Synthesis of some new inolizine and pyrrolo[1,2-a]-quinoline derivatives via nitrogen ylides

Article abstract of DOI:10.3987/COM-08-11527

The pyridinium bromides 2a,b reacted with dimethyl acetylene- dicarboxylate (DMAD) to give the indolizine derivatives 6a,b. Bromide salts 2a,b reacted also with (β-nitrostyrene, ethyl acrylate and with acrylamide to give the corresponding indolizine deriv

Full text of DOI:10.3987/COM-08-11527

HETEROCYCLES, Vol. 78, No. 1, 2009
177
HETEROCYCLES, Vol. 78, No. 1, 2009, pp. 177 - 188. © The Japan Institute of Heterocyclic Chemistry
Received, 18th August, 2008, Accepted, 18th September, 2008, Published online, 22nd September, 2008.
DOI: 10.3987/COM-08-11527
SYNTHESIS OF SOME NEW INOLIZINE AND PYRROLO[1,2-a]-
QUINOLINE DERIVATIVES VIA NITROGEN YLIDES
Nabila A. Kheder, Elham S. Darwish, and Kamal M. Dawood*
Department of Chemistry, Faculty of Science, Cairo University, Giza 12613,
Egypt
E-mail: dr_dawood@yahoo.com
Fax: 002-0235727556
Abstract – The pyridinium bromides 2a,b reacted with dimethyl acetylene-
dicarboxylate (DMAD) to give the indolizine derivatives 6a,b. Bromide salts 2a,b
reacted also with β-nitrostyrene, ethyl acrylate and with acrylamide to give the
corresponding indolizine derivatives 8a,b and 10a-d. Reaction of the quinolinium
salts 12a,b with DMAD, β-nitrostyrene and with ethyl acrylate as dipolarophiles
furnished the corresponding pyrrolo[1,2-a]quinoline derivatives 16a,b, 18a,b and
20a,b, respectively. Bromide salts 2b and 22 underwent intramolecular
cyclization via elimination of water and hydrogen bromide molecules when
heated at reflux condition to give the angularly fused indolizine
and
pyrrolo[1,2-a]quinoline structures 21 and 23, respectively.
INTRODUCTION
Indolizine derivatives have been found to possess a variety of biological activities such as
antiinflammatory,1 antiviral,2 analgestic,3 and antitumor4 activities. In addition, indolizine moiety was
found in several naturally occurring alkaloids with important biological activity.5,6 Coumarin7 and
benzofuran8,9 derivatives are well-known as highly biologically active compounds. Furthermore,
quinolinium salts were found to be potent inhibitors of lymphocyte apoptosis10 and protein kinase C.11
The use of heteroaromatic N-ylides as 1,3-dipoles has received increasing interest in the synthesis of new
condensed heterocyclic structures via 3+2 cycloaddition.12-14 As part of our research interest towards
developing new routes for the synthesis of fused heterocyclic systems,15-17 we conduct here a facile
access to some indolizine and pyrrolo[1,2-a]quinoline derivatives utilizing some new heteroaromatic
N-ylides.

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RESULTS AND DISCUSSION
Pyridinium bromides 2a,b were quantitatively obtained by treatment of 3-(2-bromoacetyl)-2H-chromen-
2-one 1 with an equivalent amount of pyridine or 2-picoline in dry benzene at refluxing condition.
Reaction of the bromide salt 2a with dimethyl acetylenedicarboxylate (DMAD) in dry benzene at
refluxing temperature, in the presence of triethylamine resulted in the formation of a single product as
1
13
examined by TLC of the crude reaction mixture. Spectroscopic data (MS, IR, H and C NMR) as well
as elemental analysis of the obtained product were in complete agreement with the assigned indolizine
1
structure 6a, as outlined in Scheme 1. The H NMR spectrum of compound 6a exhibited two singlet
peaks at δ 3.56 and 3.85 due to two methyl ester groups in addition to the aromatic multiplets in the
region δ 7.36-9.54. Its IR spectrum showed also two characteristic carbonyl absorptions at 1732 and 1695
cm-1. In the same manner, pyridinium bromide 2b reacted with DMAD under the same reaction
conditions to afford the indolizine derivative 6b, Scheme 1. Formation of the indolizine derivatives 6a,b
is assumed to be formed via 1,3-dipolar cycloaddition of DMAD to the nitrogen ylides 4a,b [which were
formed in situ through the reaction of the pyridinium bromides 2a,b with triethylamine under refluxing
benzene] to give the non-isolable intermediates 5a,b which were consequently oxidized under the
reaction conditions to give the indolizine products 6a,b.
