Syntheses of 2-substituted indoles and fused indoles by photostimulated reactions of o-iodoanilines with carbanions by the SRN1 mechanism

Article abstract of DOI:10.1021/jo026672k

2-Substituted indoles (5a,b and 7) and fused indoles (9a-c, 11a,b, and 12) have been obtained by the S_RN1 mechanism from photostimulated reactions of o-iodoaniline (1) and 1-halo-2-naphthalen-2-ylamines (3a,b) with enolate ions of acyclic (acet

Full text of DOI:10.1021/jo026672k

Syn th eses of 2-Su bstitu ted In d oles a n d F u sed In d oles by
P h otostim u la ted Rea ction s of o-Iod oa n ilin es w ith Ca r ba n ion s by
th e SRN1 Mech a n ism
Silvia M. Barolo, Andre´s E. Lukach, and Roberto A. Rossi*
INFIQC, Departamento de Quı´mica Orga´nica, Facultad de Ciencias Qu´ımicas, Universidad Nacional de
Co´rdoba, Ciudad Universitaria, 5000 Co´rdoba, Argentina
rossi@dqo.fcq.unc.edu.ar
Received November 6, 2002
2-Substituted indoles (5a ,b and 7) and fused indoles (9a -c, 11a ,b, and 12) have been obtained by
the SRN1 mechanism from photostimulated reactions of o-iodoaniline (1) and 1-halo-2-naphthalen-
2-ylamines (3a ,b) with enolate ions of acyclic (acetophenone (6), 2- (4a ) and 4-acetylpyridine (4b))
and cyclic ketones (1- (8a ) and 2-indanone (10a ), 1- (8b) and 2-tetralone (10b) and 1-benzosuberone
(8c)) in DMSO and liquid ammonia as solvents. The carbanions derived from 4a ,b, 8a , and 10b
are novel nucleophiles that form new C-C bonds by the SRN1 mechanism.
In tr od u ction
coupling reaction followed by Rh-catalyzed hydroformyl-
ation of the Heck adducts.10 Recently, a method for indole
synthesis using a palladium-catalyzed annulation be-
tween o-iodoaniline and ketones has been described.11
The development of a new method for the regioselective
synthesis of functionalized indoles through the benzyne
mechanism has also been reported.12
The SRN1 mechanism is an important route to achieve
the formation of a new C-C bond by the reaction of
aromatic substrates with carbanions.13 Good yields of
substitution are usually obtained in the reactions of
aliphatic and aromatic ketones enolate ions. These anions
react with aromatic halides under photostimulation in
liquid ammonia or in DMSO as solvents.
The SRN1 mechanism is a chain process. The initiation
step (eq 1) is an electron transfer (ET) from the nucleo-
phile to the substrate to afford a radical anion. In some
of these systems the ET step is spontaneous but in others
light is required to catalyze the reaction. Electrons (from
dissolution of alkali metals in liquid ammonia, or from a
cathode) and inorganic salts (Fe2+, SmI2) can initiate the
reaction as well. The propagation steps consist of the
fragmentation of the radical anion to afford a radical and
the nucleofugal group (eq 2) and coupling of the radical
Indoles are probably the most widely distributed
heterocyclic compounds in nature. The indole ring be-
longs to an important class of compounds due to their
pharmacological activity.1-3
There are several reported procedures to obtain in-
doles. The most used method is the Fischer synthesis,
which involves the reaction of N-arylhydrazones in acid
media or in the presence of ZnCl2.4 Most often, the indole
is obtained directly form the ketone and phenylhydrazine
without isolation of the intermediate. Recently, the
synthesis of N-arylhydrazones has been improved by
using palladium catalysis.5 Another approach utilized in
acidic media is the Bischler synthesis, which has been
modified in the last years by Moody.6
Indoles can be obtained from o-alkynylanilines by
palladium-catalyzed cyclization under acid7 or basic
conditions8 or from o-alkenylbenzonitriles by radical
cyclization.9 Another procedure is the preparation of
indoles from o-haloanilines by the palladium cross-
(1) Saxton, J . E. In The Chemistry of Heterocyclic Compounds; J ohn
Wiley and Sons: New York, 1994; Vol. 25, Part IV. Gribble, G. W. J .
Chem. Soc., Perkin Trans. 1 2000, 7, 1045. Gribble, G. W. In Second
Supplements to the 2nd Edition of Rodd’S Chemistry of Carbon
Compounds, Vol. IV - Heterocyclic Compounds; Sainsbury, M., Ed.;
Elsevier Science Publications: Amsterdam, 1997; Part B, pp 69-164.
