Short and simple method of synthesis of some pyrrolo[3,2-b]quinoline derivatives from easily available nitrobenzene derivatives

Article abstract of DOI:10.1055/s-0030-1258555

The Vilsmeier-Hack condensation of ortho-cyanomethylated nitroarenes with N-methylpyrrolidone, followed by cyclization promoted by O,N- bistrimethylsilylacetamide and DBU in DMF led directly to pyrrolo[3,2-b] quinoline derivatives. Georg Thieme Verlag Stuttgart · New York.

Full text of DOI:10.1055/s-0030-1258555

LETTER
2435
Short and Simple Method of Synthesis of Some Pyrrolo[3,2-b]quinoline
Derivatives from Easily Available Nitrobenzene Derivatives
S
imple Synthes
b
is of Som
e
P
i
yrrolo[
g
3,2-
b
]quinol
n
ine
D
erivativ
i
e
s
ew Wróbel,* Krzysztof Wojciechowski, Andrzej Kwast, Norbert Gajda
Institute of Organic Chemistry, Polish Academy of Sciences, ul. Kasprzaka 44, POB 58, 01-224 Warszawa 42, Poland
Fax +48(22)6326681; E-mail: wrobel@icho.edu.pl
Received 2 July 2010
Although condensed benzo-heterocycles are very often
synthesized by means of various condensations of ni-
troarenes, when a functionalized carbon substituent in the
ortho position is present, preparation of required starting
nitroarenes is not always an easy task, or they are not sta-
ble compounds. On the contrary, the first method (path a
in Scheme 1) does not need synthesis of any ortho substi-
tuted derivative of the nitroarene, while the synthesis of
starting materials for the second approach, can be often
accomplished easily via vicarious nucleophilic substitu-
tion of hydrogen (VNS)8 usually followed by appropriate
modification of the introduced side chain.6,7
Abstract: The Vilsmeier–Hack condensation of ortho-cyanometh-
ylated nitroarenes with N-methylpyrrolidone, followed by cycliza-
tion promoted by O,N-bistrimethylsilylacetamide and DBU in DMF
led directly to pyrrolo[3,2-b]quinoline derivatives.
Key words: indoles, cyclization, fused-ring systems, heterocycles,
annulation
In our studies on synthesis of polycyclic nitrogen hetero-
cycles from easily available, cheap, diversely substituted
nitroarenes, we explore reactions which involve bases and
Lewis acids, working in tandem in the crucial step of the
reaction, forming a new nitrogen ring.
NO2
NO2
The ring is built on the existing nitrogen atom of the nitro
group, and employs a chain connected to the ortho posi-
tion of the arene. The latter can be a side chain existing in
the substrate, or can be formed in the addition reaction of
appropriate nucleophile to the nitroarene, with formation
X
EWG
EWG
base
VNS
R
R
EWG
path a
path b
H
of σ adduct in the ortho position. Thus, two ways of the
base
reaction course can be formulated, and are depicted in
Scheme 1.
