8814
G. C. Muscia et al. / Tetrahedron Letters 47 (2006) 8811–8815
1
3
Melting points were determined in a capillary Electro-
thermal 9100 SERIES-Digital apparatus and are given
5.02 (s, 2H), 7.37–8.21 (m, 8H). C NMR (DMSO-d
6
): d
1
1
1
1
3.15, 45.46, 61.40, 124.70, 126.27, 126.57, 128.53, 128.92,
29.02, 131.36, 131.80, 132.93, 134.10, 145.10, 146.89,
52.96, 166.20. IR (cm ): m 2956, 1720, 1471, 1317, 1223,
2 2
069, 835, 703. Anal. Calcd for C19H15Cl NO : C, 63.35;
H, 4.20; N, 3.89. Found: C, 63.24; H, 4.38; N, 3.73. 7-
Chloro-9-phenyl-1,2,3,4-tetrahydroacridine (entry 5, 3e):
1
13
uncorrected. H and C NMR spectra were recorded
at rt using a Bruker 200 MHz spectrometer with TMS
as the internal standard. The chemical shifts (d) are
given in ppm. Infrared spectra were recorded on a FT
Perkin Elmer Spectrum One from KBr discs. Analytical
À1
1
H NMR (DCCl
3
): d 1.85 (m, 2H), 2.03 (m, 2H), 2.69
À1
TLC were performed on DC-Alufolien Kiesegel 60 F254
(m, 2H), 3.72 (m, 2H), 7.21–8.98 (m, 8H). IR (cm ): m
3019, 2942, 1630, 1580, 1478, 1178, 717. Anal. Calcd for
C H ClN: C, 77.68; H, 5.49; N, 4.77. Found: C, 77.74;
H, 5.85; N, 4.99. 6-Chloro-2,3-dimethyl-4-phenylquinoline
): d 2.30 (s, 3H), 3.30 (s,
H), 7.12–7.80 (m, 7H), 9.00 (d, 1H). IR (cm ): m 3083,
Merck. Microwave-assisted reactions were carried out in
a household MW oven BGH-QUICK Chef 15240. This
apparatus was modified for laboratory applications
adapting an external Liebig condenser.
1
9
16
1
(
entry 6, 3f): H NMR (DCCl
3
À1
3
1
641, 1482, 1375, 1024, 702. Anal. Calcd for C17H14ClN:
C, 76.26; H, 5.27; N, 5.23. Found: C, 76.01; H, 5.37; N,
1
Acknowledgement
5.34. 6-Chloro-2,4-diphenylquinoline (entry 7, 3g):
H
NMR (DCCl ): d 7.69–8.40 (m, 13H), 9.77 (d, 1H). IR
3
À1
We wish to thank Dr. Foluke Fakorede, TDR, WHO
(cm ): m 3053, 1611, 1162, 754, 705. Anal. Calcd for
(
Switzerland). We are grateful for the financial support
21
C H14ClN: C, 79.87; H, 4.47; N, 4.44. Found: C, 79.70;
H, 4.49; N, 4.72. Methyl 6-chloro-2-methyl-4-phenylquin-
from Universidad de Buenos Aires (UBACyT B-020).
1
oline-3-carboxylate (entry 8, 3h): H NMR (DCCl ): d 2.76
(
3
À1
s, 3H), 3.58 (s, 3H), 7.32–8.04 (m, 8H). IR (cm ): m 3067,
2
911, 1736, 1585, 1480, 1448, 1210, 828, 710. Anal. Calcd
References and notes
for C H ClNO : C, 69.35; H, 4.53; N, 4.49. Found: C,
1
8
14
2
6
9.68; H, 4.86; N, 4.41. 3-Acetyl-6-chloro-2-methyl-4-
1
1
. WHO Drug Inf. Bull. 1999, 13, 9.
3
phenylquinoline (entry 9, 3i): H NMR (DCCl ): d 1.98
2
. Ayad, F.; Tilley, L.; Deady, L. W. Bioorg. Med. Chem.
Lett. 2001, 11, 2075.
(s, 3H), 3.12 (s, 3H), 7.62–7.96 (m, 7H), 9.09 (d, 1H). IR
(cm ): m 3035, 1704, 1480, 1385, 840, 711. Anal. Calcd for
À1
3
4
5
. As ´ı s, S. E.; Bruno, A. M.; Dominici, D.; Bollini, M.;
Gaozza, C. H. J. Heterocycl. Chem. 2003, 40, 107.
. Muscia, G. C.; Bollini, M.; Bruno, A. M.; As ´ı s, S. E. J.
Chil. Chem. Soc. 2006, 51, 859.
. Sabitha, G.; Babu, R. S.; Subba Reddy, B. V.; Yadav, J. S.
Synth. Commun. 1999, 29, 4403.
C
18
H
14ClNO: C, 73.10; H, 4.77; N, 4.74. Found: C, 73.31;
H, 5.04; N, 4.93. 2-Chloro-11-phenyl-7,8,9,10-tetrahydro-
6H-cyclohepta[b]quinoline (entry 10, 3j):
(DCCl ): d 1.5–1.7 (m, 2H), 1.75–1.95 (m, 4H), 2.65–2.75
(m, 2H), 3.2–3.4 (m, 2H), 7.19–7.25 (m, 3H), 7.51–7.56 (m,
1
H NMR
3
À1
3H), 7.99 (d, 1H). IR (cm ): m 2955, 2889, 1489, 831, 707.
