V.K. Tandon et al. / European Journal of Medicinal Chemistry 44 (2009) 3130–3137
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4.2.8. 2-Amino-3-(naphthalen-1-ylsulfanyl)-
[1,4]naphthoquinone (5c)
(423): C, 73.74; H, 4.05; N, 3.31; S, 7.57; Found: C, 74.21; H, 4.08; N,
3.28; S, 7.68.
Brown powder from methanol; IR (KBr): 1585 and 1662 (>C]O
of quinone), 3270 and 3440 (NH2) cmꢁ1
;
1H NMR (300 MHz,
4.3.6. 2-(Diphenylamino)-3-(phenylthio)naphthalene-1,
CDCl3):
d
8.17 (m, 2H), 7.98 (m, 2H), 7.77 (m, 4H), 7.50 (m, 3H), 7.30
4-dione (6f)
(bs, NH2). Anal. Calcd. for C20H13NO2S (331): C, 72.49; H, 3.95; N,
4.23; S, 9.68; Found: C, 71.92; H, 3.92; N, 4.27; S, 9.60.
Red oil; IR (KBr): 1590 and 1678 (>C]O of quinone) cmꢁ1
;
1H
NMR (400 MHz, CDCl3):
d 8.04–8.08 (m, 4H), 7.94–7.98 (m, 2H),
7.60–7.80 (m, 4H), 7.43–7.49 (m, 3H), 7.02–7.11 (m, 3H), 6.60–6.69
(m, 3H); Anal. Calcd. for C28H19NO2S (434): C, 77.57; H, 4.42; N,
3.23; S, 7.40; Found: C, 77.42; H, 4.38; N, 3.18; S, 7.45.
4.3. General procedure for the synthesis of novel 2-arylamino-3-
arylsulfanyl-1,4-naphthoquinones (6)
A mixture of compounds (3a–c) (5 mmol) and aryl thiols
(5.2 mmol) in abs. MeOH (50 mL) was refluxed at different
temperatures using triethylamine (5 mmol) as base. The resulting
solution was concentrated in vacuo and the residue was subjected
to column chromatography on silica gel using EtOAc/hexane. The
product was crystallized with suitable solvent to give 6 in excellent
yields (Table 1).
4.3.7. 2-(Diphenylamino)-3-(3-methoxyphenylthio)naphthalene-
1,4-dione (6g)
Red oil; IR (KBr): 1588 and 1662 (>C]O of quinone), 2359 and
2925 (OCH3) cmꢁ1; 1H NMR (400 MHz, CDCl3):
d 8.03–8.07 (m, 4H),
7.92–7.96 (m, 2H), 7.59–7.78 (m, 4H), 7.43–7.45 (m, 2H), 7.02–7.11
(m, 3H), 6.62–6.70 (m, 3H), 3.73 (s, 3H, OCH3). Anal. Calcd. for
C29H21NO3S (464): C, 75.14; H, 4.57; N, 3.02; S, 6.92; Found: C,
75.42; H, 4.58; N, 3.08; S, 7.00.
4.3.1. 2-Phenylamino-3-(phenylthio)naphthalene-1,4-dione (6a)
Brown solid from methanol; IR (KBr): 1589 and 1664 (>C]O of
4.3.8. 2-(Diphenylamino)-3-(naphthalene-1-ylthio)naphthalene-
1,4-dione (6h)
quinone), 3265 (N–H) cmꢁ1 1H NMR (400 MHz, CDCl3):
; d 8.18 (d,
J ¼ 7.6, 1H), 8.13 (d, J ¼ 7.6, 1H), 7.93 (bs s, 1H), 7.76 (t, J ¼ 7.6, 1H),
7.69 (t, J ¼ 7.6, 1H), 7.17–7.15 (t, 2H), 7.13–6.98 (m, 4H), 6.75–6.68
(m, 4H); Anal. Calcd. for C22H15NO2S (357): C, 73.93; H, 4.23; N,
3.92; S, 8.97; Found: C, 74.22; H, 4.21; N, 3.98; S, 9.03.
Yellow powder from methanol; IR (KBr): 1590 and 1678 (>C]O
of quinone) cmꢁ1; 1H NMR (400 MHz, CDCl3):
d 8.04–8.08 (m, 4H),
7.94–7.7.98 (m, 2H), 7.60–7.80 (m, 9H), 7.43–7.49 (m, 6H). Anal.
Calcd. for C32H21NO2S (484): C, 79.48; H, 4.38; N, 2.90; S, 6.63;
Found: C, 78.98; H, 4.34; N, 2.92; S, 6.58.
4.3.2. 2-(3-Methoxyphenylthio)-3-(phenylamino)naphthalene-1,
4-dione (6b)
4.4. General procedure for the synthesis of
dihydrobenzo[f]naphtho[2,3-b][1,4]thiazepine-6,11-diones (9)
Shining brown solid from methanol; IR (KBr): 1587 and 1662
(>C]O of quinone), 2359 and 2925 (OMe), 3310 (N–H) cmꢁ1 1H
;
NMR (400 MHz, CDCl3):
d
8.18 (d, J ¼ 7.6, 1H), 8.13 (d, J ¼ 7.6, 1H),
It was synthesized according to the procedure reported by Wang
et al. [21].
