Iodine-catalysed synthesis of thiopyrano[3,4-c]quinoline derivatives via imino-Diels-Alder reaction

Article abstract of DOI:10.3184/174751912X13352797144052

A mild and efficient method for the synthesis of thiopyrano[3,4-c]quinoline derivatives via an imino-Diels-Alder reaction of an aromatic aldehyde, 5-amino-1H-indazole or 2-aminoanthracene and tetrahydrothiopyran-4-one catalysed by iodine is described. This new procedure has the advantages of mild reaction conditions, high yields and metalfree catalysis. This is useful since quinoline and its derivatives have extensive biological activities.

Full text of DOI:10.3184/174751912X13352797144052

318 RESEARCH PAPER
JUNE, 318–321
JOURNAL OF CHEMICAL RESEARCH 2012
Iodine-catalysed synthesis of thiopyrano[3,4-c]quinoline derivatives via
imino-Diels–Alder reaction
Wei Wanga,b, Ming-Yue Yina,b, Mei-Mei Zhanga,b and Xiang-Shan Wanga,b*
aSchool of Chemistry and Chemical Engineering, Jiangsu Key Laboratory of Green Synthetic Chemistry for Functional Materials, Jiangsu
Normal University, Xuzhou Jiangsu 221116, P. R. China
bThe Key Laboratory of Biotechnology on Medical Plant of Jiangsu Province, Jiangsu Normal University, Xuzhou Jiangsu 221116, P. R. China
A mild and efficient method for the synthesis of thiopyrano[3,4-c]quinoline derivatives via an imino-Diels–Alder reac-
tion of an aromatic aldehyde, 5-amino-1H-indazole or 2-aminoanthracene and tetrahydrothiopyran-4-one catalysed
by iodine is described. This new procedure has the advantages of mild reaction conditions, high yields and metal-
free catalysis. This is useful since quinoline and its derivatives have extensive biological activities.
Keywords: quinoline, 5-amino-1H-indazole, 2-aminoanthracene, iodine, synthesis
Table 1 Yield optimisation for 4a under different conditionsa
Quinoline and its derivatives occur in a large number of
biologically active natural products,1–4 so the synthesis of
quinolines has been extensively researched over the years.5–7
Povarov and coworkers8 have explored an important methodol-
ogy that provides access to quinoline derivatives from an imino
Diels–Alder reaction, using a Schiff base and an electron-rich
dienophile as reactants. This approach, also known as the
Povarov reaction, is usually catalysed by various Lewis acids
and is described elsewhere.9
This methodology has been improved greatly by using
iodine catalysis and an aliphatic aldehyde starting material,10
in which the catalysis promotes formation of the enol tautomer
which acts as a dienophile. In our previous work, the range
of dienophiles was expanded to various types of ketones,
such as aliphatic, aromatic, and cyclicketone, all gave the
satisfactory results. In connection with our continued research
on this iodine-catalysed Povarov reaction,11–13 we now report
an efficient synthesis of thiopyrano[3,4-c]pyrazolo[4,3-f ]
quinoline and thiopyrano[3,4-c]naphtho[2,3-f ] quinoline
derivatives catalysed by iodine. This novel pentacyclic ring
skeleton containing naphthalene or pyrazole, thiopyran
and quinoline rings may possess potential bioactivity for
screening.
Entry
Temp. /°C Catalyst/mol % Solvent
Yields/%b
1
2
3
Reflux
r.t.
50
0
5
5
THF
THF
THF
0
Trace
74
4
5
6
7
8
9
10
Reflux
Reflux
Reflux
Reflux
Reflux
80
1
5
10
5
5
5
5
THF
THF
THF
CH3CN
Benzene
DMF
CHCl3
80
89
89
82
78
84
80
Reflux
a Reagents and conditions: 4-chlorobenzaldehyde 1a (0.281 g,
2.0 mmol), 2 (0.266 g, 2.0 mmol), 3 (0.232 g, 2.0 mmol), solvent
(10 mL).
b Isolated yields.
of I2 at room temperature, 50 °C and reflux temperature,
resulting in the isolation of 4a in trace amount, 74% and 89%
yields (Table 1, entries 2, 3 and 5), respectively. Thus, 5 mol%
of I2 and a reaction temperature at reflux were optimal condi-
tions. In addition, CH3CN, benzene, DMF and CHCl3 (Table 1,
entries 7−10) were also tested as the solvents. In these cases,
product 4a was formed in slightly lower yields.
According to the optimised conditions, various aromatic
aldehydes 1 were then subjected to reaction with 2 and 3
to generate a library of thiopyrano[3,4-c]pyrazolo[4,3-f] quin-
oline derivatives 4a–k (Table 2). For aldehydes 1, the yields of
4 were not sensitive to the electronic properties of the aromatic
ring in the presence of electron-withdrawing groups (such as
halide) or electron-donating groups (such as alkyl or alkoxy
group, Table 2).