_
_
O
O
+
N
NO2
H
Path a consists of the reactions of carbanions and other nu-
cleophiles of allylic/benzylic character, with nitroaromat-
EWG
H
EWG
ic compounds, leading to the σ adducts, which undergo
R
R
transformation to the corresponding nitrosoarenes, for-
mally as a result of base-induced elimination of water,
which can be assisted by proton or Lewis acids. The inter-
mediates undergo cyclization to the annulated hetero-
cyclic systems such as substituted quinoline,1,2 1-
hydroxyindole,2,3 acridine4 or more complex polycyclic
heterocyclic structures.5
base
base
Lewis acid
Lewis acid
O
N
N
Path b, on the other hand, involves transformation of ben-
zylic-type anions, generated from nitroarenes possessing
an unsaturated side chain in the ortho position. The nega-
tive charge of the anion, which in fact is generated by ab-
straction of the g hydrogen, is strongly delocalized and
stabilized by electron-withdrawing group (EWG). While
cyclization of such anions can be performed with the use
of a base in protic media, it often leads nonselectively to
five-, and six-membered-ring formation.6,7 In the base/
Lewis acid systems, such as Et3N–Me3SiCl, the quinoline
derivatives are formed exclusively in high yields.7
EWG
EWG
R
R
Scheme 1
In this communication we present the results of attempted
application of the second method mentioned above, for a
short synthesis of some pyrrolo[3,2-b]quinoline deriva-
tives. While many heterocycles containing the 4-azain-
dole core, e.g. tetracyclic analogues such as cryptolepine
and its derivatives,9 have been reported to show a wide
range of biological activities, pyrrolo[3,2-b]quinolines are
less studied, and their pharmacological potential has not
been disclosed yet. Only a small number of them have
been obtained, and methods of their synthesis are rather
SYNLETT 2010, No. 16, pp 2435–2438
x
x
.x
x
.2
0
1
0
Advanced online publication: 03.09.2010
DOI: 10.1055/s-0030-1258555; Art ID: G19710ST
© Georg Thieme Verlag Stuttgart · New York

2436
Z. Wróbel et al.
LETTER
O
N
N
N
Me
Me
Me
NO2
N
NO2
NO2
N
O
N
Me
CN
CN
CN
BSA, DBU
VNS
ref. 8a
R
CN
POCl3
Et3N
R
R
R
R
1
2
3
4
5a–g
Scheme 2 Synthesis of pyrrolo[3,2-b]quinolines from nitroarenes
limited. The most popular approach consists of building been precedented in one of our paper.16 The crucial step is
of a pyrrole ring on the 2-methyl-3-aminoquinolines by a cyclization of 3 to 4. It was based on previously de-
cyclocondensation with triethyl orthoformate,10a Vilsmei- scribed reactions of some 2-propylidene derivatives of 2,
er reagent,10b and other reagents.10c Similarly, reductive which under particular conditions led to the appropriate
cyclization of 3-nitroquinoline possessing N,N-dimethyl- quinoline N-oxides.6,7 Unfortunately, none of the earlier
aminovinyl group in position 2 leads to formation of the examined conditions, including the more successful
pyrrole ring.10d Another approach involves base-catalyzed NaOH–MeOH6 and Me3SiCl–Et3N–DMF7 systems,
Friedlander reaction for construction of the pyridine ring worked in this case.
in the reaction of 3-pyrrolidone derivatives with ortho-
However, a more powerful system, composed of O,N-
aminobenzaldehydes or their acetals, which produces 2,3-
bistrimethylsilylacetamide (BSA) and DBU in DMF was
dihydro derivatives of pyrrolo[3,2-b]quinoline.11 Similar,
found effective, when applied for prolonged time at room
but more convenient route, omitting ortho-aminoalde-
temperature, or elevated temperature. We found this sys-
hydes, employs functionalized 3-pyrrolidone deriva-
tem efficient in some cyclizations of sH adducts, accord-
tives.12 An interesting two-step method, starting from
ing to the path a in Scheme 1.1b,2,5 Under such conditions,
ortho-nitrobenzaldehyde derivatives comprises their con-
the expected primary product 4 was not observed in the re-
densation with pyrrole, followed by reductive cyclization,
action mixture, instead, the deoxygenation–aromatization
involving the nitro group and one of the two pyrrole
of 4 took place spontaneously, furnishing the target pyrro-
lo[3,2-b]quinoline derivative 5.
groups, promoted by SnCl2·2H2O in refluxing metha-
nol.13a As a result, the method is limited to pyrrolo[3,2-
The examples collected in Table 1 show, that while the
b]quinolines bearing additional 2-pyrrole substituent at C-
yields of this cyclization–disproportionation step vary
9 position. Earlier attempts of similar cyclizations were
strongly with diversely substituted substrates, in several
cases they can be of practical value. Analysis of the results
indicates a disfavoring effect of electron-rich substituents,
and those located at position ortho to the nitro group.
much less effective.13b Condensation of 2-amino-5-
phenyl-3H-1,4-benzodiazepines with 1,3-dicarbonyl
compounds is a method in which both nitrogen rings are
formed in the annulation process.14
In cases, when such unfavorable conditions are not met,
the presented approach seems to offer one of the simplest
and most convenient methods of synthesis of pyrrolo[3,2-
b]quinoline derivatives from easily available nitroarenes.
