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E. Galariniotou et al. / Tetrahedron 63 (2007) 8298–8304
178 ꢀC (dec) (DCM/hexane); IR (Nujol) n (cmꢁ1): 3050,
1725, 1706, 1625; H NMR (CDCl3, 300 MHz) d: 2.78 (s,
(d, J¼7.9 Hz, 1H), 7.56 (s, 1H), 7.57 (t, J¼7.9 Hz, 1H),
8.28 (d, J¼7.9 Hz, 1H), 11.34 (s, 1H, exchanged by D2O);
13C NMR (CDCl3, 75 MHz) d: 13.8, 14.6, 18.2, 59.9,
115.3, 117.0, 122.6, 124.1, 125.3, 130.4, 130.9, 133.9,
139.0, 146.7, 151.9, 167.7; MS (EI) m/z: 271 (M+, 9), 226
(13), 199 (21), 198 (100), 183 (7), 159 (9), 130 (9), 102
(6). Anal. Calcd for C16H17NO3: C, 70.82; H, 6.32; N,
5.16. Found: C, 70.77; H, 6.33; N, 5.03.
1
3H), 4.06 (s, 3H), 6.56 (s, 1H), 7.66 (t, J¼8.9 Hz, 1H),
7.85 (t, J¼8.9 Hz, 1H), 8.02 (d, J¼8.9 Hz, 1H), 8.43 (d,
J¼8.9 Hz, 1H); 13C NMR (CDCl3, 75 MHz) d: 15.9, 53.0,
109.4, 110.6, 115.6, 116.3, 116.8, 125.8, 132.3, 140.8,
148.8, 154.4, 158.0, 160.9, 167.7; MS (EI) m/z: 269 (M+,
100), 254 (7), 237 (49), 210 (63), 209 (35), 183 (31), 181
(16), 166 (9), 154 (29). Anal. Calcd for C15H11NO4: C,
66.90; H, 4.12; N, 5.20. Found: C, 66.71; H, 4.29; N, 5.04.
3.1.3.4. 3,5-Dimethyl-2H-pyrano[3,2-c]quinolin-2-one
(12b). Reflux for 11 days. Yellow crystals (from DCM),
mp 247–249 ꢀC; yield 8%; IR (Nujol) n (cmꢁ1): 3025,
3.1.2. Procedure for the preparation of methyl 5-methyl-
2-oxo-2H-pyrano[3,2-c]quinoline-4-carboxylate (8).
Compound 7 (0.034 g, 0.113 mmol) (without solvent) was
heated at 150–160 ꢀC for 24 h. No reaction had happened
as checked by TLC. The heating was continued for 4 days
at 200–205 ꢀC. Sublimation in the upper part of the appara-
tus gave compound 8 (0.003 g, 10%).
1
1748, 1637, 1614; H NMR (CDCl3, 300 MHz) d: 2.31 (s,
3H), 2.86 (s, 3H), 7.59 (t, J¼7.9 Hz, 1H), 7.76 (t,
J¼7.9 Hz, 1H), 7.80 (s, 1H), 7.99 (d, J¼7.9 Hz, 1H), 8.36
(d, J¼7.9 Hz, 1H); 13C NMR (CDCl3, 75 MHz) d: 17.5,
22.5, 110.2, 117.3, 121.6, 125.9, 126.7, 128.5, 131.2,
136.3, 145.0, 147.7, 155.6, 160.9; MS (EI) m/z: 225 (M+,
100), 199 (11), 198 (21), 197 (44), 196 (59), 167 (21), 127
(9), 77 (21). Anal. Calcd for C14H11NO2: C, 74.64; H,
4.93; N, 6.22. Found: C, 74.71; H, 5.23; N, 5.93.
3.1.3. General procedure for the preparation of the qui-
nolinols 11a–c and the azacoumarins 12a–c. A solution
of hydroxyaldehyde
9 (2.7 mmol) and ylide 10a–c
(2.7 mmol) in dry toluene (50 ml) was heated at different
temperatures under stirring and argon atmosphere. After
cooling, quinolinols 11a,b precipitated. The filtrate was
evaporated in a rotary evaporator and the residue was sub-
jected to column chromatography (silica gel, hexane/ethyl
acetate 1:2) to give products 12a–c and 11c.
3.1.3.5. Ethyl 2-benzyl-3-(4-hydroxy-2-methyl-3-qui-
nolinyl)-2-propenoate (11c). Reflux for 6 days; eluting sec-
ond from the column chromatography. Yellow crystals (from
DCM), mp 231–233 ꢀC; yield 17%; IR (Nujol) n (cmꢁ1):
1
3467, 3102, 1700, 1626; H NMR (CDCl3, 300 MHz) d:
1.16 (t, J¼6.9 Hz, 3H), 2.30 (s, 3H), 3.66 (s, 2H), 4.11 (q,
J¼6.9 Hz, 2H), 7.02–7.16 (m, 5H), 7.34 (t, J¼7.9 Hz, 2H),
7.55 (d, J¼7.9 Hz, 1H), 7.57 (s, 1H), 8.38 (d, J¼7.9 Hz,
1H), 9.24 (s, 1H, exchanged by D2O); 13C NMR (CDCl3,
75 MHz) d: 14.1, 19.4, 34.7, 60.7, 111.8, 116.3, 117.0,
121.4, 123.8, 125.7, 126.5, 128.0, 128.4, 132.0, 134.4,
139.8, 140.1, 143.7, 150.0, 164.7; MS (EI) m/z: 347 (M+,
21), 301 (62), 273 (50), 256 (100), 228 (13), 196 (24), 91
(32), 77 (9). Anal. Calcd for C22H21NO3: C, 76.05; H,
6.10; N, 4.03. Found: C, 76.33; H, 6.00; N, 3.74.