The optimised conditions were also suitable for 2-aminoan-
thracene 5, which was reacted with a variety of aromatic
aldehydes 1 and tetrahydrothiopyran-4-one 3 (Scheme 2). The
reactions proceeded smoothly and gave thiopyrano[3,4-c]
naphtho[2,3-f]quinoline derivatives 6a–l in high yields
(Table 3). The structures of the products 4 and 6 were
characterised by 1H NMR, IR and HRMS, they are all in good
agreement with their structures.
Results and discussion
Treatment of aromatic aldehyde 1, 5-amino-1H-indazole 2 and
tetrahydrothiopyran-4-one 3 in THF in the presence of iodine
(5 mol%) under reflux conditions gave the corresponding
7-aryl-3,8,10,11-tetrahydrothiopyrano[3,4-c] pyrazolo[4,3-f]
quinoline derivatives 4 in high yields (Scheme 1).
In our initial study, the optimum amount of catalyst was
identified initially. Therefore, the model reactions were
conducted using 4-chlorobenzaldehyde (1a), 5-amino-1H-
indazole and tetrahydrothiopyran-4-one in THF at reflux in the
presence of various catalytic amounts of iodine. The screening
results from these reactions are summarised in Table 1. 1, 5
and 10 mol% iodine were used to mediate the reaction, it
was found that 5 mol% I2 at reflux in THF is sufficient to initi-
ate the reaction (Table 1, entries 4–6). To find the optimum
reaction temperature, the reaction was carried out with 5 mol%
Scheme 1
* Correspondent. E-mail: xswang1974@yahoo.com

JOURNAL OF CHEMICAL RESEARCH 2012 319
Table 2 Synthetic results of 4a–k catalysed by iodine in THFa
Table 3 Synthetic results of 6a–l catalysed by iodine in THFa
Ar
Products
Time/h
Yields/%b
Ar
Products
Time/h
Yields/%b
4-ClC6H4
4-FC6H4
4-MeC6H4
3-ClC6H4
2-ClC6H4
Piperonyl
3-MeOC6H4
2-FC6H4
3,4-Cl2C6H3
2,3-Cl2C6H3
4-MeOC6H4
4a
4b
4c
4d
4e
4f
4g
4h
4i
12
12
14
12
10
14
12
10
10
8
89
84
86
90
90
82
92
87
82
87
90
4-BrC6H4
4-MeC6H4
4-ClC6H4
3-ClC6H4
2-ClC6H4
3,4-Cl2C6H3
3,4-(MeO)2C6H3
3-MeOC6H4
4-FC6H4
2-BrC6H4
3-BrC6H4
6a
6b
6c
6d
6e
6f
6g
6h
6i
12
16
10
10
10
10
16
14
10
10
10
10
90
86
89
92
93
82
84
88
83
90
90
92
4j
4k
6j
6k
6l
15
2,3-Cl2C6H3
a Reagents and conditions: 1 (2.0 mmol), 2 (0.266 g, 2.0 mmol),
3 (0.232 g, 2.0 mmol), I2 (0.1 mmol, 0.026 g), THF (10 mL).
b Isolated yields.
aReagents and conditions: 1 (1.0 mmol), 5 (0.193 g, 1.0 mmol),
3 (0.116 g, 1.0 mmol), I2 (0.05 mmol, 0.013 g), THF (10 mL).
Experimental
7-(3-Chlorophenyl)-3,8,10,11-tetrahydrothiopyrano[3,4-c]pyra-
zolo[4,3-f]quinoline (4d): M.p. 238–240 °C; H NMR (DMSO-d6,
Melting points were determined in open capillaries and are uncor-
rected. IR spectra were recorded on a Tensor 27 spectrometer in KBr
pellet. 1H NMR spectra were obtained from a solution in DMSO-d6 or
CDCl3 with Me4Si as internal standard using a Bruker-400 spectrom-
eter. HRMS analyses were carried out using a Bruker-micro- TOF-
Q-MS analyser.
1
400 MHz): δH 3.18 (t, J = 6.0 Hz, 2H, CH2), 3.64 (s, 2H, CH2), 3.91 (s,
2H, CH2), 7.56 (s, 3H, ArH), 7.66 (s, 1H, ArH), 7.89 (d, J = 8.8 Hz,
1H, ArH), 7.94 (d, J = 8.8 Hz, 1H, ArH), 8.66 (s, 1H, ArH), 13.78 (s,
1H, NH). IR (KBr, cm–1): ν 3191, 3150, 3049, 2963, 2923, 2871,
1665, 1592, 1567, 1516, 1473, 1424, 1377, 1352, 1344, 1269, 1256,
1208, 1159, 1094, 934, 897, 885, 837, 807, 783, 733, 719. HRMS
(ESI, m/z): Calcd for C19H1535ClN3S [M+H]+ 352.0675, found
352.0686.
