Page 7 of 9
RSC Advances
DOI: 10.1039/C4RA09042J
ECSꢀ400 (or 100 MHz for 13C) spectrometers using either residual solvent
signals as an internal reference or from internal tetramethylsilane on the δ
scale ( MeOHꢀd4 δH 3.3 ppm, CDCl3 δC 77.0 ppm). The chemical shifts (δ) are
70 mixture was placed in nitrogen atmosphere and reflux at 115 oC for 24 h. After
completion of the reaction, the solvent was removed under reduced pressure to
obtain a residue which was purified by column chromatography over silica gel
(Eluent: 2% MeOH in chloroform) to furnish the pure compound 7b (40 mg, 30%)
as off white solid. 1H NMR (400 MHz, DMSOꢀD6) δ 9.63 (s, 1H), 8.53 (dd, J = 10.5
75 and 4.6 Hz, 2H), 8.29 (dd, J = 7.9 and 1.5 Hz, 1H), 8.24 – 8.17 (m, 1H), 7.98 (dd, J
= 8.3 and 7.4 Hz, 1H), 7.25 (dd, J = 8.9 and 7.6 Hz, 1H), 6.86 – 6.78 (m, 1H), 6.74
(dd, J = 5.0 and 2.7 Hz, 2H).
reported in ppm and coupling constants (J) in Hz. The following abbreviations
5
are used: s (singlet), d (doublet) m (multiplet), dd (doublet of doublet). Highꢀ
resolution mass spectra were obtained from a MicroMass ESIꢀTOF MS
spectrometer equipped with a Micromass ZꢀSpray electrospray ionization
(ESI) source (Waters Co., Synapt G2, France). Absorption spectra were
recorded on a PerkinElmer, Lambda 45 UVꢀVis spectrophotometer. Steady
10 State fluorescence experiments were carried out in a micro fluorescence
cuvette (Hellma, path length 1.0 cm) on a Fluoromax 4 instrument (Horiba
Jobin Yvon). (FTꢀIR) spectra were obtained using NICOLET 6700 FTꢀIR
spectrophotometer as KBr disc and reported in cmꢀ1. Melting points were
measured using a VEEGO Melting point apparatus. All melting points were
15 measured in open glass capillary and values are uncorrected.
2-(3-Hydroxyphenyl)-6-(piperidin-1-yl)-1H-benzo[de]isoquinoline-1,3(2H)-
dione (C23H20N2O3) 4m′: To a solution of 7b (300 mg, 0.814 mmol) in 2ꢀ
80 Methoxymethanol (10 mL) placed in 100 mL twoꢀneck round bottomed flask were
added piperidine (162 µL 1.62 mmol) slowly with stirring. The reaction mixture was
placed in nitrogen atmosphere and reflux at 125 oC for 24 h. After completion of the
reaction, the solvent was removed under reduced pressure to obtain a yellow residue
which was purified by column chromatography over silica gel (Eluent: 40% EtOAc
85 in petroleum ether) to furnish the pure compound 4m′ (290 mg, 95%) as yellow
solid M.p. = 283ꢀ284 oC; IR (KBr): νmax/cmꢀ1 3565, 1707, 1676, 1531, 1484, 1368,
1225, 770; 1H NMR (400 MHz, DMSOꢀD6) δ 9.58 (s, 1H), 8.47 – 8.26 (m, 3H), 7.77
(t, J = 7.8 Hz, 1H), 7.40 – 7.14 (m, 2H), 6.79 (d, J = 8.4 Hz, 1H), 6.68 (d, J = 8.7
Hz, 2H), 3.16 (s, 4H), 1.78 (s, 4H), 1.61 (s, 2H); 13C NMR (100 MHz DMSOꢀD6): δ
90 164.2, 163.6, 158.3, 157.2, 137.6, 132.7, 131.2, 131.1, 130.1, 129.9, 126.3, 126.0,
123.5, 120.1, 116.7, 115.9, 115.5, 115.4, 54.5, 26.2, 24.3; HRMS (ESI): Calc. for
C23H21N2O3 [M+H] +: 373.1553; Found: 373.1554.
