Synthesis of novel 2-amino-benzo[de]isoquinolin-1,3-dione derivatives

Article abstract of DOI:10.14233/ajchem.2014.16848

From a pioneer bioactive amino-benzoisoquinoline i.e. 2-amino-1H-benzo[de] isoquinolin-1,3-dione, a new series of Schiff's bases were prepared by the reaction of the active 2-amino group with a variety of aryl(hetero)aldehydes, isothiocyanides and acid anhydrides. The success of all reactions has been followed up by characterization of the synthesized target molecules through IR, Mass spectra and NMR analyses. The structural modifications were designed aiming at synthesis of valuable bioactive agents.

Full text of DOI:10.14233/ajchem.2014.16848

Asian Journal of Chemistry; Vol. 26, No. 7 (2014), 2166-2172
ASIAN JOURNAL OF CHEMISTRY
http://dx.doi.org/10.14233/ajchem.2014.16848
Synthesis of Novel 2-Amino-benzo[de]isoquinolin-1,3-dione Derivatives
1,2
R. AL-SALAHI1,* and M. MARZOUK
1Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia
2Chemistry of Natural Products Research Group, Center of Excellence for Advanced Sciences, National Research Center, Dokki, 12622,
Cairo, Egypt
*Corresponding author: E-mail: salahi76@yahoo.com
Received: 10 December 2013;
Accepted: 16 January 2014;
Published online: 22 March 2014;
AJC-14984
From a pioneer bioactive amino-benzoisoquinoline i.e. 2-amino-1H-benzo[de]isoquinolin-1,3-dione, a new series of Schiff's bases were
prepared by the reaction of the active 2-amino group with a variety of aryl(hetero)aldehydes, isothiocyanides and acid anhydrides. The
success of all reactions has been followed up by characterization of the synthesized target molecules through IR, Mass spectra and NMR
analyses. The structural modifications were designed aiming at synthesis of valuable bioactive agents.
Keywords: 2-Amino-1H-benzo[de]isoquinolin-1,3-dione, Aldehydes, Acid anhydrides, NMR.
INTRODUCTION
N
O
O
In organic and medicinal chemistry, studies in the field
of synthesis of new effective agents have recently became of
especial importance as a result of the increasing spread of
various communicable and un-communicable diseases. It was
known that many naphthalimide derivatives are famous anti-
cancer agents or DNA photocleavers, but there are few hetero-
cyclic fused naphthalimides as intercalative photocleavers for
DNA1-3. The 1H-benzo[de]isoquinolin-1,3-dione-based anti-
cancer drugs and potent HDAC inhibitors have been an indis-
pensable part in the development of antitumor agents4,5. For
example, substituted naphthalimides containing N-(2,2-
dimethylaminoethyl) chain best represented by mitonafide (5-
nitro group in the aromatic ring), amonafide (5-amino group
in the aromatic ring) and the dimer elinafide (Fig. 1) have
been shown to possess significant anticancer activities6-8. Both
Mitonafide and Amonafide have undergone Phase I and II
clinical trials with limited success9. Furthermore, some deriva-
tives of 1H-benzo[de]isoquinolin-1,3-dione were found to
possess antimicrobial activity and other combined very high
5-HT1A receptor affinity to visualize 5-HT1A receptors over
H
N
H
N
O
N
O
N
N
O
O
R
Fig. 1. Structure of Mitonafide (R = NO2), Amonafide (R = NH2) and Elinafide
EXPERIMENTAL
The melting points were determined on a Boetius stage
and are not corrected. NMR spectra were measured on a Bruker
AMX-500 spectrometer at 500 MHz for (1H) and 125 MHz
for (13C) in DMSO-d6 and the chemical shifts (δ-values) are
reported in ppm relative to TMS and coupling constants (J-
values) in Hz.
2-Amino-benzo[de]isoquinolin-1,3-dione: Off-white
amorphous powder, 80 % yield; 1H NMR (500 MHz, DMSO-
d6): δ 8.54 (br d, J = 7 Hz, 2H, H-3/8), 8.49 (br d, J = 8 Hz,
2H, H-5/6), 7.90 (t-like, J = 8 Hz, 2H, H-4/7), 5.58 (brs, 2H,
-NH2); 13C NMR (125 MHz, DMSO-d6): δ 160.3 (C-2/9), 134.5
(C-3/8), 130.8 (C-5/6), 130 (C-2a/8a), 127.3 (C-4/7), 125.9
(C-5a), 122.4 (C-2b); EI-MS, m/z (%): 212 [(M+·, 92)]; corres-
ponding for m.f.: C12H8N2O2 and m.w. 212.06.
expressed in CHO cells by fluorescence microscopy10,11
.
Although promising results have been obtained in this way,
most of the compounds were abandoned because of their
complicated synthesis6. Therefore, this led us to pay a great
attention to attempt for synthesis of a new series of 2-mino-
benzo[de]isoquinolin-1,3-dione derivatives in order to evaluate
their biological activities.
General procedure for synthesis of compounds 1-15:The
starting 2-amino-benzo[de]isoquinolin-1,3-dione (1 mmol)
was reacted with appropriate aldehyde (1.1 mmol) in absolute
DMF (8 mL) in the presence of few drops of glacial acetic
acid for 5.5 h under reflux. Afterwards the reaction mixture

Vol. 26, No. 7 (2014)
Synthesis of Novel 2-Amino-benzo[de]isoquinolin-1,3-dione Derivatives 2167
was cooled and poured into ice/water, the precipitate was
separated by filtration and washed thoroughly with diethyl
ether. Recrystallization from aqueous DMF furnished analy-
tically pure compounds.
(-OCH3); EI-MS, m/z (%): 330 [(M+·, 76)]; corresponding for
m.f.: C20H14N2O3 and m.w.: 330.1.
2-(3-Nitro-benzylidene)amino-benzo[de]isoquinolin-
1,3-dione (6): Yellow amorphous powder, 72 % yield, m.p.:
225-228 °C; 1H NMR (500 MHz, DMSO-d6): δ 9.02 (s, 1H,
H-7'), 8.79 (t-like , J = 1.5 Hz, 1H, H-2'), 8.56 (br d, J = 7.5
Hz, 2H, H-3/8), 8.52 (br d, J = 8 Hz, 2H, H-5/6), 8.49 (m, 2H,
H-4'/5'), 8.42 (br d, J = 7.5 Hz, 1H, H-6'), 7.91 (t-like, J = 8
Hz, 2H, H-4/7); 13C NMR (125 MHz, DMSO-d6): δ 169.7 (C-
7'), 160.2 (C-2/9), 148.3 (C-3'), 134.8 (C-3/8), 134.7 (C-1'),
134.4 (C-6'), 133.2 (C-5'), 131.3 (C-2a/8a), 131.2 (C-5/6),
130.9 (C-4'), 127.4 (C-4/7), 126.8 (C-5a), 122.8 (C-2'), 122.5
(C-2b); EI-MS, m/z (%): 345 [(M+·, 68)]; corresponding for
m.f.: C19H11N3O4 and m.w.: 345.07.
