Photoinduced cyclization of 3-acyl-2-halo-1-[(ω-phenylethynyl)alkyl] indoles to azaheterocyclo[1,2,3- lm ]-fused benzo[ c ]carbazoles

Article abstract of DOI:10.1021/jo200630x

A one-pot synthesis of azaheterocyclo[1,2,3-lm]-fused benzo[c]carbazoles (2 and 3) has been developed by photocyclization of 3-acyl-2-halo-1-[(ω- phenylethynyl)alkyl] indoles (1) in good to excellent yields. All products are formed from 1 via two sequential photocyclization reactions. Two products, 9-chloro-7,8-dihydro-6H-benzo[c]pyrido[1,2,3-lm]carbazole (2-h) and 7,8-dihydro-6H-benzo[c]pyrido[1,2,3-lm]carbazole (3-h), are produced in the photocyclization of 2-halo-1-[(ω-phenylethynyl)alkyl]indole-3- carbaldehydes (1-h). In contrast, only products 2-h are produced in the photocyclization of 3-acetyl-2-chloro-1-[(ω-phenylethynyl)alkyl]indole-3- carbaldehydes (1o - t). The 9-H in 3-h (n = 2) does originate from the formyl group in 1-h via 1,5-hydrogen shift. The structures of three new products, 9-bromo-7,8-dihydro-6H-benzo[c]pyrido[1,2,3-lm]carbazole (2b), 9-chloro-10-methyl-7,8-dihydro-6H-benzo[c]pyrido[1,2,3-lm]carbazole (3h) and 12-chloro-7,8-dihydro-6H-benzo[c]pyrido[1,2,3-lm]carbazole (2w), have been corroborated by single-crystal X-ray structural analyses.

Full text of DOI:10.1021/jo200630x

ARTICLE
pubs.acs.org/joc
Photoinduced Cyclization of 3-Acyl-2-halo-1-
[(ω-phenylethynyl)alkyl]indoles to Azaheterocyclo[1,2,3-lm]-Fused
Benzo[c]carbazoles
Shenci Lu, Ren Wang, Yi Yang, Yang Li, Zongjun Shi, Wei Zhang,* and Zhifeng Tu
State Key Laboratory of Applied Organic Chemistry and Department of Chemistry, Lanzhou University, Lanzhou, 730000,
People's Republic of China
S Supporting Information
b
ABSTRACT:
A one-pot synthesis of azaheterocyclo[1,2,3-lm]-fused benzo[c]carbazoles (2 and 3) has been developed by photocyclization of
3-acyl-2-halo-1-[(ω-phenylethynyl)alkyl] indoles (1) in good to excellent yields. All products are formed from 1 via two sequential
photocyclization reactions. Two products, 9-chloro-7,8-dihydro-6H-benzo[c]pyrido[1,2,3-lm]carbazole (2aꢀh) and 7,8-dihydro-
6H-benzo[c]pyrido[1,2,3-lm]carbazole (3aꢀh), are produced in the photocyclization of 2-halo-1-[(ω-phenylethynyl)alkyl]indole-
3-carbaldehydes (1aꢀh). In contrast, only products 2aꢀh are produced in the photocyclization of 3-acetyl-2-chloro-1-
[(ω-phenylethynyl)alkyl]indole-3-carbaldehydes (1oꢀt). The 9-H in 3aꢀh (n = 2) does originate from the formyl group in
1aꢀh via 1,5-hydrogen shift. The structures of three new products, 9-bromo-7,8-dihydro-6H-benzo[c]pyrido[1,2,3-lm]carbazole
(2b), 9-chloro-10-methyl-7,8-dihydro-6H-benzo[c]pyrido[1,2,3-lm]carbazole (3h) and 12-chloro-7,8-dihydro-6H-benzo[c]pyrido-
[1,2,3-lm]carbazole (2w), have been corroborated by single-crystal X-ray structural analyses.
’ INTRODUCTION
transfer photocyclization of 2-chloro-1-(ω-alkenyl)indole-3-car-
baldehydes, both chlorine-substituted benzo[c]azaheterocyclo-
[1,2,3-lm]carbazole (2) and benzo[c]azaheterocyclo[1,2,3-lm]-
carbazole (3) were obtained in excellent total yields.
Photoinduced coupling of aryl halides to alkenes1 or alkynes2
offers a convenient access for the formation of arylꢀalkyl bonds
under mild conditions, via fragmentation of an ArꢀX bond and
addition of a trappable intermediate (e.g., an aryl radical or a
cation) to double or triple bonds. It is of interest that new
heterocyclic rings could be formed from halogenated heteroar-
enes via the intramolecular coupling reactions with alkenes or
alkynes.1iꢀk In general, two possible processes have been postu-
lated for the photocoupling reaction. One is initiated by photo-
induced homolytic or photoinduced electron-transfer promoted
cleavage of an ArꢀX bond to generate aryl radicals and the
addition of aryl radicals to double bonds. The other involves
photoinduced heterolytic cleavage of an ArꢀX bond to produce
aryl cations and the addition of aryl cations to double bonds.
Another route for the addition of the CꢀX bond of 2-chloro-
indole-3-carbaldehyde (Ia) to the double bond could be one
analogous to the stepwise transfer mechanism proposed by us
earlier1j (Scheme 1) in analogy to the addition of aryl CꢀS bonds
to activated CdC double bonds as proposed by Winkler
(Scheme 2).3
Obviously, the two products 2 and 3 were all derived from two
sequential cyclization reactions. The first cyclization was an
intramolecular coupling reaction of 2-chloroindole-3-carbal-
dehyde to the tethered phenylacetylene and the second was
initiated by a deformylation. In the two products, the de-
chlorination product 3 was unexpected and the formation of
which was further approved to be derived from a hydrogen-
shift reaction as shown in Scheme 4, eq 2. Few methods
have been reported for the synthesis of azaheterocyclo[1,2,
3-lm]-fused benzo[c]carbazoles, for example, palladium-
catalyzed sequential migration/alkyne insertion/arylation of
3-(2-iodophenyl)-1-(5-phenylpent-4-ynyl)indole4a and pal-
ladium-catalyzed intramolecular annulation of 3-phenyl-2-
iodo-1-(5-phenylpent-4-ynyl)indole.4b However, these reac-
tions required the use of a transition metal catalyst, and the
yield was not satisfactory. Therefore, a metal-free process was
felt desirable.
In this paper, we report a new synthesis of azaheterocyclo-
[1,2,3-lm]-fused benzo[c]carbazoles by the photocyclization of
2-chloro-1-[(ω-phenylethynyl)alkyl]indole-3-carbaldehydes
as shown in Scheme 3. Differently from the chlorine-atom
1
Received: March 25, 2011
Published: May 31, 2011
r
2011 American Chemical Society
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ARTICLE
Scheme 1. Photocyclization of 2-Chloro-1-(3-butenyl)indole-3-carbaldehydes
Scheme 2. Photoinduced Sulfur-Transfer Cyclization of
Aromatic Sulfides to Tethered Dioxenone According to
Winkler3
bearing a 2-substituted bromine on the indole ring (1b, 1e, 1g,
1j, 1l, and 1n). For the least reactive substrate 1c bearing a
2-substituted iodine on the indole ring, the photoreaction gave
only the dechlorination product 3c (Table 2, entry 3). Further-
more, the substrates 1aꢀj with the short tethers (n = 1ꢀ2) were
more reactive than the substrates 1kꢀn with the long tethers (n =
3ꢀ4). Apparently, the five- and six-membered rings (2aꢀj and
3aꢀi) were more easily formed than the seven- and eight-
membered rings (2kꢀn and 3kꢀm). The structures of all
1
products were determined by H and 13C NMR and HRMS,
and the structures of 2b (CCDC 770239) and 3h (CCDC
784302) were further confirmed by single-crystal X-ray structure
analyses (Figure 1) (see Supporting Information).
To evaluate the selectivity of photoreaction of 1 to 2 or 3, the
acetyl group-substituted substrates 1oꢀt were also examined
under the same conditions (Table 3). Irradiation of 1oꢀt led to
cyclization products 2aꢀk as single products in excellent yields.
It was noticeable that no dechlorination products were formed as
the formyl group in 1aꢀn was replaced by acetyl group.