Next, when the pyridinium bromide 2a was allowed to react with β-nitrostyrene in refluxing benzene, in
the presence of triethylamine and manganese dioxide, it afforded only one product. The elemental
analyses and spectroscopic data of the latter product established its structure as
3-(2H-2-oxo-chromen-3-yl)carbonyl-2-phenylindolizine (8a) (Scheme 1). In a similar manner, compound
2a reacted with ethyl acrylate and with acrylamide under the same reaction conditions as mentioned
above, to give the corresponding indolizine structures 10a and 10c as shown in Scheme 1. The 1H NMR
spectrum of compound 10a revealed triplet signal at δ 1.34 and a quartet one at 4.33 due to the ethyl-ester
protons in addition to an aromatic mutiplet at δ 7.12-9.82. It mass spectrum showed a molecular ion peak
at m/z 361. The IR spectrum of compound 10a showed three carbonyl absorption bands at 1666, 1705 and
1752 cm-1.
The 2-picolinium ylide 3b, from its bromide salt 2b, reacted in a similar fashion with β-nitrostyrene, ethyl
acrylate and with acrylamide under the same reaction conditions above, to give the corresponding
indolizine derivatives 8b, 10b, and 10d, respectively as shown in Scheme 1. The above reactions are
assumed to proceed via a reaction sequence of [3+2] cycloaddition of the N-ylide with the alkene and
subsequent elimination of nitrous acid and hydrogen molecules (in case of the formation of 8a and 8b) or
two hydrogen molecules (in case of the formation of 10a-d) under the reaction conditions (Scheme 1).

HETEROCYCLES, Vol. 78, No. 1, 2009
179
The proposed mechanism is similar to analogous examples reported in literature.18,19
R
O
R
O
Br
N
Et3N
N
- HBr
PhH, reflux
O
N
O
Br
O
O
O
1
2
R
R
O
N
O
O
O
3
O
4
MeO2C
CO2Me
COR´
NO2
Ph
R
R
O
O
O
R
O
N
N
N
O
O
9
O
MeO2C
5
CO2Me
O
O
Ph
R´OC
O2N
7
-2H2
-H2
- HNO2
- H2
R
R
O
O
O
R
N
O
N
N
O
O
O
R´OC
MeO2C
CO2Me
10
O
O
Ph
6
9, 10; a: R = H, R´= OEt
b: R = Me, R´= OEt
8
2-8; a: R = H
b: R = Me
c: R = H, R´= NH2
d: R = Me, R´= NH2
Scheme 1
Similarly, treatment of 3-(2-bromoacetyl)-2H-chromen-2-one 1 or 2-(2-bromoacetyl)benzofuran 11 with
quinoline in dry benzene at refluxing temperature gave the corresponding quinolinium bromides 12a,b.
Reaction of the bromide salts 12a,b with DMAD in dry benzene at refluxing temperature, in the presence
of triethylamine, resulted in the formation the annulated dimethyl pyrrolo[1,2-a]quinoline-
2,3-dicarboxylates 16a,b, respectively, as shown in Scheme 2. Spectroscopic data as well as elemental
analyses of the obtained products were in complete agreement with the assigned structures 16a,b.

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HETEROCYCLES, Vol. 78, No. 1, 2009
O
O
Br
N
Et3N
N
X
- HBr
X
O
PhH, reflux
Br
O
O
1: X = CO
11: X = none
12
O
N
N
X
O
X
O
13
14
MeO2C
CO2Me
CO2Et
NO2
Ph
CO2Et
CO2Me
CO2Me
N
N
NO2
N
X
X
O
15
-H2
19
O
O
O
Ph
X
O
17
O
-2H2
- HNO2
- H2
CO2Me
CO2Me
N
CO2Et
N
N
X
O
O
16
X
O
O
Ph
20
X
O
O
18
12-20; a: X = CO
b: X= none
Scheme 2
Reaction of the quinolinium bromides 12a,b with β-nitrostyrene as dipolarophile in refluxing benzene, in
the presence of triethylamine and manganese dioxide, furnished the corresponding
2-phenylpyrrolo[1,2-a]quinoline derivatives 18a,b (Scheme 2). In a similar manner, quinolinium
bromides 12a,b reacted with ethyl acrylate under the same reaction conditions that mentioned above to
give the corresponding ethyl pyrrolo[1,2-a]quinoline-3-carboxylates 20a,b as shown in Scheme 2.