Bosch, J .; Bonjoch, J .; Amat, M. The Alkaloids 1996, 48, 75-189.
(9) Fukuyama, T.; Chen, X.; Peng, G. A. J . Am. Chem. Soc. 1994,
116, 3127.
(10) Dong, Y.; Busacca, C. A. J . Org. Chem. 1997, 62, 6464.
(11) Chen, C. Y.; Larsen, R. D. Org. Synth. 2000, 78, 36.
(12) Barluenga, J .; Fananas, F. J .; Sanz, R.; Fernandez, Y. Chem.
Eur. J . 2002, 8, 2034.
(13) For reviews, see: (a) Rossi, R. A.; de Rossi, R. H. In Aromatic
Substitution by the SRN1 Mechanism; Monograph 178; American
Chemical Society: Washington, DC, 1983. (b) Norris, R. K. Compre-
hensive Organic Synthesis; Trost, B. M., Ed. 1991, 4, 451. (c) Rossi, R.
A.; Pierini A. B.; Pen˜e´n˜ory, A. B. In The Chemistry of Functional
Groups; Patai S., Rappoport, Z., Ed.; Wiley: Chichester, 1995; Supple-
ment D2, Chapter 24, pp 1395-1485. (d) Rossi, R. A.; Pierini, A. B.;
Santiago, A. N. In Aromatic Substitution by the SRN1 Reaction;
Paquette, L. A., Bittman, R., Eds.; Organic Reactions Vol. 54; Wiley &
Sons: 1999; pp 1-271. (e) Rossi, R. A.; Pierini, A. B.; Pen˜e´n˜ory, A. B.
Chem. Rev. 2003, 103, 71-167.
(2) For
a
description of the biological activity of indoles, see:
Sunberg, R. J . Indoles; Academic Press: London, 1996; and references
therein.
(3) For recent developments in indole ring synthesis and applica-
tions, see: Gribble, G. W. J . Chem. Soc., Perkin. Trans. 1 2000, 7, 1045.
(4) For reviews on the Fisher indole synthesis, see: Robinson, B.
In The Fisher Indole Synthesis; J ohn Wiley and Sons: New York, 1982.
Hughes, D. L. Org. Prep. Proced. Int. 1993, 25, 607.
(5) Wasag, S.; Yang, B. H.; Buchwald, S. L. J . Am. Chem. Soc. 1997,
62, 6464.
(6) Moody, C. J .; Swann, E. Synlett 1998, 135.
(7) Cachi, S.; Carnicelli, V.; Marinelli, F. J . Organomet. Chem. 1994,
475, 289.
(8) (a) Kondo, Y.; Sakamoto, H. Heterocycles 1989, 29, 1013. (b)
Kondo, Y.; Kojima, S.; Sakamoto, H. J . Org. Chem. 1997, 62, 6507.
10.1021/jo026672k CCC: $25.00 © 2003 American Chemical Society
Published on Web 03/04/2003
J . Org. Chem. 2003, 68, 2807-2811
2807

Barolo et al.
TABLE 1. Rea ction s of 1 w ith Keton e En ola te Ion sa
X- b product aniline
with the nucleophile to afford a radical anion (eq 3),
which by ET to the substrate (eq 4) forms the intermedi-
ate necessary to continue the propagation cycle. Overall,
eqs 2-4 depict a nucleophilic substitution (eq 5) in which
radicals and radical anions are intermediates.