Thus, it could be inferred that the chlorine-retained product 2
and the dechlorinated product 3 were formed by two different
routes. To clarify the mechanism of dechlorination, we examined
the source of the 9-hydrogen in product 3a by deuterium-labeling
experiments. First, 1a was irradiated in acetone-d6 with addition
of pyridine, but it was found that no deuterated product except
the normal products 2a (41%) and 3a (56%) was detected. This
result indicated that the 9-hydrogen was not from the solvent.
Then another substrate 1u (Scheme 4, eq 1) with a deuterated
phenyl group was prepared and irradiated under the same
conditions. The result showed that only normal photocyclization
products 2u (56%) and 3u (38%) were obtained and no
deuterium-shifted product was detected. We next examined
another substrate 1v (Scheme 4, eq 2) with a deuterium-labeled
formyl group and found that a deuterium-shifted product 3v
(51%) which corresponded to dechlorination cyclization prod-
uct 3a was obtained in addition to the chlorine-retained product
2a (43%).
This result indicated that the 9-hydrogen in dehalogenation
products 3aꢀg came from the formyl group in 1aꢀn via
hydrogen shift from formyl group to vinylic carbon, and this
result also gave an explanation to why no dechlorination pro-
duct was formed in the photoreactions of 3-acetyl-2-chloro-1-
(ω-phenylalkynyl)indole (1oꢀt), because no hydrogen shift
could take place from the acetyl group in 1oꢀt. In fact,
photoinduced 1,5-hydrogen shift of a formyl hydrogen to a
vinylic carbon in o-vinylbenzaldehydes or 5-phenyl-2,4-penta-
dienaldehydes to give a ketene methide intermediate was
’ RESULTS AND DISCUSSION
The photoreaction of 2-chloro-1-(4-phenylbut-3-ynyl)indole-
3-carbaldehyde (1a) was chosen as representative for the in-
vestigation of reaction conditions. It was found that 1a could be
reacted in all selected solvents to afford two cyclization products
2a and 3a in different yields and ratio (Table 1). Comparatively,
the reaction was more efficient in acetone than in DCM (Table 1,
entry 2). This result may be derived from the sensitization effect
of acetone to 1a because the triplet energy of acetone (ET = 326
kJ molꢀ1 5a,b) is higher than that of indole-3-carbaldehyde (ET =
275 kJ molꢀ15c). The addition of pyridine to the reaction
solutions (Table 1, entries 3 and 4) increased both the conver-
sion of 1a and the total yield of 2a and 3a probably because of the
neutralization of pyridine to the produced HCl. The best result
(99% conversion and 96% total yield) was obtained when 1a was
irradiated in acetone in the presence of pyridine (Table 1, entry 4).
In view of these results, we extended the study to other
substrates 1bꢀn with variation of halogen, substituents on the
phenyl group, and N-tether length under the best condition
(Table 2). Similarly to 1a, the photoreactions of 1b and 1dꢀn
except 1c all gave a mixture of two products 2 and 3 in high total
yields. As shown in Table 2, the reactivity of 1aꢀn and the ratio
of the products 2 and 3 were influenced greatly by the substit-
uents on aromatic rings and the length of tethers. In general,the
substrates 1dꢀg bearing an electron-donating substituent
(methyl or methoxyl group) on the phenyl ring were more
reactive and afforded higher fraction of chlorine-retanined pro-
ducts 2dꢀg than these substrates having no substituent (1aꢀc)
or 4-Cl on the phenyl ring (1h). On the other hand, the
substrates having a 2-substituted chlorine on the indole ring
(1a, 1d, 1f, 1i, 1k, and 1 m) were more reactive and produced a
higher fraction of chlorine-retained products than the substrates
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Scheme 3. Photocyclization of 2-Chloro-1-[(ω-phenylethynyl)alkyl]indole-3-carbaldehydes
Scheme 4. Photocyclization of the Deuterium-Labeled
Substrates
Table 2. Photocyclization of 2-Halo-1-
[(ω-phenylethynyl)alkyl)]indole-3-carbaldehydesa
entry substrate
R
X
n
time (h) convn (%)b
yield (%)c
1
1a
1b
1c
1d
1e
1f
H
H
H
Cl
Br
I
2
2
2
2
2
2
2
2
1
1
3
3
4
4
8
99
92
86
99
95
99
96
97
98
92
95
81
90
78
2a 42 3a 54
2b 58 3a 36
2
8
3
16
6
2c
0
3a 80
4
CH3 Cl
CH3 Br
OCH3 Cl
OCH3 Br
2d 60 3d 36
2e 64 3d 31
2f 78 3f 20
2g 82 3f 16
2h 32 3h 64
2i 72 3i 23
2j 78 3i 18
2k 44 3k 48
2l 62 3k 32
2m 43 3m 46
2n 54 3m 34
5
6
Table 1. Photocyclization of 1a under Various Conditions a
6
4
7
1g
1h
1i
4
8
Cl
H
H
H
H
H
H
Cl
Cl
Br
Cl
Br
Cl
Br
8
9
8
10
11
12
13
14
1j
10
12
24
24
30
1k
1l
1m
1n
yield(%)c
a 0.3 mmol 1aꢀn was dissolved in anhydrous acetone (20 mL) contain-
ing pyridine (0.1 mL). The solution was irradiated at λ > 300 nm with a
high-pressure mercury lamp (500 W) under argon atmosphere at
ambient temperature. b Conversion was calculated based on substrate.
c Yield of isolated product based on consumed substrate.
entry
solvent
time (h)
convn (%)b
2a
3a
1
2
3
4
5
CH2Cl2
8
8
8
8
8
81
92
90
99
88
58
46
59
42
16
25
42
29
54
67
Me2CO
CH2Cl2ꢀpyridine
Me2COꢀpyridine
MeCNꢀpyridine
In this case, a product 4 (obtained in 81% yield and the configura-
tion was determined by NOE) could be isolated besides the
normal products 2w (6%) and 3w (11%) within 1 h of irradia-
tion. Compound 4 could be further converted to 2w (31%) and
3w (60%) after longer irradiation. These results indicated that
the dechlorination products 3aꢀm and 3uꢀw really did origi-
nate from the cyclization of intermediates containing a 2,4-
pentadienal structure via 1,5-hydrogen shift. Structure 2w was
further confirmed by single-crystal X-ray structure analysis
(CCDC 804083, Figure 2).
Because a ketene structure was formed after the 1,5-hydrogen
shift of the formyl hydrogen to the vinylic carbon in photoreac-
tion of 1aꢀn and 1uꢀw, the photoreaction of 4 in methanol was
carried out in order to capture the ketenes. It was found that a
product 5 (82%) (Scheme 6) containing a methyl ester group,
which was apparently derived from the addition reactions of
methanol to ketene, was really produced. This result confirmed
a 0.3 mmol 1a was dissolved in different anhydrous solvents (20 mL).
The solution was irradiated at λ > 300 nm with a medium-pressure
mercury lamp (500 W) under argon atmosphere at ambient tempera-
ture. b Conversion was calculated based on 1a. c Yield of isolated product
based on consumed 1a.
reported by several authors.6 Thus, we could deduce that the
formation of the dehalogenation product 3aꢀm, 3u, and 3v might
involve the formation of a 2,4-pentadienaldehyde structure and
subsequent 1,5-hydrogen shift of a formyl hydrogen to a vinylic
carbon. In order to confirm this guess, we monitored the reaction
solution of 1a from the beginning to the end to find an
intermediate containing a 2,4-pentadienaldehyde structure, but
no intermediates were detected by 1H NMR besides the reactant
1a and the products 2a and 3a. We next examined the photoreac-
tion of 1w (Scheme 5) in the hope to retard the deformylation.
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Figure 1. Molecular structure of (a) 2b and (b) 3h in the crystal.
’ CONCLUSIONS
Table 3. Photocyclization of 3-Acetyl-2-chloro-1-
[(ω-phenylethynyl)alkyl)]indolesa
In summary, a one-pot synthesis of five-, six-, seven-, and eight-
membered azaheterocyclo[1,2,3-lm]-fused benzo[c]carbazoles
was achieved by the photocyclization of 2-halo-1-[(ω-pheny-
lethynyl)alkyl]indole-3-carbaldehydes (1aꢀn) and 3-acetyl-2-
chloro-1-[(ω-phenylethynyl)alkyl]indoles (1oꢀt) in excellent
yields in acetone. Both 9-chloro-7,8-dihydro-6H-benzo[c]pyrido-
[1,2,3-lm]carbazole (2aꢀh) and 7,8-dihydro-6H-benzo[c]pyrido-
[1,2,3-lm]carbazole (3aꢀh) were formed in the photoreactions
of 2-halo-1-[(ω-phenylethynyl)alkyl]indole-3-carbaldehydes (1aꢀh).
