Solvent-free synthesis of δ-carbolines/carbazoles from 3-nitro-2-phenylpyridines/2-nitrobiphenyl derivatives using DPPE as a reducing agent

Article abstract of DOI:10.1016/j.tet.2011.06.027

A green and efficient preparation of functionalized δ-carbolines/ carbazoles via reductive ring closure by 1,2-bis(dipenylphosphino)ethane under solvent-free conditions is described. The starting materials 3-nitro-2-phenylpyridines/2-nitrobiphenyl derivatives are readily prepared through Suzuki-Miyaura cross-coupling reaction from commercially available compounds. And the polar by-product ethane-1,2-diylbis(diphenylphosphine oxide) is easily removed from the relatively polar reaction mixture. Various substituted δ-carbolines/carbazoles are obtained in acceptable yields. It is particularly worth mentioning that substrates with electron-withdrawing groups (EWG) also give the desired products in good yield.

Full text of DOI:10.1016/j.tet.2011.06.027

Tetrahedron 67 (2011) 5725e5731
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Solvent-free synthesis of d-carbolines/carbazoles from 3-nitro-2-phenylpyridines/
2-nitrobiphenyl derivatives using DPPE as a reducing agent
*
Haixia Peng, Xuxing Chen, Yanhong Chen, Qian He, Yuyuan Xie, Chunhao Yang
State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zuchongzhi Road, Shanghai 201203, PR China
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 18 April 2011
Received in revised form 3 June 2011
Accepted 10 June 2011
Available online 16 June 2011
A green and efficient preparation of functionalized d-carbolines/carbazoles via reductive ring closure by
1,2-bis(dipenylphosphino)ethane under solvent-free conditions is described. The starting materials 3-
nitro-2-phenylpyridines/2-nitrobiphenyl derivatives are readily prepared through SuzukieMiyaura
cross-coupling reaction from commercially available compounds. And the polar by-product ethane-1,2-
diylbis(diphenylphosphine oxide) is easily removed from the relatively polar reaction mixture. Various
substituted d-carbolines/carbazoles are obtained in acceptable yields. It is particularly worth mentioning
that substrates with electron-withdrawing groups (EWG) also give the desired products in good yield.
Keywords:
Solvent-free
Ó 2011 Elsevier Ltd. All rights reserved.
d-Carbolines
Carbazoles
Cadogen cyclization
DPPE
R1
1. Introduction
R1
Cadogan Cyclization
Carbolines and carbazoles are the key structural units for a va-
riety of biologically important natural alkaloids and
pharmaceuticals.1e6 A number of carbolines/carbazoles display
various biological properties including antimalarial, antitumor,
anti-plasmodial, and antitrypanosomal activities.7,8 In addition,
carbazoles are important building blocks in materials science.9 The
synthesis of carboline/carbazole derivatives including naturally
occurring carbolines/carbazoles has received considerable
attention.10e12 The development of green and efficient approach to
both core structures with different functional groups is a major
objective in organic synthesis currently.
N
N
H
O2
Scheme 1. Cadogan cyclization with organo-phosphorus reagents.
reactions. The reductive cyclizations with P(OEt)3 suffer from sev-
eral drawbacks: the first is the strong foul-smelling odor of this
toxic solvent; the second is that the side products N-hydroxy de-
rivatives and ethylated carbazoles or N-ethylindoles are usually
formed in those reactions, which are quite difficult to remove from
the desired products; Thirdly a large excess of P(OEt)3 was used.
The ethylation is probably due to alkylation of the nitrogen by the
solvent or generated triethyl phosphate.25e28 These side reactions
could be avoided by using PPh3 as reductant due to the non-
electrophilic property of triphenylphosphine oxide.29
Few efficient methods are described for preparing functional-
ized
literature for
d
-carbolines.13e24 And most of the syntheses reported in the
d-carbolines are low yielding and require several steps
from starting materials. Those materials are usually unstable or not
commercially available. One important general method for carba-
zole synthesis is Cadogan cyclization, while preparation of d-car-
bolines by Cadogan cyclization has not been described in the
literature. This reaction involves the reductive cyclization of 2-
ntitrobiphenyl derivatives in the presence of trivalent organo-
phosphorus reagents (Scheme 1). P(OEt)3 and PPh3 are usually
employed as reductants, and P(OEt)3 is also used as solvent in
Cadogan and co-workers described reductive cyclization of 2-
nitrobiphenyl to carbazole with molten PPh3 in a sealed tube only
in modest yield (43%).30e33 Freeman used high boiling-point o-di-
chlorobenzene (o-DCB) as solvent at high temperature (refluxed at
180 ꢀC) for long time29 and Sanz needed toxic and not-easily
obtained molybdenum complex as catalyst.34 However, in some
cases triphenylphosphine oxide could be a stumbling block in pu-
rification because it is very difficult to separate from polar
products.29,35,36
* Corresponding author. Tel./fax: þ86 21 50806770; e-mail address: chyang@
mail.shcnc.ac.cn (C. Yang).
0040-4020/$ e see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2011.06.027

5726
H. Peng et al. / Tetrahedron 67 (2011) 5725e5731
On the other hand, those reported Cadogan reactions are limited
reductive cyclization using our previously optimized conditions.
The results were summarized in Table 1.
in the diversity of functional groups (R1) on the benzene, in which
R1 represents hydrogen, halogen or electron-donating groups, such
as methoxy, alkyl group. Substrates with strong electron-
withdrawing groups as R1 are scarcely explored. Here we describe
a concise solvent-free method for the synthesis of novel or useful
Table 1
d
-Carbolines prepared by reductive cyclization of 3-nitro-2-phenylpyridinesa
H
NO2
N
DPPE 1.1eq
150 oC, 5 h
substituted
d-carbolines/carbazoles from the reductive de-
N
N
oxygenation of the nitro group of the corresponding 3-nitro-2-
phenylpyridines/2-nitrobiphenyl derivatives using a slight excess
of 1, 2-bis(dipenylphosphino)-ethane (DPPE). And the starting
materials 3-nitro-2-phenylpyridines/2-nitrobiphenyl derivatives
are easily prepared through SuzukieMiyaura cross-coupling re-
action of commercially available 2-chloro-3-nitro-pyridine/chloro-
2-nitro-benzene and various boronic acids.
