SUBSTITUTED NAPHTHOQUINONES AS MACROFILARICIDES
191
2.32 mM) was added slowly in 2 ml of DCM. Stirring was 13C-NMR (400 MHz, CDCl3): d 182.87, 180, 148.74,
continued for 5–6 h at room temperature. The reaction 134.50, 133.92, 131.71, 130.77, 126.16, 126.08, 100.06,
was monitored by TLC. The color of the reaction mixture 52.25, 46.87, 46.87, 42.98, 24.51, 11.53, 11.53. 1H-
changed from yellow to deep black. Purification was NMR (400 MHz, CDCl3): d 8.02 (d, 1H), 7.92 (d, 1H),
carried out by flash chromatography in a silica column with 7.71 (t, 1H), 7.61 (t, 1H), 5.85 (bs, 1H), 5.68 (s, 1H),
petroleum ether/chloroform/ethyl acetate 4:3:1 mobile 3.29 (t, 2H), 2.60 (m, 4H), 1.85 (t, 2H), 1.28 (m, 2H),
phase to yild orange yellow crystals: yield 261 mg 1.09 (t, 6H). IR (KBr) n: 3257, 1685, 1631 cmꢂ1
(49.1%); mp 60.21C; TLC (petroleum ether/chloroform/
.
ethyl acetate 54:3:1) Rf 0.89; HPLC Rt 2.48 min. 13C-
Synthesis of 2-f[3-(Dibutylamino)
NMR (400 MHz, CDCl3): d 182.96, 182.11, 147.15,
Propyl]AminogNaphthalene-1,4-Dione (8)
134.76, 133.68, 131.88, 130.54, 126.28, 126.14, 100.71,
To a stirred solution of 3-(dibutylamino)-1-propyl-
amine (1.56 ml, 6.96 mM) in ethanol (4 ml), 1,4-
naphthoquinone (367mg, 2.32 mM) was added slowly
in 2 ml of DCM. Stirring was continued for 5–6 h at
room temperature. The reaction was monitored by TLC.
The color of the reaction mixture was changed from
yellow to deep black. Purification was carried out by
flash chromatography in silica column with petroleum
ether/chloroform/ethyl acetate/methanol 2:5:1:1 mobile
1
49.58, 28.84, 19.23, 10.31. H-NMR (400 MHz, CDCl3):
d 8.05 (d, 1H), 8.04 (d, 1H), 7.71 (t, 1H), 7.61 (t, 1H),
5.79 (bs, 1H), 5.74 (s, 1H), 3.52 (m, 1H), 1.64 (m, 2H),
1.26 (d, 3H), 0.99 (t, 3H). IR (KBr) n: 3338, 1676,
1627 cmꢂ1
.
Synthesis of 2-f[3-(Dimethylamino)
Propyl]AminogNaphthalene-1,4-Dione (6)
To a stirred solution of 3-(dimethylamino)-1- phase to yield orange yellow crystals: 287 mg (36.1%);
propylamine (0.871 ml, 6.96 mM) in ethanol (4 ml), mp 76.71C; TLC (petroleum ether/chloroform/ethyl
1,4-naphthoquinone (367 mg, 2.32 mM) was added acetate/methanol)5 2: 5: 1: 1 Rf 0.76; HPLC Rt
slowly in 2 ml of DCM. Stirring was continued for 0.99min. 13C-NMR (400 MHz, CDCl3): d 181.86,
5–6 h at room temperature. The reaction was mon- 180.89, 147.66, 133.47, 132.88, 130.70, 129.73, 125.15,
itored by TLC. The color of the reaction mixture 125.06, 99.11, 53.81, 52.22, 52.22, 41.79, 27.89, 27.89,
1
changed from yellow to deep black. Purification was 23.85, 19.73, 19.73, 13.06, 13.06. H-NMR (400 MHz,
carried out by flash chromatography in silica column CDCl3): d 8.04 (d, 1H), 7.98 (d, 1H), 7.64 (t, 1H), 7.52
with
a petroleum ether/chloroform/ethyl acetate/ (t, 1H), 5.82 (bs, 1H), 5.61(s, 1H), 3.19 (t, 2H), 2.50
methanol 2:5:1:2 mobile phase to yield orange yellow (t, 4H), 2.49 (t, 2H), 1.76 (m, 2H), 1.41 (m, 4H),
crystals: yield 57 mg (9.5%); mp 71.31C; TLC (petro- 1.26 (m, 4H), 0.84 (t, 6H). IR (KBr) n: 3257, 1683,
leum ether/chloroform/ethyl acetate/methanol (2:5:1:2) 1629 cmꢂ1
Rf 0.37; HPLC Rt 0.96 min. 13C-NMR (400 MHz,
CDCl3): d 182, 181, 147, 133.62, 132.50, 130.86,
125.50, 125.20, 125.12, 99.39, 58, 51, 43.93, 43.93,
.
