HETEROCYCLES

Paper | Regular issue | Vol. 78, No. 1, 2009, pp. 177-188
Received, 18th August, 2008, Accepted, 18th September, 2008, Published online, 22nd September, 2008.
DOI: 10.3987/COM-08-11527

■ Synthesis and 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, University of Cairo, Giza 12613, Egypt

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.

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 examined by TLC of the crude reaction mixture. Spectroscopic data (MS, IR, 1H and 13C NMR) as well as elemental analysis of the obtained product were in complete agreement with the assigned indolizine structure 6a, as outlined in Scheme 1. The 1H 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 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).
The proposed mechanism is similar to analogous examples reported in literature.18,19

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.

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 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.

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 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%.

12b: Yield (65%), mp 222-224 °C; IR (KBr) ν 1678 (C=O) cm-1; 1H 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.

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 (m, 1H, Ar-H), 9.81 (d, 1H, Ar-H, J = 6.9 Hz); 13C 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 (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); 13C 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, Ar-H), 9.22 (d, 1H, Ar-H, J = 6.9 Hz); 13C 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%), mp 219-221 °C; IR (KBr) ν 1742, 1702, 1653 (3 C=O) cm-1; 1H 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
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 1721, 1680 (2 C=O) cm-1; 1H 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; IR (KBr) ν 1714, 1652 (2 C=O) cm-1; 1H NMR (DMSO-d6) δ: 2.45 (s, 3H, picoline-CH3), 6.68 (s, 1H), 7.49-7.87 (m, 9H, ArH), 8.09-8.27 (m, 4H, ArH); 13C 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
°C; IR (KBr) ν 1752, 1705, 1666 (3 C=O) cm-1; 1H 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 158-160 °C; IR (KBr) ν 1728, 1692, 1637 (3 C=O) cm-1; 1H 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, 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 196-198 °C; IR (KBr) ν 1605, 1709 cm-1; 1H 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 249-251 °C; IR (KBr) ν 1702, 1675 (2 C=O) cm-1; 1H NMR (DMSO-d6) δ: 7.48-7.55 (m, 11H, Ar-H), 7.83-7.87 (m, 3H, Ar-H), 8.14-8.23 (m, 3H, Ar-H); 13C 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 (KBr) ν 1652 (C=O) cm-1; 1H 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%), mp 163-165 °C; IR (KBr) ν 1730, 1702, 1655 (3 C=O) cm-1; 1H 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, 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 1704 (C=O) cm-1; 1H 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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