Synthesis of pyrrolo-, thienopyrrolo-, benzothienopyrroloquinolines as well as triazoloindole derivatives

Article abstract of DOI:10.1515/znb-1998-1019

Substituted pyrroloquinoline, thienopyrroloquinoline, benzothieno-pyrroloquinoline and triazoloindole derivatives have been synthesized starting from 6-amino-2,3-diphenylindole. The structures of the newly synthesized compounds were assigned with the help of IR, NMR and MS data.

Full text of DOI:10.1515/znb-1998-1019

Synthesis of Pyrrolo-, Thienopyrrolo-, Benzothienopyrroloquinolines
as well as Triazoloindole Derivatives
S. I. El-Desokya *, E. M. Kandeel3, A. H. Abd el-Rahmana, R. R. Shmidtb
a Chemistry Department, Faculty of Science, Mansoura University, Mansoura, A. R. Egypt
h Fakultät für Chemie, Universität Konstanz, Universitätsstraße 10, D-78434 Konstanz,
Germany
Z. Naturforsch. 53b, 1216-1222 (1988); received May 4, 1998
Pyrroloquinoline, Triazoloindole Derivatives, NMR Data, IR Data, MS Data
Substituted pyrroloquinoline, thienopyrroloquinoline, benzothieno-pyrroloquinoline and
triazoloindole derivatives have been synthesized starting from 6-amino-2,3-diphenylindole.
The structures of the newly synthesized compounds
and MS data.
were assigned with the help of IR, NMR
Indole and its derivatives represent one of the
most important classes of compounds which have
a wide spectrum of biological activity [1]. Quino-
line derivatives related to antitumor alkaloids
were synthesized they showed antileukemic and
antimalarial activities [2,3]. Significant biological
activities are also associated with substituted pyra-
Michael addition of 1 with dimethyl acetylenedi-
carboxylate proceeded smoothly to give the ena-
mine ester 7. The signal of the alkenic proton of 7
(at (3 = 5.34) lies in the region characteristic of the
vinyl resonance of fumarates [10]. Thermal cycli-
zation of 7 to give the pyrrolo[2,3-f]quinolone de-
rivative 8 was best accomplished in triethylenegly-
zoles and triazoles [4,5]. In view of these facts and col dimethyl ether (triglyme) rather than with
in continuation of our work on indoles [6 - 8], it
was worthwhile to synthesize new monocyclic or
polyphosphoric acid. The quinolone derivative 8
was converted to the required 4-chloro-2-me-
condensed heterocycles containing these struc- thoxycarbonyl-6,7-diphenylpyrrolo[2,3-f]quinoline
tural moieties.
Reaction of 6-amino-2,3-diphenylindole (1) [9]
(9) by refluxing in a phosphorus oxychloride/pyri-
dine mixture. The structures of compounds 8 and
with 3-chloro-6-methoxybenzo[b]thiophene-2-car- 9 were elucidated from ‘H NMR spectrum of com-
bonyl chloride in benzene afforded 3-chloro-6-me-
thoxy-N-(2’,3’-diphenyl-6’-indolyl) benzo[b]thio-
phene-2-carboxamide (2). Oxidative dehydrochlo-
rination of 2 via irradiation with a high pressure
mercury lamp furnished the lactam 3 which on re-
action with phosphorus pentasulphide in pyridine
pound 9 which showed two douplets at d 8.02 and
8.10 for H -8 and H-9 (7 = 9 Hz).
The synthesis of some 4-alicyclicaminopyrro-
loquinoline derivatives from the reaction of the
chloroquinoline derivative 9 with some secondary
amines was difficult [1 1 ], and instead the corre-
gave the benzothieno[3,2-c]pyrrolo[2,3-f]quinolin- sponding amides 10 were obtained. In the pres-
7(6H)thione (4). Refluxing 3 in phosphorus ox- ence of excess amine, the replacement of chlorine
ychloride yielded the 7-chlorobenzothienopyrro-
by the amine was observed and compound 11 was
loquinoline derivative 5 which was then catalyti- obtained as a minor product.
cally dechlorinated to give 10-methoxy-2,3-
diphenylf 1]benzothieno[2,3-c]pyrrolo[2,3-f]quino-
The dictamine group of alkaloids which occur
widely in Rutaceae have been characterized as de-
line (6). The structures of compounds 5 and 6 were rivatives of the furo[2,3]quinoline system [12].
