Synthesis of 9-arylamino- and (Z)-9-arylimino-9H-pyrrolo[1,2-a]indoles by reactions of 2-(pyrrol-1-yl)benzaldehydes with aryl amines

Article abstract of DOI:10.1016/j.tet.2007.02.129

Heating mixtures of 2-(pyrrol-1-yl)benzaldehydes and aryl amines under argon afforded 9-arylamino-9H-pyrrolo[1,2-a]indoles, via cyclization of the resulting 2-(pyrrol-1-yl)benzaldimine intermediates. Heating in the presence of oxygen afforded (Z)-9-arylim

Full text of DOI:10.1016/j.tet.2007.02.129

Tetrahedron 63 (2007) 4356–4359
Synthesis of 9-arylamino- and (Z)-9-arylimino-9H-pyrrolo-
[1,2-a]indoles by reactions of 2-(pyrrol-1-yl)-
benzaldehydes with aryl amines
*
Kazuhiro Kobayashi, Yasutoshi Himei, Shuhei Fukamachi, Miyuki Tanmatsu,
Osamu Morikawa and Hisatoshi Konishi
Department of Materials Science, Faculty of Engineering, Tottori University, 4-101 Koyama-minami, Tottori 680-8552, Japan
Received 26 January 2007; accepted 26 February 2007
Available online 12 March 2007
Dedicated to the memory of Professor Yoshihiko Ito
Abstract—Heating mixtures of 2-(pyrrol-1-yl)benzaldehydes and aryl amines under argon afforded 9-arylamino-9H-pyrrolo[1,2-a]indoles,
via cyclization of the resulting 2-(pyrrol-1-yl)benzaldimine intermediates. Heating in the presence of oxygen afforded (Z)-9-arylimino-9H-
pyrrolo[1,2-a]indoles, which were successfully hydrolyzed with hydrochloric acid to give pyrrolo[1,2-a]indol-9-ones.
Ó 2007 Elsevier Ltd. All rights reserved.
1. Introduction
2. Results and discussion
As a part of our program aimed at developing new methods
for the preparation of fused-heterocycles using 2-(pyrrol-
1-yl)benzaldehydes as starting materials,1 we previously
described the one-pot preparation of 9-dialkylamino-9H-
pyrrolo[1,2-a]indoles by reactions of 2-(pyrrol-1-yl)-
benzaldehydes with secondary amine hydrochlorides in the
presence of sodium iodide, chlorotrimethylsilane, and
triethylamine.1b In this paper we wish to report that 9-
arylamino- and (Z)-9-arylimino-9H-pyrrolo[1,2-a]indoles2
are conveniently prepared by simply treating 2-(pyrrol-
1-yl)benzaldehydes with aryl amines. To the best of our
knowledge, synthesis of 9H-pyrrolo[1,2-a]indole derivatives
carrying an arylamino (or arylimino) substituent at the 9-
position has not been reported, though the synthesis of
9-alkylamino and 9-alkylimino derivatives have been
recorded.3 We also report that the 9-arylimino derivatives
can be easily converted into the corresponding pyrrolo-
[1,2-a]indol-9-one derivatives.4 The 9H-pyrrolo[1,2-a]-
indole skeleton has held considerable interest, because it is
the basic framework of cytostatic mytomycine derivatives.5
2.1. Synthesis of 9-arylamino-9H-pyrrolo[1,2-a]indoles 2
Intramolecular cyclization of 2-(pyrrol-1-yl)benzaldimines,
generated from 2-(pyrrol-1-yl)benzaldehydes 1 with aryl
amines, has been used in the synthesis of 2. Thus, treatment
of 1 with 2 M amounts of aryl amines at 90 ꢀC without sol-
vent under argon for 8 h afforded 2 in generally good yields,
as shown in Scheme 1. The yields of 2b and 2e are somewhat
lower than those of the others. This may be attributable to
less reactivity of the corresponding aldimine intermediates.
