Preparation of 4,4a,9,9a-tetrahydrocarbazoles and 1,3a,4,8b-tetra- hydrocyclopenta[b]indoles

Article abstract of DOI:10.1007/s10593-006-0199-7

Halocyclization of mesylates or tosylates of 2-(cycloalk-2-en-1-yl)anilines gives N-methanesulfonyl-or N-toluenesulfonyl-1-halo-1,2,3,4,4a,9a- hexahydrocarbazoles, heating of which in DMF at 160°C or in piperidine at 110°C leads to 4,4a,9,9a-tetrahydro-3H

Full text of DOI:10.1007/s10593-006-0199-7

Chemistry of Heterocyclic Compounds, Vol. 42, No. 8, 2006
PREPARATION OF 4,4a,9,9a-TETRAHYDRO-
CARBAZOLES AND 1,3a,4,8b-TETRA-
HYDROCYCLOPENTA[b]INDOLES
R. R. Gataullin1, R. R. Ishberdina1, O. V. Shitikova1, F. F. Minnigulov1, L. V. Spirikhin1,
and I. B. Abdrakhmanov2
Halocyclization of mesylates or tosylates of 2-(cycloalk-2-en-1-yl)anilines gives N-methanesulfonyl- or
N-toluenesulfonyl-1-halo-1,2,3,4,4a,9a-hexahydrocarbazoles, heating of which in DMF at 160°C or in
piperidine at 110°C leads to 4,4a,9,9a-tetrahydro-3H-carbazoles. Heating N-methanesulfonyl-1-iodo-
1,2,3,3a,4,8b-hexahydrocyclopenta[b]indole
in
DMF
at
180-200°C
gives
1,3a,4,9b-
tetrahydrocyclopenta[b]indole, while in the presence of an ortho–methyl substituent the
dehydroiodination reaction proceeds in piperidine at 110°C in high yield. The effect of the nature of the
ortho substituent of N-methyl-1-iodo-1,2,3,3a,4,8b-hexahydrocyclopenta[b]indole on the conformational
equilibrium of the cyclopentane ring has been established by 1H NMR spectroscopy.
Keywords: cyclopenta[b]indolines, hexahydrocarbazoles, tetrahydrocarbazoles, halocyclization,
dehydroiodination, conformation.
Tetrahydrocarbazoles and cyclopenta[b]indolines are of interest as intermediate substances in the
synthesis of certain alkaloids and their analogs and have attracted the attention of a wide circle of investigators to
this area of organic chemistry [1,2].
In this work we publish results of investigations on the development of new methods of synthesizing
4,4a,9,9a-tetrahydrocarbazoles and 1,3a,4,8b-tetrahydrocyclopenta[b]indolines by the halocyclization of
2-(cyclohex-2-en-1-yl)anilines and subsequent dehydrohalogenation of the cyclization products. Thus, the
hexahydrocarbazoles 2a [3] and 2b,c, obtained by the halogen cyclization of anilides 1 [3] and 2, on heating in
DMF at 160°C or in piperidine at 110°C form exclusively tetrahydrocarbazoles 3a,b with retention of the cis
linking of the rings.
Heq
Hax
H
DMF, 160°С
I2, NaHCO3
or Br2
or
2
X
9a
1
N
C5H10NH, 110°C
1
NHR1
1a,b
N
Hax
R1
2a–c
R
H
CH2Cl2,
20°C
R
R1
R
3a,b
1a, 2a,c, 3a R = H, R1 = SO2Me, 1b–3b R = Me, R1 = Tos; 2 a, b, X = I, c X = Br
__________________________________________________________________________________________
1
Institute of Organic Chemistry, Ufa Scientific Center of the Russian Academy of Sciences, Ufa
2
450054; e-mail: chemorg@anrb.ru, railg@rambder.ru. Bashkir State Agricultural University, Ufa 450001,
Russia. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 8, pp. 1184-1190, August, 2006. Original
article submitted December 15, 2003; revision submitted March 23, 2006.
0009-3122/06/4208-1025©2006 Springer Science+Business Media, Inc.
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The indolines 5a-e obtained by the iodocyclization of mesylates 4a,b and tosylate 4c are also subject to
dehydroiodination. The dependence of the elimination conditions on the nature of the indoline ortho substituent
was discovered in this way. Compound 5a remains unchanged on heating in piperidine at 110°C. The expected
compound 6a was successfully obtained in high yield on carrying out the reaction in DMF at an oil bath
temperature of 180-200°C for 15 h. Compounds 5b and 5c undergo dehydroiodination on heating in piperidine
at 110°C with the formation of indolines 6b and 6c in good yield.