elucidated from 'H NMR spectrum of compound Therefore, we tried to build the thienoquinoline
5 which showed two douplets at d 7.9 and <3 9.04
for H-4 and H-5 (/4,5 = 9 Hz).
derivative 15 as analogous of these alkaloids. Con-
densation of y-chlorobutyroyl chloride with 1 in
dry benzene gave 6 -amino-N-(y-chlorobutyroyl)-
2,3-diphenylindole (1 2 ) which was reacted with
phosphorus oxychloride in dimethyl formamide to
yield pyrroloquinoline derivatives 13 and 14 in a
* Reprint requests to Dr. S. I. El-Desoky.
0932-0776/98/1000-1216 $06.00 © 1998 Verlag der Zeitschrift für Naturforschung, Tübingen ■www.znaturforsch.com
D
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1217
S. I. E l-D esoky et al. • Synthesis of Pyrrolo-, Thienopyrrolo-, Benzothienopyrroloquinollines
Ph
X
NH
b, = S
c, =CH2
11
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1218
S. I. E l-D esoky et al. ■Synthesis of Pyrrolo-, Thienopyrrolo-, Benzothienopyrroloquinollines
Experimental
1:3 ratio. The structures of compounds 13 and 14
were elucidated from 'H NMR spectra which
showed for compound 14 two douplets at (3 7.72
and d 7.98 ppm for the aromatic protons H-8 and
H-9, while compound 13 showed two singlets at d
8.10 and d 8.17 for H-9 and H-5. Boiling 14 with
thiourea in ethanol afforded the desired thieno-
pyrroloquinoline derivative 15.
Formation of 14 encouraged us to construct a
pyrrolo[3,2-g]quinoline system. Therefore, 1 was
allowed to react with pentane-2,4-dione in concen-
trated sulphuric acid, to give 2,4-dimethyl-6,7-di-
phenylpyrrolo[3,2-g]quinoline (16) as the hydro-
chloride. The 'H NMR spectrum showed two
singlet peaks characteristic for H-5 and H-9 at d
8.12 and 8.09 ppm.
Solvents were purified in the usual way; petro-
leum ether had the boiling range 35-60 °C. Melt-
ing points are uncorrected. 'H NMR spectra:
Brücker W M 250 Cryospec, Jeol JNM-FX 90;
solvents CDC13, unless noted otherwise, internal
standard tetramethylsilane (TMS). Column chro-
matography: Merck silica gel 60, 0.063-0.200 mm.
Flash chromatography: Merck silica gel 60, 0.040-
0.063 mm. Medium pressure liquid chromatogra-
phy (MPLC): Merck silica gel Li Chroprep Si 60,
15-25 ^m. Thin layer chromatography (TLC):
Merck plates, silica gel 6O-F254 , layer thickness
0.2 mm. Detection by treatment with a solution of
15% H2S 0 4, followed by heating at 120 C.
3-Chloro-6-methoxy-N(2',3'-diphenyl-6’-indolyl)-
benzo[b]thiophene-2-carboxamide (2)
In view of the wide spectrum of activities associ-
ated with substituted triazoles, it was planned to
synthesize indole derivatives carrying this hetero-
cycle at position 6 . 6-Azido-2,3-diphenylindole
(17) was generated from compound 1 and then re-
acted with dienophiles such as dimethylacetylene-
dicarboxylate and ethyl cyanoacetate to furnish
A solution of 1 (7.14 g, 25.1 mmol) and 3-chloro-
6 -methoxybenzo[b]thiophene-2 -carbonyl chloride
(2.8 g, 10.72 mmol) in 100 ml dry benzene was
heated at 80 C for 1 h. The yellow precipitate
formed was filtered off, washed with ethanol and
the 1,4,5-trisubstituted triazoles 18 and 19, respec- crystallized from ethanol-DMF mixture (8:2) to
give colourless crystals, yield 76%, m.p. 266-268
C. !H NMR (250 MHz, [D6] DMSO): (5 11.60 (s,
br., 1H, CONH), 10.40 (s, br, 1 H, -NH), 8.12 (s,
1H, 7-H), 7.85 (d, 1H, 5'-H), 7.72 (s, 1 H, 7'-H),
tively. Unsuccessful attempts to eliminate nitrogen
from 18 for the synthesis of the pyrrolo[2,3-e]in-
dole derivative 20 were carried out.