The quantity of aryl amines was crucial for satisfactory pro-
duction of the desired products. For example, when 1 equiv
of aniline was used in the reaction with 1a, it proceeded slug-
gishly and was incomplete; a somewhat complicated mix-
ture containing the starting 1a was obtained and the yield
of the desired product 2a was considerably decreased (36%).
N
90 ºC
Ar
N
+
ArNH2
NHAr
CHO
R
R
R
R
1a R = H
2a R = H, Ar = Ph 70%
1b R = OMe
2b R = H, Ar = o-Tol 61%
2c R = H, Ar = p-(MeO)C6H4 70%
2d R = H, Ar = p-ClC6H4 80%
2e R = OMe, Ar = Ph 65%
Keywords: 9-Arylamino-9H-pyrrolo[1,2-a]indole; 9-Arylimino-9H-pyr-
rolo[1,2-a]indole; Pyrrolo[1,2-a]indol-9-one; 2-(Pyrrol-1-yl)benzaldehyde;
2-(Pyrrol-1-yl)benzaldimine.
* Corresponding author. Tel./fax: +81 857 31 5263; e-mail: kkoba@chem.
tottori-u.ac.jp
Scheme 1.
0040–4020/$ - see front matter Ó 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2007.02.129

K. Kobayashi et al. / Tetrahedron 63 (2007) 4356–4359
4357
2.2. Synthesis of (Z)-9-arylimino-9H-pyrrolo[1,2-a]-
indoles 3
to the formation of the desired products 4 in good yields,
as shown in Scheme 4.
The synthesis of (Z)-9-arylimino-9H-pyrrolo[1,2-a]indoles
3 is outlined in Scheme 2. Thus, 2-(pyrrol-1-yl)benzalde-
hydes 1 were treated with 2 M amounts of aryl amines at
135 ꢀC for 4 h in the air to afford the corresponding desired
products 3. NOE experiments showed that the configuration
of these iminopyrroloindoles is Z. For example, irradiation
of the signal assignable to 3-H (d 5.60) of 3e resulted in an
enhancement (11%) of the signal assignable to the o-protons
of N-phenyl group (d 7.06). The results shown in Scheme 2
indicate that the yields of the products 3 depend on the
substituent of 1 and aryl amines. Thus, the substitution of a
methoxy group on the benzene nucleus of aryl amine gave
a much more satisfactory yield of the expected product 3c
but that on the benzene nucleus of 1 gave a poorer yield of
the expected product 3e, probably due to the electron dona-
tive nature of methoxy group. Preparation of the correspond-
ing 9-imino derivative from 1a and p-chloroaniline under the
same conditions proved to be unsuccessful. Oxidation of 2d
to the expected imino derivatives did not occurred under
these conditions, and 2d was obtained in good yield. In con-
trast, we found that 2-(pyrrol-1-yl)benzaldehydes carrying
a chlorine on the benzene nucleus, 1c and 1d, reacted with
aniline at 90 ꢀC in an argon atmosphere to give directly
the corresponding 9-phenyliminopyrroloindoles 3f and 3g,
respectively, in lower yields (about 30%). Oxidation of the
corresponding 9-phenylamino derivatives to 3f and 3g is
thought to take place rapidly only at 90 ꢀC presumably dur-
ing exposure to the contaminated oxygen. When the reac-
tions were conducted at 90 ꢀC in the air, the products 3f
and 3g were obtained in fair yields, as shown in Scheme 3.
aq. HCl
N
3a, 3e-g
O
DME, 60 ºC
R2
R1
4a R1 = R2 = H 64%
4e R1 = R2 = OMe 81%
4f R1= H, R2 = Cl 70%
4g R1 = Cl, R2 = H 68%
Scheme 4.