The formation of the dehalogenated products 3 from 1aꢀn were
proved to proceed via photoinduced halogen-transfer addition of
2-haloindole-3-carbaldehydes to tethered phenylacetylene and a
subsequent 1,5-hydrogen shift of the formyl hydrogen to a vinylic
carbon, ejection of carbon monooxide, the cycloaddition reaction
of a carbene center to the phenyl ring, and an elimination of HCl.
In contrast, the halogen-retained product 2 was formed by the
chlorine atom-transfer cyclization and a subsequent deformyla-
tive 6π electric cyclization. The ratio of the halogen-retained
products 2 and dehalogenated products 3 was influenced by
electronic or steric effects.
entry substrate
R
n
time (h) convn (%)b
yield (%)c
1
2
3
4
5
6
1o
1p
1q
1r
1s
1t
H
H
1
2
2
2
2
3
10
8
93
96
97
99
93
89
2i
86
96
94
97
92
84
2a
2d
2f
CH3
OCH3
Cl
8
8
8
2h
H
8
2k
a 0.3 mmol 1oꢀt was dissolved in anhydrous acetone (20 mL) contain-
ing pyridine (0.1 mL). The solution was irradiated at λ > 300 nm with a
medium-pressure mercury lamp (500 W) under argon atmosphere at
ambient temperature. b Conversion was calculated based on substrate.
c Yield of isolated product based on consumed substrate.
’ EXPERIMENTAL SECTION
2-Bromo-1H-indole-3-carbaldehyde.7. To a solution of di-
methylformamide (3.6 mL, 46 mmol) in dichloromethane (12 mL)
was added dropwise a solution of POBr3 (11.1 g, 36.6 mmol) in
dichloromethane (20 mL) at 0 °C. The white, thick mixture was refluxed
during 15 min, and then oxindole (2.053 g, 15.42 mmol) was added
portionwise. Next the mixture was stirred under reflux within 1 h.
The reaction was quenched by addition of crushed ice to the media. The
mixture was stirred for 20 min, and the two layers were separated. The
aqueous layer was neutralized with solid potassium carbonate. The pale
yellow precipitate was washed with cold water and cold dichloro-
methane, respectively, and was triturated with acetone. After evapora-
tion of solvent, pure 2- bromo-1H-indole-3-carbaldehyde was obtained
(3.44 g, 98%) as a pale yellow solid, mp 181ꢀ182 °C (lit. 186ꢀ187 °C7).
3-Acetyl-2-chloroindole8. To a solution of dimethylacetamide
(5.7 mL) and CHCl3 (20 mL) was added POCl3 (5.51 mL) at 0 °C
under stirring. Then a solution of oxindole (2.7 g; 18 mmol) in CHCl3
(20 mL) was added portionwise. Next the white, thick mixture was
heated under reflux for 5 h, and the solution was cooled and poured onto
iceꢀwater. The organic layer was extracted with ethyl acetate, and the
pH of the aqueous layer was adjusted to pH 7 with sodium acetate. The
mixture was left at room temperature overnight, and then the solid was
collected by filtration and washed with water to give the product, 2.75 g,
79%, mp 237ꢀ238 °C (lit. 240ꢀ242 °C8).
the presence of a ketene intermediate formed from the 1,5-
hydrogen shift of the formyl hydrogen to the vinylic carbon in
photoreactions of both 1aꢀn and 1uꢀw.
From the above discussion, two plausible mechanistic ratio-
nales to account for the formation of 2a and 3a are presented in
Scheme 7. First, the chlorine atom transfer cyclization occurred
from triplet 3-acyl-2-chloro-1-(4-phenyl-1-butynyl)indoles (1a
or 1p) to give the intermediate product 6a or 6p, which was
similar to our earlier report of photocyclization of 3-acyl-2-
chloro-1-(pent-4-enyl)indoles;1j then a 1,5-hydrogen shift of
the formyl hydrogen to the vinylic carbon in 6 occurred to give
the ketene methide intermediate 8, which could eject carbon
monoxide to produce a carbene.6c,d The electrophilic addition of
the carbene center to the phenyl group and a subsequent
elimination of HCl could afford the dechlorinative cyclization
product 3a (Scheme 7, route a); on the other hand, a photo-
chemical isomerization of (Ζ)-6a,p to (E)-6a,p and subsequent
electrocyclic ring closure of the latter to 9a,p, in turn undergoing
a Norrish I type elimination of formaldehyde or acetaldehyde,
respectively, could form 2a (Scheme 7, route b).
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Scheme 5. Photocyclization of 2-Chloro-1-(5-dimethylphenyl-4-propynyl)indole-3-carbaldehyde
Method B:10. To a mixture of 3-acyl-2-haloindole (0.5 mmol), the
alkynyl alcohol (0.6 mmol), and PPh3 (0.75 mmol) in CH2Cl2 (8 mL)
was added diethyl azodicarboxylate (0.75 mmol) at 0 °C. The resulting
mixture was flushed with Ar and stirred at room temperature for 24 h.
The mixture was concentrated, and the residue was purified by chro-
matography on a silica gel column. The identity and purity of the
product was confirmed by 1H and 13C NMR spectroscopic analysis.
Photochemical Reactions. General Procedure. A sample of
1a (0.096 g, 0.3 mmol) was dissolved in 25 mL of dry acetone containing
0.1 mL of pyridine. The solution was deaerated by bubbling Ar for 30
min and irradiated at λ > 300 nm with a medium-pressure mercury lamp
(500 W) at ambient temperature. The progress of reaction was
monitored by TLC at regular intervals. After the solvent was removed
under reduced pressure, the residue was separated by column chroma-
tography on silica gel eluted by hexaneꢀethyl acetate 20: 1 (v/v) to
afford products 2a and 3a. The solid was further purified by recrystalli-
zation from ethyl acetate.
Figure 2. Molecular structure of 2w in the crystal.
2-Chloro-1H-indole-3-carbaldehyde. This compound was ob-
tained by the modificated preparation of 3-acetyl-2-chloroindole.7
POCl3 (5.51 mL) was added to a mixture of DMF (5.7 mL) and CHCl3
(20 mL) under stirring at 0 °C. Then a solution of oxindole (2.7 g;
18 mmol) in CHCl3 (20 mL) was added. After the mixture was heated
under reflux for 18 h, the solution was cooled and poured onto water.
The pH of the mixture was adjusted to pH 7 with sodium carbonate.
Then the whole mixture was extracted with dichloromethane. The
organic layer was washed with brine, dried over Na2SO4, and evaporated
under reduced pressure. The mixture was separated by column chro-
matography (silica gel, hexaneꢀacetone, 10:1) to afford the title
compound, 2.1 g (65% mp 214ꢀ215 °C).
Analytical Data for Compounds 2aꢀ5. 9-Chloro-7,8-dihy-
dro-6H-benzo[c]pyrido[1,2,3-lm]carbazole (2a). Colorless solid, mp
1
104ꢀ105 °C; Rf = 0.37 (3.3% petroleum ether in acetone); H NMR
(400 MHz, CDCl3): δ ppm 8.67 (d, J = 8.0 Hz, 1H), 8.48 (d, J = 8.0 Hz,
1H), 8.43 (d, J = 8.0 Hz, 1H), 7.67 (t, J = 7.2 Hz, 1H), 7.50 (t, J = 7.2 Hz,
1H), 7.45ꢀ7.49 (m, 2H), 7.36 (td, J = 5.6 Hz, 2.4 Hz, 1H), 4.26 (t, J =
6.0 Hz, 2H), 3.25 (t, J = 6.0 Hz, 2H), 2.33ꢀ2.39 (m, 2H); 13C NMR
(100 MHz, CDCl3): δ ppm 138.7, 135.4, 129.4, 126.6, 126.5, 126.4,
125.5, 124.0, 123.3, 123.2, 123.1, 122.0, 121.1, 119.9, 111.7, 108.9, 40.7,
24.1, 22.1; MS m/z (relative intensity, %): 293 (32.3), 291 (100), 254
(30.8), 228 (11.2), 146 (8.9), 127 (13.6), 99 (6.4), 75 (8.9); ESI-HRMS:
m/z Calcd for C19H14ClN þ Hþ: 292.0888, found 292.0891; Anal.