Ph
POCI,
Cl
DMF
Ph
N
H
12
Cl
Ph
Ph
N
H
v
N
Cl
13
1 4
Thiourea
15
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1219
S. I. El-D esoky et al. ■Synthesis of Pyrrolo-, Thienopyrrolo-, Benzothienopyrroloquinollines
Me
18 R1 = R2 = COOMe
19 R1 = NH2 , R2 = COOEt
7.50-7.25 (m, 13 H, 4, 5, 4'-H, 2Ph), 3.90 (s, 3 H, C30H20N2OS2 (488.6)
o c h 3).
Calcd
C 73.74 H 4.13 N5.73%,
Found C 73.39 H 3.98 N5.63%.
C30H21N2O2SCl (509)
Calcd
C 70.79 H 4.16 N5.50%,
7-Chloro-10-methoxy-2,3-diphenyl[1Jbenzothieno-
[2,3-c]pyrrolo [2,3-f]quinoline (5)
Found C 70.52 H 4.02 N5.30%.
A mixture of 3 (0.95 g, 2 mmol) and phosphorus
oxychloride (10 ml) was refluxed for 3 h. The mix-
ture was evaporated under reduced pressure and
the residue was collected by filtration, crystallized
from ethanol-DMF mixture (8:2) to furnish yellow
crystals, yield 81%, m.p. 220-223 C, TLC (petro-
leum ether/ethyl acetate (7:3)]: Rf= 0.58, ’H NMR
(250 MHz, CDC13): <59.38 (s, 1 H, NH), 9.04, 7.90
(2d, 5,4-H, J = 9.0 Hz), 8.0 (d, 1H, 11-H, Jl2U =
8.2 Hz), 7.55-7.28 (m, 12 H, 9,12-H, 2Ph), 4.02 (s,
3H, OCH3) MS: M+ at m/e = 491.4.
10-Methoxy-2,3-diphenyl[1Jbenzothieno[2,3-
c]pyrrolo[2,3-f]-quinoline-7(6H)-one (3)
A stirred solution of 2 (3.60 g, 7.07 mmol) and
triethyl amine (6 ml) in 500 ml acetone was irradi-
ated with a high pressure mercury lamp for 72 h
under nitrogen stream. The solvent was evapo-
rated under reduced pressure and the residue was
collected, washed with water, dried and crystal-
lized from ethanol-DMF mixture (8:2) to give yel-
low crystals, yield 55%, m.p. > 300 C which were
used in the next step without further purification.
C30H 19N2OSCl.H2O (509)
Calcd
C 70.79 H 4.16 N 5.50%,
Found C 70.91 H4.12 N5.32%.
10-Methoxy-2,3-diphenyl[lJbenzothieno[2,3-
c]pyrrolo[2,3-f]quinoline-7(6H)-thione (4)
10-Methoxy-2,3-diphenyl[ljbenzothieno[2,3-
c]pyrrolo[2,3-f]quinoline (6)
A mixture of 3 (0.2 g, 4.2 mmol), phosphorus
pentasulphide (0.48 g, 2.12 mmol) in 10 ml pyri-
Compound 5 (0.49 g, 1 mmol) was treated with
dine was refluxed for 24 h. The mixture was a mixture of benzene/methanol (100 ml, 1:1) con-
poured onto 50 ml of boiling water. The solid taining 0.07 g potassium hydroxide in the presence
of 10% Pd-C (0.1 g) for 24 h at atmospheric pres-
sure and room temperature. The reaction mixture
formed was filtered off and purified by chroma-
tography [petroleum ether/ethyl acetate (7:3)]:
R f= 0.58, to give 4 (0.13 g, 63%) as yellow crystals, was filtered off and evaporated under reduced
m.p. 225-227 C. XH NMR (250 MHz, CDC13) d pressure. The residue was collected by filtration,
9.83 (s, 1 H, NH), 9.13 (d, 1H, 5-H, J54 = 9.1 Hz), washed with water, dried and purified by flash
chromatography [petroleum ether/ethyl acetate
7.29 (m, 12 H, 4,9-H, 2Ph), 4.02 (s, 3H, OCH3). (3:2)] to give yellow crystals, yield 61%, m.p. 210-
7.98, 7.85 (2d, 2 H, 11, 12-H, JU12 = 8.9 Hz), 7.55-
MS: M+at m/e = 489.9.
