in particular) are used
widely [13,2b]. Among examples of the intramolecular
cyclization leading to the formation of carbocyclic
fragment of azaazulenes the following should be
mentioned: the carbenoid insertion [14], the cascade
addition-cyclization reaction of indolyl radicals generated
from phenyl selenoesters [15] and intramolecular
cyclization of indolylborates [16]. A convenient approach
to the carbocycle construction is provided by the
intramolecular condensation of corresponding indole
derivatives in the PPA medium or under the treatment
with (CF3CO)2O in the presence of BF3 [17].
However, the synthetic routes to condensed cyclohepta-
[b]indoles with the transformations of furan ring are scarce.
We have developed an efficient approach to the
synthesis of condensed heterocyclic systems such as
benzofurans, indoles, isochromenones and isoquino-
Scheme 1
Ac
NH
Ac
R
R
R
R
N
+
-
-
ClO4
Tr ClO4
+
O
O
O
R = H, OMe

624
A.V. Butin, S.K. Smirnov, and T.A. Stroganova
Vol 43
linones based on recyclization of furan ring in substituted
benzylfurans [18]. Earlier we reported on the synthesis of
planar tetracyclic tropylium salts (Scheme 1) [19]. The
obtained salts incorporate cyclohepta[b]indole fragment
and are potential biologically active compounds.
However, the presence of perchlorate-anion makes them
unsuitable for biological activity investigations. Keeping
this in mind, we planned to substitute the perchlorate-
anion in tetracyclic indole salts by another pharma-
ceutically acceptable counter-ion such as chloride-ion [4ꢀ]
and to synthesize new salts of this type.
Table 1
Physical Data of Compounds 5
Comp.
mp
Yield Mol. Formula
Calcd. (Found) %
C
H
N
5a
5b
5c
5d
5e
5f
136-
137
143-
144
60
66
56
69
57
69
62
C19H19NO3
(309.37)
C21H23NO5
(369.42)
C23H27NO5
(397.48)
C20H19NO5
(353.38)
C22H23NO5
(381,43)
C21H21NO5
(367.41)
C19H18BrNO3
(388.26)
73.77
6.19
4.53
(73.94) (6.04) (4.79)
68.28 6.28 3.79
(68.40) (6.43) (3.96)
69.50 6.85 3.52
(69.68) (6.98) (3.73)
67.98 5.42 3.96
(68.16) (5.64) (3.79)
69.28 6.08 3.67
(69.41) (6.32) (3.85)
68.65 5.76 3.81
(68.49) (5.93) (3.99)
58.78 4.67 3.61
(58.54) (4.88) (3.50)
93-94
165-
166
134-
135
156-
157
158
Scheme 2
R1
NO2
R1
R2
NO2
HClO4
Ni/Ra
5g
R3
+
R2
NH2NH2,
EtOH
R3
O
1,4-dioxane
O
CHO
O
Results and Discussion.
R3
For this purpose we have obtained o-aminoaryldifuryl-
methanes 4 by condensation of the o-nitrobenzaldehydes
1 with 2-alkylfurans 2 and subsequent reduction of
formed o-nitrobenzylfurans 3 (Scheme 2). The interaction
of the compounds 4 with acetic anhydride resulted in o-
acetylaminobenzylfurans 5 (Table 1, 3).
3 a-g
Ac
R1
R2
NH2
R1
NH
Ac2O
R3
R3
O
R2
O
O
O
The passing of the gaseous hydrogen chloride through
methanolic solutions of the compounds 5 resulted in their
recyclization leading to tetracyclic indole salts 6 (method
A, Table 2, 3). It has been found that under conditions
employed the recyclization proceeds with the loss of the
acetyl group (Scheme 3). It is of interest that salts 6 can
be obtained directly from the amines 3, omitting the
acetylation step.
R3
R3
5 a-g
4 a-g
3, 4, 5
R1
H
OMe
OMe
R2
H
R3
Me
Me
Et
a
b
c
d
e
f
OMe
OMe
O H2O
O H2O
Me
Et
From our point of view the mechanism of the formation
of tetracyclic structure includes intermediate formation of
O H2 H2O
Br
Me
Me
g
H
Table 2
Physical Data of Compounds 6
mp (°C)
(with decomp.)