R
R
Entry
1
Substrate
Product
Yield (%)
70
1a
2a
1b
2. Results and discussion
2
85
75
We chose d-carbolines as the synthetic target compound at first
2b
because of their high polarity. We compared the efficacy of triphe-
nylphosphine and DPPE during the reductive cyclization of 2-(3,4-
dimethoxyphenyl)-3-nitropyridine (Scheme 2). Because DPPE had
two reductive groups, we employed 1.1 M equiv of DPPE as reducing
agent. The conditions were simple: 2-(3,4-dimethoxyphenyl)-3-
nitropyridine and PPh3 or DPPE were mixed well and heated at
150 ꢀC under N2 atmosphere, respectively. After 5 h TLC indicated
3
4
3b
3a
4a
36
45
the reaction was complete. When PPh3 was used, 6,7-dimethoxy-d-
4b-1
4b-2
Carboline only could be obtained in moderate yield (45%) by column
chromatography. In addition, it is very difficult to separate PPh3O
from the polar product. While DPPE was employed instead of PPh3
the purification of the d-carboline was easily achieved by simple
column chromatography in excellent yield (85%) as we expected and
the product wasnotcontaminated byanyside product DPPE dioxide.
5
6
60
65
5a
6a
5b
6b
H
OMe
N
OMe
OMe
NO2
N
PPh3 2.5 eq
150
OMe
N
45%
7
8
66
60
H
NO2
7a
8a
7b
8b
N
OMe
OMe
DPPE 1.1 eq
150
N
N
OMe
85%
OMe
Scheme 2. Reductive cyclization of 2-(3,4-dimethoxyphenyl)-3-nitropyridine to
carboline.
d-
9
50
52
50
56
90
9b
9a
Subsequently, we examined the effect of temperature on the re-
action. Increasing the temperature to 180 ꢀC made the reaction
completed within 30 min, but the yield decreased dramatically (50%).
While at 130 ꢀC, the starting material 2-(3,4-dimethoxyphenyl)-3-
nitropyridine was not consumed completely after 9 h, afforded the
product in 60% yield.
Thus, after establishing the general experimental conditions, we
set about to elaborate the substrate scope and functional group
tolerance of the method. We prepared a wide variety of 3-nitro-2-
phenylpyridines with different functional groups through Suzu-
kieMiyaura cross-coupling reactions between the appropriately
substituted phenyl boronic acids and 2-chloro-3-nitropyridine. The
cross-couplings were performed by microwave heating in common
conditions: aqueous potassium carbonate (2 equiv), 5% mol
Pd(PPh3)4 and afforded moderate to good yields (50%e92%). Once
these intermediates were accessible, they were subjected to
10
11
12
13
10b
11b
12b
13b
10a
11a
12a
13a

H. Peng et al. / Tetrahedron 67 (2011) 5725e5731
5727
Table 1 (continued )
Table 2
Carbazoles prepared by DPPE mediated reductive cyclizationa
Entry
Substrate
Product
Yield (%)
H
N
NO2
DPPE 1.1eq
150 OC, 5 h
R
R
14
15
89
50
Entry
18
Substrate
Product
Yield (%)
14a
15a
14b
65
70
15b
18b
18a
19a
19
20
16
68
60
16b
17b
16a
17a
19b
17
33
47
a
20b-1
Reactions were run on
a 100 mg scale of 3-nitro-2-phenylpyridines and
20a
1.1 equiv DPPE at 150 ꢀC for 5 h. DPPE¼1,2-bis(dipenylphosphino)ethane.
Generally, the reaction could complete within 5 h and gained
moderate to good yields. The regioselectivity of this reaction was
dependent on the nature of electron density of the carbon and the
intermediate nitrene was in favor of insertion into relatively
electron-rich carbon-hydrogen bond (entries 2 and 13e17). When
there was one methoxy group on the meta-position of benzene, the
nitrene insertion took place both at ortho- and para-position, the
yield of para-product was slightly higher than that of ortho-com-
pound (entry 4). When there are two methoxy groups on the ben-
zene ring, the nitrene insertion mainly took place at the relatively
electron rich ortho-position to the methoxy, and no para-product
was obtained (entry 2). Similarly the insertion only took place at the
20b-2
H
N
21
98
46
O
21b
H
N
O
NO2
O
22b-1
22
a
-position of thiophene (entry 17). Moreover, the reaction could
tolerate a wide range of functional groups, including not only
electron-donating groups (EDG), such as alkoxy, alkyl groups (en-
tries 4e7), but also electron-withdrawing groups (EWG) as car-
boxylic ester, nitrile, and trifluoromethyl group (entries 8e12). To
our delight, carbolines could be easily purified by simple column
chromatography and the by-product 1,2-bis(dipenylphosphino)
ethane oxide was removed completely.
22a
37
a
Reactions were run on a 100 mg scale of 2-nitro-1,10-biphenyls and 1.1eq DPPE
at 150 ꢀC for 5 h. DPPE¼1,2-bis(dipenylphosphino)ethane.
Finally, we extended our method to the syntheses of function-
alized carbazoles in good to excellent yields. Both substrates with
EDG or EWG proceeded smoothly (Table 2). Aldehyde group was also
tolerated in this reaction, and the result was similar to the substrates
with EDG (entry 20 vs entry 4). Noticeably, compound 20b-1, a key
intermediate of popular heart failure drug carvedilol, was obtained
in nearly quantitative yield (entry 21). Bautista and co-workers
reported a tedious total synthesis procedure of natural antimicro-
bial product glycozolicine 22b-1, which was also the natural pre-
cursor of mukolidine and mukoline.37 We prepared glycozolicine in
a concise two-step procedure in acceptable yield (entry 22). How-
3. Conclusion
An efficient and practical solvent-free synthesis of novel or
useful d-carbolines/carbazoles has been developed. A wide variety
of functionalized 3-nitro-2-phenylpyridines/2-nitrobiphenyl de-
rivatives were used to afford the desired aza heterocycles in ac-
ceptable to excellent yields and various functional groups are
tolerated well. The advantages of this method include its environ-
mentally benign, simple manipulation, short reaction time, and
high regioselectivity. It is the first time using DPPE as a reductant in
Cadogan cyclization. More importantly, the procedure using DPPE
as reductant may provide a better approach to construct more polar
nitrogen heterocycles than using PPh3.
ever, whenwe tried to synthesize unsubstituted b-carboline from 4-
(2-nitrophenyl)pyridine using the same protocol, the reaction only
yielded product in 30%, and it was not easy to separate the product
from DPPE dioxide due to the significant polarity of the
In order to make such a reaction practical, the solvent-free
synthesis of -carboline 3b/13b was scaled-up to yield gram
b
-carboline.
4. Experimental section
4.1. General procedure
d
quantities. For the compound 3b, starting from 2.50 g of 3a,1.50 g of
3b was produced (70% yield). In the subsequent preparation of 13b,
2.30 g of 13a was utilized to produce 1.83 g (91.5% yield).