Structures of compounds 18a,b and 20a,b were deducted from the elemental analyses and spectral data
(MS, IR, 1H and 13C NMR) of the corresponding reaction products.
2-Picolinium bromide 2b when heated at reflux in dry benzene and in the presence of triethylamine,
furnished a single product as examined by TLC. Elemental analyses and mass spectrum of the reaction
product established its molecular formula as C17H11NO2. Spectroscopic data of the reaction product were

HETEROCYCLES, Vol. 78, No. 1, 2009
181
in complete agreement with the assigned 3-(indolizin-2-yl)-2H-chromen-2-one structure 21, as outlined in
Scheme 3. Furthermore, treatment of 3-(2-bromoacetyl)-2H-chromen-2-one 1 with 2-methylquinoline in
dry benzene at refluxing temperature gave the corresponding 2-methylquinolinium bromide 22 which
underwent intramolecular cyclization via elimination of water and hydrogen bromide molecules to give
the angularly fused 2-(2H-2-oxo-chromen-3-yl)pyrrolo[1,2-a]quinoline 23 (Scheme 3). The IR spectrum
of compound 23 showed only one carbonyl absorption at 1704 cm-1 and its 1H NMR spectrum was free of
aliphatic protons and showed only peaks due to aromatic ones. Its mass spectrum showed a peak at m/z
311 due to the molecular ion.
Me
O
Et3N, PhH
N
N
reflux, - HBr, -H2O
Br
O
O
O
O
21
2b
Me
O
Et3N, PhH
ref lux,
N
N
N
Me
1
Br
O
PhH, ref lux
O
- HBr, -H2O
22
23
O
O
Scheme 3
EXPERIMENTAL
All melting points were measured on a Gallenkamp melting point apparatus. The infrared spectra were
recorded in potassium bromide disks on a Pye Unicam SP 3300 and Shimadzu FT IR 8101 PC infrared
spectrophotometers. The NMR spectra were recorded on a Varian Mercury VX-300 NMR spectrometer.
1H spectra were run at 300 MHz and 13C spectra were run at 75.46 MHz in deuterated chloroform
(CDCl3) or dimethyl sulfoxide (DMSO-d6). Chemical shifts were related to that of the solvent. Mass
spectra were recorded on a Shimadzu GCMS-QP 1000 EX mass spectrometer at 70 e.V. Elemental
analyses were carried out at the Microanalytical Center of Cairo University, Giza, Egypt.
3-(2-Bromoacetyl)-2H-chromen-2-one (1)20,21 and 2-(2-bromoacetyl)benzofuran (11)22 were prepared
according to the reported literature.
Preparation of the pyridinium and quinolinium salts 2a,b, 12a,b and 22
To a solution of 3-(2-bromoacetyl)-2H-chromen-2-one 1 or 2-(2-bromoacetyl)benzofuran 11 (5 mmol) in
dry benzene (50 mL) was add the appropriate nitrogen-heterocycle (pyridine, 2-picoline, quinoline or

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2-methylquinoline) (5 mmol). The mixture was refluxed for 30 min then left to cool. The solid product
was filtered off, washed with Et2O / benzene and dried to afford the pyridinium bromide salts 2a,b, 12a,b
and 22, respectively.
2a: Yield (85%), mp > 300 °C; IR (KBr) ν 1729, 1691 (2 C=O) cm-1; 1H NMR (DMSO-d6) δ 6.32 (s, 2H,
CH2), 7.44-7.53 (m, 3H, Ar-H), 7.75-8.28 (m, 4H, Ar-H), 8.86-8.97 (m, 2H, Ar-H), 9.01 (s, 1H, Ar-H).
Anal. Calcd for C16H12BrNO3: C, 55.51; H, 3.49; N, 4.05. Found: C, 55.85; H, 3.65; N, 4.20%.
2b: Yield (86%), mp 221-223 °C; IR (KBr) ν 1727, 1686 (2 C=O) cm-1; 1H NMR (DMSO-d6) δ 2.71 (s,
3H, CH3), 6.30 (s, 2H, CH2), 7.47-7.59 (m, 2H, Ar-H), 7.83-7.89 (m, 1H, Ar-H), 8.06-8.17 (m, 3H, Ar-H),
8.58-8.63 (m, 1H, Ar-H), 8.93 (s, 1H, Ar-H), 8.96 (s, 1H, Ar-H). Anal. Calcd for C17H14BrNO3: C, 56.69;
H, 3.92; N, 3.89. Found: C, 56.25; H, 3.90; N, 3.99%.