200-202
Yield (%)
Method A
Mol. Formula
Calcd. (Found) %
Comp.
Method B
39
(Mol. Wt)
C17H14ClNO
(283.76)
C
H
N
6a
40
58
47
63
54
54
56
71.96
4.97
4.94
(72.09) (4.79) (4.85)
66.38 5.28 4.07
(66.52) (5.15) (4.00)
67.83 5.96 3.77
(67.72) (6.09) (3.83)
65.96 4.31 4.27
(65.99) (4.27) (4.30)
67.51 5.10 3.94
(67.54) (5.12) (3.96)
66.77 4.72 4.10
(66.81) (4.65) (4.22)
3.86
O (362.66) (56.21) (3.78) (4.01)
6b
6c
6d
6e
6f
203-205
198-199
243-245
177-179
205-206
211-213
C19H18ClNO3
(343.81)
C21H22ClNO3
(371.87)
25
19
C18H14ClNO3
(327.77)
C20H18ClNO3
(355.82)
C19H16ClNO3
(341.80)
6g
C17H13BrClN 56.30 3.61

May-Jun 2006
Synthesis of Furo[2',3':3,4]cyclohepta[1,2-b]indolium Chlorides
625
indole ketone 7 arising from the recyclisation of one of
the furan rings [18b] with subsequent cyclization on the ꢀ-
position of the second furan.
also by condensation of 2-methylfuran with corre-
sponding 2-acetylaminobenzaldehydes in the presence of
an acidic catalyst. We supposed that the conditions of the
Scheme 3
Ac
H
N
R1
R2
R1
R2
R1
R2
NH2
NH
Cl-
+
R
R
O
O
R
O
O
O
R3
R3
R3
5 a-g
4 a-g
6 a-g
Table 3
H1 NMR Data of Compounds 5, 6
1H NMR (ppm, CDCl3)
1H NMR (ppm, CF3COOD)
Comp.
Comp.
5a
2.02 (s, 3H, CH3), 2.26 (s, 6H, CH3), 5.42 (s, 1H, CH), 5.92
(d, J = 3.2 Hz, 2H, HFur), 5.95 (d, J = 3.2 Hz, 2H, HFur), 7.11-
7.14 (m, 1H, HAr), 7.25-7.33 (m, 2H, HAr), 7.42 (s, 1H, NH),
7.82-7.85 (m, 1H, HAr)
2.98 (s, 3ꢁ, CH3); 3.22 (s, 3ꢁ, CH3); 7.30 (s, 1ꢁ, HFur);
7.78-7.85 (m, 1ꢁ, HAr); 8.48 (d, J = 11.0 Hz, 1ꢁ, HTrop);
6a
6b
8.90 (d, J = 11.0 Hz, 1ꢁ, HTrop); 9.03-9.07 (m, 1ꢁ, HAr
)
5b
5c
2.02 (s, 3H, CH3), 2.26 (s, 6H, CH3), 3.79 (s, 3H, OCH3), 3.87
(s, 3H, OCH3), 5.34 (s, 1H, CH), 5.92 (d, J = 3.2 Hz, 2H,
2.95 (s, 3ꢁ, CH3); 3.18 (s, 3ꢁ, CH3); 4.21 (s, 3ꢁ, OCH3);
4.26 (s, 3ꢁ, OCH3); 7.28 (s, 1ꢁ, HFur); 7.49 (s, 1ꢁ, HAr);
8.34 (d, J = 11.0 Hz, 1ꢁ, HTrop); 8.49 (s, 1ꢁ, HAr); 8.78 (d,
H
Fur), 5.94 (d, J = 3.2 Hz, 2H, HFur), 6.64 (s, 1H, HAr), 7.28 (s,
1H, NH), 7.39 (s, 1H, HAr)
J = 11.0 Hz, 1ꢁ, HTrop)
1.20 (t, J = 7.5 Hz, 6H, CH3), 2.01 (s, 3H, CH3), 2.61 (q, J =
7.5 Hz, 4H, CH2), 3.78 (s, 3H, OCH3), 3.87 (s, 3H, OCH3),
5.36 (s, 1H, CH), 5.92-5.96 (m, 4H, HFur), 6.62 (s, 1H, HAr),
7.29 (s, 1H, NH), 7.40 (s, 1H, HAr)
6c
1.62 (t, J = 7.6 Hz, 3ꢁ, CH3); 1.72 (t, J = 7.6 Hz, 3ꢁ,
CH3); 3.33 (q, J = 7.6 Hz, 2ꢁ, CH2); 3.51 (q, J = 7.6 Hz,