213 C. TLC [petroleum ether/ethyl acetate (3:2)]:
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1220
S. L E l-D esoky et al. ■Synthesis of Pyrrolo-, Thienopyrrolo-, Benzothienopyrroloquinollines
Rf = 0.38. ’H NMR (250 MHz, CDC13): (3 9.40 (s,
br, 1 H, NH), 9.10 (m, 2 H, 11, 12-H), 8.0 (s, 1 H,
9-H), 7.60-7.20 (m, 13 H, 4,5,7-H, 2Ph), 4.0 (s, 3
H, OCH3).
H, 2Ph), 4.10 (s, 3 H, COOMe), MS: M+ at m/e =
412, two fragment ions at m/e = 354 and 318.
C2,H 17N20 2C1 (412.9)
Calcd
C 72.72 H 4.15 N 6.79%,
Found C 72.76 H 4.20 N6.75%.
a-Amino-N-(2 ',3'-diphenylindole-6 ’-yl)-
dimethylfumarate (7)
Condensation of 9 with different amines
“General procedure ”
A solution of 1 (5.7 g, 0.02 mole) and dimethyla-
cetylenedicarboxylate (3.55 g, 0.025 mol) in 50 ml
methanol was refluxed for 1 h. The precipitate was
formed after cooling, filtered off and crystallized
from methanol to give golden needles, yield 90%,
m.p. 150-152 C. TLC [petroleum ether/ethyl ace-
tate (17:3)]: Rf = 0.62. 'H NMR (250 MHz,
The corresponding amine (3 mmol) was added
to a solution of 9 (0.4 g, 1 mmol) in 10 ml dry tolu-
ene and the reaction mixture was stirred at 100 °C.
When TLC showed complete conversion of the
starting material, the liquids were evaporated in
vacuo and the residue was washed with water and
CDC13): d 9.80 (s, 1 H, NH-enamine), 8.28 (s, 1 H, purified with the suitable method as follows to
NH), 7.54 (d, 1 H, 4-H, J45 = 8.5 Hz), 7.42-7.24
(m, 10 H, 2Ph), 6.98 (d, 1 H, 7-H, J75 = 1.5 Hz),
6.75 (d, 1 H, 5-H, J54 = 8.5 Hz), 5.34 (s, 1 H, ß-H),
3.74, 3.67 (2s, 6 H, 2COOMe).
give compounds lOa-c:
4-Chloro-6,7-diphenyl-2-(N-morpholinocarbonyl)-
pyrrolo[2,3-f]quinoline (10a)
Flash chromatography of the residue [petroleum
ether/ethyl acetate (1 :1 )] gives pale yellow crystals,
yield 77%, m.p. 230-232 C. TLC [petroleum
ether/ethyl acetate (1:1)]: Rf = 0.34, ‘H NMR (250
MHz, CDCU): Ö 10.23 (s, 1 H, NH), 8.09, 7.82 (2d,
2 H, 8,9-H, >89 = 9Hz), 8.00 (s, 1 H, 3-H), 7.57-
7.33 (m, 10 H, 2Ph), 3.98-3.74 (m, 8 H, 4CH2).
C26H22N20 4 (426.5)
Calcd
C 73.21 H 5.20 N 6.57%,
Found C 73.12 H 5.25 N6.60%.
2-Methoxycarbonyl-6,7-diphenylpyrrolo[2,3-f]-
4[1 HJquinolone (8 )
A solution of dimethylfumarate derivative 7
(1 g, 2.35 mmol) in triethyleneglycol dimethyl
ether (triglyme) (10 ml) was refluxed for 1 h. The
solid, formed by cooling, was filtered off, washed
with cold ether and crystallized from chloroform
to give yellow crystals, yield 81%, m.p. 240-243
C. IR (cm -1): 3440, 3360 (2NH), 1740 (COOMe),
1580-1620 (CO, C=C); lH NMR (250 MHz,
CDCI3): (3 11.29 (s, 1 H, NH pyridone), 9.49 (s, 1
H, NH pyrrole), 7.99, 7.20 (2d, 2 H, 8,9-H, / 89 = 9
Hz), 7.54-7.26 (m, 11 H, 3-H, 2Ph), 4.05 (s, 3 H,
COOMe), MS: M+ at m/e = 394.