H 8b
1
2
I2
3
NaHCO3,
CH2Cl2
N
NHR1
I
R
H3a
R
R1
5a–d
4a–d
H
DMF, 180°С, 15 h
or
C5H10NH, 110°C, 4 h
N
R
H
R1
6a–c
4-6 a R = H, R1 = SO2Me; b R = Me, R1 = SO2Me; c R = Me, R1 = Tos; 4, 5 d R = R1 = H
Unlike the sulfonamides, in the absence of an amino protecting group substitution of the halogen atom
occurs in cyclopenta[b]indole. For example, even on heating in the presence of pyridine in MeCN iodide 7 [4]
gives the quaternary salt 8 in 57% yield.
H
H
–
I
N
MeCN
80°C, 6-8 h
+
N
N
I
N
Me
H
H
Me
H
H
7
8
1
The structures of the obtained compounds were confirmed by 13C and H NMR spectra. Two
dimensional CH–CORR spectroscopy was used to correlate the carbon–proton chemical shifts. The 13C NMR
spectra were recorded in the JMOD mode. Assignment in the NMR spectra of the obtained compounds was
carried out by the double resonance method and on the basis of the data obtained their conformational state was
assessed. It was shown that hexahydrocarbazoles 2a-c have predominantly a conformation with an equatorial
disposition of halogen, shown by the large coupling constants of the H(9a) and H(1) protons [5]. Compounds 5a-c
have a cis linkage of rings with characteristic coupling constant JH-3a,H-8b = 7.8-8.6 Hz.
The dependence of the elimination conditions of indolines 5a-c is probably linked with the different
conformational states of these compounds. In compounds 5d and 7 (described previously in [4]) the coupling
1
constants in the H NMR spectra of the H(3) proton did not exceed 2 Hz, the proton at C(3) occupies a
pseudoequatorial position, and the conformation of the cyclopentane fragment is an envelope with pseudoaxial
C(3a)–N and C(3)–I bonds. In compound 5a ,with a mesyl group in the nitrogen-containing ring, JH-3,Hax-2 is 4.6 Hz,
which indicates some change in the conformation of the pentane ring compared with 7 and 5d. The signal of the
1026

H(3) proton has the form of a doublet and, on suppression of the spin-spin interaction with the 2-Hax proton at
δ 1.8 ppm, is transformed into a singlet. The coupling constant JH-3,H-3a = 0 Hz, which is possible when the
torsion angle H(3)–C(3)–C(3a)–H(3a) is close to 90°.
In the case of compound 5b, containing substituents in the nitrogen-containing and aromatic fragments,
the coupling constant of the H(3) and H(3a) protons remains at 6.0 Hz and JH-3,H-2a = 7.9 and JH-3,H-2b = 6.0 Hz are
observed, i.e. the pentane ring acquires a twist form with pseudoequatorial disposition of iodine, which is
probably linked with the presence of the ortho–methyl substituent on the phenyl ring, repelling the amino-
protecting group to the side of the cyclopentane fragment. The version of the different orientation of the iodine
atom in compounds 5a and 5b due to the difference in the mechanisms of the iodocyclization reaction of amides
4a and 4b is excluded, since the spectral characteristics of compound 5b, synthesized by the iodocyclization of
mesylate 4b, were identical to the characteristics of this same compound obtained by methanesulfonation of
heterocycle 7 in pyridine. The orientation of the halogen atom in amine 7 was confirmed previously by an NOE
experiment [4]. Compound 5c like compound 5b has a substituent in the nitrogen-containing and aromatic
fragments. As was to be expected the corresponding coupling constants of the H(3) proton also means the
conformational states of these compounds are close.
It was discovered that the H(4a) protons in partially hydrogenated carbazoles 2a,b and 3a,b and
analogously the H(8b) protons in cyclopenta[b]indoles 5a-c, and 6a-c experience different shielding depending on
the nature of the substituent of the sulfonyl group, as a result of which the signal of their protons in compounds
2b, 3b, 5c, and 6c are displaced towards high field by approximately 0.6-0.8 ppm compared with the mesylates
2a, 3a, 5a,b, and 6a,b.
