Synthesis of N-acetyl-3,3a,4,8b- and -1,3a,4,8b-tetrahydrocyclopenta[b] indoles from N- and 2-(cyclopent-2-en-1-yl)anilines

Article abstract of DOI:10.1134/S1070428012120093

Reactions of 2-bromo-N-(cyclopent-2-en-1-yl)-4-methylaniline and N-(cyclopent-2-en-1-yl)-2-iodo-4,6-dimethylaniline with acetyl bromide in the presence of potassium carbonate gave mixtures of syn and anti atropisomers of the corresponding N-acetyl derivatives at ratios of 1: 1 and 3: 2 respectively. Heating of these mixtures in toluene in the presence of Pd(OAc)₂, PPh₃, Et₃N, and K₂CO₃ (KOAc) afforded mixtures of isomeric N-acetyl-7-methyl-3,3a,4,8b- and -1,3a,4,8b-tetrahydrocyclopenta[b]indoles at a ratio of 3: 1 or N-acetyl-5,7-dimethyl-3,3a,4,8b- and -1,3a,4,8b-tetrahydrocyclopenta[b]indoles at a ratio of 2: 3. N-Acetyl-3,3a,4,8b-tetrahydrocyclopenta[b]indole was found to undergo thermal isomerization into N-acetyl-1,3a,4,8btetrahydrocyclopenta[b] indole.

Full text of DOI:10.1134/S1070428012120093

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2012, Vol. 48, No. 12, pp. 1550–1556. © Pleiades Publishing, Ltd., 2012.
Original Russian Text © D.A. Skladchikov, R.S. Buranbaeva, A.A. Fatykhov, S.P. Ivanov, R.R. Gataullin, 2012, published in Zhurnal Organicheskoi Khimii,
2012, Vol. 48, No. 12, pp. 1579–1585.
Synthesis of N-Acetyl-3,3a,4,8b- and -1,3a,4,8b-tetrahydro-
cyclopenta[b]indoles from N- and 2-(Cyclopent-2-en-1-yl)anilines
D. A. Skladchikov, R. S. Buranbaeva, A. A. Fatykhov, S. P. Ivanov, and R. R. Gataullin
Institute of Organic Chemistry, Ufa Research Center, Russian Academy of Sciences,
pr. Oktyabrya 71, Ufa, 450054 Bashkortostan, Russia
e-mail: gataullin@anrb.ru
Received April 18, 2012
Abstract—Reactions of 2-bromo-N-(cyclopent-2-en-1-yl)-4-methylaniline and N-(cyclopent-2-en-1-yl)-2-
iodo-4,6-dimethylaniline with acetyl bromide in the presence of potassium carbonate gave mixtures of syn and
anti atropisomers of the corresponding N-acetyl derivatives at ratios of 1:1 and 3:2 respectively. Heating of
these mixtures in toluene in the presence of Pd(OAc)2, PPh3, Et3N, and K2CO3 (KOAc) afforded mixtures of
isomeric N-acetyl-7-methyl-3,3a,4,8b- and -1,3a,4,8b-tetrahydrocyclopenta[b]indoles at a ratio of 3:1 or
N-acetyl-5,7-dimethyl-3,3a,4,8b- and -1,3a,4,8b-tetrahydrocyclopenta[b]indoles at a ratio of 2:3. N-Acetyl-
3,3a,4,8b-tetrahydrocyclopenta[b]indole was found to undergo thermal isomerization into N-acetyl-1,3a,4,8b-
tetrahydrocyclopenta[b]indole.
DOI: 10.1134/S1070428012120093
Cyclopenta[b]indole fragment is a structural unit
of some natural biologically active compounds, e.g.,
tremorgenic alkaloid paxilline produced by Penicillium
paxilli [1], structurally related paspaline and paspa-
licine [2], paspalinine [3], lecanindoles A–D [4], some
synthetic heterocycles [5], nodulisporic acid A [6], and
alkaloids polyavolinamide [7] and polyveoline [8].
High resistance to photoinduced degradation was the
key factor that determined the choice of the cyclo-
penta[b]indole fragment as a component of photo-
chromic molecules used as molecular switches [9–11].