C28H 22N30 2C1 (468)
Calcd
C 71.85 H 4.74 N 8.98%,
Found C 71.46 H 4.75 N 8.77%.
4-Chloro-6,7-diphenyl-2-(N-thiomorpholinocar-
bonyl)pyrrolo[2, 3-fJquinoline (10b)
Medium pressure chromatography [toluene/ace-
tone (1 2 :1 )] of the residue gave yellow crystals,
yield 62%, m.p. 232-235 C. TLC [toluene/acetone
(12:1)]: Rf = 0.44, 'H NMR (250 MHz, CDC13): 6
10.39 (s, 1 H, NH), 8.11, 7.87 (2d, 2 H, 8 ,9-H, J89 =
9.0 Hz), 7.98 (s, 1 H, 3-H), 7.63-7.38 (m, 10 H,
2Ph), 4.28-4.09 (2 m, 4 H, CH2-S-CH2), 2.98-2.85
(m, 4 H, CH2-N-CH2).
4-Chloro-2-methoxycarbonyl-6,7-
diphenylpyrrolo[2,3-f] quinoline (9)
C28H22N3OClS (484)
A mixture of 8 (1 g, 2.54 mmol), phosphoryl
chloride (6 ml), pyridine (1 ml) and water (0.5 ml)
was boiled for 1 h. The volatile liquids were re-
moved under reduced pressure and the residue
formed was washed with water and purified by
chromatography [petroleum ether/ethyl acetate
(4:1)] to give yellow crystals, m.p. 166-169 C. TLC
Calcd
C 69.48 H 4.58 N 8 .6 8 %,
Found C 69.26 H 4.70 N8.34%.
4-Chloro-6,7-diphenyl-2-(N-piperidinocarbonyl)-
pyrrolo[2,3-f] quinoline (10c)
Medium pressure chromatography of the resi-
[petroleum ether/ethyl acetate (1:1): Rf = 0.66 IR due [toluene/acetone (14:1)] gave colourless crys-
tals, m.p. 118-120 C, TLC (toluene/acetone 14:1)
(cm“1): 3460 (NH), 1724 (CO), 1605 (C=C), ‘H
NMR (250 MHz, CDC13): (3 10.26 (s, 1 H, NH), Rf = 0.30. :H NMR (250 MHz, CDCh): d 10.21 (s,
8.34 (s, 1 H, 3-H), 8.10 (d, 1 H, 9-H, / 98 = 9.0 Hz), 1 H, NH), 8.04, 7.83 (2d, 2 H, 8,9-H, / 89 = 8.9 Hz),
8.02 (d, 1 H, 8-H, / 89 = 9.0 Hz), 7.52-7.33 (m. 10 7.86 (s, 1 H. H-3), 7.52-7.34 (m, 10 H, 2Ph), 3.87-
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S. I. E l-D esoky et al. • Synthesis of Pyrrolo-, Thienopyrrolo-, Benzothienopyrroloquinollines
1221
Compound 13: TLC [petroleum ether/ethyl ace-
tate (4:1): Rf = 0.51, m.p. 205-207 C, 'H NMR
(250 MHz, CDC13): d 10.95 (s, 1 H, NH), 8.17 (s,
1 H, 5-H), 8.10 (s, 1 H, 9-H), 7.60-7.40 (m, 11 H,
4-H, 2Ph), 3.85 (t, 2 H, ß-CU 2, J = 7.6 Hz), 3.18 (t,
2 H, a-CH2, J = 6.7 Hz).
3.67 (2m, 4 H, CH2NCH2), 1.74-1.60 (m, 6 H,
2CH3).
C29H24N3OCl (466)
Caicd
C 74.75 H 5.19 N9.02%,
Found C 74.39 H 5.05 N8.81%.
6,7-Diphenyl-4(N-piperidino)-2-N-piperidinocar-
C25H 18N2C12 (417.3)
bonyl)pyrrolo (2,3-f)quinoline (11)
Calcd
C 71.95 H 4.35 N6.71%,
Found C 72.07 H4.17 N6.49%.