2-Ethylideneamino-benzo[de]isoquinolin-1,3-dione
(1): Brown amorphous powder, 56 % yield, m.p.: 282-285
°C; 1H NMR (500 MHz, DMSO-d6): δ 8.53 (br d, J = 7 Hz,
2H, H-3/8), 8.47 (br d, J = 8 Hz, 2H, H-5/6), 7.91 (m, 1H,
H-4/7, =CH-CH3), 1.90 (br s, 3H, =CH-CH3); 13C NMR (125
MHz, DMSO-d6): δ 160.5 (C-2/9), 148.5 (=CH-CH3), 134.5
(C-3/8), 131.1 (C-5/6), 130.6 (C-2a/8a), 127.5 (C-4/7), 125.6
(C-5a), 122.2 (C-2b), 14.0 (=CH-CH3); EI-MS, m/z (%): 238
[(M+·, 75)]; corresponding for m.f.: C14H10N2O2 and m.w. 238.07.
2-Propylideneamino-benzo[de]isoquinolin-1,3-dione
(2): Brown amorphous powder, 48 % yield, m.p.: 298-301
°C; 1H NMR (500 MHz, DMSO-d6): δ 8.55 (br d, J = 7 Hz,
2H, H-3/8), 8.50 (br d, J = 8 Hz, 2H, H-5/6), 7.94 (m, H-4/7,
1H, =CH-CH2-CH3), 2.60 (m, 2H, =CH-CH2-CH3), 1.10 (t,
J = 7Hz, 3H, =CH-CH2-CH3); 13C NMR (125 MHz, DMSO-
d6): δ 161.0 (C-2/9), 143.8 (=CH-CH2-CH3), 134.7 (C-3/8),
131.0 (C-5/6), 130.5 (C-2a/8a), 127.8 (C-4/7), 125.7 (C-5a),
122.5 (C-2b), 21.4 (=CH-CH2-CH3), 11.9 (=CH-CH2-CH3);
EI-MS, m/z (%): 252 [(M+·, 72)]; corresponding for m.f.:
C15H12N2O2 and m.w.: 252.07.
2-(4-Hydroxy-benzylidene)amino-benzo[de]isoquinolin-
1,3-dione (7): Pale green amorphous powder, 80 % yield, m.p.:
149-152 °C; 1H NMR (500 MHz, DMSO-d6): δ 10.36 (s, 4'-
1H, OH), 8.56 (s, 1H, H-7'), 8.54 (br d, J = 7 Hz, 2H, H-3/8),
8.51 (br d, J = 8 Hz, 2H, H-5/6), 7.92 (t-like, J = 8 Hz, 2H, H-
4/7), 7.81 (d, J = 8.5 Hz, 2H, H-2'/6'), 6.95 (d, J = 8.5 Hz, 2H,
H-3'/5'); 13C NMR (125 MHz, DMSO-d6): δ 171.4 (C-7'), 161.6
(C-4'), 160.4 (C-2/9), 134.5 (C-3/8), 131.4 (C-2a/8a), 131.0
(C-5/6), 130.9 (C-2'/6'), 127.3 (C-4/7), 126.8 (C-5a), 123.5
(C-1'), 122.4 (C-2b), 115.9 (C- 3'/5'); EI-MS, m/z (%): 316
[(M+·, 82)]; corresponding for m.f.: C19H12N2O3 and m.w.: 316.08.
2-(4-Dimethylamino-benzylidene)amino-benzo[de]
isoquinolin-1,3-dione (8): Pale brown amorphous powder,
60 % yield, m.p.: 240-243 °C. 1H NMR (500 MHz, DMSO-
d6): δ 8.53 (br d, J = 7 Hz, 2H, H-3/8), 8.51 (br d, J = 8 Hz,
2H, H-5/6), 8.45 (s, 1H, H-7'), 7.92 (t-like, J = 8 Hz, 2H, H-4/
7), 7.75 (d, J = 9 Hz, 2H, H-2'/6'), 6.95 (d, J = 9 Hz, 2H, H-3'/
5'), 3.06 (s, 6H, N-(CH3)2); 13C NMR (125 MHz, DMSO-d6):
δ 162.8 (C-7'), 160.6 (C-2/9), 157.7 (C-4'), 134.4 (C-3/8), 131.0
(C-2'/6' & 2a/8a), 130.4 (C-5/6), 127.3 (C-1' & 4/7), 126.8
(C-5a), 123.5 (C-1'), 122.5 (C-2b), 111.4 (C- 3'/5'), 40 (N-
(CH3)2); EI-MS, m/z (%): 343 [(M+·, 69)]; corresponding for
m.f.: C21H17N3O2 and m.w.: 343.07.
2-Benzylideneamino-benzo[de]isoquinolin-1,3-dione
(3): Yellow amorphous powder; 78 % yield, m.p.: 209-212
°C. 1H NMR (500 MHz, DMSO-d6): δ 8.78 (s, 1H, H-7'), 8.55
(br d, J = 7 Hz, 2H, H-3/8), 8.52 (br d, J = 8 Hz, 2H, H-5/6),
7.97 (br d, J = 7.5 Hz, 2H, H-2'/6'), 7.92 (t-like, J = 8 Hz, 2H,
H-4/7), 7.67 (t-like, J = 8 Hz, 1H, H-4'), 7.61 (t-like, J = 7.5
Hz, 2H, H-3'/5'); 13C NMR (125 MHz, DMSO-d6): δ 172 (C-
7'), 160.3 (C-2/9), 134.6 (C-3/8), 132.7 (C-4'), 132.4 (C-1'),
131.4 (C-2a/8a), 131.1 (C-5/6), 129.1 (C-2'/6'), 128.8 (C- 3'/
5'),127.3 (C-4/7), 126.8 (C-5a), 122.3 (C-2b); EI-MS, m/z (%):
300 [(M+·, 77)]; corresponding for m.f.: C19H12N2O2 and m.w.:
300.09.