In summary, we have demonstrated convenient access to
9-arylamino- and 9-arylimino-9H-pyrrolo[1,2-a]indoles,
and pyrrolo[1,2-a]indol-9-ones based on an intramolecular
cyclization of 2-(pyrrol-1-yl)benzaldimines from 2-(pyrrol-
1-yl)benzaldehydes and aryl amines. The method should
be useful in heterocycle synthesis because of the ease of
operations as well as the ready availability of the starting
materials.
3. Experimental
3.1. General
The melting points were determined on a Laboratory
Devices MEL-TEMP II melting-point apparatus and are un-
corrected. The IR spectra were recorded on a Perkin–Elmer
1600 Series FTIR spectrometer. The 1H NMR spectra were
determined using SiMe4 as an internal reference in CDCl3
with a JEOL GX270 FT NMR spectrometer operating at
270 MHz. Low-resolution mass spectra were recorded on
a JEOL AUTOMASS 20 spectrometer (Center for Joint
Research and Development, Tottori University). Thin-layer
chromatography (TLC) was carried out using Merck Kiesel-
gel 60 PF254. All of the solvents used were dried over the
appropriate drying agents and distilled under argon prior
to use.
N
135 ºC
air
Ar
+
1
ArNH2
N
R
R
3a R = H, Ar = Ph 68%
3b R = H, Ar = o-Tol 58%
3c R = H, Ar = p-(MeO)C6H4 85%
3e R = OMe, Ar = Ph 33%
3.2. Starting materials
Scheme 2.
2-(Pyrrol-1-yl)benzaldehydes 1a, 1b, and 1d were prepared
by the procedure previously reported by us.1 4-Chloro-
2-(pyrrol-1-yl)benzaldehyde (1c) was prepared from ethyl
2-amino-4-chlorobenzoate6 according to the procedure for
the preparation of the above compounds. Thus, this ester
was allowed to react with 2,5-dimethoxytetrahydrofuran in
refluxing acetic acid to give ethyl 4-chloro-2(pyrrol-1-yl)-
benzoate in 68% yield; a pale yellow liquid; bp 116 ꢀC/
N
N
90 ºC
air
Ph
+ PhNH2
CHO
N
R2
R2
R1
R1
1c R1 = Cl, R2 = H
3f R1 = Cl, R2 = H 60%
1d R1 = H, R2 = Cl
3g R1 = H, R2 = Cl 56%
1
0.26 mmHg; IR (neat) 1720 cmꢁ1; H NMR d 1.13 (3H, t,
Scheme 3.
J¼7.3 Hz), 4.16 (2H, q, J¼7.3 Hz), 6.30 (2H, dd, J¼2.3,
2.0 Hz), 6.78 (2H, dd, J¼2.3, 2.0 Hz), 7.35–7.4 (2H, m),
7.75 (1H, d, J¼8.9 Hz). Calcd for C13H12ClNO2: C, 62.53;
H, 4.84; N, 5.61. Found: C, 62.41; H, 4.90; N, 5.29. This
compound was reduced by LiAlH4 in diethyl ether at 0 ꢀC
to give 4-chloro-2-(pyrrol-1-yl)benzyl alcohol in 95% yield;
a pale yellow liquid; Rf 0.38 (1:3 AcOEt–hexane); IR (neat)
2.3. Synthesis of 9H-pyrrolo[1,2-a]indol-9-ones 4
The imino derivatives 3 were unchanged in concentrated hy-
drochloric acid–1,2-dimethoxyethane (DME) (1:5, v/v) at
room temperature for a day. However, when the solutions
were heated at 60 ꢀC, hydrolysis took place cleanly to lead
