10.1002/cmdc.202000721
ChemMedChem
FULL PAPER
A solution of 1,8-naphthalic anhydride (14) (1.0 mmol, 0.198 g), 3-
chloroaniline (3.0 mmol, 0.315 mL) and triethylamine (10 drops) in 15
mL absolute ethanol was heated to reflux for 44 h, with magnetic
stirring, then allowed to cool to room temperature. The mixture was
filtered in vacuo, the yellow precipitate washed with cold ethanol (15
mL) and cold diethyl ether (15 mL), and dried in vacuo to afford the
desired compound as an off-white solid (0.132 g, 43%), m.p.: 232-234
ºC.
1H NMR (400 MHz, CDCl3) 8.65 (d, J = 7.0 Hz, 2H), 8.29 (d, J = 8.1
Hz, 2H), 7.81 (t, J = 7.6 Hz, 2H), 7.48 (m, 7.49 – 7.48, 2H), 7.35 (s, 1H),
7.24 (m, 7.24 – 7.23, 1H); 13C NMR (101 MHz, CDCl3) δ 164.3 (2C), 136.6,
135.1, 134.7 (2C), 131.9 (2C), 130.4, 129.4, 129.2, 128.7, 127.26, 127.25
(2C), 122.7 (3C); IR (cm-1) 1667 (C=O), 774 (C-Cl); LCMS (ESI+) m/z: 308
[M+H]+ (100%), 310 [M+H]+ (35%); HRMS (ESI+) m/z calculated for
C18H11ClNO2 (M+H)+ 308.0473; compound did not ionise.
122.7 (2C), 119.6, 116.2, 115.2; IR (cm-1) 3243 (O-H), 1645 (C=O), 777
(Ar-H); LRMS (ESI+) m/z: 290 [M+H]+, (100%); (ESI-) m/z: 288 [M-H]-
(100%).
2-(3-Hydroxyphenyl)-1H-benzo[de]isoquinoline-1,3(2H)-dione (20)
A solution of 1,8-naphthalic anhydride (14) (1.0 mmol, 0.198 g), 3-
aminophenol (3.0 mmol, 0.327 g) and triethylamine (8 drops) in 15 mL
absolute ethanol was heated to reflux for 18 h, with magnetic stirring,
then allowed to cool to 0 ºC. The mixture was filtered in vacuo, the pale
brown precipitate washed with cold ethanol (3 mL) and cold diethyl
ether (3 mL), then dried in vacuo to afford the desired compound as a
creamy-coloured solid (0.166 g, 57%), m.p.: 296-298 ºC.
1H NMR (400 MHz, DMSO-d6) 9.64 (s, OH), 8.51 (d, J = 1.8 Hz, 2H),
8.49 (s, 2H), 7.90 (t, J = 7.8 Hz, 2H), 7.30 (t, J = 8.1 Hz, 1H), 6.87 – 6.84
(m, 1H), 6.79 - 6.78 (m, 2H); 13C NMR (101 MHz, DMSO-d6) δ 163.3 (2C),
153.4, 134.4 (2C), 131.5, 130.6 (2C), 130.3, 129.6, 127.9, 127.2 (2C),
122.9, 122.7 (2C), 119.1, 116.4; IR (cm-1) 3290 (O-H), 1650 (C=O), 760
(Ar-H); LRMS (ESI+) m/z: 290 [M+H]+, (100%); (ESI-) m/z: 288 [M-H]-
(100%); HRMS (ESI-) m/z calculated for C18H10NO3 (M-H)- 288.0666;
found: 287.9986.
2-(4-Chlorophenyl)-1H-benzo[de]isoquinoline-1,3(2H)-dione (17)
A solution of 1,8-naphthalic anhydride (14) (1.0 mmol, 0.198 g), 4-
chloroaniline (3.0 mmol, 0.315 mL) and triethylamine (10 drops) in 15
mL absolute ethanol was heated to reflux for 44 h, with magnetic
stirring, then allowed to cool to room temperature. The mixture was
filtered in vacuo, the yellow precipitate washed with cold ethanol (15
mL) and cold diethyl ether (15 mL), and dried in vacuo to afford the
desired compound as an off-white solid (0.139 g, 45%), m.p.: 282-284
ºC [49].