Reagents (chemicals) were purchased and used without further
purification. Analytical thin layer chromatography (TLC) used was

5728
H. Peng et al. / Tetrahedron 67 (2011) 5725e5731
HSGF 254 (0.15e0.2 mm) thickness. All products were character-
ized by NMR and MS. Chemical shifts were reported in parts per
million (ppm, d) downfield from TMS. Proton coupling patterns are
described as singlet (s), doublet (d), triplet (t), quartet (q), multiplet
(m), and broad (br). Low- and high-resolution mass spectra (LRMS
and HRMS) were obtained.
1H), 8.28 (d, J¼8.1 Hz, 1H), 7.50e7.45 (m, 1H), 7.40e7.22 (m, 3H),
7.18 (d, J¼7.7 Hz, 1H), 2.17 (s, 3H).
4.2.1.8. 2-(4-Fluorophenyl)-3-nitropyridine40
powder (65% yield), mp 108e110 ꢀC; 1H NMR (CDCl3, 300 MHz):
(8a). A
white
d
8.85 (dd, J¼4.7, 1.5 Hz, 1H), 8.15 (dd, J¼8.2, 1.5 Hz, 1H), 7.59e7.53
(m, 2H), 7.46 (dd, J¼8.2, 4.7 Hz, 1H), 7.22e7.08 (m, 2H).
4.2. Detailed synthetic protocols
4.2.1.9. 2-(4-Chlorophenyl)-3-nitropyridine (9a). A yellow pow-
der (63% yield), mp 134e136 ꢀC; 1H NMR (CDCl3, 300 MHz):
d
8.86
4.2.1. General procedures for preparations of 1ae22a. A 30-mL
screw-cap culture tube was charged with 2-chloro-3-nitropyridine
(3.16 mmol), phenyl boronic acid (3.80 mmol, 1.2 equiv), and DMF
(10 mL). Pd(PPh3)4 (5% eq) and K2CO3 (0.3 mL of 2 M aqueous solu-
tion, 0.60 mmol, 2 equiv) were added tothe tube sparged with N2 for
5 min. The reaction mixture was stirred and then irradiated for
15 min at 50 W. The resulting mixturewas diluted with ethyl acetate
and washed with water and brine, and then was dried over anhy-
drous Na2SO4. The residue was concentrated with an evaporator,
and purified by flash chromatography on silica gel using petroleum
ether/ethyl acetate as the eluent, yielded the desired product.
(dd, J¼4.7, 1.5 Hz, 1H), 8.1 (dd, J¼8.2, 1.5 Hz, 1H), 7.56e7.32 (m, 5H).
13C NMR (CDCl3, 100 MHz)
d 152.2, 151.6, 145.9, 136.0, 134.6, 132.3,
129.4, 128.9, 122.7. HRMS (m/z) calcd for C11H7ClN2O2 [M]þ,
234.0196, found 234.0195.
4.2.1.10. Methyl 4-(3-nitropyridin-2-yl)benzoate (10a). A white
powder (62% yield), mp 118e120 ꢀC; 1H NMR (CDCl3, 300 MHz):
d
8.89 (dd, J¼4.7, 1.5 Hz, 1H), 8.21 (dd, J¼8.2, 1.45 Hz, 1H), 8.14 (d,
J¼8.5 Hz, 2H), 7.63 (d, J¼8.5 Hz, 2H), 7.50 (dd, J¼8.2, 4.7 Hz, 1H),
3.94 (s, 3H). 13C NMR (CDCl3, 100 MHz)
166.4, 152.3, 152.0, 146.1,
d
140.6, 132.4, 131.1, 129.9, 128.1, 123.0, 52.3. HRMS (m/z) calcd for
C13H10N2O4 [M]þ, 258.0641, found 258.0649.
4.2.1.1. 3-Nitro-2-(2,3,4-trimethoxyphenyl)pyridine (1a). A yel-
low powder (92% yield): mp 116e118 ꢀC; 1H NMR (CDCl3,
300 MHz):
d
8.85 (dd, J¼4.8, 1.5 Hz, 1H), 8.24 (dd, J¼8.1, 1.5 Hz, 1H),
4.2.1.11. 4-(3-Nitropyridin-2-yl)benzonitrile
(11a). A
white
7.41 (dd, J¼8.1, 4.7 Hz, 1H), 7.37 (d, J¼8.8 Hz, 1H), 6.82 (d, J¼8.8 Hz,
powder (66% yield): mp 192e194 ꢀC; 1H NMR (CDCl3, 300 MHz):
d
1H), 3.92 (s, 3H), 3.85 (s, 3H), 3.69 (s, 3H). 13C NMR (100 MHz,
8.90 (dd, J¼4.7, 1.4 Hz, 1H), 8.26 (dd, J¼8.2, 1.4 Hz, 1H), 7.77 (d,
CDCl3)
d 155.4, 152.3, 150.9, 150.1, 146.4, 141.2, 131.9, 124.8, 123.6,
J¼8.2 Hz, 2H), 7.66 (d, J¼8.2 Hz, 2H), 7.55 (dd, J¼8.2, 4.7 Hz, 1H).13C
121.9, 107.4, 61.0, 60.7, 56.0. HRMS (m/z) calcd for C14H14N2O5 [M]þ
NMR (CDCl3, 100 MHz):
d 152.5, 151.1, 145.9, 140.8, 132.6, 132.4,
290.0903, found 290.0900.
128.9, 123.5, 118.2, 113.4. HRMS (m/z) calcd for C12H7N3O2 [M]þ,
225.0538, found 225.0538.
4.2.1.2. 2-(3,4-Dimethoxyphenyl)-3-nitropyridine38 (2a). A yel-
low powder (75% yield): mp 154e156 ꢀC; 1H NMR (CDCl3,
4.2.1.12. 3-Nitro-2-(4-(trifluoromethyl)phenyl)pyridine41
(12a). A yellow powder (64% yield), mp 96e98 ꢀC; 1H NMR (CDCl3,
300 MHz):
d
8.82 (dd, J¼4.8, 1.4 Hz, 1H), 8.07 (dd, J¼8.0, 1.4 Hz, 1H),
7.39 (dd, J¼8.0, 4.7 Hz, 1H), 7.26 (s, 1H), 7.19 (d, J¼1.8 Hz, 1H), 7.11
(dd, J¼8.1, 1.9 Hz, 1H), 6.92 (d, J¼8.1 Hz, 1H), 3.93 (s, 6H).