Syntheses of thiopyrano[3,4-c]pyrazolo[4,3-f] quinoline derivatives
4a–k; general procedure
A dry 50 mL flask was charged with aromatic aldehyde (2.0 mmol),
5-amino-1H-indazole (0.266 g, 2.0 mmol), tetrahydrothiopyran-4-one
(0.232 g, 2.0 mmol), I2 (0.026 g, 0.1 mmol) and THF (10 mL). The reac-
tion mixture was stirred at reflux for 8–15 h. After completion of the
reaction as indicated by TLC, part of the products dissolved out in the
boiling THF as a yellow solid; consequently a little DMF was added
to the hot mixture until it was dissolved entirely. The powder gener-
ated was collected by filtration to give 4 when the mixture was cooled
to room temperature.
7-(4-Chlorophenyl)-3,8,10,11-tetrahydrothiopyrano[3,4-c]pyra-
zolo[4,3-f]quinoline (4a): M.p. 265–267 °C; 1H NMR (DMSO-d6,
400 MHz): δH 3.18 (t, J = 6.0 Hz, 2H, CH2), 3.65 (t, J = 6.0 Hz, 2H,
CH2), 3.90 (s, 2H, CH2), 7.58 (d, J = 8.4 Hz, 2H, ArH), 7.64 (d, J = 8.4
Hz, 2H, ArH), 7.87 (d, J = 9.2 Hz, 1H, ArH), 7.93 (d, J = 8.8 Hz, 1H,
ArH), 8.65 (s, 1H, ArH), 13.74 (s, 1H, NH). IR (KBr, cm–1): ν 3201,
3038, 2932, 2889, 1660, 1595, 1556, 1529, 1491, 1435, 1421, 1396,
1373, 1354, 1267, 1172, 1085, 1014, 962, 938, 837, 811, 797, 758.
HRMS (ESI, m/z): Calcd for C19H1535ClN3S [M+H]+ 352.0675, found
352.0670.
7-(2-Chlorophenyl)-3,8,10,11-tetrahydrothiopyrano[3,4-c]pyra-
1
zolo[4,3-f]quinoline (4e): M.p. 283–285 °C; H NMR (DMSO-d6,
400 MHz): δH 3.16 (d, J = 6.0 Hz, 2H, CH2), 3.62 (s, 2H, CH2), 3.66
(s, 2H, CH2), 7.47–7.66 (m, 3H, ArH), 7.63 (d, J = 7.2 Hz, 1H, ArH),
7.86 (d, J = 8.8 Hz, 1H, ArH), 7.95 (d, J = 8.8 Hz, 1H, ArH), 8.66 (s,
1H, ArH), 13.77 (s, 1H, NH). IR (KBr, cm–1): ν 2962, 2934, 2865,
2840, 1695, 1604, 1557, 1514, 1467, 1411, 1383, 1363, 1253, 1226,
1170, 1137, 1107, 1022, 961, 893, 813, 755, 661. HRMS (ESI, m/z):
Calcd for C19H1535ClN3S [M+H]+ 352.0675, found 352.0689.
7-Piperonyl-3,8,10,11-tetrahydrothiopyrano[3,4-c]pyrazolo[4,3-f]
quinoline (4f): M.p. 255–257 °C; 1H NMR (DMSO-d6, 400 MHz): δH
3.17 (t, J = 6.0 Hz, 2H, CH2), 3.62 (s, 2H, CH2), 3.92 (s, 2H, CH2),
6.11 (s, 2H, CH2), 7.03–7.08 (m, 2H, ArH), 7.17 (s, 1H, ArH), 7.86 (d,
J = 9.2 Hz, 1H, ArH), 7.92 (d, J = 9.2 Hz, 1H, ArH), 8.64 (s, 1H,
ArH), 13.75 (s, 1H, NH). IR (KBr, cm–1): ν 3202, 3146, 3048, 2885,
1659, 1604, 1562, 1493, 1371, 1330, 1231, 1160, 1151, 1112, 1037,
939, 901, 848, 814, 785. HRMS (ESI, m/z): Calcd for C20H16N3O2S
[M+H]+ 362.0963, found 362.0933.