The multiplet signal of the H(4a) proton in the spectrum of tetrahydrocarbazole 3a at 3.7 ppm, on
simultaneous suppression of the spin-spin interaction with the C(3)H2–C(4)H2 protons, which have close chemical
shifts, acquires the form of a doublet with coupling constant JH-4a,H-9a = 8.4 Hz, which confirms the retention of a
cis linkage of the rings in the dehydrohalogenation product. The vicinal coupling constant of 10.2 Hz for the H(1)
and H(2) protons of the olefin fragment at 5.9 and 6.0 ppm is characteristic for a cyclohexene ring [5]. In
compounds 6a-c the value of the analogous constant J = ~6 Hz, which is in agreement with the data for
cyclopentenyl compounds [5], and the large constant between the H(3a) and H(8b) protons indicates the cis
junction of the rings.
EXPERIMENTAL
The IR spectra were recorded on a UR 20 instrument. The 1H and 13C NMR spectra were recorded on a
Bruker AM 300 instrument (300 and 75 MHz respectively) in CDCl3 (compounds 1-6) and DMSO-d6
(compound 8), internal standard was TMS. Elemental analysis was carried out out on a C-H-N Analyzer M 185B
instrument. Column chromatography was effected on silica gel 40/70µm (Lancaster). For qualitative TLC
analysis silufol plates (Lyuminofor, Russia) were used with detection of substances by UV irradiation
(λ 254 nm) or with iodine. Mass spectra were obtained on a MX 1320 spectrometer (70 eV). Melting points were
determined on a Boetius stage.
N-Toluenesulfonyl-2-(cyclohex-2-en-1-yl)-6-methylaniline (1b). The reaction mixture consisting of
2-(cyclohex-2-en-1-yl)-6-methylaniline (13 mmol) and p-toluenesulfonyl chloride (19.5 mmol) in pyridine
(15 ml) was maintained at room temperature for 24 h. Water (20 ml) was added, the mixture stirred for 30 min,
and extracted with CHCl3 (40 ml). The organic phase was washed with 10% aqueous NaHCO3 solution, with
water (20 ml), and dried over Na2SO4. The solvent was evaporated in vacuum, and the residue recrystallized
from ethanol. Yield 90%; mp 145-147°C. IR spectrum, ν, cm-1: 3290 (NH). 1H NMR spectrum, δ, ppm (J, Hz):
1.2-2.1 (4H, m, 2CH2); 2.2 (3H, s, CH3); 2.4 (3H, s, CH3); 3.5 (1H, m, CH); 5.7 (2H, m, 2CH); 6.2 (1H, s, NH);
7.0-7.1 (2H, m, H-3,5); 7.1(1H, t, J = 7.0, H-4); 7.2 (2H, d, J = 8.2, H-3'',5''); 7.6 (2H, d, J = 8.2, H-2'',6'').
Found, %: C 69.94; H 6.41; N 3.82; S 9.01. C20H23NO2S. Calculated, %: C 70.35; H 6.79; N 4.10; S 9.39.
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N-Toluenesulfonyl-1-iodo-8-methyl-1,2,3,4,4a,9a-hexahydrocarbazole (2b). A solution of compound
1b (5 mmol) and I2 (10 mmol) in CH2Cl2 (30 ml) was maintained at room temperature, checking the progress of
the reaction by TLC. After the disappearance of the starting material the mixture was diluted with CH2Cl2
(50 ml). The organic solution was washed with 10% Na2S2O3 solution (60 ml), with water (2 × 20 ml), and dried
over Na2SO4. After removing the solvent in vacuum, the residue was recrystallized from ethanol. Yield 96%;
mp 215-220°C (EtOH). 1H NMR spectrum, δ, ppm (J, Hz): 1.0-2.3 (6H, m, 3CH2); 2.4 (3H, s, CH3); 2.6 (3H, s,
CH3); 2.7 (1H, m, H-4a); 3.7 (1H, ddd, J = 4.0, J = 10.2, J = 13.5, H-1); 4.5 (1H, dd, J = 6.5, J = 10.2, H-9a); 6.8
(1H, d, J = 7.0, H-7); 7.1-7.2 (2H, m, H-5,6); 7.2 (2H, d, J = 8.1, H-3',5'); 7.5 (2H, d, J = 8.1, H-2',6'). Found, %: C
51.03; H 4.35; I 26.79; N 2.65; S 6.41, C20H22INO2S. Calculated, %: C 51.40; H 4.74; I 27.15; N 3.00; S 6.86.