300 MHz):
d
8.90 (d, J¼4.7 Hz, 1H), 8.23 (d, J¼8.1 Hz, 1H), 7.74 (d,
J¼8.4 Hz, 1H), 7.67 (d, J¼8.4 Hz, 1H), 7.52 (dd, J¼8.1, 4.7 Hz, 1H).
4.2.1.3. 2-(4-Methoxyphenyl)-3-nitropyridine38 (3a). A pale yel-
low powder (80% yield): mp 230e232 ꢀC; 1H NMR (DMSO-d6,
4.2.1.13. 2-(Naphthalen-2-yl)-3-nitropyridine42 (13a). A yellow
powder (50% yield), mp 160e162 ꢀC; 1H NMR (CDCl3, 300 MHz):
300 MHz):
d
8.88 (dd, J¼4.7, 1.4 Hz, 1H), 8.40 (dd, J¼8.2, 1.4 Hz, 1H),
d
8.91 (dd, J¼4.7, 1.5 Hz, 1H), 8.20 (dd, J¼8.2, 1.5 Hz, 1H), 8.11 (s, 1H),
7.62 (dd, J¼8.2, 4.7 Hz, 1H), 7.49 (d, J¼8.8 Hz, 2H), 7.06 (d, J¼8.8 Hz,
7.9e7.82 (m, 3H), 7.62 (dd, J¼8.5,1.8 Hz,1H), 7.57e7.52 (m, 2H), 7.48
(dd, J¼8.2, 4.7 Hz, 1H).
2H), 3.82 (s, 3H).
4.2.1.4. 2-(3-Methoxyphenyl)-3-nitropyridine (4a). A white
powder (70% yield), mp 114e116 ꢀC; 1H NMR (CDCl3, 300 MHz):
4.2.1.14. 2-(Naphthalen-1-yl)-3-nitropyridine (14a). A yellow
powder (60% yield), mp 184e186 ꢀC; 1H NMR (CDCl3, 300 MHz):
d
8.86 (dd, J¼4.7, 1.5 Hz, 1H), 8.13 (dd, J¼8.1, 1.5 Hz, 1H), 7.45 (dd,
d
11.38 (s, 1H), 8.97 (dd, J¼4.7, 1.5 Hz, 1H), 8.49 (dd, J¼8.2, 1.5 Hz,
J¼8.1, 4.7 Hz, 1H), 7.37 (t, J¼7.9 Hz, 1H), 7.16e7.12 (m, 1H), 7.10 (ddd,
J¼7.6, 1.6, 1.0 Hz, 1H), 7.02 (ddd, J¼8.3, 2.6, 1.0 Hz, 1H), 3.85 (s, 3H).
1H), 7.70 (dd, J¼8.2, 4.7 Hz, 1H), 7.54 (d, J¼7.9 Hz, 1H), 7.43 (t,
J¼2.8 Hz, 1H), 7.22 (t, J¼7.6 Hz, 1H), 7.15 (d, J¼7.9 Hz, 1H), 6.20 (s,
13C NMR (CDCl3, 100 MHz)
d 159.8, 152.6, 152.0, 146.3, 137.4, 132.0,
1H). 13C NMR (100 MHz, CDCl3)
d 152.6, 151.9, 146.6, 135.9, 132.8,
129.8, 122.4, 120.2, 115.8, 113.2, 55.3. HRMS (m/z) calcd for
128.0, 126.7, 125.9, 123.0, 120.9, 119.4, 112.9, 99.3. HRMS (m/z) calcd
C12H10N2O3 [M]þ, 230.0691, found 230.0697.
for C13H9N3O2 [M]þ, 239.0695, found 239.0701.
4.2.1.5. 2-(2-Methoxyphenyl)-3-nitropyridine (5a). A yellow
powder (86% yield), mp 168e170 ꢀC; 1H NMR (CDCl3, 300 MHz):
4.2.1.15. 4-(3-Nitropyridin-2-yl)-1H-indole (15a). Yellow oil
(65% yield); 1H NMR (CDCl3, 300 MHz):
d
8.97 (dd, J¼4.7,1.4 Hz,1H),
8.37 (dd, J¼8.2, 1.4 Hz, 1H), 8.02e7.88 (m, 2H), 7.62e7.40 (m, 6H).
13C NMR (101 MHz, CDCl3)
153.3, 152.6, 147.0, 134.4, 133.5, 132.2,
d
8.87 (d, J¼4.7 Hz, 1H), 8.21 (d, J¼8.5 Hz, 1H), 7.67 (dd, J¼7.7 Hz,
1H), 7.48e7.36 (m, 2H), 7.14 (t, J¼7.7 Hz, 1H), 6.91 (d, J¼8.5 Hz, 1H),
3.71 (s, 3H). 13C NMR (CDCl3, 100 MHz)
156.0, 152.4, 150.4, 146.9,
d
d
130.8, 129.7, 128.5, 126.9, 126.3, 126.2, 125.1, 124.1, 123.0. HRMS (m/
z) calcd for C15H10N2O2 [M]þ, 250.0742, found 250.0739.
131.6, 131.2, 130.4, 126.1, 122.1, 121.4, 110.5, 54.9. HRMS (m/z) calcd
for C12H10N2O3 [M]þ, 230.0691, found 230.0696.
4.2.1.6. 3-Nitro-2-(p-tolyl)pyridine39 (6a). A yellow powder
4.2.1.16. 6-(3-Nitropyridin-2-yl)-1H-indole (16a). A red power
(75% yield), mp 122e124 ꢀC; 1H NMR (CDCl3, 300 MHz):
d 8.85 (d,
(90% yield), mp 88e90 ꢀC; 1H NMR (CDCl3, 300 MHz):
d 8.84 (dd,
J¼4.7 Hz, 1H), 8.35 (s, 1H), 8.10 (d, J¼8.0 Hz, 1H), 7.71 (m, 2H), 7.39
J¼4.7, 1.5 Hz, 1H), 8.11 (dd, J¼8.4, 1.5 Hz, 1H), 7.47 (d, J¼8.4 Hz, 2H),
(dd, J¼8.0, 4.7 Hz, 1H), 7.31 (m, 2H), 6.60 (s, 1H). 13C NMR (CDCl3,
7.40 (dd, J¼8.4, 4.7 Hz, 1H), 7.27 (d, J¼8.4 Hz, 2H), 2.41 (s, 3H).