7-(3-Methoxyphenyl)-3,8,10,11-tetrahydrothiopyrano[3,4-c]pyra-
7-(4-Fluorophenyl)-3,8,10,11-tetrahydrothiopyrano[3,4-c]pyra-
zolo[4,3-f]quinoline (4b): M.p. 268–269 °C; H NMR (DMSO-d6,
1
1
zolo[4,3-f]quinoline (4g): M.p. 252–254 °C; H NMR (DMSO-d6,
400 MHz): δH 3.18 (s, 2H, CH2), 3.62 (s, 2H, CH2), 3.83 (s, 3H,
CH3O), 3.88 (s, 2H, CH2), 7.05 (d, J = 7.6 Hz, 1H, ArH), 7.13 (d,
J = 8.8 Hz, 2H, ArH), 7.43 (t, J = 7.6 Hz, 1H, ArH), 7.86 (d, J = 8.8
Hz, 1H, ArH ), 7.93 (d, J = 8.8 Hz, 1H, ArH), 8.67 (s, 1H, ArH), 13.78
(s, 1H, NH). IR (KBr, cm–1): ν 3182, 3129, 3043, 2925, 1668, 1608,
1578, 1517, 1486, 1450, 1426, 1365, 1327, 1286, 1223, 1175, 1156,
1115, 1095, 1045, 972, 932, 887, 853, 788, 733, 709. HRMS (ESI,
m/z): Calcd for C20H18N3OS [M+H]+ 348.1171, found 348.1183.
7-(2-Fluorophenyl)-3,8,10,11-tetrahydrothiopyrano[3,4-c]pyra-
400 MHz): δH 3.18 (s, 2H, CH2), 3.65 (s, 2H, CH2), 3.89 (s, 2H, CH2),
7.35 (t, J = 8.4 Hz, 2H, ArH), 7.64–7.67 (m, 2H, ArH), 7.88 (d, J = 8.8
Hz, 1H, ArH), 7.93 (d, J = 8.8 Hz, 1H, ArH), 8.65 (s, 1H, ArH), 13.74
(s, 1H, NH). IR (KBr, cm–1): ν 3204, 3150, 3056, 2959, 2924, 2885,
1661, 1604, 1509, 1420, 1364, 1326, 1268, 1224, 1157, 1094, 947,
845, 815, 740. HRMS (ESI, m/z): Calcd for C19H15FN3S [M+H]+
336.0971, found 336.1023.
7-(p-Tolyl)-3,8,10,11-tetrahydrothiopyrano[3,4-c]pyrazolo[4,3-
f]quinoline (4c): M.p. 270–272 °C; 1H NMR (DMSO-d6, 400 MHz):
δH 2.41 (s, 3H, CH3), 3.18 (t, J = 6.0 Hz, 2H, CH2), 3.64 (t, J = 5.6 Hz,
2H, CH2), 3.89 (s, 2H, CH2), 7.33 (d, J = 8.0 Hz, 2H, ArH), 7.49 (d,
J = 8.0 Hz, 2H, ArH), 7.86 (d, J = 9.2 Hz, 1H, ArH), 7.92 (d, J = 8.8
Hz, 1H, ArH), 8.64 (s, 1H, ArH), 13.73 (s, 1H, NH). IR (KBr, cm–1):
ν 3190, 3132, 3042, 2922, 2881, 1667, 1589, 1557, 1511, 1447,
1424, 1367, 1327, 1269, 1179, 1157, 1105, 935, 834, 819, 787, 738.
HRMS (ESI, m/z): Calcd for C20H18N3S [M+H]+ 332.1221, found
332.1255.
1
zolo[4,3-f]quinoline (4h): M.p. 280–282 °C; H NMR (DMSO-d6,
400 MHz): δH 3.18 (s, 2H, CH2), 3.65 (s, 2H, CH2), 3.72 (s, 2H, CH2),
7.36–7.40 (m, 2H, ArH), 7.50–7.57 (m, 2H, ArH), 7.88 (d, J = 8.4 Hz,
1H, ArH), 7.94 (d, J = 8.4 Hz, 1H, ArH), 8.66 (s, 1H, ArH), 13.78 (s,
1H, NH). IR (KBr, cm–1): ν 3193, 3130, 3036, 2915, 2878, 1615,
1573, 1561, 1520, 1490, 1446, 1373, 1332, 1280, 1253, 1206, 1158,
1091, 941, 845, 821, 786, 755. HRMS(ESI, m/z):CalcdforC19H15FN3S
[M+H]+ 336.0971, found 336.0962.
Scheme 2

320 JOURNAL OF CHEMICAL RESEARCH 2012
7-(3,4-Dichlorophenyl)-3,8,10,11-tetrahydrothiopyrano[3,4-c]
pyrazolo[4,3-f]quinoline (4i): M.p. 296–298 °C; 1H NMR (DMSO-d6,
400 MHz): δH 3.18 (s, 2H, CH2), 3.63 (s, 2H, CH2), 3.93 (s, 2H, CH2),
7.61 (d, J = 8.4 Hz, 1H, ArH), 7.77 (d, J = 8.0 Hz, 1H, ArH), 7.88 (s,
2H, ArH), 7.93 (d, J = 8.4 Hz, 1H, ArH), 8.66 (s, 1H, ArH), 13.76 (s,
1H, NH). IR (KBr, cm–1): ν 3180, 3144, 2927, 1667, 1582, 1550,
1517, 1469, 1430, 1382, 1355, 1323, 1271, 1249, 1174, 1134, 1106,
1030, 973, 946, 884, 848, 826, 786, 755. HRMS (ESI, m/z): Calcd for
C19H1435Cl2N3S [M+H]+ 386.0285, found 386.0288.