N-Methanesulfonyl-1-bromo-1,2,3,4,4a,9a-hexahydrocarbazole (2c). Bromine (1.25 mmol) in
CH2Cl2 (1 ml) was added with stirring to a solution of sulfonamide 1b (1.25 mmol) in CH2Cl2 (20 ml). The
reaction mixture was left for 30 min at 20°C with constant stirring. The solvent was evaporated. The obtained
product was recrystallized from a mixture of CHCl3–2-propanol, 7 : 3 (5 ml). The solid was filtered off. Yield
1
80%; mp 215-217°C. H NMR spectrum, δ, ppm (J, Hz): 1.2-2.3 (6H, m, 3CH2); 3.1 (3H, s, CH3); 3.8 (1H, m,
H-4a); 4.0 (1H, ddd, J = 4.0, J = 8.0, J = 11.5, H-1); 4.5 (1H, dd, J = 7.7, J = 8.0, H-9a); 7.2-7.5 (4H, m, ArH).
13C NMR spectrum, δ, ppm: 21.2 (C(3)); 24.0 (C(4)); 33.9 (C(2)); 39.3 (C(4a)); 42.8 (CH3); 52.1 (C(1)); 70.8 (C(9a));
118.4 (C(8)); 119.7 (C(6)); 126.4 (C(5)); 130.9 (C(4b)); 137.4 (C(7)); 140.6 (C(8a)). Found, %: C 47.02; H 4.65; Br
23.97; N 4.01; S 9.45. C13H16BrNO2S. Calculated, %: C 47.28; H 4.88; Br 24.20; N 4.24; S 9.71.
N-Methanesulfonyl-4,4a,9,9a-tetrahydro-3H-carbazole (3a).
A solution of 1-iodohexahydro-
carbazole 2a (1.3 g) in DMF (15 ml) was heated at 160°C for 3 h [on carrying out the reaction in piperidine
solution compounds 2a or 2c were heated in piperidine (10 ml) at 110°C for 4 h]. At the end of the
dehydroiodination reaction the solvent was evaporated in vacuum, the residue was dissolved in CH2Cl2 (50 ml),
and washed with water (2 × 20 ml). The organic phase was dried over Na2SO4, the solvent evaporated in
1
vacuum, and the residue recrystallized from EtOH. Yield 98.7%; mp 111-113°C (EtOH). H NMR spectrum,
δ, ppm (J, Hz): 1.9-2.2 (4H, m, 2CH2); 2.9 (3H, s, CH3); 3.7 (1H, m, H-4a); 4.8 (1H, ddd, J = 1.0, J = 3.1,
J = 8.4, H-9a); 5.9 (1H, ddd, J = 1.1, J = 3.1, J = 10.2, H-2); 6.0 (1H, ddd, J = 1.0, J = 3.3, J = 10.2, H-1);
7.1-7.5 (4H, m, Ar). 13C NMR spectrum, δ, ppm: 20.3 (C(3)); 23.0 (C(4)); 36.7 (SCH3); 38.7 (C(4a)); 61.2 (C(9a));
115.1 (C(8)); 123.6 (C(6)); 123.7 (C(5)); 125.2 (C(1)); 127.7 (C(2)); 131.7 (C(7)); 133.8 (C(4b)); 141.0 (C(8a)).
Found, 62.35; H 5.75; N 5.28; S 12.41. C13H15NO2S. Calculated, %: C 62.63; H 6.06; N 5.62; S 12.86.
N-Toluenesulfonyl-8-methyl-4,4a,9,9a-tetrahydro-3H-carbazole (3b) was obtained by heating
1-iodohexahydrocarbazole 2b (0.4 g: 0.8 mmol) in piperidine (2 ml) at 110°C for 4 h. The reaction mixture was
1
then processed analogously to compound 3a. Yield 98.2%; mp 168-170°C (EtOH). H NMR spectrum, δ, ppm
(J, Hz): 1.6-1.9 (4H, m, 2CH2); 2.4 (3H, s, CH3); 2.6 (3H, s, CH3); 2.5-2.6 (1H, m, H-4a); 4.8 (1H, ddd, J = 1.9,
J = 4.6, J = 7.0, H-9a); 5.6 (1H, dt, J = 2.8, J = 10.2, H-2); 6.0 (1H, dd, J = 5.0, J = 10.2, H-1); 6.8 (1H, d,
13
J = 5.6, H-5); 7.0-7.2 (4H, m, Ar); 7.4 (2H, d, J = 8.2, H-2',5'). C NMR spectrum, δ, ppm: 19.1, 21.5 (2CH3);
19.8(C(3)); 21.8 (C(4)); 37.6 (C(4a)); 63.5 (C(9a)); 120.1 (C(8)); 120.5, 125.7, 126.3, 130.2, 131.1 (C(5), C(6), C(7), C(1),
C(2)); 127.4 (C(6'), C(2')); 129.3 (C(3'), C(5')); 127.7, 133.3, 135.2, 138.7, 143.7 (C(4b), C(8), C(8a), C(1), C(4')). Found, %: C
50.98; H 4.43; I 26.76; N 2.71; S 6.43. C20H22INO2S. Calculated, %: C 51.40; H 4.74; I 27.15; N 3.00; S 6.86.