expt nucleophile
conditions
(%)
(%)
(%)
1
2
3
4
4a
4a
4a
4b
4b
4b
6
6
8a
DMSO, dark, 3 h
DMSO, hν, 3 h
DMSO, hν, 3 hc
DMSO, dark, 3 h
DMSO, hν, 3 h
DMSO, hν, 3 hc
DMSO, hν, 3 h
DMSO, hν, 3 h
DMSO, dark, 3 h
DMSO, hν, 3 h
NH3, hν, 2 h
DMSO, dark, 3 h
DMSO, hν, 3 h
DMSO, hν, 3 hc
NH3, hν, 2 h
DMSO, hν, 3 h
NH3, hν, 2 h
DMSO, hν, 3 h
NH3, hν, 2 h
DMSO, hν, 3 h
DMSO, hν, 3 hi
NH3, hν, 2 h
DMSO, hν, 3 h
DMSO, hν, 3 h
DMSO, hν, 3 h
<1
95 5a (63)
64 5a (39)
<2
23
d
5
101 5b (74)
41 5b (30)
84 7 (46)
17
d
18
37
d
6
7e
8f
90 7 (48)
9g
10g
11
12
13
14
15
16
17
18
19
20
21
22
23j
24k
25l
18 9a (14)
101 9a (71)
91 9a (65)
<2
8a
8a
31
14
8b
8b
8b
8b
8c
98 9b (58)
88 9b (48)
91 9b (54)
108 9c (58)
92 9c (71)h
100 11a (54)
97 11a (50)
101 11b (47)
100 11b (56)
92 11b (73)
96 12 (36)
82 12 (23)
82 12 (36)
34
d
13
32
d
48
11
18
d
8c
10a
10a
10b
10b
10b
8b
8b
8b
One of the most widely studied approaches to ring
closure reactions is the SRN1 substitution of aromatic
compounds that have an appropriate substituent ortho
to the leaving group.14 An important example of substitu-
tion followed by spontaneous ring closure in the reaction
media is the synthesis of indoles by the photostimulated
reaction of o-iodoaniline (1) with carbanions derived from
aliphatic ketones in liquid ammonia to give 2-substituted
indoles 2 (eq 6).15,16
d
50
23
51
a
Reactions carried out under N2 at 40 °C in 20 mL of DMSO (1
(0.50 mmol), ketone (2.50 mmol), and t-BuOK (2.55 mmol)) or in
150 mL of liquid ammonia (1 (0.50 mmol), ketone (1.50 mmol) and
b
t-BuOK (2.0 mmol)) unless otherwise indicated. Determined
d
potentiometrically. c p-DNB (20 mol %) was added. Not quanti-
fied. e The substrate was 3a (0.40 mmol), 6 (2.00 mmol), and
t-BuOK (2.20 mmol) in 10 mL of DMSO. Aniline is 2-naphthyl-
amine. f The substrate was 3b (0.26 mmol), 6 (1.30 mmol) and
t-BuOK (1.31 mmol) in 10 mL of DMSO. Aniline is 2-naphthyl-
h
i
amine. g t-BuOK (2.75 mmol) was used. Isolated yield. Reaction
carried out under N2 at 40 °C in 20 mL of DMSO: 1 (0.50 mmol),
ketone (5.0 mmol), and t-BuOK (5.05 mmol). The substrate was
j
Unsubstituted and substituted o-bromo- and o-chloro-
anilines are adequate substrates for obtaining indoles
with functionalities such as Me, Ph, or MeO groups in
50-90% yield.17
Under electrochemical initiation, the reactions of 1
with the enolate ions of acetone, isopropyl methyl ketone,
and acetaldehyde afford the respective indoles in 75-
93% yields.18
3a (0.40 mmol), 8b (2.00 mmol), and t-BuOK (2.20 mmol) in 10
k
mL of DMSO. Aniline is 2-naphthylamine. The substrate was
3a (0.40 mmol), 8b (2.00 mmol), pinacolone (2.00 mmol), and
t-BuOK (4.40 mmol) in 10 mL of DMSO. Aniline is 2-naphthyl-
l
amine. The substrate was 3b (0.35 mmol), 8b (1.60 mmol), and
t-BuOK (1.62 mmol) in 10 mL of DMSO. Aniline is 2-naphthyl-
amine.
The syntheses of benzo[e]- and benzo[g]indoles have
been performed by reaction of 2-amino-1-bromo- and
1-amino-2-bromonaphthalene with the anion of pina-
colone, respectively.19
The reactions of 1 with the enolate anions of aromatic
ketones (viz. acetophenone, 2-naphthyl-methyl ketone,
2-acetyl-N-methylpyrrole, and 2-acetylthiophene) furnish
the corresponding 2-substituted indoles 2 in good yields
in DMSO as solvent.20 Depending on the ketone enolate
ion involved, the reactions can occur under light or Fe2+
initiation.
We hereby report the syntheses of 2-pyridin-2-yl-1H-
indole, 2-pyridin-4-yl-1H-indole, and 2-phenyl-3H-benz-
(e)indole. Fused indoles are important molecules because
of their pharmaceutical applications, and they can also
be precursors to other planar molecules. In the present
study, we undertake the syntheses of these indoles,
starting from cyclic ketones and 1, and 1-halonaphthalen-
2-ylamines (3) under irradiation in DMSO and in liquid
ammonia.
Resu lts a n d Discu ssion
(14) Rossi, R. A.; Baumgartner, M. T. Synthesis of Heterocycles by
the SRN1 Mechanism. In Targets in Heterocyclic Systems: Chemistry
and Properties; Attanasi, O. A., Spinelli, D., Eds.; Soc. Chimica
Italiana: Italy, 1999; Vol. 3, pp 215-243.