6
7
. Perreux, L.; Loupy, A. Tetrahedron 2001, 57, 9199.
. Song, S. J.; Cho, S. J.; Park, D. K.; Kwon, T. W.; Jenekhe,
S. A. Tetrahedron Lett. 2003, 44, 255.
Anal. Calcd for C20H18ClN: C, 78.04; H, 5.89; N, 4.55.
Found: C, 78.20; H, 6.06; N, 4.83.
10. Palimkar, S. S.; Siddiqui, S. A.; Rajgopal, T. D.; Lahoti,
J.; Srinivasan, K. V. J. Org. Chem. 2003, 68, 9371.
11. Wang, G.; Jia, C.; Dong, Y. Tetrahedron Lett. 2006, 47,
1059.
8
. Typical procedure for compounds 3a–j: A mixture of 1a–c
(
2.16 mmol) and a-methyleneketone 2 (10.90 mmol) with
.15 mL concd HCl in a 50 mL round-bottomed flask was
0
subjected to microwave irradiation. After completion of
the reaction (TLC), the reaction mixture was diluted with
12. De, S. K.; Gibbs, R. A. Tetrahedron Lett. 2005, 46,
1647.
CH
2
Cl
2
(15 mL) and washed with satd soln NaHCO
3
13. Typical procedure for compound 4: A mixture of 3d (0.40 g,
(
10 mL) and brine (10 mL). This was then dried (Na SO )
2 3
1.10 mmol), pyperidine (0.11 mL, 1.10 mmol) and K CO
2
4
and concentrated under reduced pressure to give a solid
product which was triturated with EtOH.
(0.15 g, 1.10 mmol) with 0.15 mL concd HCl and 0.3 mL
DMF in a 50 mL round-bottomed flask was subjected to
microwave irradiation for 15 min. The reaction mixture
9
. Spectra data for products: 2,4-dimethylquinoline 3-carb-
1
oxylic acid (entry 1, 3a): H NMR (DMSO-d ): d 2.32 (s,
was diluted with CH
5% HCl (10 mL) and brine (10 mL). This was then dried
(Na SO ) and concentrated under reduced pressure to give
2 2
Cl (15 mL) and washed with water,
6
3
H), 2.44 (s, 3H), 7.21–7.83 (m, 4H), 11.99 (s, 1H). IR
À1
(
cm ): m 3468, 2930, 2848, 1692, 1655, 1432, 749. Anal.
2
4
Calcd for C12
H
11NO
2
: C, 71.63; H, 5.51; N, 6.96. Found:
a yellow solid product. This was triturated in benzene to
give a white solid powder (mp 211–213 °C, yield 70%). The
same reaction was carried out with conventional heating
for 3 h in AcOH as the solvent and the yield was 50%.
C, 71.42; H, 5.77; N, 6.60. Ethyl 2-methyl-6-nitro-4-
phenylquinoline-3-carboxylate (entry 2, 3b): H NMR
1
(
6
DMSO-d ): d 0.88 (t, 3H), 2.73 (s, 3H), 4.05–4.09 (q,
À1
2H), 7.40–8.52 (m, 8H). IR (cm ): m 3089, 2981, 1728,
Ethyl 6-chloro-4-phenyl-2-(pyperidil)methylquinolin-3-car-
): d 0.81 (t, 3H), 1.74–1.87
1
1
C
6
620, 1526, 1339, 1224, 1065, 707. Anal. Calcd for
: C, 67.85; H, 4.79; N, 8.33. Found: C,
7.79; H, 4.91; N, 8.21. Ethyl 6-chloro-2-methyl-4-phenyl-
boxylate H NMR (DMSO-d
6
H
16
N
2
O
4
(m, 6H), 3.19–3.22 (m, 2H), 3.63–3.69 (m, 2H), 4.02–4.05
19
À1
(q, 2H), 4.76 (s, 2H), 7.37–8.30 (m, 8H). IR (cm ): m 2941,
1
quinoline-3-carboxylate (entry 3, 3c): H NMR (DMSO-
1722, 1562, 1480, 1222, 1081, 833, 680. Anal. Calcd for
d ): d 0.88 (t, 3H), 2.68 (s, 3H), 3.99–4.10 (q, 2H),
24 2 2
C H25ClN O : C, 70.49; H, 6.16; N, 6.85. Found: C,
70.40; H, 6.50; N, 7.14.
6
1
3
7
6
1
1
7
4
.35–8.10 (m, 8H). C NMR (DMSO-d
1.14, 124.41, 125.21, 127.66, 128.47, 128.89, 128.99,
6
): d 13.31, 23.21,
For antimalarial activity (K1 strain is used), if the IC50 is
>5 lg/mL, the compound is classified as inactive. If the
IC50 is 0.5–5 lg/mL, the compound is classified as
moderately active. If the IC50 is <0.5 lg/mL, the com-
pound is classified as active and is further evaluated using
30.84, 130.97, 131.33, 134.13, 144.67, 145.46, 154.53,
À1
67.06. IR (cm ): m 3035, 2928, 1722, 1221, 1069, 840,
12. Anal. Calcd for C19
2
H16ClNO : C, 70.05; H, 4.95; N,
.30. Found: C, 70.28; H, 5.28; N, 4.39. Ethyl 6-chloro-2-
chloromethyl-4-phenylquinoline-3-carboxylate (entry 4, 3d):
1
6
H NMR (DMSO-d ): d 0.85 (t, 3H), 3.99–4.03 (q, 2H),