Synthesis.
28
6-Bromo-2-(2-hydroxyphenyl)-1H-benzo[de]isoquinoline-1,3(2H)-dione 7a:
To a solution of anhydride 5 (150 mg, 0.54 mmol) in pyridine (4 mL) placed in a 25
mL twoꢀneck round bottomed flask were added 2ꢀaminophenol 6a (59 mg, 0.54
20 mmol) slowly with stirring The reaction mixture was placed in nitrogen atmosphere
and reflux at 115 oC for 24 h. After completion of the reaction, the solvent was
removed under reduced pressure to obtain a yellow residue which was purified by
column chromatography over silica gel (Eluent: CH2Cl2) to furnish the pure
compound 7a (150 mg, 75%) as white solid. 1H NMR (400 MHz, DMSOꢀD6) δ 9.57
25 (s, 1H), 8.56 (ddd, J = 8.6, 7.9 and 1.0 Hz, 2H), 8.31 (d, J = 7.8 Hz, 1H), 8.22 (d, J =
7.8 Hz, 1H), 8.00 (dd, J = 8.5 and 7.4 Hz, 1H), 7.28 – 7.22 (m, 1H), 7.19 (dd, J = 7.8
and 1.6 Hz, 1H), 6.94 (dd, J = 8.2 and 1.2 Hz, 1H), 6.87 (td, J = 7.6 and 1.3 Hz, 1H).
(C18H10 BrNO3)
3-(1,3-Dioxo-6-(piperidin-1-yl)-1H-benzo[de]isoquinolin-2(3H)-yl)phenyl
2,4-
dinitrobenzenesulfonate 4m (C29H22N4O9S): To a solution of 4m′ (110 mg, 0.268
95 mmol) in dry CH2Cl2 (10 mL) placed in 100 mL two neck round bottomed flask
were added triethylamine (107 µL,0.805 mmol), 2,4ꢀdinitrobenzeneꢀ1ꢀsulfonyl
chloride (215 mg, 0.805 mmol) slowly with stirring. The reaction mixture was
placed under nitrogen atmosphere and stirred at room temperature for 3 h. After
completion of the reaction; the solvent was removed under reduced pressure. The
100 residue was poured into H2O (10 mL) and extracted with CH2Cl2 (15 mL × 3). The
combined organic layer was washed with water (10 mL × 3), brine (10 mL) and
dried over Na2SO4.The solvent was removed under reduced pressure to obtain a
yellow residue which was purified by column chromatography over silica gel
(Eluent: 45% EtOAc in petroleum ether) to furnish the pure compound 4m (70 mg,
105 43%) as yellow solid. M.p. = 175ꢀ176 oC; IR (KBr): ν max/cmꢀ1 1657, 1547, 1478,
1359, 1073, 999, 757, 729; 1H NMR (400 MHz, DMSOꢀD6) δ 9.00 (s, 1H), 8.59 (d,
J = 8.6 Hz, 1H), 8.40 (d, J = 8.4 Hz, 1H), 8.34 (d, J = 7.2 Hz, 1H), 8.26 (d, J = 8.1
Hz, 1H), 8.13 (d, J = 8.6 Hz, 1H), 7.78 (t, J = 7.8 Hz, 1H), 7.57 (t, J = 8.1 Hz, 1H),
7.42 – 7.25 (m, 1H), 7.13 (s, 3H), 3.17 (s, 4H), 1.79 (s, 4H), 1.62 (s, 2H); 13C NMR
110 (100 MHz, DMSOꢀd6): δ 164.0, 163.4, 157.4, 151.9, 148.8, 148.4, 138.2, 134.3,
2-(2-Hydroxyphenyl)-6-(piperidin-1-yl)-1H-benzo[de]isoquinoline-1,3(2H)-
30 dione 4o′ (C23H20N2O3): To
a solution of 7a (100 mg, 0.27 mmol) in 2ꢀ
Methoxymethanol (10 mL) placed in 100 mL twoꢀneck round bottomed flask were
added piperidine (160 µL 1.62 mmol) slowly with stirring. The reaction mixture was
placed in nitrogen atmosphere and reflux at 125 oC for 24 h. After completion of the
reaction, the solvent was removed under reduced pressure to obtain a yellow residue
35 which was purified by column chromatography over silica gel (Eluent: 40% EtOAc
in petroleum ether) to furnish the pure compound 4o′ (60 mg, 60%) as yellow solid.