Compound 11 was separated as a by product in
the synthesis of 10c, TLC [toluene/acetone (14:1)]:
Rf = 0.2, 'H NMR [250 MHz, CDC13): 6 10.76 (s,
1 H, NH), 7.99, 7.78 (2d, 2 H, 8,9-H), 7.67-7.32
Compound 14: TLC [petroleum ether/ethyl ace-
tate (4:1)]: Rf = 0.56, m.p. 210-212 C, !H NMR
(250 MHz, CDC13): (3 9.09 (s, br, 1 H, NH), 8.35
(s, 1 H, 4-H), 7.95, 7.72 (2d, 2 H, 8,9-H, J89 = 9.0
Hz) 7.51-7.26 (m, 10 H, 2Ph), 3.93 (t, 2 H, ß-CH i,
J = 6.7 Hz), 3.41 (t, 2 H, a-CH2, J = 6.7 Hz).
(m, 11 H, 3-H, 2Ph), 3.88-3.42 (m,
8
H,
2CH2NCH2), 2.90, 2.10, 1.20 (3 m, 12 H, 6 CH2),
MS: M+ at m/e 514.5 an elemental analysis could
not be obtained.
C25H 18N2C12 (417.3)
6-Amino-N(y-chlorobutyroyl)-2,3-diphenylindole
(12)
Calcd
C 71.95 H 4.35 N6.71%,
Found C 71.71 H 4.40 N6.35%.
To a solution of 1 (14.2 g, 0.05 mol) in 150 ml
anhydrous benzene, y-chlorobutyroyl chloride
(10.58 g, 0.075 mol) in 100 ml benzene was added
dropwisely at room temperature within 30 min.
After heating for 3 h at 80 °C, the reaction mixture
was filtered and the filtrate was stirred vigorously
into 200 ml of sodium carbonate solution (2 0 %).
The organic layer was separated, washed with
water and dried with sodium sulphate. Flash chro-
matography [petroleum ether/ethyl acetate (3:2)]
gave colourless crystals, yield 76%, m.p. 168 C,
TLC [petroleum ether/ethyl acetate (3:2)]: Rf =
0.42. *H NMR (80 MHz, CDC13): d 8.80 (s, 1 H,
CONH), 8.30 (s, 1 H, NH), 7.75 (s, 1 H, 7-H),
7.70-7.30 (m, 10 H, 2Ph), 7.00 (d, 1 H, 4-H), 6.90
(d, 1 H, 5-H, 5-H), 3.70 (t, 2 H, COCH2), 2.70-
2.10 (m, 4 H, 2CH2).
2.3-Diphenyl-8,9-dihydrothieno[2,3-b]pyrrolo-
[2,3-fJquinolinium hydrochloride (15)
Compound 14 (0.42 g, 1 mmol) was refluxed
with thiourea (0.1 g, 1.3 mmol) in 20 ml ethanol
for 12 h. The residue obtained after cooling was
filtered off and washed with ethanol. Chromatog-
raphy [petroleum ether/ethyl acetate (3:7)] gave
yellow crystals, yield 94%, m.p. > 300 C, TLC [pe-
troleum ether/ethyl acetate (3:7)]: Rf - 0.47, ‘H
NMR (250 MHz, CDC13): 6 9.11 (s, br, 1 H, NH),
8.01 (s, 1 H, 10-H), 7.76 (d, 1 H, 9-H, JH9 = 8.8
Hz), 7.75, 7.60 (2d, 2 H, 5,6-H, 7, 6 = 8.9 Hz), 7.45-
7.29 (m, 10 H, 2 Ph), 3.37 (m, 4 H, 8-2H , 9-2H ).
C2,H 19N2SC1 (415)
Calcd
C 72.35 H 4.61 N 6.75%,
Found C 72.16 H 4.38 N 6 .6 6 %.