Calcd for C19H14ClN: C, 78.21; H, 4.84; N, 4.80. Found: C, 78.25;
H, 4.81; N, 4.79.
General Procedure for the Preparation of N-Alkyl-2-halo-
3-acylindole Derivatives.
7,8-Dihydro-6H-benzo[c]pyrido[1,2,3-lm]carbazole (3a). Colorless
solid, mp 93ꢀ94 °C; Rf = 0.29 (3.3% petroleum ether in acetone);
1H NMR (400 MHz, CDCl3): δ ppm 8.66 (d, J = 8.0 Hz, 1H), 8.51 (d,
J = 8.0 Hz, 1H), 7.90 (d, J = 8.0 Hz, 1H), 7.67 (t, J = 8.0 Hz, 1H), 7.51
(s, 1H), 7.44ꢀ7.46 (m, 2H), 7.40 (t, J = 7.2 Hz, 1H), 7.33ꢀ7.38
(m, 1H), 4.23 (t, J = 6.0 Hz, 2H), 3.11 (t, J = 6.0 Hz, 2H), 2.24ꢀ2.30 (m,
2H); 13C NMR (100 MHz, CDCl3): δ ppm 138.6, 135.9, 129.49, 129.0,
128.8, 125.7, 123.6, 123.5, 123.2, 122.94, 122.90, 122.4, 122.0, 119.5,
112.6, 108.8, 41.1, 25.5, 22.5; MS m/z (relative intensity, %):, 257 (100),
241 (7.0), 228 (9.1), 128 (16.9), 114 (7.6), 100 (6.9), 39 (9.5); ESI-
HRMS: m/z Calcd for C19H15N þ Hþ: 258.1277, found 258.1276;
Anal. Calcd for C19H15N: C, 88.68; H, 5.88; N, 5.44. Found: C, 88.74;
H, 5.84; N, 5.42.
9-Bromo-7,8-dihydro-6H-benzo[c]pyrido[1,2,3-lm]carbazole (2b).
Colorless solid, mp 138ꢀ139 °C; Rf = 0.46 (3.3% petroleum ether in
acetone); 1H NMR (400 MHz, CDCl3): δ ppm 8.66 (d, J = 8.4 Hz, 1H),
8.49 (d, J = 8.0 Hz, 1H), 8.44 (d, J = 8.4 Hz, 1H), 7.66 (t, J = 7.6 Hz, 1H),
7.48ꢀ7.53 (m, 3H), 7.36 (td, J = 8.0 Hz, 4.0 Hz, 1H), 4.24 (t, J = 6.0 Hz,
2H), 3.23 (t, J = 6.0 Hz, 2H), 2.33ꢀ2.39 (m, 2H); 13C NMR (100 MHz,
CDCl3): δ ppm 138.6, 135.6, 129.6, 128.2, 127.4, 126.5, 124.1, 123.7,
Method A:9. Potassium carbonate (3 mmol) was added to a solution
of 3-acyl-2-haloindole (1 mmol) and the alkynyl halide (2 mmol) in
acetone (25 mL). The mixture was heated to reflux for 10 h. When the
starting materials were consumed completely monitored by TLC, the
reaction mixture was concentrated by vacuum and then the product was
isolated by silica gel column chromatography. The identity and purity of
the product was confirmed by 1H and 13C NMR spectroscopic analysis.
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Scheme 6. Photoreaction of 4 in Methanol
Scheme 7. A Plausible Rationale for the Formation of 2a and 3a
123.5, 123.2, 123.0, 122.1, 119.9, 119.8, 112.4, 109.0, 40.8, 27.1, 22.3;
MS m/z (relative intensity, %): 337 (93.0), 335 (100), 254 (38.1), 228
(16.1), 127 (22.8), 100 (12.4), 63 (8.9); ESI-HRMS: m/z Calcd for
C19H14BrN þ Hþ: 336.0383, found 336.0380; Anal. Calcd for C19H14BrN:
C, 67.87; H, 4.20; N, 4.17. Found: C, 67.95; H, 4.15; N, 4.14.
9-Chloro-7,8-dihydro-12-methyl-6H-benzo[c]pyrido[1,2,3-lm]car-
bazole (2d). Colorless solid, mp 164ꢀ165 °C; Rf = 0.39 (3.3%
petroleum ether in acetone); 1H NMR (400 MHz, CDCl3): δ
ppm 8.47 (d, J = 8.0 Hz, 1H), 8.41 (s, 1H), 8.28 (d, J = 8.8 Hz, 1H),
7.45 (d, J = 4.0 Hz, 2H), 7.32ꢀ7.37 (m, 2H), 4.22 (t, J = 6.0 Hz, 2H),
3.21 (t, J = 6.0 Hz, 2H), 2.64 (s, 3H), 2.30ꢀ2.36 (m, 2H); 13C NMR
(100 MHz, CDCl3): δ ppm 138.7, 136.3, 135.6, 129.6, 126.6, 125.3,
125.3, 124.5, 123.8, 123.2, 122.7, 121.9, 120.0, 119.7, 111.3, 108.8, 40.7,
24.0, 22.1, 21.9; MS m/z (relative intensity, %): 307 (35.6), 305 (100),
271 (69.6), 254 (34.3), 127 (54.8), 40 (64.6); ESI-HRMS: m/z Calcd
for C20H16ClN þ Hþ: 306.1044, found 306.1048; Anal. Calcd for
C20H16ClN: C, 78.55; H, 5.27; N, 4.58. Found: C, 78.61; H, 5.24;
N, 4.55.
7,8-Dihydro-12-methyl-6H-benzo[c]pyrido[1,2,3-lm]carbazole (3d).
Colorless solid, mp 133ꢀ134 °C; Rf = 0.36 (3.3% petroleum ether in
acetone); 1H NMR (400 MHz, CDCl3): δ ppm 8.55 (d, J = 8.0 Hz, 1H),
8.45 (s, 1H), 7.82 (d, J = 8.4 Hz, 1H), 7.44ꢀ7.52 (m, 3H), 7.36 (t,
J = 7.2 Hz, 1H), 7.25 (t, J = 5.6 Hz, 1H), 4.32 (t, J = 6.0 Hz, 2H), 3.17
(t, J = 6.0 Hz, 2H), 2.65 (s, 3H), 2.32ꢀ2.38 (m, 2H); 13C NMR
(100 MHz, CDCl3): δ ppm 138.7, 136.1, 135.5, 129.2, 128.6, 127.5,
124.5, 123.6, 123.5, 123.1, 122.5, 122.0, 121.8, 119.4, 112.3, 108.7, 41.3,
25.5, 22.6, 22.2; MS m/z (relative intensity, %): 271 (100), 254 (22.9), 149
(21.2), 121 (24.4), 40 (55.7); ESI-HRMS: m/z Calcd for C20H17N þ Hþ:
272.1444, found 272.1442; Anal. Calcd for C20H17N: C, 88.52; H, 6.31;
N, 5.16. Found: C, 88.59; H, 6.28; N, 5.12.
9-Bromo-7,8-dihydro-12-methyl-6H-benzo[c]pyrido[1,2,3-lm]car-
bazole (2e). Colorless solid, mp 179ꢀ180 °C; Rf = 0.35 (3.3%
petroleum ether in acetone); 1H NMR (400 MHz, CDCl3): δ
ppm 8.49 (d, J = 8.0 Hz, 1H), 8.48 (s, 1H), 8.31 (d, J = 8.4 Hz, 1H),
7.47 (d, J = 4.0 Hz, 2H), 7.31ꢀ7.38 (m, 2H), 4.23 (t, J = 6.0 Hz, 2H),
3.22 (t, J = 6.0 Hz, 2H), 2.65 (s, 3H), 2.32ꢀ2.38 (m, 2H); 13C NMR
(100 MHz, CDCl3): δ ppm 138.6, 136.4, 135.8, 129.8, 128.0, 125.6,
125.5, 123.9, 123.1, 122.7, 122.6, 122.1, 119.85, 119.84, 112.0, 108.9,
40.8, 27.0, 22.4, 21.9; MS m/z (relative intensity, %): 351 (100), 349
(99.6), 268 (47.4), 254 (38.3), 127 (62.8), 40 (68.1); ESI-HRMS: m/z
Calcd for C20H16BrN þ Hþ: 350.0539, found 350.0543; Anal. Calcd for
C20H16BrN: C, 68.58; H, 4.60; N, 4.00. Found: C, 68.64; H, 4.62;
N, 3.90.