12a: Yield (72%), mp 216-218 °C; IR (KBr) ν 1735, 1722 (2 C=O) cm-1; 1H NMR (DMSO-d6) δ 5.89 (s,
2H, CH2), 7.20-7.89 (m, 6H, Ar-H), 8.04-9.01 (m, 6H, Ar-H). Anal. Calcd for C20H14BrNO3: C, 60.62; H,
3.56; N, 3.53. Found: C, 60.25; H, 3.69; N, 3.30%.
1
12b: Yield (65%), mp 222-224 °C; IR (KBr) ν 1678 (C=O) cm-1; H NMR (DMSO-d6) δ 5.60 (s, 2H,
CH2), 7.34-7.57 (m, 3H, Ar-H), 7.69-8.13 (m, 5H, Ar-H), 8.23 -8.69 (m, 2H, Ar-H), 9.07 (s, 1H, Ar-H),
9.29 (s, 1H, Ar-H). Anal. Calcd for C19H14BrNO2: C, 61.97; H, 3.83; N, 3.80. Found: C, 61.25; H, 3.69; N,
3.24%.
22: Yield (85%), mp 160-162 °C; IR (KBr) ν 1727, 1686 (2 C=O) cm-1; 1H NMR (DMSO-d6) δ 3.32 (s,
3H, CH3), 5.73 (s, 2H, CH2), 7.22-7.95 (m, 6H), 8.10-8.52 (m, 4H), 8.61 (s, 1H). Anal. Calcd for
C21H16BrNO3: C, 61.48; H, 3.93; N, 3.41. Found: C, 61.25; H, 3.69; N, 3.30%.
Synthesis of the Indolizine 6a,b and Pyrrolo[1,2-a]quinoline Derivatives 16a,b
To a mixture of the appropriate pyridinium 2a,b or quinolinium 12a,b bromides (2 mmol) and dimethyl
acetylenedicarboxylate (DMAD) (0.57 g, 4 mmol) in dry benzene (30 mL), triethylamine (0.4 mL) was
added and the reaction mixture was refluxed 2~3 h, then left to cool to rt. The triethylamine
hydrobromide was removed by filtration and the filtrate was evaporated under vacuum. The residue was
triturated with MeOH where a yellow-colored precipitate was formed that was filtered off, washed with
MeOH, dried. Recrystallization from DMF/EtOH afforded the corresponding indolizine 6a,b or
pyrrolo[1,2-a]quinoline 16a,b derivatives.

HETEROCYCLES, Vol. 78, No. 1, 2009
183
Dimethyl 3-(2H-2-oxo-chromen-3-yl)carbonylindolizine-1,2-dicarboxylate (6a): Yield (75%), mp
231-232 °C; IR (KBr) ν 1730, 1702, 1669 (3 C=O) cm-1; 1H NMR (DMSO-d6) δ: 3.21 (s, 3H, COOCH3),
3.86 (s, 3H, COOCH3), 7.36-7.53 (m, 3H, Ar-H), 7.73-7.81 (m, 3H, Ar-H), 8.32 (s, 1H, Ar-H), 8.34-8.37
13
(m, 1H, Ar-H), 9.81 (d, 1H, Ar-H, J = 6.9 Hz); C NMR (DMSO-d6) δ: 51.8, 52.4, 103.7, 109.3, 116.1,
116.4, 117.6, 119.3, 125.1, 125.7, 128.2, 129.4, 130.3, 132.3, 133.6, 137.7, 143.1, 153.6, 157.3, 162.2,
165, 178.9; MS m/z (%): 405 (M+, 100), 374 (33.6), 346 (26.8), 330 (34.4), 202 (16.5), 173 (13.1), 143
(16.5), 89 (15.5). Anal. Calcd for C22H15NO7: C, 65.19; H, 3.73; N, 3.46. Found: C, 65.43; H, 3.62; N,
3.14%.