100 MHz) d 153.5, 151.8, 146.4, 135.7, 132.1, 129.5, 129.1, 126.3, 121.5,
121.1, 119.7, 111.2, 102.6. HRMS (m/z) calcd for C13H9N3O2 [M]þ,
4.2.1.7. 3-Nitro-2-(o-tolyl)pyridine39 (7a). A yellow solid (70%
yield), mp 58e60 ꢀC; 1H NMR (CDCl3, 300 MHz):
d
8.88 (d, J¼4.8 Hz,
239.0695, found 239.0701.

H. Peng et al. / Tetrahedron 67 (2011) 5725e5731
5729
4.2.1.17. 3-Nitro-2-(thiophen-3-yl)pyridine (17a). Yellow oil
(60% yield); 1H NMR (DMSO-d6, 300 MHz):
8.80 (dd, J¼4.7, 1.8 Hz,
1H), 8.03 (dd, J¼8.2, 1.8 Hz, 1H), 7.77 ( dd, J¼3.2, 1.4 Hz, 1H), 7.36 (m,
109.0, 94.7, 55.3; HRMS (m/z) calcd for C12H10N2O [MþH]þ,
d
198.0793, found 198.0801.
3H). 13C NMR (CDCl3, 100 MHz,)
d
151.7, 146.6, 145.2, 136.5, 131.5,
4.2.2.4. 6-Methoxy-5H-pyrido[3,2-b]indole
(4b-1). A white
11.48 (br
126.7, 126.6, 126.1, 121.9. HRMS (m/z) calcd for C9H6N2O2S [M]þ,
powder, mp 242e244 ꢀC; 1H NMR (DMSO-d6, 300 MHz):
d
206.0150, found 206.0154.
s,1H), 8.07 (dd, J¼4.7,1.2 Hz,1H), 7.82 (dd, J¼8.2,1.2 Hz,1H), 7.75 (d,
J¼7.6 Hz, 1H), 7.36 (dd, J¼8.2, 4.7 Hz, 1H), 7.17 (t, J¼7.9 Hz, 1H), 7.09
(d, J¼7.9 Hz, 1H), 4.00 (s, 3H). 13C NMR (DMSO-d6, 100 MHz,):
4.2.1.18. 40-Methyl-2-nitrobiphenyl (18a)43. Yellow oil (90%
yield) 1H NMR (300 MHz, CD3COCD3):
d
7.90 (dd, J¼8.1, 1.0 Hz, 1H),
d 145.9, 141.3, 141.2, 132.7, 130.6, 122.7, 120.0, 119.8, 118.3, 112.3,
7.77e7.69 (m, 1H), 7.65e7.58 (m, 1H), 7.54 (dd, J¼7.6, 1.1 Hz, 1H),
107.6, 55.5; HRMS (m/z) calcd for C12H10N2O [M]þ, 198.0793, found
198.0794.
7.32e7.18 (m, 4H), 2.38 (s, 3H).
4.2.1.19. 2-Nitro-40-trifluoromethylbiphenyl (19a). Yellow oil
4.2.2.5. 8-Methoxy-5H-pyrido[3,2-b]indole
powder, mp 158e160 ꢀC (lit.47 155 ꢀC); 1H NMR (DMSO-d6,
300 MHz):
(4b-2). A white
(75% yield); 1H NMR (CD3OD, 300 MHz):
d
7.98 (dd, J¼8.2, 1.1, 1H),
7.78e7.70 (m, 3H), 7.63 (td, J¼7.8, 1.5, 1H), 7.55e7.48 (m, 3H).
d
11.23 (br, 1H), 8.40 (d, J¼4.7 Hz, 1H), 7.84 (d, J¼8.2 Hz,
1H), 7.66 (d, J¼2.3 Hz, 1H), 7.48 (d, J¼8.8 Hz, 1H), 7.35 (dd, J¼8.3,
4.2.1.20. 20-Nitrobiphenyl-3-carbaldehyde
(20a)44. A white
4.6 Hz, 1H), 7.14 (dd, J¼8.8 Hz, 1H), 3.86 (s, 3H).
powder (86% yield), mp 93e95 ꢀC; 1H NMR (300 MHz, CDCl3):
d
10.06 (s, 1H), 8.00e7.91 (m, 2H), 7.89e7.80 (m, 1H), 7.68 (m, 1H),
4.2.2.6. 9-Methoxy-5H-pyrido[3,2-b]indole (5b). A white pow-
7.64e7.52 (m, 3H), 7.46 (dd, J¼7.5, 1.3 Hz, 1H).
der, mp 288e290 ꢀC; 1H NMR (DMSO-d6, 300 MHz):
d 11.44 (br s,
1H), 8.42 (d, J¼4.4 Hz, 1H), 7.80 (d, J¼8.2 Hz, 1H), 7.41 (t,
J¼8.2 Hz, 1H), 7.31 (dd, J¼7.9, 4.7 Hz, 1H), 7.12 (d, J¼8.2 Hz, 1H),
6.74 (d, J¼7.9 Hz, 1H), 3.98 (s, 3H); 13C NMR (DMSO-d6,
4.2.1.21. 2-Methoxy-20-nitrobiphenyl (21a)45. A yellow powder
(80% yield), mp 86e87 ꢀC (lit.46 83 ꢀC); 1H NMR (300 MHz, CDCl3):
d
7.93 (dd, J¼8.1, 1.0 Hz, 1H), 7.63 (td, J¼7.5, 1.3 Hz, 1H), 7.51e7.35
100 MHz): d 155.7, 142.1, 141.1, 140.9, 132.1, 128.4, 119.1, 117.2,
(m, 3H), 7.32 (dd, J¼7.5, 1.5 Hz, 1H), 7.08 (td, J¼7.5, 1.1 Hz, 1H), 6.91
(d, J¼8.3 Hz, 1H), 3.70 (s, 3H).
110.5, 104.3, 100.7, 55.3. HRMS (m/z) calcd for C14H14N2O [M]þ
198.0793, found 198.0785.