9-Chloro-7,8-dihydro-12-methoxy-6H-benzo[c]pyrido[1,2,3-lm]car-
bazole (2f). Colorless solid, mp 136ꢀ137 °C; Rf = 0.27 (3.3% petro-
1
leum ether in acetone); H NMR (400 MHz, CDCl3): δ ppm 8.34
(d, J = 8.0 Hz, 1H), 8.29 (d, J = 9.2 Hz, 1H), 7.90 (d, J = 2.4 Hz, 1H), 7.44
(d, J = 4.0 Hz, 2H), 7.34 (td, J = 8.0 Hz, 4.0 Hz, 1H), 7.13 (dd, J = 9.2 Hz,
2.4 Hz, 1H), 4.19 (t, J = 6.0 Hz, 2H), 4.04 (s, 3H), 3.17 (t, J = 6.0 Hz,
2H), 2.28ꢀ2.34 (m, 2H); 13C NMR (100 MHz, CDCl3): δ ppm 158.4,
138.7, 135.9, 130.5, 127.1, 126.6, 123.7, 123.2, 121.5, 121.3, 119.7, 118.4,
114.1, 111.2, 108.8, 103.4, 55.4, 40.7, 23.8, 22.1; MS m/z (relative
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intensity, %): 323 (19.2), 321 (51.6), 287 (27.7), 243 (18.5), 149 (43.5),
57 (56.1), 40 (100); ESI-HRMS: m/z Calcd for C20H16ClNO þ Hþ:
322.0993, found 322.0995; Anal. Calcd for C20H16ClNO: C, 74.65; H,
5.01; N, 4.35. Found: C, 74.69; H, 5.00; N, 4.32.
m/z (relative intensity, %): 279 (28.9), 277 (100), 241 (43.7), 213 (9.3),
120 (18.9), 106 (10.9); ESI-HRMS: m/z Calcd for C18H12ClN þ Hþ:
278.0731, found 278.0733; Anal. Calcd for C18H12ClN: C, 77.84; H,
4.35; N, 5.04. Found: C, 77.88; H, 4.34; N, 5.01.
7,8-Dihydro-12-methoxy-6H-benzo[c]pyrido[1,2,3-lm]carbazole
(3f). Colorless solid, mp 146ꢀ148 °C; Rf = 0.17 (3.3% petroleum ether
in acetone); 1H NMR (400 MHz, CDCl3): δ ppm 8.45 (d, J = 8.0 Hz,
1H), 7.99 (d, J = 2.4 Hz, 1H), 7.82 (d, J = 8.8 Hz, 1H), 7.45ꢀ7.51 (m,
3H), 7.36 (t, J = 6.8 Hz, 1H), 7.08 (dd, J = 8.8 Hz, 2.4 Hz, 1H), 4.31 (t, J =
6.0 Hz, 2H), 4.06 (s, 3H), 3.15 (t, J = 6.0 Hz, 2H), 2.30ꢀ2.36 (m, 2H);
13C NMR (100 MHz, CDCl3): δ ppm 157.9, 138.7, 136.4, 130.2, 130.0,
124.3, 123.6, 123.4, 123.1, 121.6, 120.2, 119.4, 113.5, 112.2, 108.7, 103.2,
55.3, 41.2, 25.3, 22.6; MS m/z (relative intensity, %): 287 (100), 244
(44.7), 143 (20.8), 120 (14.9), 39 (4.2); ESI-HRMS: m/z Calcd for
C20H17NO þ Hþ: 288.1383, found 288.1381; Anal. Calcd for
C20H17NO: C, 83.59; H, 5.96; N, 4.87. Found: C, 83.67; H, 5.91;
N, 4.84.
9-Bromo-7,8-dihydro-12-methoxy-6H-benzo[c]pyrido[1,2,3-lm]car-
bazole (2g). Colorless solid, mp 128ꢀ129 °C; Rf = 0.35 (3.3% petro-
leum ether in acetone); 1H NMR (400 MHz, CDCl3): δ ppm 8.34 (d,
J = 8.0 Hz, 1H), 8.31 (d, J = 9.6 Hz, 1H), 7.89 (d, J = 2.4 Hz, 1H),
7.44ꢀ7.46 (m, 2H), 7.34 (td, J = 6.0 Hz, 2.4 Hz, 1H), 7.12 (dd, J =
9.6 Hz, 2.4 Hz, 1H), 4.18 (t, J=6.0Hz, 2H), 4.04(s, 3H), 3.16 (t, J=6.0Hz,
2H), 2.28ꢀ2.34 (m, 2H); 13C NMR (100 MHz, CDCl3): δ ppm 158.4,
138.6, 136.1, 130.6, 129.7, 123.8, 123.0, 122.3, 121.6, 120.9, 119.8, 119.7,
114.4, 111.8, 108.9, 103.3, 55.4, 40.7, 26.8, 22.3; MS m/z (relative
intensity, %): 367 (52.7), 365 (51.9), 287 (57.4), 244 (35.1), 129 (49.9),
57 (51.0), 40 (100); ESI-HRMS: m/z Calcd for C20H16BrNO þ Hþ:
366.0488, found 366.0485; Anal. Calcd for C20H16BrNO: C, 65.59; H,
4.40; N, 3.82. Found: C, 65.64; H, 4.38; N, 3.79.
9,12-Dichloro-7,8-dihydro-6H-benzo[c]pyrido[1,2,3-lm]carbazole
(2h). Colorless solid, mp 150ꢀ151 °C; Rf = 0.37 (3.3% petroleum ether
in acetone); 1H NMR (400 MHz, CDCl3): δ ppm 8.51 (d, J = 2.0 Hz,
1H), 8.37 (d, J = 7.6 Hz, 1H), 8.29 (d, J = 9.2 Hz, 1H), 7.45ꢀ7.51
(m, 2H), 7.40 (td, J = 8.8 Hz, 2.0 Hz, 1H), 7.37 (td, J = 6.0 Hz, 2.4 Hz,
1H), 4.21 (t, J = 6.0 Hz, 2H), 3.19 (t, J = 6.0 Hz, 2H), 2.30ꢀ2.36
(m, 2H); 13C NMR (100 MHz, CDCl3): δ ppm 138.7, 135.8, 132.6,
129.9, 127.0, 126.4, 124.6, 124.3, 123.8, 122.7, 122.2, 121.7, 121.3, 120.2,
110.9, 109.1, 40.7, 24.0, 21.9; MS m/z (relative intensity, %): 329 (11.2),
327 (65.0), 325 (100), 254 (37.9), 126 (38.3), 43 (55.5); ESI-HRMS:
m/z Calcd for C19H13Cl2N þ Hþ: 326.0498, found 326.0497; Anal.
Calcd for C19H13Cl2N: C, 69.95; H, 4.02; N, 4.29. Found: C, 69.99; H,
4.00; N, 4.27.
12-Chloro-7,8-dihydro-6H-benzo[c]pyrido[1,2,3-lm]carbazole (3h).
Colorless solid, mp 124ꢀ126 °C; Rf = 0.23 (3.3% petroleum ether in
acetone); 1H NMR (400 MHz, CDCl3): δ ppm 8.57 (d, J = 2.0 Hz, 1H),
8.45 (d, J = 8.0 Hz, 1H), 7.80 (d, J = 8.0 Hz, 1H), 7.47ꢀ7.48 (m, 3H),
7.38 (td, J = 4.8 Hz, 3.2 Hz, 1H), 7.34 (td, J = 8.8 Hz, 2.0 Hz, 1H), 4.27
(t, J = 6.0 Hz, 2H), 3.13 (t, J = 6.0 Hz, 2H), 2.28ꢀ2.34 (m, 2H);
13C NMR (100 MHz, CDCl3): δ ppm 138.7, 136.3, 131.5, 130.1, 129.6,
127.6, 124.0, 123.17, 123.16, 123.0, 122.9, 122.1, 121.8, 119.8, 111.9,
108.9, 41.2, 25.4, 22.4; MS m/z (relative intensity, %): 293 (33.5), 291
(100), 254 (17.9), 227 (7.6), 146 (11.6), 127 (24.3), 57 (17.0), 43
(26.2); ESI-HRMS: m/z Calcd for C19H14ClN þ Hþ: 292.0888, found
292.0886; Anal. Calcd for C19H14ClN: C, 78.21; H, 4.84; N, 4.80. Found:
C, 78.28; H, 4.81; N, 4.76.