(15) Beugelmans, R.; Roussi, G. J . Chem. Soc., Chem. Commun.
1979, 950.
To study the scope and limitations of the syntheses of
2-substituted indoles and benzoindoles by the SRN
1
mechanism, we made use of several aromatic ketones on
reaction with both 1 and 3 as substrates.
(16) Beugelmans, R.; Roussi, G. Tetrahedron 1981, 37, 393.
(17) Bard, R. R.; Bunnett, J . F. J . Org. Chem. 1980, 45, 1546.
(18) Boujlet, K.; Simonet, J ., Roussi, G.; Beugelmans, R. Tetrahedron
Lett. 1982, 23, 173.
(19) Beugelmans, R.; Chbani, M. Bull. Soc. Chim. Fr. 1995, 132,
729.
The enolate ion of 2-acetylpyridine (4a ) reacts under
photostimulation with 1 to afford the 2-substituted indole
(5a ) in 64% yield (eq 7). This reaction does not occur in
the dark, and it is inhibited by p-dinitrobenzene (p-DNB),
a well-known inhibitor of SRN1 reactions13 (Table 1,
experiments 1-3). The enolate ion of the 4-acetylpyridine
(20) Baumgartner, M. T.; Nazareno, M. A.; Murgu´ıa, M. C.; Pierini,
A. B.; Rossi, R. A. Synthesis 1999, 2053.
2808 J . Org. Chem., Vol. 68, No. 7, 2003

2-Substituted Indoles and Fused Indoles
(4b) reacts under photostimulation with 1 to give the
2-pyridin-4-yl-1H-indole (5b) in 74% yield (eq 7). This
reaction does not occur in the dark, and it is inhibited
by p-DNB (Table 1, experiments 4-6). The dark reactions
of 1 with enolate ion 4 in the presence of FeBr2 afford
indoles 5 in low yield (36%).
stimulated reaction of 1 with 8c in liquid ammonia
affords indole 9c in 71% isolated yield (Table 1, experi-
ments 16-17).
5,6-Dihydroindeno[2,1-b]indole (11a ) is obtained by a
photostimulated reaction of 1 with the enolate anion of
2-indanone (10a ) in 54% yield in DMSO and in 50% yield
in liquid ammonia (eq 10, n ) 1) (Table 1, experiments
18 and 19).
The photostimulated reaction of 1-bromo-2-naphtha-
len-2-ylamine (3a ) with acetophenone enolate ion (6) in
DMSO furnishes 2-phenyl-3H-benzo(e)indole (7) in 46%
yield, together with the reduced product 2-naphthylamine
(18%) (eq 8). To asses the dependence of product yield
on substrate leaving group nature, we studied the iodo
analogue 3b. However, indole 7 was obtained in 48%
yield, and the reduced product increased in yield up to
37% (Table 1, experiments 7 and 8).
The anion derived from 2-tetralone (10b) fails to react
with alkyl halides to obtain 1-substituted-2-tetralones.
Syntheses of these compounds are carried out in good
yields by different methods.22,23 On the other hand, 10b
reacts under irradiation with iodobenzene and 1-iodo-
naphthalene in DMSO to render the substitution prod-
ucts by SRN1 reactions in good yields.24
In the photostimulated reaction of 1 with 10b, 5,7-
dihydro-6H-benzo[c]carbazole (11b) is obtained in 47%
yield. When the concentrations of 10b and t-BuOK are
increased, the yield of 11b is enhanced up to 56% in
DMSO. However, the yield of 11b is 73% upon photo-
stimulation in liquid ammonia (Table 1, experiments
20-22) (eq 10, n ) 2). Enolate ions 10a and 10b do not
react with 1 in the presence of 1 equiv of FeBr2 and
1 equiv of acetone enolate ions.
The photostimulated reactions of 3a and 3b in DMSO
as solvent with 8b furnish 36% yield of indole 12. The
yield does not improve in the presence of pinacolone
enolate ion (Table 1, experiments 23-25).
Substrate 1 reacts sluggishly in the dark in DMSO
with the enolate anion of 1-indanone (8a ) to afford 5,10-
dihydroindeno[1,2-b]indole (9a ) in 14% yield, which upon
irradiation increases to 71% yield (eq 9, n ) 1). A similar
yield of 9a is obtained by a photostimulated reaction in
liquid ammonia as solvent (Table 1, experiments 9-11).