The starting materials for the described syntheses are not
easily available, and reaction conditions are usually harsh,
which excludes synthesis of compounds with labile sub-
stituents.
Many more methods are available for the synthesis of 4-
azaindoles15 which, however, have not found applications
in synthesis of their benzo analogues, especially pyrro-
lo[3,2-b]quinolines.
Table 1 Two-Step Synthesis of Pyrrolo[3,2-b]quinolines 5 from
ortho-Cyanomethylated Nitroarenes 217,18
Entry
5
R
3 from 2 5 from 3
Yield
(%)a
Temp
Time Yield
(days) (%)a
The three steps in simple route presented in this paper,
lead to the derivatives of 1-methyl-1H-pyrrolo[3,2-
b]quinoline, substituted, in the carbocyclic ring, and with
suitable for further functionalization carbonitrile group at
C-9 position.
1
2
3
4
5
6
7
a
b
c
d
e
f
7-Cl
63
44
47
69
54b
29
r.t.
1
1
59
59
51
27
45
24
25
7-Br
r.t.
The whole synthesis started from substituted nitroarenes 1
with at least one ortho position available for nucleophilic
attack (Scheme 2). They were converted into cyanometh-
yl derivatives 2 by reaction with 4-chlorophenoxyacetoni-
trile in the presence of potassium tert-butoxide, according
to the well-known vicarious nucleophilic substitution
(VNS) scheme.8 Incorporation of the N-methylpyrroli-
done as a nitrogen-containing five-membered-ring build-
ing block via Vilsmeier–Haack-type reaction has also
7-F
r.t.
1
7-MeO
7-SPh
5,7-Cl2
r.t.
14
2
r.t.
50 °C
80 °C
7
g
5-MeO-7-Cl 85
14
a Isolated yield.
b 3-Cyano-5-phenylthio[2,1]benzisoxazole (14%) was also isolated.
Synlett 2010, No. 16, 2435–2438 © Thieme Stuttgart · New York

LETTER
Simple Synthesis of Some Pyrrolo[3,2-b]quinoline Derivatives
2437
mmol, 0.6 mL) and DBU (2.5 mmol, 0.38 mL) were added
subsequently. The reaction mixture was stirred for the time,
and at the temperature specified in Table 1, then it was
poured into diluted aq NaCl solution (50 mL), and extracted
with EtOAc (3 × 30 mL). The extracts were combined,
washed with brine, dried over Na2SO4, and the solvent was
evaporated. The residue was chromatographed on SiO2
using hexane–EtOAc mixture as an eluent.
Contrary to another reported method, also involving in-
tramolecular cyclization of the nitro group with five-
membered nitrogen ring,13a it does not require reductive
conditions, and thus seems to be more promising for sen-
sitive substituents.