6,7-Dihydrobenzo[c]pyrrolo[1,2,3-lm]carbazole (3i). Colorless sol-
id, mp 157ꢀ158 °C; Rf = 0.23 (3.3% petroleum ether in acetone); 1H
NMR (400 MHz, CDCl3): δ ppm 8.45 (d, J = 8.0 Hz, 1H), 8.35 (d, J =
8.0 Hz, 1H), 7.91 (d, J = 8.0 Hz, 1H), 7.60 (td, J = 8.0 Hz, 1.2 Hz, 1H),
7.36ꢀ7.46 (m, 4H), 7.32 (td, J = 8.0 Hz, 1.2 Hz, 1H), 4.51 (t, J = 7.2 Hz,
2H), 3.83 (t, J = 7.2 Hz, 2H); 13C NMR (100 MHz, CDCl3): δ
ppm 149.6, 138.2, 132.3, 129.7, 129.6, 128.5, 125.9, 125.8, 123.26,
123.25, 122.5, 122.2, 120.5, 119.3, 110.5, 107.5, 47.6, 33.2; MS m/z
(relative intensity, %): 243 (100), 213 (5.5), 120 (19.2), 106 (8.6), 93
(4.6), 51 (4.2); ESI-HRMS: m/z Calcd for C18H13N þ Hþ: 244.1121,
found 244.1125; Anal. Calcd for C18H13N: C, 88.86; H, 5.39; N, 5.76.
Found: C, 88.89; H, 5.40; N, 5.72.
8-Bromo-6,7-Dihydrobenzo[c]pyrrolo[1,2,3-lm]carbazole (2j). Col-
orless solid, mp 155ꢀ156 °C; Rf = 0.24 (3.3% petroleum ether in
acetone); 1H NMR (400 MHz, CDCl3): δ ppm 8.41 (d, J = 8.0 Hz, 1H),
8.34 (d, J = 8.0 Hz, 1H), 8.31 (d, J = 8.0 Hz, 1H), 7.65 (td, J = 8.0 Hz,
1.2 Hz, 1H), 7.49 (td, J = 7.2 Hz, 1.2 Hz, 1H), 7.43 (d, J = 4.4 Hz, 2H), 7.34
(td, J = 7.2 Hz, 3.6 Hz, 1H), 4.55 (t, J = 7.2 Hz, 2H), 3.83 (t, J = 7.2 Hz,
2H); 13C NMR (100 MHz, CDCl3): δ ppm 148.5, 138.3, 130.8, 129.6,
128.06, 128.05, 127.8, 126.6, 123.7, 123.6, 123.1, 122.5, 119.8, 114.1,
110.7, 107.1, 47.2, 35.1; MS m/z (relative intensity, %): 323 (100), 321
(93.8), 241 (86.2), 213 (19.5), 120 (39.1), 106 (18.9), 93 (11.5); ESI-
HRMS: m/z Calcd for C18H12BrN þ Hþ: 322.0226, found 322.0225;
Anal. Calcd for C18H12BrN: C, 67.10; H, 3.75; N, 4.35. Found: C, 67.16;
H, 3.73; N, 4.31.
10-Chloro-6,7,8,9-tetrahydrobenzo[c]azepino[1,2,3-lm]carbazole
(2k). Colorless solid, mp 138ꢀ140 °C; Rf = 0.42 (3.3% petroleum ether
in acetone); 1H NMR (400 MHz, CDCl3): δ ppm 8.74 (d, J = 8.4 Hz,
1H), 8.52 (d, J = 8.0 Hz, 1H), 8.44 (d, J = 8.4 Hz, 1H), 7.66 (td, J =
8.0 Hz, 1.2 Hz, 1H), 7.52 (td, J = 7.2 Hz, 1.2 Hz, 1H), 7.45ꢀ7.48 (m, 2H),
7.34 (td, J = 6.0 Hz, 2.0 Hz, 1H), 4.52 (t, J = 6.0 Hz, 2H), 3.60 (t, J =
6.0 Hz, 2H), 2.20ꢀ2.22 (m, 4H); 13C NMR (100 MHz, CDCl3): δ
ppm 140.6, 139.3, 129.3, 128.5, 126.8, 126.6, 126.06, 126.01, 124.2,
123.7, 123.2, 123.1, 121.9, 120.0, 114.4, 109.5, 43.3, 27.4, 27.3, 25.0; MS
m/z (relative intensity, %): 307 (36.2), 305 (100), 254 (18.4), 241
(19.1), 127 (13.6), 121 (10.8); ESI-HRMS: m/z Calcd for C20H16ClN þ
Hþ: 306.1044, found 306.1047; Anal. Calcd for C20H16ClN: C, 78.55;
H, 5.27; N, 4.58. Found: C, 78.60; H, 5.25; N, 4.55.
6,7,8,9-Tetrahydrobenzo[c]azepino[1,2,3-lm]carbazole (3k). Colorless
solid, mp 123ꢀ125 °C; Rf = 0.25 (3.3% petroleum ether in acetone);
1H NMR (400 MHz, CDCl3): δ ppm 8.74 (d, J = 8.0 Hz, 1H), 8.57 (d, J =
8.0 Hz, 1H), 7.90 (d, J = 8.0 Hz, 1H), 7.63 (td, J = 7.6 Hz, 0.8 Hz, 1H),
7.53ꢀ7.56 (m, 2H), 7.48 (t, J = 7.6 Hz, 1H), 7.42 (t, J = 7.2 Hz, 1H), 7.36
(t, J = 7.2 Hz, 1H), 4.55 (t, J = 5.2 Hz, 2H), 3.36 (t, J = 5.2 Hz, 2H),
2.21ꢀ2.30 (m, 4H); 13C NMR (100 MHz, CDCl3): δ ppm 140.3, 139.4,
129.3, 128.8, 128.3, 128.0, 126.02, 126.01, 123.8, 123.7, 122.9, 122.8, 122.0,
119.6, 115.6, 109.3, 43.6, 31.8, 27.9, 26.2; MS m/z (relative intensity, %):
271 (100), 254 (12.2), 242 (13.8), 136 (14.1), 127 (13.1), 41 (16.7); ESI-
HRMS: m/z Calcd for C20H17N þ Hþ: 272.1434, found 272.1432; Anal.
Calcd for C20H17N: C, 88.52; H, 6.31; N, 5.16. Found: C, 88.59; H, 6.28;
N, 5.12.
10-Bromo-6,7,8,9-tetrahydrobenzo[c]azepino[1,2,3-lm]carbazole
(2l). Colorless solid, mp 137ꢀ138 °C; Rf = 0.47 (3.3% petroleum ether
in acetone); 1H NMR (400 MHz, CDCl3): δ ppm 8.74 (d, J = 8.4 Hz,
1H), 8.54 (d, J = 8.0 Hz, 1H), 8.48 (d, J = 8.4 Hz, 1H), 7.66 (td, J =
7.2 Hz, 1.2 Hz, 1H), 7.48ꢀ7.54 (m, 3H), 7.36 (td, J = 6.0 Hz, 2.0 Hz, 1H),
4.56 (t, J = 6.0 Hz, 2H), 3.68 (t, J = 6.0 Hz, 2H), 2.21ꢀ2.24 (m, 4H);
13C NMR (100 MHz, CDCl3): δ ppm 140.6, 139.3, 129.5, 129.0, 128.2,
128.0, 126.6, 124.4, 124.0, 123.1, 123.0, 122.4, 122.1, 120.0, 115.0, 109.5,
43.4, 31.0, 27.2, 24.9; MS m/z (relative intensity, %): 351 (100), 349
8-Chloro-6,7-dihydrobenzo[c]pyrrolo[1,2,3-lm]carbazole (2i). Col-
orless solid, mp 146ꢀ147 °C; Rf = 0.28 (3.3% petroleum ether in
acetone); 1H NMR (400 MHz, CDCl3): δ ppm 8.44 (d, J = 8.0 Hz, 1H),
8.37 (d, J = 8.0 Hz, 1H), 8.31 (d, J = 8.0 Hz, 1H), 7.66 (t, J = 8.0 Hz, 1H),
7.50 (t, J = 8.0 Hz, 1H), 7.40ꢀ7.46 (m, 2H), 7.34 (t, J = 8.0 Hz, 1H), 4.59
(t, J = 7.2 Hz, 2H), 3.91 (t, J = 7.2 Hz, 2H); 13C NMR (100 MHz,
CDCl3): δ ppm 148.7, 138.3, 130.8, 128.8, 128.1, 126.6, 125.6, 124.4,
123.59, 123.58, 123.5, 122.9, 122.4, 119.7, 110.6, 106.6, 47.5, 33.4; MS
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(94.7), 271 (26.9), 254 (35.5), 241 (42.3), 127 (38.1), 121 (23.7); ESI-
HRMS: m/z Calcd for C20H16BrN þ Hþ: 350.0539, found 350.0538;
Anal. Calcd for C20H16BrN: C, 68.58; H, 4.60; N, 4.00. Found: C, 68.64;
H, 4.58; N, 3.96.