2-(2-Methoxy-benzylidene)amino-benzo[de]isoquinolin-
1,3-dione (4): Yellow amorphous powder; 72 % yield, m.p.:
200-203 °C; 1H NMR (500 MHz, DMSO-d6): δ 8.96 (s, 1H,
H-7'), 8.53 (br d, J = 7.5 Hz, 2H, H-3/8), 8.50 (br d, J = 8 Hz,
2H, H-5/6), 8.13 (dd, J = 8, 1.5 Hz, 1H, H-3'), 7.91 (t-like, J =
8 Hz, 2H, H-4/7), 7.65 (td, J = 8.5, 1.5 Hz, 1H, H-4'), 7.24 (br
d, J = 8.5 Hz, 1H, H-6'), 7.15 (td, J = 7.5, 1.5 Hz, 1H, H-5'),
3.89 (s, 3H, -OCH3); 13C NMR (125 MHz, DMSO-d6): δ 167.1
(C-7'), 160.4 (C-2/9), 159.1 (C-2'), 134.5 (C-4' & 3/8), 131.4
(C-2a/8a), 130.9 (C-5/6), 127.3 (C-4/7), 126.9 (C-5a/6'), 122.5
(C-2b), 120.8 (C-5'), 120.3 (C-1'), 112.3 (C-3'), 55.8 (-OCH3);
EI-MS, m/z (%): 330 [(M+·, 81)]; corresponding for m.f.:
C20H14N2O3 and m.w.: 330.1.
2-[(4-Hydroxy-3-methoxy)-benzylidene)amino]benzo
[de]isoquinolin-1,3-dione (9):Yellow amorphous powder, 70
% yield, m.p.: 152-155 °C; 1H NMR (500 MHz, DMSO-d6): δ
10.01 (s, 1H, 4'-OH), 8.54 (s, 1H, H-7'), 8.52 (br d, J = 7.5 Hz,
2H, H-3/8), 8.48 (br d, J = 8 Hz, 2H, H-5/6), 7.91 (t-like, J =
7.5 Hz, 2H, H-4/7), 7.56 (d, J = 1.5 Hz, 1H, H-2'), 7.33 (dd,
J = 8, 1.5 Hz, 1H, H-6'), 6.95 (d, J = 8 Hz, 1H, H-5'), 3.87 (s,
3H, OCH3); 13C NMR (125 MHz, DMSO-d6): δ 171.5 (C-7'),
160.5 (C-2/9), 151.2 (C-3'), 148.1 (C-4'), 134.5 (C-3/8), 131.0
(C-2a/8a), 130.8 (C-5/6), 127.3 (C-4/7), 126.8 (C-5a), 124.4
(C-6'), 122.4 (C-2b), 115.1 (C-5'), 110.9 (C-2'), 55.6 (-OCH3);
EI-MS, m/z (%): 346 [(M+·, 92)]; corresponding for m.f.:
C20H14N2O4 and m.w. 346.09.
2-(3-Methoxy-benzylidene)amino-benzo[de]isoquinolin-
1,3-dione (5): Yellow amorphous powder 74 % yield, m.p.:
171-174 °C. 1H NMR (500 MHz, DMSO-d6): δ 8.74 (s, 1H,
H-7'), 8.54 (br d, J = 7.5 Hz, 2H, H-3/8), 8.51 (br d, J = 8 Hz,
2H, H-5/6), 7.91 (t-like, J = 8 Hz, 2H, H-4/7), 7.53 (m, 3H, H-
2', 5', 6'), 7.23 (m, 1H, H-4'), 3.86 (s, 3H, -OCH3); 13C NMR
(125 MHz, DMSO-d6): δ 171.8 (C-7'), 160.3 (C-2/9), 159.6
(C-3'), 134.6 (C-3/8), 133.8 (C-1'), 131.4 (C-2a/8a), 131.1 (C-
5/6), 130.3 (C-5'), 127.3 (C-4/7), 126.8 (C-5a), 122.3 (C-2b),
121.7 (C-6'), 120.8 (C-5'), 118.9 (C-4'), 112.5 (C-2'), 55.3
2-(2,4-Dimethoxy-benzylidene)amino-benzo[de]
isoquinolin-1,3-dione (10):Yellow amorphous powder, 73 %
1
yield, m.p.: 202-205 °C; H NMR (500 MHz, DMSO-d6): δ
8.61 (s, 1H, H-7'), 8.54 (br d, J = 7 Hz, 2H, H-3/8), 8.51 (br d,
J = 8 Hz, 2H, H-5/6), 7.92 (t-like, J = 8 Hz, 2H, H-4/7), 7.59
(d, J = 1.5 Hz, 1H, H-3'), 7.45 (dd, J = 8.5, 2 Hz, 1H, H-5'),
7.16 (d, J = 8.5 Hz, 1H, H-6'), 3.89 and 3.87 (s, 3H each, 2 X-
OCH3); 13C NMR (125 MHz, DMSO-δ6): δ 166 (C-7'), 160.4
(C-2/9), 152.8 (C-4'), 149.1 (C-2'), 134.6 (C-3/8), 131.0 (C-5/

2168 Al-Salahi et al.
Asian J. Chem.
6), 130.9 (C-2a/8a), 127.3 (C-4/7), 126.9 (C-5a), 124.9 (C-1'),
124.6 (C-6'), 122.4 (C-2b), 111.4 (C-5'), 109.1 (C-3'), 55.7 and
55.5 (2 X -OCH3); EI-MS, m/z (%): 360 [(M+·, 82)];
corresponding for m.f.: C21H16N2O4 and m.w. 360.11.
(t-like, J = 7.5 Hz, 2H, H-4/7), 7.79 (dd, J = 5, 3 Hz, 1H, H-
2'), 7.71 (br d, J = 5 Hz, 1H, H-4'); 13C NMR (125 MHz,
DMSO-d6): δ 166.6 (C-6'), 160.3 (C-2/9), 135.8 (C-3'), 134.5
(C-3/8), 134.0 (C-2'), 131.2 (C-2a/8a), 131.0 (C-5/6), 128.5
(C-5'), 127.3 (C-4/7), 126.8 (C-5a), 124.9 (C-4'), 122.3 (C-
2b); EI-MS, m/z (%): 306 [(M+·, 69)]; corresponding for m.f.:
C17H10N2O2S and m.w.: 306.
2-(2,4-Dichloro-benzylidene)amino-benzo[de]isoqui-
nolin-1,3-dione (11):Yellow amorphous powder, 56 % yield,
m.p.: 191-194 °C. 1H NMR (500 MHz, DMSO-d6): δ 9.12 (s,
1H, H-7'), 8.54 (br d, J = 7 Hz, 2H, H-3/8), 8.50 (br d, J =
8 Hz, 2H, H-5/6), 8.26 (d, J = 8.5 Hz, 1H, H-6'), 7.91 (t-like,
J = 8 Hz, 2H, H-4/7), 7.89 (d, J = 2 Hz, 1H, H-3'), 7.68 (dd,
J = 8.5, 2 Hz, 1H, H-5'); 13C NMR (125 MHz, DMSO-d6): δ
166.9 (C-7'), 160.2 (C-2/9), 138.0 (C-4'), 135.8 (C-2'), 134.6
(C-3/8), 131.3 (C-2a/8a), 131.1 (C-5/6), 129.9 (C-6'), 129.4
(C-3'), 128.8 (C-1'), 128.4 (C-5'), 127.3 (C-4/7), 126.8 (C-
5a), 122.3 (C-2b); EI-MS, m/z (%): 368 [(M+·, 77)]; corres-
ponding for m.f.: C19H10N2O2Cl2 and m.w. 368.01.