Acknowledgment
(18) Analytical data for the products: (2E,Z)-(5-Chloro-2-
nitrophenyl)(1-methylpyrrolidin-2-ylidene)acetonitrile
(3a): red crystals; mp 112–115 °C. Two isomers, M (major)/
N (minor) = 1.4. 1H NMR (500 MHz, CDCl3): d = 1.85–1.92
(m, 2 H, N), 2.00–2.10 (m, 2 H, M), 2.37 (t, J = 7.7 Hz, 2 H,
N), 2.47 (s, 3 H, M), 3.06 (t, J = 7.7 Hz, 2 H, M), 3.38 (s, 3
H, N), 3.50–3.58 (m, 2 H, M + 2 H, N), 7.34–7.38 (m, 1 H,
M + 1 H, N), 7.44 (d, J = 2.0 Hz, 1 H, M), 7.46 (d, J = 2.0
Hz, 1 H, N), 7.82 (d, J = 8.7 Hz, 1 H, N), 7.88 (d, J = 8.7 Hz,
1 H, M). MS (EI, 70 eV): m/z (%) = 277 (21), 137 (100).
HRMS (EI): m/z calcd for C13H12N3O235Cl: 277.0618;
found: 277.0615. (2E,Z)-(5-Bromo-2-nitrophenyl)(1-
methyl-pyrrolidin-2-ylidene)acetonitrile (3b): red
This research was supported by the Scientific Research Committee,
Grant NN 204193038.
References and Notes
(1) (a) Wróbel, Z. Tetrahedron Lett. 1997, 38, 4913.
(b) Wróbel, Z. Tetrahedron 1998, 54, 2607. (c) Bujok, R.;
Kwast, A.; Cmoch, P.; Wróbel, Z. Tetrahedron 2010, 66,
698.
(2) Wróbel, Z. Eur. J. Org. Chem. 2000, 521.
(3) Korda, A.; Wróbel, Z. Synlett 2003, 1465.
(4) Bobin, M.; Kwast, A.; Wróbel, Z. Tetrahedron 2007, 63,
11048.
crystals; mp 105–107 °C (EtOH). Two isomers, M (major)/
N (minor) = 1.3. 1H NMR (500 MHz, CDCl3): d = 1.85–1.92
(m, 2 H, N), 2.00–2.10 (m, 2 H, M), 2.37 (t, J = 7.6 Hz, 2 H,
N), 2.47 (s, 3 H, M), 3.06 (t, J = 7.8 Hz, 2 H, M), 3.38 (s, 3
H, N), 3.50–3.58 (m, 2 H, M + 2 H, N), 7.34–7.38 (m, 1 H,
M + 1 H, N), 7.44 (d, J = 2.0 Hz, 1 H, M), 7.46 (d, J = 2.0
Hz, 1 H, N), 7.82 (d, J = 8.7 Hz, 1 H, N), 7.88 (d, J = 8.7 Hz,
1 H, M). MS (EI, 70 eV): m/z (%) = 323 (10), 321 (10), 137
(100). HRMS (EI): m/z calcd for C13H12N3O279Br: 321.0113;
found: 321.0118. (2E,Z)-(5-Fluoro-2-nitrophenyl)(1-
methylpyrrolidin-2-ylidene)acetonitrile (3c): orange
crystals; mp 120–121 °C (hexane–EtOAc). Two isomers, M
(major)/N (minor) = 1.4. 1H NMR (500 MHz, CDCl3): d =
1.84–1.92 (m, 2 H, N), 2.00–2.11 (m, 2 H, M), 2.38 (t, J =
7.7 Hz, 2 H, N), 2.47 (s, 3 H, M), 3.06 (t, J = 7.8 Hz, 2 H,
M), 3.39 (s, 3 H, N), 3.50–3.58 (m, 2 H, M + 2 H, N), 7.05–
7.10 (m, 1 H, M + 1 H, N), 7.12–7.17 (m, 1 H, M + 1 H, N),
7.92 (dd, J = 8.8, 5.3 Hz, 1 H, N), 7.99 (dd, J = 8.9, 5.3 Hz,
1 H, M). MS (EI, 70 eV): m/z (%) = 261 (11), 137 (100).
HRMS (EI): m/z calcd for C13H12N3O2F: 261.0914; found:
261.0925. (2E,Z)-(5-Methoxy-2-nitrophenyl)(1-
(5) Wróbel, Z. Synlett 2004, 1929.
(6) Wróbel, Z.; Kwast, A.; Mąkosza, M. Synthesis 1993, 31.