1
3342 cmꢁ1; H NMR d 1.64 (1H, br s), 4.55 (2H, s), 6.33

4358
K. Kobayashi et al. / Tetrahedron 63 (2007) 4356–4359
(2H, dd, J¼2.3, 2.0 Hz), 6.85 (2H, dd, J¼2.3, 2.0 Hz), 7.31
(1H, d, J¼2.0 Hz), 7.36 (1H, dd, J¼8.2, 2.0 Hz), 7.51 (1H, d,
J¼8.2 Hz). Calcd for C11H10ClNO: C, 63.62; H, 4.85; N,
6.75. Found: C, 63.33; H, 5.12; N, 6.52. This alcohol was
used in the next PCC oxidation in dichloromethane at
room temperature without any purification to give 1c in
66% yield; a pale yellow liquid; bp 145 ꢀC (oven temp)/
3.3.5. 6,7-Dimethoxy-9-phenylamino-9H-pyrrolo[1,2-a]-
indole (2e). A pale yellow solid; mp 145–147 ꢀC (hexane–
1
CH2Cl2); IR (KBr disk) 3360, 1624, 1603 cmꢁ1; H NMR
d 3.85 (3H, s), 3.96 (4H, s), 5.64 (1H, s), 6.14 (1H, ddd,
J¼3.3, 2.3, 1.0 Hz), 6.26 (1H, dd, J¼3.3, 2.6 Hz), 6.75–
6.9 (4H, m), 6.97 (1H, dd, J¼2.6, 2.3 Hz), 7.08 (1H, s),
7.2–7.3 (2H, m); MS m/z 306 (M+, 14), 214 (100). Calcd
for C19H18N2O2: C, 74.49; H, 5.92; N, 9.14. Found: C,
74.59; H, 6.07; N, 9.03.
1
0.20 mmHg; IR (neat) 2858, 2762, 1695 cmꢁ1; H NMR
d 6.41 (2H, dd, J¼2.3, 2.0 Hz), 6.92 (2H, dd, J¼2.3,
2.0 Hz), 7.4–7.5 (2H, m), 7.94 (1H, d, J¼8.9 Hz), 9.79
(1H, s). Calcd for C11H8ClNO: C, 64.25; H, 3.92; N, 6.81.
Found: C, 64.15; H, 4.04; N, 6.75. Other chemicals used in
this study were commercially available.
3.4. Typical procedure for the preparation of 9-aryl-
imino-9H-pyrrolo[1,2-a]indoles 3
3.4.1. (Z)-9-Phenylimino-9H-pyrrolo[1,2-a]indole (3a). A
mixture of 2-(pyrrol-1-yl)benzaldehyde (1a) (0.17 g,
1.0 mmol) and aniline (0.19 g, 2.0 mmol) was heated in
the air at 135 ꢀC for 4 h. The resulting mixture was purified
by preparative TLC on silica gel (1:10 AcOEt–hexane) to
give 3a (0.17 g, 68%) as a yellow solid; mp 140–141 ꢀC
3.3. Typical procedure for the preparation of 9-aryl-
amino-9H-pyrrolo[1,2-a]indoles 2
3.3.1. 9-Phenylamino-9H-pyrrolo[1,2-a]indole (2a). A
mixture of 2-(pyrrol-1-yl)benzaldehyde (1a) (0.17 g,
1.0 mmol) and aniline (0.19 g, 2.0 mmol) was heated at
90 ꢀC for 8 h under argon. After removal of excess aniline
under reduced pressure, the residual solid was recrystallized
from hexane–CH2Cl2 to give 2a (0.17 g, 70%); a pale yellow
solid; mp 100–101 ꢀC; IR (KBr disk) 3352, 1618,
(hexane–CH2Cl2); IR (KBr disk) 1637, 1616 cmꢁ1 1H
;
NMR d 5.66 (1H, dd, J¼3.6, 1.0 Hz), 6.10 (1H, dd, J¼3.6,
2.6 Hz), 7.00 (1H, dd, J¼2.6, 1.0 Hz), 7.06 (2H, dd,
J¼8.3, 1.3 Hz), 7.2–7.25 (3H, m), 7.35–7.5 (3H, m), 7.87
(1H, dd, J¼7.6, 1.3 Hz); MS m/z 244 (M+, 100). Calcd for
C17H12N2: C, 83.58; H, 4.95; N, 11.47. Found: C, 83.55;
H, 5.12; N, 11.20.