1H NMR (400 MHz, CDCl3) 8.64 (d, J = 7.7 Hz, 2H), 8.28 (d, J = 7.7
Hz, 2H), 7.80 (t, J = 7.7 Hz, 2H), 7.52 (d, J = 8.0 Hz, 2H), 7.27 (d, J = 8.0
Hz, 2H); 13C NMR (101 MHz, CDCl3) δ 164.4 (2C), 134.8, 134.6, 134.0,
131.90 (2C), 131.87 (2C), 130.2 (2C), 129.8 (2C), 128.7, 127.2 (2C), 122.8
(2C); IR (cm-1) 1701 (C=O), 776 (C-Cl); LCMS (ESI+) m/z: 308 [M+H]+
(100%), 310 [M+H]+ (35%).
2-(4-Hydroxyphenyl)-1H-benzo[de]isoquinoline-1,3(2H)-dione (21)
A solution of 1,8-naphthalic anhydride (14) (1.0 mmol, 0.198 g), 4-
aminophenol (3.0 mmol, 0.327 g) and triethylamine (8 drops) in 15 mL
absolute ethanol was heated to reflux for 18 h, with magnetic stirring,
then allowed to cool to 0 ºC. The mixture was filtered in vacuo, the dark
purple precipitate washed with cold ethanol (3 mL) and cold diethyl
ether (3 mL), and dried in vacuo to afford the desired compound as a
purple-grey solid (0.231 g, 80%), m.p.: 291-293 ºC [52].
1H NMR (400 MHz, DMSO-d6) 9.64 (s, 1H, OH), 8.49 (s, 2H), 8.48
(s, 2H), 7.89 (t, J = 7.8 Hz, 2H), 7.14 (dt, J = 8.8, 2.8 Hz, 2H), 6.87 (dt, J =
8.8, 2.8 Hz, 2H); 13C NMR (101 MHz, DMSO-d6) δ 163.9 (2C), 157.1,
134.3 (2C), 131.4, 130.7 (2C), 129.1 (2C), 127.8, 127.2 (2C), 126.9, 122.7
(2C), 115.4 (2C); IR (cm-1) 3280 (O-H), 1648 (C=O), 781 (Ar-H); LRMS
(ESI+) m/z: 290 [M+H]+, (100%); (ESI-) m/z: 288 [M-H]- (100%).
2-Phenyl-1H-benzo[de]isoquinoline-1,3(2H)-dione (18)
To a mixture of 1,8-naphthalic anhydride (14) (0.56 mmol, 0.111 g)
and aniline (0.61 mmol, 0.057 g) was added 1-butyl-3-
methylimidazolium bromide (0.8 mL). This solution was then heated,
with magnetic stirring, to 140 ºC for 18 h. The ensuing mixture was
cooled to room temperature, then treated with absolute ethanol (3 mL)
before chilling to 0 ºC. The resultant precipitate was collected by
filtration in vacuo, washed with cold ethanol (4 × 7.5 mL) and cold
diethyl ether (3 × 7.5 mL), then dried in vacuo to afford the desired
compound as a tan crystalline solid (0.153 g, 44%), m.p.: 179 ºC [50].
1H NMR (400 MHz, DMSO-d6) 8.53 (d, J = 3.6 Hz, 2H), 8.51 (d, J =
2.6 Hz, 2H), 7.91 (t, J = 7.8 Hz, 2H), 7.53 (t, J = 7.3 Hz, 2H), 7.46 (t, J = 7.3
Hz, 1H), 7.40 (t, J = 4.2 Hz, 2H); 13C NMR (101 MHz, DMSO-d6) 163.7
(2C), 136.1 (2C), 134.4 (2C), 131.5, 130.7, 129.1, 128.9, 128.2 (2C),
127.9 (3C), 127.3 (2C), 122.6; IR (cm-1) 3050 (Ar-H), 1660 (C=O), 700
(Ar-H); LCMS (ESI+) m/z: 274 [M+H]+ (100%).