Dimethyl 5-methyl-3-(2H-2-oxo-chromen-3-yl)carbonylindolizine-1,2-dicarboxylate (6b): Yield
(65%), mp 192-194 °C; IR (KBr) ν 1733, 1690, 1635 (3 C=O) cm-1; 1H NMR (DMSO-d6) δ: 3.09 (s, 3H,
picoline-CH3), 3.36 (s, 3H, COOCH3), 3.83 (s, 3H, COOCH3), 7.2 (d, 1H, Ar-H, J = 7.2 Hz), 7.45-7.52
13
(m, 2H, Ar-H), 7.63-7.85 (m, 3H, Ar-H), 8.27 (d, 1H, Ar-H, J = 7.8 Hz), 8.71 (s, 1H, Ar-H); C NMR
(DMSO-d6) δ: 51.6, 52.3, 102, 116.4, 116.8, 117.7, 117.9, 120.6, 123.1, 124.9, 125.2, 128.7, 129.9, 130.2,
134.7, 138.8, 139.1, 147.9, 154.3, 157.1, 162.4, 165.3, 178.8; MS m/z (%): 419 (M+, 100), 387 (53.9), 359
(57.6), 344 (29.5), 301 (35.4), 246 (66.8), 216 (33.2), 173 (68.5), 129 (29.5), 89 (24.6). Anal. Calcd for
C23H17NO7: C, 65.87; H, 4.09; N, 3.34. Found: C, 66.05; H, 4.12; N, 3.03%.
Dimethyl 1-(2H-2-oxo-chromen-3-yl)carbonylpyrrolo[1,2-a]quinoline-2,3-dicarboxylate (16a): Yield
(52%), mp 140-142 °C; IR (KBr) ν 1732, 1726, 1656 (3 C=O) cm-1; 1H NMR (DMSO-d6) δ: 3.61 (s, 3H,
COOCH3), 3.90 (s, 3H, COOCH3), 7.50-7.88 (m, 6H, Ar-H), 8.42-8.45 (m, 2H, Ar-H), 8.78-8.83 (m, 2H,
13
Ar-H), 9.22 (d, 1H, Ar-H, J = 6.9 Hz); C NMR (DMSO-d6) δ: 51.3, 52.5, 115.7, 116.4, 117.3, 117.7,
119.2, 123, 123.9, 124.7, 125, 125.4, 126.3, 127.5, 128.5, 129.4, 129.8, 130.5, 131.9, 133.9, 134.9, 144.3,
148.4, 153.8, 154.4, 164.6; MS m/z (%): 455 (M+, 83), 424 (25.2), 396 (19.2), 380 (15.6), 310 (20.4), 252
(24.8), 193 (14.8), 172 (26.1), 88 (33), 43 (100). Anal. Calcd for C26H17NO7: C, 68.57; H, 3.76; N, 3.08.
Found: C, 68.25; H, 3.69; N, 3.32%.
Dimethyl 1-(benzofuran-2-yl)carbonylpyrrolo[1,2-a]quinoline-2,3-dicarboxylate (16b): Yield (55%),
1
mp 219-221 °C; IR (KBr) ν 1742, 1702, 1653 (3 C=O) cm-1; H NMR (DMSO-d6) δ: 3.24 (s, 3H,
COOCH3), 3.80 (s, 3H, COOCH3), 7.47-7.82 (m, 7H, Ar-H), 8.36-8.69 (m, 3H, Ar-H), 9.61 (s, 1H); MS
m/z (%): 427 (M+, 100), 338 (16.2), 282 (13.5), 145 (38.6), 128 (10.3), 57 (6.5). Anal. Calcd for
C25H17NO6: C, 70.25; H, 4.01; N, 3.28. Found: C, 70.21; H, 4.36; N, 3.64%.
Synthesis of the Indolizine Derivatives 8a,b, 10a-d, 18a,b and 20a,b

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To a mixture of the appropriate pyridinium 2a,b or quinolinium 12a,b salts (1 mmol) and the appropriate
β-nitrostyrene or ethyl acrylate or acrylamide (6 mmol) in benzene (30 mL) in the presence of
triethylamine (0.15 mL, 1.5 mmol), manganese dioxide (0.7 g, 8 mmol) was added. The mixture was
refluxed for 4h then cooled to rt. The solid salts were removed by filtration, and the filtrate was
evaporated under vacuum. The residue was treated with MeOH, and the solid precipitate was filtered off,
washed with MeOH and dried. Recrystallization from EtOH/DMF afforded the corresponding indolizine
derivatives 8a,b, 10a-d, 18a,b and 20a,b, respectively.