General procedure for synthesis of compounds 16-18:
A mixture of 2-amino-benzo[de]isoquinolin-1,3-dione (1 mmol)
and the corresponding isothiocyanides (1.2 mmol) was heated
in DMF (10 mL) for 5 h under reflux.After cooling, the solution
was poured in ice water and the solid was collected by filtration.
Analytically pure products 16-18 were obtained by recrysta-
llization from aqueous DMF.
1-Allyl-3-(1,3-dioxo-1H,3H-benzo[de]isoquinolin-2-yl)-
thiourea (16): Pale brown amorphous powder, 70 % yield,
m.p.: 180-183 °C; 1H NMR (500 MHz, DMSO-d6): δ 8.52 (br
d, J = 8.5 Hz, 2H, H-3/8), 8.48 (br d, J = 8.5 Hz, 2H, H-5/6),
7.93 and 7.91 (s, each 1H, 2 × -NH-), 7.90 (t-like, J = 8 Hz,
2H, H-4/7), 5.92 (m, 1H, H-2'), 5.22 (dd, J = 17.5, 1.5 Hz, 1H,
H-3a'), 5.16 (dd, J = 10.5, 1.5 Hz, 1H, H-3b'), 4.69 (d, J = 5
Hz, 2H, H-1'); 13C NMR (125 MHz, DMSO-d6): δ 182.6 (C=S),
160.5 (C-2/9), 134.6 (C-3/8), 131.0 (C-2'), 130.2 (C-2a/8a),
130.8 (C-5/6), 127.3 (C-4/7), 126.0 (C-5a), 121.7 (C-2b), 117.2
(C-3'), 45.0 (C-1'); EI-MS, m/z (%): 311 [(M+·, 73)]; corres-
ponding for m.f.: C16H13N3O2S and m.w. 311.06.
2-[(2-Hydroxy-5-bromo)-benzylidene)amino]benzo-
[de]isoquinolin-1,3-dione (12): Yellow amorphous powder,
85 % yield, m.p.: 205-208 °C; 1H NMR (500 MHz, DMSO-
d6): δ 11.34 (s, 1H, 2'-OH), 8.99 (s, 1H, H-7'), 8.55 (br d, J =
7 Hz, 2H, H-3/8), 8.51 (br d, J = 8 Hz, 2H, H-5/6), 8.04 (d,
J = 2.5 Hz, 1H, H-6'), 7.92 (t-like, J = 7.5 Hz, 2H, H-4/7),
7.64 (dd, J = 9, 2.5 Hz, 1H, H-4'), 7.02 (d, J = 9 Hz, 1H, H-3');
13C NMR (125 MHz, DMSO-d6): δ 167.4 (C-7'), 160.4 (C-2/
9), 157.8 (C-2'), 136.4 (C-5'), 134.7 (C-3/8), 131.4 (C-2a/8a),
131.1 (C-5/6), 130.7 (C-1'), 127.3 (C-4/7), 126.8 (C-5a), 122.3
(C-2b), 120.1 (C-6'), 119.2 (C-3'), 110.6 (C-4'); EI-MS, m/z
(%): 394 [(M+·, 90)]; corresponding for m.f.: C19H11N2O3Br
and m.w. 394.01.
1-(1,3-Dioxo-1H,3H-benzo[de]isoquinolin-2-yl)-3-
phenyl-thiourea (17):Yellow amorphous powder, 67 % yield,
1
m.p.: 154-157 °C; H NMR (125 MHz, DMSO-d6): δ 8.66,
2-[(Pyridin-3-ylmethylene)-amino]-benzo[de]
isoquinolin-1,3-dione (13): Pale green amorphous powder,
76 % yield, m.p.: 198-201 °C. 1H NMR (500 MHz, DMSO-
d6): δ 7.08 (d, J = 1 Hz, 1H, H-2'), 8.91 (s, 1H, H-7'), 8.84 (dd,
J = 6.5, 1 Hz, 1H, H-4'), 8.55 (br d, J = 7.5 Hz, 2H, H-3/8),
8.52 (br d, J = 8 Hz, 2H, H-5/6), 8.42 (br d, J = 8.5 Hz, 1H, H-
6'), 7.93 (t-like, J = 7.5 Hz, 2H, H-4/7), 7.02 (dd, J = 8.5, 6.5
Hz, 1H, H-5'); 13C NMR (125 MHz, DMSO-d6): δ 169.7 (C-
7'), 160.2 (C-2/9), 153.2 (C-4'), 150.1 (C-2'), 135.1 (C-6'),
134.7 (C-3/8), 131.4 (C-2a/8a), 131.1 (C-5/6), 128.3 (C-1'),
127.4 (C-4/7), 126.8 (C-5a), 124.3 (C-5'), 122.2 (C-2b); EI-
MS, m/z (%): 301 [(M+·, 87)]; corresponding for m.f.:
C18H11N3O2 and m.w.: 301.06.
8.58 (br s, each 1H, 2 × -NH-), 8.52 (br d, J = 7 Hz, 2H, H-3/
8), 8.48 (br d, J = 8.5 Hz, 2H, H-5/6), 7.89 (t-like, J = 8 Hz,
2H, H-4/7), 7.46 (br d, J = 8 Hz, 2H, H-2'/6'), 7.27 (t-like, J =
8 Hz, 2H, H-3'/5'), 6.96 (br t-like, J = 7.5 Hz, 1H, H-4'); 13C
NMR (500 MHz, DMSO-d6): δ 182.5 (C=S), 160.5 (C-2/9),
139.5 (C-1'), 134.5 (C-3/8 & 3'/5'), 131.2 (C-2a/8a), 130.8
(C-5/6), 128.5 (C-2'/6'), 127.3 (C-4/7), 126.7 (C-5a), 122.4
(C-2b), 118.0 (C-4'); EI-MS, m/z (%): 347 [(M+·, 85)];
corresponding for m.f.: C19H13N3O2S and m.w.: 347.11.