M.p. = 248ꢀ249 oC; IR (KBr): ν/cmꢀ1 3565, 1694, 1578, 1372, 1232, 779, 747; 1H
NMR (400 MHz, DMSOꢀD6) δ 8.60 (dd, J = 7.3 and 1.2 Hz, 1H), 8.52 (d, J = 8.2
Hz, 1H), 8.42 (dd, J = 8.4 and 1.1 Hz, 1H), 7.68 (dd, J = 8.4 and 7.3 Hz, 1H), 7.31 –
40 7.25 (m, 1H), 7.22 – 7.16 (m, 2H), 7.07 – 6.96 (m, 2H), 5.80 (s, 1H), 3.42 – 3.05 (m,
4H), 1.88 (p, J = 5.9 Hz, 4H), 1.77 – 1.68 (m, 2H); 13C NMR (100 MHz DMSOꢀD6):
δ 164.0, 163.5, 157.2, 153.9, 132.6, 131.1, 131.0, 130.8, 130.2, 129.9, 126.3, 126.1,
123.7, 119.5, 116.8, 116.2, 115.4, 54.5, 26.2, 24.3; HRMS (ESI): Calc. for
C23H21N2O3 [M+H] +: 373.1553; Found: 373.1555.
132.6, 131.3, 130.9, 130.7, 130.0, 128.1, 126.2, 125.9, 123.8, 123.4, 122.5, 121.6,
+
115.7, 115.3, 54.4, 26.1, 24.3; HRMS (ESI): Calc. for C29H23N4O9S [M+H]
603.1186; Found: 603.1177.
:
6-Bromo-2-(4-hydroxyphenyl)-1H-benzo[de]isoquinoline-1,3(2H)-dione
7c
45 2-(1,3-Dioxo-6-(piperidin-1-yl)-1H-benzo[de]isoquinolin-2(3H)-yl)phenyl
2,4-
115 (C18H10 BrNO3): To a solution of 5 (500 mg, 1.80 mmol) in pyridine (10 mL)
placed in a 100 mL twoꢀneck round bottomed flask were added 4ꢀaminophenol 6c
(196 mg, 1.80 mmol) slowly with stirring The reaction mixture was placed in
nitrogen atmosphere and reflux at 115 oC for 24 h. After completion of the reaction,
the solvent was removed under reduced pressure to obtain a yellow residue which
120 was purified by column chromatography over silica gel (Eluent: 2% MeOH in
chloroform) to furnish the pure compound 7c (350 mg, 53%) as white solid. M.p. ≥
294 oC; IR (KBr): νmax/cmꢀ1 3565, 1676, 1614, 1484, 782; 1H NMR (400 MHz,
DMSOꢀD6) δ 9.64 (s, 1H), 8.54 (q, J = 7.6 Hz, 2H), 8.29 (d, J = 7.8 Hz, 1H), 8.20
(d, J = 7.8 Hz, 1H), 7.98 (t, J = 7.9 Hz, 1H), 7.10 (d, J = 7.7 Hz, 2H), 6.82 (d, J =
125 8.6 Hz, 2H); 13C NMR (100 MHz DMSOꢀD6): δ 163.9, 163.8, 157.7, 133.1, 132.0,
131.9, 131.4, 130.3, 129.5, 129.3, 129.2, 127.1, 123.9, 123.1, 115.9; HRMS (ESI):
Calc. for C18H11 BrNO3 [M+H] +: 367.9923; Found: 367.9915.