Some cyclopenta[b]indoles exhibited biological activ-
ity comparable with the activity of prostaglandins [12]
or inhibited acid corrosion of metals [13]. Taking into
account the above useful properties, cyclopenta[b]-
indoles attract researchers’ attention [14–17].
mers of Ib were isolated as individual substances by
HPLC. The structure of different isomers of Ia and Ib
was assigned on the basis of their H NMR spectra
1
with account taken of published data [20]. In partic-
ular, olefinic protons in the cyclopentene ring of the
anti-atropisomer of N-acetyl-N-(cyclohex-2-en-1-yl)-
2-haloaniline Ia resonated in a weaker field as com-
pared to the syn isomer. Analogous difference was also
observed in the positions of the corresponding protons
1
in the H NMR spectra of the syn- and anti-atrop-
isomers of Ib.
In the 1H NMR spectra of Ia and Ib the signal from
1′-H in the cyclopentene ring is low informative, for its
position was the same for the syn- and anti-isomers of
both bromo derivative Ia and iodo-substituted com-
pound Ib. Some differences in the spectrum of
syn/anti-isomer mixture Ia were observed only for the
olefinic protons in the cyclopentene ring and for aro-
In the present work we synthesized 3,3a,4,8b- and
1,3a,4,8b-tetrahydrocyclopenta[b]indole structures
starting from N- and 2-(cyclopent-2-en-1-yl)anilines
[18, 19]. The alkylation of 2-haloanilines IXa and IXb
with 3-chlorocyclopentene in the presence of triethyl-
amine and subsequent treatment of N-(cyclopent-2-en-
1-yl)anilines Xa and Xb gave compounds Ia and Ib as
mixtures of syn- and anti-atropisomers at ratios of 1:1
and 3:2, respectively (Scheme 1). We failed to isolate
individual atropisomers of Ia because of the low bar-
rier to their interconversion, but syn- and anti-atropiso-
1
matic protons. Taking into account the H NMR data
for the syn- and anti-atropisomers of Ib, we succeeded
in reliably assigning only the 3′-H proton in anti-Ia
(δ 5.85 ppm). The signals from 3′-H in syn-Ia and 2′-H
in both atropisomers of Ia overlapped each other.
Compound Ia was subjected to heterocyclization on
heating in toluene in the presence of Pd(OAc)2, PPh3,
Et3N, and K2CO3 to obtain cyclopenta[b]indole IIa and
its regioisomer IIIa [19] at a ratio of 3:1 (HPLC).
1550

SYNTHESIS OF N-ACETYL-3,3a,4,8b- AND -1,3a,4,8b-TETRAHYDRO...
1551
Scheme 1.
H
H
Ac
Ac
HN
N
N
AcBr, K2CO3
CH2Cl2
Me
X
R
X
R
X
X
R
Et3N
+
+
Cl
NH2
R
Me
Me
Me
anti-Ia, anti-Ib
IXa, IXb
Xa, Xb
syn-Ia, syn-Ib
X
PdLn
X
H
Me
PdLn
Me
Pd(OAc)2, PPh3, Et3N, K2CO3
(or KOAc), MePh, reflux
H
N
N
Ac
R
Ac
R
VII
VIII
1
H
H
Me
Me
syn-Elimination
PhMe, reflux
3
+
IIa, IIb
IIIa, IIIb
–[HPdL2X]
H
H
N
N
Ac
Ac
R
R
IIa, IIb
IIIa, IIIb
Me
Me
Ia, Ib
N
NH
Ac
R
Ac
R
IVa, IVb
Va, Vb
H
Pd(OAc)2, PPh3, Et3N
K2CO3, MePh, reflux
Me
IIIa, IIIb
PdLn
H
N
Ac
VIa, VIb
R
R = H, X = Br (a); R = Me, X = I (b).
Likewise, heterocyclization of syn/anti-Ib [Pd(OAc)2,
PPh3, KOAc] gave isomeric cyclopenta[b]indoles IIb
and IIIb at a ratio of 2:3 (overall yield 69%, con-
version 85%).
ative Va or Vb. However, this assumption was not
confirmed. Amide IVa remained unchanged upon pro-
longed heating under analogous conditions.