The enolate ions of 1-tetralone (8b) have been arylated
by the SRN1 mechanism in DMSO and in liquid ammonia
to afford products in variables yields (35-80%).21 There
is no reaction of 1 with 8b in the dark in DMSO; however,
upon photostimulation, 5,11-dihydro-6H-benzo[a]carba-
zole (9b) is obtained in 58% yield (eq 9, n ) 2). This
reaction is partially inhibited by p-DNB. Similar yields
of 9b are obtained in liquid ammonia (Table 1, experi-
ments 12-15).
The enolate ions of 6,7,8,9-tetrahydrobenzocyclohepten-
5-one (1-benzosuberone) (8c) react with 1 under photo-
stimulation in DMSO to afford the indole 5,6,7,12-
tetrahydrobenzo[6,7]cyclohepta[1,2-b]indole (9c) in 58%
yield (eq 9, n ) 3). The dark reaction catalyzed by FeBr2
renders indole 9c in poor yield. However, the photo-
Con clu sion s
We have found that carbanions derived from 1-in-
danone (8a ), 2-tetralone (8b), and 2- and 4-acetyl-
pyridines (4a and 4b) are novel nucleophiles that form
new C-C bonds by the SRN1 mechanism in fairly good
yields.
The photostimulated reactions of several cyclic and
acyclic ketone enolate ions with substrate 1 in DMSO
and liquid ammonia afford 2-substituted indoles and
fused indoles in acceptable yields by the SRN1 mechanism
(50-74%) (comparable to the Fisher indole synthesis),
together with the reduced product aniline. An exception
in favor of our methodology is to be found with 2-in-
danone enolate ion (10a ) that affords 54% of product 11a
(21) (a) Nair, V.; Chamberlain, S. D. J . Am. Chem. Soc. 1985, 107,
2183. (b) Nair, V.; Chamberlain, S. D. J . Org. Chem. 1985, 50, 5069.
(c) Beugelmans, R.; Bois-Choussy, M. Heterocycles 1987, 26, 1863. (d)
Beugelmans, R.; Chastanet, J .; Ginsburg, H.; Quinteros-Cortes, L.;
Roussi, G. J . Org. Chem. 1985, 50, 4933.
(22) Pride, D. C.; Henry, S. S.; Meyers, A. I. Tetrahedron Lett. 1996,
37, 3243.
(23) J ensen, B. L.; Slobodzian, S. V. Tetrahedron Lett. 2000, 41,
6029.
(24) Barolo, S. M.; Lukach, A. E.; Rossi, R. A. Unpublished results.
J . Org. Chem, Vol. 68, No. 7, 2003 2809

Barolo et al.
P h otostim u la ted Rea ction of 1-Tetr a lon e En ola te Ion s
(8b) w ith 1 in Liqu id Am m on ia . The following procedure
is representative of all these reactions. Into a three-necked,
250 mL, round-bottomed flask equipped with a coldfinger
condenser charged with dry ice-ethanol, a nitrogen inlet, and
a magnetic stirrer was condensed 150 mL of ammonia previ-
ously dried with sodium metal under nitrogen. The t-BuOK
(2.0 mmol) and 1-tetralone (1.5 mmol) were added. To this
solution was added 0.5 mmol of 1, and the mixture was
irradiated for 120 min. The reaction was quenched by addition
of ammonium nitrate in excess, and the ammonia was allowed
to evaporate. The residue was dissolved with water and then
extracted with methylene chloride, and the organic extract was
washed with water and dried over anhydrous Na2SO4. The
iodide ions in the aqueous solution were determined poten-
tiometrically. The product was quantified by GLC using the
internal standard method. In other runs, the solvent was
removed under reduced pressure and the residue obtained was
purified by radial TLC (eluted with petroleum ether (60-80
°C): acetone).
by the SRN1 mechanism and only 8% yield by the Fisher
indole synthesis.25
Although we found that FeBr2 induced the reaction of
ketone enolate ions to form indoles in high yields by the
S
RN1 mechanism,20 the ketone enolate ions studied in the
present investigation cannot be induced to react by the
inorganic salt intermediacy. The role of Fe2+ ion in the
reaction still remains intriguing. Its presence is required
from catalytic to equimolecular amounts, which depends
on the leaving group and the nucleophile used.
In the photostimulated reactions of substrate 3 and the
ketone enolate ions 6 (46-48% yields of indole 7), and
8b (36% of the fused indole 12), the product yields are
lower than those with substrate 1. However, considering
the availability/simplicity of the starting materials, and
the readiness of the procedure, this reaction becomes a
valid alternative to the synthesis of indoles.