(7) Wróbel, Z.; Mąkosza, M. Tetrahedron 1993, 49, 5315.
(8) (a) Mąkosza, M.; Winiarski, J. Acc. Chem. Res. 1987, 20,
282. (b) Mąkosza, M.; Wojciechowski, K. Liebigs Ann./
Recl. 1997, 1805. (c) Mąkosza, M.; Kwast, A. J. Phys. Org.
Chem. 1998, 11, 341.
(9) (a) Mardenborough, L.; Zhu, X.; Fan, P.; Jacob, M.; Khan,
S.; Walkerb, L.; Ablordeppey, S. Bioorg. Med. Chem. 2005,
13, 3955; and references cited therein. (b) Lavrado, J.;
Paulo, A.; Gut, J.; Rosenthal, P. J.; Moreira, R. Bioorg. Med.
Chem. Lett. 2008, 18, 1378.
(10) (a) Parrick, J.; Wilcox, R. J. Chem. Soc., Perkin Trans. 1
1976, 2121. (b) Clark, B. A. J.; Parrick, J.; West, P. J.; Kelly,
A. H. J. Chem. Soc. 1970, 498. (c) Khan, H.; Rocha, J.
Heterocycles 1977, 6, 1927. (d) Davydova, N. K.;
Solov’eva, N. P.; Chistyakov, V. V.; Marchenko, N. B.;
Glushkov, R. G. Khim. Geterotsikl. Soedin. 1989, 5, 633.
(11) (a) Zalkow, L.; Nabors, J.; French, K.; Bisarya, S. J. Chem.
Soc. C 1971, 3552. (b) Akue-Gedu, R.; Gautret, P.; Lelieur,
J.-P.; Rigo, B. Synthesis 2007, 3319; and references cited
therein.
methylpyrrolidin-2-ylidene)acetonitrile (3d):16 red
crystals; mp 89–92 °C. Two isomers, M (major)/N (minor)
= 2. 1H NMR (500 MHz, CDCl3): d = 1.82–1.88 (m, 2 H, N),
2.00–2.09 (m, 2 H, M), 2.34 (t, J = 7.7 Hz, 2 H, N), 2.44 (s,
3 H, M), 3.06 (t, J = 7.7 Hz, 2 H, M), 3.44–3.65 (m, 2 H, M
+ 2 H, N), 3.88 (s, 3 H, N), 3.89 (s, 3 H, M), 3.99 (s, 3 H, N),
6.86–6.90 (m, 2 H, M + 2 H, N), 7.97 (d, J = 9.0 Hz, 1 H, N),
8.02 (d, J = 9.0 Hz, 1 H, M). MS (EI, 70 eV): m/z (%) = 274
(14), 137 (100). Anal. Calcd for C14H15N3O3: C, 61.53; H,
5.53; N, 15.38. Found: C, 61.59; H, 5.46; N, 15.22.
(12) Boisse, T.; Gautret, P.; Rigo, B.; Goossens, L.; Henichart,
J.-P.; Gavara, L. Tetrahedron 2008, 64, 7266.
(13) (a) Sharma, S.; Kundu, B. Tetrahedron Lett. 2008, 49, 7062.
(b) Jones, G.; McKinley, W. H. J. Chem. Soc., Perkin Trans.
1 1979, 599.
(14) Szmuszkovicz, J.; Baczynskyj, L.; Chidester, C.; Duchamp,
D. J. Org. Chem. 1976, 41, 1743.
(15) Popowycz, F.; Mérour, J.-Y.; Joseph, B. Tetrahedron 2007,
63, 8689.