C24H21N2OCl (388.9)
Calcd
C 74.12 H 5.44 N 7.20%,
2.4-Dimethyl-6,7-diphenylpyrrolo[3,2-g]-
Found C 74.02 H 5.46 N7.15%.
quinolinium hydrochloride (16)
2-Chloro-3-(2’-chloroethyl)-6,7-diphenylpyrrolo-
[3,2-g]quinoline (13) and 2-chloro-3-(2’-chloro-
ethyl)-6,7-diphenylpyrrolo[2,3-f]-quinoline (14)
A mixture of 1 (7.1 g, 25 mmol), pentandione
(6 g, 100 mmol) and concentrated hydrochloric
acid (35%, 4 drops) was heated on a steam bath
for 30 min, then boiled at 140 C for 1 h. The cooled
mixture was dissolved in concentrated sulphuric
acid, left at room temperature for 24 h, poured
onto crushed ice and made basic using ammonium
hydroxide. The solid formed was extracted with
To a solution of 12 (3.89 g, 10 mmol) in DMF
(4 ml) was added 4.4 ml (7.65 g, 50 mmol) of
POCl3 within 1 h (the temperature should not
increase above 20 °C). The reaction mixture was
stirred at room temperature for 1 h, then for 4 h
at 75 C. After cooling, the reaction mixture was dichloromethane and the extract was washed with
poured into crushed ice to give a yellow residue. acetic acid then basified with ammonium hydrox-
ide. Crystallization from dichloromethane gave
Flash chromatography [petroleum ether/ethyl ace-
tate (7:3)] gave yellow crystals (13) and white crys- pale yellow crystals, yield 41%, m.p. > 300 C, 'H
NMR (250 MHz, DMSO [D6]): d = 12.05 (s, br, 1
tals (14) in a ratio of about 1:3.
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1222
S. I. E l-D esoky et al. ■Synthesis of Pyrrolo-, Thienopyrrolo-, Benzothienopyrroloquinollines
H, NH), 8.12 (s, 1 H, 5-H), 8.09 (s, 1 H, 9-H), 7.55-
7.34 (m, 10 H, 2Ph), 7.26 (s, 1 H, 3-H), 2.71-2.70
(2 singlets, 6 H, 2Me).
C26H20N4O4 (452.5)
Calcd
C 69.01 H 4.46 N 12.38%,
Found C 68.87 H 4.63 N 12.36%.
C2,H 21N2C1 (384.9)
5-Amino-4-ethoxycarbonyl-1 -(2\3 ’-diphenyl-6 ’-
indolyl)triazole (19)
Calcd
C 78.01 H 5.50 N 7.28%,
Found C 78.22 H 5.68 N7.31%.
To a solution of 17 (3.5 g, 11.28 mmol) in etha-
nol (20 ml) was added ethyl cyanoacetate (1.28 g,
11.32 mmol), sodium ethoxide (2 g sodium in
10 ml ethanol) and the mixture was heated at 100
C. After 1 h, a colourless precipitate was filtered
off, washed with water, dried and crystallized from
ethanol to give colourless needles, yield 78%, m.p.
251-253 C, 'H NMR (250 MHz, DMSO-D6): (3
11.68 (s, 1 H, NH), 7.85 (s, 1 H, 7’-H) 7.72 (d, 1 H,
4-H, y4-5’ = 8.2), 7.63-7.20 (m, 10 H, 2Ph), 7.17 (d,
6-Azido-2,3-diphenylindole (17)
Compound 17 was prepared following a known
procedure [13], m.p. 110 C.
4,5-Dimethoxycarbonyl-1 -(2’,3 '-diphenyl-6
indolyl)triazole (18)
To a solution of 17 (3.1 g, 0.01 mmol) in toluene
was added dimethyl acetylenedicarboxylate
(1.71 g, 0.012 mmol) and the mixture was boiled
for 40 h. The solvent was evaporated in vacuo and
the residue was collected by filtration, crystallized
from dichloromethane/petroleum ether (1 :1 ) to
give colourless needles, yield 82%, m.p. 180-183
C. TLC [petroleum ether/ethyl acetate (3:2)]: Rf =
0.41, ]H NMR (80 MHz, CDC13): (3 9.15 (s, br, 1
H, NH), 7.90 (d, 1 H, 4’-H), 7.60-7.30 (m, 12 H,
5’,7’-H, 2Ph), 3.95 (s, 6 H, 2 COOMe).
1 H, 5’-H,
= 8.2 Hz, Jy r = 1.8 Hz), 6.15 (s,
br, 2 H, NH2), 4.40 (q, 2H, CH2), 1.41 (t, 3 H, Me)
(disappearance of the signals at 11.68 and 6.15 af-
ter adding deutrated methanol [D4], MS: M+ at m /
e = 423.9.
C25H 21N50 2 (423.5)
Calcd
C 70.90 H 5.00 N 16.54%,
Found C 70.97 H 5.05 N 16.50%.
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