In parallel, o-cyclopentenylanilide Va was subject-
ed to Pd(OAc)2-catalyzed oxidative cyclization, which
afforded a mixture of isomers IIa and IIIa at a ratio of
1:3 in an overall yield of 59%, as well as a consider-
able amount of anilide XI [21] (Scheme 2).
It would be presumed that compounds IIIa and
IIIb were formed as a result of a series of consecutive
reactions, including the formation of amide IVa or IVb
via replacement of the bromine or iodine atom by
hydrogen, catalyzed by compounds present in the reac-
tion mixture, aromatic amino-Claisen rearrangement,
and oxidative cyclization of ortho-substituted deriv-
Compound III is formed via thermal isomerization
of II in the course of cyclization of anilide I. After
heating of individual compound IIa in boiling toluene
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 48 No. 12 2012

SKLADCHIKOV et al.
1552
Scheme 2.
H
H
Pd(OAc)2, PhMe–C5H5N (5:1)
air, reflux
Me
Me
Me
PdLn
–[PdH]Ln
H
H
N
N
NHAc
Ac
Ac
Va
IIa
H
Me
Me
+
+
H
N
NHAc
Ac
IIIa
XI
H
Me
PdLn
[PdH]Ln
IIIa
IIa
–[PdH]Ln
H
N
Ac
Scheme 3.
H
Pd(OAc)2, PhMe–C5H5N (5:1)
air
Ac2O
H
N
Ac
XIIIa, XIIIb
NH2
NHAc
R
XIVa, XIVb
R
R
XIIa, XIIb
R = Me (a), MeO (b).
for 80 h, the signal intensity ratio of the 8b-H or 3a-H
protons in the H NMR spectrum of mixture IIa/IIIa
reached 1:1. When compound IIIa was heated for
a long time in boiling toluene or piperidine, no ap-
preciable change in the composition of the solution
was observed. Presumably, the formation of IIa in the
oxidative cyclization of Va is the result of subsequent
catalytic transformation of compound IIIa. Palla-
dium(II) acetate-catalyzed oxidative cyclization of
XIIa and XIIb gave cyclopenta[b]indoles XIIIa and
XIIIb in 38 and 49%, respectively (Scheme 3).
1
The H and 13C NMR spectra of IIa displayed
1
double sets of signals (see figure). The signal intensity
ratio for 8b-H or 3a-H depended on the solvent nature
and was 4:1 in CDCl3 and 5:1 in C6D6. We previously
55°C
1
observed doubling of signals in the H NMR spectrum
of cyclopenta[b]indole IIIa [19]. This pattern is likely
to result from restricted rotation about the formally
single C–N bond between the endocyclic nitrogen
atom and acetyl carbonyl carbon atom [22, 23]. If the
ortho position is occupied by a substituent, such rota-
tion becomes impossible. The existence of an energy
barrier to such rotation makes it possible to distinguish
metastable cis and trans isomers of IIa with syn or
anti arrangement of the acetyl methyl group with
respect to C3a. No signal doubling was observed in the
1H NMR spectra of IIa recorded at 55°C in CDCl3 and
at 38°C in C6D6.
30°C
20°C
5.4
5.2
5.0
4.8
4.6
4.4
4.2
δ, ppm
Resonance region of the 2-H and 3-H protons in the 1H NMR
spectrum of compound IIa in CDCl3 at different tempera-
tures.
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SYNTHESIS OF N-ACETYL-3,3a,4,8b- AND -1,3a,4,8b-TETRAHYDRO...
1553
Using one-dimensional difference NOE experi-
ments we found that the major signals belong to
syn-IIa. Saturation of the COCH3 signal increased the
intensity of the 3a-H signal only of the major isomer,
whereas the intensity of the minor signal (δ 5.16 ppm)
did not change.