dinitrobenzenesulfonate 4o (C29H22N4O9S): To a solution of 4o′ (150 mg, 0.402
mmol) in dry CH2Cl2 (10 mL) placed in 100 mL two neck round bottomed flask
were added triethylamine (168 µL,1.206 mmol), 2,4ꢀdinitrobenzeneꢀ1ꢀsulfonyl
chloride (322 mg, 1.206 mmol) slowly with stirring. The reaction mixture was
50 placed under nitrogen atmosphere and stirred at room temperature for 3 h. After
completion of the reaction; the solvent was removed under reduced pressure. The
residue was poured into H2O (10 mL) and extracted with CH2Cl2 (15 mL × 3). The
combined organic layer was washed with water (10 mL × 3), brine (10 mL) and
dried over Na2SO4.The solvent was removed under reduced pressure to obtain a
55 yellow residue which was purified by column chromatography over silica gel
(Eluent: 45% EtOAc in petroleum ether) to furnish the pure compound 4o (200 mg,
83%) as yellow solid. M.p. = 283ꢀ284 oC; IR (KBr): ν/cmꢀ1 1659, 1578, 1546, 1485,
1348, 1085, 781, 752; 1H NMR (400 MHz, DMSOꢀD6) δ 8.34 (dd, J = 8.7 and 2.4
Hz, 2H), 8.29 – 8.20 (m, 2H), 8.06 (d, J = 8.1 Hz, 1H), 7.99 (d, J = 8.7 Hz, 1H), 7.75
60 – 7.66 (m, 1H), 7.59 (d, J = 3.5 Hz, 1H), 7.51 (dt, J = 13.4 and 6.1 Hz, 2H), 7.15 (d,
J = 8.1 Hz, 1H), 3.20 (s, 4H), 1.80 (s, 4H), 1.65 (s, 2H); 13C NMR (100 MHz,
DMSOꢀD6): δ 163.3, 162.8, 157.6, 151.0, 147.3, 145.9, 133.9, 132.8, 132.4, 132.1,
2-(4-Hydroxyphenyl)-6-(piperidin-1-yl)-1H-benzo[de]isoquinoline-1,3(2H)-
dione 4p′ (C23H20N2O3): To
a solution of 7c (230 mg, 0.62 mmol) in 2ꢀ
130 Methoxymethanol (10 mL) placed in 100 mL twoꢀneck round bottomed flask were
added piperidine (124 µL 1.24 mmol) slowly with stirring. The reaction mixture was
placed in nitrogen atmosphere and reflux at 125 oC for 24 h. After completion of the
reaction, the solvent was removed under reduced pressure to obtain a yellow residue
which was purified by column chromatography over silica gel (Eluent: 40% EtOAc
135 in petroleum ether) to furnish the pure compound 4p′ (232 mg, 97%) as yellow
solid. M.p. = 292ꢀ293 oC; IR (KBr): νmax/cmꢀ1 3418, 1692, 1580, 1376, 1231, 856,
828; 1H NMR (400 MHz, DMSOꢀD6) δ 9.58 (s, 1H), 8.42 – 8.14 (m, 3H), 7.67 (s,
1H), 7.19 (d, J = 8.2 Hz, 1H), 6.94 (d, J = 8.6 Hz, 2H), 6.70 (d, J = 8.3 Hz, 2H), 3.06
131.7 131.2, 130.8, 129.8, 129.0, 128.6, 128.1, 126.1, 125.6, 124.4, 122.6, 120.3,
+
115.0, 114.6, 54.4, 26.2, 24.4; HRMS (ESI): Calc. for C29H23N4O9S [M+H]
65 603.1186; Found: 603.1196.
:
6-bromo-2-(3-hydroxyphenyl)-1H-benzo[de]isoquinoline-1,3(2H)-dione
7b
(C18H10 BrNO3):29 To a solution of 4ꢀBromoꢀ1, 8ꢀnapthalic anhydride 5 (100 mg,
0.36 mmol) in pyridine (5 mL) placed in a 25 mL twoꢀneck round bottomed flask
were added 3ꢀaminophenol 6b (39 mg, 0.36 mmol) slowly with stirring The reaction
6
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