2ꢁ, CH2); 4.23 (s, 3ꢁ, OCH3); 4.27 (s, 3ꢁ, OCH3); 7.33
(s, 1ꢁ, HFur); 7.50 (s, 1ꢁ, HAr); 8.38 (d, J = 11.0 Hz, 1ꢁ,
H
Trop); 8.50 (s, 1ꢁ, HAr); 8.82 (d, J = 11.0 Hz, 1ꢁ, HTrop)
5d
5e
2.03 (s, 3H, CH3), 2.26 (s, 6H, CH3), 5.33 (s, 1H, CH), 5.91
(d, J = 3.2 Hz, 2H, HFur), 5.93 (d, J = 3.2 Hz, 2H, HFur), 6.59
(s, 1H, HAr), 7.16 (s, 1H, NH), 7.22 (s, 1H, HAr)
6d
6e
2.94 (s, 3ꢁ, CH3); 3.16 (s, 3ꢁ, CH3); 6.29 (s, 2ꢁ, CH2);
7.24 (s, 1ꢁ, HFur); 7.34 (s, 1ꢁ, HAr); 8.30 (d, J = 11.0 Hz,
1ꢁ, HTrop); 8.31 (s, 1ꢁ, HAr); 8.69 (d, J = 11.0 Hz, 1ꢁ,
HTrop
)
1.20 (t, J = 7.5 Hz, 6H, CH3), 2.02 (s, 3H, CH3), 2.61 (q, J =
7.5 Hz, 4H, CH2), 5.34 (s, 1H, CH), 5.93 (s, 4H, HFur), 6.58 (s,
1H, HAr), 7.20 (s, 1H, NH), 7.23 (s, 1H, HAr)
1.60 (t, J = 7.6 Hz, 3ꢁ, CH3); 1.68 (t, J = 7.6 Hz, 3ꢁ,
CH3); 3.32 (q, J = 7.6 Hz, 2ꢁ, CH2); 3.48 (q, J = 7.6 Hz,
2ꢁ, CH2); 6.28 (s, 2ꢁ, CH2); 7.28 (s, 1ꢁ, HFur); 7.35 (s,
1ꢁ, HAr); 8.31 (s, 1ꢁ, HAr); 8.33 (d, J = 11.0 Hz, 1ꢁ,
H
Trop); 8.78 (d, J = 11.0 Hz, 1ꢁ, HTrop)
5f
2.00 (s, 3H, CH3), 2.25 (s, 6H, CH3), 4.22 (s, 4H, CH2CH2),
5.30 (s, 1H, CH), 5.90 (d, J = 3.2 Hz, 2H, HFur), 5.93 (d, J =
3.2 Hz, 2H, HFur), 6.63 (s, 1H, HAr), 7.15 (s, 1H, NH), 7.27 (s,
1H, HAr)
6f
2.94 (s, 3ꢁ, CH3); 3.16 (s, 3ꢁ, CH3); 4.54-4.58 (m, 4ꢁ,
CH2CH2); 7.22 (s, 1ꢁ, HFur); 7.41 (s, 1ꢁ, HAr); 8.33 (d, J
= 11.0 Hz, 1ꢁ, HTrop); 8.47 (s, 1ꢁ, HAr); 8.66 (d, J = 11.0
Hz, 1ꢁ, HTrop
)
5g
2.01 (s, 3H, CH3), 2.26 (s, 6H, CH3), 5.37 (s, 1H, CH), 5.93
(d, J = 3.1 Hz, 2H, HFur), 5.97 (d, J = 3.1 Hz, 2H, HFur), 6.99
(d, J = 8.1 Hz, 1H, HAr), 7.24 (d, J = 8.1 Hz, 1H, HAr), 7.44
(br s, 1H, NH), 8.12 (s, 1H, HAr)
6g
2.97 (s, 3ꢁ, CH3); 3.23 (s, 3ꢁ, CH3); 7.33 (s, 1ꢁ, HFur);
7.93 (d, J = 8.7 Hz, 1ꢁ, HAr); 8.16 (s, 1ꢁ, HAr); 8.53 (d, J
= 11.0 Hz, 1ꢁ, HTrop); 8.88 (d, J = 8.7 Hz, 1ꢁ, HAr); 8.90
(d, J = 11.0 Hz, 1ꢁ, HTrop
)
Disproportionation of the resulted cycloheptatriene 8 under
the action of the excess of hydrogen chloride accomplishes the
formation of chlorides 6 (Scheme 4). A similar transformation
was observed earlier under the treatment of 2-hydroxybenzyl-
furans with excess of perchloric acid [20]
recyclization (gaseous hydrogen chloride/methanol) are
suitable for the preparation of the salts 6 directly from the
aldehydes 11 and 2-methylfuran without the isolation of
the intermediate compounds 5. For this purpose we
synthesized o-acetylaminobenzaldehydes 11 (Scheme 5).