Thus, both palladium-catalyzed intramolecular
Heck reaction of N-acetyl-2-bromo-N-(cyclopent-2-en-
1-yl)-4-methylaniline and N-acetyl-N-(cyclopent-2-en-
1-yl)-2-iodo-4,6-dimethylaniline as mixtures of syn-
and anti-atropisomers and palladium(II) acetate-cata-
lyzed oxidative cyclization of N-acetyl-2-(cyclopent-2-
en-1-yl)-4-methylaniline on heating in toluene lead to
the formation of mixtures of regioisomeric N-acetyl-
3,3a,4,8b- and -1,3a,4,8b-tetrahydrocyclopenta[b]in-
doles. Restricted rotation about the amide C–N bond in
N-acetyl-7-methyl-3,3a,4,8b- and -1,3a,4,8b-tetrahy-
drocyclopenta[b]indoles is responsible for signal
doubling in their NMR spectra. No such doubling is
observed in the spectra of their analogs having a sub-
stituent on C5.
H
H
Me
Me
H
H
O
N
N
Me
O
Me
syn-IIa
anti-IIa
H
H
Me
Me
EXPERIMENTAL
H
H
O
N
N
Me
The IR spectra were recorded on a Shimadzu IR
Prestige-21 spectrometer with Fourier transform. The
1H and 13C NMR spectra were measured on a Bruker
AM 300 instrument at 300.13 and 75.45 MHz, respec-
tively, and on a Bruker Avance III 500 spectrometer at
500.13 and 125.73 MHz, respectively. The chemical
shifts were determined relative to tetramethylsilane as
internal reference. The elemental compositions were
determined on a Hewlett Packard M-185B CHN ana-
lyzer. The mass spectrum (atmospheric pressure chem-
ical ionization) was obtained on an LCMS-2010EV
instrument using methanol–water (50:50) as eluent.
The purity of liquid samples was checked by GLC on
a Khromos GKh-1000 chromatograph equipped with
a flame ionization detector and a 1-m×3-mm column
packed with 5% of SE 30 on Chromaton N-AW;
carrier gas helium. Qualitative TLC analysis was per-
formed on Sorbfil PTSKh-AF-V-UF plates (Sorb-
polimer Ltd., Krasnodar, Russia); spots were detected
under UV light (λ 254 nm) or by treatment with iodine
vapor.
O
Me
syn-IIIa
anti-IIIa
The use of IR spectroscopy turned out not to be
helpful in detecting amide conjugation. Compound IIa
displayed in the IR spectrum a strong absorption band
at 1649 cm–1 which, in keeping with published data,
may be assigned equally to carbonyl stretching vibra-
tions [22, 24] and cis-configured double C1=C2 bond in
the cyclopentene ring [24].
One-dimensional difference NOE experiments with
indole IIIa showed 3.35% increase in the intensity of
the acetyl proton signal upon saturation of the 3a-H
resonance at δ 5.34 ppm [19], which is possible for
structure syn-IIIa. Analogous NOE experiments
allowed us to assign signals from the 1-HA and 1-HB
protons, as well as their orientation with respect to
8b-H. Saturation of the 1-HA resonance signal
(δ 2.65 ppm) [19] did not change the intensity of the
8b-H signal, indicating their mutual trans orientation.
Correspondingly, cis arrangement of 8b-H and 1-HB
followed from the 3.11% increase of the 8b-H signal
intensity upon saturation of the 1-HB resonance at
δ 2.95 ppm (d.d.q).
2-Bromo-4-methyl-N-(cyclopent-2-en-1-yl)acet-
anilide (Ia, a mixture of syn- and anti-atropisomers).
Acetyl bromide, 1.4 ml (20 mmol), was added to a so-
lution of 2.52 g (10 mmol) of compound Xa in 10 ml
of chloroform. The mixture was stirred for 30 min, and
2.76 g (20 mmol) of potassium carbonate was added.
When the reaction was complete, 50 ml of chloroform
and a saturated solution of NaHCO3 were added, the
mixture was shaken until carbon dioxide no longer
evolved, the organic phase was separated, washed with
water (3×100 ml), dried over MgSO4, and evaporated,
and the residue was subjected to chromatography on
1
The H NMR spectra of cyclopenta[b]indoles IIb,
IIIb, XIIIa, and XIIIb having a substituent in the
ortho position of the benzene fragment contained only
one set of signals.