4.2.1.22. 30-Methoxy-5-methyl-2-nitrobiphenyl (22a). Yellow oil
4.2.2.7. 7-Methyl-5H-pyrido[3,2-b]indole (6b). A pale yellow
(80% yield), 1H NMR (300 MHz, DMSO-d6):
d
7.89 (d, J¼8.3 Hz, 1H),
7.46e7.30 (m, 3H), 6.99 (d, J¼8.2 Hz,1H), 6.93e6.80 (m, 2H), 3.79 (s,
3H), 2.45 (s, 3H). 13C NMR (100 MHz, CDCl3)
159.47, 146.76, 143.31,
powder, mp 212e214 ꢀC; 1H NMR (DMSO-d6, 300 MHz):
d 10.78
(br s, 1H), 8.89 (d, J¼5.4 Hz, 1H), 8.57 (d, J¼8.2 Hz, 1H), 8.26 (d,
J¼8.2 Hz, 1H), 7.82 (s, 1H), 7.75 (dd, J¼8.0, 4.7 Hz, 1H), 7.55 (d,
J¼7.9 Hz, 1H), 2.96 (s, 3H); 13C NMR (DMSO-d6, 100 MHz):
d
139.00, 136.12, 132.32, 129.50, 128.63, 124.12, 120.07, 113.45, 113.33,
55.08, 21.20. HRMS (m/z) calcd for C14H13NO3 [M]þ, 243.0895, found
243.0890.
d
141.3, 141.0, 140.9, 137.2, 132.8, 120.9, 119.7, 119.6, 119.3, 117.6,
111.5, 21.4. HRMS (m/z) calcd for C12H10N2 [M]þ 182.0844, found
182.0835.
4.2.2. General procedures for the preparation of carbolines and
carbazoles. 3-Nitro-2-phenylpyridine (0.34 mmol) and DPPE
(0.37 mmol, 1.1 equiv) were mixed well in a 10 mL round bottle
without solvent, and the bottle was immersed in an oil bath of
150 ꢀC under N2 atmosphere. The reaction was cooled after 5 h
and the residue was subjected to column chromatography on silica
gel using petroleum ether/ethyl acetate as eluants to give the
product.
4.2.2.8. 9-Methyl-5H-pyrido[3,2-b]indole (7b). A white powder,
mp 190e192 ꢀC; 1H NMR (DMSO-d6, 300 MHz):
d 11.36 (br s, 1H),
8.47 (dd, J¼4.7, 1.4 Hz, 1H), 7.85 (dd, J¼8.2, 1.4 Hz, 1H), 7.35 (m, 3H),
6.70 (t, J¼4.4 Hz, 1H), 2.95 (s, 3H); 13C NMR (DMSO-d6, 100 MHz):
d
142.4, 141.0, 140.6, 133.4, 132.8, 127.0, 120.4, 119.7, 119.3, 117.4,
108.9, 19.31; HRMS (m/z) calcd for C12H10N2 [M]þ, 82.0844, found
182.0838.
4.2.2.1. 7,8,9-Trimethoxy-5H-pyrido[3,2-b]indole (1b). A white
4.2.2.9. 7-Fluoro-5H-pyrido[3,2-b]indole
(8b). A
yellowish
powder: mp180e182 ꢀC; 1H NMR (DMSO-d6, 300 MHz):
d 11.30 (br
brown powder, mp 290e292 ꢀC; 1H NMR (DMSO-d6, 300 MHz):
s, 1H), 8.41 (d, J¼4.7 Hz, 1H), 7.77 (d, J¼7.9 Hz, 1H), 7.26 (dd, J¼8.0,
d
11.27 (br s, 1H), 8.38 (d, J¼4.7 Hz, 1H), 8.02 (d, J¼7.9 Hz, 1H), 7.80
4.7 Hz, 1H), 6.84 (s, 1H), 4.16 (s, 3H), 3.90 (s, 3H), 3.74 (s, 3H); 13C
(d, J¼8.3 Hz, 1H), 7.34e7.28 (m, 2H), 7.05 (d, J¼7.9 Hz, 1H). 13C NMR
NMR (DMSO-d6, 75 MHz) :
d
154.3, 148.2, 140.9, 140.7, 138.1, 135.4,
(DMSO-d6,100 MHz):
d
162.1 (d, J¼240 Hz),141.5,141.1 (d, J¼13 Hz),
132.5, 118.3, 116.9, 107.7, 90.0, 61.1, 61.0, 55.9; HRMS (m/z) calcd for
140.8, 133.4, 121.6 (d, J¼15 Hz),119.9,118.3,118.0,107.7 (d, J¼26 Hz),
98.1 (d, J¼26 Hz). HRMS (m/z) calcd for C11H7FN2 [M]þ, 186.0593,
found 186.0589.
C14H14N2O3 [M]þ 258.1004, found 258.0996.
4.2.2.2. 6,7-Dimethoxy-5H-pyrido[3,2-b]indole (2b). A white
powder, mp 186e188 ꢀC; 1H NMR (DMSO-d6, 300 MHz):
d
11.36 (br
4.2.2.10. 7-Chloro-5H-pyrido[3,2-b]indole (9b). A white pow-
s, 1H), 8.37 (d, J¼4.7 Hz, 1H), 7.85 (d, J¼8.5 Hz, 1H), 7.76 (d, J¼8.2 Hz,
der, mp >300 ꢀC; 1H NMR (DMSO-d6, 300 MHz):
d 11.57 (br s,
1H), 7.30 (dd, J¼8.2, 5.0 Hz, 1H), 7.03 (d, J¼8.5 Hz, 1H), 3.92 (s, 6H);
1H), 8.46 (dd, J¼4.7, 1.2 Hz, 1H), 8.15 (d, J¼8.8 Hz, 1H), 7.90 (dd,
J¼8.2, 1.2 Hz, 1H), 7.60 (d, J¼1.7 Hz, 1H), 7.40 (dd, J¼8.5, 4.7 Hz,
1H), 7.24 (dd, J¼8.5, 1.7 Hz, 1H). 13C NMR (DMSO-d6, 100 MHz)
13C NMR (DMSO-d6, 100 MHz):
d 166.7, 142.1, 140.0, 139.6, 134.4,
128.0, 125.0, 121.5, 120.0, 119.8, 118.8, 113.1, 52.1; HRMS (m/z) calcd
for C13H12N2O2 [M]þ, 228.0899, found 228.0896.
d 141.7, 140.8, 140.4, 133.2, 131.6, 121.3, 120.5, 120.5, 119.6, 118.3,
111.3. HRMS (m/z) calcd for C11H7ClN2 [M]þ, 202.0298, found
4.2.2.3. 7-Methoxy-5H-pyrido[3,2-b]indole (3b). A white pow-
202.0296.