(2E,Z)-(1-Methylpyrrolidin-2-ylidene)[2-nitro-5-
(phenylthio)phenyl]acetonitrile (3e): red crystals; mp
147–151 °C (hexane–EtOAc). Two isomers, M (major)/N
(minor) = 1.5. 1H NMR (500 MHz, CDCl3): d = 1.80–1.88
(m, 2 H, N), 1.95–2.10 (m, 2 H, M), 2.30 (t, J = 7.6 Hz, 2 H,
N), 2.42 (s, 3 H, M), 3.00–3.05 (m, 2 H, M), 3.36 (s, 3 H, N),
3.46–3.56 (m, 2 H, M + 2 H, N), 6.99–7.06 (m, 1 H, M + 1
H, N), 7.15 (d, J = 2.0 Hz, 1 H, M), 7.17 (d, J = 1.9 Hz, 1 H,
N), 7.42–7.47 (m, 3 H, M + 3 H, N), 7.50–7.55 (m, 2 H, M
+ 2 H, N), 7.76 (d, J = 8.6 Hz, 1 H, N), 7.82 (d, J = 8.6 Hz,
1 H, M). MS (EI, 70 eV): m/z (%) = 351 (38), 252 (76), 223
(54), 137 (100). HRMS (EI): m/z calcd for C19H17N3SO2:
351.1041; found: 351.1050. (2E,Z)-(3,5-Dichloro-2-
nitrophenyl)(1-methylpyrrolidin-2-ylidene)acetonitrile
(3f): pale yellow crystals; mp 163–167 °C (hexane–EtOAc).
(16) Mąkosza, M.; Wróbel, Z. Rev. Roum. Chim. 1991, 36, 563;
Chem. Abstr. 1992, 117, 26036.
(17) General Procedure for the Synthesis of 5 from 2: The
cyanomethylated nitroarene 2 (2 mmol) dissolved in anhyd
N-methylpyrrolidone (10 mL) was cooled to 0 °C and Et3N
(3 mL) was added followed by slow addition of POCl3 (0.5
mL). The cooling bath was then removed, and the reaction
mixture was stirred for 30 min at r.t. The mixture was treated
with diluted, cold, aq NaCl (200 mL) and extracted with
EtOAc (3 × 50 mL). The combined extracts were washed
with brine and dried with Na2SO4. The solvent was
evaporated and the residue was chromatographed on SiO2
using hexane–EtOAc mixture as an eluent. The obtained 3
(0.5 mmol) was dissolved in anhyd DMF (3 mL). BSA (2.5
Synlett 2010, No. 16, 2435–2438 © Thieme Stuttgart · New York

2438
Z. Wróbel et al.
LETTER
125.1 (d, JC-F = 10.2 Hz), 129.7, 133.8 (d, JC-F = 9.3 Hz),
Two isomers, M/N = 1. 1H NMR (500 MHz, CDCl3): d =
1.85–1.92 (m, 2 H, N), 1.98–2.06 (m, 2 H, M), 2.43 (t, J =
7.8 Hz, 2 H, M or N), 2.56 (s, 3 H, M or N), 2.96–3.02 (m, 2
H, M or N), 3.33 (s, 3 H, M or N), 3.48–3.55 (m, 2 H, M + 2
H, N), 7.33 (d, J = 2.1 Hz, 1 H, M or N), 7.33 (d, J = 2.0 Hz,
1 H, M or N), 7.45 (d, J = 2.0 Hz, 1 H, M or N), 7.46 (d, J =
2.1 Hz, 1 H, M or N). MS (EI, 70 eV): m/z (%) = 311 (9), 137
(100). HRMS (EI): m/z calcd for C13H11N3O235Cl2:
141.6 (d, JC-F = 1.0 Hz), 142.1, 151.9 (d, JC-F = 2.4 Hz), 161.8