3-(2H-2-Oxo-chromen-3-yl)carbonyl-2-phenylindolizine (8a): Yield (65%), mp >300 °C; IR (KBr) ν
1
1721, 1680 (2 C=O) cm-1; H NMR (DMSO-d6) δ: 7.28-7.53 (m, 7H, Ar-H), 7.68-7.83 (m, 5H, Ar-H),
8.05-8.45 (m, 2H, Ar-H), 8.80 (d, 1H, J = 6.9 Hz); MS m/z (%): 365 (M+, 65), 306 (20.4), 288 (34.5), 273
(14.6), 203 (13.5), 192 (14.8), 173 (16.2), 149 (20.8), 115 (13.6), 77 (100). Anal. Calcd for C24H15NO3: C,
78.89; H, 4.14; N, 3.83. Found: C, 78.95; H, 4.69; N, 3.29%.
5-Methyl-3-(2H-2-oxo-chromen-3-yl)carbonyl-2-phenylindolizine (8b): Yield (68%), mp 275-277 °C;
1
IR (KBr) ν 1714, 1652 (2 C=O) cm-1; H NMR (DMSO-d6) δ: 2.45 (s, 3H, picoline-CH3), 6.68 (s, 1H),
13
7.49-7.87 (m, 9H, ArH), 8.09-8.27 (m, 4H, ArH); C NMR (DMSO-d6) δ: 17.4, 114.3, 115.4, 116.9,
117.8, 119.7, 124.6, 125.7, 128.2, 128.6, 129.1, 129.7, 131.9, 132.1, 133.4, 134.8, 137.9, 139.1, 142.5,
147.3, 153.4, 164.8, 178.1; MS m/z (%): 379 (M+, 22.6), 309 (56.8), 261 (73.9), 218 (100), 181 (54.5),
171 (43.9), 130 (41.3), 102 (35.2), 77 (45.5), 65 (41.9). Anal. Calcd for C25H17NO3: C, 79.14; H, 4.52; N,
3.69. Found: C, 79.00; H, 4.65; N, 3.44%.
Ethyl 3-(2H-2-oxo-chromen-3-yl)carbonylindolizine-1-carboxylate (10a): Yield (70%), mp 211-213
1
°C; IR (KBr) ν 1752, 1705, 1666 (3 C=O) cm-1; H NMR (DMSO-d6) δ: 1.34 (t, 3H, COOCH2CH3, J =
7.2 Hz), 4.33 (q, 2H, COOCH2CH3, J = 7.2 Hz), 7.12-7.18 (m, 2H, Ar-H), 7.29-36 (m, 4H, Ar-H),
7.63-7.69 (m, 1H, Ar-H), 8.31-8.35 (m, 1H, Ar-H), 8.54 (s, 1H, Ar-H),9.81 (d, 1H, Ar-H, J = 6.9 Hz); 13C
NMR (DMSO-d6) δ: 14.3, 59.7, 105.7, 116.1, 116.3, 118.8, 121.9, 122.4, 124.3, 127.7, 127.9, 128.4,
128.6, 128.8, 132.1, 134.3, 139.2, 151.2, 162.9, 166.8, 183.8; MS m/z (%): 361 (M+, 35.3), 288 (46.8),
188 (13.6), 173 (100), 146 (18.9), 115 (31.4), 79 (31.6). Anal. Calcd for C21H15NO5: C, 69.80; H, 4.18; N,
3.88. Found: C, 69.52; H, 4.59; N, 3.54%.
Ethyl 5-methyl-3-(2H-2-oxo-chromen-3-yl)carbonylindolizine-1-carboxylate (10b): Yield (70%), mp
1
158-160 °C; IR (KBr) ν 1728, 1692, 1637 (3 C=O) cm-1; H NMR (DMSO-d6) δ: 1.17 (t, 3H,
COOCH2CH3, J = 7.5 Hz), 2.48 (s, 3H, picoline-CH3), 3.80 (q, 2H, COOCH2CH3, J = 7.5 Hz), 6.30 (s, 1H,

HETEROCYCLES, Vol. 78, No. 1, 2009
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Ar-H), 7.47-7.83 (m, 3H, Ar-H), 8.16-8.27 (m, 3H, Ar-H), 8.71 (m, 1H, Ar-H), 8.94 (s, 1H, Ar-H); MS
m/z (%): 375 (M+, 14.2), 348 (30.3), 298 (100), 202 (20), 173 (16.7), 145 (12.1), 129 (6.8), 93 (15.1), 77
(11.2). Anal. Calcd for C22H17NO5: C, 70.39; H, 4.56; N, 3.73. Found: C, 70.29; H, 4.69; N, 3.35%.