1
1605 cmꢁ1; H NMR d 4.00 (1H, br s), 5.71 (1H, s), 6.18
(1H, ddd, J¼3.3, 2.3, 1.0 Hz), 6.30 (1H, dd, J¼3.3,
2.6 Hz), 6.75–6.9 (3H, m), 7.04 (1H, dd, J¼2.6, 2.3 Hz),
7.09 (1H, dd, J¼7.6, 1.0 Hz), 7.2–7.3 (3H, m), 7.34 (1H,
tt, J¼7.6, 1.0 Hz), 7.50 (1H, d, J¼7.6 Hz); MS m/z 246
(M+, 15), 154 (100). Calcd for C17H14N2: C, 82.90; H,
5.73; N, 11.37. Found: C, 82.77; H, 5.83; N, 11.37.
3.4.2. (Z)-9-(2-Methylphenylimino)-9H-pyrrolo[1,2-a]-
indole (3b). A yellow solid; mp 64–66 ꢀC (pentane–
CH2Cl2); IR (KBr disk) 1637, 1616 cmꢁ1; 1H NMR d 2.16
(3H, s), 5.51 (1H, dd, J¼3.6, 1.0 Hz), 6.09 (1H, dd, J¼3.6,
2.6 Hz), 6.91 (1H, dd, J¼7.6, 1.3 Hz), 6.99 (1H, dd, J¼2.6,
1.0 Hz), 7.09 (1H, td, J¼7.6, 1.3 Hz), 7.15–7.3 (4H, m),
7.43 (1H, td, J¼7.6, 1.3 Hz), 7.90 (1H, dd, J¼7.6, 1.3 Hz);
MS m/z 258 (M+, 100). Calcd for C18H14N2: C, 83.69; H,
5.46; N, 10.84. Found: C, 83.39; H, 5.65; N, 10.65.
3.3.2. 9-(2-Methylphenylamino)-9H-pyrrolo[1,2-a]indole
(2b). A yellow solid; mp 127–128 ꢀC (hexane–CH2Cl2); IR
(KBr disk) 3377, 1620, 1603 cmꢁ1; 1H NMR d 2.09 (3H, s),
3.89 (1H, d, J¼8.8 Hz), 5.74 (1H, d, J¼8.8 Hz), 6.22 (1H,
ddd, J¼3.3, 2.6, 1.1 Hz), 6.31 (1H, dd, J¼3.3, 3.0 Hz),
6.76 (1H, td, J¼7.3, 1.1 Hz), 7.0–7.15 (4H, m), 7.15–7.3
(2H, m), 7.35 (1H, t, J¼7.3 Hz), 7.53 (1H, d, J¼7.3 Hz);
MS m/z 260 (M+, 18), 154 (100). Calcd for C18H16N2: C,
83.04; H, 6.19; N, 10.76. Found: C, 82.64; H, 6.50; N, 10.65.
3.4.3. (Z)-9-(4-Methoxyphenylimino)-9H-pyrrolo[1,2-a]-
indole (3c). A orange solid; mp 143–145 ꢀC (hexane–
CH2Cl2); IR (KBr disk) 1636, 1618 cmꢁ1; 1H NMR d 3.85
(3H, s), 5.88 (1H, dd, J¼3.6, 1.0 Hz), 6.13 (1H, dd, J¼3.6,
2.6 Hz), 6.95 (2H, d, J¼8.9 Hz), 7.00 (1H, dd, J¼2.6,
1.0 Hz), 7.07 (2H, d, J¼8.9 Hz), 7.15–7.25 (2H, m), 7.41
(1H, td, J¼7.6, 1.3 Hz), 7.86 (1H, dd, J¼7.6, 1.3 Hz); MS
m/z 274 (M+, 63), 259 (100). Calcd for C18H14N2O: C,
78.81; H, 5.14; N, 10.21. Found: C, 78.61; H, 5.36; N, 10.07.