N-Methanesulfonyl-2-(cyclopent-2-en-1-yl)aniline (4a). The reaction mixture consisting of
2-(cyclopent-2-en-1-yl)aniline (33 mmol) and methanesulfonyl chloride (49.5 mmol) in pyridine (15 ml) was
maintained at room temperature for 24 h. At the end of the reaction the pyridine was evaporated in vacuum, the
residue was dissolved in CH2Cl2 (50 ml), washed with 10% aqueous NaHCO3 solution (20 ml), with water
(2 × 20 ml), and dried over Na2SO4. The solvent was evaporated in vacuum. The yield of viscous orange oil was
1
93.6%. H NMR spectrum, δ, ppm (J, Hz): 1.6-1.8 (1H, m, CH); 2.4-2.7 (3H, m, CH2, CH); 3.0 (3H, s, CH3);
4.0-4.2 (1H, m, CH); 5.7-5.8 (1H, m, HC=C); 6.0-6.1 (1H, m, C=CH); 6.7 (1H, br s, NH); 7.1-7.3 (3H, m,
H Ar); 7.5 (1H, d, J = 8.0, H Ar). 13C NMR spectrum, δ, ppm: 32.3, 32.4 (2CH2); 39.7 (CH3); 46.3 (C(1')); 123.3
(C(4)); 126.2 (C(6)); 127.0 (C(5)); 128.5 (C(1')); 132.9 (C(3)); 133.2 (C(2')); 133.9 (C(2)); 138.8 (C(1)). Found, %:
C 60.19; H 5.95; N 5.23; S 13.03. C12H15NO2S. Calculated, %: C 60.73; H 6.37; N 5.90; S 13.51.
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N-Methanesulfonyl-2-(cyclopent-2-en-1-yl)-6-methylaniline (4b) was obtained analogously to
compound 4a from 2-(cyclopent-2-en-1-yl)-6-methylaniline (3 mmol) and methanesulfonyl chloride (4.5 mmol).
After chromatography through a thin layer of silica gel (eluent CCl4) yield 89%; mp 115-116°C, Rf 0.2 (CH2Cl2).
1
IR spectrum, ν, cm-1: 3290 (NH). H NMR spectrum, δ, ppm (J, Hz): 1.6-1.7 (2H, m, CH2); 2.1 (3H, s, CH3);
2.4-2.5 (2H, m, CH2); 3.0 (3H, s, SCH3 ); 4.4 (1H, m, H-1'); 5.7 (1H, m, H-2'); 6.0 (1H, m, H-3'); 6.3 (1H, br s,
NH); 7.1-7.2 (3H, m, H Ar). 13C NMR spectrum, δ, ppm: 19.5 (CH3); 32.5 (C(4')); 33.6 (C(5')); 41.5 (SCH3); 46.1
(C(1')); 126.1 (C(6)); 128.5 (C(3')); 131.6 (C(5)); 132.1 (C(2)); 134.1 (C(2')); 137.2 (C(4)); 146.0 (C(1)). Found, %:
C 61.90; H 6.65; N 5.34; S 12.54. C13H17NO2S. Calculated, %: C 62.12; H 6.82; N 5.57; S 12.76.