7-(2,3-Dichlorophenyl)-3,8,10,11-tetrahydrothiopyrano[3,4-c]
pyrazolo[4,3-f]quinoline (4j): M.p. 295–298 °C; 1H NMR (DMSO-d6,
400 MHz): δH 3.17 (s, 2H, CH2), 3.59–3.68 (m, 4H, 2CH2), 7.46 (d,
J = 7.2 Hz, 1H, ArH), 7.51–7.55 (m, 1H, ArH), 7.79 (d, J = 8.0 Hz,
1H, ArH), 7.86 (d, J = 8.8 Hz, 1H, ArH), 7.94 (d, J = 8.8 Hz, 1H,
ArH), 8.66 (s, 1H, ArH), 13.78 (s, 1H, NH). IR (KBr, cm–1): ν 3188,
3141, 3047, 2979, 2932, 1671, 1605, 1586, 1557, 1517, 1453, 1407,
1365, 1327, 1277, 1190, 1152, 1089, 1048, 940, 883, 843, 813, 783,
745, 720, 700. HRMS (ESI, m/z): Calcd for C19H1435Cl2N3S [M+H]+
386.0285, found 386.0290.
ArH), 8.42 (s, 1H, ArH), 8.93 (s, 1H, ArH) .. IR (KBr, cm–1): ν 3047,
2909, 1594, 1546, 1531, 1470, 1410, 1384, 1361, 1285, 1258, 1141,
1077, 955, 890, 814, 791, 743, 704. HRMS (ESI, m/z): Calcd for
C26H1935ClNS [M+H]+ 412.0927, found 412.0942.
5-(2-Chlorophenyl)-2,4-dihydro-1H-thiopyrano[3,4-c]naphtho
[2,3-f]quinoline (6e): M.p. 219–220°C; 1H NMR (CDCl3, 400 MHz):
δH 2.70–2.76 (m, 1H, CH2), 3.04–3.09 (m, 1H, CH2), 3.67 (d, J = 14.8 Hz,
1H, CH2), 3.83–3.94 (m, 2H, CH2), 4.26–4.32 (m, 1H, CH2), 7.42–
7.64 (m, 6H, ArH), 7.82 (d, J = 8.8 Hz, 1H, ArH), 7.98 (d, J = 9.2 Hz,
1H, ArH), 8.10 (dd, J = 9.6 Hz, J’ = 7.2 Hz, 2H, ArH), 8.43 (s, 1H,
ArH), 9.01 (s, 1H, ArH). IR (KBr, cm–1): ν 3051, 2917, 2853, 1548,
1529, 1468, 1429, 1381, 1361, 1285, 1275, 1119, 1046, 952, 887, 819,
747, 708. HRMS (ESI, m/z): Calcd for C26H1935ClNS [M+H]+
412.0927, found 412.0957.
5-(3,4-Dichlorophenyl)-2,4-dihydro-1H-thiopyrano[3,4-c]naphtho
[2,3-f]quinoline (6f): M.p. 226–229°C; 1H NMR (CDCl3, 400 MHz):
δH 2.89 (t, J = 2.8 Hz, 2H, CH2), 3.95 (s, 2H, CH2), 4.05 (t, J = 6.0 Hz,
2H, CH2), 7.50 (dd, J = 8.4 Hz, J’ = 2.0 Hz, 1H, ArH), 7.60–7.64 (m,
3H, ArH), 7.77–7.81 (m, 2H, ArH), 7.98 (d, J = 9.2 Hz, 1H, ArH),
8.10 (dd, J = 8.8 Hz, J’ = 4.4 Hz, 2H, ArH), 8.43 (s, 1H, ArH), 8.93 (s,
1H, ArH). IR (KBr, cm–1): ν 3053, 2914, 2854, 1546, 1533, 1469,
1383, 1361, 1267, 1246, 1181, 1115, 1067, 1028, 956, 895, 837, 749,
709. HRMS (ESI, m/z): Calcd for C26H1835Cl2NS [M+H]+ 446.0537,
found 446.0556.