3.3.3. 9-(4-Methoxyphenylamino)-9H-pyrrolo[1,2-a]-
indole (2c). A pale yellow solid; mp 98–99 ꢀC (hexane–
CH2Cl2); IR (KBr disk) 3370, 1618 cmꢁ1; 1H NMR d 3.70
(1H, br s), 3.78 (3H, s), 5.62 (1H, s), 6.13 (1H, ddd,
J¼3.3, 2.3, 1.0 Hz), 6.29 (1H, dd, J¼3.3, 3.0 Hz), 6.80
(2H, d, J¼8.9 Hz), 6.83 (2H, d, J¼8.9 Hz), 7.0–7.15 (2H,
m), 7.22 (1H, d, J¼7.6 Hz), 7.33 (1H, dd, J¼7.6, 7.3 Hz),
7.48 (1H, d, J¼7.3 Hz); MS m/z 276 (M+, 3.7), 275 (19),
153 (100). Calcd for C18H16N2O: C, 78.24; H, 5.84; N,
10.14. Found: C, 78.03; H, 5.88; N, 10.14.
3.4.4. (Z)-6,7-Dimethoxy-9-(4-phenylimino)-9H-pyr-
rolo[1,2-a]indole (3e). A pale yellow solid; mp 49–50 ꢀC
(hexane–CH2Cl2); IR (KBr disk) 1635, 1614 cmꢁ1 1H
;
NMR d 3.95 (3H, s), 3.99 (3H, s), 5.60 (1H, dd, J¼3.6,
1.0 Hz), 6.04 (1H, dd, J¼3.6, 2.6 Hz), 6.75 (1H, s), 6.91
(1H, dd, J¼2.6, 1.0 Hz), 7.06 (2H, dd, J¼8.6, 1.3 Hz),
7.18 (1H, tt, J¼7.3, 1.3 Hz), 7.35–7.45 (3H, m); MS m/z
304 (M+, 100). Calcd for C19H16N2O2: C, 74.98; H, 5.30;
N, 9.20. Found: C, 74.90; H, 5.24; N, 9.00.
3.3.4. 9-(4-Chlorophenylamino)-9H-pyrrolo[1,2-a]indole
(2d). A yellow solid; mp 111–112 ꢀC (hexane–Et2O); IR
(KBr disk) 3354, 1620 cmꢁ1 1H NMR d 4.02 (1H, d,
;
J¼8.1 Hz), 5.65 (1H, d, J¼8.1 Hz), 6.15 (1H, ddd, J¼3.3,
2.2, 1.1 Hz), 6.30 (1H, dd, J¼3.3, 3.0 Hz), 6.74 (2H, d,
J¼8.8 Hz), 7.0–7.15 (2H, m), 7.18 (2H, d, J¼8.8 Hz), 7.23
(1H, d, J¼7.3 Hz), 7.35 (1H, t, J¼7.3 Hz), 7.48 (1H, d,
J¼7.3 Hz); MS m/z 280 (M+, 3.7), 278 (4.0), 154 (51), 127
(100). Calcd for C17H13ClN2: C, 72.73; H, 4.67; N, 9.98.
Found: C, 72.49; H, 4.74; N, 9.98.
3.4.5. (Z)-7-Chloro-9-(4-phenylimino)-9H-pyrrolo[1,2-a]-
indole (3f). The heating of a mixture of 5-chloro-2-(pyr-
rol-1-yl)benzaldehyde (1c) (0.11 g, 0.50 mmol) and aniline
(93 mg, 1.0 mmol) in the air at 90 ꢀC for 2 h gave, after
purification by preparative TLC on silica gel (1:5 AcOEt–
hexane), 3f (83 mg, 60%) as a yellow solid; mp

K. Kobayashi et al. / Tetrahedron 63 (2007) 4356–4359
4359
132–133 ꢀC (hexane–CH2Cl2); IR (KBr disk) 1632,
(1H, dd, J¼3.6, 0.7 Hz), 7.06 (1H, dd, J¼2.6, 0.7 Hz),
7.05–7.15 (2H, m), 7.50 (1H, d, J¼8.6 Hz); MS m/z 203
(100). Calcd for C11H6ClNO: C, 64.88; H, 2.97; N, 6.88.