Isola tion a n d Id en tifica tion of P r od u cts. 2-P yr id in -2-
yl-1H-in d ole (5a ). Compound 5a was purified by radial TLC
(eluent: gradient 98-90% petroleum ether:acetone); light
yellow crystals were obtained. Mp: 150-152 °C (lit.28 mp 154-
Exp er im en ta l Section
Gen er a l Meth od s. 1H NMR (200.13 MHz) and 13C NMR
(50.32 MHz) spectra were conducted in CDCl3 or acetone-d6
as solvents. Coupling constants (J ) are given in Hz. The
internal standard method was used for quantitative GC
analysis using authentic samples, the column employed was
an HP1 column (0.53 mm × 5m) with an HP data system.
Liquid chromatographic analyses were performed with a
gradient pump with a variable-wavelength monitor (program-
mable detector, covering the 190 nm to 600 nm UV range)
using a Spherisorb ODS 2 column (4.0 mm × 250 mm). The
purification of the products was done with radial TLC using
silica gel 60 PF-254 with calcium sulfate as binder. Irradiation
was conducted in a photochemical reactor equipped with two
400-W Hg lamps emitting maximally at 350 nm (air and water
refrigerated). Potentiometric titration of halide ions was
performed in a pHmeter using a Ag/Ag+ electrode. Melting
points were uncorrected.
Ma ter ia ls. t-BuOK was commercially available and used
as received. DMSO was distilled under vacuum and stored
under molecular sieves (4 Å). o-Iodoaniline, 2-acetylpyridine,
4-acetypyridine, 1-tetralone, 2-tetralone, 1-indanone, 2-in-
danone, acetophenone, and 1-benzosuberone were commer-
cially available and distilled under reduced pressure. 1-Bromo-
2-naphthylamine19 and 1-iodo-2-naphthylamine26,27 wereprepared
as previously reported.
P h otostim u la ted Rea ction of 1-Tetr a lon e En ola te Ion s
(8b) w ith o-Iod oa n ilin e (1) in DMSO. The following proce-
dure is representative of all these reactions. They were carried
out in a 50 mL three-neck round-bottomed flask equipped with
nitrogen inlet and magnetic stirrer. To 20 mL of dry and de-
oxygenated DMSO under nitrogen was added 2.55 mmol (0.286
g) of t-BuOK and 2.50 mmol (0.365 g) of 1-tetralone. After 15
min, 1 (0.50 mmol, 0.110 g) was added and the reaction
mixture was irradiated for 180 min. The reaction was quenched
with an excess of ammonium nitrate and water. The mixture
was extracted with methylene chloride, and the organic extract
was washed with water, dried over anhydrous Na2SO4, and
then quantified by GLC using the internal standard method.
The iodide ions in the aqueous solution were determined
potentiometrically.
1
155 °C). H NMR (CDCl3) δH: 9.91 (1H, br s); 8.56 (1H, ddd,
J ) 4.8, 1.8, 1.1); 7.79 (1H, td, J ) 8.0, 1.1); 7.68 (1H, td, J )
8.0, 1.8); 7.64 (1H, dt, J ) 8.0); 7.35 (1H, br d, J ) 8.0); 7.23-
7.05 (3H, cplx m); 7.01 (1H, dd, J ) 2.2, 0.7). 13C NMR (CDCl3)
δC: 150.44; 149.07; 136.72; 136.59; 129.10; 123.11; 121.93;
121.12; 120.09; 119.88; 111.36; 100.58. GC/MS EI, m/z: 195
(13); 194 (100); 193 (34); 167 (8); 166 (8); 97 (10); 89 (10); 83
(6); 78 (7); 63 (6).
2-P yr id in -4-yl-1H-in d ole (5b). Compound 5b was purified
by radial TLC (eluent: gradient 100-70% petroleum ether/
acetone); white crystals were obtained. Recrystallization from
ethanol produces needlelike white crystals. Mp: 204-206 °C
1
(lit.29 mp 208-209 °C). H NMR (CD3COCD3) δH: 10.91 (2 H,
br s); 8.61 (2 H, dd, J ) 4.4, 1.5); 7.78 (1H, dd, J ) 4.4, 1.8);
7.63 (1H, br d, J ) 7.9); 7.45 (1H, dd, J ) 7.9, 0.74); 7.22-
7.03 (3H, cplx.m). 13C NMR (CD3COCD3) δC: 151.30; 140.32;
138.91; 135.89; 129.80; 123.97; 121.81; 120.98; 119.91; 112.43;
102.79. GC/MS EI, m/z: 195 (14); 194 (100); 193 (20); 167 (7);
166 (9); 140 (6); 139 (8); 97 (11); 90 (10); 89 (12); 83 (6); 70 (9).