In fact, under the passing of gaseous hydrogen chloride
through methanolic solutions of the aldehydes 11 and 2-
2-Acetylaminobenzylfurans 5, which are starting
compounds for preparation of the salts 6, can be prepared

626
A.V. Butin, S.K. Smirnov, and T.A. Stroganova
Vol 43
Scheme 4
R
R1
R2
H
H
R1
R1
N
N
N
H+
H+
6
5
R2
H+
R2
-H2O
O
OH
R3
R3
R3
O
O
O
R3
R3
R3
8
7
R = Ac or H
and left overnight. The precipitated product was collected by
filtration, washed with water. A recrystallization from ethanol
gave 11.35 g (60%) of 3g as yellow-green crystals, mp 80-81°C
(ethanol). 1H NMR (200 MHz, CDCl3): ꢀ 2.25 (s, 6H, CH3), 5.90
(d, J = 3.1 Hz, 2H, 4-HFur), 5.95 (d, J = 3.1 Hz, 2H, 3-HFur), 6.15
(s, 1H, CH), 7.26 (d, J = 8.4 Hz, 1H, HAr), 7.65 (d.d, J = 2.1, 8.4
Hz, 1H, HAr), 8.08 ppm (d, J = 2.1 Hz, 1H, HAr).
methylfuran the tetracyclic salts 6 (method B) (Scheme 6)
were isolated as main products. At the same time all
attempts to obtain such salts directly from aminobenzal-
dehydes 10 and 2-methylfuran failed.
Scheme
5
Anal. Calcd. for C17H14BrNO4 (376.21): C, 54.28; H, 3.75; N,
3.72. Found: C, 53.98; H, 3.93; N, 3.89.
Compounds 3a-f were obtained analogously, and physical
data are in accordance with those reported earlier [21].
Ac
R1
R2
R1
R1
R2
NH
NO2
NH2
Fe
Ac2O
O
O
O
H2O, AcOH
R2
9 a-c
10 a-c
General Procedure for the Synthesis of 2-Aminoaryldifuryl-
methanes 4.
11 a-c
9, 10, 11
R1 = R2
a
b
c
A mixture of compound 3 (6 mmol), Raney Ni (1.5 g), ethanol
(20 mL) and hydrazine-hydrate (2 mL) was refluxed until the
completion of the reduction (TLC control). The nickel was filtered
off and the filtrate was evaporated to dryness. Obtained amines 4
were used at the next step without further purification.
OMe OCH2O OCH2CH2O
Thus we elaborated the methods of the synthesis of the
tetracyclic salts containing indole fragment and pharma-
ceutically acceptable counter-ion. The new method that
allows the preparation of the condensed tetracyclic salts
directly from 2-acetylaminobenzaldehydes and 2-methyl-
furan is proposed.
General Procedure for the Synthesis of 2-Acetylaminoaryldifur-
ylmethanes 5.
A mixture of 2-aminoaryldifurylmethane 4 (15 mmol) and
acetic anhydride (30 mmol) was left at 35-40°ꢀ for 20-25 min
until full consumption of the starting compound 4 was observed
(TLC control). The reaction mixture was poured into water (400
mL) and left overnight. The separated product was collected by
filtration and recrystallized from CH2Cl2/hexane mixture.
2-Acetylamino-4-bromophenylbis(5-methylfur-2-yl)-methane
(5g) was obtained according to the general method except the
reaction mixture was kept at 20-25°ꢀ.