(d, JC-F = 247.8 Hz). MS (EI, 70 eV): m/z (%) = 225 (100),
197 (15), 183 (10), 171 (6). HRMS (EI): m/z calcd for
C13H8N3F: 225.0702; found: 225.0709. 7-Methoxy-1-
methyl-1H-pyrrolo[3,2-b]quinoline-9-carbonitrile (5d):
yellow crystals; mp 217–218 °C (EtOAc). 1H NMR (400
MHz, THF-d8): d = 3.99 (s, 3 H), 4.16 (s, 3 H), 6.73 (d, J =
3.5 Hz, 1 H), 7.32 (dd, J = 9.3, 2.8 Hz, 1 H), 7.45 (d, J = 2.8
Hz, 1 H), 7.69 (d, J = 3.5 Hz, 1 H), 8.03 (dd, J = 9.3, 0.3 Hz,
1 H). 13C NMR (100 MHz, THF-d8): d = 34.7, 55.9, 93.8,
101.8, 103.3, 116.3, 121.5, 125.9, 129.5, 132.6, 139.8,
141.4, 150.0, 159.6. MS (EI, 70 eV): m/z (%) = 237 (100),
222 (39), 194 (69). HRMS (EI): m/z calcd for C14H11N3O:
237.0902; found: 237.0896. 1-Methyl-7-(phenylthio)-1H-
pyrrolo[3,2-b]quinoline-9-carbonitrile (5e): yellow
crystals; mp 186–188 °C (EtOAc). 1H NMR (500 MHz,
THF-d8): d = 4.16 (s, 3 H), 6.76 (d, J = 3.5 Hz, 1 H), 7.30–
7.40 (m, 3 H), 7.46–7.49 (m, 2 H), 7.50 (dd, J = 9.0, 2.0 Hz,
1 H), 7.81 (J = 3.5 Hz, 1 H), 8.05 (J = 9.0, 0.5 Hz, 1 H), 8.11
(J = 2.0, 0.5 Hz, 1 H). 13C NMR (125 MHz, THF-d8): d =
33.8, 93.5, 102.3, 114.6, 123.6, 123.7, 127.8, 128.6, 128.7,
129.4, 130.8, 132.1, 134.2, 135.7, 140.8, 142.9, 151.1. MS
(EI, 70 eV): m/z (%) = 315 (100), 299 (12), 194 (8). HRMS
(EI): m/z calcd for C19H13N3S: 315.0830; found: 315.0837.
5,7-Dichloro-1-methyl-1H-pyrrolo[3,2-b]quinoline-9-
carbonitrile (5f): pale brown crystals; mp 252 °C (dec.). 1H
NMR (500 MHz, THF-d8): d = 4.22 (s, 3 H), 6.91 (d, J = 3.5
Hz, 1 H), 7.90 (d, J = 2.2 Hz, 1 H), 7.96 (d, J = 3.5 Hz, 1 H),
8.17 (d, J = 2.2 Hz, 1 H). 13C NMR (125 MHz, THF-d8): d =
34.8, 95.3, 103.8, 115.3, 122.8, 125.6, 128.8, 130.0, 132.2,
136.4, 139.4, 143.5, 152.7. MS (EI, 70 eV): m/z (%) = 277
(70), 275 (100). HRMS (EI): m/z calcd for C13H7N335Cl2:
275.0017; found: 275.0025. 7-Chloro-5-methoxy-1-
methyl-1H-pyrrolo[3,2-b]quinoline-9-carbonitrile (5g):
pale brown crystals; mp >250 °C. 1H NMR (500 MHz, THF-
d8): d = 4.06 (s, 3 H), 4.19 (s, 3 H), 6.82 (d, J = 3.5 Hz, 1 H),
7.08 (d, J = 2.0 Hz, 1 H), 7.75 (d, J = 2.0 Hz, 1 H), 7.83 (d,
J = 3.5 Hz, 1 H). 13C NMR (125 MHz, THF-d8): d = 34.7,
56.6, 94.2, 103.9, 107.8, 114.9, 115.8, 125.7, 129.7, 133.7,
136.0, 141.6, 150.9, 158.4. MS (EI, 70 eV): m/z (%) = 271
(95), 242 (100), 236 (35), 206 (11). HRMS (EI): m/z calcd
for C14H10N3O35Cl: 271.0512; found: 271.0519.