The structure of the newly synthesized compounds
was determined on the basis of their elemental compo-
sitions and spectral parameters. Signals from protons
therein were assigned using HH COSY, H–15N
1
HMBC, and 1H–13C HSQC techniques.
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SKLADCHIKOV et al.
1554
silica gel (230–400 mesh) using benzene as eluent to
isolate 0.65 g (26%) of the initial aniline. Subsequent
elution with benzene–ethyl acetate (9:1) gave 1.97 g
(67%) of Ia (90% on the reacted compound Xa; con-
(59%) of a 3:1 mixture (HPLC) of compounds IIa and
IIIa, Rf 0.35 (PhH–EtOAc, 9:1). Pure compound IIa,
0.02 g, was isolated by HPLC, mp 122°C. IR spectrum,
ν, cm–1: 1649 s (C=O or C1=C2), 1489 s, 1458 m,
1
1
version 74%); Rf 0.55 (PhH–EtOAc, 4:1). H NMR
1388 s, 817 m, 727 m. H NMR spectrum (CDCl3), δ,
spectrum (CDCl3), δ, ppm: 1.77 s and 1.78 s (3H each,
CH3), 1.80–2.53 m (8H, CH2), 2.35 s (6H, CH3), 5.54–
5.61 m (2H, 1′-Hsyn, 1′-Hanti), 5.70–5.80 m (3H, 2′-Hsyn,
2′-Hanti, 3′-Hsyn), 5.85 d.q (1H, 3′-Hanti, J = 2.0, 5.6 Hz),
7.00 d and 7.03 d (1H each, 6-H, J = 8.3 Hz), 7.10 m
(2H, 5-Hsyn, 5-Hanti), 7.47 d and 7.49 d (1H each, 3-H,
J = 1.3 Hz). 13C NMR spectrum (CDCl3), δC, ppm:
20.6, 20.7, 22.9, 23.0 (CH3); 26.2, 30.8, 31.1, 31.2 (C4′,
C5′); 61.9, 62.5 (C1′); 125.1, 125.5, 128.8, 128.9, 129.0,
130.0 (C2′, C6, C7); 130.8, 131.0 (C3); 133.8, 133.9
(C3′); 134.7, 135.2 (C2); 136.4, 137.6 (C4); 139.9,
140.0 (C1); 170.3, 170.4 (C=O). Found, %: C 57.11;
H 5.41; Br 27.08; N 4.72. C14H16BrNO. Calculated, %:
C 57.16; H 5.48; Br 27.16; N 4.76.
ppm: 2.27 s (3H, CH3), 2.34 s (3H, CH3), 2.59 d (1H,
3-HA, J = 17.4 Hz), 3.11 d.d (1H, 3-HB, J = 8.7,
17.4 Hz), 4.35 (minor, 1H, 8b-H, J = 8.7 Hz), 4.52 d
(major, 1H, 8b-H, J = 8.7 Hz), 5.03 d.t (major, 1H,
3a-H, J = 3.6, 8.7 Hz), 5.20 d.t (minor, 1H, 3a-H, J =
3.6, 8.7 Hz), 5.71–5.90 m (2H, 1-H, 2-H), 6.95–7.05 m
(2H, Harom), 8.10 d (1H, 6-H, J = 8.2 Hz). 13C NMR
spectrum (CDCl3), δC, ppm (major isomer): 20.9, 24.0
(CH3); 42.6 (C3), 53.0 (C8b), 63.3 (C3a), 117.3 (C2);
124.2, 128.2, 129.3, 131.0 (C1, C5, C6, C8); 133.1,
133.5, 139.7 (C4a, C7, C8a); 168.6 (C=O). 15N NMR
spectrum (CDCl3): δN 155 ppm (N4). Found, %:
C 78.64; H 6.90; N 6.37. C14H15NO. Calculated, %:
C 78.84; H 7.09; N 6.57.