Synthesis of 2-[(1,3-Dimethylbutyl)
Amino]Naphthalene-1,4-Dione (9)
1
23.71. H-NMR (400 MHz, CDCl3): d 8.016 (d, 1H),
To a stirred solution of 1,3-dimethylbutylamine
(0.977 ml, 6.96 mM) in ethanol (4 ml), 1,4-naphthoqui-
none (367 mg, 2.32 mM) was added slowly in 2 ml of
DCM. Stirring was continued for 5–6 h at room
temperature. The reaction was monitored by TLC.
The color of the reaction mixture changed from yellow
to deep black. Purification was carried out by flash
7.98 (d, 1H), 7.67 (t, 1H), 7.56 (t, 1H), 5.85 (bs, 1H),
5.64 (s, 1H), 3.22 (t, 2H), 2.49 (t, 2H), 2.31 (s, 6H), 1.85
(m, 2H). IR (KBr) n: 3348, 1680, 1597 cmꢂ1
.
Synthesis of 2-f[3-(Diethylamino)
Propyl]AminogNaphthalene-1,4-Dione (7)
To a stirred solution of 3-(diethylamino)-1-pro- chromatography in silica column with a petroleum
pylamine (1.09 ml, 6.96 mM) 3 in ethanol (4 ml), 1,4- ether/chloroform/ethyl acetate 2:3:1 mobile phase to
naphthoquinone (367 mg, 2.32 mM) was added slowly yield orange yellow crystals: 254 mg (42.5%); mp
in 2 ml of DCM. Stirring was continued for 5–6 h at 81.51C; TLC (petroleum ether: chloroform: ethyl
room temperature. The reaction was monitored by acetate): 2:3:1 Rf 0.96; HPLC Rt 3.16 min. 13C-NMR
TLC. The color of the reaction mixture was changed (400 MHz, CDCl3): d 181.93, 181.11, 146.01, 133.74,
from yellow to deep black. Purification was carried out 132.68, 130.83, 129.52, 125.25, 125.12, 99.42, 45.31,
1
by flash chromatography in silica column with petro- 44.52, 24.03, 21.55, 21.55, 18.90. H-NMR (400 MHz,
leum ether/chloroform/ethyl acetate/methanol 2:5:1:2 CDCl3): d 8.04 (d, 1H), 7.96 (d, 1H), 7.66 (t, 1H), 7.55
mobile phase to yield a dark red liquid: yield 306 mg (t,1H), 5.95 (bs, 1H), 5.77 (s, 1H), 3.48 (m, 1H), 1.49
(46.1%); TLC (petroleum ether/chloroform/ethyl (m, 1H), 1.34 (m, 2H), 1.17 (d, 3H), 0.87 (dd, 6H). IR
acetate/methanol) 2:5:1:2 Rf 0.52; HPLC Rt 0.98 min. (KBr) n: 3315, 1678, 1618 cmꢂ1
.
Drug Dev. Res.