N-Toluenesulfonyl-2-(cyclopent-2-en-1-yl)-6-methylaniline (4c). A mixture of 2-(cyclopent-2-en-1-
yl)-6-methylaniline (6 mmol), p-toluenesulfonyl chloride (9 mmol), and pyridine (10 ml) was maintained at
room temperature for 24 h. Water (2 ml) was added, and the pyridine was evaporated in vacuum. The residue
was dissolved in CHCl3 (40 ml), washed with 10% NaHCO3 solution (20 ml), with water (20 ml), and dried over
Na2SO4. The solvent was evaporated in vacuum, and the residue recrystallized from ethanol. Yield 98.4%; mp
132-135°C. 1H NMR spectrum, δ, ppm (J, Hz): 2.0 (6H, m, 3CH2); 2.1 (3H, s, CH3); 4.1 (1H, m, CH); 5.4 (2H,
m, 2CH); 6.2 (1H, s, NH); 7.0 (2H, d, J = 8.1, H-3'',5''); 7.1 (1H, t, J = 7.0, H-4); 7.3 (2H, m, H-3,5); 7.6 (2H, d,
J = 8.1, H-2'',6''). Found, %: C 69.67; H 6.43; N 4.27; S 9.77. C19H20NO2S. Calculated, %: C 69.69; H 6.46;
N 4.28; S 9.79.
N-Methanesulfonyl-3-iodo-1,2,3,3a,4,8b-hexahydrocyclopenta[b]indole (5a).
A
solution of
compound 4a (5 mmol) and I2 (10 mmol) in CH2Cl2 (25 ml) was maintained at 20°C, checking the progress of
the reaction by TLC. At the disappearance of the initial sulfonanilamide 4a the reaction mixture was diluted with
CH2Cl2 (50 ml), and the solid was filtered off. The organic solution was washed with 10% Na2S2O3 solution (60
ml), with water (2 × 20 ml), and dried over Na2SO4. After removing the solvent in vacuum, the residue was
1
recrystallized from ethanol. Yield 96.8%; mp 150-153°C (EtOH). H NMR spectrum, δ, ppm (J, Hz): 1.8, (1H,
dddd, JH-2b,H-3 = 4.6, JH-2b,H-1b = 6.5, JH-2b,H-1a = 12.6, Jgem = 14.1, H-2b); 1.9 (1H, dd, JH-1b,H-2b = 6.5, JHgem = 12.6,
H-1b); 2.0 (1H, dd, JH-2a,H-1a = 6.0, Jgem = 14.1, H-2a); 2.7 (1H, tdd, JH-1a,H-2a = 6.0, JH-1a,H-2b = 12.6, JH-1a,H-8b = 8.6,
Jgem = 12-6, H-1a); 2.9 (3H, s, CH3); 4.0 (1H, t, JH-8b,H-3a = 8.6, JH-8b,H-1a = 8.6, H-8b); 4.8 (1H, d, JH-3,H-2b = 4.6,
H-3 ); 4.9 (1H, d, JH-3a,H-8b = 8.6, H-3a); 7.1 (1H, t, J = 7.5, H Ar); 7.1-7.2 (2H, m, H Ar); 7.4 (1H, d, J = 7.6,
H Ar). Found, %: C 39.01; H 2.90; I 34.21; N 3.33; S 8.40. C12H14INO2S. Calculated, %: C 39.68; H 3.88;
I 34.94; N 3.86; S 8.83.
N-Methanesulfonyl-3-iodo-5-methyl-1,2,3,3a,4,8b-hexahydrocyclopenta[b]indole (5b). Compound
4b (2 mmol) and I2 (4 mmol) were dissolved in CH2Cl2 (10 ml). The mixture was processed analogously to
compound 5a. Yield 37%; mp 85-97°C (EtOH). 1H NMR spectrum, δ, ppm (J, Hz): 1.5-2.2 (4H, m, 2CH2); 2.4
(3H, s, CH3); 3.0 (3H, s, CH3); 3.9 (1H, dt, J = 3.0, J = 8.1, H-8b); 4.00 (1H, dt, J = 6.1, J = 7.9, H-3); 5.0 (1H,
dd, J = 6.1, J = 8.1, H-3a); 7.0-7.2 (3H, m, H Ar). Found, %: C 41.06; H 3.89; I 33.22; N 3.29; S 8.16.
C13H16INO2S. Calculated, %: C 41.39; H 4.27; I 33.64; N 3.71; S 8.50.