2-P h en yl-3H-ben zo(e)in d ole (7). Compound 7 was puri-
fied by radial TLC (eluent: hexanes); white crystals were
obtained. Mp: 135-136 °C (lit.30 mp 132 °C). 1H NMR (CDCl3)
δH: 8.62 (1H, br s); 8.26 (1H, br d, J ) 8.0); 7.89 (1H, br d, J
) 8.0); 7.72-7.68 (2H, cplx m); 7.62-7.24 (8H, cplx m). 13C
NMR (CDCl3) δC: 136.11; 133.25; 132.47; 129.37; 129.07;
128.61; 128.07; 127.35; 125.84; 124.84; 124.30; 123.52; 123.33;
122.95; 112.50; 99.32. GC/MS EI, m/z: 244 (21); 243 (100); 242
(13); 215 (8); 140 (9); 139 (17); 122 (30); 121 (15); 106 (5); 94
(8). Compound 7 was quantified by HPLC with MeOH/H2O
(75:25) as eluent.
5,10-Dih yd r oin d en o[1,2-b]in d ole (9a ). Compound 9a was
purified by radial TLC (eluent: petroleum ether); light yellow
crystals were obtained. Mp: 208-210 °C dec (lit.31 mp 226-
227 °C, lit.32 mp 235 °C dec, lit.33 mp 249-255 °C dec). 1H NMR
(CD3COCD3) δH: 10.63 (1H, br s); 7.61-7.44 (4H, cplx m); 7.32
(1H, br t, J ) 7.4); 7.19 (1H, td, J ) 7.4, 1.1); 7.12-7.02 (2H,
10 lines); 3.71 (2H, br s). 13C NMR (CDCl3) δC: 147.83; 143.36;
140.69; 135.03; 130.88; 128.80; 126.57; 125.51; 124.79; 121.74;
Alternatively, in other runs the solvent was removed under
reduced pressure and the residue obtained was purified by
radial TLC (eluted with petroleum ether (60-80 °C): acetone).
(28) Liu, S.-F.; Wu, Q.; Schmider, H. L.; Aziz, H.; Hu, N.-X.; Popovic,
Z.; Wang, S. J . Am. Chem. Soc. 2000, 122, 3671.
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1523.
(32) Brown, R. F. C.; Coulston, K. J .; Eastwood, F. W.; Moffat, M.
R. Tetrahedron 1992, 48, 7763.
(33) Abraham, T.; Curran, D. P. Tetrahedron 1982, 38, 1019.
(25) Brown, D. W.; Graupner, P. R.; Sainsbury, M.; Shertzer, H. G.
Tetrahedron 1991, 47, 4383.
(26) Kalinin, V. N.; Shostakovsky, M. V.; Ponomaryov, A. B.
Tetrahedron Lett. 1992, 33, 373.
(27) Brewster, R. Q. Organic Syntheses; Wiley: New York, 1943;
Collect. Vol. II, p 347.
2810 J . Org. Chem., Vol. 68, No. 7, 2003

2-Substituted Indoles and Fused Indoles
120.26; 118.99; 117.29; 112.06; 30.34. GC/MS EI, m/z: 206 (14);
205 (100); 204 (80); 176 (9); 102 (40); 89 (6); 88 (17).
5,7-Dih ydr o-6H-ben zo[c]car bazole (11b). Compound 11b
was purified by radial TLC (eluent: petroleum ether); white
needles were obtained. Mp: 99-101 °C (lit.34 mp 102-103 °C).
1H NMR (CDCl3) δH: 8.04-7.98 (1H, cplx m); 7.88 (br NH,
overlapped); 7.84 (1H, br d, J ) 7.7); 7.33-7.15 (5H, cplx m);
7.07 (1H, td, J ) 7.3, 1.5); 2.96 (4H, cplx m). 13C NMR (CDCl3)
δC: 137.16; 136.16; 133.82; 133.25; 127.94; 126.89; 124.92;
124.27; 122.25; 121.39; 120.53; 119.45; 111.07; 110.69; 29.46;
22.45. GC/MS EI, m/z: 220 (19); 219 (100); 218 (93); 217 (86);
110 (12); 109 (39); 95 (14); 94 (13); 82 (7); 44 (8).