Found: C, 64.79; H, 3.25; N, 6.84.
1
1616 cmꢁ1; H NMR d 5.73 (1H, dd, J¼3.6, 1.0 Hz), 6.12
(1H, dd, J¼3.6, 2.4 Hz), 6.97 (1H, dd, J¼2.6, 1.0 Hz),
7.0–7.1 (3H, m), 7.11 (1H, s), 7.20 (1H, tt, J¼7.3, 1.3 Hz),
7.35–7.45 (3H. m); MS m/z 278 (M+, 100). Calcd for
C17H11N2Cl: C, 73.25; H, 3.98; N, 10.05. Found: C, 73.08;
H, 4.09; N, 9.99.
3.5.4. 7-Chloropyrrolo[1,2-a]indol-9-one (4g). A yellow
solid; mp 140–141 ꢀC (hexane–CH2Cl2); IR (KBr disk)
1691, 1616 cmꢁ1
;
1H NMR d 6.33 (1H, dd, J¼4.0,
3.4.6. (Z)-6-Chloro-9-(4-phenylimino)-9H-pyrrolo[1,2-a]-
indole (3g). Heating a mixture of 4-chloro-2-(pyrrol-1-
yl)benzaldehyde (1d) (0.41 g, 2.0 mmol) and aniline
(0.37 mg, 4.0 mmol) in the air at 90 ꢀC for 2 h gave, after
purification by preparative TLC on silica gel (1:5 AcOEt–
hexane), 3g (0.31 g, 56%) as a yellow solid; mp 154–
2.6 Hz), 6.81 (1H, dd, J¼4.0, 1.0 Hz), 7.0–7.1 (2H, m),
7.40 (1H, dd, J¼8.2, 2.0 Hz), 7.54 (1H, dd, J¼2.6,
1.0 Hz); MS m/z 203 (100). Calcd for C11H6ClNO: C,
64.88; H, 2.97; N, 6.88. Found: C, 64.84; H, 3.01; N, 6.85.
155 ꢀC (hexane–CH2Cl2); IR (KBr disk) 1631, 1612 cmꢁ1
;
References and notes
1H NMR d 5.70 (1H, dd, J¼3.6, 0.7 Hz), 6.13 (1H, dd,
J¼3.6, 2.6 Hz), 6.97 (1H, dd, J¼2.6, 0.7 Hz), 7.05 (2H,
dd, J¼8.2, 1.3 Hz), 7.1–7.25 (3H, m), 7.41 (2H, t, J¼
8.2 Hz), 7.77 (1H, d, J¼8.6 Hz); MS m/z 278 (M+, 100).
Calcd for C17H11N2Cl: C, 73.25; H, 3.98; N, 10.05. Found:
C, 73.36; H, 4.10; N, 9.97.
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O.; Konishi, H. Tetrahedron 2006, 62, 3158–3161; (c)
Kobayashi, K.; Takanohashi, A.; Hashimoto, K.; Morikawa,
O.; Konishi, H. Tetrahedron 2006, 62, 10379–10382.