1-Cyclohexyl-3-(1,3-dioxo-1H,3H-benzo[de] isoquinolin-
2-yl)thiourea (18): Pale green amorphous powder, 79 % yield,
1
m.p.: 227-230 °C; H NMR (500 MHz, DMSO-d6): δ 9.85,
8.62 (br s, each 1H, 2 × -NH-), 8.54 (br d, J = 7 Hz, 2H, H-3/
8), 8.51 (br d, J = 7 Hz, 2H, H-5/6), 7.91 (t-like, J = 8 Hz, 2H,
H-4/7), 5.08 (m, 1H, H-1'), 3.35 (br s, 4H, CH2-2'/6'), 2.89
(m, 4H, CH2-3'/5'), 2.73 (br s, 2H, CH2-4'); 13C NMR (125
MHz, DMSO-d6): δ 182.4 (C=S), 162.2 (C-2/9), 134.7 (C-3/
8), 131.5 (C-2a/8a), 131 (C-5/6), 127.6 (C-5a), 127.3 (C-4/7),
122.8 (C-2b), 46.0 (C-1'), 38.9 (C-2'/6'), 35.7 (3'/5'), 30.7 (C-
4'; EI-MS, m/z (%): 353 [(M+·, 77)]; corresponding for m.f.:
C19H19N3O2S and m.w.: 353.13.
2-[(Furan-2-ylmethylene)amino]benzo[de]isoquinolin-
1,3-dione (14): Yellow amorphous powder, 70 % yield, m.p.:
144-147 °C; 1H NMR (500 MHz, DMSO-d6): δ 8.60 (s, 1H,
H-6'), 8.53 (2H, br d, J = 7.5 Hz, H-3/8), 8.50 (2H, br d, J = 8
Hz, H-5/6), 8.12 (1H, br s, H-5'), 7.91 (2H, t-like, J = 7.5 Hz,
H-4/7), 7.38 (1H, br s, H-3'), 6.85 (1H, br s, H-4'); 13C NMR
(125 MHz, DMSO-d6): δ 181.2 (C-6'), 160.2 (C-2/9), 159.9
(C-2'), 147.7 (C-5'), 134.6 (C-3/8), 131.4 (C-2a/8a), 131.0 (C-
5/6), 127.3 (C-4/7), 126.7 (C-5a), 122.3 (C-2b), 119.8 (C-3'),
112.8 (C-4'); EI-MS, m/z (%): 290 [(M+·, 60)]; corresponding
for m.f.: C17H10N2O3 and m.w. 290.13.
General procedure for synthesis of compounds 19-24:
A mixture of 2-amino-benzo[de]isoquinolin-1,3-dione (1
mmol) and the corresponding acid anhydride (1.1 mmol) was
heated in glacial acetic acid (15 mL) for 6 h under reflux.
After cooling, the solution was poured in ice water and the
resulted product was collected by filtration, washing with
water, dried. Analytically pure products 19-24 were obtained
by recrystallization from aqueous DMF.
2-[(Thiophen-3-ylmethylene)amino]benzo[de]-
isoquinolin-1,3-dione (15): Yellow amorphous powder, 73 %
1
yield, m.p.: 188-191 °C; H NMR (500 MHz, DMSO-d6): δ
8.72 (s, 1H, H-6'), 8.53 (br d, J = 7.5 Hz, 2H, H-3/8), 8.50 (br
d, J = 8 Hz, 2H, H-5/6), 8.32 (br d, J = 2.5 Hz, 1H, H-5'), 7.91

Vol. 26, No. 7 (2014)
Synthesis of Novel 2-Amino-benzo[de]isoquinolin-1,3-dione Derivatives 2169
2-(2,5-Dioxo-pyrrolidin-1-yl) benzo[de]isoquinolin-
1,3-dione (19):Yellow amorphous powder, 80 % yield, m.p.:
260-263 °C; 1H NMR (500 MHz, DMSO-d6): δ 8.65 (br d, J =
8 Hz, 2H, H-3/8), 8.63 (br d, J = 7.5 Hz, 2H, H-5/6), 7.99 (t-
like, J = 8 Hz, 2H, H-4/7), 3.12 (br s, 4H, 2 × -CH2-3'/4'); 13C
NMR (125 MHz, DMSO-d6): δ 172.8 (C-2'/5'), 159.9 (C-2/
9), 136.4 (C-3/8), 133.2 (C-2a/8a), 132.5 (C-5/6), 127.7 (C-4/
7), 126.1 (C-5a), 120.3 (C-2b), 26.6 (C-3'/4'); EI-MS, m/z (%):
294 [(M+·, 92)]; corresponding for m.f.: C16H10N2O4 and m.w.:
294.09.
131.8 (C-2a/8a & 2a"/8a"), 129.7 (C-5/6 & 5"/6"), 127.9
(C-4/7 & 4"/7"), 126.5 (C-5a/5a"), 121.3 (C-2b/2b"), 120.3
(C-3'/7'); EI-MS, m/z (%): 606 [(M+·, 89)]; corresponding for
m.f.: C34H14N4O8 and m.w.: 606.11.
RESULTS AND DISCUSSION
In present methodology, three main reactions were designed
using 2-amino-benzo[de]isoquinolin-1,3-dione as starting
compound to afford the target products 1-15, 16-18 and 19-
24 (Scheme-I and Table-1). In the first reaction, 2-amino-
benzo[de]isoquinolin-1,3-dione was treated with a variety of
aryl(hetero)aldehydes in dimethylformamide in the presence
of few drops of glacial acetic acid for 5.5 h under reflux
condition, affording the desired products 1-15 with satisfac-
tory yields12-14. The second group of compounds 16-18 were
2-(2,5-Dioxo-2,5-dihydro-pyrrol-1-yl)benzo[de]-
isoquinolin-1,3-dione (20): Pale green amorphous powder,
76 % yield, m.p.: 284-287 °C; 1H NMR (500 MHz, DMSO-
d6): δ 8.65 (br d, J = 8 Hz, 2H, H-3/8), 8.63 (br d, J = 7.5 Hz,
2H, H-5/6), 7.94 (t-like, J = 8 Hz, 2H, H-4/7), 6.90 (br s, 2H,
2 × -CH-3'/4'); 13C NMR (125 MHz, DMSO-d6): δ 171.1
(C-2'/5'), 161.5 (C-2/9), 136.4 (C-3/8), 134.6 (C-3'/4'), 132.9
(C-2a/8a), 132.5 (C-5/6), 127.7 (C-4/7), 126.6 (C-5a), 120.5
(C-2b); EI-MS, m/z (%): 292 [(M+·, 72)]; corresponding for
m.f.: C16H8N2O4 and m.w.: 292.01.
TABLE-1
SYNTHESIZED 2-AMINO-BENZO
[DE]ISOQUINOLIN-1,3-DIONE DERIVATIVES
R
R
Cpd. Nr
1
Cps.