N-Toluenesulfonyl-3-iodo-5-methyl-1,2,3,3a,4,8b-hexahydrocyclopenta[b]indole (5c). Compound 4c
(1.2 mmol) and I2 (2.4 mmol) were dissolved in CH2Cl2 (10 ml). The mixture was processed analogously to
1
compound 5a. Yield 65%; mp 174-177°C (EtOH). H NMR spectrum, δ, ppm (J, Hz): 1.5-1.8 (2H, m, CH2);
1.9-2.0 (2H, m, CH2); 2.1-2.2 (2H, m, CH2); 2.4 (3H, s, CH3); 2.6 (3H, s, CH3); 2.8 (1H, dt, J = 3.0, J = 7.4,
H-8b); 4.1 (1H, dt, J = 5.0, J = 6.0, H-3); 4.7 (1H, dd, J = 5.0, J = 7.7, H-3a); 6.8 (1H, d, J = 6.0, H-8); 7.0-7.2
(4H, m, H Ar); 7.3 (2H, d, J = 8.3, H-2',5'). Found, %: C 49.90; H 4.05; I 27.68; N 2.74; S 6.68. C19H20INO2S.
Calculated, %: C 50.34; H 4.45; I 27.99; N 3.09; S 7.07.
N-Methanesulfonyl-1,3a,4,8b-tetrahydrocyclopenta[b]indole (6a). A solution of compound 5a
(1.4 mmol) in DMF (2 ml) was heated at 180-200°C for 15 h. The solvent was evaporated in vacuum, the residue
dissolved in CH2Cl2 (50 ml), and washed with water (2 × 20 ml). The organic phase was dried over Na2SO4, the
1
solvent removed in vacuum, and the residue recrystallized from EtOH. Yield 90%; mp 115-118°C (EtOH). H
NMR spectrum, δ, ppm (J, Hz): 2.5 (1H, dq, J1 = 1.9, Jgem = 16.9, H-1a); 2.8 (3H, s, CH3); 2.9 (1H,
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qdd, J1 = 2.0, J2 = 8.5, Jgem = 16.9, H-1b); 4.0 (1H, t, J = 8.5, H-8b); 5.4 (1H, d, J = 8.5, H-3a); 5.8 (1H, dd,
J = 2.0, J = 6.2, H-2); 5.9 (1H, dd, J = 1.9, J = 6.2, H-3); 7.0 (1H, t, J = 7.5, H-6); 7.1-7.2 (2H, m, H-7,8); 7.32
(1H, d, J = 7.4, H-5). 13C NMR spectrum, δ, ppm: 35.7 (CH3); 39.6 (C(1)); 42.2 (C(8b)); 73.2 (C(3a)); 114.9 (C(7));
124.1 (C(5)); 125.0 (C(6)); 128.1 (C(8)); 129.4 (C(2)); 133.7 (C(3)); 135.8, 140.0 (C(4a), C(8a)). Found, %: C 60.91;
H 2.17; N 5.21; S 13.32. C12H13NO2S. Calculated, %: C 61.25; H 5.57; N 5.95; S 13.63.
N-Methanesulfonyl-5-methyl-1,3a,4,8b-tetrahydrocyclopenta[b]indole (6b). A solution of compound
5b (0.4 mmol) in piperidine (10 ml) was heated at 110°C for 4 h. The solvent was evaporated in vacuum, the
residue dissolved in CH2Cl2 (50 ml), and washed with water (2 × 20 ml). The organic phase was dried over
Na2SO4, and after removing the solvent in vacuum the yield of crude 6b was 99%. According to the spectral
characteristics this was the sole product. After recrystallization from EtOH the yield of amide 6b was 82.8%; mp
156-159°C (EtOH). 1H NMR spectrum, δ, ppm (J, Hz): 2.3 (3H, s, CH3); 2.5 (1H, d, Jgem = 16.7, H-1a); 2.6 (3H,
s, CH3); 2.8 (1H, ddq, J1 = 2.0, J2 = 7.2, Jgem = 16.7, H-1b); 4.0 (1H, t, J = 7.2, H-8b); 5.4 (1H, dq, J = 2.0, J =
7.2, H-3a); 5.63 (1H, dddd, J = 0.8, J = 1.4, J = 2.0, J = 6.4, H-2); 5.7 (1H, dddd, J = 0.7, J = 0.9, J = 2.0, J =
6.4, H-3); 7.0-7.1 (3H, m, H Ar). Found, %: C 62.28; H 5.79; N 5.24; S 12.41. C13H15NO2S. Calculated, %: C
62.63; H 6.06; N 5.62; S 12.86.