1H NMR (400 MHz, CDCl3): δ ppm 8.67 (d, J = 8.4 Hz, 1H), 8.53 (d,
J = 8.0 Hz, 1H), 7.92 (d, J = 8.0 Hz, 1H), 7.63 (td, J = 8.0 Hz, 0.8 Hz, 1H),
7.45ꢀ7.52 (m, 2H), 7.35ꢀ7.43 (m, 2H), 4.32 (t, J = 6.0 Hz, 2H), 3.18
(t, J = 6.0 Hz, 2H), 2.32ꢀ2.38 (m, 2H); 13C NMR (100 MHz, CDCl3):
δ ppm 138.7, 135.9, 129.4, 129.0, 128.7, 125.8, 123.6, 123.5, 122.9,
122.8, 122.5, 122.0, 119.5, 112.7, 108.8, 41.2, 25.5, 22.6; MS m/z
(relative intensity, %): 258 (100), 257 (50.6), 242 (12.9), 149 (11.9),
127 (33.1), 40 (78.9); ESI-HRMS: m/z Calcd for C19H14DN þ Hþ:
259.1340, found 259.1342; Anal. Calcd for C19H14DN: C, 88.34; H,
6.24; N, 5.42. Found: C, 88.39; H, 6.22; N, 5.39.
9-Chloro-7,8-dihydro-10-methyl-6H-benzo[c]pyrido[1,2,3-lm]carbazole
(2w). Colorless solid, mp 162ꢀ163 °C; Rf = 0.27 (3.3% petroleum ether
in acetone); 1H NMR (400 MHz, CDCl3): δ ppm 8.65 (d, J = 8.4 Hz,
1H), 8.51 (d, J = 8.4 Hz, 1H), 7.46ꢀ7.53 (m, 3H), 7.36 (t, J = 7.2 Hz,
1H), 7.28 (d, J = 7.2 Hz, 1H), 4.28 (t, J = 6.4 Hz, 2H), 3.26 (t, J = 6.0 Hz,
2H), 3.17 (s, 3H), 2.37ꢀ2.43 (m, 2H); 13C NMR (100 MHz, CDCl3): δ
ppm 139.0, 136.2, 135.2, 131.2, 128.1, 127.2, 126.0, 125.9, 124.0, 123.2,
122.4, 122.2, 122.1, 119.9, 112.5, 109.0, 40.6, 27.2, 24.7, 22.3; MS m/z
(relative intensity, %): 307 (33.3), 305 (100), 254 (12.9), 149 (11.9),
127 (33.1), 40 (78.9); ESI-HRMS: m/z Calcd for C20H16ClN þ Hþ:
306.1044, found 306.1041; Anal. Calcd for C20H16ClN: C, 78.55; H,
5.27; N, 4.58. Found: C, 78.62; H, 5.23; N, 4.55.
7,8-Dihydro-10-methyl-6H-benzo[c]pyrido[1,2,3-l,m]carbazole (3w).
Colorless solid, mp 192ꢀ194 °C; Rf = 0.22 (3.3% petroleum ether in
acetone); 1H NMR (400 MHz, CDCl3): δ ppm 8.59 (d, J = 8.4 Hz, 1H),
8.54 (d, J = 7.6 Hz, 1H), 7.76 (s, 1H), 7.45ꢀ7.54 (m, 3H), 7.35 (td, J =
7.2 Hz, 1.2 Hz, 1H), 7.27 (d, J = 7.2 Hz, 1H), 4.33 (t, J = 6.0 Hz, 2H), 3.22
(t, J = 6.0 Hz, 2H), 2.77 (s, 3H), 2.33ꢀ2.39 (m, 2H); 13C NMR (100 MHz,
CDCl3): δ ppm 138.8, 135.7, 134.9, 129.1, 128.2, 125.4, 123.84, 123.83,
123.6, 122.4, 122.2, 121.4, 119.47, 119.43, 113.2, 108.7, 41.2, 25.8, 22.7,
20.6; MS m/z (relative intensity, %): 271 (100), 257 (50.6), 242 (19.8),
149 (56.), 127 (45.6), 40 (92.1); ESI-HRMS: m/z Calcd for C20H17N þ
Hþ: 272.1434, found 272.1438, Anal. Calcd for C20H17N: C, 88.52; H,
6.31; N, 5.16. Found: C, 88.61; H, 6.28; N, 5.10.
(Z)-9-((2,6-Dimethylphenyl)chloromethylenyl-6,7,8,9-tetrahydro-
pyrido[1,2-a]indole-10-carbaldehyde (4). Colorless solid, mp 175ꢀ176 °C;
Rf = 0.22 (10.0% petroleum ether in acetone); 1H NMR (400 MHz, CDCl3):
δ ppm 9.38 (s, 1H), 8.17 (d, J = 8.0 Hz, 1H), 7.20ꢀ7.34 (m, 3H), 7.09 (t,
J = 7.6 Hz, 1H), 6.96 (d, J = 7.6 Hz, 2H), 4.17 (t, J = 6.4 Hz, 2H), 3.13 (t, J =
6.4 Hz, 2H), 2.24ꢀ2.30 (m, 2H), 2.12 (s, 6H),; 13C NMR (100 MHz,
CDCl3): δ ppm 184.7, 142.6, 136.6, 136.3, 135.1, 129.1, 128.3, 128.1, 128.0,
125.2, 123.8, 123.0, 122.6, 112.9, 109.0, 42.3, 30.9, 23.5, 20.3; MS m/z
(relative intensity, %): 351 (33.4), 349 (100), 314 (68.4), 254 (20.1), 228
(10.9), 120 (9.5), 55 (8.5);ESI-HRMS:m/z Calcd for C22H20ClNO þ Hþ:
350.1306, found 350.1309, Anal. Calcd for C22H20ClNO: C, 75.53; H, 5.76;
N, 4.00. Found: C, 75.59; H, 5.72; N, 3.88.
11-Chloro-6,7,8,9-tetrahydro-10H-benzo[c]azocino[1,2,3-lm]carba-
zole (2m). Colorless solid, mp 195ꢀ196 °C; Rf = 0.46 (3.3% petroleum
1
ether in acetone); H NMR (400 MHz, CDCl3): δ ppm 8.82 (d, J =
8.4 Hz, 1H), 8.59 (d, J = 8.0 Hz, 1H), 8.47 (d, J = 8.4 Hz, 1H), 7.69 (td,
J = 7.6 Hz, 0.8 Hz, 1H), 7.46ꢀ7.55 (m, 3H), 7.37 (td, J = 7.2 Hz, 0.8 Hz,
1H), 4.86 (br, 2H), 3.84 (br, 2H), 2.01ꢀ2.08 (m, 4H), 1.35 (br, 2H);
13C NMR (100 MHz, CDCl3): δ ppm 139.6, 139.0, 130.0, 129.3, 126.7,
126.5, 126.1, 124.2, 124.1, 123.6, 123.1, 122.7, 122.0, 119.9, 113.6, 108.8,
43.3, 29.8, 28.8, 27.4, 21.4; MS m/z (relative intensity, %): 321 (30.0), 319
(100), 254 (20.1), 228 (10.9), 120 (9.5), 55 (8.5); ESI-HRMS: m/z Calcd
for C21H18ClN þ Hþ: 320.1201, found 320.1204; Anal. Calcd for
C21H18ClN: C, 78.86; H, 5.67; N, 4.38. Found: C, 78.92; H, 5.65; N, 4.34.