1'
H3C CH-
2'
2-(1,3-Dioxo-1,3-dihydro-isoindol-2-yl)benzo[de]-
isoquinolin-1,3-dione (21): Pale green amorphous powder,
80 % yield, m.p.: 225-228 °C; 1H NMR (500 MHz, DMSO-
d6): δ 8.69 (br d, J = 7.5 Hz, 2H, H-3/8), 8.67 (br d,
J = 8 Hz, 2H, H-5/6), 8.17 (m, 2H, H-3'/6'), 8.09 (m, 2H, H-4'/
N
13
CH-
6'
7'
2'
CH-
2
14
CH-
6'
O
1'
13
5'), 8.01 (t-like, J = 8 Hz, 2H, H-4/7); C NMR (125 MHz,
6'
7'
DMSO-δ6): δ 166.0 (C-2'/7'), 159.5 (C-2/9), 136.8 (C-4'/5'),
136.2 (C-3/8), 132.7 (C-5/6), 131.6 (C-2a/8a), 128.4 (C-2a/
6a), 127.8 (C-4/7), 126.6 (C-5a), 124.6 (C-3'/6'), 122 (C-2b);
EI-MS, m/z (%): 342 [(M+·, 84)]; corresponding for m.f.:
C20H10N2O4 and m.w. 342.08.
CH-
3
4
5
15
16
CH-
1'
S
O
1'
CH2-
CH-
O
1'
[2,2']Bi[benzo[de]isoquinolinyl]-1,3,1',3'-tetraone (22):
obtain as yellow amorphous powder, 87 % yield, m.p.: 205-
208 °C; 1H NMR (500 MHz, DMSO-d6): δ 8.57 (br d, J = 8.5
Hz, 4H, 2 × H-3/8), 8.54 (br d, J = 7.5 Hz, 4H, 2 × H-5/6),
7.92 (t-like, J = 8 Hz, 4H, 2 × H-4/7); 13C NMR (125 MHz,
DMSO-d6): δ 160.7 (2 × C-2/9), 135.4 (2 × C-3/8), 132.4 (2 ×
C-5/6), 131.4 (2 × C-2a/8a), 129.7 (2 × C-5a), 127.5 (2 × C-4/
7), 119.0 (2 × C-2b); EI-MS, m/z (%): 392 [(M+·, 95)]; corres-
ponding for m.f.: C24H12N2O4 and m.w.: 392.06.
17
18
CH-
1'
CH-
6
7
O2N
O
CH-
HO
19
N
1'
2'
O
6-(1,3-Dioxo-1H,3H-benzo[de]isoquinolin-2-yl)-2-oxo-
6-aza-s-indacene-1,3,5,7-tetraone (23): Green amorphous
powder, 50 % yield, m.p.: 257-260 °C; 1H NMR (500 MHz,
DMSO-d6): δ 8.68 (br d, J = 7.5 Hz, 2H, H-3/8), 8.66 (br d,
J = 8 Hz, 2H, H-5/6), 8.43 (s, 2H, H-3'/7'), 8.03 (t-like, J = 8
Hz, 2H, H-4/7); 13C NMR (125 MHz, DMSO-d6): δ 166.6 (C-
4'/6'), 162.5 (C-2'/8'), 160.5 (C-2/9), 136.8 (C-3a'/6a'), 136.6
(C-2a'/7a'), 134.5 (C-3/8), 131.9 (C-2a/8a), 130.4 (C-5/6),
127.7 (C-4/7), 126.4 (C-5a), 122.3 (C-2b), 120.4 (C-3'/7'); EI-
MS, m/z (%): 412 [(M+·, 61)]; corresponding for m.f.: C22H8N2O7
and m.w.: 412.09.
O
8
CH-
N
20
21
22
N
O
O
O
6'a
2'a
1'
9
CH-
HO
N
2'
3'
O
O
O
8'a
1'
10
CH-
O
N
5'a
O
2,6-Bis-(1,3-dioxo-1H,3H-benzo[de]isoquinolin-2-
yl)pyrrolo[3,4-f]isoindole-1,3,5,7-tetraone (24): Yellow
amorphous powder, 64 % yield, m.p.: 246-249 °C; H-NMR
(500 MHz, DMSO-d6): δ 8.69 (br d, J = 8 Hz, 4H, H-3/8 & 3"/
8"), 8.67 (br d, J = 7.5 Hz, 4H, H-5/6 & 5"/6"), 8.39 (s, 2H, H-
Cl
O
O
O
O
7'
3'
6'
1'
11
12
23
24
CH-
Cl
5'
N
O
OH
CH-
O
O
9''
O
8'
13
1'
1''
3'/7'), 8.02 (t-like, J = 8 Hz, 4H, H-4/7 & 4"/7"); C NMR
(125 MHz, DMSO-d6): δ 162.4 (C-2'/8' & 4'/6'), 160.2 (C-2/9
& 2"/9"), 134.0 (C-2a'/7a' & 3a'/6a'), 133.0 (C-3/8 & 3"/8"),
N
O
5''a
N
N
Br
O
O

2170 Al-Salahi et al.
Asian J. Chem.
8
7
1.10 (t, J = 7), assignable for methine, methylene and methyl
groups, respectively. Their 13C-signals were detected at 143.8,
21.4 and 11.9 which were considered as confirmative document
for the condensation product with propanal. EI-MS of imine
2 exhibited a moleculer ion peak at 252 with more 14 mu than
that of 1, corresponding to extra CH2 group. The success of
condensation reactions with aromatic aldehydes to form the
products 3-12 has been unambiguously proven from the
characteristic downfield singlet signal of methine proton in
the range of about 9.1-8.6 (H-7') and corresponding 13C-signal
in the range of δC ppm 172-166, except for 8, in which H-7'
was detected relatively upfield at 8.45 ppm and its own C-
signal at 162.8 due to the anisotropic and +R effects of dimethyl-
amino group at p-position. The intrinsic splitting pattern
(multiplicity & J-values) of the aromatic resonances in the 1H
NMR spectra represented a finger print in each case of conden-
sation products with aromatic aldehydes (3-12). An unsubsti-
tuted phenyl group was deduced in compound 3 from its pattern
of three signals at 7.97 (br d, J = 7.5), 7.67 (t-like, J = 8) and
7.61 (t-like, J = 7.5), interpretable for H-2'/6', H-4' and H-3'/5'
and their 13C-signals at 132.7 (C-4'), 129.1 (C-2'/6') and 128.8
(C- 3'/5'). In case of 2'-methoxyphenyl derivative (4), four
protons were detected at 8.13 (dd, J = 8, 1.5, H-3'), 7.65 (td,
J = 8.5, 1.5 Hz, H-4'), 7.24 (br d, J = 8.5 Hz, H-6'), 7.15 (td,
J = 7.5, 1.5 Hz, H-5') with intrinsic J-values for meta- and
ortho-coupling together with a methoxyl singlet at 3.89. The
characteristic four resonances of that ring was assigned
according to the effect of methoxylation at C-2', where it caused
special downfield shift of the adjacent proton i.e. H-3' in 1H
NMR, while in 13C NMR C-2' was noticed downfield at 159.1
with about ∆ +30 ppm and the adjacent C-3' at 112.3 upfield
with ∆ -12 ppm according to α-down-/β-upfield substituent
additive rules relative to benzene carbons. The 3'-methoxy-
lation in derivative 5 was followed from the downfield shift of
O
N
O
9
8a
6
1
2b
N
R
N
5a
NH2
2
5
2a
O
O
1-15
O
3
4
O
S
N
R
N
N
H
NHR
16-18
O
19-24
O
Scheme-I: Main routes for synthesis of the target compounds (1-24)
synthesized by the reaction of the starting material with appro-
priate isothiocyanides for 5 h, under reflux, as well. The last
set of target compounds 19-24 were obtained by the reaction
of 2-amino-benzo[de]isoquinolin-1,3-dione with the conve-
nient acid anhydrides in boiling glacial acetic acid for 6 h.