2-(3-Aminophenyl)-1H-benzo[de]isoquinoline-1,3(2H)-dione (22)
A solution of 1,8-naphthalic anhydride (14) (1.34 mmol, 0.266 g),
m-phenylenediamine (4.38 mmol, 0.474 g) and triethylamine (10
drops) in absolute ethanol (20 mL) was heated to reflux, with magnetic
stirring, for 36 h. Upon cooling to room temperature, the mixture was
filtered in vacuo, and the resultant yellow precipitate was washed with
ethanol (2 × 15 mL) cold diethyl ether (2 × 15 mL), and dried in vacuo to
afford the desired compound as a yellow solid (0.308 g, 80%), m.p.:
>250 ºC (decomp.).
1H NMR (400 MHz, DMSO-d6) 8.50 (s, 2H), 8.48 (s, 2H), 7.89 (t, J =
8.0 Hz, 2H), 7.13 (t, J = 8.0 Hz, 1H), 6.65 (d, J = 8.0 Hz, 1H), 6.51 (s, 1H),
6.48 (d, J = 12.0 Hz, 1H), 5.23 (bs, NH2); 13C NMR (101 MHz, DMSO-d6)
163.5 (2C), 149.4, 136.6, 134.3 (2C), 131.4, 130.7 (2C), 129.1 (2C),
127.8, 127.2 (2C), 122.6, 116.0, 114.3, 113.6; IR (cm-1) 3411 (NH2), 3348
(NH2), 2971 (Ar-H), 1658 (C=O), 776 (Ar-H); LCMS (ESI+) m/z: 289
[M+H]+ (100%); HRMS (ESI+) m/z calculated for C18H13N2O2 (M+H)+
289.0972; found: 289.0973.
2-(2-Hydroxyphenyl)-1H-benzo[de]isoquinoline-1,3(2H)-dione (19)
A solution of 1,8-naphthalic anhydride (14) (1.0 mmol, 0.198 g), 2-
aminophenol (3.0 mmol, 0.327 g) and triethylamine (8 drops) in 15 mL
absolute ethanol was heated to reflux for 18 h, with magnetic stirring,
then allowed to cool to 0°C. The mixture was filtered in vacuo, the pale
brown solid washed with cold ethanol (3 mL) and cold diethyl ether (3
mL), and dried in vacuo to afford the desired compound as a creamy-
coloured solid (0.167 g, 58%), m.p.: 310-312 ºC [51].
1H NMR (400 MHz, DMSO-d6) 9.64 (s, OH), 8.51 (d, J = 1.8 Hz, 2H),
8.49 (s, 2H), 7.90 (t, J = 7.8 Hz, 2H), 7.30 (t, J = 8.1 Hz, 1H), 6.87 – 6.84
(m, 1H), 6.79 - 6.78 (m, 2H); 13C NMR (101 MHz, DMSO-d6) δ 163.6 (2C),
157.8, 137.0, 134.4 (2C), 131.4, 130.7 (2C), 129.4, 127.8, 127.2 (2C),
2-(4-Aminophenyl)-1H-benzo[de]isoquinoline-1,3(2H)-dione (23)
A solution of 1,8-naphthalic anhydride (14) (0.99 mmol, 0.198 g), p-
phenylenediamine (3.13 mmol, 0.339 g) and triethylamine (10 drops)
in ethanol (15 mL) was heated to reflux, with magnetic stirring, for 20
h. After cooling to room temperature, the mixture was filtered in vacuo,
and the reddish-brown precipitate was washed with ethanol (20 mL)
and cold diethyl ether (20 mL), and dried in vacuo to afford the desired
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