6,7,8,9-Tetrahydro-10H-benzo[c]azocino[1,2,3-lm]carbazole (3m).
Colorless solid, mp 162ꢀ163 °C; Rf = 0.43 (3.3% petroleum ether in
acetone); 1H NMR (400 MHz, CDCl3): δ ppm 8.81 (d, J = 8.4 Hz, 1H),
8.63 (d, J = 8.0 Hz, 1H), 7.92 (d, J = 8.0 Hz, 1H), 7.66 (td, J = 8.0 Hz,
0.8 Hz, 1H), 7.57 (s, 1H), 7.44ꢀ7.55 (m, 3H), 7.39 (t, J = 6.8 Hz, 1H), 4.82
(br, 2H), 3.51 (br, 2H), 2.01ꢀ2.09 (m, 4H), 1.41 (br, 2H); 13C NMR
(100 MHz, CDCl3): δ ppm 139.4, 139.1, 129.2, 129.1, 128.3, 128.2,
126.1, 126.0, 123.7, 123.2, 122.8, 122.7, 121.9, 119.5, 114.6, 108.5, 43.0,
33.4, 29.77, 29.73, 21.5; MS m/z (relative intensity, %): 285 (100), 254
(12.8), 241 (8.4), 230 (12.7), 127 (5.5); ESI-HRMS: m/z Calcd for
C21H19N þ Hþ: 286.1590, found 286.1593; Anal. Calcd for C21H19N:
C, 88.38; H, 6.71; N, 4.91. Found: C, 88.45; H, 6.67; N, 4.88.
11-Bromo-6,7,8,9-tetrahydro-10H-benzo[c]azocino[1,2,3-lm]car-
bazole (2n). Colorless solid, mp 173ꢀ174 °C; Rf = 0.41 (3.3% petro-
leum ether in acetone); 1H NMR (400 MHz, CDCl3): δ ppm 8.84 (d,
J = 8.4 Hz, 1H), 8.62 (d, J = 8.0 Hz, 1H), 8.52 (d, J = 8.4 Hz, 1H), 7.69 (t,
J = 8.0 Hz, 1H), 7.48ꢀ7.60 (m, 3H), 7.38 (t, J = 8.0 Hz, 1H), 4.93 (br,
2H), 3.94 (t, J = 7.2 Hz, 2H), 2.05ꢀ2.11 (m, 4H), 1.38 (br, 2H); 13C
NMR (100 MHz, CDCl3): δ ppm 139.6, 139.1, 129.5, 129.1, 127.9, 126.7,
126.49, 126.48, 124.4, 123.9, 123.1, 122.7, 122.1, 120.1, 114.4, 108.9, 43.5,
32.5, 29.9, 27.2, 21.4; MS m/z(relative intensity, %): 365 (99.4), 363 (100),
254 (61.6), 127 (27.2), 55 (82.1), 41 (90.5); ESI-HRMS: m/z Calcd for
C21H18BrN þ Hþ: 364.0696, found 364.0694; Anal. Calcd for C21H18BrN:
C, 69.24; H, 4.98; N, 3.85. Found: C, 69.28; H, 4.97; N, 3.82.
9-Chloro-7,8-dihydro-6H-benzo[c]pyrido[1,2,3-lm]carbazole-10,1,1,12,
13-d4 (2u). Colorless solid, mp 108ꢀ109 °C; Rf = 0.33 (3.3% petroleum
1
ether in acetone); H NMR (400 MHz, CDCl3): δ ppm 8.48 (d, J =
8.0 Hz, 1H), 7.47ꢀ7.50 (m, 2H), 7.37 (td, J = 5.6 Hz, 2.4 Hz, 1H), 4.26
(t, J = 6.0 Hz, 2H), 3.25 (t, J = 6.0 Hz, 2H), 2.33ꢀ2.39 (m, 2H); 13C
NMR (100 MHz, CDCl3): δ ppm 138.8, 135.4, 129.3, 126.6, 126.4, 124.0,
123.1, 121.9, 121.1, 119.9, 111.8, 108.9, 40.7, 24.1, 22.1; MS m/z (relative
intensity, %): 297 (33.5), 295 (100), 261 (50.9), 149 (35.0), 129 (64.4), 83
(41.2), 43 (41.4); ESI-HRMS: m/z Calcd for C19H10D4ClN þ Hþ:
296.1139, found 296.1137; Anal. Calcd for C19H10D4ClN: C, 77.15; H,
6.13; N, 4.74. Found: C, 77.22; H, 6.10; N, 4.70.
7,8-Dihydro-6H-benzo[c]pyrido[1,2,3-lm]carbazole-10,1,1,12,13-d4
(3u). Colorless solid, mp 92ꢀ93 °C; Rf = 0.35 (3.3% petroleum ether in
acetone); 1H NMR (400 MHz, CDCl3): δ ppm 8.51 (d, J = 8.0 Hz, 1H),
7.53 (s, 1H), 7.43ꢀ7.48 (m, 2H), 7.35 (td, J = 6.0 Hz, 2.4 Hz, 1H), 4.26
(t, J = 6.0 Hz, 2H), 3.13 (t, J = 6.0 Hz, 2H), 2.27ꢀ2.33 (m, 2H); 13C
NMR (100 MHz, CDCl3): δ ppm 138.7, 135.9, 129.4, 128.9, 123.6,
123.5, 123.2, 122.8, 122.0, 119.5, 112.7, 108.8, 41.2, 25.5, 22.6; MS m/z
(relative intensity, %): 261 (100), 258 (16.7), 149 (8.6), 129 (19.1), 40
(86.5); ESI-HRMS: m/z Calcd for C19H11D4N þ Hþ: 262.1529, found
262.1527; Anal. Calcd for C19H11D4N: C, 87.32; H, 7.32; N, 5.33.
Found: C, 87.40; H, 7.30; N, 5.27.
(E)-Methyl 9-(2,6-Dimethylbenzylidenyl)-6,7,8,9-tetrahydropyrido-
[1,2-a]indole-10-carboxylate (5). Colorless solid, mp 147ꢀ148 °C;
1
Rf = 0.32 (10.0% petroleum ether in acetone); H NMR (400 MHz,
CDCl3): δ ppm 7.83 (d, J = 8.0 Hz, 1H), 7.21ꢀ7.31 (m, 2H), 7.16 (td,
J = 8.0 Hz, 0.8 Hz, 1H), 7.01 (t, J = 7.2 Hz, 1H), 6.92 (d, J = 7.2 Hz, 2H),
6.62 (s, 1H), 4.24 (t, J = 6.8 Hz, 2H), 3.33 (s, 3H), 2.86 (t, J = 6.8 Hz,
2H), 2.37ꢀ2.43 (m, 2H), 1.96 (s, 6H),; 13C NMR (100 MHz, CDCl3):
δ ppm 165.1, 139.3, 136.2, 135.9, 135.7, 129.6, 129.4, 127.6, 126.9,
126.6, 122.6, 121.5, 121.4, 108.9, 105.5, 50.4, 42.6, 33.1, 25.2, 20.1; MS
m/z (relative intensity, %): 345 (100), 254 (50.6), 178 (19.9), 127
(26.1), 71 (52.3), 43 (62.1); ESI-HRMS: m/z Calcd for C23H23NO2 þ
Hþ: 346.1802, found 346.1806; Anal. Calcd for C23H23NO2: C, 79.97;
H, 6.71; N, 4.05. Found: C, 80.06; H, 6.67; N, 4.00.
’ ASSOCIATED CONTENT
S
Supporting Information. Experimental procedures, sol-
7,8-Dihydro-6H-benzo[c]pyrido[1,2,3-lm]carbazole-9-d (3v). Col-
orless solid, mp 93ꢀ94 °C; Rf = 0.37 (3.3% petroleum ether in acetone);
b
ubility data, spectroscopic data, and 1H and 13C NMR spectra for
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dx.doi.org/10.1021/jo200630x |J. Org. Chem. 2011, 76, 5661–5669

The Journal of Organic Chemistry
ARTICLE
all new compounds. This material is available free of charge via
the Internet at http://pubs.acs.org
’ AUTHOR INFORMATION
Corresponding Author
*E-mail: zhangwei6275@lzu.edu.cn.
’ ACKNOWLEDGMENT
We are grateful to the National Natural Science Foundation of
China (Grant No. 20872056) and the award “Young Scholar of
Distinction of Lanzhou University” for financial support.
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