The structures of all products 1-24 were characterized by IR
(1776-1700 cm-1) and MS spectra and have been unambi-
guously proven by 1H- and 13C NMR (see experimental data).
An empirical numeration system was chosen for parent
compound (Scheme-I) and target molecules (Table-1) in order
to simplify understanding of the experimental data and
discussion of their structures.
1H NMR played an essential role for proving the structures
of the target molecules. This is based on the fact of the symmetric
structure for 2-amino-1H-benzo[de]isoquinolin-1,3-dione as
starting compound and parent moiety in all compounds 1-24
due to the presence of 2-fold plane or axis of symmetry. In the
1H NMR spectrum of the parent amine, the symmetric structure
was simply detected as three pairs of two equivalent aromatic
protons in the form of A2B2M2-spin coupling system at δH
ppm 8.54 (br d, J = 7), 8.49 (br d, J = 8) and 7.90 (t-like, J =
8), attributable to H-3/8, H-5/6 and H-4/7, respectively. As
will as the corresponding 13C-signals were assigned at δC ppm
134.5, 130.8 and 127.3, respectively in its 13C NMR spectrum
as three key-signals together with the two equivalent imide
carbonyl carbon at 160.3 (C-2/9), among a total of seven
resonances due to symmetric structure. The most upfield two
carbons at 125.9 (C-5a) and 122.4 (C-2b) were another two
key signals in all spectra for the junction position. The presence
of free amino group was concluded from a broad singlet at
5.58 integrated to two protons. A final proof for the structure
of starting compound was acheived from the moleculer ion
peak at m/z 212 [(M+•)] in its EI-MS spectrum.All synthesized
1
the adjacent H-2' at 7.53 in the H NMR, whereas C-3' was
downfield shifted to 159.6 and C-2' upfield at 112.5. The same
splitting pattern was observed in case of 3-nitro derivative (6),
1
where the nitro group led to similar effects on H and 13C
spectra, whereby H-2' was drasticlly downfield shifted at δH
ppm 8.79 in the form of t-like due to meta-coupling of the
same J-value (1.5) with both H-4' and H-6'. Similarely, in the
13C NMR and according to the substitution additive rules, C-
3' was interpreted downfield at δC ppm 148.3 and C-2' upfield
at 122.8 by the effect of 3'-nitro group. It is of great importance
to notice that H-7' has the strongest downfield shift to 9.02
ppm by -I and -R effects of nitro group in the 1H NMR of 6.
The condensation products with para-substituted aromatic
aldehydes (7,8) was clearly explained on the basis of the
appearance of their aromatic protons in the form of twoA2×2-
spin coupling systems as two ortho-doublets at δH ppm 7.81
and 6.95 (J = 8.5) in case of 7 and at 7.75 and 6.95 (J = 9) in
product 8, assignable for H-2'/6' and H-3'/5', respectively. In
their 13C NMR, the corresponding resonances were detected
as two pairs of equivalent C-signals at δC ppm 130.9 (C-2'/6')
and 115.9 (C-3'/5') and at 131 (C-2'/6') and 111.4 (C-3'/5') in
case of 7 and 8, respectively.As final confirmation for conden-
sation with 4'-OH aldehyde was concluded from the charac-
teristic downfield location of C-4' at 161.6 in 7, while in 8, C-
4' was detected at 157.7 by the deshielding effect of N-dimethyl
1
compounds showed more or less the same previous key H-
and 13C-signals of 2-amino-benzo[de]isoquinolin-1,3-dione
basic structure as confirmative document of the reaction
completion; in addition to the corresponding resonances of
new inserted functional group in each case. The condensation
product (1) that produced with acetaldehyde was confirmed
from its intrinsic imine methine proton at 7.91 and methyl at
1.90 (br s) and their own 13C-signals at δC ppm 148.5 and 14.0,
respectively, alongside the moleculer ion peak at m/z 238
[(M+•)] with more 26 mu relative to the parent due to extra
C2H2 moiety. Similarely, the new imide (2) showed the extra
1H-signals of propimide moiety at 7.94 (m) , 2.60 (m) and

Vol. 26, No. 7 (2014)
Synthesis of Novel 2-Amino-benzo[de]isoquinolin-1,3-dione Derivatives 2171
group that was appeared at its intrensic positions of 3.06 and
40 ppm in 1H and 13C NMR spectra. The condensation products
with disubstituted aldehydes (9-12) were easily interpreted on
the basis of their splitting pattern of the three aromatic proton
types as meta doublet, ortho-meta doublet of doublet and ortho
doublet. The 1H and 13C spectra of 9 were characterized by the
downfield shift of H-2' at 7.56 (d, J = 1) due to the effect of
methoxyl group and coupling with H-6' and characteristic
downfield location of C-3' and C-4' at 151.2 and 148.1, respec-
tively, because of their oxygenation (∆+30). Whereas H-3'
was strongly downfield located at 7.59 (d, J = 1.5) due to the
downfield effect by the two methoxyls attached to the two
neighbouring carbons in the 1H NMR of 10. Taking into account
thiophenaldehyde product (15) showed characteristic splitiing
pattern and different small J-values for allyl coupled protons
H-2', H-5' and H-4' at 8.32 (br d, J = 2.5), 7.79 (dd, J = 5, 3)
and 7.71 (br d, J = 5), respectively; in addition their charac-
teristic 13C-signals at 135.8 (C-3'), 134 (C-2'), 128.5 (C-5')
and 124.9 (C-4') by the effect of the ring-S and deshielding by
imine double bond. The synthesized coupling products (16-
18) were established by interpretation of their own intrinsic
key-signals of isothiocyanide structural residues as allyl (16),
13
phenyl (17) and cyclohexyl (18) amine in 1H and C NMR,
especially the most downfield thione-carbonyl carbon at about
δC ppm 182.5. The allyl residue was revealed by its own splitting
pattern for H-1', H-2' and H-3' geminal olifenic protons (see
13
1
13
the substitution additive rules, its C spectrum was charac-