N-Toluenesulfonyl-5-methyl-1,3a,4,8b-tetrahydrocyclopenta[b]indole (6c). A solution of compound
5c (1.2 mmol) in piperidine (2 ml) was heated at 110°C for 4 h. The solvent was evaporated in vacuum, the
residue was dissolved in CH2Cl2 (50 ml), and washed with water (2 × 20 ml). The organic phase was dried over
Na2SO4, and after removing the solvent in vacuum the yield of crude 6c was 96%. After recrystallization from
EtOH yield 60%; mp 165-168°C (EtOH). 1H NMR spectrum, δ, ppm (J, Hz): 2.3 (1H, d, Jgem = 16.6, H-1a); 2.4
(3H, s, CH3); 2.6 (3H, s, CH3); 2.6 (1H, ddd, J1 = 2.0, J2 = 7.6, Jgem = 16.6, H-1b); 2.8 (1H, t, J = 7.0, H-8b); 5.2
(1H, dq, J = 2.0, J = 7.0, H-3a); 5.7 (1H, dd, J = 2.0, J = 6.0, H-2); 5.8 (1H, dd, J = 1.9, J = 6.0, H-3); 6.8 (1H, d,
J = 7.0, H Ar); 7.0-7.1 (4H, m, H Ar); 7.3 (2H, d, J = 8.6, H-2',5'). Found, %: C 69.76; H 5.47; N 3.98; S 9.57.
C12H13NO2S. Calculated, %: C 70.13; H 5.88; N 4.30; S 9.85.
3-(5-Methyl-1,2,3,3a,4,8b-hexahydrocyclopenta[b]indolyl)pyridinium Iodide (8). A solution of
amine 7 (3 mmol) in MeCN (20 ml) and pyridine (6 mmol) was heated at 75-80°C for 6-8 h. The solvent was
evaporated in vacuum, the residue dissolved in hot water, and decanted from the oily insoluble solid. The
crystals of compound 8, which precipitated on cooling to room temperature, were filtered off, and dried in
vacuum. Yield 57%; mp 203-205°C (H2O). IR spectrum, ν, cm-1: 3220 (NH). 1H NMR spectrum, δ, ppm (J, Hz):
1.6-1.8 (2H, m, CH2); 2.2-2.4 (2H, m, CH2); 4.1 (1H, m, H-8b); 4.6 (1H, dd, J = 1.0, J = 7.0, H-3a); 4.9 (1H, m,
H-3); 6.0 (1H, br s, NH); 6.6 (1H, t, J = 7.3, H-7); 6.8 (1H, d, J = 7.3, H Ar); 6.9 (1H, d, J = 7.3, H Ar); 8.2 (2H,
m, H-3',5'); 8.7 (1H, t, J = 7.7, H-4'); 9.3 (2H, d, J = 5.8, H-2',6'). 13C NMR spectrum, δ, ppm: 16.8 (CH3); 31.1,
32.5 (2CH2); 46.0 (C(8b)); 69.1 (C(3)); 79.7 (C(3a)); 117.9 (C(8a)); 118.0 (C(7)); 128.2 (C(3',5')); 128.4 (C(8)); 130.8
(C(5)); 143.6 (C(2',6')); 145.6 (C(4')); 148.3 (C(4a)). Found, %: C 53.68; H 5.36; I 33.25; N 7.11. C17H19IN2.
Calculated, %: C 53.98; H 5.06; I 33.55; N 7.41.
3-Iodo-1,2,3,3a,4,8b-hexahydrocyclopenta[b]indole (5d). Compound 4d (3 mmol) and I2 (6 mmol)
1
were dissolved in CH2Cl2 (10 ml). Processing was analogous to compound 5a. Yield 82%. H NMR spectrum,
δ, ppm (J, Hz): 1.8-2.7 (4H, m, 2CH2); 3.8 (1H, br s, NH); 4.0 (1H, t, J = 8.0, H-8b); 4.2 (1H, m, H-3); 4.8 (1H,
dd, J1 = 1.1, J2 = 8.0, H-3a); 6.5 (1H, d, J = 7.8, H Ar); 6.7 (1H, dt, J1 = 0.9, J2 = 8.3, H Ar); 7.0-7.1 (2H, m,
H Ar). Found, %: C 46.32; H 4.23; I 44.49; N 4.90. C11H12IN. Calculated, %: C 46.34; H 4.24; I 44.51; N 4.91.
The work was carried out with the financial support of the Science School of Academician G. A. Tolstikov
(Grant of the President of the Russian Federation No. NSh-1488.2003.3).
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