Scheme 6
H
R1
N
Ac
-
Cl
R1
R2
NH
+
R2
+
O
O
O
General Procedure for the Synthesis of Furo[2',3':3,4]cyclo-
hepta[1,2-b]indolium Chlorides 6 (method A).
11 a-c
6 b,d,f
Compound 5 (10 mmol) was dissolved in methanol (50 mL)
at 50-55°C and gaseous hydrogen chloride was passed through
the solution until the precipitation of crystalline compound was
completed (~ 70-80 min). The reaction mixture was left for 10
hours at room temperature; the solid was collected by filtration
and washed with small amount of ether.
Analogously furo[2',3':3,4]cyclohepta[1,2-b]indolium chlorides 6
were obtained by passing the hydrogen chloride through
methanolic solution of the compounds 4.
EXPERIMENTAL
1H NMR spectra were recorded in CDCl3 and in CF3COOD
on a Bruker AC 200 spectrometer at 200 MHz. Chemical shifts
are reported in ppm relative to tetramethylsilane as an internal
standard. IR spectra were recorded on InfraLUM FT-02. Melting
points are uncorrected.
2-Nitro-4-bromophenylbis(5-methyl-2-furyl)methane (3g).
General Procedure for the Synthesis of 2-Aminobenzaldehydes 10.
To a solution of 2-nitro-4-bromobenzaldehyde (11.5 g, 50
mmol) and 2-methylfuran (15 mL, 167 mmol) in dioxane (50 mL)
perchloric acid (1 mL) was added. The reaction mixture was
maintained at 70–75°ꢀ until the reaction was completed (TLC
control). The reaction mixture was poured into water (500 mL)
A mixture of 2-nitrobenzaldehyde 9 (24 mmol), iron powder
(15 g), ethylacetate (14 mL), water (180 mL) and glacial acetic
acid (5 ml) was brought up carefully to reflux under vigorous
stirring and was allowed to boil for additional 20-30 minutes.
After the reduction was completed (TLC control), the mixture

May-Jun 2006
Synthesis of Furo[2',3':3,4]cyclohepta[1,2-b]indolium Chlorides
627
was neutralized with NaHCO3 (40 g) and the solid was filtered
off. The organic layer was separated, and the water layer was
extracted with ethylacetate (3 ꢀ 20 mL). The combined organic
extract was purified with active charcoal and evaporated to
dryness. The aminobenzaldehyde obtained was used at the next
step without further purification.
Acknowledgements
Financial support was provided by the Russian Foundation of
Basic Research (grant 03-03-32759) and Bayer HealthCare AG.
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2ꢁ, NH2); 6.82 (s, 1ꢁ, HAr); 9.61 ppm (s, 1ꢁ, CHO).
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8.48. Found: ꢂ, 58.31; ꢁ, 4.36; N, 8.62.
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General Procedure for the Synthesis of 2-Acetylaminobenz-
aldehydes 11.
The mixture of 2-aminobenzaldehyde 10 (10 mmol) and acetic
anhydride (30 mmol) was kept at 55-60°ꢂ for 10-15 min (TLC
control). The reaction mixture was poured into water (300 mL) and
left overnight at room temperature. The precipitate was collected
by filtration, washed with water and recrystallized from ethanol.
[5] A. Mouaddib, B. Joseph, A. Hasnaoui, J.-Y. Merour and S.
Leonce, Heterocycles, 51, 2127 (1999).
2-Acetylamino-4,5-dimethoxybenzaldehyde (11a).
[6a]
M. K. Eberle, U.S. Pat. Appl. US 3696118 (1972), Chem.
Abstr., 78, 29807 (1973); [b] L. M. Rice, E. Hertz and M. E. Freed, J.
Med. Chem., 5, 313 (1964); [c] H. H. Haeck, D. Hamminga, I. Van
Wijngaarden and W. Wouters, Eur. Pat. Appl. EP 338650 (1989), Chem.
Abstr., 112, 216929 (1990).