311.0228; found: 311.0222. (2E,Z)-(5-Chloro-3-methoxy-
2-nitrophenyl)(1-methylpyrrolidin-2-ylidene)-
acetonitrile (3g): yellow crystals; mp 146–149 °C (EtOH).
Two isomers, M (major)/ N (minor) = 1.2. 1H NMR (500
MHz, CDCl3): d = 1.82–1.90 (m, 2 H, N), 1.96–2.04 (m, 2
H, M), 2.44 (t, J = 7.8 Hz, 2 H, N), 2.57 (s, 3 H, M), 2.95–
3.01 (m, 2 H, M), 3.32 (s, 3 H, N), 3.46–3.54 (m, 2 H, M + 2
H, N), 6.96–7.00 (m, 2 H, M + 2 H, N). MS (EI, 70 eV):
m/z (%) = 307 (24), 137 (100). 7-Chloro-1-methyl-1H-
pyrrolo[3,2-b]quinoline-9-carbonitrile (5a): yellow
crystals; mp 198–201 °C. 1H NMR (500 MHz, THF-d8): d =
4.19 (s, 3 H), 6.79 (d, J = 3.5 Hz, 1 H), 7.65 (dd, J = 9.1, 2.3
Hz, 1 H), 7.86 (d, J = 3.5 Hz, 1 H), 8.14 (d, J = 9.1 Hz, 1 H),
8.19 (d, J = 2.3 Hz, 1 H). 13C NMR (125 MHz, THF-d8): d =
34.8, 94.5, 103.4, 115.5, 123.4, 124.8, 128.8, 129.7, 132.8,
133.2, 142.4, 143.3, 152.6. MS (EI, 70 eV): m/z (%) = 241
(100), 240 (31), 179 (5). HRMS (EI): m/z calcd for
C13H8N335Cl: 241.0407; found: 241.0410. 7-Bromo-1-
methyl-1H-pyrrolo[3,2-b]quinoline-9-carbonitrile (5b):
yellow crystals; mp 209–211 °C. 1H NMR (500 MHz, THF-
d8): d = 4.20 (s, 3 H), 6.80 (d, J = 3.5 Hz, 1 H), 7.78 (dd, J =
8.9, 2.2 Hz, 1 H), 7.88 (d, J = 3.5 Hz, 1 H), 8.07 (d, J = 8.9
Hz, 1 H), 8.36 (d, J = 2.2 Hz, 1 H). 13C NMR (125 MHz,
THF-d8): d = 33.8, 93.4, 102.4, 114.5, 120.4, 124.3, 125.7,
128.6, 130.4, 131.8, 141.6, 142.4, 151.6. MS (EI, 70 eV):
m/z (%) = 287 (88), 285 (100), 205 (10), 179 (9). HRMS
(EI): m/z calcd for C13H8N379Br: 284.9902; found: 284.9911.
7-Fluoro-1-methyl-1H-pyrrolo[3,2-b]quinoline-9-
carbonitrile (5c): pale green crystals; mp 182–185 °C
(hexane–EtOAc). 1H NMR (500 MHz, THF-d8): d = 4.18 (s,
3 H), 6.79 (d, J = 3.5 Hz, 1 H), 7.53 (ddd, J = 9.3, 8.1, 2.8
Hz, 1 H), 7.83 (d, J = 3.5 Hz, 1 H), 7.84 (ddd, J = 9.7, 2.8,
0.5 Hz, 1 H), 8.19 (ddd, J = 9.3, 5.7, 0.5 Hz, 1 H). 13C NMR
(125 MHz, THF-d8): d = 34.8, 94.7 (d, JC-F = 5.9 Hz), 103.4,
107.8 (d, JC-F = 24.5 Hz), 115.7, 118.4 (d, JC-F = 26.4 Hz),
Synlett 2010, No. 16, 2435–2438 © Thieme Stuttgart · New York