N-(Cyclopent-2-en-1-yl)-2-iodo-4,6-dimethyl-
acetanilide (Ib, a mixture of syn- and anti-atrop-
isomers) was synthesized in a similar way from 2.1 g
(6.8 mmol) of N-cyclopentenylaniline Xb. Yield 1.31 g
(54%), viscous material, Rf 0.3 (PhH–EtOAc, 9:1).
Analytical samples of individual atropisomers, 0.02 g
N-Acetyl-5,7-dimethyl-3,3a,4,8b-tetrahydrocy-
clopenta[b]indole (IIb). The cyclization of atrop-
isomer mixture Ib was performed in a similar way. By
chromatography on silica gel using benzene as eluent
we isolated 0.16 g (69%) of a mixture of compounds
IIb and IIIb at a ratio of 2:3 (1H NMR), Rf 0.46
1
1
each, were isolated by HPLC. H NMR spectrum
(PhH–EtOAc, 9:1). H NMR spectrum (CDCl3), δ,
(CDCl3), δ, ppm: syn-Ib: 1.72 s (3H, CH3), 2.17 s (3H,
CH3), 2.28 s (3H, CH3), 2.00 m (1H, 5′-HA), 2.23–
2.50 m (2H, CH2), 2.62 m (1H, 5′-HB), 5.23–5.29 m
(1H, 1′-H), 5.32 d.q (1H, 2′-H, J = 2.3, 5.6 Hz),
5.77 d.q (1H, 3′-H, J = 2.3, 5.6 Hz), 7.01 s (1H, Harom),
7.57 s (1H, Harom); anti-Ib: 1.73 s (3H, CH3), 1.87 m
(1H, 5′-HA), 2.21 s (3H, CH3), 2.28 s (3H, CH3), 2.23–
2.43 m (3H, CH2, 5′-HB), 5.23–5.29 m (1H, 1′-H), 5.60
d.q (1H, 2′-H, J = 2.0, 5.6 Hz), 5.83 d.q (1H, 3′-H, J =
2.0, 5.6 Hz), 7.03 s (1H, Harom), 7.57 s (1H, Harom).
Found, %: syn-Ib: C 50.63; H 5.02; I 35.60; N 3.88;
anti-Ib: C 50.64; H 5.06; I 35.67; N 3.90. C15H18INO.
Calculated, %: C 50.72; H 5.11; I 35.73; N 3.94.
ppm: 2.27 s (3H, CH3), 2.31 s (3H, CH3), 2.34 s (3H,
CH3), 2.48 d (1H, 3-HA, J = 17.4 Hz), 3.08 d.d.t (1H,
3-HB, J = 2.2, 8.9, 17.1 Hz), 4.50 d (1H, 8b-H, J =
7.7 Hz), 5.09 br.s (1H, 3a-H), 5.78–5.81 m (1H, 1-H),
5.91–5.97 m (1H, 2-H), 6.84 s (1H, Harom), 6.91 s (1H,
Harom). Found, %: C 79.18; H 7.45; N 6.09. C15H17NO.
Calculated, %: C 79.26; H 7.54; N 6.16.
N-Acetyl-5-methyl-1,3a,4,8b-tetrahydrocyclo-
penta[b]indole (IIIa). A solution of 0.215 g (1 mmol)
of acetanilide Va, 0.027 g (0.1 mmol) of palladium(II)
acetate in a mixture of 1 ml of toluene and 0.2 ml of
pyridine was heated for 4 h in a 10-ml pear-shaped
flask while continuously bubbling air through the solu-
tion. The solvent was evaporated under reduced pres-
sure, and the residue was subjected to column chroma-
tography on silica gel (1 g) using benzene as eluent to
isolate 0.123 g (59%) of a mixture of compounds IIIa
and IIa at a ratio of 3:1. An analytical sample of IIIa
was isolated by HPLC; its physical constants were
identical to those reported in [19]. Further elution gave
0.032 g (15%) of compound XI [21].