3.5. Typical procedure for the preparation of
pyrrolo[1,2-a]indol-9-ones 4
2. For previous reports on the synthesis of 9H-pyrrolo[1,2-a]indole
derivatives, see pertinent references cited in Ref. 1b. See also:
ꢀ
ꢀ
ꢀ
(a) Gonzalez-Perez, P.; Perez-Serrano, L.; Casarrubios, L.;
ꢀ
ꢀ
3.5.1. Pyrrolo[1,2-a]indol-9-one (4a). To a stirred solution
of 3a (83 mg, 0.34 mmol) in 1,2-dimethoxyethane (DME)
(5 mL) at room temperature was added 1.0 mL of concen-
trated hydrochloric acid. After the mixture was heated at
60 ꢀC for 20 min, DME was evaporated and 10 mL of water
was added. The crude product was extracted with CH2Cl2
three times (10 mL each). The combined extracts were
washed with brine and dried over anhydrous MgSO4. After
evaporation of the solvent, the residue was purified by pre-
parative TLC on silica gel (1:5 AcOEt–hexane) to give 4a
(37 mg, 64%) as a yellow solid; mp 121–122 ꢀC (hexane–
CH2Cl2) (lit.,7 121–122 ꢀC); IR (KBr disk) 1684 and
Domınguez, G.; Perez-Castells, J. Tetrahedron Lett. 2002, 43,
4765–4767; (b) Feidman, K. S.; Lyer, M. R.; Keith Hester, D.,
II. Org. Lett. 2006, 8, 3113–3116.
3. For the syntheses and biological activities of 9-alkylamino- and
9-alkylimino-9H-pyrrolo[1,2-a]indoles, see: (a) Rault, S.; de
ꢀ
Sevricourt, M. C.; Godard, A. G.; Robba, M. Tetrahedron Lett.
1985, 26, 2305–2308; (b) Rault, S.; Lancelot, J. C.; Robba,
M.; Quermonne, M. A.; Nammathao, B.; Louchahi-Raoul, J.;
Marcy, R. Eur. J. Med. Chem. 1991, 26, 939–946.
4. For recent syntheses of pyrrolo[1,2-a]indol-9-ones, see: (a)
Yavari, I.; Adib, M.; Sayahi, M. H. J. Chem. Soc., Perkin
Trans. 1 2002, 1517–1519; (b) Campo, M. A.; Larock, R. C.
J. Org. Chem. 2002, 67, 5616–5620; (c) Kashulin, I. A.;
Nifant’ev, I. E. J. Org. Chem. 2004, 69, 5476–5479; The use
of this class of molecules as photosensitizers has appeared:
Bauer, R.; Heisler, G.; Koenigstein, C. Spectrochim. Acta, Part
A 1994, 50A, 57–67.
5. Foggasy, K.; Kovacs, K.; Keseru, G. N.; Toke, L.; Faigl, F.
J. Chem. Soc., Perkin Trans. 1 2001, 1039–1043 and pertinent
references cited therein.
6. Keyser, G. E.; Leonard, N. J. J. Org. Chem. 1976, 41, 3529–
3532.
1
1620 cmꢁ1; the H NMR data of this product are identical
to those described in the literature.8
3.5.2. 6,7-Dimethoxypyrrolo[1,2-a]indol-9-one (4e). An
orange solid; mp 166–167 ꢀC (hexane–CH2Cl2); IR (KBr
1
disk) 1686, 1616 cmꢁ1; H NMR d 3.82 (3H, s), 3.92 (3H,
˜
ꢀ
s), 6.16 (1H, dd, J¼3.6, 2.6 Hz), 6.62 (1H, s), 6.64 (1H,
dd, J¼3.6, 1.0 Hz), 6.91 (1H, dd, J¼2.6, 1.0 Hz), 7.19
(1H, s); MS m/z 229 (100). Calcd for C13H11NO3: C,
68.11; H, 4.84; N, 6.11. Found: C, 68.04; H, 5.09; N, 6.07.
7. Josey, A. D.; Jenner, E. L. J. Org. Chem. 1962, 27, 2466–
2470.
8. Cartoon, M. E. K.; Cheeseman, G. W. H. J. Organomet. Chem.
1981, 212, 1–9.
3.5.3. 6-Chloropyrrolo[1,2-a]indol-9-one (4f). A red solid;
mp 179–180 ꢀC (hexane–CH2Cl2); IR (KBr disk) 1685,
1
1614 cmꢁ1; H NMR d 6.40 (1H, dd, J¼3.6, 2.6 Hz), 6.81