3-(2H-2-Oxo-chromen-3-yl)carbonylindolizine-1-carboxamide (10c): Yield (82%), mp 250-252 °C;
IR (KBr) ν 3213, 3139 (NH2), 1732, 1693 (C=O) cm-1; 1H NMR (DMSO-d6) δ: 7.47-7.59 (m, 4H, Ar-H),
7.82-7.86 (m, 1H, Ar-H), 8.07-8.28 (m, 3H, Ar-H), 8.69-8.96 (m, 4H, Ar-H and NH2); MS m/z (%): 332
(M+, 10.2), 288 (31.6), 173 (56.4), 159 (11.9), 144 (12.8), 130 (17.5), 115 (8.9), 89 (27.3), 78 (14.9), 52
(100). Anal. Calcd for C19H12N2O4: C, 68.67; H, 3.64; N, 8.43%. Found: C, 68.21; H, 3.29; N, 8.24%.
5-Methyl-3-(2H-2-oxo-chromen-3-yl)carbonylindolizine-1-carboxamide (10d): Yield (76%), mp
1
196-198 °C; IR (KBr) ν 1605, 1709 cm-1; H NMR (DMSO-d6) δ: 2.51 (s, 3H, picoline-CH3), 6.52-6.78
(m, 2H, Ar-H), 6.97 (s, 1H, Ar-H), 7.36-7.46 (m, 3H, Ar-H), 7.56-7.80 (m, 2H, Ar-H), 8.31 (br.s, 2H,
NH2), 8.51 (s, 1H, Ar-H); MS m/z (%): 346 (M+, 3.27), 172 (76), 144 (88.2), 132 (100), 117 (72), 90
(84.2), 73 (84.2). Anal. Calcd for C20H14N2O4: C, 69.36; H, 4.07; N, 8.09. Found: C, 69.55; H, 3.99; N,
8.24%.
1-(2H-2-Oxo-chromen-3-yl)carbonyl-2-phenylpyrrolo[1,2-a]quinoline (18a): Yield (62%), mp
1
249-251 °C; IR (KBr) ν 1702, 1675 (2 C=O) cm-1; H NMR (DMSO-d6) δ: 7.48-7.55 (m, 11H, Ar-H),
13
7.83-7.87 (m, 3H, Ar-H), 8.14-8.23 (m, 3H, Ar-H); C NMR (DMSO-d6) δ: 115.2, 116.6, 117.8, 118.2,
120.8, 120.9, 121.8, 123.7, 126.3, 127.7, 128.5, 128.9, 129.1, 129.7, 130.2, 131.9, 132.4, 133.8, 134.6,
137.9, 139.2, 141.3, 145.3, 156.9, 161.8, 175.2; MS m/z (%): 415 (M+, 13.2), 346 (6.1), 245 (2.3), 191
(6.9), 149 (13.4), 115 (8.1), 102 (30.4), 77 (77.4), 65 (21.5), 40 (100). Anal. Calcd for C28H17NO3: C,
80.95; H, 4.12; N, 3.37. Found: C, 80.25; H, 4.69; N, 3.35%.
1-(Benzofuran-2-yl)carbonyl-2-phenylpyrrolo[1,2-a]quinoline (18b): Yield (62%), mp 176-178 °C; IR
1
(KBr) ν 1652 (C=O) cm-1; H NMR (DMSO-d6) δ: 7.15-7.47 (m, 7H, Ar-H), 7.50-7.61 (m, 5H, Ar-H),
8.10-8.35 (m, 3H, Ar-H), 8.88-8.98 (m, 2H, Ar-H); MS m/z (%): 387 (M+, 100), 358 (53), 241 (50.2), 145
(39.1), 89 (46.1). Anal. Calcd for C27H17NO2: C, 83.70; H, 4.42; N, 3.62. Found: C, 83.35; H, 4.59; N,
3.34%.
Ethyl 1-(2H-2-oxo-chromen-3-yl)carbonypyrrolo[1,2-a]quinoline-3-carboxylate (20a): Yield (66%),
1
mp 163-165 °C; IR (KBr) ν 1730, 1702, 1655 (3 C=O) cm-1; H NMR (DMSO-d6) δ: 1.30 (t, 3H,
COOCH2CH3, J = 6.9 Hz), 4.33 (q, 2H, COOCH2CH3, J = 6.9 Hz), 7.14-7.45 (m, 7H, Ar-H), 7.66 (d, 2H,

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Ar-H, J = 8.4 Hz), 8.05 (d, 2H, Ar-H, J = 8.4 Hz), 8.38 (s, 1H, Ar-H); MS m/z (%): 411 (M+, 15.6), 336
(30.4), 283 (26.6), 238 (3.5), 214 (8.3), 172 (18.1), 165 (4.4), 143 (6.8), 130 (30.8), 77 (100). Anal. Calcd
for C25H17NO5: C, 72.99; H, 4.16; N, 3.40. Found: C, 72.25; H, 4.69; N, 3.30%.