5-(3,4-Dimethoxyphenyl)-2,4-dihydro-1H-thiopyrano[3,4-c]naphtho
[2,3-f]quinoline (6g): M.p. 227–229°C; 1H NMR (CDCl3, 400 MHz):
δH 2.90 (t, J = 6.0 Hz, 2H, CH2), 3.97 (d, J = 5.2 Hz, 6H, 2CH3O), 4.03
(s, 2H, CH2), 4.05 (d, J = 6.0 Hz, 2H, CH2), 7.02 (d, J = 8.0 Hz, 1H,
ArH), 7.35 (dd, J = 8.0 Hz, J’ = 1.6 Hz, 1H, ArH), 7.27 (s, 1H, ArH),
7.61 (dd, J = 6.4 Hz, J’ = 3.2 Hz, 2H, ArH), 7.83 (d, J = 9.2 Hz, 1H,
ArH), 7.96 (d, J = 9.2 Hz, 1H, ArH), 8.09 (dd, J = 8.8 Hz, J’ = 5.6 Hz,
2H, ArH), 8.42 (s, 1H, ArH), 8.93 (s, 1H, ArH). IR (KBr, cm–1): ν
3055, 2927, 2835, 1602, 1583, 1536, 1514, 1461, 1448, 1425, 1372,
1326, 1256, 1229, 1166, 1136, 1026, 900, 880, 803, 746. HRMS (ESI,
m/z): Calcd for C28H22NO2S [M-H]+ 436.1370, found 436.1363.
5-(3-Methoxyphenyl)-2,4-dihydro-1H-thiopyrano[3,4-c]naphtho
[2,3-f]quinoline (6h): M.p. 209–211°C; 1H NMR (CDCl3, 400 MHz):
δH 2.89 (t, J = 6.0 Hz, 2H, CH2), 3.90 (s, 3H, CH3O), 3.99 (s, 2H,
CH2), 4.05 (t, J = 6.0 Hz, 2H, CH2), 7.01–7.03 (m, 1H, ArH), 7.21 (d,
J = 7.2 Hz, 2H, ArH), 7.42–7.46 (m, 1H, ArH), 7.61 (dd, J = 6.0 Hz,
J’ = 3.6 Hz, 2H, ArH), 7.83 (d, J = 9.2 Hz, 1H, ArH), 7.97 (d, J = 8.8
Hz, 1H, ArH), 8.09 (dd, J = 9.2 Hz, J’ = 6.0 Hz, 2H, ArH), 8.42 (s, 1H,
ArH), 8.94 (s, 1H, ArH). IR (KBr, cm–1): ν 3043, 2994, 2946, 2927,
2839, 1605, 1575, 1544, 1474, 1449, 1433, 1373, 1327, 1314, 1282,
1270, 1245, 1222, 1163, 1109, 1039, 952, 894, 872, 825, 787, 754,
702. HRMS (ESI, m/z): Calcd for C27H21NO2S [M+H]+ 408.1422,
found 408.1420.
5-(4-Fluorophenyl)-2,4-dihydro-1H-thiopyrano[3,4-c]naphtho
[2,3-f]quinoline (6i): M.p. 254–256°C; 1H NMR (CDCl3, 400 MHz):
δH 2.90 (t, J = 6.0 Hz, 2H, CH2), 3.96 (s, 2H, CH2), 4.05 (t, J = 6.0 Hz,
2H, CH2), 7.22 (d, J = 8.8 Hz, 2H, ArH), 7.61–7.68 (m, 4H, ArH),
7.82 (d, J = 9.2 Hz, 1H, ArH), 7.98 (d, J = 8.8 Hz, 1H, ArH), 8.10 (dd,
J = 8.4 Hz, J’ = 4.4 Hz, 2H, ArH), 8.43 (s, 1H, ArH), 8.93 (s, 1H,
ArH). IR (KBr, cm–1): ν 3040, 2947, 2924, 2851, 1601, 1550, 1537,
1506, 1478, 1437, 1421, 1390, 1371, 1286, 1261, 1217, 1180, 1156,
1139, 1118, 1093, 956, 894, 842, 812, 747. HRMS (ESI, m/z): Calcd
for C26H19FNS [M+H]+ 396.1222, found 396.1218.
5-(2-Bromophenyl)-2,4-dihydro-1H-thiopyrano[3,4-c]naphtho
[2,3-f]quinoline (6j): M.p. 225–227 °C; 1H NMR (CDCl3, 400 MHz):
δH 2.70–2.76 (m, 1H, CH2), 3.04–3.08 (m, 1H, CH2), 3.66 (d, J = 14.8
Hz, 1H, CH2), 3.84–3.92 (m, 2H, CH2), 4.26–4.32 (m, 1H, CH2),
7.32–7.36 (m, 1H, ArH), 7.48–7.55 (m, 2H, ArH), 7.61–7.63 (m, 2H,
ArH), 7.71 (d, J = 8.0 Hz, 1H, ArH), 7.82 (d, J = 9.2 Hz, 1H, ArH),
7.98 (d, J = 9.2 Hz, 1H, ArH), 8.08–8.12 (m, 2H, ArH), 8.43 (s, 1H,
ArH), 9.02 (s, 1H, ArH). IR (KBr, cm–1): ν 3050, 2927, 2910, 1547,
1530, 1468, 1426, 1382, 1360, 1286, 1274, 1257, 1116, 1025, 953,
889, 821, 815, 745. HRMS (ESI, m/z): Calcd for C26H1979BrNS [M+H]+
456.0422, found 456.0420.