12,13-Dih yd r o-7H -d ib en zo[a ,g]ca r b a zole (12). Com-
pound 12 was purified by radial TLC (eluent: petroleum ether/
dichloromethane 99:1); white crystals were obtained. Mp:
191-193 °C (lit.36 mp 197 °C). 1H NMR (CDCl3) δH: 8.53 (1H,
br s); 8.40 (1H, br d, J ) 8.4); 7.90 (1H, dd, J ) 8.0, 1.5); 7.59-
7.11 (8H, cplx m); 3.45 (2H, cplx m, J ) 8.0); 3.14 (2H, br t, J
) 8.0). 13C NMR (CDCl3) δC: 135.54; 133.44; 131.42, 129.93;
129.23; 128.94; 128.80; 128.37; 126.70; 126.43; 125.59; 123.60;
123.44; 123.11; 120.90; 119.45; 114.79; 112.79; 29.67; 22.53.
GC/MS EI, m/z: 271 (22); 270 (92); 269 (100); 268 (78); 134
(38); 133 (25); 132 (9); 121 (7); 120 (8); 119 (6). Compound 12
was quantified by HPL with MeOH/H2O (85:15) as eluent.
5,11-Dih yd r o-6H-ben zo[a ]ca r ba zole (9b). Compound 9b
was purified by radial TLC (eluent: petroleum ether/acetone
95:5). It was recrystallized from n-hexane to give needlelike
white crystals. Mp: 160-161 °C (lit.34 mp 164-165 °C). 1H
NMR (CDCl3) δH: 8.16 (1H, br s); 7.55 (1H, cplx d, J ) 8.0);
7.40-7.07 (7H, cplx m); 3.02 (4H, cplx m). 13C NMR (CDCl3)
δC: 137.13; 136.67; 133.17; 129.02; 128.61; 127.59; 126.83;
126.75; 122.47; 120.01, 119.93, 118.91; 112.82; 111.25; 29.64;
19.80. GC/MS EI, m/z: 220 (10); 219 (66); 218 (100); 217 (46);
189 (6); 109 (48); 108 (10); 96 (11); 94 (15).
5,6,7,12-Te t r a h yd r ob e n zo[6,7]cycloh e p t a [1,2-b]in -
d ole (9c). Compound 9c was purified by radial TLC (eluent:
petroleum ether/acetone 99:1); white crystals were obtained.
Mp: 95-96 °C (lit.35 mp 98-99 °C). 1H NMR (CDCl3) δH: 8.05
(1H, br s); 7.62-7.56 (2H, cplx m); 7.42-7.13 (6H, cplx m);
3.14 (2H, t, J ) 6.8); 2.94 (2H, m); 2.20 (2H, q, J ) 6.8). 13C
NMR (CDCl3) δC: 142.33; 136.27; 132.68; 131.77; 130.04;
129.75; 127.00; 126.46; 125.13; 122.79; 119.50; 118.64; 114.68;
110.58; 35.28; 26.76; 26.00. GC/MS EI, m/z: 234 (12); 233 (80);
232 (100); 230 (18); 217 (28); 115 (17); 109 (36); 102 (12).
5,6-Dih yd r oin d en o[2,1-b]in d ole (11a ). Compound 11a
was purified by radial TLC (eluent: petroleum ether/acetone
98:2). It was recrystallized from chloroform to give colorless
Ack n ow led gm en t . This work was supported in
part by the Agencia Co´rdoba Ciencia de la Provincia
de Co´rdoba, the Consejo Nacional de Investigaciones
Cient´ıficas y Te´cnicas (CONICET), SECYT, Universidad
Nacional de Co´rdoba, and FONCYT, Argentina. S.M.B.
gratefully acknowledges receipt of a fellowship from
CONICET.
1
needles. Mp: 205-207 °C dec (lit.25 mp 205 °C dec). H NMR
(CDCl3) δH: 8.24 (1H, br s); 7.87-7.83 (1H, cplx m); 7.64 (1H,
br d, J ) 7.3); 7.42-7.05 (6H, cplx m); 3.70 (2H, s s). 13C NMR
(CDCl3) δC: 146.00; 142.49; 140.61; 139.99; 127.56; 127.02;
124.68; 122.55; 122.20; 121.50; 120.39; 119.23; 118.42; 111.77;
31.19. GC/MS EI, m/z: 206 (15); 205 (100); 204 (69); 176 (13);
102 (32); 89 (9); 88 (22); 76 (7); 75 (8).
J O026672K
(34) Katritzky, A. R.; Wang, Z. J . Heterocycl. Chem. 1988, 25, 671.
(35) Catala´n, J .; Mena, E.; Fabero, F. J . Chem. Phys. 1992, 96, 2005.
(36) Buu-Ho¨ı, N. P.; Hoa´n, N.; Khoi, N. H. J . Org. Chem. 1949, 14,
492.
J . Org. Chem, Vol. 68, No. 7, 2003 2811