der, mp 228e230 ꢀC; 1H NMR (DMSO-d6, 300 MHz):
d 11.29 (br s,
1H), 8.38 (dd, J¼4.7, 1.1 Hz, 1H), 8.04 (d, J¼8.5 Hz, 1H), 7.80 (dd,
J¼8.2, 1.1 Hz, 1H), 7.29 (dd, J¼8.2, 4.7 Hz, 1H), 7.03 (d, J¼2.1 Hz, 1H),
6.86 (dd, J¼8.5, 2.1 Hz, 1H), 3.88 (s, 3H); 13C NMR (DMSO-d6,
4.2.2.11. Methyl 5H-pyrido[3,2-b]indole-7-carboxylate (10b). A
white powder, mp 274e276 ꢀC; 1H NMR (DMSO-d6, 300 MHz):
d
11.74 (br s, 1H), 8.54 (d, J¼4.1 Hz, 1H), 8.29 (d, J¼8.2 Hz, 1H), 8.19
100 MHz): d 159.9, 142.1, 141.5, 140.9, 132.8, 120.9, 118.8, 117.3, 115.2,
(s, 1H), 7.99 (d, J¼9.1 Hz, 1H), 7.84 (d, J¼8.2 Hz, 1H), 7.48 (dd, J¼8.2,

5730
H. Peng et al. / Tetrahedron 67 (2011) 5725e5731
4.7 Hz, 1H), 3.91 (s, 3H). 13C NMR (DMSO-d6, 100 MHz):
141.8, 140.9, 135.0, 133.5, 133.4, 119.3, 117.6, 117.4, 115.4, 106.8, 60.4,
56.5. HRMS (m/z) calcd for C13H10N2O2 [M]þ, 226.0742, found
226.0736.
d
151.2,
(d, J¼7.4 Hz, 1H), 7.35 (d, J¼8.2 Hz, 1H), 7.31 (s, 1H), 7.16e7.11 (m,
1H), 7.01 (d, J¼8.2 Hz, 1H), 2.48 (s, 3H).
4.2.2.20. 2-(Trifluoromethyl)-9H-carbazole (19b). A white pow-
der, mp 209e211 ꢀC (lit.51 210e211 ꢀC); 1H NMR (CD3COCD3,
4.2.2.12. 5H-Pyrido[3,2-b]indole-7-carbonitrile (11b). A white
300 MHz):
d
10.77 (br s, 1H), 8.34 (d, J¼8.8 Hz, 1H), 8.24 (d,
powder, mp >300 ꢀC; 1H NMR (DMSO-d6, 300 MHz):
d
11.93 (br s,
J¼8.2 Hz,1H), 7.88 (s,1H), 7.62 (d, J¼7.4 Hz,1H), 7.50 (m, 2H), 7.27 (t,
J¼7.6 Hz, 1H).
1H), 8.57 (d, J¼4.6 Hz, 1H), 8.35 (d, J¼8.2 Hz, 1H), 8.10 (s, 1H), 8.00
(d, J¼8.2 Hz, 1H), 7.62 (d, J¼8.3 Hz, 1H), 7.52 (dd, J¼8.2, 4.7 Hz, 1H).
13C NMR (DMSO-d6, 100 MHz):
d
142.6, 139.6, 139.0, 134.4, 124.8,
4.2.2.21. 9H-Carbazole-1-carbaldehyde52 (20b-1). A yellow
powder, mp 143e145 ꢀC (143 ꢀC); 1H NMR (DMSO-d6, 300 MHz):
122.1, 121.9, 121.0, 119.7, 119.1, 116.3, 108.6. HRMS (m/z) calcd for
C12H7N3 [M]þ, 193.0640, found 193.0653.
d
11.86 (br s, 1H), 10.23 (br s, 1H), 8.50 (d, J¼7.9 Hz, 1H), 8.20 (d,
J¼7.9 Hz, 1H), 8.00 (d, J¼7.3 Hz, 1H), 7.75 (d, J¼7.6 Hz, 1H),
7.49e7.42 (m, 1H), 7.41e7.35 (m, 1H), 7.28e7.21 (m, 1H).
4.2.2.13. 7-(Trifluoromethyl)-5H-pyrido[3,2-b]indole48 (12b). A
white powder, mp >300 ꢀC; 1H NMR (DMSO-d6, 300 MHz):
d 10.80
(br s, 1H), 8.55 (d, J¼4.7 Hz, 1H), 8.39 (d, J¼8.2 Hz, 1H), 8.02 (d,
J¼8.5 Hz, 1H), 7.92 (s, 1H), 7.54 (d, J¼8.2 Hz, 1H), 7.50 (dd, J¼8.2,
4.7 Hz, 1H).
4.2.2.22. 9H-Carbazole-3-carbaldehyde53 (20b-2). An earth yel-
low powder, mp 157e159 ꢀC (lit.54 158e159 ꢀC); 1H NMR (DMSO-
d6, 300 MHz): d 11.85 (br s, 1H), 10.03 (br s, 1H), 8.72 (s, 1H), 8.24 (d,
J¼8.2 Hz, 1H), 7.91 (d, J¼8.2 Hz, 1H), 7.61 (d, J¼8.5 Hz, 1H), 7.55 (d,
4.2.2.14. 11H-Benzo[g]pyrido[3,2-b]indole (13b). A yellow pow-
J¼7.6 Hz, 1H), 7.46 (t, J¼7.8 Hz, 1H), 7.25 (t, J¼8.1 Hz, 1H).
der, mp >300 ꢀC; 1H NMR (DMSO-d6, 300 MHz):
d 12.40 (br s, 1H),
8.53 (m, 2H), 8.23 (d, J¼8.2 Hz, 1H), 8.09 (d, J¼8.4 Hz, 1H), 8.02 (dd,
4.2.2.23. 4-Methoxy-9H-carbazole (21b). A yellow powder, mp
138e139 ꢀC (lit.55 135e136 ꢀC); 1H NMR (300 MHz, DMSO-d6)
J¼8.5, 1.2 Hz, 1H), 7.66 (m, 3H), 7.41 (dd, J¼8.3, 4.7 Hz, 1H). 13C NMR
(DMSO-d6, 100 MHz,):
d
142.0, 141.5, 136.7, 132.8, 131.8, 128.7, 126.1,
d
11.28 (s, 1H), 8.14 (d, J¼7.8 Hz, 1H), 7.46 (d, J¼8.1 Hz, 1H),
125.9, 121.8, 121.3, 120.1, 119.3, 118.7, 118.4, 116.5. HRMS (m/z) calcd
7.28e7.37 (m, 2H), 7.14 (m, 1H), 7.09 (d, J¼8.1 Hz, 1H), 6.71 (d,
J¼7.9 Hz, 1H), 4.02 (s, 3H).
for C15H10N2 [M]þ, 218.0844, found 218.0841.