7-(4-Methoxyphenyl)-3,8,10,11-tetrahydrothiopyrano[3,4-c]
1
pyrazolo[4,3-f]quinoline (4k): M.p. 254–257 °C; H NMR (DMSO-
d6, 400 MHz): δH 3.18 (s, 2H, CH2), 3.63 (s, 2H, CH2), 3.84 (s, 3H,
CH3O), 3.91 (s, 2H, CH2), 7.07 (d, J = 7.6 Hz, 2H, ArH), 7.55 (d,
J = 7.6 Hz, 2H, ArH), 7.87 (d, J = 8.4 Hz, 1H, ArH), 7.91 (d, J = 8.8
Hz, 1H, ArH), 8.64 (s, 1H, ArH), 13.72 (s, 1H, NH). IR (KBr, cm–1): ν
3178, 3123, 3080, 3035, 3007, 2920, 1610, 1560, 1510, 1458, 1425,
1367, 1326, 1297, 1257, 1175, 1106, 1028, 930, 836, 820, 790, 742.
HRMS (ESI, m/z): Calcd for C20H18N3OS [M+H]+ 348.1171, found
348.1174.
Syntheses of 5-aryl-2,4-dihydro-1H-thiopyrano[3,4-c]naphtho[2,3-f]
quinoline derivatives 6a-l; general procedure
A dry 50 mL flask was charged with aromatic aldehyde (1.0 mmol),
2-aminoanthracene (0.193 g, 1.0 mmol), tetrahydrothiopyran-4-one
(0.116 g, 1.0 mmol), I2 (0.013 g, 0.05 mmol) and THF (10 mL). The
reaction mixture was stirred at reflux for 10–16 h. After completion of
the reaction as indicated by TLC, part of the products dissolved out in
the boiling THF as yellow solid; consequently a little DMF was added
to the hot mixture until it was dissolved entirely. The generated powder
was collected by filtration to give 6 when the mixture was cooled to
room temperature.
5-(4-Bromophenyl)-2,4-dihydro-1H-thiopyrano[3,4-c]naphtho
[2,3-f]quinoline (6a): M.p. 239–241°C; 1H NMR (CDCl3, 400 MHz):
δH 2.90 (t, J = 6.4 Hz, 2H, CH2), 3.95 (s, 2H, CH2), 4.05 (t, J = 6.4 Hz,
2H, CH2), 7.54–7.69 (m, 6H, ArH), 7.81 (d, J = 8.8 Hz, 1H, ArH),
7.97 (d, J = 9.2 Hz, 1H, ArH), 8.10 (dd, J = 9.2 Hz, J’ = 4.4 Hz, 2H,
ArH), 8.43 (s, 1H, ArH), 8.93 (s, 1H, ArH). IR (KBr, cm–1): ν 3047,
2924, 1588, 1547, 1474, 1439, 1421, 1386, 1264, 1176, 1113, 1100,
1070, 1010, 954, 892, 836, 825, 811, 746. HRMS (ESI, m/z): Calcd
for C26H1979BrNS [M+H]+ 456.0422, found 456.0422.
5-(p-Tolyl)-2,4-dihydro-1H-thiopyrano[3,4-c]naphtho[2,3-f]quino-
line (6b): M.p. 233–236°C; 1H NMR (CDCl3, 400 MHz): δH 2.45 (s,
3H, CH3), 2.89 (t, J = 6.0 Hz, 2H, CH2), 4.00 (s, 2H, CH2), 4.03 (t,
J = 6.0 Hz, 2H, CH2), 7.34 (d, J = 7.6 Hz, 2H, ArH), 7.55–7.62 (m,
4H, ArH), 7.82 (d, J = 9.2 Hz, 1H, ArH), 7.95 (d, J = 9.2 Hz, 1H,
ArH), 8.09 (dd, J = 9.2 Hz, J’ = 6.0 Hz, 2H, ArH), 8.41 (s, 1H, ArH),
8.93 (s, 1H, ArH). IR (KBr, cm–1): ν 3060, 3031, 2939, 2917, 2849,
1611, 1543, 1477, 1436, 1387, 1369, 1286, 1265, 1225, 1213, 1180,
1140, 1112, 1016, 949, 892, 827, 743. HRMS (ESI, m/z): Calcd for
C27H22NS [M+H]+ 392.1473, found 392.1483.