This compound was obtained from the 2-amino-4,5-
dimethoxybenzaldehyde (10a) according to the general method
in 61% yield as yellow crystals, mp 169-170°ꢂ. H NMR (200
MHz, CDCl3), ꢀ 2.23 (s, 3ꢁ, CH3); 3.91 (s, 3ꢁ, OCH3); 3.98 (s,
3ꢁ, OCH3); 7.03 (s, 1ꢁ, HAr); 8.47 (s, 1ꢁ, HAr); 9.75 (s, 1ꢁ,
CHO); 11.31 ppm (br s, 1ꢁ, NH).
Anal. Calcd. for C11H13NO4 (223.23): ꢂ, 59.19; ꢁ, 5.87; N,
6.27. Found: ꢂ, 59.23; ꢁ, 5.96; N, 6.41.
1
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Yukio, N. Hayashi, M. Toda and R. A. Bulman, Heterocycl. Comm., 9, 9
(2003); [j] J. G. Rodriguez, Y. Benito and F. Temprano, J. Heterocyclic
Chem., 22 (5), 1207 (1985).
2-Acetylamino-4,5-methylenedioxybenzaldehyde (11b).
This compound was obtained from 2-amino-4,5-methylene-
dioxybenzaldehyde (10b) according to the general method in 68%
yield as yellow crystals, mp 164-165°ꢂ. 1H NMR (200 MHz,
CDCl3), ꢀ 2.22 (s, 3ꢁ, CH3); 6.05 (s, 2ꢁ, CH2); 6.99 (s, 1ꢁ, HAr);
8.34 (s, 1ꢁ, HAr); 9.67 (s, 1ꢁ, CHO); 11.44 ppm (br. s, 1ꢁ, NH).
Anal. Calcd. for C10H9NO4 (207.19): ꢂ, 57.97; ꢁ, 4.38; N,
6.76. Found: ꢂ, 58.09; ꢁ, 4.45; N, 6.84.
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Davies, M.-T. Teh and D. Sugden, J. Med. Chem., 41, 451 (1998).
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and P. J. Reider, J. Org. Chem., 62, 2676 (1997).
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Tetrahedron Lett., 43, 1621 (2002); [c] T. L. Scott and B. C. G.
Söderberg, Tetrahedron, 59, 6323 (2003).
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Tetrahedron, 55, 4341 (1999); [b] J. Bergman, T. Janosik, L. Yudina, E.
Desarbre, G. Lidgren and L. Venemalm, Tetrahedron, 56, 1911 (2000).
[13a] M. Murase, K. Watanabe, T. Kurihara and S. Tobinaga,
Chem. Pharm. Bull., 46, 889 (1998); [b] O. Cornec, B. Joseph and J.-Y.
Merour, Tetrahedron Lett., 36, 8587 (1995); [c] B. Joseph, O. Cornec
and J.-Y. Merour, Tetrahedron, 54, 7765 (1998).
2-(Acetylamino)-4,5-ethylenedioxybenzaldehyde (11c).
This compound was obtained from the 2-amino-4,5-ethylene-
dioxybenzaldehyde (10c) according to the general method in
63% yield as yellow crystals, mp 142-143°ꢂ. 1H NMR (200
MHz, CDCl3), ꢀ 2.20 (s, 3ꢁ, CH3); 4.25-4.27 (m, 2ꢁ, CH2);
4.33-4.35 (m, 2ꢁ, CH2); 7.11 (s, 1ꢁ, HAr); 8.27 (s, 1ꢁ, HAr);
9.68 (s, 1ꢁ, CHO); 11.02 ppm (br. s, 1ꢁ, NH).
Anal. Calcd. for C11H11NO4 (221.21): ꢂ, 59.73; ꢁ, 5.01; N,
6.33. Found: ꢂ, 59.87; ꢁ, 5.11; N, 6.47.
General Procedure for the Synthesis of Furo[2',3':3,4]cyclohepta-
[1,2-b]indolium Chlorides 6 (method B).
Gaseous hydrogen chloride was passed through the hot
solution of the compound 11 (4.5 mmol) in methanol (20 mL)
for 50-60 min. The reaction mixture maintained for 2 hours at
room temperature. The precipitated compound 6 was collected
by filtration and washed with a small amount of ether.
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Chem., 66, 7547 (2001).
[16] M. Ishikura and H. Kato, Tetrahedron, 58, 9827 (2002).

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A.V. Butin, S.K. Smirnov, and T.A. Stroganova
Vol 43
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