N-Acetyl-7-methyl-3,3a,4,8b-tetrahydrocyclo-
penta[b]indole (IIa). A solution of 0.025 g
(0.12 mmol) of Pd(OAc)2 and 0.06 g (0.24 mmol) of
PPh3 in 2 ml of toluene was heated for 15 min, 0.35 g
(1.2 mmol) of compound Ia and 0.3 ml (0.3 mmol) of
triethylamine were added, the mixture was heated for
5 h under reflux, and additional portions of Pd(OAc)2
(0.12 mmol) and PPh3 (0.24 mmol) were added two
times. The mixture was analyzed by TLC every 10 h.
The solvent was evaporated under reduced pressure,
and the residue was subjected to chromatography on
silica gel using benzene as eluent to isolate 0.15 g
N-Acetyl-5,7-dimethyl-1,3a,4,8b-tetrahydro-
cyclopenta[b]indole (IIIb). A sample of IIIb, 0.035 g,
containing 85% of the main substance was isolated by
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SYNTHESIS OF N-ACETYL-3,3a,4,8b- AND -1,3a,4,8b-TETRAHYDRO...
1555
1
HPLC from a mixture of IIb with IIIb. H NMR
spectrum (CDCl3), δ, ppm: 2.26 s (3H, CH3), 2.30 s
(3H, CH3), 2.35 s (3H, CH3), 2.58 d (1H, 1-HA, J =
16.5 Hz), 2.89 d.d.q (1H, 1-HB, J = 2.0, 7.7, 16.5 Hz),
4.00 br.s (1H, 8b-H), 5.37 br.s (1H, 3a-H), 5.75–
5.80 m (1H, 1-H), 5.88–5.92 m (1H, 2-H), 6.85 s (1H,
5 h at 90°C, cooled to 20°C, treated with 20 ml of 10%
aqueous sodium hydroxide under thorough stirring,
and extracted with benzene. The extract was dried over
potassium hydroxide and evaporated, and the residue
was subjected to chromatography on silica gel using
petroleum ether–benzene (9:1) as eluent. Yield 3.68 g
(66%), yellowish transparent liquid, Rf 0.4 (petroleum
ether–benzene, 2:1). IR spectrum: ν 3407 cm–1 (NH).
1H NMR spectrum (CDCl3), δ, ppm: 1.75 d.q (1H,
5′-HA, J = 2.0, 17.0 Hz), 2.15–2.30 m (2H, CH2),
2.25 s (3H, CH3), 2.35 s (3H, CH3), 2.50–2.60 m (1H,
5′-HB), 3.30 br.s (1H, NH), 4.35 m (1H, 1′-H), 5.80–
5.95 m (2H, HC=CH), 6.95 s (1H, Harom), 7.45 s
(1H, Harom). Found, %: C 49.78; H 5.09; I 40.41;
N 4.40. C13H16IN. Calculated, %: C 49.86; H 5.15;
I 40.52; N 4.47.
H
arom), 6.88 s (1H, Harom). Found, %: C 79.19; H 7.47;
N 6.11. C15H17NO. Calculated, %: C 79.26; H 7.54;
N 6.16.
N-(Cyclopent-2-en-1-yl)-4-methylacetanilide
(IVa). Acetic anhydride, 1 ml (9.8 mmol), was added
to 1.1 g (6.5 mmol) of N-cyclopentenylaniline Xb [18].
The mixture was poured into a saturated solution of
sodium hydrogen carbonate, and the precipitate was
filtered off, washed with water, and dried under
reduced pressure. Yield 1.3 g (93%), mp 56°C, Rf 0.46
1
N-Acetyl-5-methyl-1,3a,4,8b-tetrahydrocyclo-
penta[b]indole (XIIIa) was synthesized as described
above for IIIa from 0.392 g (1.82 mmol) of anilide
XIIa. Conversion 92%, yield 0.15 g (38%), mp 86–
88°C. IR spectrum, ν, cm–1: 1662 s, 1647 m (C=O or
C1=C2), 1462 s, 1442 m, 1396 s, 1379 m, 1261 m,
(PhH–EtOAc, 9:1). H NMR spectrum (CDCl3), δ,
ppm: 1.60–2.20 m (4H, CH2), 1.70 s and 2.25 s (3H
each, CH3), 5.50–5.70 m (2H, HC=CH), 5.75–5.80 m
(1H, 3′-H), 6.85 d (2H, 2-H, 6-H, J = 8.1 Hz), 7.05 d
(2H, 3-H, 5-H, J = 8.1 Hz). 13C NMR spectrum
(CDCl3), δC, ppm: 20.8 and 23.0 (CH3), 27.8 and 30.9
(CH2), 60.8 (C1′), 129.4 (C2, C3, C5, C6), 130.3 and
134.5 (HC=CH), 137.0 and 137.6 (C1, C4), 170.4
(C=O). Found, %: C 78.04; H 7.91; N 6.47. C14H17NO.