7.96 (bs, 1H), 7.77 (t, J ¼ 7.6, 1H), 7.69 (t, J ¼ 7.6, 1H), 7.19–7.17 (t, 2H,
Ar-H), 7.15–7.09 (t, 1H, Ar-H), 6.96–6.92 (t, 1H, Ar-H), 6.73–6.71 (d,
2H, Ar-H), 6.60–6.58 (d, 1H, Ar-H), 6.38–6.39 (d, 1H), 6.22 (s, 1H, Ar-
H), 3.63 (s, 3H, OCH3), Mass (Fab): Mþ ¼ 387, Mþ þ 1 ¼388,
4.4.1. 12-Phenyl-12,13-dihydrobenzo[f]naphtho
[2,3-b][1,4]thiazepine-6,11-dione (9a)
M
þ þ 2 ¼ 389; 13C NMR (400 MHz, CDCl3):
d 54, 112 (2C) 113, 114,
Dark red solid after column chromatography on silica gel G
using ethyl acetate in hexane as solvent (10–50%); IR (KBr): 1654,
120,122,124,126 (2C),127,128,130,132,133,134 (2C),136,142,159,
180 (2C). Anal. Calcd. for C23H17NO3S (387): C, 71.30; H, 4.42; N,
3.62; S, 8.28; Found: C, 71.24; H, 4.39; N, 3.58; S, 8.32.
1723, 2961 cmꢁ1 1H NMR (300 MHz, CDCl3):
; d 8.04–8.11 (m, 3H),
7.61–7.68 (m, 3H), 6.62–7.05 (m, 7H), 4.50 (s, 2H). Mass (Fab):
M
þ þ 1 ¼370. Anal. Calcd. for C23H15NO2S (369): C, 74.78; H, 4.09;
4.3.3. 2-(Naphthalene-1-ylthio)-3-(phenylamino)naphthalene-1,
4-dione (6c)
N, 3.79; S, 8.68; Found: C, 75.12; H, 4.12; N, 3.82; S, 8.70.
Light brown solid from methanol; IR (KBr): 1590 and 1662
4.4.2. 3-Methoxy-12-phenyl-12,13-dihydrobenzo[f]naphtho[2,3-
b][1,4]thiazepine-6,11-dione (9b)
(>C]O of quinone), 3329 (N–H) cmꢁ1; 1H NMR (400 MHz, CDCl3):
d
8.04–8.08 (m, 4H), 7.94–7.98 (m, 2H), 7.68–7.80 (m, 4H), 7.43–7.49
Dark brown solid after column chromatography on silica gel G
using ethyl acetate in hexane as solvent (10–50%); IR (KBr): 1650,
(m, 3H) 7.32–7.26 (m, 2H), 6.62–6.56 (m, 2H). Anal. Calcd. for
C26H17NO2S (407): C, 76.64; H, 4.21; N, 3.44; S, 7.87; Found: C,
75.92; H, 4.19; N, 3.41; S, 7.91.
1726, 2370, 2961 cmꢁ1; 1H NMR (300 MHz, CDCl3):
d 7.98–8.10 (m,
3H), 7.64–7.66 (m, 3H), 6.70–6.98 (m, 6H), 4.52 (s, 2H), 3.81 (s, 3H);
Anal. Calcd. for C24H17NO3S (399): C, 72.16; H, 4.29; N, 3.51; S, 8.03;
Found: C, 71.88; H, 4.04; N, 3.48; S, 7.92.
4.3.4. 2-(4-Hydroxyphenylamino)-3-(phenylthio)naphthalene-1,
4-dione (6d)
Shining brown solid from methanol; IR (KBr): 1546 and 1624
(>C]O of quinone), 3315 (N–H), 3375 (O–H) cmꢁ1
;
1H NMR
4.5. General procedure for the synthesis of isoindoline-1,3-dione
(400 MHz, CDCl3):
d
8.18 (d, J ¼ 7.2, 1H), 8.12 (d, J ¼ 7.2, 1H), 7.90 (bs,
derivatives of 1,4-naphthoquinone (13)
1H), 7.68–7.76 (m, 3H) 7.31 (m, 1H), 7.03–7.05 (m, 3H), 6.77–6.80
(m, 2H), 6.62 (m, 3H); Anal. Calcd. for C22H15NO3S (373): C, 70.76; H,
4.05; N, 3.75; S, 8.59; Found: C, 70.02; H, 4.01; N, 3.70; S, 8.63.
A mixture of phthalic anhydride (10) (130 mmole) and ethyl-
enediamine (11) (200 mmole) in acetic acid (10 mL) was stirred at
100 ꢀC for 1h. 2-(2-aminoethyl)isoindoline-1,3-dione (12) was
obtained as colorless crystals. A mixture of naphthoquinone (1a–b)
(5 mmol) and compound 12 (5 mmol), K2CO3 (5 mmol) and abs.
EtOH (50 mL) was refluxed at 90 ꢀC for 24 h . The resulting solution
was concentrated in vacuo and the residue was subjected to
column chromatography on silica gel using EtOAc/hexane. The
product was crystallized with EtOAc/hexane to give 13 (Table 1).
4.3.5. 2-(4-Hydroxyphenylamino)-3-(naphthalene-1-
ylthio)naphthalene-1,4-dione (6e)
Red oil; IR (KBr): 1593 and 1678 (>C]O of quinone), 3230
(N–H), 3469 (O–H) cmꢁ1 1H NMR (400 MHz, CDCl3):
; d 8.05–8.08
(m, 4H), 7.92–7.97 (m, 2H), 6.58–6.64 (m, 2H) 7.69–7.85 (m, 4H),
7.45–7.50 (m, 3H), 7.33–7.27 (m, 2H); Anal. Calcd. for C26H17NO3S