4.2.2.15. 7H-Benzo[e]pyrido[3,2-b]indole (14b). A yellow pow-
4.2.2.24. 1-Methoxy-6-methyl-9H-carbazole (22b-1). A white
powder, mp 137e139 ꢀC (lit.56 137e138 ꢀC); 1H NMR (300 MHz,
der, mp 244e246 ꢀC; 1H NMR (DMSO-d6, 300 MHz):
d 11.91 (br s,
1H), 9.44 (d, J¼8.2 Hz, 1H), 8.63 (d, J¼4.6 Hz, 1H), 8.02 (m, 3H), 7.80
DMSO-d6)
d
11.14 (s, 1H), 7.84 (s, 1H), 7.63 (d, J¼7.7 Hz, 1H), 7.35 (d,
(d, J¼8.8 Hz, 1H), 7.73 (t, J¼8.2 Hz, 1H), 7.50 (t, J¼8.2 Hz, 1H), 7.45
J¼8.2 Hz, 1H), 7.17 (d, J¼8.2 Hz, 1H), 7.05 (t, J¼7.7 Hz, 1H), 6.94 (d,
(dd, J¼8.2, 4.7 Hz, 1H). 13C NMR (DMSO-d6, 100 MHz,)
d 142.3, 142.1,
J¼7.6 Hz, 1H), 3.96 (s, 3H), 2.44 (s, 3H).
138.4, 131.6, 128.9, 128.5, 128.4, 128.3, 126.9, 123.9, 123.3, 118.6,
118.4, 113.6, 113.1. HRMS (m/z) calcd for C15H10N2 [M]þ, 218.0844,
found 218.0845.
4.2.2.25. 3-Methoxy-6-methyl-9H-carbazole (22b-2). A white
powder, mp 181e182 ꢀC (lit.57 180 ꢀC); 1H NMR (300 MHz, DMSO-
d6)
d
10.86 (s, 1H), 7.87 (s, 1H), 7.61 (d, J¼1.9 Hz, 1H), 7.34 (d,
4.2.2.16. 3,6-Dihydropyrido[3,2-b]pyrrolo[3,2-e]indole (15b). An
earth yellow powder, mp 280e282 ꢀC; 1H NMR (DMSO-d6,
J¼8.3 Hz, 1H), 7.31 (d, J¼8.9 Hz, 1H), 7.17 (d, J¼8.2 Hz, 1H), 6.98 (dd,
J¼8.2, 1.9 Hz, 1H), 3.82 (s, 3H), 2.44 (s, 3H).
300 MHz):
d
11.30 (br s, 1H), 11.26 (br s, 1H), 8.47 (dd, J¼4.4, 1.1 Hz,
1H), 7.83 (d, J¼6.8 Hz, 1H), 7.58 (d, J¼8.5 Hz, 1H), 7.46 (t, J¼2.6 Hz,
Acknowledgements
1H), 7.29 (m, 2H), 7.06 (br s, 1H). 13C NMR (DMSO-d6, 100 MHz):
d
142.0, 140.8, 135.7, 131.8, 130.5, 124.9, 120.3, 118.1, 117.1, 112.6,
This work was financially supported by National Science and
Technology Major Project ‘Key New Drug Creation and
Manufacturing Program’, China (No. 2009ZX09301-001), the Na-
tional Natural Science Foundation of China (21072205), and by
Shanghai Municipality Science and Technology Development Fund
(09JC1416600, 09ZR1437900).
112.3, 106.1, 100.4. HRMS (m/z) calcd for C13H9N3 [M]þ, 207.0796,
found 207.0792.
4.2.2.17. 1,10-Dihydropyrido[3,2-b]pyrrolo[3,2-g]indole (16b). An
earth yellow powder, mp >300 ꢀC; 1H NMR (DMSO-d6,
300 MHz):
d
10.75 (br s, 1H), 8.88 (dd, J¼4.7, 1.5 Hz, 1H), 8.28 (dd,
J¼8.2, 1.4 Hz, 1H), 7.75 (br s, 1H), 7.65 (d, J¼8.5 Hz, 1H), 7.58 (dd,
J¼8.2, 4.7 Hz, 1H), 7.45 (d, J¼3.3 Hz, 1H), 7.24 (dd, J¼8.2, 1.5 Hz,
1H), 6.52 (d, J¼3.0 Hz, 1H). 13C NMR (DMSO-d6, 100 MHz):
References and notes
1. Gul, W.; Hamann, M. T. Life Sci. 2005, 78, 442e453.
2. Harbert, C. A. Mol. Pharmacol. 1980, 17, 38e42.
d
142.6, 140.9, 131.2, 127.9, 127.5, 124.4, 121.5, 118.1, 117.9, 115.3,
3. Inman, W. D.; Bray, W. M.; Gassner, N. C.; Lokey, R. S.; Tenney, K.; Shen, Y. Y.;
TenDyke, K.; Suh, T.; Crews, P. J. Nat. Prod. 2009, 73, 255e257.
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2010, 53, 5054e5058.
113.0, 111.6, 103.1. HRMS (m/z) calcd for C13H9N3 [M]þ, 207.0796,
found 207.0799.
4.2.2.18. 8H-Thieno[30,20:4,5]pyrrolo[3,2-b]pyridine (17b). A yel-
low powder, mp 294e296 ꢀC; 1H NMR (DMSO-d6, 300 MHz):
€
6. Fotso, S.; Maskey, R. P.; Schroder, D.; Ferrer, A. S.; Grǖn-Wollny, I.; Laatsch, H. J.
Nat. Prod. 2008, 71, 1630e1633.
ꢀ
7. Arzel, E.; Rocca, P.; Grellier, P.; Labaed, M.; Frappier, F.; Gueritte, F.; Gaspard, C.;
d
11.80 (br s, 1H), 8.33 (d, J¼4.7 Hz, 1H), 7.84 (d, J¼8.2 Hz, 1H), 7.43
(dd, J¼5.3, 0.9 Hz, 1H), 7.18 (dd, J¼8.2, 4.7 Hz, 1H), 7.14 (dd, J¼5.2,
0.9 Hz, 1H). 13C NMR (DMSO-d6, 100 MHz):
144.8, 141.3, 139.4,
ꢀ
Marsais, F.; Godard, A.; Queguiner, G. J. Med. Chem. 2001, 44, 949e960.
8. Bonjoch, J. D. F.; Pages, L.; Perez, D.; Soca, L.; Miralpeix, M.; Vilella, D.; Anton, P.;
Puig, C. Bioorg. Med. Chem. Lett. 2009, 19, 4299e4302.
9. Song, S. H. ,Y. E. J.; Shim, J. Y.; Kim, S. H.; Lee, K. H.; Suh, H. S. Adv. Sci. Technol.
d
134.8, 123.6, 118.6, 118.4, 117.2, 116.8. HRMS (m/z) calcd for C9H6N2S
2010, 75, 97e102.
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