Calculated, %: C 78.10; H 7.96; N 6.51.
1
786 m, 763 m, 715 m, 659 m, 424 m. H NMR spec-
trum (CDCl3), δ, ppm: 2.20 s (3H, CH3), 2.35 s (3H,
CH3), 2.57 d (1H, 1-HA, J = 16.6 Hz), 2.90 d.d.q (1H,
1-HB, J = 2.0, 8.0, 16.6 Hz), 4.05 t (1H, 8b-H, J =
8.0 Hz), 5.40 br.s (1H, 3a-H), 5.74–5.77 m (1H, 3-H),
5.85–5.87 m (1H, 2-H), 6.97–7.03 m (3H, Harom).
Found, %: C 78.71; H 6.95; N 6.48. C14H15NO. Cal-
culated, %: C 78.84; H 7.09; N 6.57.
2-Bromo-4-methyl-N-(cyclopent-2-en-1-yl)-
aniline (Xa). Excess 3-chlorocyclopentene was added
to a solution of 6.2 g (0.033 mol) of 2-bromo-4-
methylaniline (IXa) in 20 ml of triethylamine, and the
mixture was heated for 4 h at 90°C (on a water bath).
The mixture was cooled to room temperature, 30 ml of
benzene was added, the mixture was neutralized with
excess alkali solution, and the organic phase was sepa-
rated and dried over pelletized potassium hydroxide.
The solvent was removed, and the residue was distilled
under reduced pressure. Yield 5.46 g (65%), bp 144°C
N-Acetyl-5-methoxy-1,3a,4,8b-tetrahydrocyclo-
penta[b]indole (XIIIb) was synthesized as described
above for IIIa from 0.46 g (1.99 mmol) of acetanilide
XIIb. Yield 0.225 g (49%), viscous material, Rf 0.5
1
(PhH–EtOAc, 2:1). H NMR spectrum (CDCl3), δ,
ppm: 2.13 s (3H, CH3), 2.53 d (1H, 1-HA, J = 16.6 Hz),
2.89 d.d.t (1H, 1-HB, J = 2.0, 4.0, 16.6 Hz), 3.83 s (3H,
OCH3), 3.93 t (1H, 8b-H, J = 7.6 Hz), 5.70–5.85 m
(3H, 2-H, 3-H, 3a-H), 6.79 d (1H, Harom, J = 8.3 Hz),
6.86 d (1H, Harom, J = 7.6 Hz), 7.09 d.d (1H, 7-H, J =
8.3, 7.6 Hz). Found, %: C 73.22; H 6.51; N 6.02.
C14H15NO2. Calculated, %: C 73.34; H 6.59; N 6.11.
1
(2 mm). IR spectrum: ν 3402 cm–1 (NH). H NMR
spectrum (CDCl3), δ, ppm: 1.60–1.70 m (1H, 5′-HA),
2.20 s (3H, CH3), 2.30–2.55 m (3H, 5′-HB, 4′-H),
4.10 br.s (1H, NH), 4.55 br.s (1H, 1′-H), 5.80–5.95 m
(2H, HC=CH), 6.64 d (1H, Harom, J = 8.3 Hz), 6.98 d
(1H, Harom, J = 8.3 Hz), 7.25 s (1H, 3-H). Found, %:
C 57.11; H 5.56; Br 31.62; N 5.49. C12H14BrN. Cal-
culated, %: C 57.16; H 5.60; Br 31.69; N 5.55.
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