5-(4-Chlorophenyl)-2,4-dihydro-1H-thiopyrano[3,4-c]naphtho
[2,3-f]quinoline (6c): M.p. 243–246°C; 1H NMR (CDCl3, 400 MHz):
δH 2.89 (t, J = 6.4 Hz, 2H, CH2), 3.95 (s, 2H, CH2), 4.04 (t, J = 6.4 Hz,
2H, CH2), 7.51 (d, J = 8.4 Hz, 2H, ArH), 7.61–7.63 (m, 4H, ArH),
7.79 (d, J = 8.8 Hz, 1H, ArH), 7.97 (d, J = 9.2 Hz, 1H, ArH), 8.09 (dd,
J = 9.2 Hz, J’ = 4.4 Hz, 2H, ArH), 8.42 (s, 1H, ArH), 8.93 (s, 1H,
ArH). IR (KBr, cm–1): ν 3048, 2932, 2869, 1596, 1547, 1476, 1440,
1422, 1388, 1285, 1263, 1215, 1174, 1171, 1087, 1012, 954, 934, 891,
838, 746. HRMS (ESI, m/z): Calcd for C26H1935ClNS [M+H]+
412.0927, found 412.0954.
5-(3-Bromophenyl)-2,4-dihydro-1H-thiopyrano[3,4-c]naphtho
[2,3-f]quinoline (6k): M.p. 214–215°C; 1H NMR (CDCl3, 400 MHz):
δH 2.90 (t, J = 6.0 Hz, 2H, CH2), 3.96 (s, 2H, CH2), 4.05 (t, J = 6.0 Hz,
2H, CH2), 7.38–7.42 (m, 1H, ArH), 7.57–7.63 (m, 4H, ArH), 7.80 (d,
J = 8.8 Hz, 1H, ArH), 7.85 (s, 1H, ArH), 7.98 (d, J = 9.2 Hz, 1H,
ArH), 8.10 (dd, J = 9.2 Hz, J’ = 5.2 Hz, 2H, ArH), 8.43 (s, 1H, ArH),
8.94 (s, 1H, ArH). IR (KBr, cm–1): ν 3061, 2930, 2861, 1591, 1543,
1467, 1444, 1426, 1382, 1370, 1264, 1224, 1181, 1142, 1064, 996,
5-(3-Chlorophenyl)-2,4-dihydro-1H-thiopyrano[3,4-c]naphtho
[2,3-f]quinoline (6d): M.p. 209–210°C; 1H NMR (CDCl3, 400 MHz):
δH 2.89 (t, J = 6.0 Hz, 2H, CH2), 3.96 (s, 2H, CH2), 4.04 (t, J = 6.0 Hz,
2H, CH2), 7.45–7.47 (m, 2H, ArH), 7.52–7.55 (m, 1H, ArH), 7.61–
7.63 (m, 2H, ArH), 7.69 (s, 1H, ArH), 7.80 (d, J = 9.2 Hz, 1H, ArH),
7.97 (d, J = 9.2 Hz, 1H, ArH), 8.09 (dd, J = 9.2 Hz, J’ = 5.6 Hz, 2H,

JOURNAL OF CHEMICAL RESEARCH 2012 321
964, 890, 824, 805, 787, 770, 751, 701. HRMS (ESI, m/z): Calcd for
C26H1979BrNS [M+H]+ 456.0422, found 456.0420.
the Graduate Foundation of Jiangsu Normal University
and Qing Lan Project (08QLT001, 10QLD008) of Jiangsu
Education Committee for financial support.
5-(2,3-Dichlorophenyl)-2,4-dihydro-1H-thiopyrano[3,4-c]naphtho
[2,3-f]quinoline (6l): M.p. 241–244°C; 1H NMR (CDCl3, 400 MHz):
δH 2.71–2.77 (m, 1H, CH2), 3.03–3.09 (m, 1H, CH2), 3.65 (d, J = 14.8
Hz, 1H, CH2), 3.84–3.91 (m, 2H, CH2), 4.25–4.32 (m, 1H, CH2),
7.37–7.41 (m, 1H, ArH), 7.46 (dd, J = 7.6 Hz, J’ = 1.6 Hz, 1H, ArH),
7.58–7.65 (m, 3H, ArH), 7.79 (d, J = 9.2 Hz, 1H, ArH), 7.99 (d,
J = 9.2 Hz, 1H, ArH), 8.10 (dd, J = 9.6 Hz, J’ = 6.8 Hz, 2H, ArH),
8.43 (s, 1H, ArH), 9.01 (s, 1H, ArH). IR (KBr, cm–1): ν 3054, 2969,
2921, 2852, 1548, 1480, 1437, 1422, 1408, 1389, 1375, 1270, 1178,
1154, 1135, 1045, 948, 891, 805, 788, 745, 716. HRMS (ESI, m/z):
Calcd for C26H1835Cl2NS [M+H]+ 446.0537, found 446.0523.
Received 27 October 2011; accepted 20 March 2012
Paper 1100956 doi: 10.3184/174751912X13352797144052
Published online: 4 June 2012
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In conclusion, we have found a mild and efficient method
for the synthesis of thiopyrano[3,4-c]pyrazolo[4,3-f]quinoline
and thiopyrano[3,4-c]naphtho[2,3-f] quinoline derivatives via
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We are grateful to a Project Funded by the Priority Academic
Program Development of Jiangsu Higher Education Institutions,

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