Ethyl 1-(benzofuran-2-yl)carbonylpyrrolo[1,2-a]quinoline-3-carboxylate (20b): Yield (72%), mp
207-209 °C; IR (KBr) ν 1697, 1647 (2 C=O) cm-1; 1H NMR (DMSO-d6) δ: 1.17 (t, 3H, COOCH2CH3, J =
6.9 Hz), 4.07 (q, 2H, COOCH2CH3, J = 6.9 Hz), 6.27 (m, 1H, Ar-H), 6.72 (d, 1H, Ar-H, J = 8.1 Hz), 7.03
(m, 1H, Ar-H), 7.31-7.49 (m, 5H, Ar-H), 7.62-7.94 (m, 3H, Ar-H), 8.24 (s, 1H, Ar-H); 13C NMR
(DMSO-d6) δ: 14.6, 58.1, 89.4, 111.5, 112.4, 112.6, 115.3, 116.8, 117.3, 121, 121.8, 123.9, 124.3, 126.6,
128.2, 129.2, 131.2, 135.6, 138.3, 148.9, 151.3, 155.6, 164.6, 184.6; MS m/z (%): 383 (M+, 68.6), 338
(42.1), 281 (32.5), 240 (67), 167 (100), 89 (36.9). Anal. Calcd for C24H17NO4: C, 75.19; H, 4.47; N, 3.65.
Found: C, 75.25; H, 4.69; N, 3.24%.
Synthesis of 2-(2H-2-oxo-chromen-3-yl)indolizine 21 and 2-(2H-2-oxo-chromen-3-yl)pyrrolo-
[1,2-a]quinoline 23
To a solution of the appropriate 2-picolinium 2b or 2-methylquinolinium bromide 22 (1 mmol) in dry
benzene (20 mL), triethylamine (0.2 mL) was added and the reaction mixture was refluxed 4 h then left to
cool to rt. The triethylamine-hydrobromide salt was removed by filtration and the filtrate was evaporated
under vacuum. The residue was triturated with MeOH and the solid product was filtered off, washed with
MeOH and dried. Recrystallization from the proper solvent afforded the indolizine 21 or
pyrrolo[1,2-a]quinoline 23 derivatives, respectively.
3-(Indolizin-2-yl)-2H-chromen-2-one (21): Yield (52%), mp 203-205 °C; IR (KBr) ν 1708 (C=O) cm-1;
1H NMR (DMSO-d6) δ: 6.52-6.74 (m, 2H, Ar-H), 6.96 (s, 1H, Ar-H), 7.36-7.79 (m, 5H, Ar-H), 8.30 (s,
1H, Ar-H), 8.51 (s, 1H, Ar-H); MS m/z (%): 261 (M+, 100), 233 (55.8), 204 (36.7), 130 (7.3), 102 (10.1),
63 (6.4), 50 (11.9). Anal. Calcd for C17H11NO2: C, 78.15; H, 4.24; N, 5.36. Found: C, 78.25; H, 4.61; N,
5.22%.
2-(2H-2-Oxo-chromen-3-yl)pyrrolo[1,2-a]quinoline (23): Yield (55%), mp 229-231 °C; IR (KBr) ν
1
1704 (C=O) cm-1; H NMR (DMSO-d6) δ: 6.50-6.73 (m, 4H, Ar-H), 7.06-7.09 (m, 2H, Ar-H), 7.24-7.41
(m, 5H, Ar-H), 7.83 (s, 1H, Ar-H), 8.20 (d, 1H, Ar-H, J = 8.4 Hz); MS m/z (%): 311 (M+, 10.6), 309
(83.5), 294 (100), 184 (11.3), 165 (17.2), 147 (16.5), 131 (17.1), 109 (17.6), 77 (37.3), 67 (39.0). Anal.
Calcd for C21H13NO2: C, 81.01; H, 4.21; N, 4.50. Found: C, 81.25; H, 4.69; N, 4.30%.

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