experimental H NMR data) and intrinsic C signals at 131
(C-2'), 117.2 (C-3') and 45 (C-1'). The N-phenyl derivative
was simply confirmed through characteristic three resonances
as anA2M2M'-spin coupling system at 7.46 (br d, J = 8), 7.27
(t-like, J = 8), 6.96 (br t-like, J = 7.5) assignable to H-2'/6', H-
3'/5' and H-4', respectively, together with phenyl four 13C-
resonances at 139.5 (C-1'), 134.5 (C-3'/5'), 128.5 (C-2'/6'), 118
terized by strong downfield location of C-4' and C-2' at 152.8
and 149.1 due to direct substitution with two OCH3-groups
that resulted in sharp dublicated upfield shift of C-3' into 109.1
13
ppm (∆-20). Furthermore, C NMR of 11 showed intrinsic
downfield shift of C-4' and C-2' at 138 and 135.8, respectively
due to electron withdrawing effect by chlorine atoms. As well
as the brominated C-5' resulted in characteristic downfield shift
of both H-6' and H-4' to 8.04 (d, J = 2.5) and 7.64 (dd, J = 9,
2.5), in the 1H NMR spectrum of condensated product 12 and
its 13C NMR showed characteristic downfield location of C-2'
at 157.8 and C-5' at 136.4 due to the presence of hydroxyl and
bromo groups which were resulted in upfield of both C-3' and
C-4' at 119.2 and 110.6, respectively.
1
(C-4'). In the aliphatic region of H NMR for derivative 18,
characteristic four 1H-signals were clearly detected at 5.08
(m, H-1'), 3.35 (br s, CH2-2'/6'), 2.89 (m, CH2-3'/5') and 2.73
(br s, CH2-4') and their 13C-signals at 46 (C-1'), 38.9 (C-2'/6'),
35.7 (3'/5') and 30.7 (C-4′), respectively. Concerning products
19-24, their NMR spectra reserved the same pattern of the
parent moity along with various aliphatic (19, 20) or aromatic
(21-24) resonances corresponding to the anhydride moiety.
Because of the symmetric structure of 19 due to symmetric
structures of its components, its 1H NMR displayed an aliphatic
singlet for the two equivalent methylene protons together with
the same pattern of parent moiety. 13C NMR showed typical
seven signals for the parent moiety and two characteristic
resonances at 172.8 (C-2'/5'), 26.6 (C-3'/4') for the two equiva-
lent succinimide carbonyls and methylene carbons.Also, based
on the structural symmetry in the molecule of 20, its 1H NMR
spectrum revealed a singlet at 6.90 of the two equivalent
olifenic methine protons (H-3'/4') that were supported by their
own 13C resonance at 134.6 and the carbonyl resonance at 171.1
(C-2'/5'). Moreover, based on the structural symmetry of 21,
the phthalimide residue was simply explained in the 1H NMR
data as a pair of ortho doublets at 8.17 and 8.09 (d, J = 8),
attributable to H-3'/6' and H-4'/5' in the form of A2B2-spin
coupling system. The 13C NMR showed typical four resonances
for phthalimide moiety in particular that of equivalent imide
carbonyls at 166 (C-2'/7').As it was expected, heating a sample
of the parent amine in glacial acetic acid resulted in the forma-
tion of its symmetric dimer (22), which gave the same 1H and
13C NMR spectra of the parent. With respect to 23, depending
on the same structural feature of symmetry, a 2-fold axis or
plane of symmetry led to the appearence of the new coplanar
part in the form of only strongly deshielded singlet at 8.43 of
the two equivalent protons H-3'/7'.
The methoxyl groups in compounds 4, 5, 9 and 10 were
interpreted in the 1H NMR at about 3.9-3.8 and 56-55.5 ppm
13
in the C NMR spectra. Further confirmative document for
the exchangable OHs-protons in 7, 9 and 12 was followed
from its own highly deshielded singlets at 10.36, 10.01 and
11.34, respectively. The products (13-15), which are prepared
1
from the heterocyclic aldehydes gave characteristic H- and
13C NMR of the new inserted heteroimine ring together with
more or less the same paterrn for the parent structure (2-amino-
benzoisoquinoline). The 1H NMR of 13-15 showed an intrinsic
singlet of imine CH-proton at δH ppm 8.91, 8.60 and 8.72,
assignable for H-7' and H-6', respectively, corresponding to
characteristic 13C-signals at 169.7 (C-7'), 181.2 and 166.6 (C-
6'). The strong downfield shift of H-2' and H-4' to 9.09 (d, J =
1) and 8.84 (dd, J = 6.5, 1) and their corresponding C-signals
at 153.2 (C-4'), 150.1 (C-2'), was confirmative document for
the condensated product 13 due to the -I and -R effects of the
ring-N atom and conjugation with imine double bond. In
1
addition the characteristic strong downfield shift of H-
resonances (by the effect of O-ring and imine double bond
deshielding) and their splitting pattern was clear indication
for the successful preparation of furanimine product (14),
where all three protons (H-5', H-3' and H-4') appeared at 8.12,
7.38 and 6.85 as broad singlets due to their known very small
J-values of furan ring. According to the same deshielding
structural parametrs and substituent additive rules C-2' and C-
5' were assigned downfield at 159.9 and 147.7, but C-3' and
C-4' were upfield located at 119.8 and 112.8 by the effect of
β-upfield shift. As an intrinsic structural feature, C-6'-imine
was assigned at the largest δC-value (181.2 ppm) among all
imine carbons of the prepared 24 products. Similarly, 3-
The two carbonyls of the dianhydride moiety were
assigned at 166.6 and 162.5 (C-4′/6′ and 2′/8′). In compound
24, the pyromellitic diimide moiety showed a singlet at 8.39
(H-3′/7′) and 13C-resonances at 162.4, 134.0 and 120.3 to
confirm its co-planar symmetric structure.

2172 Al-Salahi et al.
ACKNOWLEDGEMENTS
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The authors extended their appreciation to the Deanship
of Scientific Research at King Saud University for funding
this work through research group No RGP-VPP-291.
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