3.1.3.1. Ethyl 3-(4-hydroxy-2-methylquinolinyl)-2-
propenoate (11a). Heating at 60 ꢀC for 48 h. Yellow crys-
tals (from DCM/hexane), mp 157–159 ꢀC; yield 72%; IR
(Nujol) n (cmꢁ1): 3459, 3064, 1707, 1615; 1H NMR
(CDCl3+DMSO-d6, 300 MHz) d: 1.31 (t, J¼6.9 Hz, 3H),
2.63 (s, 3H), 4.21 (q, J¼6.9 Hz, 2H), 7.33 (t, J¼7.9 Hz,
1H), 7.48–7.62 (m, 3H), 7.74 (d, J¼14.8 Hz, 1H), 8.26 (d,
J¼7.9 Hz, 1H), 11.70 (s, 1H, exchanged by D2O); 13C
NMR (CDCl3+DMSO-d6, 75 MHz) d: 13.8, 18.1, 59.0,
112.2, 117.3, 117.4, 123.3, 124.8, 125.3, 131.0, 136.9, 137.9,
148.4, 151.1, 168.2; MS (EI) m/z: 257 (M+, 43), 212 (44),
211 (34), 184 (98), 183 (100), 154 (87), 128 (50), 127 (39).
Anal. Calcd for C15H15NO3: C, 70.01; H, 5.88; N, 5.45.
Found: C, 70.19; H, 5.81; N, 5.17.
3.1.3.6. 3-Benzyl-5-methyl-2H-pyrano[3,2-c]quinolin-
2-one (12c). Reflux for 6 days; eluting first from the column
chromatography. Yellow crystals (from DCM), mp 163–
165 ꢀC; yield 7%; IR (Nujol) n (cmꢁ1): 3058, 1724, 1634;
1H NMR (CDCl3, 300 MHz) d: 2.75 (s, 3H), 3.96 (s, 2H),
7.26–7.48 (m, 5H), 7.57 (t, J¼7.9 Hz, 1H), 7.61 (s, 1H),
7.74 (t, J¼7.9 Hz, 1H), 7.98 (d, J¼7.9 Hz, 1H), 8.35 (d,
J¼7.9 Hz, 1H); 13C NMR (CDCl3, 75 MHz) d: 22.2, 36.9,
110.2, 117.2, 121.7, 126.8, 127.0, 128.4, 128.7, 128.9,
129.2, 131.4, 136.3, 137.2, 147.7, 155.7, 155.8, 160.3; MS
(EI) m/z: 301 (M+, 87), 300 (37), 287 (15), 273 (100), 244
(20), 202 (49), 196 (70), 167 (47), 105 (35), 91 (61), 77
(52). Anal. Calcd for C20H15NO2: C, 79.71; H, 5.02; N,
4.64. Found: C, 80.01; H, 5.05; N, 4.37.
3.1.3.2.
5-Methyl-2H-pyrano[3,2-c]quinolin-2-one
(12a). Heating at 60 ꢀC for 48 h. Yellow crystals (from
DCM/hexane), mp 159–161 ꢀC; yield 7%; IR (Nujol) n
(cmꢁ1): 3059, 1736, 1626; H NMR (CDCl3, 300 MHz) d:
1
2.89 (s, 3H), 6.55 (d, J¼9.8 Hz, 1H), 7.62 (t, J¼7.9 Hz, 1H),
7.81 (t, J¼7.9 Hz, 1H), 8.03 (d, J¼7.9 Hz, 1H), 8.05 (d,
J¼9.8 Hz, 1H), 8.42 (d, J¼7.9 Hz, 1H); 13C NMR (CDCl3,
75 MHz) d: 22.5, 104.6, 116.3, 122.0, 126.9, 128.7, 132.0,
140.7, 148.6, 151.8, 152.6, 154.7, 160.6; MS (EI) m/z: 211
(M+, 78), 183 (100), 154 (29), 128 (16), 127 (17), 102
(18), 77 (38), 76 (31). Anal. Calcd for C13H9NO2: C,
73.91; H, 4.30; N, 6.63. Found: C, 73.81; H, 4.11; N, 6.53.
3.1.4. Alternative procedure for the synthesis of ethyl 3-
(4-hydroxy-2-methylquinolinyl)-2-propenoate (11a) and
5-methyl-2H-pyrano[3,2-c]quinolin-2-one (12a). A mix-
ture of hydroxyaldehyde 9 (0.187 g, 1 mmol) and ylide
10a (0.39 g, 1 mmol) in dry toluene (5 ml) in a conical flask
was irradiated in a commercial microwave oven (800 W) for
3 min. The mixture, after the evaporation of the solvent, was
separated by column chromatography (silica gel, ethyl ace-
tate/hexane 7:3) to give compound 12a (10 mg, 2%) and
compound 11a (0.11 g, 16%).
3.1.3.3. Ethyl 3-(4-hydroxy-2-methyl-3-quinolinyl)-2-
methyl-2-propenoate (11b). Reflux for 11 days. Yellow
crystals (from DCM), mp 199–201 ꢀC; yield 76%; IR (Nu-
1
jol) n (cmꢁ1): 3434, 3062, 1702, 1635; H NMR (CDCl3,
300 MHz) d: 1.33 (t, J¼6.9 Hz, 3H), 2.35 (s, 3H), 2.83 (s,
3H), 4.23 (q, J¼6.9 Hz, 2H), 7.29 (t, J¼7.9 Hz, 1H), 7.47